Miracle-dz/UniFAR-FTUs huggingface dataset:
Natural History of Anal Papillomavirus Infection in HIV-Negative Men Who Have Sex With Men Based on a Markov Model: A 5-Year Prospective Cohort Study

Objective Men who have sex with men (MSM) are at increased risk for Human papillomavirus (HPV) infection compared to women and heterosexual men. We aimed to assess the incidence, clearance and duration of anal human papillomavirus (HPV) infection in HIV-negative MSM and the influencing factors in a 5-year prospective cohort study. Methods From April 2016 to April 2021, HIV-negative MSM were recruited and followed every 6 months in Urumqi, Xinjiang, China. Questionnaires and anal swabs were collected at baseline and every 6 months. We detected 37 anal HPV genotypes using the HPV Geno Array Diagnostic Kit Test. Incidence and clearance rates of anal HPV infection and the influencing factors were estimated using a two-state Markov model. Results A total of 585 MSM were included with a median age of 37 years [interquartile range (IQR): 31–43 years] and were followed for a median 2.8 years (IQR: 1.8–3.6 years). Incidence rates for any HPV and high-risk HPV (Hr-HPV) were 53.4 [95% confidence interval (CI): 49.1–58.0] and 39.0 (95% CI: 35.7–42.5)/1,000 person-months. Median duration of infection was 9.67 (95% CI: 8.67–10.86) and 8.51 (95% CI: 7.57–9.50) months, respectively. Clearance rates for any HPV and Hr-HPV were 50.9 (95% CI: 46.7–55.3) and 62.1 (95% CI: 56.8–66.7)/1,000 person-months, respectively. HPV16 and HPV6 had the highest incidence, lowest clearance rate and longest duration of infection among Hr-HPV and low-risk HPV (Lr-HPV) types, respectively. Receptive anal sex is a risk factor for any HPV [hazard ratio (HR) = 1.66, 95% CI: 1.16–2.38] and Hr-HPV infection (HR = 1.99, 95% CI:1.39–2.85). Recent anal sex without condom use was significantly associated with any HPV (HR = 1.80, 95% CI: 1.10–2.94) and Hr-HPV infection (HR = 2.60, 95% CI: 1.42–4.77). Age ≥35 years was significantly associated with Lr-HPV HPV infection only (HR = 1.40, 95% CI: 1.02–1.93). Both inserted and receptive anal sex (HR = 0.60, 95% CI: 0.40–0.89) and anal sex ≥2 times per week (HR = 0.61, 95% CI: 0.43–0.87) were associated with reduced Hr-HPV clearance. Six of the nine-valent vaccine types (HPV6, 11, 16, 18, 52 and 58) occurred most frequently, which indicates the need for high vaccination coverage in MSM. Conclusions In this cohort study, high incidence and low clearance of any HPV, Hr-HPV and individual HPV infections emphasize the importance of MSM vaccination. Modifiable behavioral factors such as condoms and drug use should be incorporated into HPV prevention strategies.
Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?

The type 5 metabotropic glutamate receptor, mGlu5, has been proposed as a potential therapeutic target for the treatment of several neurodegenerative diseases. In preclinical neurodegenerative disease models, novel allosteric modulators have been shown to improve cognitive performance and reduce disease-related pathology. A common pathological hallmark of neurodegenerative diseases is a chronic neuroinflammatory response, involving glial cells such as astrocytes and microglia. Since mGlu5 is expressed in astrocytes, targeting this receptor could provide a potential mechanism by which neuroinflammatory processes in neurodegenerative disease may be modulated. This review will discuss current evidence that highlights the potential of mGlu5 allosteric modulators to treat neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Furthermore, this review will explore the role of mGlu5 in neuroinflammatory responses, and the potential for this G protein-coupled receptor to modulate neuroinflammation.
Key pedagogical and technological factors for effective blended learning design

This summary describes a new design framework to support science education through blended learning, based on a participatory and interactive approach supported by ICTbased tools, called Science Learning Activities Model (SLAM). This design framework is important as a response to complex changes in society and education (e.g. high turnover rate of knowledge, changing labour market), which require a more creative response of learners to the world problems that surround them. The framework is concerned with the assumption that science-learning activities should be applicable and relevant to contemporary life and transferable to ‘real-world’ situations. The design framework proposes three design dimensions: context, technology and pedagogy, and aims at integrating learning in formal and informal contexts through blended learning scenarios by using today’s flexible, interactive and immersive technologies (e.g. mobile, augmented reality, virtual reality). EMPOWER expert pools: Institutional Support, Curriculum development & Course design
Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol

Although resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the biotransformation of RES, as its metabolites may contribute profound biological effects. After 4-week oral administration, 11 metabolites of RES were identified and quantified in mice by HPLC-MS/MS, including dihydro-resveratrol (DHR), lunularin (LUN), and conjugates (sulfates and glucuronides) of RES, DHR and LUN. Importantly, DHR, LUN, and their conjugates were much more abundantly distributed in tissues, gastrointestinal tract (GIT), and biological fluids compared to RES and its conjugates. Moreover, we established that DHR and LUN were gut bacteria-derived metabolites of RES, as indicated by their depletion in antibiotic-treated mice. Furthermore, the biological activities of RES, DHR, and LUN were determined at physiologically relevant levels. DHR and LUN exhibited stronger anti-inflammatory and anti-cancer effects than RES at the concentrations found in mouse tissues. In summary, our study profiled the tissue distribution of the metabolites of RES after its oral administration in mice and uncovered the important role of gut microbial metabolites of RES in the biological activities of RES in vivo.
Increased miR-155 in Microglial Exosomes Following Heat Stress Accelerates Neuronal Autophagy via Their Transfer Into Neurons

Background Heat stroke is the outcome of excessive heat stress, which results in core temperatures exceeding 40°C accompanied by a series of complications. The brain is particularly vulnerable to damage from heat stress. In our previous studies, both activated microglia and increased neuronal autophagy were found in the cortices of mice with heat stroke. However, whether activated microglia can accelerate neuronal autophagy under heat stress conditions is still unknown. In this study, we aimed to investigate the underlying mechanism that caused neuronal autophagy upregulation in heat stroke from the perspective of exosome-mediated intercellular communication. Methods In this study, BV2 and N2a cells were used instead of microglia and neurons, respectively. Exosomes were extracted from BV2 culture supernatants by ultracentrifugation and then characterized via transmission electron microscopy, nanoparticle tracking analysis and Western blotting. N2a cells pretreated with/without miR-155 inhibitor were cocultured with microglial exosomes that were treated with/without heat stress or miR-155 overexpression and subsequently subjected to heat stress treatment. Autophagy in N2a cells was assessed by detecting autophagosomes and autophagy-related proteins through transmission electron microscopy, immunofluorescence, and Western blotting. The expression of miR-155 in BV2 and BV2 exosomes and N2a cells was measured using real-time reverse transcription polymerase chain reaction. Target binding analysis was verified via a dual-luciferase reporter assay. Results N2a autophagy moderately increased in response to heat stress and accelerated by BV2 cells through transferring exosomes to neurons. Furthermore, we found that neuronal autophagy was positively correlated with the content of miR-155 in microglial exosomes. Inhibition of miR-155 partly abolished autophagy in N2a cells, which was increased by coculture with miR-155-upregulated exosomes. Mechanistic analysis confirmed that Rheb is a functional target of miR-155 and that microglial exosomal miR-155 accelerated heat stress-induced neuronal autophagy mainly by regulating the Rheb-mTOR signaling pathway. Conclusion Increased miR-155 in microglial exosomes after heat stroke can induce neuronal autophagy via their transfer into neurons. miR-155 exerted these effects by targeting Rheb, thus inhibiting the activity of mTOR signaling. Therefore, miR-155 could be a promising target for interventions of neuronal autophagy after heat stroke.
How Donor and Surgical Factors Affect the Viability and Functionality of Human Hepatocytes Isolated From Liver Resections

Liver resections are a significant source of primary human hepatocytes used mainly in artificial liver devices and pharmacological and biomedical studies. However, it is not well known how patient-donor and surgery-dependent factors influence isolated hepatocytes’ yield, viability, and function. Hence, we aimed to analyze the impact of all these elements on the outcome of human hepatocyte isolation. Patients and methods Hepatocytes were isolated from liver tissue from patients undergoing partial hepatectomy using a two-step collagenase method. Hepatocyte viability, cell yield, adhesion, and functionality were measured. In addition, clinical and analytical patient variables were collected and the use or absence of vascular clamping and its type (continuous or intermittent) plus the ischemia times during surgery. Results Malignant disease, previous chemotherapy, and male gender were associated with lower hepatocyte viability and isolation cell yields. The previous increase in transaminases was also associated with lower yields on isolation and lower albumin production. Furthermore, ischemia secondary to vascular clamping during surgery was inversely correlated with the isolated hepatocyte viability. An ischemia time higher than 15 min was related to adverse effects on viability. Conclusion Several factors correlated with the patient and the surgery directly influence the success of human hepatocyte isolation from patients undergoing liver resection.
HMGB1: A Potential Target of Nervus Vagus Stimulation in Pediatric SARS-CoV-2-Induced ALI/ARDS

From the start of pandemics, children were described as the ones who were less affected by SARS-Cov-2 or COVID-19, which was mild in most of the cases. However, with the growing vaccination rate of the adult population, children became more exposed to the virus and more cases of severe SARS-CoV-2-induced ARDS are being diagnosed with the disabling consequences or lethal outcomes associated with the cytokine storm. Thus, we do hypothesize that some of the children could benefit from nervus vagus stimulation during COVID-19 ARDS through the inhibition of HMGB1 release and interaction with the receptor, resulting in decreased neutrophil accumulation, oxidative stress, and coagulopathy as well as lung vascular permeability. Moreover, stimulation through alpha-7 nicotinic acetylcholine receptors could boost macrophage phagocytosis and increase the clearance of DAMPs and PAMPs. Further rise of FGF10 could contribute to lung stem cell proliferation and potential regeneration of the injured lung. However, this stimulation should be very specific, timely, and of proper duration, as it could lead to such adverse effects as increased viral spread and systemic infection, especially in small children or infants due to specific pediatric immunity state and anatomical features of the respiratory system.
A Clinical Trial of the Effects of a Dietary Pattern on Health Metrics and Fecal Metabolites in Volunteers With Risk of Cardiovascular Disease

The phenomenon of longevity in Guangxi of China proved to be closely relevant to its specific dietary habits, but the exact effects of this diet on health remain to be explored. In this work, fourteen screened volunteers with cardiovascular disease (CVD) risk followed a novel dietary pattern derived from centenarians of Guangxi, China for 2 weeks, then the effects of diet on human health were explored by measuring the health metrics and fecal metabolites. The results showed that the short-term dietary intervention significantly decreased the body weight, body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), mean systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels, while it significantly increased high-density lipoprotein cholesterol (HDL-c) levels. Orthogonal partial least squares discriminant analysis (OPLS-DA) indicated a distinct separation in the fecal metabolic profiles of volunteers before and after the intervention. Nine of these metabolites showed significant differences, including two metabolites increased (butyrate and citrulline), seven metabolites decreased (threonine, choline, glycine, aspartate, alanine, N-acetylglutamic acid and lysine). Pathway and enrichment analysis showed that the reduction in CVD risk by dietary intervention mainly affected five pathways, which include arginine biosynthesis; aminoacyl-tRNA biosynthesis; glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; and valine, leucine and isoleucine biosynthesis. Herein, the Guangxi longevity dietary pattern can provide a feasible healthy diet strategy for reducing the CVD risk and human beings. Clinical Trial Registration [http://www.chictr. org.cn], identifier [ChiCTR220 0058216]. Graphical Abstract Schematic diagram of the study design (2 weeks dietary intervention, single arm intervention).
Wildlife and Antibiotic Resistance

Antibiotic resistance is a major human health problem. While health care facilities are main contributors to the emergence, evolution and spread of antibiotic resistance, other ecosystems are involved in such dissemination. Wastewater, farm animals and pets have been considered important contributors to the development of antibiotic resistance. Herein, we review the impact of wildlife in such problem. Current evidence supports that the presence of antibiotic resistance genes and/or antibiotic resistant bacteria in wild animals is a sign of anthropic pollution more than of selection of resistance. However, once antibiotic resistance is present in the wild, wildlife can contribute to its transmission across different ecosystems. Further, the finding that antibiotic resistance genes, currently causing problems at hospitals, might spread through horizontal gene transfer among the bacteria present in the microbiomes of ubiquitous animals as cockroaches, fleas or rats, supports the possibility that these organisms might be bioreactors for the horizontal transfer of antibiotic resistance genes among human pathogens. The contribution of wildlife in the spread of antibiotic resistance among different hosts and ecosystems occurs at two levels. Firstly, in the case of non-migrating animals, the transfer will take place locally; a One Health problem. Paradigmatic examples are the above mentioned animals that cohabit with humans and can be reservoirs and vehicles for antibiotic resistance dissemination. Secondly, migrating animals, such as gulls, fishes or turtles may participate in the dissemination of antibiotic resistance across different geographic areas, even between different continents, which constitutes a Global Health issue.
Sortilin Modulates Schwann Cell Signaling and Remak Bundle Regeneration Following Nerve Injury

Peripheral nerve regeneration relies on the ability of Schwann cells to support the regrowth of damaged axons. Schwann cells re-differentiate when reestablishing contact with the sprouting axons, with large fibers becoming remyelinated and small nociceptive fibers ensheathed and collected into Remak bundles. We have previously described how the receptor sortilin facilitates neurotrophin signaling in peripheral neurons via regulated trafficking of Trk receptors. This study aims to characterize the effects of sortilin deletion on nerve regeneration following sciatic crush injury. We found that Sort1–/– mice displayed functional motor recovery like that of WT mice, with no detectable differences in relation to nerve conduction velocities and morphological aspects of myelinated fibers. In contrast, we found abnormal ensheathment of regenerated C-fibers in injured Sort1–/– mice, demonstrating a role of sortilin for Remak bundle formation following injury. Further studies on Schwann cell signaling pathways showed a significant reduction of MAPK/ERK, RSK, and CREB phosphorylation in Sort1–/– Schwann cells after stimulation with neurotrophin-3 (NT-3), while Schwann cell migration and myelination remained unaffected. In conclusion, our results demonstrate that loss of sortilin blunts NT-3 signaling in Schwann cells which might contribute to the impaired Remak bundle regeneration after sciatic nerve injury.
Plasmalogens and Photooxidative Stress Signaling in Myxobacteria, and How it Unmasked CarF/TMEM189 as the Δ1′-Desaturase PEDS1 for Human Plasmalogen Biosynthesis

Plasmalogens are glycerophospholipids with a hallmark sn-1 vinyl ether bond that endows them with unique physical-chemical properties. They have proposed biological roles in membrane organization, fluidity, signaling, and antioxidative functions, and abnormal plasmalogen levels correlate with various human pathologies, including cancer and Alzheimer’s disease. The presence of plasmalogens in animals and in anaerobic bacteria, but not in plants and fungi, is well-documented. However, their occurrence in the obligately aerobic myxobacteria, exceptional among aerobic bacteria, is often overlooked. Tellingly, discovery of the key desaturase indispensable for vinyl ether bond formation, and therefore fundamental in plasmalogen biogenesis, emerged from delving into how the soil myxobacterium Myxococcus xanthus responds to light. A recent pioneering study unmasked myxobacterial CarF and its human ortholog TMEM189 as the long-sought plasmanylethanolamine desaturase (PEDS1), thus opening a crucial door to study plasmalogen biogenesis, functions, and roles in disease. The findings demonstrated the broad evolutionary sweep of the enzyme and also firmly established a specific signaling role for plasmalogens in a photooxidative stress response. Here, we will recount our take on this fascinating story and its implications, and review the current state of knowledge on plasmalogens, their biosynthesis and functions in the aerobic myxobacteria.
Flame-Retardant Properties and Mechanism of Polylactic Acid-Conjugated Flame-Retardant Composites

The DOPO derivative-conjugated flame retardant 4, 4'-{1'', 4'' - phenylene - bis [amino - (10‴ - oxy -10‴-hydro-9‴-hydrogen-10‴ λ5 -phosphaphenanthrene-10''-yl)-methyl]}-diphenol (P-PPD-Ph) with two hydroxyl groups was synthesized. Polylactic acid conjugated flame-retardant composites with P-PPD-Ph were papered by using a twin-screw extruder. The flame-retardant properties of polylactic acid-conjugated flame-retardant composites were investigated. The flame-retardant properties of PLA-conjugated flame-retardant composites were characterized by the limiting oxygen index (LOI) and the vertical burning test (UL94). The results showed that the PLA-conjugated flame-retardant composites achieved a V-0 rating (UL-94, 3.2 mm) when the conjugated flame retardant was added at 5 wt%, and increase in LOI value from 22.5% to 31.4% relative to composites without added conjugated flame retardant. The flame-retardant mechanism of PLA-conjugated flame-retardant composites were further studied by TG-FTIR, the results showed that the P-PPD-Ph promoted the PLA-conjugated flame-retardant composites to decompose and also released fragments with quenching and dilution, which suggests that P-PPD-Ph for PLA-conjugated flame-retardant composites mainly play a role of the gas-phase flame retardant.
Collection Time, Location, and Mosquito Species Have Distinct Impacts on the Mosquito Microbiota

The mosquito microbiota affects many aspects of mosquito biology including development and reproduction. It also strongly impacts interactions between the mosquito host and pathogens that cause important disease in humans, such as dengue and malaria. Critically, the mosquito microbiota is highly diverse and can vary in composition in response to multiple environmental variables, but these effects are not always consistent. Understanding how the environment shapes mosquito microbial diversity is a critical step in elucidating the ubiquity of key host-microbe-pathogen interactions in nature. To that end, we examined the role of time of collection, collection location and host species on mosquito microbial diversity by repeating collections at two-month intervals on a trapping grid spanning three distinct biomes. We then used 16S rRNA sequencing to compare the microbiomes of Aedes taeniorhynchus, Anopheles crucians, and Culex nigripalpus mosquitoes from those collections. We saw that mosquito diversity was strongly affected by both time and collection location. We also observed that microbial richness and diversity increased from March to May, and that An. crucians and Cx. nigripalpus had greater microbial diversity than Ae. taeniorhynchus. However, we also observed that collection location had no impact on microbial diversity except for significantly lower bacterial richness observed in mosquitoes collected from the mangrove wetlands. Our results highlight that collection time, collection location, and mosquito species each affect aspects of mosquito microbial diversity, but their importance is context dependent. We also demonstrate that these variables have differing impacts on mosquito diversity and mosquito microbial diversity. Our findings suggest that the environment likely plays an important but variable role in influencing the composition of the mosquito microbiota.