Huang Lian Jie Du decoction attenuates inflammation in septic rats by activating autophagy and altering the intestinal microbiome.

Aims: The aim of this study was to investigate the protective effect of HLJDD on septic rats and the underlying mechanisms. Materials and methods: Adult male Sprague-Dawley (SD) adult rats (150-180 g) were randomly divided into the following 5 groups (n = 7 per group): the Sham group, caecal ligation and puncture (CLP) group, HLJDD + CLP (Huang Lian Jie Du Decoction, HLJDD) group (1 g/mL/100 g), HLJDD + Rap + CLP (H. Rap) group (Rap: 3 mg/kg), and HLJDD+3-MA + CLP (H. 3-MA) group (3-MA: 30 mg/kg). Rapamycin (Rap) and 3-methyladenosine (3-MA) were used to activate and inhibit autophagy, respectively. HLJDD was purchased from Beijing Tong Ren Tang Guiyang Branch and verified by experts as a genuine product. We used CLP to establish an animal model of sepsis in the last four groups. Survival was analysed by the Kaplan‒Meier method. Then, we examined autophagy-related genes (Atgs) and proteins using real-time PCR and Western blotting, respectively. The microstructure of the ileum and the number of autophagosomes were observed by transmission electron microscopy (TEM). Analyses of HE-stained pathological ileum and inflammatory factor levels were examined to assess the extent of septic injury. The effect of HLJDD on the gut microbiota was analysed by 16S rRNA gene sequencing of faeces. Results: In this study, we identified the protective effects of HLJDD on mortality and inflammation in septic rats. Several key proteins, including LC3-II, Beclin-1 and p62, were examined and showed that HLJDD could effectively reverse the sepsis-induced decrease in autophagy. TEM was performed and the expression of Atgs was assessed to evaluate fluctuations in autophagy. Then, we examined the intestinal tight junction protein zona occludens (ZO-1), lipopolysaccharide (LPS) and inflammatory factors, and found that HLJDD effectively alleviated the increase in ZO-1 gene expression, the level of LPS and serum level of inflammatory factors caused by sepsis. These results were consistent with those obtained from pathological sectioning and TEM analysis. Moreover, autophagy activation effectively ameliorated sepsis, and autophagy inhibition exacerbated the systemic symptoms caused by infection. By examining the expression of key proteins upstream of the autophagy pathway, we found that HLJDD inhibited mTOR via the MAPK/PI3K signalling pathway to promote autophagy in septic rats. 16S rRNA sequencing revealed that HLJDD significantly affected the diversity and physiological function of the gut microbiota in septic rats. Conclusions: The results of this study indicate that autophagy activation is a potential mechanism underlying the protective effect of HLJDD on the intestine in septic rats.

[Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice].

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

The PCM scaffold enables RNA localization to centrosomes.

As microtubule-organizing centers, centrosomes direct assembly of the bipolar mitotic spindle required for chromosome segregation and genome stability. Centrosome activity requires the dynamic assembly of pericentriolar material (PCM), the composition and organization of which changes throughout the cell cycle. Recent studies highlight the conserved localization of several mRNAs encoded from centrosome-associated genes enriched at centrosomes, including Pericentrin-like protein (Plp) mRNA. However, relatively little is known about how RNAs localize to centrosomes and influence centrosome function. Here, we examine mechanisms underlying the subcellular localization of Plp mRNA. We find that Plp mRNA localization is puromycin-sensitive, and the Plp coding sequence is both necessary and sufficient for RNA localization, consistent with a co-translational transport mechanism. We identify regions within the Plp coding sequence that regulate Plp mRNA localization. Finally, we show that protein-protein interactions critical for elaboration of the PCM scaffold permit RNA localization to centrosomes. Taken together, these findings inform the mechanistic basis of Plp mRNA localization and lend insight into the oscillatory enrichment of RNA at centrosomes.

Associations of ambient ozone exposure and CD4+ T cell levels with mortality among people living with HIV: An eight-year longitudinal study.

There has been a consistent upward trend in ground-level ozone (O3) concentration in China. People living with HIV (PLWH) may be more vulnerable to the health impacts of O3 exposure due to their immunosuppressed state. This study aims to investigate the association between ambient O3 exposure and mortality among PLWH, as well as the potential exacerbating effects of a decreased CD4+ T cell level. Daily maximum 8-hour O3 concentrations were assigned to 7270 PLWH at a county level in Guangxi, China. Every 10-unit increase in ambient O3 concentration was associated with a significant rise in all-cause mortality ranging from 7.3 % to 28.7 % and a significant rise in AIDS-related mortality ranging from 8.4 % to 14.5 %. When PLWH had a higher CD4+ count (≥350 cells/µL), elevated O3 concentration was associated with increased blood CD4+ count at lag0 [percent change with 95 % confidence interval, 0.20(0.00, 0.40)], lag1 [0.26(0.06, 0.47)], and lag2 [0.23(0.03, 0.44)]; however, an opposite association was observed when CD4+ count was <350 cells/µL for half-year average [-2.45(-4.71, -0.14)] and yearly average [-3.42(-5.51, -1.29)] of O3 exposure. The association of O3 exposure with all-cause and AIDS-related mortality was more prominent among those with higher CD4+ count. Exploratory analysis revealed possible associations between O3 exposure and respiratory infections and clinical symptoms. These findings suggest potential synergistic effects between a compromised immune status and elevated O3 exposure levels on mortality risk among PLWH. Ambient O3 exposure should be considered as an emerging mortality risk factor for PLWH in the era of antiretroviral therapy, requiring further attention from researchers and healthcare professionals.

Hesperidin Protects Against High-Fat Diet-Induced Lipotoxicity in Rats by Inhibiting Pyroptosis.

It is currently thought that excess fatty acid-induced lipotoxicity in hepatocytes is a critical initiator in the development of nonalcoholic fatty liver disease (NAFLD). Lipotoxicity can induce hepatocyte death; thus, reducing lipotoxicity is one of the most effective therapeutic methods to combat NAFLD. Abundant evidence has shown that hesperidin (HSP), a type of flavanone mainly found in citrus fruits, is able to ameliorate NAFLD, but the molecular mechanisms are unclear. We previously reported that pyroptosis contributed to NAFLD development and that inhibiting pyroptosis contributed to blunting the progression of NAFLD in rat models. Therefore, we questioned whether HSP could contribute to ameliorating NAFLD by modulating pyroptosis. In this study, a high-fat diet (HFD) induced dyslipidemia and hepatic lipotoxicity in rats, and HSP supplementation ameliorated dyslipidemia and insulin resistance. In addition, the HFD also caused pyroptosis in the liver and pancreas, while HSP supplementation ameliorated pyroptosis. In vitro, we found that HSP ameliorated palmitic acid-induced lipotoxicity and pyroptosis in HepG2 and INS-1E cells. In conclusion, we showed for the first time that HSP has a protective effect against liver and pancreas damage in terms of pyroptosis and provides a novel mechanism for the protective effects of HSP on NAFLD.

Nobiletin Ameliorates Hepatic Lipid Deposition, Oxidative Stress, and Inflammation by Mechanisms That Involve the Nrf2/NF-κB Axis in Nonalcoholic Fatty Liver Disease.

Nobiletin (NOB), a flavonoid with significant antioxidant potential, holds promise for treating nonalcoholic fatty liver disease (NAFLD). In this work, we aim to assess the effects and investigate the molecular mechanisms of NOB on NAFLD. After using a methionine choline-deficient diet to induce C57BL/6J mice, as well as oleic acid to induce HepG2 and L02 cells, we administered NOB as an intervention. The results indicated that the NOB significantly ameliorated lipid deposition, oxidative stress, and inflammation in NAFLD in both models. Its mechanism may involve the Nrf2, SREBP-1c, and NF-κB signaling pathways. Furthermore, Nrf2 is not only a direct target for NOB to improve oxidative damage but also indirectly involved in lipid-lowering and anti-inflammatory processes in NAFLD. By inhibiting Nrf2, we found that the regulatory role of Nrf2 in lipid metabolism is not related to SREBP-1c but is closely associated with NF-κB in terms of inflammation. Our results suggest that Nrf2 is one of the most critical targets for NOB against NAFLD in multiple aspects.

Cardiac telerehabilitation under 5G internet of things monitoring: a randomized pilot study.

Owing to issues such as time and cost, patients often show poor acceptance of and adherence to center-based cardiac rehabilitation (CBCR), which impacts the effectiveness of rehabilitation. Therefore, there is growing interest in home-based cardiac rehabilitation and cardiac telerehabilitation (CTR), which entail less time and cost than CBCR. This study aimed to compare the changes in physiological and psychological indicators, compliance, and satisfaction after CTR and CBCR. In this single-blind, randomized, controlled trial, the intervention group received CTR via the 5G Internet of Things platform, while the control group received CBCR. Data from 50 patients (age 66.28 ± 4.01 years) with acute myocardial infarction who underwent percutaneous coronary intervention were analyzed. After an intervention period of three months, the maximal oxygen uptake and metabolic equivalent of task were 5.53 ± 0.12 and 19.32 ± 0.17, respectively, in the intervention group, and 4.15 ± 0.13 and 16.52 ± 0.18, respectively, in the control group. After three months of intervention, there were significant differences between the two groups in all observed indicators (p < 0.05), except for low-density lipoprotein and the incidence of major adverse cardiovascular events (p > 0.05). The use of a 5G Internet of Things platform cardiac rehabilitation model effectively improved outcomes in patients with acute myocardial infarction who underwent percutaneous coronary intervention. Trials registry: The study protocol was registered at Chinese Clinical Trials Registry (ChiCTR), first trial registration 07/08/2023, identification number ChiCTR2300074435.

Knowledge mapping of immunotherapy for thyroid cancer from 1980 to 2022: A review.

With the gradual development of immunotherapy for thyroid cancer, relevant research has increased. To better understand the current situation, development trend, evolution process, and research hotspots of this field, we conducted this comprehensive bibliometrics visual analysis. We retrieved papers published from 1980 to 2022 from Web of Science Core Collection on January 31, 2023. CiteSpace, Pajek, VOSviewer, R-Bibliometrix, and Scimago Graphics are the tools to perform the analysis. Analysis methods mainly include co-occurrence analysis and cluster analysis. Analysis objects are countries or regions, institutions, authors, journals, and keywords, etc. In terms of publication number, the recent decade has witnessed rapid growth. USA was the most prolific country and has the most influence in the cooperation team. Sweden took the lead in focus on this research field and lasted for 21 years. Garden State Cancer Center was released most papers (28). INSERM played a major role in institutional cooperation. Goldenberg DM published the most papers (48), with H-Index 25 and G-Index 43. Journal of Nuclear Medicine has the greatest papers published (41). The average impactor factor of the top 10 journals is 7.2058. The top keywords with high burst strength are: radioimmunotherapy (14.85), monoclonal antibody (13.78), non hodgkins lymphoma (12.54). The research field of immunotherapy for thyroid cancer will be further developed. This study provides a valuable reference for future research in the field.

Mesenchymal Stem Cells Inhibit Epithelial-to-Mesenchymal Transition by Modulating the IRE1α Branch of the Endoplasmic Reticulum Stress Response.

Background: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease, and it carries a poor prognosis due to a lack of efficient diagnosis methods and treatments. Epithelial-mesenchymal transition (EMT) plays a key role in IPF pathogenesis. Endoplasmic reticulum (ER) stress contributes to fibrosis via EMT-mediated pathways. Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for pulmonary fibrosis and ameliorates lung fibrosis in animal models via paracrine effects. However, the specific mechanisms underlying the effect of transplanted MSCs are not known. We previously reported that MSCs attenuate endothelial injury by modulating ER stress and endothelial-to-mesenchymal transition. The present study investigated whether modulation of ER stress- and EMT-related pathways plays essential roles in MSC-mediated alleviation of IPF. Methods and Results: We constructed a A549 cell model of transforming growth factor-ß1 (TGF-ß1)-induced fibrosis. TGF-ß1 was used to induce EMT in A549 cells, and MSC coculture decreased EMT, as indicated by increased E-cadherin levels and decreased vimentin levels. ER stress participated in TGF-ß1-induced EMT in A549 cells, and MSCs inhibited the expression of XBP-1s, XBP-1u, and BiP, which was upregulated by TGF-ß1. Inhibition of ER stress contributed to MSC-mediated amelioration of EMT in A549 cells, and modulation of the IRE1α-XBP1 branch of the ER stress pathway may have played an important role in this effect. MSC transplantation alleviated bleomycin (BLM)-induced pulmonary fibrosis in mice. MSC treatment decreased the expression of ER stress- and EMT-related genes and proteins, and the most obvious effect of MSC treatment was inhibition of the IRE1α/XBP1 pathway. Conclusions: The present study demonstrated that MSCs decrease EMT by modulating ER stress and that blockade of the IRE1α-XBP1 pathway may play a critical role in this effect. The current study provides novel insight for the application of MSCs for IPF treatment and elucidates the mechanism underlying the preventive effects of MSCs against pulmonary fibrosis.

Family outcome disparities between sexual minority and heterosexual families: a systematic review and meta-analysis.

BACKGROUND: The number of children in sexual minority parent families has increased. This systematic review aims to synthesise the evidence of disparities in family outcomes between sexual minority and heterosexual families and to identify specific social risk factors of poor family outcomes. METHODS: We systematically searched PubMed, the Web of Science, Embase, the Cochrane Library and APA PsycNet for original studies that compared family outcomes between sexual minority and heterosexual families. Two reviewers independently selected studies and assessed the risk of bias of included studies. Narrative synthesis and meta-analysis were conducted to synthesise evidence. RESULTS: Thirty-four articles were included. The narrative synthesis results revealed several significant findings for children's gender role behaviour and gender identity/sexual orientation outcomes. Overall, 16 of 34 studies were included in the meta-analyses. The quantitative synthesis results suggested that sexual minority families may perform better in children's psychological adjustment and parent-child relationship than heterosexual families (standardised mean difference (SMD) -0.13, 95% CI -0.20 to -0.05; SMD 0.13, 95% CI 0.06 to 0.20), but not couple relationship satisfaction (SMD 0.26, 95% CI -0.13 to 0.64), parental mental health (SMD 0.00, 95% CI -0.16 to 0.16), parenting stress (SMD 0.01, 95% CI -0.20 to 0.22) or family functioning (SMD 0.18, 95% CI -0.11 to 0.46). CONCLUSION: Most of the family outcomes are similar between sexual minority and heterosexual families, and sexual minority families have even better outcomes in some domains. Relevant social risk factors of poor family outcomes included stigma and discrimination, poor social support and marital status, etc. The next step is to integrate multiple aspects of support and multilevel interventions to reduce the adverse effects on family outcomes with a long-term goal of influencing policy and law making for better services to individuals, families, communities and schools.

Nobiletin Intake Attenuates Hepatic Lipid Profiling and Oxidative Stress in HFD-Induced Nonalcoholic-Fatty-Liver-Disease Mice.

Nobiletin (NOB) is a naturally occurring compound, commonly found in citrus peel, that shows hepatoprotective and lipid-reducing effects. However, the lipid biomarkers and the potential improvement mechanisms have not been adequately explored. Therefore, we investigated the ameliorative effect and the molecular mechanism of NOB on NAFLD induced by a high-fat diet in mice. The results showed that supplementation with NOB over 12 weeks markedly improved glucose tolerance, serum lipid profiles, inflammatory factors, hepatic steatosis, and oxidative stress. These beneficial effects were mainly related to reduced levels of potential lipid biomarkers including free fatty acids, diacylglycerols, triacylglycerols, and cholesteryl esters according to hepatic lipidomic analysis. Twenty lipids, including DGs and phosphatidylcholines, were identified as potential lipid biomarkers. Furthermore, RT-qPCR and Western blot analysis indicated that NOB inhibited the expression of lipogenesis-related factors such as SREBP-1c, SCD-1, and FAS, and upregulated the expression of lipid oxidation (PPARα) and cholesterol conversion (LXRα, CYP7A1, and CYP27A1) genes as well as antioxidation-related factors (Nucl-Nrf2, NQO1, HO-1, and GCLC), indicating that NOB intake may reduce lipid biosynthesis and increase lipid consumption to improve hepatic steatosis and oxidative stress. This study is beneficial for understanding the ameliorative effects of NOB on NAFLD.

International performance of acupuncture for shoulder pain over more than four decades: a bibliometric study.

PURPOSE: This bibliometric study aims to reveal the current situation, cooperative teams, and future development trends of acupuncture for shoulder pain (SP). MATERIALS AND METHODS: The data source is the Web of Science Core Collection. The software programs used in this study are VOSviewer, Pajek, CiteSpace, Scimago Graphica, and Microsoft Excel. Co-occurrence analysis, descriptive statistical analysis, and burst keywords analysis are applied to analyze paper authors, institutions, countries or regions, keywords, and citations. RESULTS: This study included 350 papers. In the first 30 years since 1976, the number of papers published was very limited. Since 2004, it has shown rapid growth momentum. High-yield countries and institutions were China (92) and Kyung Hee University (18), respectively. In terms of the cooperative relationship, the USA (centrality 0.34) and Beijing University of Chinese Medicine (centrality 0.15) play central roles in the team. The author Macpherson H ranked first with 10 published papers. Evidence Based Complementary and Alternative Medicine (27) has published the most papers. The keywords are grouped into five clusters. The most recent burst keywords include stroke, electroacupuncture, diagnosis, disability, stimulation, mechanism, bee venom acupuncture, and systematic review. CONCLUSION: In general, the research and international cooperation of acupuncture for SP will continue to emerge. Most of the current studies believe that acupuncture for SP is effective, and more studies will appear to verify its effectiveness. More well-designed trials will be introduced. More classification and detailed treatment methods for SP will be introduced to this research field.

Knowledge Mapping of International Research on Acupuncture for Chronic Pain: A Bibliometric Analysis.

Introduction: With the wide acceptance of acupuncture, many papers and guidelines recommend that acupuncture is effective for chronic pain (CP). In this study, we applied bibliometric methods to analyze the current research situation of acupuncture intervention in CP, to gain insight into the current situation and future development trend of this field. Material and Methods: Science Citation Index Expanded was searched for publications related to acupuncture for CP between 1900 and 2022. VOSviewer, CiteSpace and Thomson Data Analyzer were used to analyze the annual publication, authors and cited authors and their countries (regions) and institutions, journals and cited journals, cited references, co-occurrence keywords, burst keywords, and the relevant centrality. Results: A total of 1968 papers were retrieved, the annual publications have shown a rapid growth trend in the recent 20 years. The USA (708) and the Kyung Hee University (31) were the most productive country and institution, respectively, while the USA (0.37) and University of Maryland (0.13) had the highest centrality. MacPherson, Hugh published the most papers in this field (29), and Vickers, A J were the most influential author (289 times cited). Journal of Alternative and Complementary Medicine was the most productive journal (92), whereas PAIN was the most influential one (4743 times cited). Breivik, H's (2006) paper had the most citation count (3025), while Furlan's (2005) paper had the highest centrality (0.23). The research focuses in this field mainly include pain, electroacupuncture, Low back pain, Systematic review, Randomized controlled trial etc. Researchers are currently paying more attention to the psychological problems caused by CP. Conclusion: The research of acupuncture for CP will be further expanded. International cooperation of this research field needs to be further strengthened. More high-quality designed trials need to be conducted.

High baseline body mass index predicts recovery of CD4+ T lymphocytes for HIV/AIDS patients receiving long-term antiviral therapy.

The relationship between baseline BMI and CD4+ T cells during follow-up in HIV patients in China requires further evaluation. We conducted a retrospective cohort study based on adult AIDS patients who underwent or received antiretroviral therapy from 2003 to 2019 in Guangxi, China. BMI was divided into categories and compared, and after adjusting for BMI being related to the change in CD4 lymphocyte count, with normal weight as the reference group, the BMI before treatment was positively correlated with the changes in CD4+ T cells at different time periods. Among them, obese patients had significant CD4+ cell gain. In patients with pretreatment CD4+ T lymphocyte counts <200 cells/µL, a higher BMI was associated with an increased likelihood of achieving immunologic reconstitution [≥350 cells/µL: AHR: 1.02(1.01, 1.04), P = 0.004; ≥500 cells/µL: AHR: 1.03 (1.01, 1.05), P = 0.004]. Underweight in HIV patients was a risk factor for poor viral suppression [AHR: 1.24 (1.04, 1.48), P = 0.016]. Our study demonstrated that HIV/AIDS patients receiving ART with higher baseline BMI had better immune reconstitution and that baseline BMI could be an important predictor of immune reconstitution in patients receiving ART. Baseline BMI was not associated with virological failure, but a lower baseline BMI indicated poor viral suppression during follow-up.

Usability of dual HIV/syphilis self-testing among men who have sex with men in China: study protocol for a three-arm randomised controlled trial.

INTRODUCTION: HIV self-testing (HIVST) provides a key measure for the early detection of HIV infection in men who have sex with men (MSM). However, dual HIV/syphilis self-testing in the MSM population has not been studied. We describe a randomised controlled trial to evaluate the effect of dual HIV/syphilis self-testing on the testing frequency among MSM in China. METHODS AND ANALYSIS: This randomised controlled trial will be implemented in Guangxi, China. 330 MSM, including 255 frequent testers and 75 less frequent testers, will be recruited and randomly assigned in a 1:1:1 ratio into one of three arms: a site-based testing arm, a single HIVST arm and a dual HIV/syphilis self-testing arm. Participants in the single HIVST arm and dual HIV/syphilis self-testing arm will receive two free finger-prick-based HIVST or HIV/syphilis self-testing kits at enrolment. The data will be collected at five separate times: baseline, 3 months, 6 months, 9 months and 12 months. The primary outcome is the mean frequency of HIV testing used by MSM after intervention comparing each group during the study period. The secondary outcome includes changes in sex behaviours (eg, number of male sex partners and the proportion of consistent condom use) and the mean number of HIV tests used by the social network members over the study period. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the Medical Ethics Committee of Guangxi Medical University, China (20210173). The study results will be disseminated through conferences and academic journals. TRIAL REGISTRATION NUMBER: ChiCTR2100050898.

Mechanisms Underlying the Differences in the Pharmacokinetics of Six Active Constituents of Huangqi Liuyi Decoction between Normal and Diabetic Nephropathy Mouse Models.

The aim of this study was to explore the mechanisms underlying the differences in the pharmacokinetics of Huangqi Liuyi decoction extract (HQD) under physiological and pathological conditions. The roles of liver cytochrome P450 metabolic enzymes (Cyp450) and small intestinal transporters were also investigated. The cocktail probe drug method was used to investigate the effects of diabetic nephropathy (DN) and HQD on metabolic enzyme activity. The expression levels of liver Cyp450 metabolic enzymes (Cyp1A2, Cyp2C37, Cyp3A11, Cyp2E1, and Cyp2C11) and small intestinal transporters (breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), organic cation transporters (OCTs), and multidrug resistance-associated protein (MRPs) were determined using western blot. Compared to normal mice, the expression of OCT1, OCT2, MRP1, and MRP2 was increased in DN mice, while that of P-gp and BCRP (P < 0.05 and P < 0.001) was inhibited. HQD inhibited expression of Cyp1A2 and Cyp3A11 and increased the expression of P-gp and BCRP in normal mice. In DN mice, HQD induced expression of BCRP and inhibited expression of Cyp2C37, Cyp3A11, OCT2, MRP1, and MRP2. The activity of each Cyp450 enzyme was consistent with changes in expression. The changes in pharmacokinetic parameters of HQD in DN might, in part, be secondary to decreased expression of P-gp and BCRP. HQD varied in regulating transporter activities between health and disease. These findings support careful application of HQD-based treatment in DN, especially in combination with other drugs.

Carbene and photocatalyst-catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles to form ketones.

The carbene and photocatalyst co-catalyzed radical coupling of acyl electrophile and a radical precursor is emerging as attractive method for ketone synthesis. However, previous reports mainly limited to prefunctionalized radical precursors and two-component coupling. Herein, an N-heterocyclic carbene and photocatalyst catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles is disclosed, in which the carboxylic acids are directly used as radical precursors. The acyl imidazoles could also be generated in situ by reaction of a carboxylic acid with CDI thus furnishing a formally decarboxylative coupling of two carboxylic acids. In addition, the reaction is successfully extended to three-component coupling by using alkene as a third coupling partner via a radical relay process. The mild conditions, operational simplicity, and use of carboxylic acids as the reacting partners make our method a powerful strategy for construction of complex ketones from readily available starting materials, and late-stage modification of natural products and medicines.

Sex Difference of Effect of Sophora flavescens on Gut Microbiota in Rats.

Objective: By observing the sex difference of the gut microbiota in rats and the influence of Sophora flavescens (S. flavescens) on the gut microbiota in rats of different genders, it is hoped that it can provide reference materials for the rational use of S. flavescens in clinical practice. Method: Taking samples of the jejunum (containing intestinal contents) and feces of 8-week-old rats, and detecting the composition of gut microbiota of females and males by 16S rRNA sequencing technology; At the same time, 8-week-old rats were gavaged with different doses of S. flavescens decoction, and the duodenum, jejunum, ileum, and colon (including the intestinal contents) samples were collected at 1, 2, and 3 weeks, using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) technology and real-time fluorescent quantitative PCR (qRT-PCR) technology to observe the changes in the structure and the quantitative changes of 4 major intestinal dominant bacteria Enterococcus, Bacteriodes, Lactobacillus, and Clostridium in each intestinal segment, respectively. Result: (1) The gut microbiota of normal rats without administration also had obvious gender differences; (2) S. flavescens significantly affects the composition of gut microbiota, and in different intestinal segments, this effect was different between genders under different dosages and different continuous administration times. Conclusion: The effect of S. flavescens on the gut microbiota of rats had gender differences.

Carbene-catalyzed atroposelective synthesis of axially chiral styrenes.

Axially chiral styrenes bearing a chiral axis between a sterically non-congested acyclic alkene and an aryl ring are difficult to prepare due to low rotational barrier of the axis. Disclosed here is an N-heterocyclic carbene (NHC) catalytic asymmetric solution to this problem. Our reaction involves ynals, sulfinic acids, and phenols as the substrates with an NHC as the catalyst. Key steps involve selective 1,4-addition of sulfinic anion to acetylenic acylazolium intermediate and sequential E-selective protonation to set up the chiral axis. Our reaction affords axially chiral styrenes bearing a chiral axis as the product with up to > 99:1 e.r., > 20:1 E/Z selectivity, and excellent yields. The sulfone and carboxylic ester moieties in our styrene products are common moieties in bioactive molecules and asymmetric catalysis.

Hope as a Process in Understanding Positive Mood and Suicide Protection.

Background: According to the broaden-and-build model of positive mood, positive emotions are believed to broaden cognition resources and build psychological resiliency, to help incur positive psychological outcomes. Aim: We examined hope as a potential mediator of the association between positive mood and suicide protection (viz., life satisfaction and reasons for living) in adults. We hypothesized that positive mood would be associated with greater suicide protection through broadening hope agency and building hope pathways. Method: A sample of 320 college students completed measures of positive emotions, hope, and suicide protection. Results: Results from bootstrapped mediation testing indicated that hope agency, but not hope pathways, partially or fully mediated the relationship between positive mood and suicide protection. Limitations: It is not clear whether these findings are generalizable to a more diverse adult population. Also, it is not possible to rule out alternative causal models involving positive emotions and suicide protection. Conclusion: These findings provide some promising preliminary evidence for how positive emotions might help build hope agency to foster greater suicide protection in adults.