Datasets:

andersonbcdefg

/

pubmed_pairs_part3

like 0

Advances in malaria pharmacology and the online guide to MALARIA PHARMACOLOGY: IUPHAR review 38.

Antimalarial drug discovery has until recently been driven by high-throughput phenotypic cellular screening, allowing millions of compounds to be assayed and delivering clinical drug candidates. In this review, we will focus on target-based approaches, describing recent advances in our understanding of druggable targets in the malaria parasite. Targeting multiple stages of the Plasmodium lifecycle, rather than just the clinically symptomatic asexual blood stage, has become a requirement for new antimalarial medicines, and we link pharmacological data clearly to the parasite stages to which it applies. Finally, we highlight the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY, a web resource developed for the malaria research community that provides open and optimized access to published data on malaria pharmacology.

Care coordination across healthcare systems: development of a research agenda, implications for practice, and recommendations for policy based on a modified Delphi panel.

For large, integrated healthcare delivery systems, coordinating patient care across delivery systems with providers external to the system presents challenges. We explored the domains and requirements for care coordination by professionals across healthcare systems and developed an agenda for research, practice and policy.

Coping strategies of the incarcerated during the COVID-19 pandemic: a scoping review protocol of quantitative and qualitative evidence.

To reduce the transmission of COVID-19, regulations included the use of cloth masks, sanitising regularly, maintaining social distance and having minimal personal contact. COVID-19 affected many different groups of people including service providers and users of correctional centres. In this protocol, we aim to establish evidence on the challenges and coping strategies adopted by the incarcerated and service providers of the incarcerated during the COVID-19 pandemic.

ADAMS project: a genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis based in the UK.

Genetic studies of multiple sclerosis (MS) susceptibility and severity have focused on populations of European ancestry. Studying MS genetics in other ancestral groups is necessary to determine the generalisability of these findings. The genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis (ADAMS) project aims to gather genetic and phenotypic data on a large cohort of ancestrally-diverse individuals with MS living in the UK.

Phage-Displayed SH2 Domain Libraries: From Ultrasensitive Tyrosine Phosphoproteome Probes to Translational Research.

Tyrosine phosphorylation is a critical regulator of cell signaling. A large fraction of the tyrosine phosphoproteome, however, remains uncharacterized, largely due to a lack of robust and scalable methods. The Src homology 2 (SH2) domain, a structurally conserved protein domain present in many intracellular signal-transducing proteins, naturally binds phosphorylated tyrosine (pTyr) residues, providing an ideal scaffold for the development of sensitive pTyr probes. Its modest affinity, however, has greatly limited its application. Phage display is an in vitro technique used for identifying ligands for proteins and other macromolecules. Using this technique, researchers have been able to engineer SH2 domains to increase their affinity and customize their specificity. Indeed, highly diverse phage display libraries have enabled the engineering of SH2 domains as affinity-purification (AP) tools for proteomic analysis as well as probes for aberrant tyrosine signaling detection and rewiring, and represent a promising class of novel diagnostics and therapeutics. This review describes the unique structure-function characteristics of SH2 domains, highlights the fundamental contribution of phage display in the development of technologies for the dissection of the tyrosine phosphoproteome, and highlights prospective uses of SH2 domains in basic and translational research.

Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease.

Clonal hematopoiesis of indeterminate potential (CHIP)-the age-related clonal expansion of blood stem cells with leukemia-associated mutations-is a novel cardiovascular risk factor. Whether CHIP remains prognostic in individuals with established atherosclerotic cardiovascular disease (ASCVD) is less clear.

Evaluation of the relationship between values and psychological resilience of individuals diagnosed with substance use disorder: A cross-sectional study.

The purpose of this study was to determine the relationship between values and psychological resilience in individuals with substance use disorder. This descriptive and correlational study was conducted with 70 individuals diagnosed with substance use disorder who had applied to the Alcohol and Drug Addiction Treatment and Research Center between February and April 2022 and volunteered to participate in the study. The data were collected using the Personal Information Form, Values Scale, and Brief Resilience Scale (BRS). All participants were male, the average age of substance use onset was 17.67 ± 5.95 years, and they had been receiving addiction treatment for 1.97 ± 2.30 years on average. The average total score of the individuals on the BRS scale was 17.18 ± 1.45. A significant positive correlation was found between the social values, intellectual values, spiritual values, materialistic values, human dignity, and freedom sub-dimensions of the Values Scale and psychological resilience (p < .001). Additionally, spiritual values were found to have the highest positive effect on the psychological resilience levels of individuals (B = 0.185; p < .05). Individuals with higher levels of social values, intellectual values, spiritual values, materialistic values, human dignity, and freedom were found to have higher psychological resilience. Nursing care provided by taking into account the values of the individual and strengthening their values may contribute to the psychological resilience of the patient.

Anticholinergic burden in older adults with psychiatric illnesses: A cross-sectional study.

We aimed in this study to determine the extent of exposure to anticholinergic drugs in older adults with psychiatric illnesses using the anticholinergic cognitive burden (ACB) scale and to identify the factors associated with anticholinergic drugs use and higher ACB scores.

Narrative enhancement and cognitive therapy for perceived stigma of chronic schizophrenia: A multicenter randomized controlled trial study.

This study explored the effects of NECT on self-stigma among people with schizophrenia. Eighty-six participants were recruited and assigned to two groups. The NECT group received 20-session group meetings, while the control group received routine care. Self-stigma was measured by Internalized Stigma of Mental Illness Scale (ISMIS) and Discrimination and Stigma Scale (DISC). Generalized estimating equations were employed to explore the intervention's effectiveness. The NECT group showed a significant reduction in ISMIS total scores after 20 sessions and Stopping Self subscale scores of DISC decreased over time. The intervention is effective for improving self-stigma in people with schizophrenia.

Adapting the COVID Stress Scale (CSS) to investigate the level of stress among Hong Kong Chinese people 1 year after the COVID-19 pandemic.

Stress is a crucial driver that affects hygiene behavior. The Hong Kong population lacks a COVID-19 or pandemic related stress measure investigating the COVID-19 related stress after one year of outbreak.

Global Impact of Obesity.

The prevalence of preobesity and obesity is rising globally, multiple epidemiologic studies have identified preobesity and obesity as predisposing factors to a number of noncommunicable diseases including type 2 diabetes (T2DM), cardiovascular disease (CVD), and cancer. In this review, we discuss the epidemiology of obesity in both children and adults in different regions of the world. We also explore the impact of obesity as a disease not only on physical and mental health but also its economic impact.

The Effects of Obesity on Health Care Delivery.

The rates of obesity continue to rise among adults and children in the United States; hence, it is natural that obesity is reshaping health care delivery. This is seen in numerous ways, including physiologic, physical, social, and economic impacts. This article reviews a broad range of topics, from the effects of increased adiposity on drug pharmacokinetics and pharmacodynamics to the changes health care environments are making to accommodate patients with obesity. The significant social impacts of weight bias are reviewed, as are the economic consequences of the obesity epidemic. Finally, a patient case that demonstrates the effects of obesity on health care delivery is examined.

Obesity Management in Children and Adolescents.

Obesity in the pediatric population is increasing in the United States and globally. Childhood obesity is associated with cardiometabolic and psychosocial comorbidities and decreased overall life span. The cause of pediatric obesity is multifactorial and includes genetic predisposition, lifestyle, behavioral patterns, and consequences of social determinants of health. Routine screening of BMI and comorbid conditions is essential to identifying patients who require treatment. The AAP recommends immediate Intensive Health Behavior and Lifestyle Treatment for children with obesity, encompassing lifestyle changes, behavioral changes, and mental health treatments. Pharmacologic interventions and metabolic and bariatric surgery are also available when indicated.

Voice of persons with a life-limiting illness in conversation with healthcare professionals: systematic review and meta-synthesis.

Healthcare organisations are transforming the way care is delivered to people with a life-limiting illness with an increased focus on recognising the voice of the persons experiencing the illness and putting them in the centre of decision-making. However, the clinical practice remains largely based on the views of healthcare professionals and families or carers of the person with the illness.

Benchmarking Enrichment Efforts in the US & Canada Across Species and Enrichment Categories.

Enrichment is important for animal welfare and data quality. Provision of enrichment opportunities varies between species and enrichment category. However, data benchmarking these differences does not exist. Our objective was to characterize enrichment provision and associated factors across species in the US and Canada. Personnel who work with research animals (n = 1098) in the US and Canada voluntarily responded to online promotions and completed a survey about enrichment used for the species they worked with most, their control of and wish for more enrichment, stress or pain in the animals they worked the most with, and demographics. All participants (except those working with rats) received the same questionnaire regardless of species to allow objectivity, as the effects of many enrichment items on some species have not yet been determined. The questionnaire asked about enrichments that were beneficial to at least one species. The provision of enrichment was allocated into 2 outcome variables: diversity and frequency per enrichment category. Results showed a significant interaction between enrichment category and species. Generally, physical, nutritional, and sensory enrichments were provided less often than social enrichment. In addition, nonhuman primates received more diverse and more frequent enrichment than did other species (twice as much as rats and mice). Enrichment was provided less frequently by personnel who wished they could do more than the status quo. Both enrichment frequency and diversity were higher in respondents from Canada, those who had more control over provision, and those who had been in the field longer. While our results cannot be used to determine the quality of enrichment provided to various species, they do provide information on current enrichment practices in the US and Canada and identify differences in implementation by species and enrichment category. The data also indicate provision of enrichment is influenced by factors such as country and individual control over enrichment. This information can also be used to identify areas for greater enrichment efforts for some species (for example, rats and mice) and categories, with the ultimate goal of improving animal welfare.

Soil moisture drives differences in the diversity and trophic complexity of high Arctic tundra soils.

The Arctic soil communities play a vital role in stabilizing and decomposing soil carbon, which affects the global carbon cycling. Studying the food web structure is critical for understanding biotic interactions and the functioning of these ecosystems. Here, we studied the trophic relationships of (microscopic) soil biota of two different Arctic spots in Ny-Ålesund, Svalbard, within a natural soil moisture gradient by combining DNA analysis with stable isotopes as trophic tracers. The results of our study suggested that the soil moisture strongly influenced the diversity of soil biota, with the wetter soil, having a higher organic matter content, hosting a more diverse community. Based on a Bayesian mixing model, the community of wet soil formed a more complex food web, in which bacterivorous and detritivorous pathways were important in supplying carbon and energy to the upper trophic levels. In contrast, the drier soil showed a less diverse community, lower trophic complexity, with the green food web (via unicellular green algae and gatherer organisms) playing a more important role in channelling energy to higher trophic levels. These findings are important to better understand the soil communities inhabiting the Arctic, and for predicting how the ecosystem will respond to the forthcoming changes in precipitation regimes.

Occlusion of the infarct-related coronary artery presenting as acute coronary syndrome with and without ST-elevation: impact of inflammation and outcomes in a real-world prospective cohort.

Patients with ST-segment elevation typically feature total coronary occlusion (TCO) of the infarct-related artery (IRA) on angiography, which may result in worse outcomes. Yet, relying solely on electrocardiogram (ECG) findings may be misleading and those presenting with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs) may have TCO as well. Herein, we aimed to delineate clinical characteristics and outcomes of patients with ACS stratified by IRA location.

Tako-Tsubo Syndrome Following Pulmonary Vein Isolation for Atrial Fibrillation in a Patient with Primary Aldosteronism.

Tako-tsubo syndrome (TTS) can be triggered by emotional or physical stress and is characterized by transient left ventricular dysfunction with apical ballooning. Some neurologic disorders and pheochromocytoma serve as triggers for TTS, however, its association with primary aldosteronism (PA) is not well known. Pulmonary vein isolation (PVI) with catheter ablation for atrial fibrillation (AF) has been performed worldwide, and TTS following PVI has been reported as a rare complication. Sympathetic stimulation can play an important role in TTS development, however, its mechanism and risk factors are not yet understood.We describe a 72-year-old woman with PA who developed TTS after PVI with radiofrequency catheter ablation (RFCA) for symptomatic paroxysmal AF. Complete isolation of the pulmonary vein was carried out without any complications, however, she complained of epigastric discomfort 7 hours after the procedure. An electrocardiogram showed recurrent AF with a new negative-T wave and prolonged QT interval. Transthoracic echocardiography revealed apical ballooning and basal hypercontraction, characteristic of TTS, and coronary angiography showed no significant stenosis. She was diagnosed with TTS following RFCA for AF and managed well with conservative therapy.The present case suggests that TTS should be recognized as a complication associated with AF ablation. Moreover, PA may be involved in TTS development by increasing sympathetic activity. Further studies on the mechanism and characteristics of TTS are required.

Clinical Value of Platelet Indices in Premature Coronary Artery Disease.

Platelets play an important role in the pathophysiology of coronary artery disease. However, the clinical value of platelet indices in premature coronary heart disease remains largely unknown.Consecutive patients referred for coronary angiography were evaluated (n = 1675). Patients were stratified into premature coronary heart disease (n = 679, age < 55 for male and age < 65 for female), late-onset coronary heart disease (n = 772, age ≥ 55 for male and age ≥ 65 for female), and control (n = 224, age < 55 for male and age < 65 for female). Their clinical and laboratory parameters were collected. The relationship between platelet indices and premature coronary artery disease was analyzed.In univariate analysis, platelet indices showed no significant association with the presence of premature coronary heart disease (P > 0.05). After adjustment for traditional risk factors, mean platelet volume (0.823 [0.683-0.993], P = 0.042) and platelet-large cell ratio (0.976 [0.954-0.999], P = 0.040) were negatively correlated with the presence of premature coronary heart disease. The platelet-to-lymphocyte ratio was statistically significant among different numbers of coronary lesions (P = 0.035). In subgroup analysis, platelet-large cell ratio (1.190 [1.010-1.403], P = 0.038) was an independent risk factor of coronary restenosis after percutaneous coronary intervention.Platelet indices were associated with the prevalence, severity, and coronary restenosis after percutaneous coronary intervention suggesting their possible clinical application in premature coronary heart disease.

Flanged Bentall and Cabrol Procedures for Complex Aortic Root Diseases.

For complex aortic root lesions, the flanged Bentall procedure has more advantages than the traditional one. Here, we report two patients with complex root lesions treated with the flanged Bentall and Cabrol procedure: one was a 25-year-old male with interventricular septal dissection with Behçet's disease, and the other was a 4-year-old female with a very large ascending aortic aneurysm with a small annulus and Loeys-Dietz syndrome. Both patients recovered uneventfully and obtained good short-term results.

Stable potassium isotope distribution in mouse organs and red blood cells: implication for biomarker development.

Potassium (K) is an essential electrolyte for cellular functions in living organisms, and disturbances in K+ homeostasis could lead to various chronic diseases (e.g. hypertension, cardiac disease, diabetes, and bone health). However, little is known about the natural distribution of stable K isotopes in mammals and their application to investigate bodily homeostasis and/or as biomarkers for diseases. Here, we measured K isotopic compositions (δ41K, per mil deviation of 41K/39K from the NIST SRM 3141a standard) of brain, liver, kidney, and red blood cells (RBCs) from 10 mice (five females and five males) with three different genetic backgrounds. Our results reveal that different organs and RBCs have distinct K isotopic signatures. Specifically, the RBCs have heavy K isotopes enrichment with δ41K ranging from 0.67 to 0.08‰, while the brains show lighter K isotopic compositions with δ41K ranging from -1.13 to -0.09‰ compared to the livers (δ41K = -0.12 ± 0.58‰) and kidneys (δ41K = -0.24 ± 0.57‰). We found that the K isotopic and concentration variability is mostly controlled by the organs, with a minor effect of the genetic background and sex. Our study suggests that the K isotopic composition could be used as a biomarker for changes in K+ homeostasis and related diseases such as hypertension, cardiovascular, and neurodegenerative diseases.

Preliminary experience with diffuse correlation spectroscopy in acute ischemic stroke neurointerventional procedures.

Diffuse correlation spectroscopy (DCS) is a non-invasive optical technique that enables continuous blood flow measurements in various organs, including the brain. DCS quantitatively measures blood flow from temporal fluctuations in the intensity of diffusely reflected light caused by the dynamic scattering of light from moving red blood cells within the tissue.

Rescue stenting after failure of endovascular thrombectomy for acute vertebrobasilar artery occlusion: data from the PERSIST registry.

Among acute vertebrobasilar artery occlusion (VBAO) patients, successful reperfusion is a strong predictor of favorable outcomes. However, failed reperfusion (FR) with endovascular thrombectomy (EVT) in VBAO was observed to occur in 18-50% of cases. We aim to evaluate the safety and efficacy of rescue stenting (RS) for VBAO after failed EVT.

Increased care-need in older long-term care insurance users after the 2018 Japan Floods: a retrospective cohort study based on the Japanese long-term care insurance claims.

Level of care-need (LOC) is an indicator of elderly person's disability level and is officially used to determine the care services provided in Japan's long-term care insurance (LTCI) system. The 2018 Japan Floods, which struck western Japan in July 2018, were the country's second largest water disaster. This study determined the extent to which the disaster affected the LOC of victims and compared it with that of non-victims.

Masseter and digastric muscle activity evaluation using a novel electromyogram that utilizes elastic sheet electrodes.

To evaluate the reproducibility and reliability of a novel electromyogram (EMG) device with a flexible sheet sensor for measuring muscle activity related to mastication and swallowing.

Gaps in the Care of Subjects with Familial Hypercholesterolemia: Insights from the Thai Familial Hypercholesterolemia Registry.

Familial hypercholesterolemia (FH) is currently underdiagnosed and undertreated. The establishment of a FH registry could facilitate a deeper understanding of this disease. We described the clinical characteristics of subjects with FH from the Thai FH Registry, compared our data with the regional and global data, and identified gaps in the care of these subjects.

Relief of Obstructive Shock with a Large Hiatal Hernia Occupying the Posterior Mediastinum by Urgent Endoscopy: A Case Report.

A 78-year-old man was admitted to our hospital with obstructive shock caused by a large hiatal hernia that occupied the posterior mediastinum. Tension gastro-duodenothorax was detected in his stomach and duodenum, and we performed urgent endoscopy to relieve shock. Large hiatal hernia occasionally leads to cardiac failure. This is the first reported use of urgent endoscopy to treat a large hiatal hernia.

A Case of Successful Catheter Ablation for Paroxysmal Supraventricular Tachycardia with Two Alternating Cycle Lengths.

A 62-year-old male was transferred to our hospital complaining of palpitations. His heart rate was 185/min. Electrocardiogram showed a narrow QRS regular tachycardia and the tachycardia changed spontaneously to another narrow QRS tachycardia with two alternating cycle lengths. The arrhythmia was stopped by the administration of adenosine triphosphate. Findings from electrophysiological study suggested that there was an accessory pathway (AP) and dual atrioventricular (AV) nodal pathways. After AP ablation, any other tachyarrythmias were not induced. We supposed that the tachycardia was paroxysmal supraventricular tachycardia involving AP and anterograde conduction alternating between slow and fast AV nodal pathways.

[Transition of Japanese clinical guidelines for myasthenia gravis].

The Japanese clinical guidelines for myasthenia gravis (MG) were revised in 2022. The major revision points in these guidelines are as follows. 1) A description of Lambert-Eaton myasthenic syndrome (LEMS) was included for the first time. 2) Revised diagnostic criteria of both MG and LEMS are proposed. 3) A high-dose oral steroid regimen with escalation and de-escalation schedule is not recommended. 4) Refractory MG is defined. 5) The use of molecular-targeted drugs is included. 6) MG is divided into six clinical subtypes. 7) Treatment algorithms for both MG and LEMS are presented.

[A case of lithium intoxication with reversible parkinsonism].

A 73-year-old man, who had been treated for bipolar disorder since he was 39 years old, was admitted because he had developed difficulty in walking and moving his hands for the past 2 months. He was suspected of having Parkinson's syndrome. On admission, his blood lithium level was at the upper limit of normal (1.34 mEq/l), but his food intake gradually decreased and his communication difficulties worsened. On the sixth day of hospitalization, his blood lithium level was in the toxic range (2.44 mEq/l). His general condition, including motor symptoms, improved after lithium medication was discontinued and infusions (normal saline) were started. On the 24th day of admission, he was transferred to the psychiatry department for a psychotropic medication adjustment. It is important to note that chronic intoxication can occur even at the upper limit of the therapeutic range and that salt reduction at the start of the inpatient diet may be a trigger for intoxication.

Genetic and epidemiological analyses of infection load and its relationship with psychiatric disorders.

Severe infections and psychiatric disorders have a large impact on both society and the individual. Studies investigating these conditions and the links between them are therefore important. Most past studies have focused on binary phenotypes of particular infections or overall infection, thereby losing some information regarding susceptibility to infection as reflected in the number of specific infection types, or sites, which we term infection load. In this study we found that infection load was associated with increased risk for attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, schizophrenia and overall psychiatric diagnosis. We obtained a modest but significant heritability for infection load (

Fetal pulmonary artery Doppler blood flow velocity measures and early infant lung function. A prospective cohort study.

Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function.

Evaluation of genetic demultiplexing of single-cell sequencing data from model species.

Single-cell sequencing (sc-seq) provides a species agnostic tool to study cellular processes. However, these technologies are expensive and require sufficient cell quantities and biological replicates to avoid artifactual results. An option to address these problems is pooling cells from multiple individuals into one sc-seq library. In humans, genotype-based computational separation (i.e., demultiplexing) of pooled sc-seq samples is common. This approach would be instrumental for studying non-isogenic model organisms. We set out to determine whether genotype-based demultiplexing could be more broadly applied among species ranging from zebrafish to non-human primates. Using such non-isogenic species, we benchmark genotype-based demultiplexing of pooled sc-seq datasets against various ground truths. We demonstrate that genotype-based demultiplexing of pooled sc-seq samples can be used with confidence in several non-isogenic model organisms and uncover limitations of this method. Importantly, the only genomic resource required for this approach is sc-seq data and a de novo transcriptome. The incorporation of pooling into sc-seq study designs will decrease cost while simultaneously increasing the reproducibility and experimental options in non-isogenic model organisms.

Drop-Set Resistance Training versus Pyramidal and Traditional Sets Elicits Greater Psychophysiological Responses in Men.

We compared the effects of resistance training (ResisT) to pyramidal and traditional weightlifting sets on men's psychophysiological responses. In a randomized crossover design, 24 resistance-trained males performed drop-set, descending pyramid, and traditional ResisT in the barbell back squat, 45° leg press, and seated knee extension. We assessed participants' rating of perceived exertion (RPE) and feelings of pleasure/displeasure (FPD) at the end of each set and at 10, 15, 20, and 30 minutes post-session. No differences were detected across ResisT Methods in total training volume (

Discriminating Single Nucleotide Variations in Solid-State Nanopores by Evaluating the Combination Efficiency between DNA Polymerase and Its Substrate.

A single nucleotide variant present between two otherwise identical nucleic acids will have unexpected functional consequences frequently. Here, a neoteric single nucleotide variation (SNV) detection assay that integrates two complementary nanotechnology systems, nanoassembly technology and an ingenious nanopore biosensing platform, has been applied to this research. Specifically, we set up a detection system to reflect the binding efficiency of the polymerase and nanoprobe through the difference of nanopore signals and then explore the effect of base mutation at the binding site. In addition, machine learning based on support vector machines is used to automatically classify characteristic events mapped by nanopore signals. Our system reliably discriminates single nucleotide variants at binding sites, even possessing the recognition among transitions, transversions, and hypoxanthine (base I). Our results demonstrate the potential of solid-state nanopore detection for SNV and provide some ideas for expanding solid-state nanopore detection platforms.

Communication functions of adult patients admitted to intensive care: A multicentre, binational point prevalence study.

Patient communication is profoundly impacted during the intensive care unit (ICU) stay. While the impacts of altered communication are recognised, there is a paucity of data on the prevalence of communication attempts as well as modes utilised by patients and unit practices to manage communication function.

International investigation on temporary anchorage device use: A survey of orthodontists.

This study investigates characteristics of temporary anchorage devices (TADs) use by surveying a sample of international orthodontists. Furthermore, the survey investigates the stability, insertion technique, and failure rate of TADs and professionals' experience in residency, and it also attempts to establish guidelines for its use in everyday practice.

Within-host modeling to measure dynamics of antibody responses after natural infection or vaccination: A systematic review.

Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This systematic review aims to summarize which within-host methodology has been used to study and quantify antibody kinetics after infection or vaccination. In particular, we focus on data-driven and theory-driven mechanistic models.

Influences of sociodemographic characteristics and parental HPV vaccination hesitancy on HPV vaccination coverage in five US states.

In the United States (US), half of new human papillomavirus (HPV) infections occur among young people aged 15-24 years. Despite the effectiveness of HPV vaccination in protecting against HPV-associated cancers, its coverage among adolescents remains suboptimal. This study examined the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage in five US states with disproportionately low adolescent coverage rates compared to the national average.

Preferred and actual involvement of caregivers in oncologic treatment decision-making: A systematic review.

Treatment decision-making in cancer is complex and many patients bring their caregiver to appointments to help them make those decisions. Multiple studies show the importance of involving caregivers in the treatment decision-making process. We aimed to explore the preferred and actual involvement of caregivers in the decision-making process of patients with cancer and to see if there are age or cultural background related differences in caregiver involvement.

What is malignant hyperthermia susceptibility?

The molecular mechanisms of susceptibility to malignant hyperthermia are complex. The malignant hyperthermia susceptibility phenotype should be reserved for patients who have a personal or family history consistent with malignant hyperthermia under anaesthesia and are subsequently demonstrated through diagnostic testing to be at risk.

From mouthpiece of an emerging specialty to voice for high-quality research: the first 100 years of the British Journal of Anaesthesia.

The British Journal of Anaesthesia (BJA) celebrates its centenary in 2023, and with it 100 yr of continuous anaesthesia research publication. As an editorially and financially independent journal, the BJA faced a rapidly changing anaesthesia profession, health system, and publishing world without the security of institutional support. In its early days, the Journal was vocal about the challenging conditions faced by anaesthetists before the National Health System was established, and was essential in advocating for the specialty. Although the years after World War II brought improving fortunes for the specialty, the BJA found itself struggling to publish. As the Journal's fortunes began to improve, a new research and healthcare context emerged, radically changing the face of anaesthesia research and practice, to which the Journal needed to adapt. In spite of a range of challenges throughout the years, the BJA has developed into an international, future-focused, well-respected publication. This could not have been achieved without continual transformation, and the willingness to take risks and meet the changing times head on.

Actionable artificial intelligence: Overcoming barriers to adoption of prediction tools.

Clinical prediction models based on artificial intelligence algorithms can potentially improve patient care, reduce errors, and add value to the health care system. However, their adoption is hindered by legitimate economic, practical, professional, and intellectual concerns. This article explores these barriers and highlights well-studied instruments that can be used to overcome them. Adopting actionable predictive models will require the purposeful incorporation of patient, clinical, technical, and administrative perspectives. Model developers must articulate a priori clinical needs, ensure explainability and low error frequency and severity, and promote safety and fairness. Models themselves require ongoing validation and monitoring to address variations in health care settings and must comply with an evolving regulatory environment. Through these principles, surgeons and health care providers can leverage artificial intelligence to optimize patient care.

Effects of Multimodal Exercise on Health-related Physical Fitness and Quality of Life in Patients with Nasopharyngeal Carcinoma during Radiotherapy.

The health-related physical fitness of patients with nasopharyngeal carcinoma can decrease significantly during radiotherapy, which can adversely affect their quality of life.

Mortality related to pressure ulcers in Czech Republic - Analyses of national health registries.

Pressure ulcers/pressure injuries (PUs/PIs) relate to decreasing quality of life, prolonged hospitalisation, the increased economic cost of care, and increased mortality. That's why this study focused on one of the mentioned factors - mortality.

An analog-digital hybrid technique for immediate dentures with idealized border extensions.

In patients with severe tooth mobility, conventional impression making can be challenging because of the risk of accidental tooth extraction. Digital intraoral scanning avoids such a complication but does not capture optimal border extensions for a complete denture. This clinical report presents a combined digital and analog recording technique which allows the recording of optimal vestibular border extensions without the risk of tooth extraction.

Leveraging eco-evolutionary models for gene drive risk assessment.

Engineered gene drives create potential for both widespread benefits and irreversible harms to ecosystems. CRISPR-based systems of allelic conversion have rapidly accelerated gene drive research across diverse taxa, putting field trials and their necessary risk assessments on the horizon. Dynamic process-based models provide flexible quantitative platforms to predict gene drive outcomes in the context of system-specific ecological and evolutionary features. Here, we synthesize gene drive dynamic modeling studies to highlight research trends, knowledge gaps, and emergent principles, organized around their genetic, demographic, spatial, environmental, and implementation features. We identify the phenomena that most significantly influence model predictions, discuss limitations of biological complexity and uncertainty, and provide insights to promote responsible development and model-assisted risk assessment of gene drives.

Transoral endoscopic thyroidectomy vestibular approach (TOETVA). Recommendations of the AFCE (Francophone Association of Endocrine Surgery) with the SFE (French Society of Endocrinology) and the SFMN (French Society of Nuclear Medicine).

Transoral endoscopic thyroidectomy vestibular approach (TOETVA) can be proposed for selected patients with a thyroid volume<45mL and/or a nodule<4cm (for Bethesda category II, III or IV lesions), or<2cm (for Bethesda category V or VI lesions), with no suspicion of lateral nodal involvement or mediastinal extension who wish to avoid a cervical scar. Such patients should have satisfactory dental status, have been educated on the specific risks of the transoral route and the need for perioperative oral care, and also fully informed regarding the lack of proof of TOETVA effectiveness in terms of quality of life and patient satisfaction. The patient should be made aware of the possibility of postoperative pain in the neck cervical and chin, which may persist for several days to a few weeks after the intervention. Transoral endoscopic thyroidectomy should be performed in centers with expertise in thyroid surgery.

A core set of quality performance indicators for HPB procedures: a global consensus for hepatectomy, pancreatectomy, and complex biliary surgery.

Surgery for hepatopancreaticobiliary (HPB) conditions is performed worldwide. This investigation aimed to develop a set of globally accepted procedural quality performance indicators (QPI) for HPB surgical procedures.

Nontechnical Skills for Surgeons as a Framework to Evaluate Cardiopulmonary Bypass Management Skills of Resident Trainees.

Nontechnical skills are critical in cardiac surgery but currently there is no formal paradigm to teach these in residency training. We investigated the use of the Nontechnical skills for surgeons (NOTSS) system as a framework to assess and teach nontechnical skills related to cardiopulmonary bypass (CPB) management.

Role of Quantitation of Saline Bubble Studies in Patients with Liver Cirrhosis.

Microbubble contrast echocardiography with a late positive signal enables the detection of intrapulmonary vascular dilation, including hepatopulmonary syndrome, in patients with end-stage liver disease. We assessed the relationship between the severity of bubble study and clinical outcome.

Pharmacy faculty experiences and perceptions of academic dishonesty.

Academic dishonesty (AD) continues to be an area of concern in pharmacy education. While studies have been conducted evaluating various forms and interventions to address AD, few have looked at faculty experiences and perceptions of AD in doctor of pharmacy (PharmD) programs in the United States.

Fecal cytolysin does not predict disease severity in acutely decompensated cirrhosis and acute-on-chronic liver failure.

Cirrhosis with acute decompensation (AD) and acute-on-chronic liver failure (ACLF) are characterized by high morbidity and mortality. Cytolysin, a toxin from Enterococcus faecalis (E. faecalis), is associated with mortality in alcohol-associated hepatitis (AH). It is unclear whether cytolysin also contributes to disease severity in AD and ACLF.

Overground walking with a constraint force on the nonparetic leg during swing improves weight shift toward the paretic side in people after stroke.

Targeting enhancing the use of the paretic leg during locomotor practice might improve motor function of the paretic leg. The purpose of this study was to determine whether application of constraint force to the nonparetic leg in the posterior direction during overground walking would enhance the use of the paretic leg in people with chronic stroke. Fifteen individuals after stroke participated in two experimental conditions, i.e., overground walking with a constraint force applied to the nonparetic leg and overground walking only. Each participant was tested in the following procedures that consisted of overground walking with either constraint force or no constraint force, instrumented split-belt treadmill walking, and pressure-sensitive gait mat walking before and after the overground walking. Overground walking practice with constraint force resulted in greater enhancement in lateral weight shift toward the paretic side (

The role of rumination in the relationship between symptoms of insomnia and depression in adolescents.

There is a strong relationship between the symptoms of insomnia and depression, however, little is understood about the factors that mediate this relationship. An understanding of these underlying mechanisms may inform the advancement of existing treatments to optimise reductions in insomnia and depression when they co-occur. This study examined rumination and unhelpful beliefs about sleep as mediators between symptoms of insomnia and depression. It also evaluated the effect of cognitive behavioural therapy for insomnia (CBT-I) on rumination and unhelpful beliefs about sleep, and whether these factors mediated the effect of CBT-I on depressive symptoms. A series of mediation analyses and linear mixed modelling were conducted on data from 264 adolescents (12-16 years) who participated in a two-arm (intervention vs. control) randomised controlled trial of Sleep Ninja®, a CBT-I smartphone app for adolescents. Rumination, but not unhelpful beliefs about sleep, was a significant mediator between symptoms of insomnia and depression at baseline. CBT-I led to reductions in unhelpful beliefs about sleep, but not in rumination. At the between-group level, neither rumination, nor unhelpful beliefs about sleep emerged as mechanisms underlying improvement in depression symptoms, however, rumination mediated within-subject improvements following CBT-I. The findings suggest rumination links symptoms of insomnia and depression and provide preliminary evidence that reductions in depression following CBT-I occurs via improvements in rumination. Targeting rumination may improve current therapeutic approaches.

Social Media for Chemistry Scholars.

Used by nearly 60 % of the world's population, social media are highly interactive websites ("platforms") today widely used also by researchers. This perspective aims at identifying the main benefits of social media utilization by chemistry scholars with respect to the three main dimensions (research, education and societal service) of scholarly activity. The main risks arising from the use of social media, as we suggest in the conclusions, must be managed and new education on their purposeful utilization should be planned and delivered.

The EZH2-PRC2-H3K27me3 axis governs the endometrial cell cycle and differentiation for blastocyst invasion.

Infertility occurs in 15% of couples worldwide. Recurrent implantation failure (RIF) is one of the major problems in in vitro fertilization and embryo transfer (IVF-ET) programs, and how to manage patients with RIF to achieve successful pregnancy outcomes remains unresolved. Here, a uterine polycomb repressive complex 2 (PRC2)-regulated gene network was found to control embryo implantation. Our RNA-seq analyses of the human peri-implantation endometrium obtained from patients with RIF and fertile controls revealed that PRC2 components, including its core enzyme enhancer of zeste homolog 2 (EZH2)-catalyzing H3K27 trimethylation (H3K27me3) and their target genes are dysregulated in the RIF group. Although fertility of uterine epithelium-specific knockout mice of Ezh2 (eKO mice) was normal, Ezh2-deleted mice in the uterine epithelium and stroma (uKO mice) exhibited severe subfertility, suggesting that stromal Ezh2 plays a key role in female fertility. The RNA-seq and ChIP-seq analyses revealed that H3K27me3-related dynamic gene silencing is canceled, and the gene expression of cell-cycle regulators is dysregulated in Ezh2-deleted uteri, causing severe epithelial and stromal differentiation defects and failed embryo invasion. Thus, our findings indicate that the EZH2-PRC2-H3K27me3 axis is critical to preparing the endometrium for the blastocyst invasion into the stroma in mice and humans.

Ultralong 100 ns spin relaxation time in graphite at room temperature.

Graphite has been intensively studied, yet its electron spins dynamics remains an unresolved problem even 70 years after the first experiments. The central quantities, the longitudinal (T

Dysfunction of the neurovascular unit in brain aging.

An emerging concept termed the neurovascular unit (NVU) underlines neurovascular coupling. It has been reported that NVU impairment can result in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Aging is a complex and irreversible process caused by programmed and damage-related factors. Loss of biological functions and increased susceptibility to additional neurodegenerative diseases are major characteristics of aging. In this review, we describe the basics of the NVU and discuss the effect of aging on NVU basics. Furthermore, we summarize the mechanisms that increase NVU susceptibility to neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Finally, we discuss new treatments for neurodegenerative diseases and methods of maintaining an intact NVU that may delay or diminish aging.

Nuclear softening mediated by Sun2 suppression delays mechanical stress-induced cellular senescence.

Nuclear decoupling and softening are the main cellular mechanisms to resist mechanical stress-induced nuclear/DNA damage, however, its molecular mechanisms remain much unknown. Our recent study of Hutchinson-Gilford progeria syndrome (HGPS) disease revealed the role of nuclear membrane protein Sun2 in mediating nuclear damages and cellular senescence in progeria cells. However, the potential role of Sun2 in mechanical stress-induced nuclear damage and its correlation with nuclear decoupling and softening is still not clear. By applying cyclic mechanical stretch to mesenchymal stromal cells (MSCs) of WT and Zmpset24

Gender specific factors contributing to cognitive resilience in APOE ɛ4 positive older adults in a population-based sample.

Although APOE ɛ4 has been identified as the strongest genetic risk factor for Alzheimer's Disease, there are some APOE ɛ4 carriers who do not go on to develop Alzheimer's disease or cognitive impairment. This study aims to investigate factors contributing to this "resilience" separately by gender. Data were drawn from APOE ɛ4 positive participants who were aged 60 + at baseline in the Personality and Total Health Through Life (PATH) Study (N = 341, Women = 46.3%). Participants were categorised into "resilient" and "non-resilient" groups using Latent Class Analysis based on their cognitive impairment status and cognitive trajectory across 12 years. Logistic regression was used to identify the risk and protective factors that contributed to resilience stratified by gender. For APOE ɛ4 carriers who have not had a stroke, predictors of resilience were increased frequency of mild physical activity and being employed at baseline for men, and increased number of mental activities engaged in at baseline for women. The results provide insights into a novel way of classifying resilience among APOE ɛ4 carriers and risk and protective factors contributing to resilience separately for men and women.

Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia.

Our previous study has announced that phosphorylated microtubule-associated protein 4 (p-MAP4) accelerated keratinocytes migration and proliferation under hypoxia through depolymerizing microtubules. However, p-MAP4 should exhibit inhibitory effects on wound healing, for it also impaired mitochondria. Thus, figuring out the outcome of p-MAP4 after it impaired mitochondria and how the outcome influenced wound healing were far-reaching significance. Herein, the results revealed that p-MAP4 might undergo self-degradation through autophagy in hypoxic keratinocytes. Next, p-MAP4 activated mitophagy which was unobstructed and was also the principal pathway of its self-degradation triggered by hypoxia. Moreover, both Bcl-2 homology 3 (BH3) and LC3 interacting region (LIR) domains had been verified in MAP4, and they endowed MAP4 with the capability to synchronously function as a mitophagy initiator and a mitophagy substrate receptor. And, mutating any one of them ruined hypoxia-induced self-degradation of p-MAP4, resulting in destroyed proliferation and migration responses of keratinocytes to hypoxia. Our findings unviewed that p-MAP4 experienced mitophagy-associated self-degradation through utilizing its BH3 and LIR domains under hypoxia. As a result, the mitophagy-associated self-degradation of p-MAP4 guaranteed the migration and proliferation responses of keratinocytes to hypoxia. Together, this research provided a bran-new pattern of proteins in regulating wound healing, and offered a new direction for intervening wound healing.

hucMSC-derived exosomes protect ovarian reserve and restore ovarian function in cisplatin treated mice.

Anti-cancer therapy often causes premature ovarian insufficiency and infertility as the ovarian follicle reserve is extremely sensitive to chemotherapy drugs, such as cisplatin. Various fertility preservation methods have been explored for women, especially prepubertal girls undergoing radiotherapy and chemotherapy due to cancer. In recent years, mesenchymal stem cell-derived exosomes (MSC-exos) have been reported to play an important role in tissue repair and the treatment of various diseases. In the current study, we observed that human umbilical cord-derived MSC-exos (hucMSC-exos) after short-term culture improved follicular survival and development while receiving cisplatin treatment. Moreover, intravenous injection of hucMSC-exos improved ovarian function and ameliorated inflammatory environment within the ovary. The underlying mechanism of hucMSC-exos on fertility preservation was associated with the down-regulation of p53-related apoptosis and their anti-inflammatory function. Based on these findings, we propose that hucMSC-exos may be a potential approach to improve fertility in women diagnosed with cancer.

Structural analysis and architectural principles of the bacterial amyloid curli.

Two decades have passed since the initial proposition that amyloids are not only (toxic) byproducts of an unintended aggregation cascade, but that they can also be produced by an organism to serve a defined biological function. That revolutionary idea was borne out of the realization that a large fraction of the extracellular matrix that holds Gram-negative cells into a persistent biofilm is composed of protein fibers (curli; tafi) with cross-β architecture, nucleation-dependent polymerization kinetics and classic amyloid tinctorial properties. The list of proteins shown to form so-called functional amyloid fibers in vivo has greatly expanded over the years, but detailed structural insights have not followed at a similar pace in part due to the associated experimental barriers. Here we combine extensive AlphaFold2 modelling and cryo-electron transmission microscopy to propose an atomic model of curli protofibrils, and their higher modes of organization. We uncover an unexpected structural diversity of curli building blocks and fibril architectures. Our results allow for a rationalization of the extreme physico-chemical robustness of curli, as well as earlier observations of inter-species curli promiscuity, and should facilitate further engineering efforts to expand the repertoire of curli-based functional materials.

Wood xerogel for fabrication of high-performance transparent wood.

Optically transparent wood has been fabricated by structure-retaining delignification of wood and subsequent infiltration of thermo- or photocurable polymer resins but still limited by the intrinsic low mesopore volume of the delignified wood. Here we report a facile approach to fabricate strong transparent wood composites using the wood xerogel which allows solvent-free infiltration of resin monomers into the wood cell wall under ambient conditions. The wood xerogel with high specific surface area (260 m

The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson's disease in mainland China.

So far, over 20 causative genes of monogenic Parkinson's disease (PD) have been identified. Some causative genes of non-parkinsonian entities may also manifest with parkinsonism mimicking PD. This study aimed to investigate the genetic characteristics of clinically diagnosed PD with early onset age or family history. A total of 832 patients initially diagnosed with PD were enrolled, of which, 636 were classified into the early-onset group and 196 were classified into the familial late-onset group. The genetic testing included the multiplex ligation-dependent probe amplification and next generation sequencing (target sequencing or whole-exome sequencing). The dynamic variants of spinocerebellar ataxia were tested in probands with family history. In the early-onset group, 30.03% of patients (191/636) harbored pathogenic/likely pathogenic (P/LP) variants in known PD-related genes (CHCHD2, DJ-1, GBA (heterozygous), LRRK2, PINK1, PRKN, PLA2G6, SNCA and VPS35). Variants in PRKN were the most prevalent, accounting for 15.72% of the early-onset patients, followed by GBA (10.22%), and PLA2G6 (1.89%). And 2.52% (16/636) had P/LP variants in causative genes of other diseases (ATXN3, ATXN2, GCH1, TH, MAPT, GBA (homozygous)). In the familial late-onset group, 8.67% of patients (17/196) carried P/LP variants in known PD-related genes (GBA (heterozygous), HTRA2, SNCA) and 2.04% (4/196) had P/LP variants in other genes (ATXN2, PSEN1, DCTN1). Heterozygous GBA variants (7.14%) were the most common genetic cause found in familial late-onset patients. Genetic testing is of vital importance in differential diagnosis especially in early-onset and familial PD. Our findings may also provide some clues to the nomenclature of genetic movement disorders.

A Doppler-exclusive non-invasive computational diagnostic framework for personalized transcatheter aortic valve replacement.

Given the associated risks with transcatheter aortic valve replacement (TAVR), it is crucial to determine how the implant will affect the valve dynamics and cardiac function, and if TAVR will improve or worsen the outcome of the patient. Effective treatment strategies, indeed, rely heavily on the complete understanding of the valve dynamics. We developed an innovative Doppler-exclusive non-invasive computational framework that can function as a diagnostic tool to assess valve dynamics in patients with aortic stenosis in both pre- and post-TAVR status. Clinical Doppler pressure was reduced by TAVR (52.2 ± 20.4 vs. 17.3 ± 13.8 [mmHg], p < 0.001), but it was not always accompanied by improvements in valve dynamics and left ventricle (LV) hemodynamics metrics. TAVR had no effect on LV workload in 4 patients, and LV workload post-TAVR significantly rose in 4 other patients. Despite the group level improvements in maximum LV pressure (166.4 ± 32.2 vs 131.4 ± 16.9 [mmHg], p < 0.05), only 5 of the 12 patients (41%) had a decrease in LV pressure. Moreover, TAVR did not always improve valve dynamics. TAVR did not necessarily result in a decrease (in 9 out of 12 patients investigated in this study) in major principal stress on the aortic valve leaflets which is one of the main contributors in valve degeneration and, consequently, failure of heart valves. Diastolic stresses increased significantly post-TAVR (34%, 109% and 81%, p < 0.001) for each left, right and non-coronary leaflets respectively. Moreover, we quantified the stiffness and material properties of aortic valve leaflets which correspond with the reduced calcified region average stiffness among leaflets (66%, 74% and 62%; p < 0.001; N = 12). Valve dynamics post-intervention should be quantified and monitored to ensure the improvement of patient conditions and prevent any further complications. Improper evaluation of biomechanical valve features pre-intervention as well as post-intervention may result in harmful effects post-TAVR in patients including paravalvular leaks, valve degeneration, failure of TAVR and heart failure.

Underweight and risk of fractures in adults over 40 years using the nationwide claims database.

We aimed to investigate how underweight affects the incidence of fractures, as well as the influence of cumulative, longitudinal periods of low body mass index (BMI) and changes in body weight on fracture development. Data on adults aged 40-year and over who had three health screenings between January 1, 2007, and December 31, 2009 were used to determine the incidence of new fractures. The hazard ratios (HRs) for new fractures depending on BMI, total cumulative number of underweight, and weight change over time were calculated using Cox proportional hazard analysis. In this study, 15,955 (2.8%) of the 561,779 adults were diagnosed with fractures more than once over three health examinations. The fully adjusted HR for fractures in underweight individuals was 1.173 (95% Confidence interval [CI] 1.093-1.259). Underweight individuals diagnosed only once, twice, or three times had an adjusted HR of 1.227 (95%CI 1.130-1.332), 1.174 (95%CI 1.045-1.319), and 1.255 (95%CI 1.143-1.379), respectively. Although the adjusted HR was higher in adults who consistently had underweight (HR; 1.250 [95%CI 1.146-1.363]), those with underweight had an increased risk of fractures regardless of weight change (HR; 1.171 [95%CI 1.045-1.312], and 1.203[95%CI 1.075-1.346]). Underweight is a risk factor for fractures in adults over the age of 40 years, even if they returned to normal weight.

Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice.

Apigenin (APN), a flavone found in several plant foods with various biological properties such as anti-obesity, anti-inflammation and other abilities, alleviates atherosclerosis and non-alcoholic fatty liver disease (NAFLD) induced by a high fat diet (HFD) in mice. However, the underlying mechanisms have not been fully understood. In this study, we investigated the role of NLRP3 in anti-atherosclerosis and anti-NAFLD effect of APN in mouse models with NLRP3 deficiency. Atherosclerosis and NAFLD models were established by treatment of low density lipoprotein receptor-deficient (Ldlr

A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity.

Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization (dpf) to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-α and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal model also proved to be appropriate and effective in evaluating the inflammatory process, comparable to humans.

Pharmacological inhibition of BCL-2 with the FDA-approved drug venetoclax impairs longitudinal bone growth.

Treatment-related skeletal complications are common in childhood cancer patients and survivors. Venetoclax is a BCL-2 inhibitor that has shown efficacy in hematological malignancies in adults and is being investigated in pediatric cancer clinical trials as a promising therapeutic modality. Venetoclax triggers cell death in cancer cells, but whether it exerts similar effects in normal bone cells, is unknown. Chondrogenic ATDC5 cells, E20 fetal rat metatarsal bones, and human growth plate biopsies were treated with different concentrations of venetoclax. Female NMRI nu/nu mice were treated with venetoclax or vehicle for 15 days. Mice were X-rayed at baseline and at the end of the experiment to assess longitudinal bone growth and body weight was monitored throughout the study. Histomorphometric and immunohistochemical analyses were performed to evaluate treatment effects on the growth plate cartilage. Venetoclax decreased the viability of chondrocytes and impaired the growth of ex vivo cultured metatarsals while reducing the height of the resting/proliferative zone and the hypertrophic cell size. When tested in vivo, venetoclax suppressed bone growth and reduced growth plate height. Our experimental data suggest that venetoclax directly targets growth plate chondrocytes suppressing bone growth and we, therefore, encourage careful monitoring of longitudinal bone growth if treating growing children with venetoclax.

Indel driven rapid evolution of core nuclear pore protein gene promoters.

Nuclear pore proteins (Nups) prominently are among the few genes linked to speciation from hybrid incompatibility in Drosophila. These studies have focused on coding sequence evolution of Nup96 and Nup160 and shown evidence of positive selection driving nucleoporin evolution. Intriguingly, channel Nup54 functionality is required for neuronal wiring underlying the female post-mating response induced by male-derived sex-peptide. A region of rapid evolution in the core promoter of Nup54 suggests a critical role for general transcriptional regulatory elements at the onset of speciation, but whether this is a general feature of Nup genes has not been determined. Consistent with findings for Nup54, additional channel Nup58 and Nup62 promoters also rapidly accumulate insertions/deletions (indels). Comprehensive examination of Nup upstream regions reveals that core Nup complex gene promoters accumulate indels rapidly. Since changes in promoters can drive changes in expression, these results indicate an evolutionary mechanism driven by indel accumulation in core Nup promoters. Compensation of such gene expression changes could lead to altered neuronal wiring, rapid fixation of traits caused by promoter changes and subsequently the rise of new species. Hence, the nuclear pore complex may act as a nexus for species-specific changes via nucleo-cytoplasmic transport regulated gene expression.

SIRT6-PAI-1 axis is a promising therapeutic target in aging-related bone metabolic disruption.

The mechanistic regulation of bone mass in aged animals is poorly understood. In this study, we examined the role of SIRT6, a longevity-associated factor, in osteocytes, using mice lacking Sirt6 in Dmp-1-expressing cells (cKO mice) and the MLO-Y4 osteocyte-like cell line. cKO mice exhibited increased osteocytic expression of Sost, Fgf23 and senescence inducing gene Pai-1 and the senescence markers p16 and Il-6, decreased serum phosphate levels, and low-turnover osteopenia. The cKO phenotype was reversed in mice that were a cross of PAI-1-null mice with cKO mice. Furthermore, senescence induction in MLO-Y4 cells increased the Fgf23 and Sost mRNA expression. Sirt6 knockout and senescence induction increased HIF-1α binding to the Fgf23 enhancer sequence. Bone mass and serum phosphate levels were higher in PAI-1-null aged mice than in wild-type mice. Therefore, SIRT6 agonists or PAI-1 inhibitors may be promising therapeutic options for aging-related bone metabolism disruptions.

Selective area multilayer graphene synthesis using resistive nanoheater probe.

Graphene has been a material of interest due to its versatile properties and wide variety of applications. However, production has been one of the most challenging aspects of graphene and multilayer graphene (MLG). Most synthesis techniques require elevated temperatures and additional steps to transfer graphene or MLG to a substrate, which compromises the integrity of the film. In this paper, metal-induced crystallization is explored to locally synthesize MLG directly on metal films, creating an MLG-metal composite and directly on insulating substrates with a moving resistive nanoheater probe at much lower temperature conditions (~ 250 °C). Raman spectroscopy shows that the resultant carbon structure has properties of MLG. The presented tip-based approach offers a much simpler MLG fabrication solution by eliminating the photolithographic and transfer steps of MLG.

MSHF: A Multi-Source Heterogeneous Fundus (MSHF) Dataset for Image Quality Assessment.

Image quality assessment (IQA) is significant for current techniques of image-based computer-aided diagnosis, and fundus imaging is the chief modality for screening and diagnosing ophthalmic diseases. However, most of the existing IQA datasets are single-center datasets, disregarding the type of imaging device, eye condition, and imaging environment. In this paper, we collected a multi-source heterogeneous fundus (MSHF) database. The MSHF dataset consisted of 1302 high-resolution normal and pathologic images from color fundus photography (CFP), images of healthy volunteers taken with a portable camera, and ultrawide-field (UWF) images of diabetic retinopathy patients. Dataset diversity was visualized with a spatial scatter plot. Image quality was determined by three ophthalmologists according to its illumination, clarity, contrast and overall quality. To the best of our knowledge, this is one of the largest fundus IQA datasets and we believe this work will be beneficial to the construction of a standardized medical image database.

Essential oil yield and compositions of Dracocephalum moldavica L. in intercropping with fenugreek, inoculation with mycorrhizal fungi and bacteria.

Intercropping is one of the most important components of sustainable agriculture. The effects of chemical fertilizer (CF), arbuscular mycorrhizal fungi (AMF) (Glomus sp.) and AMF + nitrogen-fixing bacteria (NFB) including Azospirillum and Azotobacter (AMF + NFB) was studied on essential oil yield and compositions of Moldavian balm (Mb) (Dracocephalum moldavica L.) in sole cropping and intercropping with fenugreek (F) (Trigonella foenum-graecum L.). The experiment was conducted during 2020 and 2021 growing seasons in East Azarbayhan, Iran. The highest dry herbage yield (6132 kg ha

Targeting strategies for bone diseases: signaling pathways and clinical studies.

Since the proposal of Paul Ehrlich's magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has been considered a promising therapeutic approach for handling such drawbacks. With the deepening understanding of bone biology, improvements in some established bone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the horizon. In this review, we provide a panoramic summary of recent advances in therapeutic strategies based on bone targeting. We highlight targeting strategies based on bone structure and remodeling biology. For bone-targeted therapeutic agents, in addition to improvements of the classic denosumab, romosozumab, and PTH1R ligands, potential regulation of the remodeling process targeting other key membrane expressions, cellular crosstalk, and gene expression, of all bone cells has been exploited. For bone-targeted drug delivery, different delivery strategies targeting bone matrix, bone marrow, and specific bone cells are summarized with a comparison between different targeting ligands. Ultimately, this review will summarize recent advances in the clinical translation of bone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and future trends in this area.

The impact of affective states and traits on perceptual stability during binocular rivalry.

Affective states and traits have been associated with different measures of perceptual stability during binocular rivalry. Diverging approaches to measuring perceptual stability as well as to examination of the role of affective variables have contributed to an inconclusive pattern of findings. Here, we studied the influence of affective traits, such as depressiveness and trait anxiety, and states, which were manipulated with a musical mood induction paradigm, on different measures of perceptual stability (dominance ratios and phase durations) during binocular rivalry. Fifty healthy participants reported alternations in two conditions: a biased perception condition with an unequal probability of perceiving stimuli, using an upright versus a tilted face with a neutral expression, and a control condition with equal chances of perceiving stimuli, using Gabors of different orientations. Baseline positive state affect significantly predicted longer phase durations whereas affective traits did not yield any such effect. Furthermore, in an exploratory analysis, induced negative affect attenuated stimulus related bias in predominance ratios. Overall, we found a strong correlation between both measures of perceptual stability (phase durations and dominance ratios). Our findings thus question the distinction between different measures of perceptual stability during binocular rivalry and highlight the role of affective states in its formation.

Happiness predicts compliance with preventive health behaviours during Covid-19 lockdowns.

To combat the public health crisis of Covid-19, governments and public health officials have been asking individuals to substantially change their behaviours for prolonged periods of time. Are happier people more willing to comply with such measures? Using independent, large-scale surveys covering about 79,000 adult respondents across 29 countries, including longitudinal data from the UK, we find that life satisfaction predicts compliance with preventive health behaviours during Covid-19 lockdowns, especially the number of weekdays stood at home (β = 0.02, p < 0.01). The association is stronger for higher levels of life satisfaction (e.g. β = 0.19, p < 0.01, 7 on a 0-to-10 scale). Lower life satisfaction, on the contrary, predicts lower compliance (e.g. β = 0.02, p > 0.10, 2 on a 0-to-10 scale). We explore risk-avoidance and pro-social motivations for this relationship, and find suggestive evidence that people who are older or have certain medical preconditions seem to be behave in line with risk-avoidance, whereas motivations of people who are less at risk of Covid-19 seem more mixed. While it is difficult to estimate the relationship between life satisfaction and compliance behaviour due to potential confounders and unobserved heterogeneity, our findings suggest that life satisfaction is important, both for complying with preventive health measures and as a policy end in itself.

UHPLC-HRMS-based metabolomic and lipidomic characterization of glioma cells in response to anlotinib.

Anlotinib, as a promising oral small-molecule antitumor drug, its role in glioma has been only reported in a small number of case reports. Therefore, anlotinib has been considered as a promising candidate in glioma. The aim of this study was to investigate the metabolic network of C6 cells after exposure to anlotinib and to identify anti-glioma mechanism from the perspective of metabolic reprogramming. Firstly, CCK8 method was used to evaluate the effects of anlotinib on cell proliferation and apoptosis. Secondly, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomic and lipidomic were developed to characterize the metabolite and lipid changes in cell and cell culture medium (CCM) caused by anlotinib in the treatment of glioma. As a result, anlotinib had concentration-dependent inhibitory effect with the concentration range. In total, twenty-four and twenty-three disturbed metabolites in cell and CCM responsible for the intervention effect of anlotinib were screened and annotated using UHPLC-HRMS. Altogether, seventeen differential lipids in cell were identified between anlotinib exposure and untreated groups. Metabolic pathways, including amino acid metabolism, energy metabolism, ceramide metabolism, and glycerophospholipid metabolism, were modulated by anlotinib in glioma cell. Overall, anlotinib has an effective treatment against the development and progression of glioma, and these remarkable pathways can generate the key molecular events in cells treated with anlotinib. Future research into the mechanisms underlying the metabolic changes is expected to provide new strategies for treating glioma.

Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease.

Genome-wide association studies (GWAS) of Alzheimer's disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an additional GWAS from a Caribbean Hispanic population using previously reported genotype data to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer's disease and related dementias to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci with a posterior probability >0.8 and globally assessed the heterogeneity of known risk factors across populations. Additionally, we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to risk of Alzheimer's disease and related dementias.

The impact of methicillin resistance on clinical outcome among patients with Staphylococcus aureus osteomyelitis: a retrospective cohort study of 482 cases.

This study was designed to evaluate the impact of methicillin resistance on the outcomes among patients with S. aureus osteomyelitis. We reviewed all extremity osteomyelitis patients treated in our clinic center between 2013 and 2020. All adult patients with S. aureus pathogen infection were included. Clinical outcome in terms of infection control, length of hospital stay, and complications were observed at the end of a 24-month follow-up and retrospectively analyzed between populations with/without methicillin resistance. In total, 482 osteomyelitis patients due to S. aureus were enrolled. The proportion of methicillin-resistant S. aureus (MRSA) was 17% (82) and 83% (400) of patients had Methicillin-sensitive S. aureus (MSSA). Of 482 patients, 13.7% (66) presented with infection persistence after initial debridement and antibiotic treatment (6 weeks), needed repeated debridement, 8.5% (41) had recurrence after all treatment end and a period infection cure, complications were observed in 17 (3.5%) patients (pathologic fracture; 4, nonunion; 5, amputation; 8) at final follow-up. Following multivariate analysis, we found patients with S. aureus osteomyelitis due to MRSA are more likely to develop a persistent infection (OR: 2.26; 95% CI 1.24-4.13) compared to patients with MSSA. Patients infected with MRSA also suffered more complications (8.5% vs. 2.5%, p = 0.015) and longer hospital stays (median: 32 vs. 23 days, p < 0.001). No statistically significant differences were found in recurrence. The data indicated Methicillin resistance had adverse clinical implication for infection persistence among patients with S. aureus osteomyelitis. These results will help for patients counsel and preparation for treatment.

The diagnostic utility of inspiratory-expiratory radiography for the assessment of phrenic nerve palsy associated with brachial plexus injury.

The phrenic nerve is commonly injured with trauma to the brachial plexus. Hemi-diaphragmatic paralysis may be well-compensated in healthy individuals at rest but can be associated with persistent exercise intolerance in some patients. This study aims to determine the diagnostic value of inspiratory-expiratory chest radiography compared to intraoperative stimulation of the phrenic nerve for assessing phrenic nerve injury associated with brachial plexus injury.

Evaluating the Social Impact of a Proposed Orthopedic Center of Excellence in Northern Tanzania: A Novel Use of the Impact Multiple of Money Methodology.

Musculoskeletal injuries-often a result of Road Traffic Accidents (RTAs)-represent a significant burden in sub-Saharan Africa. RTA victims are faced with lifelong disability and diminished employment. Northern Tanzania in particular lacks the orthopedic surgical capacity needed to provide patients with definitive surgical fixation. While there is great potential in establishing an Orthopedic Center of Excellence (OCE), the precise social impact of such an initiative is currently unknown.

Structural integrity assessment of Inconel 617/P92 steel dissimilar welds for different groove geometry.

The work is focused on examining the effect of the weld groove geometry on microstructure, mechanical behaviour, residual stresses and distortion of Alloy 617/P92 steel dissimilar metal weld (DMW) joints. Manual multi-pass tungsten inert gas welding with ERNiCrCoMo-1 filler was employed to fabricate the DMW for two different groove designs: Narrow V groove (NVG) and Double V groove (NVG). The microstructural examination suggested a heterogeneous microstructure evolution at the interface of the P92 steel and ERNiCrCoMo-1 weld, including the macrosegregation and element diffusion near the interface. The interface structure included the beach parallel to the fusion boundary at the P92 steel side, the peninsula connected to the fusion boundary and the island within the weld metal and partially melted zone along Alloy 617 fusion boundary. An uneven distribution of beach, peninsula and island structures along the fusion boundary of P92 steel was confirmed from optical and SEM images of interfaces. The major diffusion of the Fe from P92 steel to ERNiCrCoMo-1 weld and Cr, Co, Mo, and Ni from ERNiCrCoMo-1 weld to P92 steel were witnessed from SEM/EDS and EMPA map. The Mo-rich M

Single-Center Preliminary Experience with Gutter-Plugging Chimney Stent-Graft for Aortic Dissection.

To report the early 2-year results and experience of a novel gutter-plugging chimney stent-graft in a single center that participated in the clinical trial of Prospective Study for Aortic Arch Therapy with stENt-graft for Chimney technology.

Sophorolipid inhibits histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity.

Biosurfactants are attracting much interest due to their potential application as therapeutic agents in the medical and cosmetic field. Previous studies have demonstrated that biosurfactant such as sophorolipid (SL) exhibits immunomodulatory effects. In this article, we found the potential of sophorolipid for inhibiting histamine-induced itch and preliminarily explored its molecular basis. First, behavioral tests indicated that SL can remit the histamine-induced scratching behaviors of mice. Second, SL can suppress the the calcium influx induced by histamine, HTMT and VUF8430 in HaCaT cells. RT-PCR analysis showed that the histamine-induced upregulation of mRNA levels of phospholipase Cγ1, 1,4,5-trisphosphate receptor (IP3R), and protein kinase Cα can be inhibted by SL, suggesting that SL may impede the PLC/IP3R signaling pathway activated by histamine. In further tests, the capsaicin-induced calcium influx can also be inhibited by SL. The immunofluorescence and molecular docking analysis indicated that SL acts as an inhibitor of transient receptor potential vanilloid-1 (TRPV1) activation to decrease calcium influx against stimuli. In summary, these results revealed that SL may inhibit histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity. This paper indicates that SL can be a useful treatment for histamine-dependent itch.

A holistic and proactive approach to forecasting cyber threats.

Traditionally, cyber-attack detection relies on reactive, assistive techniques, where pattern-matching algorithms help human experts to scan system logs and network traffic for known virus or malware signatures. Recent research has introduced effective Machine Learning (ML) models for cyber-attack detection, promising to automate the task of detecting, tracking and blocking malware and intruders. Much less effort has been devoted to cyber-attack prediction, especially beyond the short-term time scale of hours and days. Approaches that can forecast attacks likely to happen in the longer term are desirable, as this gives defenders more time to develop and share defensive actions and tools. Today, long-term predictions of attack waves are mostly based on the subjective perceptiveness of experienced human experts, which can be impaired by the scarcity of cyber-security expertise. This paper introduces a novel ML-based approach that leverages unstructured big data and logs to forecast the trend of cyber-attacks at a large scale, years in advance. To this end, we put forward a framework that utilises a monthly dataset of major cyber incidents in 36 countries over the past 11 years, with new features extracted from three major categories of big data sources, namely the scientific research literature, news, blogs, and tweets. Our framework not only identifies future attack trends in an automated fashion, but also generates a threat cycle that drills down into five key phases that constitute the life cycle of all 42 known cyber threats.

Promoting active site renewal in heterogeneous olefin metathesis catalysts.

As an atom-efficient strategy for the large-scale interconversion of olefins, heterogeneously catalysed olefin metathesis sees commercial applications in the petrochemical, polymer and speciality chemical industries

Generation of iPSC-derived human forebrain organoids assembling bilateral eye primordia.

Induced pluripotent stem cell-derived brain organoids enable the developmental complexities of the human brain to be deconstructed. During embryogenesis, optic vesicles (OVs), the eye primordium attached to the forebrain, develop from diencephalon. However, most 3D culturing methods generate either brain or retinal organoids individually. Here we describe a protocol to generate organoids with both forebrain entities, which we call OV-containing brain organoids (OVB organoids). In this protocol, we first induce neural differentiation (days 0-5) and collect neurospheres, which we culture in a neurosphere medium to initiate their patterning and further self-assembly (days 5-10). Then, upon transfer to spinner flasks containing OVB medium (days 10-30), neurospheres develop into forebrain organoids with one or two pigmented dots restricted to one pole, displaying forebrain entities of ventral and dorsal cortical progenitors and preoptic areas. Further long-term culture results in photosensitive OVB organoids constituting complementary cell types of OVs, including primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections and electrically active neuronal networks. OVB organoids provide a system to help dissect interorgan interactions between the OVs as sensory organs and the brain as a processing unit, and can help model early eye patterning defects, including congenital retinal dystrophy. To conduct the protocol, experience in sterile cell culture and maintenance of human induced pluripotent stem cells is essential; theoretical knowledge of brain development is advantageous. Furthermore, specialized expertise in 3D organoid culture and imaging for the analysis is needed.

Novel stereological method for estimation of cell counts in 3D collagen scaffolds.

Current methods for assessing cell proliferation in 3D scaffolds rely on changes in metabolic activity or total DNA, however, direct quantification of cell number in 3D scaffolds remains a challenge. To address this issue, we developed an unbiased stereology approach that uses systematic-random sampling and thin focal-plane optical sectioning of the scaffolds followed by estimation of total cell number (StereoCount). This approach was validated against an indirect method for measuring the total DNA (DNA content); and the Bürker counting chamber, the current reference method for quantifying cell number. We assessed the total cell number for cell seeding density (cells per unit volume) across four values and compared the methods in terms of accuracy, ease-of-use and time demands. The accuracy of StereoCount markedly outperformed the DNA content for cases with ~ 10,000 and ~ 125,000 cells/scaffold. For cases with ~ 250,000 and ~ 375,000 cells/scaffold both StereoCount and DNA content showed lower accuracy than the Bürker but did not differ from each other. In terms of ease-of-use, there was a strong advantage for the StereoCount due to output in terms of absolute cell numbers along with the possibility for an overview of cell distribution and future use of automation for high throughput analysis. Taking together, the StereoCount method is an efficient approach for direct cell quantification in 3D collagen scaffolds. Its major benefit is that automated StereoCount could accelerate research using 3D scaffolds focused on drug discovery for a wide variety of human diseases.

Comparative Analysis of Rhizosphere and Endophytic Microbial Communities Between Root Rot and Healthy Root of Psammosilene tunicoides.

The wild resources of Psammosilene tunicoides have decreased sharply because of the long-term mining and excavation, which has led to the increased demand for its artificial cultivation. However, root rot represents a significant obstacle leading to a poor quality and product of P. tunicoides. Previous reports have not focused on root rot in P. tunicoides. Therefore, this study explores the rhizospheric and root endophytic microbial community structure and composition of healthy and root rot P. tunicoides to understand the mechanism underlying root rot. The properties of the rhizosphere soil were assessed using physiochemical methods, and the bacterial and fungal populations were studied through amplicon sequencing of the 16S rRNA genes and ITS regions in the root and soil. Compared to healthy samples, the pH, hydrolysis N, available P, and available K were significantly decreased in the diseased samples while the organic matter and total organic carbon were significantly increased in the diseased samples. Redundancy analysis (RDA) showed that soil environmental factors are related to changes in the root and rhizosphere soil microbial community of P. tunicoides indicating that the physiochemical properties of soil affect plant health. Alpha diversity analysis showed that the microbial communities of healthy and diseased samples were similar. Some bacterial and fungal genera were significantly increased or decreased (P < 0.05) in diseased P. tunicoides, and certain microbial factors that antagonized root rot were further explored. This study provides an abundant microbial resource for future studies and contributes to improving soil quality and P. tunicoides agricultural production.

New secondary metabolites produced by Paraphoma radicina FB55 as potential antifungal agents.

Microorganisms in specific environments are rich sources of bioactive natural products as they produce compounds that can aid their survival in harsh environments. In an effort to investigate antifungal compounds produced by microorganisms, the fungal strain Paraphoma radicia FB55, isolated from a marine sediment of the Beaufort Sea, north of Alaska, was subjected to chemical investigation. Chromatography of the culture extracts yielded two new compounds (1 and 2) and eight known compounds (3-10). Their structures were determined using spectroscopic and chemical methods. Compound 1 was a new analog of the known compound (3) with an isobenzofuranone skeleton. The absolute configuration of the chiral center in 1 was established by comparison of its ECD and specific rotation values with those for a known analogue. Compound 2 is a polyketide-amino acid hybrid. Comprehensive Nuclear Magnetic Resonance (NMR) analysis indicated that 2 consisted of two substructures:5-methyl-6-oxo-2,4-heptadienoic acid and isoleucinol. The absolute configuration of the isoleucinol moiety in 2 was determined to be D using Marfey's method. All the isolated compounds were evaluated for antifungal activities. Although the antifungal activity of the isolated compounds was not potent, co-treatment of compounds 7 and 8 with a clinically available amphotericin B (AmB) lowered the IC

DeepBindPPI: Protein-Protein Binding Site Prediction Using Attention Based Graph Convolutional Network.

Due to the importance of protein-protein interactions in defence mechanism of living body, attempts were made to investigate its attributes, including, but not limited to, binding affinity, and binding region. Contemporary strategies for binding site prediction largely resort to deep learning techniques but turned out to be low precision models. As laboratory experiments for drug discovery tasks utilize this information, increased false positives devalue the computational methods. This emphasize the need to develop enhanced strategies. DeepBindPPI employs deep learning technique to predict the binding regions of proteins, particularly antigen-antibody interaction sites. The results obtained are applied in a docking environment to confirm their correctness. An integration of graph convolutional network with attention mechanism predicts interacting amino acids with improved precision. The model learns the determining factors in interaction from a general pool of proteins and is then fine-tuned using antigen-antibody data. Comparison of the proposed method with existing techniques shows that the developed model has comparable performance. The use of a separate spatial network clearly improved the precision of the proposed method from 0.4 to 0.5. An attempt to utilize the interface information for docking using the HDOCK server gives promising results, with high-quality structures appearing in the top10 ranks.

Serine-arginine protein kinases and their targets in viral infection and their inhibition.

Accumulating evidence has consolidated the interaction between viral infection and host alternative splicing. Serine-arginine (SR) proteins are a class of highly conserved splicing factors critical for the spliceosome maturation, alternative splicing and RNA metabolism. Serine-arginine protein kinases (SRPKs) are important kinases that specifically phosphorylate SR proteins to regulate their distribution and activities in the central pre-mRNA splicing and other cellular processes. In addition to the predominant SR proteins, other cytoplasmic proteins containing a serine-arginine repeat domain, including viral proteins, have been identified as substrates of SRPKs. Viral infection triggers a myriad of cellular events in the host and it is therefore not surprising that viruses explore SRPKs-mediated phosphorylation as an important regulatory node in virus-host interactions. In this review, we briefly summarize the regulation and biological function of SRPKs, highlighting their involvement in the infection process of several viruses, such as viral replication, transcription and capsid assembly. In addition, we review the structure-function relationships of currently available inhibitors of SRPKs and discuss their putative use as antivirals against well-characterized viruses or newly emerging viruses. We also highlight the viral proteins and cellular substrates targeted by SRPKs as potential antiviral therapeutic candidates.

Integrated application of green zero-valent iron and electrokinetic remediation of metal-polluted sediment.

In recent years, more focus has been placed on integrated metal removal processes. Electrokinetic (EK) treatment is superior to other technologies because it can be applied to a variety of mediums. Green nanoparticles, on the other hand, have the potential to significantly reduce pollutant concentrations in a short period of time. In this study, we investigated the possibility of combining green zero-valent iron (nZVI) with EK on Cd and Zn-contaminated sediment. For green synthesis, extracts of dry leaves of mulberry (ML-nZVI) and oak (OL-nZVI) were used, both abundantly present in the Republic of Serbia. The results show that, despite the fact that their availability was greatly reduced, the metals were concentrated and stabilized to a significant extent in the middle of the EK cell (z/L 0.5) after all treatments. When the results were compared, OL-nZVI proved to be a more effective nanomaterial even with smaller doses of OL-nZVI, which is important in terms of achieving better economic benefits. This study identified green nano zero-valent iron as a powerful tool for metal removal when combined with electrokinetic (EK) treatment, which improves green nZVI longevity and migration. This study of the combined green nZVI-EK remediation treatment, in particular, will have an impact on future research in this field, given the achieved efficiency.

DNA controllable peroxidase-like activity of Ti

The peroxidase-like activity of Ti

A practice study of land and water comprehensive remediation in urban-rural fringe-with Sichuan River Shaanxi Province, Northwest China, as an example.

Urban-rural fringe area (URFa) is an active and expansive region, and its environment is complex and frangible. Previous studies have focused on the landscape spatial pattern changes, the spatial-temporal variability of soil pollutants and the land management and policy issues, etc., but it is lack of the practice study of land and water comprehensive remediation in URFa. This article is taking the Sichuan River, a typical URFa, as an example. Based on field investigation and lab tests, the main characteristic form of the URFa and land and water comprehensive remediation measures are summarized in this paper. The results show that it is feasible to turn wasteland, low-efficiency land, and old deserted beach into farm land, residential land, and ecological land by comprehensive land improvement. For the farm land reconstruction, the texture is an important indicator. The content of soil organic matter (SOM), carbon, nitrogen, and phosphorus has increased after remediation. For the SOM, 58.3% are more than 10.0 g·kg

Analysis and subcellular distribution of organophosphate esters (OPEs) in rice tissues.

Recent studies have identified the ability of plants to uptake and translocate organophosphate esters (OPEs) within cells. In response to the increasing interest in OPEs and their occurrence in paddy fields and rice, the current study aimed to present an effective and sensitive GC-MS based methodology for quantitative determination of 11 OPEs with octanol-water coefficients ranging from 1.6 to 10. Rice was sonicated with hexane and dichloromethane, and fractionated on two columns: one consisting of neutral alumina, and neutral silica, and the other consisting of graphitized carbon black. Method precision was validated using spiked rice (n = 30) and procedural blanks (n = 9). The mean recovery of matrix spikes for all target OPEs were within 78-110% with relative standard deviation lower than 25%, with a few exceptions. This method was applied to process the wild rice (O. sativa) in which tri-n-propyl phosphate was the dominant targeted OPE. The recoveries of surrogate standards were 81 ± 17% for d

Anti-inflammatory Therapy Progress in Major Adverse Cardiac Events after PCI: Chinese and Western Medicine.

Acute coronary syndrome (ACS) is one of the leading causes of death in cardiovascular disease. Percutaneous coronary intervention (PCI) is an important method for the treatment of coronary heart disease (CHD), and it has greatly reduced the mortality of ACS patients since its application. However, a series of new problems may occur after PCI, such as in-stent restenosis, no-reflow phenomenon, in-stent neoatherosclerosis, late stent thrombosis, myocardial ischemia-reperfusion injury, and malignant ventricular arrhythmias, which result in the occurrence of major adverse cardiac events (MACE) that seriously reduce the postoperative benefit for patients. The inflammatory response is a key mechanism of MACE after PCI. Therefore, examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE. The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified. Many Chinese medicine (CM) preparations have been widely used in the treatment of CHD. Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone. The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE. The results provide a theoretical basis for further research and clinical treatment.