Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4)

The cysteine-rich LIM-only protein 4 (CRP4), a LIM-domain and zinc finger containing adapter protein, has been implicated as a downstream effector of the second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) pathway in multiple cell types, including vascular smooth muscle cells (VSMCs). VSMCs and nitric oxide (NO)-induced cGMP signaling through cGMP-dependent protein kinase type I (cGKI) play fundamental roles in the physiological regulation of vascular tone and arterial blood pressure (BP). However, it remains unclear whether the vasorelaxant actions attributed to the NO/cGMP axis require CRP4. This study uses mice with a targeted deletion of the CRP4 gene (CRP4 KO) to elucidate whether cGMP-elevating agents, which are well known for their vasorelaxant properties, affect vessel tone, and thus, BP through CRP4. Cinaciguat, a NO- and heme-independent activator of the NO-sensitive (soluble) guanylyl cyclase (NO-GC) and NO-releasing agents, relaxed both CRP4-proficient and -deficient aortic ring segments pre-contracted with prostaglandin F2α. However, the magnitude of relaxation was slightly, but significantly, increased in vessels lacking CRP4. Accordingly, CRP4 KO mice presented with hypotonia at baseline, as well as a greater drop in systolic BP in response to the acute administration of cinaciguat, sodium nitroprusside, and carbachol. Mechanistically, loss of CRP4 in VSMCs reduced the Ca2+-sensitivity of the contractile apparatus, possibly involving regulatory proteins, such as myosin phosphatase targeting subunit 1 (MYPT1) and the regulatory light chain of myosin (RLC). In conclusion, the present findings confirm that the adapter protein CRP4 interacts with the NO-GC/cGMP/cGKI pathway in the vasculature. CRP4 seems to be part of a negative feedback loop that eventually fine-tunes the NO-GC/cGMP axis in VSMCs to increase myofilament Ca2+ desensitization and thereby the maximal vasorelaxant effects attained by (selected) cGMP-elevating agents.
Ordinal Time Series Forecasting of the Air Quality Index

This research models and forecasts daily AQI (air quality index) levels in 16 cities/counties of Taiwan, examines their AQI level forecast performance via a rolling window approach over a one-year validation period, including multi-level forecast classification, and measures the forecast accuracy rates. We employ statistical modeling and machine learning with three weather covariates of daily accumulated precipitation, temperature, and wind direction and also include seasonal dummy variables. The study utilizes four models to forecast air quality levels: (1) an autoregressive model with exogenous variables and GARCH (generalized autoregressive conditional heteroskedasticity) errors; (2) an autoregressive multinomial logistic regression; (3) multi-class classification by support vector machine (SVM); (4) neural network autoregression with exogenous variable (NNARX). These models relate to lag-1 AQI values and the previous day’s weather covariates (precipitation and temperature), while wind direction serves as an hour-lag effect based on the idea of nowcasting. The results demonstrate that autoregressive multinomial logistic regression and the SVM method are the best choices for AQI-level predictions regarding the high average and low variation accuracy rates.
Challenges in Documenting Non-Fatal Drowning Disability in Bangladesh: A Community-Based Survey

Limited access to health care and the lack of robust data systems means non-fatal drownings are largely missed in low-and middle-income countries. We report morbidity among individuals who experienced non-fatal drowning in the Barishal Division, Bangladesh. A representative household survey was conducted in the Barishal Division in southern Bangladesh between September 2016 and February 2017, covering a population of 386,016. The burden of non-fatal drowning was assessed using the WHODAS 2.0 disability assessment tool, a generic assessment instrument for health and disability. A total of 5164 non-fatal drowning events occurred in the one year preceding the survey. Among these 18% were multiple events. From these, 4235 people were administered the WHODAS 2.0 questionnaire. Non-fatal drowning incidence rates were highest in children aged 1–4 years at 5810 per 100,000 population, and among males. Non-fatal drowning was associated with lower socio-economic status and larger family sizes. Few respondents (6.5%; 95% CI: 4.5–8.4%) reported some level of disability (WHODAS-12 score > 8). Incidence of non-fatal drowning is high in the population, however limited impact on morbidity was found. There is a need to develop tools and methodologies for reliable and comparable data for non-fatal drowning, especially to capture post-event disability in children.
Beyond the X Factor: Relevance of Sex Hormones in NAFLD Pathophysiology

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, being frequently associated with obesity, unbalanced dietary regimens, and reduced physical activity. Despite their greater adiposity and reduced physical activity, women show a lower risk of developing NAFLD in comparison to men, likely a consequence of a sex-specific regulation of liver metabolism. In the liver, sex differences in the uptake, synthesis, oxidation, deposition, and mobilization of lipids, as well as in the regulation of inflammation, are associated with differences in NAFLD prevalence and progression between men and women. Given the major role of sex hormones in driving hepatic sexual dimorphism, this review will focus on the role of sex hormones and their signaling in the regulation of hepatic metabolism and in the molecular mechanisms triggering NAFLD development and progression.
In Silico Evaluation of Iranian Medicinal Plant Phytoconstituents as Inhibitors against Main Protease and the Receptor-Binding Domain of SARS-CoV-2

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in Wuhan, China, in December 2019. Elderly individuals and those with comorbid conditions may be more vulnerable to this disease. Consequently, several research laboratories continue to focus on developing drugs to treat this infection because this disease has developed into a global pandemic with an extremely limited number of specific treatments available. Natural herbal remedies have long been used to treat illnesses in a variety of cultures. Modern medicine has achieved success due to the effectiveness of traditional medicines, which are derived from medicinal plants. The objective of this study was to determine whether components of natural origin from Iranian medicinal plants have an antiviral effect that can prevent humans from this coronavirus infection using the most reliable molecular docking method; in our case, we focused on the main protease (Mpro) and a receptor-binding domain (RBD). The results of molecular docking showed that among 169 molecules of natural origin from common Iranian medicinal plants, 20 molecules (chelidimerine, rutin, fumariline, catechin gallate, adlumidine, astragalin, somniferine, etc.) can be proposed as inhibitors against this coronavirus based on the binding free energy and type of interactions between these molecules and the studied proteins. Moreover, a molecular dynamics simulation study revealed that the chelidimerine–Mpro and somniferine–RBD complexes were stable for up to 50 ns below 0.5 nm. Our results provide valuable insights into this mechanism, which sheds light on future structure-based designs of high-potency inhibitors for SARS-CoV-2.
Rapid Tumor Targeting of Renal-Clearable ZW800-1 Conjugate for Efficient Photothermal Cancer Therapy

The combination of near-infrared (NIR) fluorophores and photothermal therapy (PTT) provides a new opportunity for safe and effective cancer treatment. However, the precise molecular design of functional NIR fluorophores with desired properties, such as high tumor targetability and low nonspecific uptake, remains challenging. In this study, a renal-clearable NIR fluorophore conjugate with high tumor targetability was developed for efficient photothermal cancer therapy. The isoniazid (INH)–ZW800-1 conjugate (INH–ZW) was synthesized by conjugating an antibiotic drug, INH, with a well-known zwitterionic NIR fluorophore, ZW800-1, to improve in vivo performance and fluorescence-guided cancer phototherapy. INH–ZW not only showed rapid tumor accumulation without nonspecific tissue/organ uptake within 1 h after the injection but also generated thermal energy to induce cancer cell death under NIR laser irradiation. Compared with previously reported ZW800-1 conjugates, INH–ZW preserved the ideal biodistribution of ZW800-1 and facilitated improved tumor targeting and PTT. Together, these results demonstrate that the INH–ZW conjugate has great potential to serve as an effective PTT agent capable of rapid tumor targeting and high renal clearance, with excellent photothermal efficacy.
How to Promote the Performance of Parametric Volatility Forecasts in the Stock Market? A Neural Networks Approach

This study uses the fourteen stock indices as the sample and then utilizes eight parametric volatility forecasting models and eight composed volatility forecasting models to explore whether the neural network approach and the settings of leverage effect and non-normal return distribution can promote the performance of volatility forecasting, and which one of the sixteen models possesses the best volatility forecasting performance. The eight parametric volatility forecasts models are composed of the generalized autoregressive conditional heteroskedasticity (GARCH) or GJR-GARCH volatility specification combining with the normal, Student’s t, skewed Student’s t, and generalized skewed Student’s t distributions. Empirical results show that, the performance for the composed volatility forecasting approach is significantly superior to that for the parametric volatility forecasting approach. Furthermore, the GJR-GARCH volatility specification has better performance than the GARCH one. In addition, the non-normal distribution does not have better forecasting performance than the normal distribution. In addition, the GJR-GARCH model combined with both the normal distribution and a neural network approach has the best performance of volatility forecasting among sixteen models. Thus, a neural network approach significantly promotes the performance of volatility forecasting. On the other hand, the setting of leverage effect can encourage the performance of volatility forecasting whereas the setting of non-normal distribution cannot.
Now or Later? Stress-Induced Increase and Decrease in Choice Impulsivity Are Both Associated with Elevated Affective and Endocrine Responses

Exposure to acute stress elicit physiological and psychological responses that can impact decision-making, often expressed as an increased tendency to act in an impulsive manner following stress. Delay discounting (DD) task has emerged as a reliable measure of impulsive behavior in the form of choice impulsivity (CI). Interestingly, studies that examined the effect of acute stress on DD performance reported mixed results. To address this, we conducted a within-subject examination of the impact of acute stress on CI, focusing on individual differences in response patterns. One hundred and fifty healthy female participants completed the DD task twice, before and after undergoing an acute laboratory stress induction procedure. Saliva samples and self-report mood and affect measures were collected at four time points throughout the session. Fifty-nine matched healthy control participants completed only the DD task twice, with no stress in between. Results indicate that the acute stress procedure elicited the expected effects of increased cortisol release and increased negative mood and affect, at the group level. With respect to DD, stress indeed increased CI at the group level, yet participants differed in the magnitude and direction of this effect. Interestingly, regression analysis revealed quadratic relations between stress-induced changes in CI and cortisol release. Indeed, dividing the sample into three sub-groups based on the impact of stress on CI revealed that, compared to participants that exhibited no substantial change in their CI following stress, participants that exhibited either stress-induced increase or decrease in their CI also exhibited more stress-induced cortisol release, as well as more negative affect. Taken together, these findings suggest that elevated physiological and psychological responses to stress are associated with either increased or decreased choice impulsivity, thus depicting quadratic relations between stress and impulsivity.
Extracellular Reactive Oxygen Species (ROS) Production in Fresh Donkey Sperm Exposed to Reductive Stress, Oxidative Stress and NETosis

Jenny shows a large endometrial reaction after semen influx to the uterus with a large amount of polymorphonuclear neutrophils (PMN) migrating into the uterine lumen. PMN act as a sperm selection mechanism through phagocytosis and NETosis (DNA extrudes and, together with proteins, trap spermatozoa). While a reduced percentage of spermatozoa are phagocytosed by PMN, most are found to be attached to neutrophil extracellular traps (NETs). This selection process together with sperm metabolism produces a large amount of reactive oxygen species (ROS) that influence the reproductive success. The present study aimed to determine the extracellular ROS production in both sperm and PMN. With this purpose, (1) donkey sperm were exposed to reductive and oxidative stresses, through adding different concentrations of reduced glutathione (GSH) and hydrogen peroxide (H2O2), respectively; and (2) PMN were subjected to NETosis in the presence of the whole semen, sperm, seminal plasma (SP) or other activators such as formyl-methionyl-leucyl-phenylalanine (FMLP). Extracellular ROS production (measured as H2O2 levels) was determined with the Amplex® Red Hydrogen Peroxide/Peroxidase Assay Kit. Donkey sperm showed more resilience to oxidative stress than to the reductive one, and GSH treatments led to greater H2O2 extracellular production. Moreover, not only did SP appear to be the main inducer of NETosis in PMN, but it was also able to maintain the extracellular H2O2 levels produced by sperm and NETosis.
Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer

There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. This influx of cholesterol may be important for many cellular functions, including the synthesis of androgens. Castration-resistant prostate cancer tumors can synthesize androgens de novo to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR-B1 may impact the ability of prostate cancer cells, particularly those of the castration-resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. SR-B1 expression is elevated in CRPC models and has been linked to poor survival of patients. The overarching belief has been that cholesterol modulation, through either synthesis or uptake inhibition, will impact essential signaling processes, impeding the proliferation of prostate cancer. The reduction in cellular cholesterol availability can impede prostate cancer proliferation through both decreased steroid synthesis and steroid-independent mechanisms, providing a potential therapeutic target for the treatment of prostate cancer. In this article, we discuss and highlight the work on SR-B1 as a potential novel drug target for CRPC management.
Lower Dietary Intake of Plant Protein Is Associated with Genetic Risk of Diabetes-Related Traits in Urban Asian Indian Adults

The increasing prevalence of type 2 diabetes among South Asians is caused by a complex interplay between environmental and genetic factors. We aimed to examine the impact of dietary and genetic factors on metabolic traits in 1062 Asian Indians. Dietary assessment was performed using a validated semi-quantitative food frequency questionnaire. Seven single nucleotide polymorphisms (SNPs) from the Transcription factor 7-like 2 and fat mass and obesity-associated genes were used to construct two metabolic genetic risk scores (GRS): 7-SNP and 3-SNP GRSs. Both 7-SNP GRS and 3-SNP GRS were associated with a higher risk of T2D (p = 0.0000134 and 0.008, respectively). The 3-SNP GRS was associated with higher waist circumference (p = 0.010), fasting plasma glucose (FPG) (p = 0.002) and glycated haemoglobin (HbA1c) (p = 0.000066). There were significant interactions between 3-SNP GRS and protein intake (% of total energy intake) on FPG (Pinteraction = 0.011) and HbA1c (Pinteraction = 0.007), where among individuals with lower plant protein intake (<39 g/day) and those with >1 risk allele had higher FPG (p = 0.001) and HbA1c (p = 0.00006) than individuals with ≤1 risk allele. Our findings suggest that lower plant protein intake may be a contributor to the increased ethnic susceptibility to diabetes described in Asian Indians. Randomised clinical trials with increased plant protein in the diets of this population are needed to see whether the reduction of diabetes risk occurs in individuals with prediabetes.
New Interventional Therapies beyond Stenting to Treat ST-Segment Elevation Acute Myocardial Infarction

Myocardial infarction remains the principal cause of death in Europe. In patients with ST-segment-elevation myocardial infarction (STEMI), a promptly revascularization with primary percutaneous intervention (PCI) has transformed prognosis in the last decades. However, despite increasing successful PCI procedures, mortality has remained unchanged in recent years. Also, due to an unsatisfactory reperfusion, some patients have significant myocardial damage and suffer left ventricular adverse remodeling with reduced function—all that resulting in the onset of heart failure with all its inherent clinical and socioeconomic burden. As a consequence of longer ischemic times, distal thrombotic embolization, ischemia-reperfusion injury and microvascular dysfunction, the resultant myocardial infarct size is the major prognostic determinant in STEMI patients. The improved understanding of all the pathophysiology underlying these events has derived to the development of several novel therapies aiming to reduce infarct size and to improve clinical outcomes in these patients. In this article, based on the mechanisms involved in myocardial infarction prognosis, we review the new interventional strategies beyond stenting that may solve the suboptimal results that STEMI patients still experience.
Thromboelastometric Analysis of Anticancer Cerrena unicolor Subfractions Reveal Their Potential as Fibrin Glue Drug Carrier Enhancers

In this study, the influence of two subfractions (with previously proven anti-cancer properties) isolated from wood rot fungus Cerrena unicolor on the formation of a fibrin clot was investigated in the context of potential use as fibrin glue and sealant enhancers and potential wound healing agents. With the use of ROTEM thromboelastometry, we demonstrated that, in the presence of fibrinogen and thrombin, the S6 fraction accelerated the formation of a fibrin clot, had a positive effect on its elasticity modulus, and enhanced the degree of fibrin cross-linking. The S5 fraction alone showed no influence on the fibrin coagulation process; however, in the presence of fibrin, it exhibited a decrease in anti-proliferative properties against the HT-29 line, while it increased the proliferation of cells in general at a concentration of 100 µg/mL. Both fractions retained their proapoptotic properties to a lesser degree. In combination with the S6 fraction in the ratio of 1:1 and 1:3, the fractions contributed to increased inhibition of the activity of matrix metalloproteinases (MMPs). This may suggest anti-metastatic activity of the combined fractions. In conclusion, the potential of the fractions isolated from the C. unicolor secretome to be used as a means of improving the wound healing process was presented. The potential for delivering agents with cytostatic properties introduced far from the site of action or exerting a pro-proliferative effect at the wound site with the aid of a fibrin sealant was demonstrated.
Fungal Guttation, a Source of Bioactive Compounds, and Its Ecological Role—A Review

Guttation is a common phenomenon in the fungal kingdom. Its occurrence and intensity depend largely on culture conditions, such as growth medium composition or incubation temperature. As filamentous fungi are a rich source of compounds, possessing various biological activities, guttation exudates could also contain bioactive substances. Among such molecules, researchers have already found numerous mycotoxins, antimicrobials, insecticides, bioherbicides, antiviral, and anticancer agents in exudate droplets. They belong to either secondary metabolites (SMs) or proteins and are secreted with different intensities. The background of guttation, in terms of its biological role, in vivo, and promoting factors, has been explored only partially. In this review, we describe the metabolites present in fungal exudates, their diversity, and bioactivities. Pointing to the significance of fungal ecology and natural products discovery, selected aspects of guttation in the fungi are discussed.
The Prevalence and Overlaps of Temporomandibular Disorders in Patients with Myofascial Pain with Referral—A Pilot Study

The aim of the study was to evaluate the temporomandibular joint, the prevalence of single and multiple diagnosis and potential sided domination of temporomandibular dysfunction in patients with temporomandibular disorder—myofascial pain with referral. The study group enrolled 50 people—37 females and 13 males between 18 and 25 years old with an average age of 23.36 ± 2.14. The patients underwent joint vibration analysis. Sixty seven percent of all examined tem-poromandibular joints were classified as group I according to Mark Piper’s classification. Class IIIA appeared in 17% of joints. Eight percent of temporomandibular joints were classified as class IVA. There were no statistically significant differences in the prevalence of temporomandibular disorder with respect to gender (p = 0.838639). The relatively high prevalence of multiple diagnoses proved the overlapping nature of muscle and intraarticular disorders. Twenty eight percent of the subjects suffered from a combination of myofascial pain with referral and bilateral temporoman-dibular dysfunction. In 62% of the patients a lack of intraarticular disorders was reported. The suggestion that there exists sided domination in the occurrence of temporomandibular disorders has not been confirmed. Due to the small sample size, such differences cannot be excluded. Fur-ther research is needed.