Sulphated Fucooligosaccharide from Sargassum Horneri: Structural Analysis and Anti-Alzheimer Activity.

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO3-)-1→4-α-L-fucp(2,3-SO3-)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.

Trajectories of anxiety and depression among Chinese men who have sex with men on pre-exposure prophylaxis: a group-based trajectory model approach.

BACKGROUND: Anxiety and depression can influence adherence to Pre-exposure Prophylaxis (PrEP). However, there is limited research on the temporal dynamics of anxiety and depression among men who have sex with men (MSM) using PrEP. METHODS: From December 2018 to November 2020, we administered the Hospital Anxiety and Depression Scale (HADS) to participants in the China Real-World Oral Intake of PrEP (CROPrEP) to measure their anxiety and depression levels. The group-based trajectory model (GBTM) depicted the dynamic changes of anxiety and depression scores over time. RESULTS: A total of 1023 MSM were included, with 4523 follow-up assessments. The GBTM categorized the trajectories into three distinct patterns: consistently low (54.8% for anxiety, 60.7% for depression), consistently moderate (39.3% for anxiety, 31.4% for depression), and high but bell-shaped (5.9% for anxiety, 7.9% for depression). Higher anxiety levels were associated with being aged 18-30 years old, earning less than US$619 per month, female-identifying, adopting the bottom sexual role with men, and having two or more anal sex partners in the past three months; similarly, higher depression levels correlated with a monthly income under US$619, female-identifying, sexual behavior as bottom and a positive syphilis at baseline. PrEP adherence was notably lower in the high but bell-shaped anxiety and depression group compared to the other groups, particularly at the 12th-month follow-up. CONCLUSIONS: Close monitoring of anxiety and depression levels in MSM on PrEP is crucial. Provision of targeted mental health support is essential to enhance PrEP effectiveness.

Alterations in levels of cytokine following treatment to predict outcome of sepsis: A meta-analysis.

BACKGROUND: The mortality rate of patients with sepsis has been increasing in recent years. Alterations of biomarkers levels during treatment are important in evaluating treatment efficacy and predicting outcomes in sepsis. This meta-analysis investigated the relationship between changes in cytokine levels after treatment compared with those on hospital admission, and their relationship with the prognosis of patients with sepsis. METHODS: From conception until August 4, 2021, a complete literature search of the PubMed, Web of Science, and Cochrane Library electronic databases was done. Observational studies where the outcomes of sepsis patients were divided into non-survivors and survivors and which reported cytokine levels at least before treatment in ICU were included in the current study. Standardized mean difference (SMD) with 95% confidence intervals (CI) values from individual studies were pooled using a random-effects model. Quality assessment, subgroup analysis, publication bias, and sensitivity analyses were all carried out. RESULTS: A total of 2570 patients with sepsis from 25 eligible studies were included, and 14 of them measured the cytokine levels before and after treatment in ICU. Among IL-6, TNF-α, IL-1ß and IL-10 levels, those of IL-6 were significantly lower after treatment in ICU than at baseline in patients with sepsis in the survival group (SMD = -0.69, P < 0.0001), but were comparable in the non-survival group (SMD = -0.99, P = 0.0575). Similarly, post-treatment TNF-α levels were significantly lower than those at baseline only in patients with sepsis in the survival group (SMD = -0.44, P < 0.0001), but not in the non-survival group (SMD =-0.17, P = 0.0842). CONCLUSION: This meta-analysis shows that reduced IL-6 and TNF-α levels after sepsis treatment in ICU may be indicators of better prognosis and survival of patients with sepsis.

The development of autoverification system of lymphocyte subset assays on the flow cytometry platform.

OBJECTIVES: Peripheral blood lymphocyte subsets are important parameters for monitoring immune status; however, lymphocyte subset detection is time-consuming and error-prone. This study aimed to explore a highly efficient and clinically useful autoverification system for lymphocyte subset assays performed on the flow cytometry platform. METHODS: A total of 94,402 lymphocyte subset test results were collected. To establish the limited-range rules, 80,427 results were first used (69,135 T lymphocyte subset tests and 11,292 NK, B, T lymphocyte tests), of which 15,000 T lymphocyte subset tests from human immunodeficiency virus (HIV) infected patients were used to set customized limited-range rules for HIV infected patients. Subsequently, 13,975 results were used for historical data validation and online test validation. RESULTS: Three key autoverification rules were established, including limited-range, delta-check, and logical rules. Guidelines for addressing the issues that trigger these rules were summarized. The historical data during the validation phase showed that the total autoverification passing rate of lymphocyte subset assays was 69.65% (6,941/9,966), with a 67.93% (5,268/7,755) passing rate for T lymphocyte subset tests and 75.67% (1,673/2,211) for NK, B, T lymphocyte tests. For online test validation, the total autoverification passing rate was 75.26% (3,017/4,009), with 73.23% (2,191/2,992) for the T lymphocyte subset test and 81.22% (826/1,017) for the NK, B, T lymphocyte test. The turnaround time (TAT) was reduced from 228 to 167 min using the autoverification system. CONCLUSIONS: The autoverification system based on the laboratory information system for lymphocyte subset assays reduced TAT and the number of error reports and helped in the identification of abnormal cell populations that may offer clues for clinical interventions.

Association between rectal douching and HIV acquisition: the mediating role of condom use and rectal bleeding in a national online sample of Chinese men who have sex with men.

OBJECTIVES: Previous studies have demonstrated that rectal douching (RD) is associated with HIV acquisition among men who have sex with men (MSM). However, the precise mechanism underlying the association between RD and HIV remains unclear. METHODS: We recruited participants over WeChat from October 2017 to October 2018. Respondents received mailed HIV self-testing kits, uploaded images of HIV self-test results and completed an online electronic questionnaire simultaneously. The questionnaire assessed sociodemographic characteristics, RD practices and sexual risk behaviours. HIV status was measured as the result of the HIV self-testing. The Baron and Kenny statistical method was used to assess the association between RD and HIV, controlling for condomless anal intercourse (CAI) and rectal bleeding. RESULTS: Of 1365 participants, 39.93% (545/1365) reported RD in the past 6 months, 60.07% had multiple male sexual partners and 43.08% had CAI in the past 6 months. The prevalence of HIV, based on self-testing, was 3.37% (46/1365). Multivariable logistic analysis showed RD was significantly associated with bottom sexual role (adjusted OR (aOR) 14.0; 95% CI 9.8 to 20.2), having multiple male sexual partners (aOR 1.8; 95% CI 1.4 to 2.2), CAI (aOR 1.3; 95% CI 1.0 to 1.6), rectal bleeding (aOR 2.0; 95% CI 1.6 to 2.6) and HIV infection (aOR 1.9; 95% CI 1.0 to 3.4). Baron and Kenny analysis found both CAI (aOR 2.2; 95% CI 1.2 to 4.1) and rectal bleeding (aOR 1.9; 95% CI 1.0 to 3.4) play a mediating role in the association between RD and HIV. CONCLUSIONS: Our study results confirmed the relationship between RD and HIV, and found CAI and rectal bleeding mediated HIV infection in Chinese MSM who douched. Strategies should be encouraged to strengthen health education and reduce high-risk sexual behaviour in order to reduce the risk of HIV in MSM who use enemas. Rectal microbicides may represent an efficient means of providing HIV prophylaxis among MSM.

A new indolizinium alkaloid from marine-derived Streptomyces sp. HNA39.

A new indolizinium alkaloid, named as cyclizidine J (1), was identified from Gause's liquid fermentation of marine-derived Streptomyces sp. HNA39. Its structure was elucidated by extensive NMR spectroscopic methods, HRESIMS data, and ECD calculations. To our best knowledge, compound 1 was a unique cyclizidine-type alkaloid that contain a chlorine atom substituted at position C-8. Unfortunately, biological evaluation of 1 exhibited no active against PC-3 cancer cell line, BRD4, and ROCK2 protein kinase.

Gephyromycin C, a novel small-molecule inhibitor of heat shock protein Hsp90, induces G2/M cell cycle arrest and apoptosis in PC3 cells in vitro.

Gephyromycin C (GC), a natural compound isolated from a marine-derived actinomycete Streptomyces sp. SS13I, which exerts anti-proliferative effect on PC3 cells. However, its underlying mechanism of the anti-cancer effect remains unknown. The results of SRB assays showed that GC inhibited the proliferation of PC3 cells with an IC50 value of 1.79 ± 0.28 µM. GC also induced G2/M cell cycle arrest which was accompanied by declining levels of cyclin proteins. Possible mechanisms were investigated and it was found that GC bound to Hsp90 and caused the degradation of Hsp90 client proteins (AKT, CHK1, P53, CDK4, Raf-b, and Raf-1). The fluorescent polarization assay with FITC-labeled geldanamycin (FITC-GA) demonstrated that GC was able to compete with FITC-GA in binding to wild type Hsp90 with an IC50 of 2.15 µM. Results of a docking study also suggested that GC interacted with the N-terminal domain of Hsp90. Our results showed that GC could bind to Hsp90, which resulted in down-regulation of Hsp90 client proteins and G2/M arrest in PC3 cells. Since the antitumor effects of this kind of angucycline via targeting Hsp90 has not been reported before, our results indicate that GC is a novel inhibitor of Hsp90 from marine resources and worthy of further study.

Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection.

BACKGROUND: Disease progression in the absence of therapy varies significantly in mono-HIV and HCV infected individuals. Virus-specific CD8+ T cells play an important role in restricting lentiviral replication and determining the rate of disease progression during HIV and HCV mono- and co-infection. Thus, understanding the similarities in the characteristics of CD8+ T cells in mono-HIV and HCV infection at the transcriptomic level contributes to the development of antiviral therapy. In this study, a meta-analysis of CD8+ T cell gene expression profiles derived from mono-HIV and HCV infected individuals at different stages of disease progression, was conducted to understand the common changes experienced by CD8+ T cells. METHODS: Five microarray datasets, reporting CD8+ T cell mRNA expression of the mono-HIV and HCV infected patients, were retrieved from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified via integrative meta-analysis of expression data (INMEX) program. Network analysis methods were used to assess protein-protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs. MirDIP and miRDB online prediction tools were used to predict potential microRNAs (miRNAs) targeting hub genes. RESULTS: First, we identified 625 and 154 DEGs in the CD8+ T cells originating from mono-HIV and HCV chronic progressor patients, respectively, compared to healthy individuals. Among them, interferon-stimulated genes (ISGs) including ISG15, IFIT3, ILI44L, CXCL8, FPR1 and TLR2, were upregulated after mono-HIV and HCV infection. Pathway enrichment analysis of DEGs showed that the "cytokine-cytokine receptor interaction" and "NF-kappa B" signaling pathways were upregulated after mono-HIV and HCV infection. In addition, we identified 92 and 50 DEGs in the CD8+ T cells of HIV non-progressor and HCV resolver patients, respectively, compared with corresponding chronic progressors. We observed attenuated mitosis and reduced ISG expression in HIV non-progressors and HCV resolvers compared with the corresponding chronic progressors. Finally, we identified miRNA-143-3p, predicted to target both IFIT3 in HIV and STAT5A in HCV infection. CONCLUSIONS: We identified DEGs and transcriptional patterns in mono-HIV and HCV infected individuals at different stages of disease progression and identified miRNA-143-3p with potential to intervene disease progression, which provides a new strategy for developing targeted therapies.

CD4+CD38+ central memory T cells contribute to HIV persistence in HIV-infected individuals on long-term ART.

BACKGROUND: Despite the effective antiretroviral treatment (ART) of HIV-infected individuals, HIV persists in a small pool. Central memory CD4+ T cells (Tcm) make a major contribution to HIV persistence. We found that unlike HLA-DR, CD38 is highly expressed on the Tcm of HIV-infected subjects receiving ART for > 5 years. It has been reported that the half-life of total and episomal HIV DNA in the CD4+CD38+ T cell subset, exhibits lower decay rates at 12 weeks of ART. Whether CD38 contributes to HIV latency in HIV-infected individuals receiving long-term ART is yet to be addressed. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of HIV-infected subjects receiving suppressive ART. The immunophenotyping, proliferation and apoptosis of CD4+ T cell subpopulations were detected by flow cytometry, and the level of CD38 mRNA and total HIV DNA were measured using real-time PCR and digital droplet PCR, respectively. A negative binomial regression model was used to determine the correlation between CD4+CD38+ Tcm and total HIV DNA in CD4+ T cells. RESULTS: CD38 was highly expressed on CD4+ Tcm cells from HIV infected individuals on long-term ART. Comparing with HLA-DR-Tcm and CD4+HLA-DR+ T cells, CD4+CD38+ Tcm cells displayed lower levels of activation (CD25 and CD69) and higher levels of CD127 expression. The proportion of CD38+ Tcm, but not CD38- Tcm cells can predict the total HIV DNA in the CD4+ T cells and the CD38+ Tcm subset harbored higher total HIV DNA copy numbers than the CD38- Tcm subset. After transfected with CD38 si-RNA in CD4+ T cells, the proliferation of CD4+ T cells was inhibited. CONCLUSION: The current date indicates that CD4+CD38+ Tcm cells contribute to HIV persistence in HIV-infected individuals on long-term ART. Our study provides a potential target to resolve HIV persistence.

Decreased CD4+CD8low T cells in early HIV infection are associated with rapid disease progression.

BACKGROUND: HIV rapid progressors (RPs) present with a rapid decline of CD4+ T cells within a few years of infection. Determining the underlying mechanisms throughout this decline is important to identify prognostic biomarkers and intervention strategies. Determining the numbers of CD4+ and CD8+ T cells is essential for monitoring the immune status of HIV infected patients. There are additional kinds of cell subtypes in T cells, but their relationship to the rapid progression of HIV disease is not well defined. METHODS: Nineteen RPs and twenty-one chronic progressors (CPs) were enrolled in this study. Based on the intensity of CD4 and CD8 expression, different T cell subtypes were identified, including CD4+CD8+T cells, CD4-CD8- T cells, CD4+CD8low T cells and CD4-CD8low T cells. Alterations in these T cell subtypes in early HIV infection (within 120 days of infection) between RPs and CPs were measured, and the relationships between these subtypes and HIV disease progression were investigated. In addition, expression of IFN-γ in T cell subtypes after PMA stimulation was analyzed by flow cytometry. RESULTS: We found that during early HIV infection, CD4+CD8low T cells both significantly decreased in numbers and percentages in RPs compared to CPs. Furthermore, baseline CD4+CD8low T cells positively correlated not only with baseline CD4+T cells but also with CD4+T cells 12 months after infection. Moreover, survival analysis indicated that low levels of baseline CD4+CD8low T cells significantly accelerated the decline in CD4+ T cells as well as increased viral loads. CD4+CD8low T cells secreted significantly more IFN-γ after PMA stimulation compared to CD4+CD8-T cells and CD4-CD8+T cells, which may be beneficial for the prevention of disease progression. CONCLUSIONS: Our results identified that in early stage HIV-1 infection, a subtype of T cells, CD4+CD8low, are associated with subsequent disease progression.

Increasing Condomless Anal Intercourse and HIV Prevalence Among Men Who Have Sex with Men Who Have Never Been Tested for HIV Before: A Serial Cross-Sectional Study in Shenyang, China from 2012 to 2016.

Despite the high HIV incidence among men who have sex with men (MSM) in China, over half of MSM have never been tested for HIV before (MSMNT). Through a serial cross-sectional study from 2012 to 2016 in Shenyang, China, we studied 1036 MSMNT, and diagnosed 16.2% (168/1036) with HIV. The percentage of MSMNT who had condomless anal intercourse (CAI) in the past year increased from 42.1% (130/309) in 2012 to 63.4% (102/161) in 2016 (P < 0.001). 61.9% (104/168) of HIV-positive MSMNT had CAI and this percentage remained constant for the study period (P = 0.593). 53.3% (463/868) of HIV-negative MSMNT had CAI and this percentage significantly increased over the study period (P < 0.001). Encouraging HIV testing in this key subset through online HIV risk self-evaluation tools and HIV self-testing kits may help mitigate the overall MSM HIV incidence.

A new compound from the marine-derived Streptomyces sp. SS13M.

As part of our efforts toward search for structurally new and bioactive natural products from marine-derived microorganisms, one new compound (1) was characterized from a marine-derived actinomycete Streptomyces sp. SS13M. The structure of new compound was elucidated by the analysis of HRESIMS, 1D, and 2D NMR spectroscopic data, and the absolute configuration was determined by ECD calculations.[Formula: see text].

Reduced eIF3d accelerates HIV disease progression by attenuating CD8+ T cell function.

BACKGROUND: In human immunodeficiency virus (HIV) infection, 10-15% of individuals exhibit a rapid decline in CD4+ T cells and become rapid progressors (RPs). Overall, understanding the factors affecting rapid disease progression in early HIV infection (EHI) can aid in treatment initiation. Recent studies show that eIF3s, classic scaffold proteins during the translation initiation process, can directly promote or inhibit the translation of mRNA, therefore participating in the regulation of cell function. However, to our knowledge, it has not been addressed whether eIF3s are involved in the diverse prognosis of HIV infection. METHODS: Expression of eIF3s in primary cells from early or chronic HIV-infected patients was detected by real-time PCR. To investigate the potential mechanisms of eIF3d in the regulation of CD8+ T cell function, complete transcriptomes of eIF3d-inhibited Jurkat T cells were sequenced by RNA sequencing (RNA-Seq). Additionally, to examine the effect of eIF3d on CD8+ T cell function, eIF3d expression was inhibited alone or in combination with SOCS-7 knockdown by siRNA in isolated CD8+ T cells. CD8+ T cell proliferation, IFN-r secretion and apoptosis were detected by flow cytometry. Moreover, the effect of eIF3d on HIV replication was evaluated in Jurkat cells, peripheral blood mononuclear cells (PBMCs) and CD4+ T cells with eIF3d knockdown using a pNL4-3 pseudotyped virus. RESULTS: At approximately 100 days of infection, only eIF3d was markedly decreased in RPs compared with chronic progressors (CPs). Expression of eIF3d correlated significantly with disease progression in EHI. Based on in vitro analyses, reduced eIF3d expression led to decreased proliferation and IFN-γ secretion and increased apoptosis in CD8+ T cells. Inhibited expression of eIF3d caused enhanced expression of SOCS-7, and inhibiting SOCS-7 expression by siRNA rescued the attenuated CD8+ T cell function caused by eIF3d. Finally, when eIF3d was inhibited in Jurkat cells, PBMCs and CD4+ T cells, pNL4-3-VSV-G virus replication was enhanced. CONCLUSIONS: The current data highlight the importance of eIF3d in HIV infection by inhibiting CD8+ T cell function and promoting viral replication. Our study provides potential targets for improved immune intervention.

Efficacy and cost-effectiveness of early antiretroviral therapy and partners' pre-exposure prophylaxis among men who have sex with men in Shenyang, China: a prospective cohort and costing study.

BACKGROUND: Biomedical interventions such as antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are highly effective for prevention of human immunodeficiency virus (HIV) infection. However, China has not released national PrEP guidelines, and HIV incidence among men who have sex with men (MSM) is unchanged despite substantial scale-up of ART. We evaluated reductions in HIV transmission that may be achieved through early initiation of ART plus partners' PrEP. METHODS: Six intervention scenarios were evaluated in terms of their impact on HIV transmission and their cost-effectiveness for 36 months post-infection. Three scenarios were based on observed data: non-ART, standard-ART, and early-ART. Another three scenarios were based on observed and hypothetical data: non-ART plus partners' PrEP, standard-ART plus partners' PrEP, and early-ART plus partners' PrEP. The number of onward transmissions was calculated according to viral load and self-reported sexual behaviors, and calibrated by the prevalence and incidence of HIV among Chinese MSM. Cost-effectiveness outcomes were quality-adjusted life-years (QALYs) and cost-utility ratio (CUR). RESULTS: The estimated number of onward transmissions by every 100 HIV-positive cases 36 months post-infection was 41.83 (95% credible interval: 30.75-57.69) in the non-ART scenario, 7.95 (5.85-10.95) in the early-ART scenario, and 0.79 (0.58-1.09) in the early-ART plus partners' PrEP scenario. Compared with non-ART, the early-ART and early-ART plus partners' PrEP scenarios were associated with an 81.0 and 98.1% reduction in HIV transmission, and had a CUR of $12,864/QALY and $16,817/QALY, respectively. CONCLUSIONS: Integrated delivery of early ART and sexual partners' PrEP could nearly eliminate HIV transmission and reduce costs during the first 36 months of HIV infection. Our results suggest a feasible and cost-effective strategy for reversing the HIV epidemic among MSM in China.

Female and younger subjects have lower adherence in PrEP trials: a meta-analysis with implications for the uptake of PrEP service to prevent HIV.

OBJECTIVE: To estimate the medicine-taking compliance (MTC) level, explore its facilitators and barriers, and quantify the association between MTC level and pre-exposure prophylaxis (PrEP) protective efficacy in individuals at risk of acquiring HIV being administered oral PrEP. DESIGN: Meta-analysis. DATA SOURCES: We searched PubMed, Cochrane and Embase databases for published randomized controlled trials (RCTs) pertaining to MTC of oral PrEP for HIV prevention up to 16 January 2017. REVIEW METHODS: The pooled proportion of MTC and risk ratio (RR) of HIV incidences between intervention group and control group were estimated. RESULTS: We identified 10 eligible studies with 24 193 participants. The overall pooled MTC for oral HIV PrEP was 59.9% (95% CI 43.1% to 74.6%). Subgroup analyses revealed that the MTC level of participants aged <30 years was lower than those equal or older than 30 years (34.9% vs 69.6%, p<0.001); those studies that enrolled only women as participants had lower MTC than those only recruiting either only men or both men and women (31.3% vs 71.7% and 31.3% vs 71.0%, all p<0.01). Additionally, the HIV infection risk increased as the MTC level declines, with the incidence RRs being 0.28 (95% CI 0.19 to 0.41), 0.42 (95% CI 0.29 to 0.62) and 0.75 (95% CI 0.45 to 1.25) in the good (≥80%), moderate (60%~80%) and poor (<60%) MTC subgroups, respectively (linear trend test p<0.01). CONCLUSION: According to the pooled proportion, the MTC of oral HIV PrEP is almost moderate, and its proportion in women and younger participants was relatively low. The protective efficacy of oral PrEP for HIV prevention increased with MTC level. These findings indicated that it is necessary to identify measures to enhance MTC of oral PrEP in future clinical usage, especially in women and younger participants with high HIV infection risk.

High-risk behaviour and HIV infection risk among non-local men who have sex with men with less than a single year's residence in urban centres: a multicentre cross-sectional study from China.

OBJECTIVES: Traditionally, subjects' migration status has usually been defined on the basis of their registered residency status. We attempted to redefine migration based on the duration of residency in their cities of migration and to explore more precisely the impact of migration on HIV infection risk in men who have sex with men (MSM). METHODS: A multisite cross-sectional study was conducted during 2012-2013 in seven Chinese cities. Questionnaire surveys were conducted and blood was drawn to test for antibodies to HIV, syphilis and herpes simplex virus-2 (HSV-2). MSM who were unregistered local residents and had resided in their cities of migration for ≤1 or >1 year were defined as migrant MSM, or transitional MSM, respectively. RESULTS: Compared with transitional MSM and local MSM, migrant MSM had poorer HIV knowledge and higher rates of high-risk behaviour, including earlier sexual debut, multiple sexual partners, participation in commercial sex and recreational drug use. Multivariate logistic regression analysis showed that HIV prevalence among migrant MSM was higher than local MSM (p<0.05). This relationship, however, did not hold for transitional MSM and local MSM (p>0.05). Male sex work, recreational drug use, syphilis infection and HSV-2 infection were independently associated with HIV infection among migrant MSM. CONCLUSIONS: Non-local MSM with shorter residence were at greater risk of HIV acquisition. More focus should be placed on HIV behavioural interventions targeting non-local MSM with temporary residence.

HIV Incidence and Care Linkage among MSM First-Time-Testers in Shenyang, China 2012-2014.

HIV testing is the first step to the fulfillment of Treat as Prevention (TasP) and reaching the 90-90-90 goal in HIV control. However, there are still a large number of Men who have Sex with Men (MSM) have never been tested for HIV before, and little is known about the HIV incidence and care linkage among this population. A Mixed method was used to recruit MSM who had never tested for HIV before from January 2012 to December 2014 in Shenyang, China. Potential MSM participants were invited to attend the enrollment for HIV and syphilis testing at a general hospital-based voluntary counseling and test (VCT). HIV confirmed positive subjects were further tested by BED HIV-1 capture enzyme immunoassay (BED-CEIA) to determine the HIV incidence. Syphilis was screened by the rapid plasma reagent test (RPR) and confirmed by Treponema pallidum particle assay (TPPA). All the HIV positive subjects were referred to the local Center for Disease Control and Prevention (CDC) and clinics for HIV primary care and follow-ups. In total 646 HIV first-time-testers of MSM (FMSM) attended this study, 73.4% (474/646) were aged under 31-year-old and 57.3% (370/646) and used the Internet as their major cruising avenue for seeking male sexual partners. The average prevalence of HIV and current syphilis infection was 10.8% (70/646) and 11.0% (71/646), respectively. The HIV incidence was 10.3 (95% confidence interval [CI] 6.1-14.5)/100PY. Multivariate logistic analysis showed that factors such as use of the Internet as the major cruising avenue (adjusted OR [AOR] 2.7, 95% CI 0.9-7.6) and having a current syphilis infection (AOR 4.2, 95% CI 1.8-12.2) were independent correlates of a recent HIV infection. Of the 95 HIV screening test positive FMSM, 73.7% (70/95) returned and be confirmed positive, 92.9% (65/70) of confirmed patients were linked to care. Among those retained and underwent CD4+ T cell test, 76.3% (42/55) started HIV antiretroviral therapy. Among the unconfirmed, 84.0% (21/25) were non-local migrants. The HIV incidence of FMSM in Shenyang was high. Future HIV testing program needs to keep on expanding among the MSM who have never been tested for HIV yet. The Internet-based campaigns and syphilis testing and treatment could represent an opportunity to get access to this hard-to-reach population and link them to HIV care. Future linkage to HIV care of this population should underscore the usage of HIV rapid diagnostic tests to prevent lost at early steps of linkage.

Cyclizidine-Type Alkaloids from Streptomyces sp. HNA39.

Eight new cyclizidine-type alkaloids (1-8) and one known alkaloid (9) were identified from the chemical investigations of a marine-derived actinomycete, Streptomyces sp. HNA39. Among these alkaloids, compounds 3, 7, and 8 contain a chlorine atom, and the known alkaloid, (+)-ent-cyclizidine (9), is now first reported as a natural product. Their structures were elucidated by extensive NMR-spectroscopic analysis and HRESIMS data. The absolute configurations of all of the compounds were established by ECD calculations. Cytotoxicity evaluations of all of the compounds showed that compound 2 exhibited significant activity against the PC3 and HCT116 human-cancer-cell lines with IC50 values of 0.52 ± 0.03 and 8.3 ± 0.1 µM, respectively. Interestingly, compounds 2, 5, 7, and 8 exhibited moderate inhibition against the ROCK2 protein kinase with IC50 values from 7.0 ± 0.8 to 42 ± 3 µM.

Medermycin-Type Naphthoquinones from the Marine-Derived Streptomyces sp. XMA39.

Four new medermycin-type naphthoquinones, strepoxepinmycins A-D (1-4), and one known compound, medermycin (5), were identified from Streptomyces sp. XMA39. Their structures were elucidated by analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and ECD calculations. Among these compounds, strepoxepinmycin A (1) represents a rare 5,10-oxepindione ring system typically formed by a Baeyer-Villiger oxidation, and strepoxepinmycin B (2) is an isolation artifact derived from 1. Bioactivity evaluations of these compounds showed that compounds 3 and 4 exhibited cytotoxicity against HCT-116 and PC-3 cancer cell lines and 4 exhibited moderate inhibition of ROCK 2 protein kinase. In addition, all of the new compounds showed antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus and antifungal activity against Candida albicans.

Transcriptomic meta-analysis identifies gene expression characteristics in various samples of HIV-infected patients with nonprogressive disease.

BACKGROUND: A small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (<50 copies/ml) and long-term nonprogressors (LTNPs) who maintain normal CD4+ T cell counts for prolonged periods (>10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers. METHODS: Using the INMEX (integrative meta-analysis of expression data) program, we performed the meta-analysis to identify consistently differentially expressed genes (DEGs) in nonprogressors and further performed functional interpretation (gene ontology analysis and pathway analysis) of the DEGs identified in the meta-analysis. Five microarray datasets (81 cases and 98 controls in total), including whole blood, CD4+ and CD8+ T cells, were collected for meta-analysis. RESULTS: We determined that nonprogressors have reduced expression of important interferon-stimulated genes (ISGs), CD38, lymphocyte activation gene 3 (LAG-3) in whole blood, CD4+ and CD8+ T cells. Gene ontology (GO) analysis showed a significant enrichment in DEGs that function in the type I interferon signaling pathway. Upregulated pathways, including the PI3K-Akt signaling pathway in whole blood, cytokine-cytokine receptor interaction in CD4+ T cells and the MAPK signaling pathway in CD8+ T cells, were identified in nonprogressors compared with progressors. In each metabolic functional category, the number of downregulated DEGs was more than the upregulated DEGs, and almost all genes were downregulated DEGs in the oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle in the three types of samples. CONCLUSIONS: Our transcriptomic meta-analysis provides a comprehensive evaluation of the gene expression profiles in major blood types of nonprogressors, providing new insights in the understanding of HIV pathogenesis and developing strategies to delay HIV disease progression.