Miracle-dz/UniFAR-FTUs huggingface dataset:
Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway

Neuropathic pain is a complex disease with high incidence. Adenosine triphosphate (ATP) and its activated P2X7 receptor are involved in the signal transmission of neuropathic pain. Gallic acid (3,4,5-trihydroxybenzoic acid) is a traditional Chinese medicine obtained from natural plants that exhibit anti-inflammatory, analgesic, and antitumor effects. However, the underlying mechanism for gallic acid in analgesia remains unknown. This study aims to reveal how gallic acid alleviates neuropathic pain behaviors in a rat model with chronic constriction injury (CCI). Real-time PCR, western blotting, double-label immunofluorescence, molecular docking, and whole-cell patch clamp technology were used to explore the therapeutic action of gallic acid on neuropathic pain. The results showed that after CCI rats were treated with gallic acid for 1 week, the mechanical withdrawal threshold and thermal withdrawal latency were increased, accompanied by inhibition of the upregulated expression of P2X7 and TNF-α at both mRNA and protein levels, and reduced NF-κB and phosphorylated-STAT3 in the dorsal root ganglia. At the same time, gallic acid significantly decreased the coexpression of P2X7 and glial fibrillary acidic protein in the dorsal root ganglia. In addition, gallic acid could suppress ATP-activated current in human embryonic kidney 293 (HEK293) cells transfected with the plasmid expressing P2X7 but had no effect on ATP activation current of P2X7-mutant plasmid (with the point mutation sequence of the key site where gallic acid binds to the P2X7 receptor). Therefore, our work suggests that gallic acid may alleviate neuropathic pain in CCI rats by inhibiting the P2X7 receptor and subsequent activation of the TNF-α/STAT3 signaling pathway.
Stimulation of the Epithelial Na+ Channel in Renal Principal Cells by Gs-Coupled Designer Receptors Exclusively Activated by Designer Drugs

The activity of the Epithelial Na+ Channel (ENaC) in renal principal cells (PC) fine-tunes sodium excretion and consequently, affects blood pressure. The Gs-adenylyl cyclase-cAMP signal transduction pathway is believed to play a central role in the normal control of ENaC activity in PCs. The current study quantifies the importance of this signaling pathway to the regulation of ENaC activity in vivo using a knock-in mouse that has conditional expression of Gs-DREADD (designer receptors exclusively activated by designer drugs; GsD) in renal PCs. The GsD mouse also contains a cAMP response element-luciferase reporter transgene for non-invasive bioluminescence monitoring of cAMP signaling. Clozapine N-oxide (CNO) was used to selectively and temporally stimulate GsD. Treatment with CNO significantly increased luciferase bioluminescence in the kidneys of PC-specific GsD but not control mice. CNO also significantly increased the activity of ENaC in principal cells in PC-specific GsD mice compared to untreated knock-in mice and CNO treated littermate controls. The cell permeable cAMP analog, 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate, significantly increased the activity and expression in the plasma membrane of recombinant ENaC expressed in CHO and COS-7 cells, respectively. Treatment of PC-specific GsD mice with CNO rapidly and significantly decreased urinary Na+ excretion compared to untreated PC-specific GsD mice and treated littermate controls. This decrease in Na+ excretion in response to CNO in PC-specific GsD mice was similar in magnitude and timing as that induced by the selective vasopressin receptor 2 agonist, desmopressin, in wild type mice. These findings demonstrate for the first time that targeted activation of Gs signaling exclusively in PCs is sufficient to increase ENaC activity and decrease dependent urinary Na+ excretion in live animals.
Effects of Vanillic Acid on Dynamic Fermentation Parameter, Nitrogen Distribution, Bacterial Community, and Enzymatic Hydrolysis of Stylo Silage

Vanillic acid (VA) is a phenolic acid derivative commonly found in plants and foods, with a pleasant creamy odor and pharmacologic activities, which is hypothesized to help improve silage fermentation. The silage profile of stylo silage ensiled with addition of VA was evaluated. The results showed that VA addition resulted in the decrease of pH value (5.22 vs. 4.33), dry matter loss (5.37 vs. 2.51% DM), and ammonia-N proportion (14.57 vs. 1.51% CP) of stylo silage as well as the increase of lactic acid concentration (0.51 vs. 1.17% DM), true protein proportion (51.18 vs. 58.47% CP), and saccharification yield (113.64 vs. 126.40 mg/g DM). Meanwhile, bacterial community of stylo silage was altered, where the relative abundance of Enterobacter, Clostridium, and Kosakonia decreased and that of Commensalibacter and Methylobacterium increased. In conclusion, it is suggested that VA could be used as a novel silage additive to improve silage fermentation and nutrient preservation of stylo silage.
Efficiency and Safety of the Selective Relaxant Binding Agent Adamgammadex Sodium for Reversing Rocuronium-Induced Deep Neuromuscular Block: A Single-Center, Open-Label, Dose-Finding, and Phase IIa Study

Background: Rapid reversal of neuromuscular block after surgery and anesthesia is often necessary. Here, we reported the primary efficacy and safety data from a phase IIa study on adamgammadex sodium, a newly developed modified γ-cyclodextrin derivative. Methods: This was a phase IIa, single-center, randomized, open-label, and dose-finding study that enrolled 35 patients under general anesthesia who received the neuromuscular blocking agent rocuronium for induction and maintenance of neuromuscular blockade. The subjects were randomized to one of the five adamgammadex dose groups (2, 4, 6, 8, and 10 mg kg−1) and to the 4 mg kg−1 sugammadex group. Pharmacological efficacy was the recovery time from the start of adamgammadex or sugammadex administration to train-of-four (TOF) ratio ≥0.9, 0.8, and 0.7 among the different dose groups. Adverse events were recorded throughout the study. Results: The efficacy in reversing deep neuromuscular block was the same between 4 mg kg−1 sugammadex and adamgammadex. However, in the lowest dose groups of 2 and 4 mg kg−1 adamgammadex, adequate reversal could not be achieved in all subjects. The recovery time of TOF ratio to 0.9, 0.8, and 0.7 was shorter in the adamgammadex 10 mg kg−1 group than in the sugammadex 4 mg kg−1 group. The average values of the TOF ratio after 3 min of administration of adamgammadex 8 and 10 mg kg−1 and sugammadex 4 mg kg−1 were >90%. There were no serious adverse events after the use of adamgammadex, and no subjects had to be withdrawn from the trial. Conclusions: Adamgammadex enabled quick, predictable, and tolerable reversion of rocuronium-induced deep neuromuscular block in a dose-dependent manner. Adamgammadex doses of 6–10 mg kg−1 might be the recommended dose range for further exploration of efficacy. Clinical Trial Registration: This study was registered at chictr.org. cn, identifier: ChiCTR2000038391.
Adverse Cardiovascular Effects of Anti-COVID-19 Drugs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 infection is the cause of the ongoing global pandemic. Mortality from COVID-19 infection is particularly high in patients with cardiovascular diseases. In addition, COVID-19 patients with preexisting cardiovascular comorbidities have a higher risk of death. Main cardiovascular complications of COVID-19 are myocardial infarction, myocarditis, acute myocardial injury, arrhythmias, heart failure, stroke, and venous thromboembolism. Therapeutic interventions in terms of drugs for COVID-19 have many cardiac adverse effects. Here, we review the relative therapeutic efficacy and adverse effects of anti-COVID-19 drugs.
Construction of Consensus Genetic Map With Applications in Gene Mapping of Wheat (Triticum aestivum L.) Using 90K SNP Array

Wheat is one of the most important cereal crops worldwide. A consensus map combines genetic information from multiple populations, providing an effective alternative to improve the genome coverage and marker density. In this study, we constructed a consensus map from three populations of recombinant inbred lines (RILs) of wheat using a 90K single nucleotide polymorphism (SNP) array. Phenotypic data on plant height (PH), spike length (SL), and thousand-kernel weight (TKW) was collected in six, four, and four environments in the three populations, and then used for quantitative trait locus (QTL) mapping. The mapping results obtained using the constructed consensus map were compared with previous results obtained using individual maps and previous studies on other populations. A simulation experiment was also conducted to assess the performance of QTL mapping with the consensus map. The constructed consensus map from the three populations spanned 4558.55 cM in length, with 25,667 SNPs, having high collinearity with physical map and individual maps. Based on the consensus map, 21, 27, and 19 stable QTLs were identified for PH, SL, and TKW, much more than those detected with individual maps. Four PH QTLs and six SL QTLs were likely to be novel. A putative gene called TraesCS4D02G076400 encoding gibberellin-regulated protein was identified to be the candidate gene for one major PH QTL located on 4DS, which may enrich genetic resources in wheat semi-dwarfing breeding. The simulation results indicated that the length of the confidence interval and standard errors of the QTLs detected using the consensus map were much smaller than those detected using individual maps. The consensus map constructed in this study provides the underlying genetic information for systematic mapping, comparison, and clustering of QTL, and gene discovery in wheat genetic study. The QTLs detected in this study had stable effects across environments and can be used to improve the wide adaptation of wheat cultivars through marker-assisted breeding.
Factors Related to Mental Health During the COVID-19 Lockdown in Spain

The COVID-19 disease has forced governments to adopt exceptional measures. The lockdown decreed in Spain in 2020 required citizens to stay confined at home, which might have affected their mental health. The objective is to identify factors that influenced adults' mental health during this period. A sample of 3,508 adults from the Spanish general population completed an online survey that collected sociodemographic data and information about daily planning and activities, healthy habits, loneliness, coping humor and mental health. Data were analyzed using Structural Equation Modeling. According to the results, the proposed model showed good fit values, and latent variables explained 30% of the variance in mental health. Loneliness, coping humor, healthy habits, age and gender had a significant weight in the prediction of mental health during lockdown. Area of residence, number of days of confinement and number of people in the household were not related to mental health. This study addresses the effect of COVID-19 and social distancing measures by identifying risk and protective factors for the development of mental health difficulties. There is a need to target specific and early interventions aimed at mitigating the psychological impact of the pandemic while increasing well-being, especially in more vulnerable groups.
Implementation and Access to Pre-exposure Prophylaxis for Human Immunodeficiency Virus by Men Who Have Sex With Men in Europe

Pre-exposure prophylaxis (PrEP) is a significant public health intervention with proven efficacy and safety in the prevention of human immunodeficiency virus (HIV) infection, which has taken a considerable amount of time to reach Europe in relation to their transatlantic counterparts, namely, the United States of America (USA). There, it is perceived as being an essential prevention tool to be integrated within existing medical, behavioral and structural interventions in place for the management and containment of HIV infection in men who have sex with men (MSM). In a region such as Europe, with approximately double the USA population, it is estimated that not even 10% have proper access to PrEP, and given the lack of coordination with healthcare, taking PrEP has to be at their own expense. Here, we identify the reasons behind the 4-year lag in the approval of PrEP in the European Union/European Economic Area (and Europe in general) and explore the efficacy and effectiveness of PrEP needed to be confirmed with some implementation or demonstration studies conducted in the region. Independent of the data gathered, access of MSM to PrEP is far from ideal in Europe and much still needs to be done. The demonstration of the cost-effectiveness of PrEP alongside other social and behavioral factors needs to be addressed, while the clear populations within MSM that will benefit from this intervention are properly identified and make use of the latest recommendations of the World Health Organization that consider not only daily PrEP but also event-driven PrEP. The momentum for the proper implementation of PrEP in the EU is not lost, and with the existence of generics and even new formulations, there is a renewed opportunity for unleashing the public health benefits arising from this pharmacological tool with other interventions in place (e.g., condoms, testing, and counseling).
Imaging Voltage with Microbial Rhodopsins

Membrane potential is the critical parameter that reflects the excitability of a neuron, and it is usually measured by electrophysiological recordings with electrodes. However, this is an invasive approach that is constrained by the problems of lacking spatial resolution and genetic specificity. Recently, the development of a variety of fluorescent probes has made it possible to measure the activity of individual cells with high spatiotemporal resolution. The adaptation of this technique to image electrical activity in neurons has become an informative method to study neural circuits. Genetically encoded voltage indicators (GEVIs) can be used with superior performance to accurately target specific genetic populations and reveal neuronal dynamics on a millisecond scale. Microbial rhodopsins are commonly used as optogenetic actuators to manipulate neuronal activities and to explore the circuit mechanisms of brain function, but they also can be used as fluorescent voltage indicators. In this review, we summarize recent advances in the design and the application of rhodopsin-based GEVIs.
The Association Between Internet Addiction and Anxiety in Nursing Students: A Network Analysis

Background: Nursing students who suffer from co-occurring anxiety experience added difficulties when communicating and interacting with others in a healthy, positive, and meaningful way. Previous studies have found strong positive correlations between Internet addiction (IA) and anxiety, suggesting that nursing students who report severe IA are susceptible to debilitating anxiety as well. To date, however, network analysis (NA) studies exploring the nature of association between individual symptoms of IA and anxiety have not been published. Objective: This study examined associations between symptoms of IA and anxiety among nursing students using network analysis. Methods: IA and anxiety symptoms were assessed using the Internet Addiction Test (IAT) and the Generalized Anxiety Disorder Screener (GAD-7), respectively. The structure of IA and anxiety symptoms was characterized using “Strength” as a centrality index in the symptom network. Network stability was tested using a case-dropping bootstrap procedure and a Network Comparison Test (NCT) was conducted to examine whether network characteristics differed on the basis of gender and by region of residence. Results: A total of 1,070 nursing students participated in the study. Network analysis showed that IAT nodes, “Academic decline due to Internet use,” “Depressed/moody/nervous only while being off-line,” “School grades suffer due to Internet use,” and “Others complain about your time spent online” were the most influential symptoms in the IA-anxiety network model. Gender and urban/rural residence did not significantly influence the overall network structure. Conclusion: Several influential individual symptoms including Academic declines due to Internet use, Depressed/moody/nervous only while being off-line, School grades suffering due to Internet use and Others complain about one's time spent online emerged as potential targets for clinical interventions to reduce co-occurring IA and anxiety. Additionally, the overall network structure provides a data-based hypothesis for explaining potential mechanisms that account for comorbid IA and anxiety.
Perfectionism in Adolescence: Associations With Gender, Age, and Socioeconomic Status in a Norwegian Sample

Background: Perfectionism in adolescence has received increased attention, but few studies have examined this in non-clinical samples. This study investigated perfectionism among adolescents from the general population in relation to demographic factors. Methods: The present study is cross-sectional and draws on the epidemiological youth@hordaland study. The sample consisted of 10.217 adolescents aged 16–19 years (52.9% girls). Self-reported perfectionism was assessed by the EDI-P scale from the Eating Disorder Inventory with two dimensions of perfectionism, namely self-oriented (SOP) and socially prescribed (SPP) perfectionism, and a total score. Perfectionism was analyzed in relation to age, gender, and socioeconomic status (SES) by perceived economic well-being and parental education level. Chi-squared tests, t-tests, and regression analyses were performed. Results: There were few gender differences on the mean scores on perfectionism, with similar levels on the total score of EDI-P and SOP, while girls scored slightly higher on SPP (p < 0.001). The latter gender difference represented a small effect size (Cohen's d = 0.053). Chi-square analyses with perfectionism split at the 90th percentile across gender showed that there were significantly more girls than boys among the high scorers both for EDI-P, EDI-SOP, and EDI-SPP. There were no significant differences between levels of perfectionism between the three age groups. The logistic regression analyses adjusted by age and gender showed that adolescents with a better perceived economic well-being had increased odds of high perfectionism. This was evident for overall EDI-P (OR = 1.760, 95% CI = 1.493–2.076), SOP (OR = 1.543, 95% CI = 1.292–1.843), and SPP (OR = 1.836, 95% CI = 1.559–2.163). Parental education was not significantly associated with perfectionism scores among the adolescents. Conclusions: The levels of perfectionism were relatively similar between the genders in the present study, besides slightly higher SPP among girls than boys. There were also significantly more girls than boys among the high scorers on overall perfectionism, SOP, and SPP, respectively. High perfectionism was related to SES for perceived economic well-being, but not for parental education level. Implications for further research and clinical interventions were suggested.
COVID-19 Pneumonia: The Great Ultrasonography Mimicker

The pandemic spread of the new severe acute respiratory syndrome coronavirus 2 has raised the necessity to identify an appropriate imaging method for early diagnosis of coronavirus disease 2019 (COVID-19). Chest computed tomography (CT) has been regarded as the mainstay of imaging evaluation for pulmonary involvement in the early phase of the pandemic. However, due to the poor specificity of the radiological pattern and the disruption of radiology centers' functionality linked to an excessive demand for exams, the American College of Radiology has advised against CT use for screening purposes. Lung ultrasound (LUS) is a point-of-care imaging tool that is quickly available and easy to disinfect. These advantages have determined a “pandemic” increase of its use for early detection of COVID-19 pneumonia in emergency departments. However, LUS findings in COVID-19 patients are even less specific than those detectable on CT scans. The scope of this perspective article is to discuss the great number of diseases and pathologic conditions that may mimic COVID-19 pneumonia on LUS examination.
Acute Effects of the Wim Hof Breathing Method on Repeated Sprint Ability: A Pilot Study

The Wim Hof breathing method (WHBM) combines periods of hyperventilation (HV) followed by voluntary breath-holds (BH) at low lung volume. It has been increasingly adopted by coaches and their athletes to improve performance, but there was no published research on its effects. We determined the feasibility of implementing a single WHBM session before repeated sprinting performance and evaluated any acute ergogenic effects. Fifteen amateur runners performed a single WHBM session prior to a Repeated Ability Sprint Test (RAST) in comparison to voluntary HV or spontaneous breathing (SB) (control) in a randomized cross-over design. Gas exchange, heart rate, and finger pulse oxygen saturation (SpO2) were monitored. Despite large physiological effects in the SpO2 and expired carbon dioxide (VCO2) levels of both HV and WHBM, no significant positive or negative condition effects were found on RAST peak power, average power, or fatigue index. Finger SpO2 dropped to 60 ± 12% at the end of the BHs. Upon the last HV in the WHBM and HV conditions, end-tidal CO2 partial pressure (PETCO2) values were 19 ± 3 and 17 ± 3 mmHg, indicative of respiratory alkalosis with estimated arterial pH increases of +0.171 and of +0.181, respectively. Upon completion of RAST, 8 min cumulated expired carbon dioxide volumes in the WHBM and HV were greater than in SB, suggesting lingering carbon dioxide stores depletion. These findings indicate that despite large physiological effects, a single WHBM session does not improve anaerobic performance in repeated sprinting exercise.
Extracellular and Intracellular Angiotensin II Regulate the Automaticity of Developing Cardiomyocytes via Different Signaling Pathways

Angiotensin II (Ang II) plays an important role in regulating various physiological processes. However, little is known about the existence of intracellular Ang II (iAng II), whether iAng II would regulate the automaticity of early differentiating cardiomyocytes, and the underlying mechanism involved. Here, iAng II was detected by immunocytochemistry and ultra-high performance liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry in mouse embryonic stem cell–derived cardiomyocytes (mESC-CMs) and neonatal rat ventricular myocytes. Expression of AT1R-YFP in mESC-CMs revealed that Ang II type 1 receptors were located on the surface membrane, while immunostaining of Ang II type 2 receptors (AT2R) revealed that AT2R were predominately located on the nucleus and the sarcoplasmic reticulum. While extracellular Ang II increased spontaneous action potentials (APs), dual patch clamping revealed that intracellular delivery of Ang II or AT2R activator C21 decreased spontaneous APs. Interestingly, iAng II was found to decrease the caffeine-induced increase in spontaneous APs and caffeine-induced calcium release, suggesting that iAng II decreased spontaneous APs via the AT2R- and ryanodine receptor–mediated pathways. This is the first study that provides evidence of the presence and function of iAng II in regulating the automaticity behavior of ESC-CMs and may therefore shed light on the role of iAng II in fate determination.