bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic Connection of Holobiont Components and the Essential Roles of Core Microbes in the Holobiont Formation of Feral Brassica napus
Authors: Chun Seong-Jun , Cui Yingshun , Yoo Su-Hyang , Lee Jung Ro
Published: July 2022

Brassica napus (Rapeseed) is an econfomically important oil-producing crop. The microbial interactions in the plant holobiont are fundamental to the understanding of plant growth and health. To investigate the microbial dynamics in the holobiont of feral B. napus, a total of 215 holobiont samples, comprised of bulk soil, primary root, lateral root, dead leaf, caulosphere, basal leaf, apical leaf, carposphere, and anthosphere, were collected from five different grassland sites in South Korea. The soil properties differed in different sampling sites, but prokaryotic communities were segregated according to plant holobiont components. The structures of the site-specific SparCC networks were similar across the regions. Recurrent patterns were found in the plant holobionts in the recurrent network. Ralstonia sp., Massilia sp., and Rhizobium clusters were observed consistently and were identified as core taxa in the phyllosphere, dead leaf microbiome, and rhizosphere, respectively. Arthropod-related microbes, such as Wolbachia sp., Gilliamella sp., and Corynebacteriales amplicon sequence variants, were found in the anthosphere. PICRUSt2 analysis revealed that microbes also possessed specific functions related to holobiont components, such as functions related to degradation pathways in the dead leaf microbiome. Structural equation modeling analysis showed the organic connections among holobiont components and the essential roles of the core microbes in the holobiont formations in natural ecosystem. Microbes coexisting in a specific plant showed relatively stable community structures, even though the regions and soil characteristics were different. Microbes in each plant component were organically connected to form their own plant holobiont. In addition, plant-related microbes, especially core microbes in each holobiont, showed recurrent interaction patterns that are essential to an understanding of the survival and coexistence of plant microbes in natural ecosystems.
Indole-Acetic Acid Promotes Ammonia Removal Through Heterotrophic Nitrification, Aerobic Denitrification With Mixed Enterobacter sp. Z1 and Klebsiella sp. Z2
Authors: Zhang Yuxiao , Xu Qing , Wang Gejiao , Shi Kaixiang
Published: July 2022

Mixed Enterobacter sp. Z1 and Klebsiella sp. Z2 displayed an outstanding ammonia removal capacity than using a single strain. Metabolomics, proteomics, and RNA interference analysis demonstrated that the HNAD process was closely related to indole-acetic acid (IAA). Under the cocultured conditions, the excess IAA produced by Z2 could be absorbed by Z1 to compensate for the deficiency of IAA in the cells. IAA directly induced the expression of denitrifying enzymes and further activated the IAA metabolism level, thus greatly improving the nitrogen removal ability of Z1. In turn, nitrate and nitrite induced the expression of key enzymes in the IAA pathways. Moreover, Z1 and Z2 enhanced two IAA metabolic pathways in the process of mixed removal process. The activated hydrolysis-redox pathway in Z1 reduced the oxidative stress level, and the activated decarboxylation pathway in Z2 promoted intracellular energy metabolism, which indirectly promoted the process of HNAD in the system.
Effects of a Dark Septate Fungal Endophyte on the Growth and Physiological Response of Seedlings to Drought in an Epiphytic Orchid
Authors: Liu Na , Jacquemyn Hans , Liu Qiang , Shao Shi-Cheng , Ding Gang , Xing Xiaoke
Published: July 2022

Dark septate endophytes (DSE) are a group of facultative biotrophic root-colonizing fungi that live within a plant for a part of their life cycle without causing any apparent, overt negative effects. These fungi have been found in >600 different plant species, including orchids. Although the precise ecological functions of dark septate fungal endophytes are not yet well understood, there is increasing evidence that they enhance host growth and nutrient acquisition, and improve the plant’s ability to tolerate biotic and abiotic stresses. In this research, we tested the effects of a DSE isolated from the roots of the epiphytic orchid Coelogyne viscosa on the growth and drought tolerance of orchid seedlings. Our results showed that addition of DSE inoculum significantly enhanced biomass of seedlings and increased the activities of drought resistance related enzymes and the accumulation of osmoregulatory substances. These results suggest that DSE can fulfill important ecological functions in stressful environments and potentially play an important role in the life cycle of epiphytic orchids.
A Curvilinear-Path Umbrella Sampling Approach to Characterizing the Interactions Between Rapamycin and Three FKBP12 Variants
Authors: Joshi Dhananjay C. , Gosse Charlie , Huang Shu-Yu , Lin Jung-Hsin
Published: July 2022

Rapamycin is an immunosuppressant macrolide that exhibits anti-proliferative properties through inhibiting the mTOR kinase. In fact, the drug first associates with the FKBP12 enzyme before interacting with the FRB domain of its target. Despite the availability of structural and thermodynamic information on the interaction of FKBP12 with rapamycin, the energetic and mechanistic understanding of this process is still incomplete. We recently reported a multiple-walker umbrella sampling simulation approach to characterizing the protein–protein interaction energetics along curvilinear paths. In the present paper, we extend our investigations to a protein-small molecule duo, the FKBP12•rapamycin complex. We estimate the binding free energies of rapamycin with wild-type FKBP12 and two mutants in which a hydrogen bond has been removed, D37V and Y82F. Furthermore, the underlying mechanistic details are analyzed. The calculated standard free energies of binding agree well with the experimental data, and the roles of the hydrogen bonds are shown to be quite different for each of these two mutated residues. On one hand, removing the carboxylate group of D37 strongly destabilizes the association; on the other hand, the hydroxyl group of Y82 is nearly unnecessary for the stability of the complex because some nonconventional, cryptic, indirect interaction mechanisms seem to be at work.
Hypothalamic Neurochemical Changes in Long-Term Recovered Bilateral Subdiaphragmatic Vagotomized Rats
Authors: Kobrzycka Anna Teresa , Stankiewicz Adrian Mateusz , Goscik Joanna , Gora Monika , Burzynska Beata , Iwanicka-Nowicka Roksana , Pierzchala-Koziec Krystyna , Wieczorek Marek
Published: July 2022

Background

Vagus nerve is one of the crucial routes in communication between the immune and central nervous systems. The impaired vagal nerve function may intensify peripheral inflammatory processes. This effect subsides along with prolonged recovery after permanent nerve injury. One of the results of such compensation is a normalized plasma concentration of stress hormone corticosterone – a marker of hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, we strive to explain this corticosterone normalization by studying the mechanisms responsible for compensation-related neurochemical alterations in the hypothalamus.

Materials and Methods

Using microarrays and high performance liquid chromatography (HPLC), we measured genome-wide gene expression and major amino acid neurotransmitters content in the hypothalamus of bilaterally vagotomized rats, 1 month after surgery.

Results

Our results show that, in the long term, vagotomy affects hypothalamic amino acids concentration but not mRNA expression of tested genes.

Discussion

We propose an alternative pathway of immune to CNS communication after vagotomy, leading to activation of the HPA axis, by influencing central amino acids and subsequent monoaminergic neurotransmission.
New Insights Into Diuretic Use to Treat Congestion in the ICU: Beyond Furosemide
Authors: Escudero Victor Joaquin , Mercadal Jordi , Molina-Andújar Alícia , Piñeiro Gaston J. , Cucchiari David , Jacas Adriana , Carramiñana Albert , Poch Esteban
Published: July 2022

Diuretics are commonly used in critically ill patients with acute kidney injury (AKI) and fluid overload in intensive care units (ICU), furosemide being the diuretic of choice in more than 90% of the cases. Current evidence shows that other diuretics with distinct mechanisms of action could be used with good results in patients with selected profiles. From acetazolamide to tolvaptan, we will discuss recent studies and highlight how specific diuretic mechanisms could help to manage different ICU problems, such as loop diuretic resistance, hypernatremia, hyponatremia, or metabolic alkalosis. The current review tries to shed some light on the potential use of non-loop diuretics based on patient profile and give recommendations for loop diuretic treatment performance focused on what the intensivist and critical care nephrologist need to know based on the current evidence.
Automated Supra- and Infratentorial Brain Infarct Volume Estimation on Diffusion Weighted Imaging Using the RAPID Software
Authors: Lakatos Lehel , Bolognese Manuel , Müller Martin , Österreich Mareike , von Hessling Alexander
Published: July 2022

Purpose

The present computerized techniques have limits to estimate the ischemic lesion volume especially in vertebrobasilar ischemia (VBI) automatically. We investigated the ability of the RAPID AI (RAPID) software on diffusion-weighted imaging (DWI) to estimate the infarct size in VBI in comparison to supratentorial ischemia (STI).

Methods

Among 123 stroke patients (39 women, 84 men, mean age 66 ± 11 years) having undergone DWI, 41 had had a VBI and 82 a STI. The infarct volume calculation by RAPID was compared to volume calculations by 2 neurologists using the ABC/2 method. For inter-reader and between-method analysis intraclass correlation coefficient (ICC), area under the curve (AUC) estimations, and Bland–Altman plots were used.

Results

ICC between the two neurologists and each neurologist and RAPID were >0.946 (largest 95% CI boundaries 0.917–0.988) in the STI group, and > 0.757 (95% CI boundaries between 0.544 and 0.982) in the VBI group. In the STI group, AUC values ranged between 0.982 and 0.999 (95% CI 0.971–1) between the 2 neurologists and between 0.875 and 1 (95% CI 0.787–1) between the neurologists and RAPID; in the VBI group, they ranged between 0.925 and 0.965 (95% CI 0.801–1) between the neurologists, and between 0.788 and 0.931 (95% CI 0.663–1) between RAPID and the neurologists. Compared to the visual DWI interpretation by the neurologists, RAPID did not recognize a substantial number of infarct volumes of ≤ 2 ml.

Conclusion

The ability of the RAPID software to depict strokes in the vertebrobasilar artery system seems close to its ability in the supratentorial brain tissue. However, small lesion volumes ≤ 2 ml remain still undetected in both brain areas.
Mental State Classification Using Multi-Graph Features
Authors: Chen Guodong , Helm Hayden S. , Lytvynets Kate , Yang Weiwei , Priebe Carey E.
Published: July 2022

We consider the problem of extracting features from passive, multi-channel electroencephalogram (EEG) devices for downstream inference tasks related to high-level mental states such as stress and cognitive load. Our proposed feature extraction method uses recently developed spectral-based multi-graph tools and applies them to the time series of graphs implied by the statistical dependence structure (e.g., correlation) amongst the multiple sensors. We study the features in the context of two datasets each consisting of at least 30 participants and recorded using multi-channel EEG systems. We compare the classification performance of a classifier trained on the proposed features to a classifier trained on the traditional band power-based features in three settings and find that the two feature sets offer complementary predictive information. We conclude by showing that the importance of particular channels and pairs of channels for classification when using the proposed features is neuroscientifically valid.
How Staying Negative Is Good for the (Adult) Brain: Maintaining Chloride Homeostasis and the GABA-Shift in Neurological Disorders
Authors: Hui Kelvin K. , Chater Thomas E. , Goda Yukiko , Tanaka Motomasa
Published: July 2022

Excitatory-inhibitory (E-I) imbalance has been shown to contribute to the pathogenesis of a wide range of neurodevelopmental disorders including autism spectrum disorders, epilepsy, and schizophrenia. GABA neurotransmission, the principal inhibitory signal in the mature brain, is critically coupled to proper regulation of chloride homeostasis. During brain maturation, changes in the transport of chloride ions across neuronal cell membranes act to gradually change the majority of GABA signaling from excitatory to inhibitory for neuronal activation, and dysregulation of this GABA-shift likely contributes to multiple neurodevelopmental abnormalities that are associated with circuit dysfunction. Whilst traditionally viewed as a phenomenon which occurs during brain development, recent evidence suggests that this GABA-shift may also be involved in neuropsychiatric disorders due to the “dematuration” of affected neurons. In this review, we will discuss the cell signaling and regulatory mechanisms underlying the GABA-shift phenomenon in the context of the latest findings in the field, in particular the role of chloride cotransporters NKCC1 and KCC2, and furthermore how these regulatory processes are altered in neurodevelopmental and neuropsychiatric disorders. We will also explore the interactions between GABAergic interneurons and other cell types in the developing brain that may influence the GABA-shift. Finally, with a greater understanding of how the GABA-shift is altered in pathological conditions, we will briefly outline recent progress on targeting NKCC1 and KCC2 as a therapeutic strategy against neurodevelopmental and neuropsychiatric disorders associated with improper chloride homeostasis and GABA-shift abnormalities.
Probiotic Supplementation Prevents the Development of Ventilator-Associated Pneumonia for Mechanically Ventilated ICU Patients: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials
Authors: Li Cong , Lu Fangjie , Chen Jing , Ma Jiawei , Xu Nana
Published: July 2022

Background

Ventilator-associated pneumonia (VAP) is one of the common critical complications of nosocomial infection (NI) in invasive mechanically ventilated intensive care unit (ICU) patients. The efficacy of total parenteral nutrition (TPN), enteral nutrition and/or adjuvant peripheral parenteral nutrition (EPN) supplemented with or without probiotic, prebiotic, and synbiotic therapies in preventing VAP among these patients has been questioned. We aimed to systematically and comprehensively summarize all available studies to generate the best evidence of VAP prevention for invasive mechanically ventilated ICU patients.

Methods

Randomized controlled trials (RCTs) for the administration of TPN, EPN, probiotics-supplemented EPN, prebiotics-supplemented EPN, and synbiotics-supplemented EPN for VAP prevention in invasive mechanically ventilated ICU patients were systematically retrieved from four electronic databases. The incidence of VAP was the primary outcome and was determined by the random-effects model of a Bayesian framework. The secondary outcomes were NI, ICU and hospital mortality, ICU and hospital length of stay, and mechanical ventilation duration. The registration number of Prospero is CRD42020195773.

Results

A total of 8339 patients from 31 RCTs were finally included in network meta-analysis. The primary outcome showed that probiotic-supplemented EPN had a higher correlation with the alleviation of VAP than EPN in critically invasive mechanically ventilated patients (odds ratio [OR] 0.75; 95% credible intervals [CrI] 0.58–0.95). Subgroup analyses showed that probiotic-supplemented EPN prevented VAP in trauma patients (OR 0.30; 95% CrI 0.13–0.83), mixed probiotic strain therapy was more effective in preventing VAP than EPN therapy (OR 0.55; 95% CrI 0.31–0.97), and low-dose probiotic therapy (less than 1010 CFU per day) was more associated with lowered incidence of VAP than EPN therapy (OR 0.16; 95% CrI 0.04–0.64). Secondary outcomes indicated that synbiotic-supplemented EPN therapy was more significantly related to decreased incidence of NI than EPN therapy (OR 0.34; 95% CrI 0.11–0.85). Prebiotic-supplemented EPN administration was the most effective in preventing diarrhea (OR 0.05; 95% CrI 0.00–0.71).

Conclusion

Probiotic supplementation shows promise in reducing the incidence of VAP in critically invasive mechanically ventilated patients. Currently, low quality of evidence reduces strong clinical recommendations. Further high-quality RCTs are needed to conclusively prove these findings.

Systamatic Review Registration

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020195773], identifier [CRD42020195773].
The Effect of Green Tea as an Adjuvant to Enzyme Replacement Therapy on Oxidative Stress in Fabry Disease: A Pilot Study
Authors: Bertoldi Giovanni , Carraro Gianni , Ravarotto Verdiana , Di Vico Valentina , Baldini Anastasio Paola , Vitturi Nicola , Francini Francesco , Stefanelli Lucia Federica , Calò Lorenzo A.
Published: July 2022

Enzymatic replacement therapy (ERT) is not very effective in halting the progression of Fabry disease (FD) toward cardiovascular (CV)-renal remodeling, particularly in case of late diagnosis. FD patients have increased oxidative stress (OS), critical for the induction of CV-renal remodeling. We investigated the effects of an adjuvant antioxidant treatment to ERT on OS and the possible advantages for related complications. OS was evaluated in 10 patients with FD before ERT, after 12 months of ERT, and after 6 months of adjuvant green tea (GT) to ERT by the following experiments: expression of p22phox; phosphorylation state of MYPT-1 and ERK 1/2 (by western blotting); and quantification of malondialdehyde (MDA) and heme oxygenase (HO)-1 levels (by ELISA). p22phox and MYPT-1 phosphorylation decreased after ERT and significantly further decreased after GT. ERK 1/2 phosphorylation and MDA levels remained unchanged after ERT, but significantly decreased after GT. HO-1 significantly increased after ERT and further increased after GT. This study provides preliminary data highlighting the antioxidant effect exerted by ERT itself, further amplified by the adjuvant antioxidant treatment with GT. The results of this study provide evidence of the positive effect of early additive antioxidant treatment to reduce OS and prevent/alleviate cardio and cerebrovascular-renal complications related to OS.
Case Report: Hyperammonemic Encephalopathy Linked to Ureaplasma spp. and/or Mycoplasma hominis Systemic Infection in Patients Treated for Leukemia, an Emergency Not to Be Missed
Authors: Delafoy Manon , Goutines Juliette , Fourmont Aude-Marie , Birgy André , Chomton Maryline , Levy Michaël , Naudin Jérôme , Zafrani Lara , Le Mouel Lou , Yakouben Karima , Cointe Aurélie , Caseris Marion , Lafaurie Matthieu , Bonacorsi Stéphane , Mechinaud Françoise , Pereyre Sabine , Boissel Nicolas , Baruchel André
Published: July 2022

Background

Hyperammonemic encephalopathy caused by Ureaplasma spp. and Mycoplasma hominis infection has been reported in immunocompromised patients undergoing lung transplant, but data are scarce in patients with hematological malignancies.

Case Presentation

We describe the cases of 3 female patients aged 11–16 years old, developing initially mild neurologic symptoms, rapidly evolving to coma and associated with very high ammonia levels, while undergoing intensive treatment for acute leukemia (chemotherapy: 2 and hematopoietic stem cell transplant: 1). Brain imaging displayed cerebral edema and/or microbleeding. Electroencephalograms showed diffuse slowing patterns. One patient had moderate renal failure. Extensive liver and metabolic functions were all normal. Ureaplasma spp. and M. hominis were detected by PCR and specific culture in two patients, resulting in prompt initiation of combined antibiotics therapy by fluoroquinolones and macrolides. For these 2 patients, the improvement of the neurological status and ammonia levels were observed within 96 h, without any long-term sequelae. M. hominis was detected post-mortem in vagina, using 16S rRNA PCR for the third patient who died of cerebral edema.

Conclusion

Hyperammonemic encephalopathy linked to Ureaplasma spp. and M. hominis is a rare complication encountered in immunocompromised patients treated for acute leukemia, which can lead to death if unrecognized. Combining our experience with the few published cases (n=4), we observed a strong trend among female patients and very high levels of ammonia, consistently uncontrolled by classical measures (ammonia-scavenging agents and/or continuous kidney replacement therapy). The reversibility of the encephalopathy without sequelae is possible with prompt diagnosis and adequate combined specific antibiotherapy. Any neurological symptoms in an immunocompromised host should lead to the measurement of ammonia levels. If increased, and in the absence of an obvious cause, it should prompt to perform a search for Ureaplasma spp. and M. hominis by PCR as well as an immediate empirical initiation of combined specific antibiotherapy.
Gastric Metastasis of Primary Lung Cancer: Case Report and Systematic Review With Pooled Analysis
Authors: Tang Dong , Lv Jianjian , Liu Zhijing , Zhan Shuhui , Gao Yuqiang
Published: July 2022

Background

Gastric metastasis from lung cancer (GMLC) is a rare occurrence. The clinicopathological characteristics, outcomes, and prognostic factors remain largely elusive.

Methods

We conducted a systematic review on case reports and case series of GMLC by scanning MEDLINE, Embase, and ISI Web of Knowledge. Data involving the clinicopathological features, treatment, and outcomes were extracted and analyzed. Survival analysis was performed using Kaplan–Meier method. The Cox proportional hazards regression model was used to identify potential prognostic factors associated with survival. Furthermore, a case of metastatic gastric adenocarcinoma of pulmonary origin with epidermal growth factor receptor (EGFR) L858R+T790M mutation was also described and included.

Results

Seventy-eight records involving 114 cases (including ours) were finally included. The median age on admission was 65 years with a male predominance of 79.8%. Lung adenocarcinoma (42.1%), located in the right upper lobe (30.3%), was the most frequent primary tumor. Bleeding (36.7%) and abdominal pain (35.8%) were the two most common symptoms. Endoscopically, gastric lesions were typically presented as elevated lesions with or without volcano-like ulceration, or ulcerative lesions, mostly involving the gastric corpus. The median overall survival time and survival time after diagnosis of metastatic cancer were 11 months [95% confidence interval (CI): 7–14] and 4.5 months (95% CI: 3–9), respectively. The survival analyses revealed that surgical interventions (including lung surgery and/or abdominal surgery) and systemic therapy (including chemotherapy, radiotherapy, and/or targeted therapy) seemed to be positive prognostic factors for both overall survival and survival after diagnosis of metastatic cancer.

Conclusions

Clinicians should be alerted to the occurrence of gastric metastasis in lung cancer patients. Comprehensive evaluation and appropriate treatment for specific patients may improve the survival rate of GMLC patients.
Case Report: Dramatic Cholestasis Responsive to Steroids in a Newborn Homozygous for H63D HFE Variant
Authors: Filippi Luca , Tamagnini Sara , Lorenzoni Francesca , Caciotti Anna , Morrone Amelia , Scaramuzzo Rosa
Published: July 2022

In a newborn with very precocious liver failure, cholestatic jaundice, and low γ-glutamyl transpeptidase, progressive hepatosplenomegaly induced a progressively worsening respiratory distress, that was successfully treated with steroids. Laboratory and genetic tests did not find any disease usually associated with neonatal cholestasis. However, the patient was positive for a homozygous mutation of the HFE gene, which is associated with hereditary hemochromatosis, a disease with typical onset in adulthood. Although no firm conclusions can be drawn from a single clinical case, this experience suggests that hereditary hemochromatosis could have played a role in the induction of this serious cholestasis, probably already arisen in the uterus. We suggest that hereditary hemochromatosis ought to be included in the panel of the possible causes of neonatal cholestasis and that steroids ought to be added to the pharmacological armamentarium for treating specific conditions which cause cholestasis in newborns.
Hypoplastic Left Heart Syndrome: Is There a Role for Fetal Therapy?
Authors: Tulzer Andreas , Huhta James C. , Hochpoechler Julian , Holzer Kathrin , Karas Thomas , Kielmayer David , Tulzer Gerald
Published: July 2022

During fetal life some cardiac defects may lead to diminished left heart growth and to the evolution of a form of hypoplastic left heart syndrome (HLHS). In fetuses with an established HLHS, severe restriction or premature closure of the atrial septum leads to left atrial hypertension and remodeling of the pulmonary vasculature, severely worsening an already poor prognosis. Fetal therapy, including invasive fetal cardiac interventions and non-invasive maternal hyperoxygenation, have been introduced to prevent a possible progression of left heart hypoplasia, improve postnatal outcome, or secure fetal survival. The aim of this review is to cover patient selection and possible hemodynamic effects of fetal cardiac procedures and maternal hyperoxygenation in fetuses with an evolving or established hypoplastic left heart syndrome.
Storax Inhibits Caveolae-Mediated Transcytosis at Blood-Brain Barrier After Ischemic Stroke in Rats
Authors: Zhou Min , Li Dongna , Shen Qian , Gao Lei , Zhuang Pengwei , Zhang Yanjun , Guo Hong
Published: July 2022

Background and Purpose: Blood-brain barrier (BBB) disruption following ischemic stroke (IS) contributes to hemorrhagic transformation, brain edema, increased neural dysfunction, secondary injury, and mortality. The prevailing view attributes the destruction of tight junction proteins (TJs) to the resulting BBB damage following IS. However, recent studies define a stepwise impairment of the transcellular barrier followed by the paracellular barrier which accounts for the BBB leakage in IS. The increased endothelial transcytosis that has been proven to be caveolae-mediated, preceding and independent of TJs disintegration. Emerging experimental investigations suggested Storax attenuates BBB damage after stroke. This study aimed to test our hypothesis that Storax inhibits caveolae-mediated transcytosis at BBB after ischemic stroke in rats.

Methods: Male Wistar rats (250–300 g) were subjected to transient middle cerebral artery occlusion (t-MCAO). Brain water content and the cerebral infarction size were assessed by brain tissue drying-wet method and 2,3,5-triphenyltetrazolium chloride (TTC) staining. BBB permeability was detected by the leakage of Evans blue and Albumin-Alexa594. The ultrastructure of BBB was examined by transmission electron microscopy (TEM). Cav-1 and Mfsd2a were quantified by western blotting and immunofluorescence staining, AQP4, PDGFR-β, ZO-1 and Occludin were quantified by western blotting.

Results: Storax treatment of 0.1 g/kg had no significant effects on brain lesions. Storax treatment of 0.2, 0.4, and 0.8 g/kg led to a significant decrease in infarction size, and the Storax 0.4, 0.8 g/kg groups displayed a significant reduction in brain water content. Storax treatment of 0.8 g/kg showed mild toxic reactions. Thus, 0.4 g/kg Storax was selected as the optimal dose for subsequent studies. Storax significantly inhibited the fluorescent albumin intensity in the brain parenchyma and the number of caveolae in ECs, alongside attenuating the ultrastructural disruption of BBB at 6 h after stroke. Meanwhile, Storax significantly increased the expression of Mfsd2a and PDGFR-β, and decrease the expression of Cav-1 and AQP4, corresponding to the significantly decreased Cav-1 positive cells and increased Mfsd2a positive cells. However, Storax has no significant effects on Evan blue leakage or the expression ZO-1, Occludin.

Conclusion: Our experimental findings demonstrate Storax treatment inhibits caveolae-mediated transcytosis at BBB in the focal stroke model of rats. We also speculate that regulation of Cav-1, Mfsd2a, AQP4, and PDGFR-β expressions might be associated with its beneficial pharmacological effect, but remain to define and elucidate in future investigation.
In Vitro, Ex Vivo, and In Vivo Evaluation of Nanoparticle-Based Topical Formulation Against Candida albicans Infection
Authors: Sadozai Sajid Khan , Khan Saeed Ahmad , Baseer Abdul , Ullah Rooh , Zeb Alam , Schneider Marc
Published: July 2022

Ketoconazole is commonly used in the treatment of topical fungal infections. The therapy requires frequent application for several weeks. Systemic side effects, allergic reactions, and prolonged treatment are often associated with non-compliance and therapy failure. Hence, we developed an optimized topical antifungal gel that can prolong the release of drug, reduce systemic absorption, enhance its therapeutic effect, and improve patient compliance. Ketoconazole-loaded PLGA nanoparticles were prepared by the emulsion/solvent evaporation method and were characterized with respect to colloidal properties, surface morphology, and drug entrapment efficiency. The optimized ketoconazole-loaded PLGA nanoparticles and commercially available silver nanoparticles were incorporated into a Carbopol 934P-NF gel base. This arrangement was characterized and compared with commercially available 2% ketoconazole cream to assess physical characteristics of the gel, in vitro drug release, ex vivo skin permeation and retention, and in vivo studies on Wister male albino rats. The results showed that polymeric PLGA nanoparticles were very effective in extending the release of ketoconazole in our optimized formulation. Nanoparticles were smooth, spherical in shape, and below 200 nm in size which is consistent with the data obtained from light scattering and SEM images. The ex vivo data showed that our gel formulation could strongly reduce drug permeation through the skin, and more than 60% of the drug was retained on the upper surface of the skin in contrast to 38.42% of the commercial cream. The in vivo studies showed that gel formulation could effectively treat the infection. This study demonstrates that our topical gel could be effective in sustaining the release of drug and suggests its potential use as a possible strategy to combat antifungal-resistant Candida albicans.
Role of Homoclinic Breathers in the Interpretation of Experimental Measurements, With Emphasis on the Peregrine Breather
Authors: Osborne Alfred R.
Published: July 2022

A class of generalized homoclinic solutions of the nonlinear Schrödinger (NLS) equation in 1+1 dimensions is studied. These are homoclinic breathers that are shown to be derivable from the ratio of Riemann theta functions for the genus-2 solutions of the nonlinear Schrödinger equation. We discuss how these solutions behave in the homoclinic limit for which a fundamental parameter ε goes to zero, ε→0 (such that two points of simple spectrum converge to double points at some particular lambda-plane eigenvalue). The homoclinic solutions cover the entire lambda plane (the Riemann surface of the NLS equation) and are given in terms of simple trigonometric functions. When the spectral eigenvalues converge to the carrier amplitude in the lambda plane we have the Peregrine breather. While the Peregrine solution is often called a soliton, it is in reality a breather, albeit occurring at the “singular point” corresponding to the carrier eigenvalue in the lambda plane and consequently “breathes” only once in its lifetime. The Peregrine breather separates small-amplitude modulations below the carrier from large amplitude modulation above the carrier. This fact means that the Peregrine breather has a “central” role in the lambda plane characterization of the NLS nonlinear spectrum. The Akhmediev breather occurs somewhat below the carrier (and is therefore a small-amplitude modulation) and the Kuznetsov-Ma breather occurs above the carrier (and is therefore a large-amplitude modulation). The general homoclinic solutions can be constructed everywhere in the lambda plane and are shown to be a useful tool to interpret the nonlinear Fourier spectrum of space and time series recorded in the laboratory and ocean environment. Nonlinear filtering is suggested as a way to extract breather trains from experimental time series. The generalized homoclinic breathers can be thought of as “extreme wave packets” or “rogue wave” solutions of water waves for scientific and engineering applications in various fields of physics including physical oceanography and nonlinear optics.
Endothelial Dysfunction in Heart Failure With Preserved Ejection Fraction: What are the Experimental Proofs?
Authors: Cornuault Lauriane , Rouault Paul , Duplàa Cécile , Couffinhal Thierry , Renault Marie-Ange
Published: July 2022

Heart failure with preserved ejection fraction (HFpEF) has been recognized as the greatest single unmet need in cardiovascular medicine. Indeed, the morbi-mortality of HFpEF is high and as the population ages and the comorbidities increase, so considerably does the prevalence of HFpEF. However, HFpEF pathophysiology is still poorly understood and therapeutic targets are missing. An unifying, but untested, theory of the pathophysiology of HFpEF, proposed in 2013, suggests that cardiovascular risk factors lead to a systemic inflammation, which triggers endothelial cells (EC) and coronary microvascular dysfunction. This cardiac small vessel disease is proposed to be responsible for cardiac wall stiffening and diastolic dysfunction. This paradigm is based on the fact that microvascular dysfunction is highly prevalent in HFpEF patients. More specifically, HFpEF patients have been shown to have decreased cardiac microvascular density, systemic endothelial dysfunction and a lower mean coronary flow reserve. Importantly, impaired coronary microvascular function has been associated with the severity of HF. This review discusses evidence supporting the causal role of endothelial dysfunction in the pathophysiology of HFpEF in human and experimental models.
Sleep Restriction and Recurrent Circadian Disruption Differentially Affects Blood Pressure, Sodium Retention, and Aldosterone Secretion
Authors: McMullan Ciaran J. , McHill Andrew W. , Hull Joseph T. , Wang Wei , Forman John P. , Klerman Elizabeth B.
Published: July 2022

Prolonged exposure to chronic sleep restriction (CSR) and shiftwork are both associated with incident hypertension and cardiovascular disease. We hypothesized that the combination of CSR and shiftwork’s rotating sleep schedule (causing recurrent circadian disruption, RCD) would increase blood pressure, renal sodium retention, potassium excretion, and aldosterone excretion. Seventeen healthy participants were studied during a 32-day inpatient protocol that included 20-h “days” with associated scheduled sleep/wake and eating behaviors. Participants were randomly assigned to restricted (1:3.3 sleep:wake, CSR group) or standard (1:2 sleep:wake, Control group) ratios of sleep:wake duration. Systolic blood pressure during circadian misalignment was ∼6% higher in CSR conditions. Renal sodium and potassium excretion showed robust circadian patterns; potassium excretion also displayed some influence of the scheduled behaviors (sleep/wake, fasting during sleep so made parallel fasting/feeding). In contrast, the timing of renal aldosterone excretion was affected predominately by scheduled behaviors. Per 20-h “day,” total sodium excretion increased, and total potassium excretion decreased during RCD without a change in total aldosterone excretion. Lastly, a reduced total renal sodium excretion was found despite constant oral sodium consumption and total aldosterone excretion, suggesting a positive total body sodium balance independent of aldosterone excretion. These findings may provide mechanistic insight into the observed adverse cardiovascular and renal effects of shiftwork.
New Insights on Bone Tissue and Structural Muscle-Bone Unit in Constitutional Thinness
Authors: Bailly Mélina , Boscaro Audrey , Thomas Thierry , Féasson Léonard , Costes Frédéric , Pereira Bruno , Hager Jorg , Estour Bruno , Galusca Bogdan , Metz Lore , Courteix Daniel , Thivel David , Verney Julien , Germain Natacha
Published: July 2022

While few studies pointed out low bone mineral densities in constitutionally thin women, little is known about potential explanations. The objective was to further explore bone architecture in both women and men with constitutional thinness to investigate their mechanical muscle-bone coupling (or uncoupling). Thirty constitutionally thin people and 31 normal weight controls participated in the study. Body composition, hip structural analysis, and trabecular bone score were assessed by dual-energy X-ray absorptiometry, bone architecture using high-resolution peripheral quantitative computed tomography, and muscle explorations through histological staining on muscle biopsies. Thirty-two out of the 48 indexes relative to density, geometry, texture, and architecture of bones were found significantly lower (p < 0.05) in constitutionally thin individuals compared with controls. This observation was particularly pronounced in constitutionally thin men. Bone microarchitecture was more altered in weight-supporting bone (tibia) than in non-weight-supporting (radius) bone, which might refer to a normal physiological adaptation (Frost’s mechanostat theory). Yet, the heat-maps of correlations analyses showed many alterations of body weight or muscle associations with bone parameters in constitutionally thin individuals contrary to controls. Present results might support the idea of intrinsic disturbances of bone cells independently to the small muscle structure, particularly in men.
Differential Gene Analysis of Trastuzumab in Breast Cancer Based on Network Pharmacology and Medical Images
Authors: Lu Yuan , Bi Juan , Li Fei , Wang Gang , Zhu Junjie , Jin Jiqing , Liu Yueyun
Published: July 2022

The purpose of this study was to use network pharmacology, biomedical images and molecular docking technology in the treatment of breast cancer to investigate the feasible therapeutic targets and mechanisms of trastuzumab. In the first place, we applied pubchem swisstarget (http://www.swisstargetprediction.ch/), (https://pubchem.ncbi.nlm.nih.gov/) pharmmapper (http://lilab-ecust.cn/pharmmapper/), and the batman-tcm (http://bionet.ncpsb.org.cn/batman-tcm/) database to collect the trastuzumab targets. Then, in NCBI-GEO, breast cancer target genes were chosen (https://www.ncbi.nlm.nih.gov/geo/). The intersection regions of drug and disease target genes were used to draw a Venn diagram. Through Cytoscape 3.7.2 software, and the STRING database, we then formed a protein-protein interaction (PPI) network. Besides, we concluded KEGG pathway analysis and Geen Ontology analysis by using ClueGO in Cytospace. Finally, the top 5 target proteins in the PPI network to dock with trastuzumab were selected. After screening trastuzumab and breast cancer in databases separately, we got 521 target genes of the drug and 1,464 target genes of breast cancer. The number of overlapping genes was 54. PPI network core genes include GAPDH, MMP9, CCNA2, RRM2, CHEK1, etc. GO analysis indicated that trastuzumab treats breast cancer through abundant biological processes, especially positive regulation of phospholipase activity, linoleic acid metabolic process, and negative regulation of endothelial cell proliferation. The molecular function is NADP binding and the cellular component is tertiary granule lumen. The results of KEGG enrichment analysis exhibited four pathways related to the formation and cure of breast cancer, containing Drug metabolism, Glutathione metabolism, Pyrimidine metabolism and PPAR signaling pathway. Molecular docking showed that trastuzumab has good binding abilities with five core target proteins (GAPDH, MMP9, CCNA2, RRM2, CHEK1). This study, through network pharmacology and molecular docking, provides new pieces of evidence and ideas to understand how trastuzumab treats breast cancer at the gene level.
Reliability and Variability of Lower Limb Muscle Activation as Indicators of Familiarity to Submaximal Eccentric Cycling
Authors: Walsh Joel A. , McAndrew Darryl J. , Shemmell Jonathan , Stapley Paul J.
Published: July 2022

Submaximal eccentric (ECC) cycling exercise is commonly used in research studies. No previous study has specified the required time naïve participants take to familiarize with submaximal ECC cycling. Therefore, we designed this study to determine whether critical indicators of cycling reliability and variability stabilize during 15 min of submaximal, semi-recumbent ECC cycling (ECC cycling). Twenty-two participants, aged between 18–51 years, volunteered to complete a single experimental session. Each participant completed three peak eccentric torque protocol (PETP) tests, nine countermovement jumps and 15 min of submaximal (i.e., 10% peak power output produced during the PETP tests) ECC cycling. Muscle activation patterns were recorded from six muscles (rectus femoris, RF; vastus lateralis, VL; vastus medialis, VM; soleus, SOL; medial gastrocnemius, GM; tibialis anterior, TA), during prescribed-intensity ECC cycling, using electromyography (EMG). Minute-to-minute changes in the reliability and variability of EMG patterns were examined using intra-class correlation coefficient (ICC) and variance ratios (VR). Differences between target and actual power output were also used as an indicator of familiarization. Activation patterns for 4/6 muscles (RF, VL, VM and GM) became more consistent over the session, the RF, VL and VM increasing from moderate (ICC = 0.5–0.75) to good (ICC = 0.75–0.9) reliability by the 11th minute of cycling and the GM good reliability from the 1st minute (ICC = 0.79, ICC range = 0.70–0.88). Low variability (VR ≤ 0.40) was maintained for VL, VM and GM from the 8th, 8th and 1st minutes, respectively. We also observed a significant decrease in the difference between actual and target power output (χ214 = 30.895, p = 0.006, W = 0.105), expressed primarily between the 2nd and 3rd minute of cycling (Z = -2.677, p = 0.007). Indicators of familiarization during ECC cycling, including deviations from target power output levels and the reliability and variability of muscle activation patterns stabilized within 15 min of cycling. Based upon this data, it would be reasonable for future studies to allocate ∼ 15 min to familiarize naïve participants with a submaximal ECC cycling protocol.
Resource Translocation Modelling Highlights Density-Dependence Effects in Fruit Production at Various Levels of Organisation
Authors: Génard Michel , Lescourret Françoise , Bertin Nadia , Vercambre Gilles
Published: July 2022

The size of fruit cells, seeds and fruits depends on their number. Could this density-dependence effect result from sugar resource sharing and, if so, does it involve phloem sugar flow or the intensity of sugar unloading to the sink? A density-dependence model (DDM) describing these processes was designed and parameterised for six species at five levels of organisation: cells and seeds within fruits, fruits within clusters, fruits within plants and plants within plots. Sugar flow was driven by phloem conductance, determined by parametersα, governing the shape of its relationship to population size, andκ, its value for a population size of one. Sugar unloading followed Michaelis–Menten kinetics with parametersVm(maximal unloading rate) andKm(Michaelis constant). The DDM effectively reproduced the observed individual mass dynamics, the undercompensating density dependence observed in most species at all sub-plant levels and the undercompensating, exact and overcompensating density dependence observed at the plant level. Conductance (κ) was a scaling factor varying with the level of organisation.Vmwas positively correlated with density dependence, and α was negatively correlated with density dependence only if the plant-within-plot level was not considered. Analysis of the model’s behaviour indicates that density dependence of fruit growth could be a result of sugar sharing, and that both phloem sugar flow and sugar unloading contribute to these effects.
Priming Behavioral Control Enhances Sharing in Preschoolers
Authors: Lee Chanmi , Song Hyun-joo
Published: July 2022

Although young children demonstrate knowledge of fairness norms, their actual sharing is often inconsistent with their understanding. A possible explanation for this discrepancy is the failure of behavioral control in young children. Thus, the present research manipulated behavioral control experimentally and examined its effect on the sharing behavior in 3- to 4-year-olds (N = 64). Children were randomly assigned to either the behavioral control or the neutral prime conditions. In the behavioral control prime condition, the children listened to a story in which a protagonist exerted behavioral control actively, refraining from eating candies. In the neutral prime condition, the children listened to a story in which a protagonist did not explicitly engage in behavioral control. The children then participated in the dictator game. The experimenter asked the children to share as many stickers as they wanted or should with an anonymous child. Children in the behavioral control prime condition shared more stickers than those in the neutral prime condition. However, the two groups did not differ in their judgments of fairness and emotional experiences. The current research provides evidence that preschoolers’ sharing behaviors can be facilitated by behavioral control.
Psychological Responses of Health Care Workers Are Strongly Associated With Pandemic Management
Authors: Pacutova Veronika , Madarasova Geckova Andrea , Kizek Peter , Novotny Martin , de Winter Andrea F. , Reijneveld Sijmen A.
Published: July 2022

Background

Globally, governments adopted protective measures to stabilize the worsening COVID-19 pandemic situation. These measures had a large impact on health care workers (HCWs) and could make the work environment more stressful for them. Therefore, we explored the associations of the psychological responses of HCWs and pandemic management among Slovak health care workers during the second wave of the pandemic.

Materials and Methods

We obtained data about psychological responses, COVID-19 experiences, information overload, non-adherence of the public, work stress and barriers and facilitators of health care provision from HCWs at the COVID-19-related departments of one hospital that mainly covered eastern Slovakia (215 health care professionals, 77.7% females, M/SD = 44.4). Data were analyzed using logistic regression models adjusted for gender.

Results

Pandemic management was most strongly associated with psychological responses, such as irritability, sadness, anxiety, dizziness, and back pain, in health care workers. The non-adherence of the public had the strongest associated psychological impact on HCWs, mostly affecting anxiety and irritability (odds ratios, ORs varying from 3.9 to 7.0). From the barriers and facilitators of health care provision, the use of personal protective equipment had the most impact psychologically, whereas efficient department management was most protective, with ORs around 0.3.

Conclusion

Pandemic management has a large impact on health care workers, and promoting resilience may seriously decrease job-related stress and associated psychological responses of HCWs.