Miracle-dz/UniFAR-FTUs huggingface dataset:
Disparity of Gut Microbiota Composition Among Elite Athletes and Young Adults With Different Physical Activity Independent of Dietary Status: A Matching Study

Objective This study aimed to investigate the disparity of gut microbiota among elite athletes and young adults with different physical activity independent of dietary status. Methods In Hangzhou, China, an age and sex matching study was conducted between April and May 2021. A total of 66 Chinese young adults were recruited in this study and divided into an elite athlete group, physically active group, and physically inactive group. Fecal samples were collected to assess gut microbiota composition. Dietary status was measured using a food-frequency questionnaire. Comparisons in gut microbiota and blood biomarkers among three groups were analyzed by using the analysis of covariance. Results The findings depicted a tendency to form clusters for beta diversity among three groups, while no significant difference was observed in both alpha and beta diversity. In the multiple analysis model, by adjusting dietary status, a significantly higher abundance of Clostridiaceae (p = 0.029) and Megamonas_rupellensis (p = 0.087) was observed in elite athletes compared to that in general young adults. Furthermore, inflammation-related bacteria such as Bilophila (p = 0.011) and Faecalicoccus (p = 0.050) were enriched in physically inactive young adults compared to two other groups. Pearson's correlation analysis showed a positive association between Bilophila and circulating white body cell count (r = 0.332, p = 0.006) and its subtypes including neutrophils (r = 0.273, p = 0.027), and lymphocytes (r = 0.327, p = 0.007). Megamonas_rupellensis has been shown associated positively with serum lymphocytes levels (r = 0.268, p = 0.03). Although no significant differences were observed, the elite athletes tended to have lower levels of blood biomarkers of immunity within a normal range, which may reflect a better immune function. Conclusion This matching study indicated that physically inactive young adults are more likely to have a lower immune function and a higher abundance of pro-inflammatory gut bacteria than elite athletes and physically active young adults. Dietary status should be considered as an important factor that may affect the association of physical activity with immune function and gut microbiota.
Prognostic and Predictive Value of Liquid Biopsy-Derived Androgen Receptor Variant 7 (AR-V7) in Prostate Cancer: A Systematic Review and Meta-Analysis

In advanced prostate cancer, access to recent diagnostic tissue samples is restricted and this affects the analysis of the association of evolving biomarkers such as AR-V7 with metastatic castrate resistance. Liquid biopsies are emerging as alternative analytes. To clarify clinical value of AR-V7 detection from liquid biopsies, here we performed a meta-analysis on the prognostic and predictive value of androgen receptor variant 7 (AR-V7) detected from liquid biopsy for patients with prostate cancer (PC), three databases, the Embase, Medline, and Scopus were searched up to September 2021. A total of 37 studies were included. The effects of liquid biopsy AR-V7 status on overall survival (OS), radiographic progression-free survival (PFS), and prostate-specific antigen (PSA)-PFS were calculated with RevMan 5.3 software. AR-V7 positivity detected in liquid biopsy significantly associates with worse OS, PFS, and PSA-PFS (P <0.00001). A subgroup analysis of patients treated with androgen receptor signaling inhibitors (ARSi such as abiraterone and enzalutamide) showed a significant association of AR-V7 positivity with poorer OS, PFS, and PSA-PFS. A statistically significant association with OS was also found in taxane-treated patients (P = 0.04), but not for PFS (P = 0.21) or PSA-PFS (P = 0.93). For AR-V7 positive patients, taxane treatment has better OS outcomes than ARSi (P = 0.01). Study quality, publication bias and sensitivity analysis were integrated in the assessment. Our data show that liquid biopsy AR-V7 is a clinically useful biomarker that is associated with poor outcomes of ARSi-treated castrate resistant PC (CRPC) patients and thus has the potential to guide patient management and also to stratify patients for clinical trials. More studies on chemotherapy-treated patients are warranted. Systematic Review Registration PROSPERO, CRD42021239353.
Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in E2a-/- T Acute Lymphoblastic Leukemia

T lymphocyte acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease affecting T cells at multiple stages of their development and is characterized by frequent genomic alterations. The transcription factor LEF1 is inactivated through mutation in a subset of T-ALL cases but elevated LEF1 expression and activating mutations have also been identified in this disease. Here we show, in a murine model of T-ALL arising due to E2a inactivation, that the developmental timing of Lef1 mutation impacts its ability to function as a cooperative tumor suppressor or oncogene. T cell transformation in the presence of LEF1 allows leukemic cells to become addicted to its presence. In contrast, deletion prior to transformation both accelerates leukemogenesis and results in leukemic cells with altered expression of genes controlling receptor-signaling pathways. Our data demonstrate that the developmental timing of Lef1 mutations impact its apparent oncogenic or tumor suppressive characteristics and demonstrate the utility of mouse models for understanding the cooperation and consequence of mutational order in leukemogenesis.
Monsoon Fringe Area Moisture Transportation Revealed by Water Stable Isotopes: A Lanzhou River Valley Case Study

Because of global warming, the water cycle has intensified and precipitation has changed, with monsoons evolving to become more complex, particularly in monsoon fringe areas. Therefore, it is important to use stable isotopes to trace moisture sources in monsoon fringe areas, such as semiarid areas. In this study, in situ measurements of water vapor isotopes were obtained in the monsoon fringe areas of Lanzhou (36.1° N, 103.7° E), between May and November 2019 with the aim of analyzing the stable isotope composition and atmospheric water vapor variation to improve our understanding of moisture transport. The following results were obtained: stable isotopic variation of atmospheric water vapor shows an alternation between west and southwest moisture with wind directions and sources of water vapor, with δ18O and δ2H varying from high to low. In the Lanzhou valley, water vapor isotopes show a distinct daily cycle of δ17O, δ18O, and δ2H and are consistent with temperature changes. Water vapor isotopes, particularly d-excess, are correlated with temperature and absolute humidity. With regard to the local atmospheric water vapor line (LAVL), we show that the slope and intercept of the LAVL are affected by sub-cloud secondary evaporation and topography.
The Moderating Effects of Social Media Activities on the Relationship Between Effort-Reward Imbalance and Health and Wellbeing: A Case Study of the Oil and Gas Industry in Malaysia

Background Social media activities affect every aspect of human life, be it personal, social or professional. Previous studies have confirmed the role of social media in affecting health in terms of releasing stress and providing social support. Increased occupational health disorders and increased time spent on social media activities motivate us to investigate this phenomenon in the context of occupational health. Therefore, the objective of this study is to measure the effects of social media activities related to personal and social life as well as work-life on health and wellbeing of office employees, on their job efforts and job rewards, and in moderating the effect of effort-reward imbalance on health and wellbeing. Methods Initially, to develop constructs related to social media activities, web-based structured interviews were conducted with five office employees working in the oil and gas industry for the last 5 years. Then, using an online questionnaire survey, data was collected from 424 office employees working in the oil and gas industry in Malaysia. Using statistical software for social science (SPSS) and Smart PLS, exploratory factor analysis and confirmatory factor analysis were conducted to identify reliability and validity (discriminant validity, convergent validity and composite validity) of the constructs. Following this, path analysis was conducted and the moderating effects were identified. Results Social media activities related to work-life decrease health and wellbeing by 11% and weaken the negative effect of effort-reward-imbalance on health and wellbeing by 17.6% at a 1% level of significance. The results of social media activities related to personal and social life strengthen the negative effect of effort-reward imbalance on health and wellbeing by 12% and negatively affects health and wellbeing and job rewards by 13, 55%, respectively. The direct effect of effort-reward imbalance and job efforts is significantly negative on health and wellbeing by 59 and 10%, respectively. Conclusion It is concluded that social media activities of the office employees significantly moderate the effect of effort-reward imbalance on health and wellbeing and intervene in job rewards in the organizations. Hence, the effect of social media activities reduces the health and wellbeing of office employees.
The Lack of Dopamine Transporter Is Associated With Conditional Associative Learning Impairments and Striatal Proteomic Changes

Dopamine (DA) is critically involved in different functions of the central nervous system (CNS) including control of voluntary movement, affect, reward, sleep, and cognition. One of the key components of DA neurotransmission is DA reuptake by the DA transporter (DAT), ensuring rapid clearance of DA from the synaptic cleft. Thus, lack of DAT leads to persistent high extracellular DA levels. While there is strong evidence for a role of striatal dopaminergic activity in learning and memory processes, little is known about the contribution of DAT deficiency to conditional learning impairments and underlying molecular processes. DAT-knockout (DAT-KO) rats were tested in a set of behavioral experiments evaluating conditional associative learning, which requires unaltered striatal function. In parallel, a large-scale proteomic analysis of the striatum was performed to identify molecular factors probably underlying behavioral patterns. DAT-KO rats were incapable to acquire a new operant skill in Pavlovian/instrumental autoshaping, although the conditional stimulus–unconditional stimulus (CS-US) association seems to be unaffected. These findings suggest that DAT directly or indirectly contributes to the reduction of transference of incentive salience from the reward to the CS. We propose that specific impairment of conditional learning might be caused by molecular adaptations to the hyperdopaminergic state, presumably by dopamine receptor 1 (DRD1) hypofunction, as proposed by proteomic analysis. Whether DRD1 downregulation can cause cognitive deficits in the hyperdopaminergic state is the subject of discussion, and further studies are needed to answer this question. This study may be useful for the interpretation of previous and the design of future studies in the dopamine field.
c-Abl Activation Linked to Autophagy-Lysosomal Dysfunction Contributes to Neurological Impairment in Niemann-Pick Type A Disease

Niemann-Pick type A (NPA) disease is a fatal lysosomal neurodegenerative disorder caused by the deficiency in acid sphingomyelinase (ASM) activity. NPA patients present severe and progressive neurodegeneration starting at an early age. Currently, there is no effective treatment for this disease and NPA patients die between 2 and 3 years of age. NPA is characterized by an accumulation of sphingomyelin in lysosomes and dysfunction in the autophagy-lysosomal pathway. Recent studies show that c-Abl tyrosine kinase activity downregulates autophagy and the lysosomal pathway. Interestingly, this kinase is also activated in other lysosomal neurodegenerative disorders. Here, we describe that c-Abl activation contributes to the mechanisms of neuronal damage and death in NPA disease. Our data demonstrate that: 1) c-Abl is activated in-vitro as well as in-vivo NPA models; 2) imatinib, a clinical c-Abl inhibitor, reduces autophagy-lysosomal pathway alterations, restores autophagy flux, and lowers sphingomyelin accumulation in NPA patient fibroblasts and NPA neuronal models and 3) chronic treatment with nilotinib and neurotinib, two c-Abl inhibitors with differences in blood-brain barrier penetrance and target binding mode, show further benefits. While nilotinib treatment reduces neuronal death in the cerebellum and improves locomotor functions, neurotinib decreases glial activation, neuronal disorganization, and loss in hippocampus and cortex, as well as the cognitive decline of NPA mice. Our results support the participation of c-Abl signaling in NPA neurodegeneration and autophagy-lysosomal alterations, supporting the potential use of c-Abl inhibitors for the clinical treatment of NPA patients.
Atorvastatin Effectively Inhibits Ancestral and Two Emerging Variants of SARS-CoV-2 in vitro

This article evaluated the in vitro antiviral effect of atorvastatin (ATV) against SARS-CoV-2 and identified the interaction affinity between this compound and two SARS-CoV-2 proteins. The antiviral activity of atorvastatin against this virus was evaluated by three different treatment strategies [(i) pre-post treatment, (ii) pre-infection treatment, and (iii) post-infection treatment] using Vero E6 and Caco-2 cells. The interaction of atorvastatin with RdRp (RNA-dependent RNA polymerase) and 3CL protease (3-chymotrypsin-like protease) was evaluated by molecular docking. The CC50s (half-maximal cytotoxic concentrations) obtained for ATV were 50.3 and 64.5 μM in Vero E6 and Caco-2, respectively. This compound showed antiviral activity against SARS-CoV-2 D614G strain in Vero E6 with median effective concentrations (EC50s) of 15.4, 12.1, and 11.1 μM by pre-post, pre-infection, and post-infection treatments, respectively. ATV also inhibited Delta and Mu variants by pre-post treatment (EC50s of 16.8 and 21.1 μM, respectively). In addition, ATV showed an antiviral effect against the D614G strain independent of the cell line (EC50 of 7.4 μM in Caco-2). The interaction of atorvastatin with SARS-CoV-2 RdRp and 3CL protease yielded a binding affinity of −6.7 kcal/mol and −7.5 kcal/mol, respectively. Our study demonstrated the in vitro antiviral activity of atorvastatin against the ancestral SARS-CoV-2 D614G strain and two emerging variants (Delta and Mu), with an independent effect of the cell line. A favorable binding affinity between ATV and viral proteins by bioinformatics methods was found. Due to the extensive clinical experience of atorvastatin use, it could prove valuable in the treatment of COVID-19.
Influenza A Virus-Driven Airway Inflammation may be Dissociated From Limb Muscle Atrophy in Cigarette Smoke-Exposed Mice

Limb muscle dysfunction is a hallmark of Chronic Obstructive Pulmonary Disease (COPD) which is further worsened following a viral-induced acute exacerbation of COPD (AECOPD). An amplified airway inflammation underlies the aggravated respiratory symptoms seen during AECOPD, however, its contributory role to limb muscle dysfunction is unclear. The present study examined the impact of influenza A virus (IAV)-induced exacerbation on hind limb muscle parameters. Airway inflammation was established in male BALB/c mice by exposure to cigarette smoke (CS) for 8 weeks. Exacerbation was then induced via inoculation with IAV, and various lung and muscle parameters were assessed on day 3 (peak of airway inflammation) and day 10 (resolution phase) post-infection. IAV infection exacerbated CS-induced airway inflammation as evidenced by further increases in immune cell counts within bronchoalveolar lavage fluid. Despite no significant impact on muscle mass, IAV exacerbation worsened the force-generating capacity of the tibialis anterior (TA) muscle. Protein oxidation and myogenic disruption was observed in the TA following CS exposure, however, IAV exacerbation did not augment these detrimental processes. To further explore the contributory role of airway inflammation on myogenic signaling, cultured myotubes were exposed to conditioned medium (CM) derived from bronchial epithelial cells stimulated with polyinosinic:polycytidylic acid and cigarette smoke extract (CSE). Despite an amplified inflammatory response in the lung epithelial cells, the CM derived from these cells did not potentiate myogenic disruption in the C2C12 myotubes. In conclusion, our data suggest that certain parameters of limb muscle dysfunction seen during viral-induced AECOPD may be independent of airway inflammation.
Changes in Gut Microbiota by the Lactobacillus casei Anchoring the K88 Fimbrial Protein Prevented Newborn Piglets From Clinical Diarrhea

In the last 20 years, accumulating evidence indicates that the gut microbiota contribute to the development, maturation, and regulation of the host immune system and mediate host anti-pathogen defenses. Lactobacillus casei (L.casei) is a normal flora of the gastrointestinal tract in mammals and, as a great mucosal delivery vehicle, has wide use in bioengineering. However, the diarrhea prevention role of commensal intestinal microbiota interfered by the recombinant L.casei (rL.casei) in newborn piglets is not well understood. In our study, newborn piglets orally fed with the rL.casei surface displayed the fimbrial protein K88 of enterotoxigenic Escherichia coli (ETEC) and their feces were collected for a period of time after feeding. The next-generation sequencing of these fecal samples showed that the relative abundance of L.casei was significantly increased. The oral administration of rL.casei altered the intestinal microbial community as evidenced by altered microbial diversity and microbial taxonomic composition. Remarkably, the functional enhancing of the intestinal bacterial community by rL.casei was positively correlated with membrane transport, replication, and repair (p < 0.05). The specific antibody detection indicates that high levels of anti-K88 secretory immunoglobulin A (sIgA) were induced in fecal samples and systemic immunoglobulin G was produced in serum. The diarrhea rate in piglets caused by ETEC K88 was decreased by about 24%. Thus, the oral administration of rL.casei not only activated the mucosal and humoral immune responses in vivo but also contributed to shape the intestinal probiotics in newborn piglets and to significantly reduce the diarrhea rates of newborn piglets.
Population Diversity of Antibiotic Resistant Enterobacterales in Samples From Wildlife Origin in Senegal: Identification of a Multidrug Resistance Transposon Carrying blaCTX–M–15 in Escherichia coli

Introduction The role of wildlife in the transmission of antimicrobial resistant (AMR) is suspected but scarcely reported in current studies. Therefore, we studied the dynamics and prevalence of antibiotic-resistant Enterobacterales in antibiotic-limited areas of Senegal. Materials and Methods We collected fecal samples from monkeys and apes (N = 226) and non-fecal environmental samples (N = 113) from Senegal in 2015 and 2019. We grew the samples on selective media, subsequently isolated AMR Enterobacterales, and then sequenced their genomes. Results We isolated 72 different Enterobacterales among which we obtained a resistance rate of 65% for colistin (N = 47/72) and 29% for third generation-cephalosporin (C3G) (29%, N = 21/72). Interestingly, almost 46% of our isolates, among Enterobacter sp. , Citrobacter cronae and Klebsiella aerogenes, belong to 34 new STs. Moreover, the genes blaCTX–M–15, blaTEM1B, sul2, dfrA14, qnrs, aph(3′′), aph(6), tetA, and tetR harbored within a transposon on the IncY plasmid of ST224 Escherichia coli were transferred and inserted into a ST10 E. coli phage coding region. Conclusion Wildlife constitutes a rich, unexplored reservoir of natural microbial diversity, AMR genes and international resistant clones pathogenic in humans. The presence of a transposon that carries AMR genes is intriguing since no antibiotics are used in the non-human primates we studied.
Gender Differences in the Perceived Behavior of Narcissistic Leaders

Although narcissists often emerge as leaders, the relationship between leader narcissism and follower performance is ambiguous and often even found to be negative. For women, narcissism seems especially likely to lead to negative evaluations. Since narcissists have the tendency to be impulsive and change their minds on a whim, they may come across as inconsistent. We propose “inconsistent leader behavior” as a new mechanism in the relationship between leader narcissism and follower performance and argue that leader gender plays an important role in whether narcissistic leaders are perceived as inconsistent. Specifically, we expect leader narcissism to have a negative relationship with follower performance through perceived inconsistent leader behavior, especially for female leaders. Thus, we examine leader gender as a personal factor moderating the relationship between narcissism and perceived inconsistent behavior. Also, as perceived inconsistency is likely less problematic when a good relationship exists, we examine leader–member exchange (LMX) as a contextual condition moderating the relationship between leader behavior and follower performance. We test our moderated mediation model in a multi-source study with 165 unique leader–follower dyads. As expected, leader narcissism was positively related to perceived inconsistent leader behavior, and this relationship was stronger for female leaders. Inconsistent leader behavior was negatively related to follower performance, but only when LMX was low. Our research highlights that perceived behavioral inconsistency can be problematic and—for female leaders—provides an explanation of the negative relation of leader narcissism with follower performance and of the inconsistencies in evaluations of narcissistic leaders’ effectiveness.