Factors related to the mortality risk of severe hand, foot, and mouth diseases (HFMD): a 5-year hospital-based survey in Guangxi, Southern China.

BACKGROUND: To understand the factors influencing clinical outcomes of severe hand, foot, and mouth diseases (HFMD), and to provide scientific evidence for reducing the mortality risk of severe HFMD. METHODS: From 2014 to 2018, children diagnosed with severe HFMD cases in Guangxi, China, were enrolled in this hospital-based study. The epidemiological data obtained through face-to-face interviews with the parents and guardians. Univariate and multivariate logistics regression models were used to analyze the factors influencing the clinical outcomes of severe HFMD. The impact of the EV-A71 vaccination on inpatient mortality was analyzed by a comparison approach. RESULTS: A total of 1565 severe HFMD cases were enrolled in this survey, including 1474 (94.19%) survival cases and 91 (5.81%) death cases. The multivariate logistic analysis demonstrated that HFMD history of playmates in the last three months, first visit to the village hospital, time from the first visit to admission less than two days, no correct diagnosis for HFMD at the first visit, and having no rash symptoms were the independent risk factors for severe HFMD cases (all p < 0.05). While EV-A71 vaccination was a protective factor (p < 0.05). The EV-A71 vaccination group versus the non-vaccination group showed 2.23% of death in the vaccination group and 7.24% of death in the non-vaccination group. The EV-A71 vaccination protected 70.80% of the death of severe HFMD cases, with an effective index of 4.79. CONCLUSIONS: The mortality risk of severe HFMD in Guangxi was related to playmates had HFMD history in last 3 months, hospital grade, EV-A71 vaccination, patients visit hospital previously, and rash symptom. EV-A71 vaccination can significantly reduce mortality among severe HFMD. The findings are of great significance for the effective prevention and control of HFMD in Guangxi, southern China.

Potential Inhibitors of Monkeypox Virus Revealed by Molecular Modeling Approach to Viral DNA Topoisomerase I.

The monkeypox outbreak has become a global public health emergency. The lack of valid and safe medicine is a crucial obstacle hindering the extermination of orthopoxvirus infections. The identification of potential inhibitors from natural products, including Traditional Chinese Medicine (TCM), by molecular modeling could expand the arsenal of antiviral chemotherapeutic agents. Monkeypox DNA topoisomerase I (TOP1) is a highly conserved viral DNA repair enzyme with a small size and low homology to human proteins. The protein model of viral DNA TOP1 was obtained by homology modeling. The reliability of the TOP1 model was validated by analyzing its Ramachandran plot and by determining the compatibility of the 3D model with its sequence using the Verify 3D and PROCHECK services. In order to identify potential inhibitors of TOP1, an integrated library of 4103 natural products was screened via Glide docking. Surface Plasmon Resonance (SPR) was further implemented to assay the complex binding affinity. Molecular dynamics simulations (100 ns) were combined with molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) computations to reveal the binding mechanisms of the complex. As a result, three natural compounds were highlighted as potential inhibitors via docking-based virtual screening. Rosmarinic acid, myricitrin, quercitrin, and ofloxacin can bind TOP1 with KD values of 2.16 µM, 3.54 µM, 4.77 µM, and 5.46 µM, respectively, indicating a good inhibitory effect against MPXV. The MM/PBSA calculations revealed that rosmarinic acid had the lowest binding free energy at -16.18 kcal/mol. Myricitrin had a binding free energy of -13.87 kcal/mol, quercitrin had a binding free energy of -9.40 kcal/mol, and ofloxacin had a binding free energy of -9.64 kcal/mol. The outputs (RMSD/RMSF/Rg/SASA) also indicated that the systems were well-behaved towards the complex. The selected compounds formed several key hydrogen bonds with TOP1 residues (TYR274, LYS167, GLY132, LYS133, etc.) via the binding mode analysis. TYR274 was predicted to be a pivotal residue for compound interactions in the binding pocket of TOP1. The results of the enrichment analyses illustrated the potential pharmacological networks of rosmarinic acid. The molecular modeling approach may be acceptable for the identification and design of novel poxvirus inhibitors; however, further studies are warranted to evaluate their therapeutic potential.

Construction of Thioamide Peptides from Chiral Amino Acids.

Thioamide peptides were synthesized in a straightforward one-pot process via the linkage of diverse natural amino acids in the presence of thiolphosphonate and trichlorosilane, wherein carbonyl groups were replaced with thiono compounds with minimal racemization. Experimental and computational mechanistic studies demonstrated that the trichlorosilane enables the activation of carboxylic acids via intense interactions with the Si-O bond, followed by coupling of the carboxylic acids with thiolphosphonate to obtain the key intermediate S-acyl dithiophosphate. Silyl-activated quadrangular metathesis transition states afforded the thioamide peptides. The potential applications of these thioamide peptides were further highlighted via late-stage linkages of diverse natural products and pharmaceutical drugs and the thioamide moiety.

Acceptance of COVID-19 vaccination and influencing factors among people living with HIV in Guangxi, China: a cross-sectional survey.

BACKGROUND: Vaccination has been proven to be an effective approach against the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to determine the acceptance rate and factors influencing acceptance of COVID-19 vaccination among people living with HIV (PLWH) in Guangxi, China. METHODS: A cross-sectional survey was carried out in five cities in Guangxi, China from May 7 to June 1, 2021. Questionnaires on the acceptance of COVID-19 vaccination and the related factors were conducted among PLWH recruited by simple random sampling. Univariate and multivariate logistic regression analyses were performed to identify factors associated with acceptance of COVID-19 vaccination. RESULTS: Of all valid respondents (n = 903), 72.9% (n = 658) were willing to receive COVID-19 vaccination. Fear of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was the main reason for being willing to receive vaccination (76.0%), while the main reasons for not willing were the concerns about vaccine safety (54.7%) and the vaccination's effect on antiretroviral therapy (ART) (50.6%). The most important factors influencing acceptance were the perception that vaccination is unsafe for HIV-infected people (aOR = 0.082, 95% CI = 0.024-0.282) and the poor efficacy in preventing SARS-CoV-2 infection in HIV-infected people (aOR = 0.093, 95% CI = 0.030-0.287). Other factors associated with acceptance included Zhuang ethnicity (aOR = 1.653, 95% CI = 1.109-2.465), highest education level of middle school, high school or above (aOR = 1.747, 95% CI = 1.170-2.608; aOR = 2.492, 95% CI = 1.326-4.682), and the vaccination having little effect on ART efficacy (aOR = 2.889, 95% CI = 1.378-6.059). CONCLUSIONS: Acceptance rate of the COVID-19 vaccination is relatively low among PLWH compared to the general population in China, although some patients refused vaccination due to concerns about vaccine safety and vaccination affecting ART efficacy. More research is needed to investigate the impact of the COVID-19 vaccines on ART efficacy and the effectiveness in preventing SARS-CoV-2 infection among PLWH.

High HIV prevalence, low awareness of and willingness to use HIV pre-exposure prophylaxis among male migrant workers in Southwestern, China: a short report.

Little is known about pre-exposure prophylaxis (PrEP) awareness and willingness among male rural-to-urban migrant workers, a high-risk population of HIV infection and transmission in China. The aim of this study was to assess the awareness of and willingness to use PrEP among this vulnerable population in two cities in Guangxi Zhuang autonomous region, a province in southwestern China. A cross-sectional survey was conducted among male rural-to-urban migrant workers in Guangxi province, during June to August, 2015. Multivariable logistic regression analysis was used to examine the factors related to PrEP acceptance. Among 669 male rural-to-urban migrant workers surveyed, the HIV prevalence was 1.79%. Among the 657 HIV-negative participants, 23.0% had heard of PrEP, 1.2% had used PrEP, and 64.7% were willing to use PrEP. Being afraid of HIV/AIDS (OR = 2.08, 95%CI: 1.04-4.19) and willing to have an HIV test (OR = 3.74, 95%CI: 1.64-8.52) were associated with willingness to use PrEP. The findings suggest that among male migrant workers in Southwestern China, the awareness of and willingness to use PrEP were relatively low. Given the fact that the HIV prevalence was high among this population, more educational campaigns about PrEP and targeted interventions are necessary for this high-risk population in Guangxi.

Comparative proteomic analysis reveals cytotoxicity induced by graphene oxide exposure in A549 cells.

Several studies in recent years have demonstrated the broad application prospects of graphene and its derivatives in many fields such as composite material industry, energy storage, antimicrobial materials, and biomedicine. Large-scale production and wide application also bring greater potential exposure risks, and there has been an increasing concern about the potential health hazards of graphene nanomaterials. In the present study, we exploited nonlabeled proteomics and bioinformatics analysis to examine the proteomic response to graphene oxide (GO) and unveil a systematic view of molecular targets and possible mechanisms underlying cytotoxicity of GO in A549 cells. Overall, 89 proteins were found to be differentially expressed at different exposure levels. These differentially expressed proteins were involved in several biological processes and signal transduction pathways such as messenger RNA (mRNA) splicing, negative regulation of plasminogen activation, extracellular matrix organization, positive regulation of cell migration, complement and coagulation cascades, p53 signaling pathway, and transcriptional misregulation in cancer. It is suggested that GO may exert toxic effects on cells by regulating gene transcription, immune response, cell growth, and apoptosis. Ingenuity pathway analysis showed that SMARCA4, TGF-ß1, and TP53 were located at the center of the protein interaction network and considered as key node proteins regulating GO toxicity. In general, these findings will augment our knowledge of the involved mechanisms and aid in developing develop useful biomarkers for GO-induced pulmonary toxicity.

Vietnamese female sex workers in rural cross-border areas of Guangxi, China: migration and HIV/STI risk behaviors.

China's HIV/AIDS epidemic continues to grow in rural and less developed areas. This consecutive cross-sectional study examines demographic and behavioral factors associated with HIV/STI infection, Hepatitis C (HCV) and other sexually transmitted infections (STIs) among Vietnamese female sex workers (FSW), a vulnerable population who cross into Guangxi, China. This study is a secondary data analysis of 303 Vietnamese and 4,348 Chinese FSWs recruited over seven years from two Chinese counties that border Vietnam. Logistic regression models compared demographics, HIV/STI status, HIV/AIDS-related knowledge, attitudes, and risk behaviors between Vietnamese FSWs and Chinese FSWs. Compared with Chinese FSWs, Vietnamese FSWs were younger, had attained lower education levels, were highly mobile, more likely to report using drugs, and were more vulnerable to HIV/STIs. Younger age, less educational attainment, shorter time in their current working location, no voluntary HIV testing in the last year, greater drug use, and not using condoms for all commercial sex in the last month were associated with higher HIV/STIs. In conclusion, several factors were associated with HIV/STI risk in Vietnamese cross-border FSWs. There is a pressing need to improve support systems for Vietnamese cross-border FSW and health system cooperation across the Chinese/Vietnamese border.

Cytotoxic Nitrogenated Azaphilones from the Deep-Sea-Derived Fungus Chaetomium globosum MP4-S01-7.

Eight new nitrogenated azaphilones (1-8) and two known compounds (chaetoviridin A and chaetoviridin E, 9, 10) were isolated from the culture of the deep-sea-derived fungus Chaetomium globosum MP4-S01-7. The absolute configurations of new compounds were elucidated by HSQC-HECADE NMR data, J-based configuration analysis, and modified Mosher's method and finally verified by comparison of recorded and computed NMR chemical shifts from quantum chemical calculations coupled with a statistical procedure (DP4+). All of the compounds were evaluated for their in vitro cytotoxicities against the gastric cancer cell lines MGC803 and AGS, and most of them showed significant inhibition on cancer cell viability at 10 µM. Among them, compounds 1, 2, and 5 exerted the most potent cytotoxic activities, with IC50 values less than 1 µM. Further studies showed that compound 2 inhibited cell cycle progression, and both compounds 1 and 2 induced apoptosis of gastric cancer cells in a concentration-dependent manner.

Aspeterreurone A, a Cytotoxic Dihydrobenzofuran-Phenyl Acrylate Hybrid from the Deep-Sea-Derived Fungus Aspergillus terreus CC-S06-18.

A new dihydrobenzofuran-phenyl acrylate hybrid, aspeterreurone A (1), was obtained from the culture of the deep-sea-derived fungus Aspergillus terreus CC-S06-18. The relative configuration of 1 was elucidated by HSQMBC NMR, calculated NMR chemical shifts coupled with a statistical procedure (DP4+), and the absolute configuration was established by ECD calculations. 1 exhibited cytotoxicities against the gastric cancer cell lines HGC27, MGC803, BGC823, and AGS, with minimal effects on normal gastric epithelial cell line GES-1. Further studies showed that 1 inhibited cell cycle progression and induced apoptosis of gastric cancer MGC803 cells in a concentration-dependent manner. Western blot analysis indicated that 1 inhibited the phosphorylation of STAT3, which might contribute to its cytotoxic activity.

Migrant female sex workers working at the Sino-Vietnamese border for a short time have a higher risk of HIV transmission: a consecutive cross-sectional study.

OBJECTIVES: For migrant female sex workers (FSWs) at the Sino-Vietnamese border, the impact of work time in their current location on the spread of HIV/AIDS is not clear. METHODS: Data were collected from the Sino-Vietnamese border cities of Guangxi, China. Migrant FSWs working in these cities were studied. FSWs who worked less than 6 months in their current location were assigned to the short-term work group (ST FSWs), and FSWs who worked equal to or longer than 6 months in their current location were assigned to the long-term work group (LT FSWs). Logistic regression was performed to examine the impact of work time in the current location and factors associated with HIV infection. RESULTS: Among the 1667 migrant FSWs, 586 (35.2%) and 1081 (64.9%) were assigned to the ST FSW and LT FSW groups, respectively. Compared to LT FSWs, ST FSWs were more likely to be of Vietnamese nationality, be less than 18 years old when they first engaged in commercial sex work, and have a low-level of HIV-related knowledge and had higher odds of using condoms inconsistently, having more male clients, having no regular male clients, and having a history of male clients who used aphrodisiacs but lower odds of receiving free condoms distribution and education/HIV counselling and testing programme. The analysis of factors associated with HIV infection revealed that Vietnamese FSWs, less than 18 years old when they first engaged in commercial sex work, having no regular male clients, and having lower average charge per sex transaction were correlated with HIV infection. CONCLUSION: FSWs with short-term work at the Sino-Vietnamese border had a higher risk of risky sex and were correlated with HIV risk factors. Vietnamese FSWs were at higher risk of HIV infection, and they were more likely to have short-term work. More targeted HIV prevention should be designed for new FSWs who recently began working in a locality to further control the spread of HIV, particularly cross-border FSWs.

HIV late presentation and advanced HIV disease among patients with newly diagnosed HIV/AIDS in Southwestern China: a large-scale cross-sectional study.

OBJECTIVE: This study aimed to investigate the prevalence of HIV late presentation and advanced HIV disease and to identify the factors associated with HIV late presentation and advanced HIV disease among patients with newly diagnosed HIV/AIDS in the Guangxi Zhuang Autonomous Region, in Southwestern China. METHODS: Patients with newly diagnosed HIV registered in the HIV surveillance system of Guangxi Centers for Disease Control between January 2012 and December 2016 were included in this study. RESULTS: Of 45,118 newly diagnosed patients, 70.2% had late presentation, and 45.1% had advanced HIV disease. A higher prevalence of late presentation and advanced HIV disease was found in male heterosexuals and female people who use drugs (PWID). Heterosexuals (OR 2.11 [95% CI 1.90-2.34]) and PWID (OR 1.55 [95% CI 1.30-1.84]) had a higher risk of late presentation than men who have sex with men (MSM). Blood testing of the blood receivers (OR 1.75 [95% CI 1.36-2.26]) and diagnosed in hospital (OR 1.74 [95% CI 1.65-1.84]) had an increased risk of late presentation compared to those who diagnosis in voluntary counseling and testing (VCT). Heterosexuals (OR 2.86 [95% CI 2.51-3.27]), PWID (OR 2.23 [95% CI 1.83-2.71]), blood testing of the blood receivers (OR 1.58 [95% CI 1.29-1.94]) and diagnosed in hospital (OR 1.85 [95% CI 1.76-1.94]) were also independent risk factors associated with advanced HIV disease. Older age, lower level of education and being divorced or widowed were also associated with late presentation and advanced HIV disease. CONCLUSIONS: Late presentation and advanced HIV disease were very common among patients with newly diagnosed HIV in Guangxi, China during 2012-2016. Targeted programs are urgently required to reduce HIV late diagnosis in Guangxi, especially for male heterosexuals, PWID, and patients with characteristics such as older age, lower level of education, divorced or widowed.

Citrinin Monomer and Dimer Derivatives with Antibacterial and Cytotoxic Activities Isolated from the Deep Sea-Derived Fungus Penicillium citrinum NLG-S01-P1.

Two previously unreported citrinin dimer derivatives, penicitol D (1) and 1-epi-citrinin H1 (2), were isolated from the culture of a deep sea-derived fungus Penicillium citrinum NLG-S01-P1, together with 11 biogenetic related compounds (3⁻13). A plausible biogenetic pathway for compounds 2⁻4 was proposed. Their structures, including absolute configurations, were established through analysis of extensive spectroscopic data and time-dependent density functional theory (TD-DFT) ECD calculations. Compounds 1 and 2 showed antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA). Compounds 5 and 10 displayed relatively stronger activities than the other compounds against Vibrio vulnificus and Vibrio campbellii. Compound 1 showed the most potent cytotoxic activity towards the HeLa cell.

Lipidomic alteration and stress-defense mechanism of soil nematode Caenorhabditis elegans in response to extremely low-frequency electromagnetic field exposure.

To assess the impacts of man-made extremely low-frequency electromagnetic field (ELF-EMF) on soil ecosystems, the soil nematode was applied as a biological indicator to characterize ecotoxicity of ELF-EMF. In this paper, a soil-living model organism, Caenorhabditis elegans (C. elegans) was exposed to 50 Hz, 3 mT ELF-EMF. The integrated lipidome, proteome and transcriptome analysis were applied to elucidate physiological acclimations. Lipidomic analysis showed that ELF-EMF exposure induced significant alterations of 64 lipids, including significant elevation of triacylglycerols (TGs). Proteome results implied 157 changed protein expressions under ELF-EMF exposure. By transcriptomic analysis, 456 differently expressed genes were identified. Gene Ontology (GO) function and pathway analyses showed lipidomic alteration, mitochondrial dysfunction and the stress defense responses following ELF-EMF exposure in C. elegans. Conjoint analysis of proteome and transcriptome data showed that a higher expression of genes (sip-1, mtl-1 and rpl-11.1, etc.) were involved in stress defense responses to ELF-EMF exposure. These results indicated that ELF-EMF can induce effects on soil nematodes, mainly through disturbing lipid metabolism such as increasing TGs content, and eliciting stress defense responses. This study provided a new understanding in ELF-EMF exposure effects on soil nematodes and suggested a potential way of interpreting ELF-EMF influences on soil ecosystems.

[Extremely low frequency electromagnetic radiation enhanced energy metabolism and induced oxidative stress in Caenorhabditis elegans].

The aim of this study was to determine the effects of extremely low frequency electromagnetic field (ELF-EMF) on energy metabolism and oxidative stress in Caenorhabditis elegans (C. elegans). Worms in three adult stages (young adult stage, egg-laying stage and peak egg-laying stage) were investigated under 50 Hz, 3 mT ELF-EMF exposure. ATP levels, ATP synthase activity in vivo, reactive oxygen species (ROS) content, and changes of total antioxidant capacity (TAC) were detected, and worms' oxidative stress responses were also evaluated under ELF-EMF exposure. The results showed that ATP levels were significantly increased under this ELF-EMF exposure, and mitochondrial ATP synthase activity was upregulated simultaneously. In young adult stage, worms' ROS level was significantly elevated, together with upregulated TAC but with a decreased ROS-TAC score indicated by principal component analysis. ROS level and TAC of worms had no significant changes in egg-laying and peak egg-laying stages. Based on these results, we concluded that ELF-EMF can enhance worm energy metabolism and elicit oxidative stress, mainly manifesting as ATP and ROS level elevation together with ATP synthase upregulation and ROS-TAC score decrease in young adult C. elegans.

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients.

OBJECTIVES: The epidemiological evidence is inconsistent about whether HIV-positive injection drug users (IDUs) are at higher risk of developing antiretroviral resistance than any other HIV-positive populations. This study aims to investigate and compare transmitted drug resistance (TDR) between IDUs and non-IDUs in Lingshan County, an HIV-hit region in Guangxi, China, where IDU and heterosexual transmission were the two dominant transmission routes and roughly equally contributed to the local HIV transmission. METHODS: A cross-sectional study was conducted among newly diagnosed and antiretroviral-treatment (ART)-naïve HIV-1 patients from Lingshan County. The pol gene of HIV-1 from the individuals was sequenced followed by genotyping and TDR analysis. RESULTS: Two dominant transmission routes, heterosexual contact and IDU, accounted for 49.2 and 45.9% of 183 HIV-1 infection cases, respectively. Three genotypes, including CRF08_BC (70.6%), CRF01_AE (24.4%), and CRF07_BC (5.0%), and three unique recombinant forms (1.6%), were identified. There was a significant difference in genotype distribution among the different transmission routes (F = 21.814, p < 0.001). The overall TDR prevalence was 5.5%. There were no significant differences in TDR prevalence among the different transmission routes (F = 1.420, p = 0.439). CONCLUSIONS: Injection drug use has little impact on TDR prevalence compared with other routes of transmission.

HIV prevalence among female sex workers in Guigang City, Guangxi, China: an 8-year consecutive cross-sectional study.

BACKGROUND: Female sex workers (FSW) are a population that are at high risk for HIV infection, and their HIV/AIDS knowledge levels and sexual behaviors are of concern. This study describes changes in HIV prevalence and factors associated among female sex workers in Guigang City, Guangxi, one of the highest HIV prevalence areas in China. METHODS: Data were derived from an annual cross-sectional venue-based survey, 2008 to 2015, in the form of sentinel surveillance. The participants were recruited using cluster sampling. FSW aged 16 years and above who completed a questionnaire and HIV testing. Both descriptive and multi-level analyses were used to explore factors associated with changes in HIV prevalence. RESULTS: Seven thousand four hundred ninety-six FSW were recruited in this study. HIV prevalence among FSW in Guigang City fell into two periods, one with an increasing trend (2008-2011) and one with a decline (2012-2015). Differences between these time periods included age, relationship status, HIV knowledge, consistent condom use, lifetime illicit drug use, history of sexually transmitted infection in the past year, HIV testing, receipt of a condom distribution and education program or HIV counseling and testing, and peer education services. CONCLUSIONS: Since 2012, a reduction in HIV prevalence among FSW in Guigang City has been observed. The decline of HIV prevalence was associated with coinciding changes in demographic characteristics of FSW, improvement of HIV knowledge and safer sexual behaviors, and a program that promotes condom use, HIV counseling & testing, and peer education.

Chlorinated Azaphilone Pigments with Antimicrobial and Cytotoxic Activities Isolated from the Deep Sea Derived Fungus Chaetomium sp. NA-S01-R1.

Four novel compounds, chaephilone C (1), chaetoviridides A-C (2-4), were obtained from the culture of a deep sea derived fungus Chaetomium sp. NA-S01-R1, together with four known compounds-chaetoviridin A (5), chaetoviridine E (6), chaetomugilin D (7) and cochliodone A (8). Their structures, including absolute configurations, were assigned based on NMR, MS and time-dependent density functional theory (TD-DFT) ECD calculations. A plausible biogenetic pathway for compounds 1-3 was proposed. Compounds 2 and 3 exhibited antibacterial activities against Vibrio rotiferianus and Vibrio vulnificus. Compounds 1, 3 and 4 displayed similar anti-methicillin resistant Staphylococcus aureus (anti-MRSA) activities in comparison to chloramphenicol. Compound 2 showed the most potent cytotoxic activities towards the Hep G2 cell and compounds 1 and 3 demonstrated relatively stronger cytotoxic activities than the other compounds against the HeLa cell.

Cytotoxic and Antibacterial Compounds from the Coral-Derived Fungus Aspergillus tritici SP2-8-1.

Three novel compounds, 4-methyl-candidusin A (1), aspetritone A (2) and aspetritone B (3), were obtained from the culture of a coral-derived fungus Aspergillus tritici SP2-8-1, together with fifteen known compounds (4-18). Their structures, including absolute configurations, were assigned based on NMR, MS, and time-dependent density functional theory (TD-DFT) ECD calculations. Compounds 2 and 5 exhibited better activities against methicillin-resistant strains of S. aureus (MRSA) ATCC 43300 and MRSA CGMCC 1.12409 than the positive control chloramphenicol. Compound 5 displayed stronger anti-MRSA and lower cytotoxic activities than 2, and showed stronger antibacterial activities against strains of Vibrio vulnificus, Vibrio rotiferianus, and Vibrio campbellii than the other compounds. Compounds 2 and 10 exhibited significantly stronger cytotoxic activities against human cancer cell lines HeLa, A549, and Hep G2 than the other compounds. Preliminary structure-activity relationship studies indicated that prenylation of terphenyllin or candidusin and the tetrahydrobenzene moiety in anthraquinone derivatives may influence their bioactivity.

Dolutegravir(DTG, S/GSK1349572) combined with other ARTs is superior to RAL- or EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of randomized controlled trials.

BACKGROUND: The first-generation integrase inhibitors (INIs) raltegravir (RAL) and elvitegravir (EVG) have shown efficacy against HIV infection, but they have the limitations of once-more daily dosing and extensive cross-resistance. Dolutegravir (DTG, S/GSK1349572), a second-generation drug that overcomes such shortcomings, is under spotlight. The purpose of this study is to review the evidence for DTG use in clinical settings, including its efficacy and safety. METHODS: PubMed, EMbase, Ovid, Web of Science, Science Direct, and related websites were screened from establishment until July 2013, and scientific meeting proceedings were manually searched. Two reviewers independently screened 118 citations repeatedly to identify randomized controlled trials comparing the efficacy and safety of DTG-based regimen with those of RAL- or elvitegravir-based regimens. Using the selected studies with comparable outcome measures and indications, we performed a meta-analysis based on modified intention-to-treat (mITT), on-treatment (OT), and as-treated (AT) virological outcome data. Independent data extraction and quality assessment were conducted. RESULTS: Four unique studies were included with the use of DTG in antiretroviral therapy-naive patients. In therapy-naive patients, DTG combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) resulted in a significantly better virological outcome with a mITT relative risk (RR)of 1.07 (95 % confidence interval (95 % CI 1.03-1.12). Evidence further supported use of DTG had a better virological suppression in the 50 mg once daily group (mITT RR 1.07; 95 % CI 1.03-1.12) as well as in the sub-analysis in dolutegravir/efavirenz(DTG/EFV) and dolutegravir/raltegravir (DTG/RAL) groups (RR 1.09, 95 % CI 1.03-1.15; RR 1.06, 95 % CI 0.98-1.15, respectively). In the matter of safety of DTG-based regimen, the risk of any event was RR 0.98 (95 % CI 0.94-1.01), the risk of serious adverse events (AEs) was RR 0.84 (95 % CI 0.62-1.15), and the risk of drug-related serious AEs was RR 0.33 (95 % CI 0.13-0.79). CONCLUSION: In general, DTG 50 mg given once daily combined with an active background drug is a better choice in terms of both efficacy and safety.

CD4/CD8 Ratio Recovered as a Predictor of Decreased Liver Damage in Adults Infected With HIV: 16-Year Observational Cohort Study.

BACKGROUND: As the life expectancy of individuals infected with HIV continues to increase, vigilant monitoring of non-AIDS-related events becomes imperative, particularly those pertaining to liver diseases. In comparison to the general population, patients infected with HIV experience a higher frequency of liver-related deaths. The CD4/CD8 ratio is emerging as a potential biomarker for non-AIDS-related events. However, few existing studies have been specially designed to explore the relationship between the CD4/CD8 ratio and specific types of non-AIDS-related events, notably liver damage. OBJECTIVE: This study aimed to investigate the potential association between the CD4/CD8 ratio and the development of liver damage in a sizable cohort of patients infected with HIV receiving antiretroviral treatment (ART). Additionally, the study sought to assess the effectiveness of 3 antiretroviral drugs in recovering the CD4/CD8 ratio and reducing the occurrence of liver damage in this population. METHODS: We conducted an observational cohort study among adults infected with HIV receiving ART from 2004 to 2020 in Guangxi, China. Propensity score matching, multivariable Cox proportional hazard, and Fine-Gray competing risk regression models were used to determine the relationship between the CD4/CD8 ratio recovered and liver damage. RESULTS: The incidence of liver damage was 20.12% among 2440 eligible individuals during a median follow-up period of 4 person-years. Patients whose CD4/CD8 ratio did not recover to 1.0 exhibited a higher incidence of liver damage compared to patients with a CD4/CD8 ratio recovered (adjusted hazard ratio 7.90, 95% CI 4.39-14.21; P<.001; subdistribution hazard ratio 6.80, 95% CI 3.83-12.11; P<.001), findings consistent with the propensity score matching analysis (adjusted hazard ratio 6.94, 95% CI 3.41-14.12; P<.001; subdistribution hazard ratio 5.67, 95% CI 2.74-11.73; P<.001). The Efavirenz-based regimen exhibited the shortest time for CD4/CD8 ratio recovery (median 71, IQR 49-88 months) and demonstrated a lower prevalence of liver damage (4.18/100 person-years). CONCLUSIONS: Recovery of the CD4/CD8 ratio was associated with a decreased risk of liver damage in patients infected with HIV receiving ART, adding evidence for considering the CD4/CD8 ratio as a potential marker for identifying individuals at risk of non-AIDS-related diseases. An efavirenz-based regimen emerged as a recommended choice for recovering the CD4/CD8 ratio and mitigating the risk of liver damage.