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Abstract Background The consequences of trace element exposure on cognitive function in elderly adults have been recognized as primarily attributed to the inflammatory response. It is noteworthy that diet can either exacerbate or reduce the inflammatory response. Despite this, there have been limited studies about the effects of diet on the relationship between trace element exposure and cognitive function. Methods A cross-sectional study utilized data from the 2011–2014 NHANES survey to explore the association between trace element exposure and cognitive function in elderly adults. The study enrolled 1726 participants, and generalized linear regression model (GLM), Bayesian kernel machine regression model (BKMR), weighted quantile sum regression (WQS), and quantile g-computation regression analysis (Qg-comp) were conducted to assess the impact of five trace elements (lead, cadmium, mercury, manganese, and selenium) in blood on cognitive function under the anti-inflammatory and pro-inflammatory diet. Results The GLM analysis showed a positive correlation between selenium (Se) and both the instant recall test (IRT) and digit symbol substitution test (DSST) (β = 2.06, 95% CI: 0.70 ~ 3.41; and β = 6.41, 95% CI: 2.35 ~ 10.46, respectively). In contrast, cadmium (Cd) was negatively associated with DSST (β = -1.17, 95% CI: -2.13~ -0.22), and lead (Pb) was negatively associated with IRT (β = -0.47, 95% CI: -0.82~ -0.11). For the animal fluency test (AFT), the highest quartile of manganese (Mn) was negatively associated with the lowest quartile (β = -0.72, 95% CI: -1.34~-0.10), while mercury (Hg) showed no significant associations with cognitive function tests. Subgroup analysis revealed the effects of Cd on IRT and DSST and Se on DSST under the pro-inflammatory diet. Furthermore, The BKMR analysis showed an inverted U-shaped curve with the negative impact of trace element mixtures and DSST and a linearly negative trend with IRT in the pro-inflammatory diet. Among them, Cd was emphasized as the most potent risk factor, and Se was the most vital protective factor for IRT and DSST in WQS and Qg-comp analysis. Conclusions The study suggests that a high-quality diet might alleviate the adverse effects of Cd on IRT and DSST. High Se levels were also associated with better IRT and DSST scores in the pro-inflammatory diet. These findings provide valuable insights into the connection between diet, trace element exposure, and cognitive function in elderly adults.

G protein-coupled receptors (GPCRs), widely expressed in the human central nervous system (CNS), perform numerous physiological functions and play a significant role in the pathogenesis of diseases. Consequently, identifying key therapeutic GPCRs targets for CNS-related diseases is garnering immense interest in research labs and pharmaceutical companies. However, using GPCRs drugs for treating neurodegenerative diseases has limitations, including side effects and uncertain effective time frame. Recognizing the rich history of herbal treatments for neurological disorders like stroke, Alzheimer's disease (AD), and Parkinson's disease (PD), modern pharmacological research is now focusing on the understanding of the efficacy of traditional Chinese medicinal herbs and compounds in modulating GPCRs and treatment of neurodegenerative conditions. This paper will offer a comprehensive, critical review of how certain natural products and compounds target GPCRs to treat neurological diseases. Conducting an in-depth study of herbal remedies and their efficacies against CNS-related disorders through GPCRs targeting will augment our strategies for treating neurological disorders. This will not only broaden our understanding of effective therapeutic methodologies but also identify the root causes of altered GPCRs signaling in the context of pathophysiological mechanisms in neurological diseases. Moreover, it would be informative for the creation of safer and more effective GPCR-mediated drugs, thereby establishing a foundation for future treatment of various neurological diseases.

Abstract BackgroundSexual transmission among men who have sex with men (MSM) has become the major HIV transmission route. However, limited research has been conducted to investigate the association between transactional sex (TS) and HIV incidence in China. ObjectiveThis study aims to investigate HIV incidence and distinguish sociodemographic and sexual behavioral risk factors associated with HIV incidence among MSM who engage in TS (MSM-TS) in China. MethodsWe conducted a prospective cohort study using a WeChat-based platform to evaluate HIV incidence among Chinese MSM, including MSM-TS in Ningbo, recruited from July 2019 until June 2022. At each visit, participants completed a questionnaire and scheduled an appointment for HIV counseling and testing on the WeChat-based platform before undergoing offline HIV tests. HIV incidence density was calculated as the number of HIV seroconversions divided by person-years (PYs) of follow-up, and univariate and multivariate Cox proportional hazards regression was conducted to identify factors associated with HIV incidence. ResultsA total of 932 participants contributed 630.9 PYs of follow-up, and 25 HIV seroconversions were observed during the study period, resulting in an estimated HIV incidence of 4.0 (95% CI 2.7-5.8) per 100 PYs. The HIV incidence among MSM-TS was 18.4 (95% CI 8.7-34.7) per 100 PYs, which was significantly higher than the incidence of 3.2 (95% CI 2.1-5.0) per 100 PYs among MSM who do not engage in TS. After adjusting for sociodemographic characteristics, factors associated with HIV acquisition were MSM-TS (adjusted hazard ratio [aHR] 3.93, 95% CI 1.29-11.93), having unprotected sex with men (aHR 10.35, 95% CI 2.25-47.69), and having multiple male sex partners (aHR 3.43, 95% CI 1.22-9.64) in the past 6 months. ConclusionsThis study found a high incidence of HIV among MSM-TS in Ningbo, China. The risk factors associated with HIV incidence include TS, having unprotected sex with men, and having multiple male sex partners. These findings emphasize the need for developing targeted interventions and providing comprehensive medical care, HIV testing, and preexposure prophylaxis for MSM, particularly those who engage in TS.

Heavy metals and per- and polyfluoroalkyl substances (PFASs) have become particularly important when studying the development of depression, a common illness that severely restricts psychosocial functioning and diminishes quality of life. Therefore, the potential joint effects of heavy metal and PFAS exposure on depression, as well as the underlying mechanisms involved, were investigated by using integrated epidemiological and bioinformatic approaches in the present study. A thorough analysis of 7301 samples from the National Health and Nutrition Examination Survey (NHANES) cycles that occurred between 2005 and 2018 was performed. Single-exposure studies have shown that cadmium exposure is positively associated with depression, whereas perfluorooctanesulfonic acid (PFOS) exposure and perfluorodecanoic acid (PFDE) exposure are negatively associated with depression. Furthermore, the Bayesian kernel machine regression (BKMR) and quantile g-computation (QGcomp) models were employed to investigate the collective impact of exposure to mixed metals on depression. Cadmium emerged as the principal contributor to depression. Moreover, the addition of PFAS to the metal mixture had an antagonistic effect on depression, with PFOS having the most prominent influence. Analysis of the effects of co-exposure to cadmium and PFOS confirmed the presence of an antagonistic effect. The inflection points of cadmium and PFOS were determined to be −1.11 and 2.27, respectively. Additionally, exposure to cadmium and PFOS had the opposite effects on two crucial pathways, namely, the rap1 and calcium signaling pathways, which involve core genes related to depression such as ADORA2A, FGF2, and FGFR1. These findings have significant implications for future studies and provide new strategies for exploring the mechanisms underlying co-exposure effects.

Abstract Background As the HIV epidemic continues to grow, transmitted drug resistance(TDR) and determining relationship of HIV transmission are major barriers to reduce the risk of HIV transmissions.This study aimed to examine the molecular epidemiology and TDR and evaluated the transmission pattern among newly diagnosed people living with HIV/AIDS(PLWHA) in Ningbo city, which could contribute to the development of targeted precision interventions. Methods Consecutive cross-sectional surveys were conducted in Ningbo City between January 2018 and December 2021. The HIV-1 pol gene region was amplified and sequenced for drug resistance and genetic transmission network analysis. TDR was determined using the Stanford University HIV Drug Resistance Database. Genetic transmission network was visualized using Cytoscape with the genetic distance threshold of 0.013. Results A total of 1006 sequences were sequenced successfully, of which 61 (6.1%) showed evidence of TDR. The most common mutations were K103N (2.3%), E138A/G/Q (1.7%) and V179D/E (1.2%). 12 HIV-1 genotypes were identified, with CRF07_BC being the major genotype (43.3%, 332/767), followed by CRF01_AE (33.7%, 339/1006). 444 (44.1%) pol sequences formed 856 links within 120 transmission clusters in the network. An increasing trend in clustering rate between 2018 and 2021(χ 2 = 9.546, P = 0.023) was observed. The odds of older age (≥ 60 years:OR = 2.038, 95%CI = 1.072 ~ 3.872, compared to

Background: A phytochemical 5-demethylnobiletin from Citrus reticulata Blanco has a broad spectrum of pharmacological effects on anti-inflammatory, cardiovascular and neuroprotective effects, however, its in vivo effect on depigmentation remains unknown. Objective: To investigate how 5-demethylnobiletin regulates melanogenesis, both in vitro and in vivo experiments were conducted to evaluate its efficacy and mechanisms in human epidermal melanocyte and mice model of chemical-induced vitiligo. Methods: C57BL/6 mice were induced with 1% hydroquinone (HQ) to shaved dorsal skin and applied with 5-demethylnobiletin or 8-methoxypsoralen (8-MOP, positive control). Melanin contents measurement, immunohistochemistry, Fontana-Masson and HE histological analysis were used to determine melanin contents in follicles. q-PCR, Western blot, dichlorofluorescein (DCF) assay and computational docking were adopted to investigate the molecular mechanisms of 5-demethylnobiletin in the vitiligo mice model. Besides, acute dermal irritation test was conducted to evaluate the biological safety of 5-demethylnobiletin in mice. Results: 5-demethylnobiletin possessed in vitro anti-oxidative effect, significantly increased melanin content in hair and ameliorated hypopigmentation in mice. The expression level of melanogenesis-related genes such as MITF, tyrosinase, Trp-1 and Trp-2 were significantly upregulated in 5-demethylnobiletin-treated groups. Molecular docking results support that 5-demethylnobiletin is able to bind to tyrosinase, the key enzyme for regulating melanogenesis, suggesting the potential molecular target of 5-demethylnobiletin. Conclusions: 5-demethylnobiletin has potential therapeutic effect on delaying the onset of depigmentation in vivo, lessened depigmentation incidence which contributes to melanogenesis. The newly revealed biological activity indicates 5-demethylnobiletin may be a potential natural pharmaceutical for the treatment and prevention of chemical-induced depigmentation disorders, and as the components for anti-gray hair products.

Abstract Background Men who have sex with men and women (MSMW) are the most important bridge population for HIV transmission. Condom use plays an important role for HIV infection. However the predictors for condom ues with females are not well characterized. Methods This was a cross-sectional study. Participants were enrolled by four community-based organizations (CBOs) by offline (bathrooms, bars), and online (gay applications, chat room) from April to December 2019. Electronic questionnare was fulfilled after a face-to-face training led by CBOs. We identified predictors of inconsistent condom use with females by creating a risk score based on regression coefficients. We externally validated this score via an independent cross-sectional survey conducted in Zhejiang Province in 2021. A total of 917, 615 MSMW were included in analysis in 2019 and 2021, seperately. Results Among 917 MSMW, 73.2% reported heterosexual behavior in the prior 6 months and 38.3% reported inconsistent condom use with females (ICUF) over that time. Compared with heterosexual/unsure MSMW, bisexual MSMW reported more male and female sex partners, higher proportion of inconsistent condom use with males, less commercial sex with males (p

Background: The association between soy product consumption and cancer risk varies among studies. Therefore, this comprehensive meta-analysis of observational studies examines the association between soy product consumption and total cancer risk. Methods: This study was conducted following the PRISMA guidelines. Up to October 2023, all eligible published studies were searched through PubMed and Web of Science databases. Results: A total of 52 studies on soy product consumption were included in this meta-analysis (17 cohort studies and 35 case–control studies). High consumption of total soy products (RR: 0.69; 95% CI: 0.60, 0.80), tofu (RR: 0.78; 95% CI: 0.70, 0.86), and soymilk (RR: 0.75; 95% CI: 0.60, 0.93) were associated with reduced total cancer risk. No association was found between high consumption of fermented soy products (RR: 1.18; 95% CI: 0.95, 1.47), non-fermented soy products (RR: 0.95; 95% CI: 0.77, 1.18), soy paste (RR: 1.00; 95% CI: 0.88, 1.14), miso soup (RR: 0.99; 95% CI: 0.87, 1.12), or natto (RR: 0.96; 95% CI: 0.82, 1.11) and cancer risk. A 54 g per day increment of total soy products reduced cancer risk by 11%, a 61 g per day increment of tofu reduced cancer risk by 12%, and a 23 g per day increment of soymilk reduced cancer risk by 28%, while none of the other soy products were associated with cancer risk. Conclusion: Our findings suggest that high total soy product consumption, especially soymilk and tofu, is associated with lower cancer risk. More prospective cohort studies are still needed to confirm the causal relationship between soy product consumption and cancer risk.

Tricin, a natural nontoxic flavonoid distributed in grasses and euphorbia plants, has been reported to scavenge free radicals, possess anti-inflammatory and antioxidative effects. However, its autophagic effect on Parkinson's disease (PD) has not been elucidated. By adopting cellular and C. elegans models of PD, the autophagic effect of tricin was identified based on the level of autophagy markers (LC3-II and p62). Besides, the pharmacological effects on neurotransmitters (dopamine), inflammatory cytokines (IFN γ, TNFα, MCP-1, IL-10, IL-6 and IL-17A), histology (hematoxylin & eosin and Nissl staining) and behavioural pathology (open-field test, hindlimb clasping, Y-maze, Morris water-maze and nest building test) were also confirmed in the A53T-α-synuclein transgenic PD mouse model. Further experiments demonstrated that tricin induced autophagic flux and lowered the level of α-synuclein through AMPK-p70s6K- and ATG7-dependent mechanism. Compared to the existing clinical PD drugs, tricin mitigated pathogenesis and symptoms of PD with no observable side effects. In summary, tricin is proposed as a potential adjuvant remedy or nutraceutical for the prevention and treatment of PD.

Alzheimer's disease is a neurodegenerative disorder characterized by a decline in cognitive function. The β-amyloid (Aβ) hypothesis suggests that Aβ peptides can spontaneously aggregate into β-fragment-containing oligomers and protofibrils, and this activation of the amyloid pathway alters Ca2+ signaling in neurons, leading to neurotoxicity and thus apoptosis of neuronal cells. In our study, a blood-brain barrier crossing flavonol glycoside hyperoside was identified with anti-Aβ aggregation, BACE inhibitory, and neuroprotective effect in cellular or APP/PSEN1 double transgenic Alzheimer's disease mice model. While our pharmacokinetic data confirmed that intranasal administration of hyperoside resulted in a higher bio-availability in mice brain, further in vivo studies revealed that it improved motor deficit, spatial memory and learning ability of APP/PSEN1 mice with reducing level of Aβ plaques and GFAP in the cortex and hippocampus. Bioinformatics, computational docking and in vitro assay results suggested that hyperoside bind to Aβ and interacted with ryanodine receptors, then regulated cellular apoptosis via endoplasmic reticulum-mitochondrial calcium (Ca2+) signaling pathway. Consistently, it was confirmed that hyperoside increased Bcl2, decreased Bax and cyto-c protein levels, and ameliorated neuronal cell death in both in vitro and in vivo model. By regulating Aβ-induced cell death via regulation on Ca2+ signaling cascade and mitochondrial membrane potential, our study suggested that hyperoside may work as a potential therapeutic agent or preventive remedy for Alzheimer's disease.

Introduction: Far-infrared radiation (FIR) is widely used in the treatment of various diseases such as insomnia and cardiovascular risk. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which the therapeutic potential of FIR in RA is unclear. Objectives: To determine the therapeutic potential and mechanistic actions of FIR in treatment of RA. Methods: Adjuvant-induced arthritis (AIA) rat models were established to assess the therapeutic potency of FIR in RA treatment. The scoring parameters such as arthritis score, swelling of the hind paw, spleen and thymus indices, micro-CT analysis indices were adopted to estimate the beneficial effects of FIR during RA treatment in AIA model. PCR gene expression arrays were used to analyze inflammatory and autoimmune genes expression profiles in rat synovium. The inflammatory and immunity genes profiling was further analyzed through transcription factor prediction using PROMO. A signaling network map of possible molecular circuits connecting the identified differential genes to the RA's pathogenesis was constructed based on extensive literature reviews, and the major signaling pathways were validated by Western blotting. Results: Thirty minutes of FIR treatment significantly improved the symptoms of AIA in rats. Gene expression profiling indicated that 27 out of 370 genes were down-regulated by FIR. AP-1, CEBPα, CEBPβ, c-Fos, GR, HNF-3β, USF-1, and USF-2 were predicted as key transcription factors that regulated the identified differential genes. In addition, MAPK, PI3K-Akt, and NF-κB signaling are the major molecular pathways down-regulated by FIR treatment. Conclusion: FIR may provide beneficial effects on the AIA rat model of arthritis by suppression of the MAPK, PI3K-Akt and NF-κB signaling pathways. Therefore, we believe that FIR may provide an alternative non-pharmacological and non-surgical therapeutic approach for the treatment of RA.

ObjectiveTo evaluate the efficiency of dual test of severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antigen and nucleic acid among freight truck drivers and workers passing through expressway toll gates. MethodsDual tests of SARS-CoV-2 antigen and nucleic acid were conducted among 48 734 freight truck drivers and workers passing through 8 expressway toll gates in Ningbo city from provinces other than Zhejiang province during the period of March 20 – April 17, 2022. The test results were statistically analyzed. ResultsTotally 9 infections of SARS-CoV-2 Omicron variant were detected; of which, 6 were diagnosed clinically as mild coronavirus disease 2019 (COVID-19) case and 3 as asymptomatic infection. No subsequent COVID-19 case was confirmed. For the SARS-CoV-2 antigen test, the sensitivity and specificity were 55.5% (5/9) and 99.9% (48 717/48 725); the positive and negative predictive value were 38.5% (5/13) and 99.9% (48 717/48 721), respectively. For multiplex fluorescence PCR test of SARS-CoV-2 nucleic acid among the participants with positive SARS-CoV-2 antigen result, the Ct values of ORF1ab and N gene M (25th percentile, 75th percentile) were 19.0 (17.1, 21.5) and 19.0 (16.6, 22.5); while, the Ct values of the participants with negative result was significantly higher than those of the participants with positive SARS-CoV-2 antigen result (P < 0.05). ConclusionIn this study, the sensitivity of SARS-CoV-2 antigen test is low but the specificity of the test is high for the detection of SARS-CoV-2 infection. The results suggest that dual test of SARS-CoV-2 antigen and nucleic acid should be implemented to reduce the risk of imported case-induced local COVID-19 epidemic.

BackgroundDepressive symptoms were common among HIV/AIDS patients. Previous studies had shown that HIV-infected patients were twice as likely to be diagnosed with depression as the general population. However, only few studies have explored the prevalence and related factors of depressive symptoms among HIV/AIDS in China.Materials and methodsA cross-sectional study was conducted to study the prevalence of depressive symptoms among HIV/AIDS from January to December 2021 through the database of HIV/AIDS antiretroviral therapy and psychological evaluation system in Ningbo, China. The Patient Health Questionnaire-2 (PHQ-2) was used to screen for depressive symptoms (PHQ-2 > 0), the Patient Health Questionnaire-9 (PHQ-9) was used to diagnose depressive symptoms, and multivariate Logistic regression model was carried on to evaluate the related factors.ResultsA total of 3,939 HIV/AIDS patients were enrolled, and the age of initiation of antiretroviral therapy was 37.15 (IQR = 28.41–48.73) years. Among them, 3,230 (82.00%) were male, 3,844 (97.59%) were Han nationality, 1,391 (35.49%) were unmarried, 1,665 (42.27%) were homosexual transmission, and 2,194 (55.70%) were HIV-infected patients. There were 265 patients (6.73%) with depressive symptoms, and the proportion of mild, moderate, moderate and severe depressive symptoms was 4.01% (158/3939), 1.65% (65/3939), 0.76% (30/3939), and 0.30% (12/3939), respectively. Multivariate analysis showed that married [odds ratio (OR) = 0.675, 95% CI = 0.501–0.908], divorced or widowed (OR = 0.571, 95% CI = 0.380–0.860), homosexual transmission (OR = 1.793, 95% CI = 1.349–2.396) were associated with depressive symptoms among HIV/AIDS.ConclusionThe prevalence of depressive symptoms among HIV/AIDS patients was 6.73% in Ningbo, China. More attention should be paid to the psychological status of unmarried and homosexual HIV/AIDS patients in Ningbo and timely psychological intervention or treatment should be given to those patients with depressive symptoms.

Abstract Background HIV testing and early linkage to care are critical for reducing the risk of HIV transmission. HIV self-testing (HIVST) is a useful tool for increasing HIV testing frequency.This study aimed to investigate HIVST rates among men who have sex with men (MSM), the characteristics of MSM who had HIVST, and factors associated with HIVST uptake among MSM in Ningbo, China. Methods A cross-sectional study was conducted from April to October 2019 in Ningbo,China. Participants were aged at least 18 years and having had sexual contact with men in the past year. Proportions were used for categorical variables. Adjusted Odds Ratio (AOR) and 95% Confidence Interval (CI) for characteristics associated with HIVST uptake was processed by multivariable logistic regression models. Results Among a sample of 699 MSM recruited, 38.2% had reported previous use of an HIV self-test kit. A greater proportion of HIVST users had a higher frequency of HIV testing (≥ 2 times: 70.0% versus 41.2%, p

Autophagy has been implicated in the regulation of neuroinflammation and neurodegenerative disorders. Licochalcone B (LCB), a chalcone from Glycyrrhiza inflata, has been reported to have anti-cancer, anti-oxidation and anti-β–amyloid fibrillation effects; however, its effect in autophagy remain un-investigated. In the current study, the potential neuro-protective role of LCB in terms of its anti-oxidative, anti-apoptotic, and autophagic properties upon oxidative stress-induced damage in neuronal cells was investigated. With the production of reactive oxygen species (ROS) as a hallmark of neuroinflammation and neurodegeneration, hydrogen peroxide (H2O2) was adopted to stimulate ROS-induced cell apoptosis in PC-12 cells. Our findings revealed that LCB reduced cell cytotoxicity and apoptosis of PC-12 cells upon H2O2-stimulation. Furthermore, LCB increased the level of the apoptosis-associated proteins caspase-3 and cleaved caspase-3 in H2O2-induced cells. LCB effectively attenuated the level of oxidative stress markers such as MDA, SOD, and ROS in H2O2-induced cells. Most importantly, LCB was confirmed to possess its anti-apoptotic effects in H2O2-induced cells through the induction of ATG7-dependent autophagy and the SIRT1/AMPK signaling pathway. As a novel autophagic inducer, LCB increased the level of autophagy-related proteins LC3–II and decreased p62 in both neuronal cells and Caenorhabditis elegans (C. elegans) models. These results suggested that LCB has potential neuroprotective effects on oxidative damage models via multiple protective pharmacological mechanisms.

Exosomes are nano-extracellular vesicles with diameters ranging from 30 to 150 nm, which are secreted by the cell. With their role in drug cargo loading, exosomes have been applied to carry compounds across the blood–brain barrier in order to target the central nervous system (CNS). In this study, high-purity exosomes isolated by the ultra-high-speed separation method were applied as the natural compound carrier, with the loading efficiency confirmed by UHPLC-MS analysis. Through the optimization of various cargo loading methods using exosomes, this study compared the efficiency of different ways for the separation of exosomes and the exosome encapsulation of natural compounds with increasing molecular weights via extensive in vitro and in vivo efficacy studies. In a pharmacokinetic study, our data suggested that the efficiency of compound’s loading into exosomes is positively correlated to its molecular weight. However, with a molecular weight of greater than 1109 Da, the exosome-encapsulated natural compounds were not able to pass through the blood–brain barrier (BBB). In vitro cellular models confirmed that three of the selected exosome-encapsulated natural compounds—baicalin, hederagenin and neferine—could reduce the level of neurodegenerative disease mutant proteins—including huntingtin 74 (HTT74), P301L tau and A53T α-synuclein (A53T α-syn)—more effectively than the compounds alone. With the traditional pharmacological role of the herbal plant Nelumbo nucifera in mitigating anxiety, exosome-encapsulated-neferine was, for the first time, reported to improve the motor deficits of APP/PS1 (amyloid precursor protein/ presenilin1) double transgenic mice, and to reduce the level of β-amyloid (Aβ) in the brain when compared with the same concentration of neferine alone. With the current trend in advocating medicine–food homology and green healthcare, this study has provided a rationale from in vitro to in vivo for the encapsulation of natural compounds using exosomes for the targeting of BBB permeability and neurodegenerative diseases in the future.

INTRODUCTION:Increasing evidence suggests an association between synthetic drug use and HIV infection among men who have sex with men (MSM). The aim of this study was to evaluate synthetic drug use prevalence, describe characteristics of synthetic drug users, and investigate whether synthetic drug use is associated with HIV infection among Chinese MSM. METHODS:A cross-sectional survey was conducted in 16 Chinese cities among males >18 years old who reported having had sex with men in the prior 3 months, but did not already have a known HIV-positive serostatus. Participants were grouped according to lifetime synthetic drug use and characteristics were compared using Chi-square test. Determinants of HIV infection were assessed using univariate and multivariate regression. RESULTS:Among 3,135 participants, 1,249 reported lifetime synthetic drug use, for a prevalence of 39.8%. Nearly all users (96.3%) reported using inhaled alkyl nitrites ("poppers"). Synthetic drug users were more likely to be younger (

Background: Rheumatoid arthritis (RA) is an autoimmune inflammation disease characterized by imbalance of immune homeostasis. p53 mutants are commonly described as the guardian of cancer cells by conferring them drug-resistance and immune evasion. Importantly, p53 mutations have also been identified in RA patients, and this prompts the investigation of its role in RA pathogenesis. Methods: The cytotoxicity of disease-modifying anti-rheumatic drugs (DMARDs) against p53 wild-type (WT)/mutant-transfected RA fibroblast-like synoviocytes (RAFLSs) was evaluated by MTT assay. Adeno-associated virus (AAV) was employed to establish p53 WT/R211* adjuvant-induced arthritis (AIA) rat model. The arthritic condition of rats was assessed by various parameters such as micro-CT analysis. Knee joint samples were isolated for total RNA sequencing analysis. The expressions of cytokines and immune-related genes were examined by qPCR, ELISA assay and immunofluorescence. The mechanistic pathway was determined by immunoprecipitation and Western blotting in vitro and in vivo. Results: Among p53 mutants, p53R213* exhibited remarkable DMARD-resistance in RAFLSs. However, AAV-induced p53R211* overexpression ameliorated inflammatory arthritis in AIA rats without Methotrexate (MTX)-resistance, and our results discovered the immunomodulatory effect of p53R211* via suppression of T-cell activation and T helper 17 cell (Th17) infiltration in rat joint, and finally downregulated expressions of pro-inflammatory cytokines. Total RNA sequencing analysis identified the correlation of p53R211* with immune-related pathways. Further mechanistic studies revealed that p53R213*/R211* instead of wild-type p53 interacted with TANK-binding kinase 1 (TBK1) and suppressed the innate immune TBK1–Interferon regulatory factor 3 (IRF3)–Stimulator of interferon genes (STING) cascade. Conclusions: This study unravels the role of p53R213* mutant in RA pathogenesis, and identifies TBK1 as a potential anti-inflammatory target. [ABSTRACT FROM AUTHOR]