Dynamic m6 A profiles reveal the role of YTHDC2-TLR2 signaling axis in Talaromyces marneffei infection.

Talaromyces marneffei (TM) immune evasion is an important factor leading to the high mortality rate of Penicilliosis marneffei. N6 -methyladenosine (m6 A) plays important roles in host immune response to various pathogen infections, yet its role in TM and HIV/TM coinfection remains largely unexplored. Here we reported genome-wide transcriptional m6 A profiles of TM mono-infection and HIV/TM coinfection. Our finding revealed dynamic alterations in global m6 A levels and upregulation of the m6 A reader YTH N6 -methyladenosine RNA binding protein C2 (YTHDC2) in TM-infected macrophages. Knockdown of YTHDC2 in TM-infected cells showed an elevated expression of TLR2 through m6 A-dependence, along with upregulation of TNF-α and IL1-ß. Overall, we characterized the m6 A profiles of the host and fungus before and after TM infection, and demonstrated that YTHDC2 mediates the key m6 A site of TLR2 to exert its function. These findings provide new insights into the underlying mechanisms and novel therapeutic approaches for TM diseases.

Causal relationship between gut microbiota and tuberculosis: a bidirectional two-sample Mendelian randomization analysis.

BACKGROUND: Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional. METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method. RESULTS: In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found. CONCLUSION: Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.

A bibliometric analysis of m6A methylation in viral infection from 2000 to 2022.

BACKGROUND: N6-methyladenosine (m6A) methylation has become an active research area in viral infection, while little bibliometric analysis has been performed. In this study, we aim to visualize hotspots and trends using bibliometric analysis to provide a comprehensive and objective overview of the current research dynamics in this field. METHODS: The data related to m6A methylation in viral infection were obtained through the Web of Science Core Collection form 2000 to 2022. To reduce bias, the literature search was conducted on December 1, 2022. Bibliometric and visual analyzes were performed using CiteSpace and Bibliometrix package. After screening, 319 qualified records were retrieved. RESULTS: These publications mainly came from 28 countries led by China and the United States (the US), with the US ranking highest in terms of total link strength.The most common keywords were m6A, COVID-19, epitranscriptomics, METTL3, hepatitis B virus, innate immunity and human immunodeficiency virus 1. The thematic map showed that METTL3, plant viruses, cancer progression and type I interferon (IFN-I) reflected a good development trend and might become a research hotspot in the future, while post-transcriptional modification, as an emerging or declining theme, might not develop well. CONCLUSIONS: In conclusion, m6A methylation in viral infection is an increasingly important topic in articles. METTL3, plant viruses, cancer progression and IFN-I may still be research hotspots and trends in the future.

The origin, dissemination, and molecular networks of HIV-1 CRF65_cpx strain in Hainan Island, China.

BACKGROUND: HIV-1 CRF65_cpx strain carries drug-resistant mutations, which raises concerns about its potential for causing virologic failure. The CRF65_cpx ranks as the fourth most prevalent on Hainan Island, China. However, the origin and molecular epidemiology of CRF65_cpx strains in this area remain unclear. This study aims to estimate the spatial origins and dissemination patterns of HIV-1 CRF65_cpx in this specific region. METHODS: Between 2018 and 2021, a total of 58 pol sequences of the CRF65_cpx were collected from HIV-positive patients on Hainan Island. The available CRF65_cpx pol sequences from public databases were compiled. The HIV-TRACE tool was used to construct transmission networks. The evolutionary history of the introduction and dissemination of HIV-1 CRF65_cpx on Hainan Island were analyzed using phylogenetic analysis and the Bayesian coalescent-based approach. RESULTS: Among the 58 participants, 89.66% were men who have sex with men (MSM). The median age was 25 years, and 43.10% of the individuals had a college degree or above. The results indicated that 39 (67.24%) sequences were interconnected within a single transmission network. A consistent expansion was evident from 2019 to 2021, with an incremental annual addition of four sequences into the networks. Phylodynamic analyses showed that the CRF65_cpx on Hainan Island originated from Beijing (Bayes factor, BF = 17.4), with transmission among MSM on Hainan Island in 2013.2 (95%HPD: 2012.4, 2019.5), subsequently leading to an outbreak. Haikou was the local center of the CRF65_cpx epidemic. This strain propagated from Haikou to other locations, including Sanya (BF > 1000), Danzhou (BF = 299.3), Chengmai (BF = 27.0) and Tunchang (BF = 16.3). The analyses of the viral migration patterns between age subgroups and risk subgroups revealed that the viral migration directions were from "25-40 years old" to "17-24 years old" (BF = 14.6) and to "over 40 years old" (BF = 17.6), and from MSM to heterosexuals (BF > 1000) on Hainan Island. CONCLUSION: Our analyses elucidate the transmission dynamics of CRF65_cpx strain on Hainan Island. Haikou is identified as the potential hotspot for CRF65_cpx transmission, with middle-aged MSM identified as the key population. These findings suggest that targeted interventions in hotspots and key populations may be more effective in controlling the HIV epidemic.

Development of an HSV-1 production process involving serum-reduced culturing and bead-to-bead transfer.

Herpes simplex virus type 1 (HSV-1) plays an important role in the field of gene therapy and viral vaccines, especially as an oncolytic virus. However, the mass production of HSV-1 viral vectors remains a challenge in the industry. In this study, a microcarrier-mediated serum-reduced medium culture was used to improve the bioprocess of HSV-1 production and increase HSV-1 yields. The composition of the culture media, which included a basal medium, serum concentration, and glutamine additive, was optimized. The process was successfully conducted in a 1 L bioreactor, and virus production was threefold greater than that of conventional processes with a 10% serum medium. The bead-to-bead transfer process was also developed to further increase scalability. In spinner flasks, the detachment rate increased from 49.4 to 80.6% when combined agitation was performed during digestion; the overall recovery proportion increased from 37.9 to 71.1% after the operational steps were optimized. Specifically, microcarrier loss was reduced during aspiration and transfer, and microcarriers and detached cells were separated with filters. Comparable cell growth was achieved with the baseline process using 2D culture as the inoculum by exchanging the subculture medium. To increase virus production after bead-to-bead transfer, critical parameters, including shear stress during digestion, TrypLE and EDTA concentrations in the subculture, and the CCI, were identified from 47 parameters via correlation analysis and principal component analysis. The optimized bead-to-bead transfer process achieved an average of 90.4% overall recovery and comparable virus production compared to that of the baseline process. This study is the first to report the optimization of HSV-1 production in Vero cells cultured on microcarriers in serum-reduced medium after bead-to-bead transfer. KEY POINTS: • An HSV-1 production process was developed that involves culturing in serum-reduced medium, and this process achieved threefold greater virus production than that of traditional processes. • An indirect bead-to-bead transfer process was developed with over 90% recovery yield in bioreactors. • HSV-1 production after bead-to-bead transfer was optimized and was comparable to that achieved with 2D culture as inoculum.

Effectiveness of human immunodeficiency virus prevention strategies by mapping the geographic dispersion pattern of human immunodeficiency virus prevalence in Nanning, China.

BACKGROUND: The Guangxi government initiated two rounds of the Guangxi AIDS Conquering Project (GACP) in 2010 (Phase I) and 2015 (Phase II) to control human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemics. However, the effectiveness of GACP in HIV prevention and treatment has rarely been reported. This study aimed to assess the effectiveness of the GACP implemented in Guangxi, China and provide data for strategy and praxis improvements to achieve Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95 targets. METHODS: We used spatial approaches to trace the spatiotemporal distribution properties, epidemic trends, and correlation between macroscopic factors and HIV incidence using data from the Chinese HIV/AIDS case reporting system to explore the effects of the GACP. RESULTS: During the GACP era, the HIV epidemic stabilized in urban centers, showing a downward trend in the Hengzhou and Binyang Counties in the eastern region, whereas it continued to increase in rural areas of the northwest region, such as the Long'an, Mashan, Shanglin, and Wuming Districts. The linear directional mean (LDM) of HIV infection reported cases displayed a southeast-northwest direction, with an LDM value of 12.52°. Compared with that in Phase I, Hengzhou withdrew from the high-high clustering area, and the west-north suburban counties pulled out the low-low clustering area during Phase II. Significant HIV clusters were identified in the eastern region during Phase I, whereas these clusters emerged in the northwestern areas during Phase II. Regarding HIV, socioeconomic status, population mobility, and medical care levels were the key social drivers of heterogeneous spatial distribution. CONCLUSIONS: The GACP assisted in effectively managing the HIV epidemic in urban and eastern areas of Nanning City. However, prevention and control efforts in rural regions, particularly those located in the northwest, may not have yielded comparable outcomes. To address this disparity, allocating additional resources and implementing tailored intervention measures for these rural areas are imperative.

The effects of meteorological factors and air pollutants on the incidence of tuberculosis in people living with HIV/AIDS in subtropical Guangxi, China.

BACKGROUND: Previous studies have shown the association between tuberculosis (TB) and meteorological factors/air pollutants. However, little information is available for people living with HIV/AIDS (PLWHA), who are highly susceptible to TB. METHOD: Data regarding TB cases in PLWHA from 2014 to2020 were collected from the HIV antiviral therapy cohort in Guangxi, China. Meteorological and air pollutants data for the same period were obtained from the China Meteorological Science Data Sharing Service Network and Department of Ecology and Environment of Guangxi. A distribution lag non-linear model (DLNM) was used to evaluate the effects of meteorological factors and air pollutant exposure on the risk of TB in PLWHA. RESULTS: A total of 2087 new or re-active TB cases were collected, which had a significant seasonal and periodic distribution. Compared with the median values, the maximum cumulative relative risk (RR) for TB in PLWHA was 0.663 (95% confidence interval [CI]: 0.507-0.866, lag 4 weeks) for a 5-unit increase in temperature, and 1.478 (95% CI: 1.116-1.957, lag 4 weeks) for a 2-unit increase in precipitation. However, neither wind speed nor PM10 had a significant cumulative lag effect. Extreme analysis demonstrated that the hot effect (RR = 0.638, 95%CI: 0.425-0.958, lag 4 weeks), the rainy effect (RR = 0.285, 95%CI: 0.135-0.599, lag 4 weeks), and the rainless effect (RR = 0.552, 95%CI: 0.322-0.947, lag 4 weeks) reduced the risk of TB. Furthermore, in the CD4(+) T cells < 200 cells/µL subgroup, temperature, precipitation, and PM10 had a significant hysteretic effect on TB incidence, while temperature and precipitation had a significant cumulative lag effect. However, these effects were not observed in the CD4(+) T cells ≥ 200 cells/µL subgroup. CONCLUSION: For PLWHA in subtropical Guangxi, temperature and precipitation had a significant cumulative effect on TB incidence among PLWHA, while air pollutants had little effect. Moreover, the influence of meteorological factors on the incidence of TB also depends on the immune status of PLWHA.

Time series prediction for the epidemic trends of monkeypox using the ARIMA, exponential smoothing, GM (1, 1) and LSTM deep learning methods.

Monkeypox is a critical public health emergency with international implications. Few confirmed monkeypox cases had previously been reported outside endemic countries. However, since May 2022, the number of monkeypox infections has increased exponentially in non-endemic countries, especially in North America and Europe. The objective of this study was to develop optimal models for predicting daily cumulative confirmed monkeypox cases to help improve public health strategies. Autoregressive integrated moving average (ARIMA), exponential smoothing, long short-term memory (LSTM) and GM (1, 1) models were employed to fit the cumulative cases in the world, the USA, Spain, Germany, the UK and France. Performance was evaluated by minimum mean absolute percentage error (MAPE), among other metrics. The ARIMA (2, 2, 1) model performed best on the global monkeypox dataset, with a MAPE value of 0.040, while ARIMA (2, 2, 3) performed the best on the USA and French datasets, with MAPE values of 0.164 and 0.043, respectively. The exponential smoothing model showed superior performance on the Spanish, German and UK datasets, with MAPE values of 0.043, 0.015 and 0.021, respectively. In conclusion, an appropriate model should be selected according to the local epidemic characteristics, which is crucial for monitoring the monkeypox epidemic. Monkeypox epidemics remain severe, especially in North America and Europe, e.g. in the USA and Spain. The development of a comprehensive, evidence-based scientific programme at all levels is critical to controlling the spread of monkeypox infection.

Construction of a murine model of latent infection and reactivation induced by Talaromyces marneffei.

OBJECTIVE: To establish a murine model of Talaromyces marneffei (T. marneffei) latent infection and reactivation, providing a foundation for exploring the molecular mechanisms underlying disease relapse. METHODS: BALB/c mice were tail vein injected with T. marneffei at 0 days post-infection (dpi) and treated with cyclophosphamide (CTX) intraperitoneally every four days, starting from 21 dpi or 42 dpi. Mice were observed for body weight changes, liver and spleen indices, histological characteristics of liver and spleen, fungal load detection in liver and spleen, and Mp1p qualitation in liver and spleen to assess T. marneffei infection severity. RESULTS: T. marneffei-infected mice exhibited a trend of initial weight loss followed by recovery and a subsequent decrease in weight after CTX injection throughout the observation period. Liver and spleen indices, as well as tissue damage, significantly increased during infection but later returned to normal levels, with a gradual rise observed after immunosuppression. Fungal load analysis revealed positive T. marneffei cultures in the liver and spleen at 7 dpi and 14 dpi, followed by negative T. marneffei cultures from 21 dpi until day 21 post-immunosuppression (42 dpi or 63 dpi); however, the spleen remained T. marneffei-cultured negative, consistent with the trend observed in Mp1p detection results. CONCLUSION: A latent infection and reactivation model of T. marneffei in mice was successfully established, with the liver likely serving as a key site for latent T. marneffei.

Spectrum and mortality of opportunistic infections among HIV/AIDS patients in southwestern China.

We describe the opportunistic infections (OIs) of HIV/AIDS to understand the spectrum, mortality, and frequency of multiple coinfected OIs among HIV/AIDS patients in southern China, where OIs are severe. We carried out a retrospective cohort study of hospitalized HIV-infected individuals at the Fourth People's Hospital of Nanning, Guangxi, China, from Jan. 2011 to May. 2019. The chi-square test was used to analyze cross-infection; the Kaplan‒Meier analysis was used to compare mortality. A total of 12,612 HIV-infected patients were admitted to this cohort study. Among them, 8982 (71.2%) developed one or more OIs. The overall in-hospital mortality rate was 9.0%. Among the patients, 35.6% coinfected one OI, and 64.4% coinfected more than two OIs simultaneously. Almost half of the patients (60.6%) had CD4 + T-cell counts < 200 cells/µL. Pneumonia (39.8%), tuberculosis (35.3%), and candidiasis (28.8%) were the most common OIs. Coinfected cryptococcal meningitis and dermatitis are the most common combined OIs. The rate of anaemia (17.0%) was highest among those common HIV-associated complications. Multiple OIs are commonly found in hospitalized HIV/AIDS patients in southwestern China, which highlights the need for improved diagnosis and treatment.

Application of deep learning algorithm in the recognition of cryptococcosis and talaromycosis skin lesions.

BACKGROUND: Cryptococcosis and talaromycosis are known as 'neglected epidemics' due to their high case fatality rates and low concern. Clinically, the skin lesions of the two fungal diseases are similar and easily misdiagnosed. Therefore, this study aims to develop an algorithm to identify cryptococcosis/talaromycosis skin lesions. METHODS: Skin images of tararomiasis and cryptococcosis were collected from published articles and augmented using the Python Imaging Library (PIL). Then, five deep artificial intelligence models, VGG19, MobileNet, InceptionV3, Incept ResNetV2 and DenseNet201, were developed based on the collected datasets using transfer learning technology. Finally, the performance of the models was evaluated using sensitivity, specificity, F1 score, accuracy, AUC and ROC curve. RESULTS: In total, 159 articles (79 for cryptococcosis and 80 for talaromycosis), including 101 cryptococcosis skin lesion images and 133 talaromycosis skin lesion images, were collected for further mode construction. Five methods showed good performance for prediction but did not yield satisfactory results for all cases. Among them, DenseNet201 performed best in the validation set, followed by InceptionV3. However, InceptionV3 showed the highest sensitivity, accuracy, F1 score and AUC values in the training set, followed by DenseNet201. The specificity of DenseNet201 in the training set is better than that of InceptionV3. CONCLUSIONS: DenseNet201 and InceptionV3 are equivalent to the optimal model in these conditions and can be used in clinical settings as decision support tools for the identification and classification of skin lesions of cryptococcus/talaromycosis.

Biological Characteristics and Functional Analysis of the Linoleic Acid Synthase Gene ZjFAD2 in Jujube.

Jujube fruit is rich in linoleic acid and other bioactive components and has great potential to be used for the development of functional foods. However, the roles of FAD2 genes in linoleic acid biosynthesis in jujube fruit remain unclear. Here, we identified 15 major components in jujube and found that linoleic acid was the main unsaturated fatty acid; major differences in the content and distribution of linoleic acid in the pulp and seeds were observed, and levels of linoleic acid decreased during fruit maturation. Analysis of the fatty acid metabolome, genome, and gene expression patterns of cultivated and wild-type jujube revealed five ZjFAD2 family members highly related to linoleic acid biosynthesis. The heterologous expression of these five ZjFAD2 family members in tobacco revealed that all five of these genes increased the content of linoleic acid. Additionally, transient expression of these genes in jujube fruit and the virus-induced gene silencing (VIGS) test further confirmed the key roles of ZjFAD2-11 and ZjFAD2-1 in the biosynthesis of linoleic acid. The results of this research provide valuable insights into the molecular mechanism underlying linoleic acid synthesis in jujube and will aid the development of quality-oriented breeding strategies.

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.

CASA: a comprehensive database resource for the COVID-19 Alternative Splicing Atlas.

BACKGROUND: As a key process in transcriptional regulatory mechanisms, alternative splicing (AS) plays a crucial role in maintaining the diversity of RNA and protein expression, and mediates the immune response in infectious diseases, especially for the COVID-19. Therefore, urgent data gathering and more research of AS profiles in microbe-infected human cells are needed to improve understanding of COVID-19 and related infectious diseases. Herein, we have created CASA, the COVID-19 Alternative Splicing Atlas to provide a convenient computing platform for studies of AS in COVID-19 and COVID-19-related infectious diseases. METHODS: In CASA, we reanalyzed thousands of RNA-seq datasets generated from 65 different tissues, organoids and cell lines to systematically obtain quantitative data on AS events under different conditions. A total of 262,994 AS events from various infectious diseases with differing severity were detected and visualized in this database. In order to explore the potential function of dynamics AS events, we performed analysis of functional annotations and drug-target interactions affected by AS in each dataset. RNA-binding proteins (RBPs), which may regulate these dynamic AS events are also provided for users in this database. RESULTS: CASA displays microbe-induced alterations of the host cell splicing landscape across different virus families and helps users identify condition-specific splicing patterns, as well as their potential regulators. CASA may greatly facilitate the exploration of AS profiles and novel mechanisms of host cell splicing by viral manipulation. CASA is freely available at http://www.splicedb.net/casa/ .

Learning to autofocus in whole slide imaging via physics-guided deep cascade networks.

Whole slide imaging (WSI), is an essential technology for digital pathology, the performance of which is primarily affected by the autofocusing process. Conventional autofocusing methods either are time-consuming or require additional hardware and thus are not compatible with the current WSI systems. In this paper, we propose an effective learning-based method for autofocusing in WSI, which can realize accurate autofocusing at high speed as well as without any optical hardware modifications. Our method is inspired by an observation that sample images captured by WSI have distinctive characteristics with respect to positive / negative defocus offsets, due to the asymmetry effect of optical aberrations. Based on this physical knowledge, we develop novel deep cascade networks to enhance autofocusing quality. Specifically, to handle the effect of optical aberrations, a binary classification network is tailored to distinguish sample images with positive / negative defocus. As such, samples within the same category share similar characteristics. It facilitates the followed refocusing network, which is designed to learn the mapping between the defocus image and defocus distance. Experimental results demonstrate that our method achieves superior autofocusing performance to other related methods.

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.

Trends and associated factors in the uptake of HIV testing among female sex workers in Sino-Vietnam border areas in Guangxi, China: a cross-sectional study.

BACKGROUND: HIV testing is a primary prevention strategy against the HIV epidemic and an entry point for HIV/AIDS-related care, prevention and treatment. This study aimed to estimate the uptake of HIV testing among Sino-Vietnam female sex workers (FSWs) in Guangxi, China, from 2016 to 2018, and to identify the factors influencing HIV testing uptake. METHODS: A cross-sectional survey was conducted among FSWs in two Sino-Vietnam border cities of Guangxi, China. The survey was conducted through face-to-face interview, the data were collected by a structured questionnaire, and HIV-1 infection was detected simultaneously. Logistic regression analysis was used to determine the factors associated with uptake of HIV testing. RESULTS: In total, 4565 Chinese local FSWs (CL-FSWs) and 636 cross-border migrant Vietnamese FSWs (CMV-FSWs) were recruited into this study. HIV-1 prevalence in CL-FSWs and CMV-FSWs was 0.70% and 3.14%, respectively. The rate of self-reported uptake of HIV testing in CL-FSWs and CMV-FSWs was 54.56% and 45.44%, respectively. The rates of self-reported uptake of HIV testing declined in both groups from 2016 to 2018. Logistic regression analysis indicated that a number of factors, including socio-demographic characteristics (age < 35 years, higher education, location in Chongzuo City), behaviour factors (having received free AIDS education, condom distribution services and peer education services, high risk sexual behaviours such as inconsistent condom use, having regular commercial sexual partners, etc.), psychological factors (perception of vulnerability to HIV/STIs, perception of risk for HIV infection) were the factors significantly related to uptake of HIV testing. CONCLUSION: In recent years, the rate of HIV testing uptake among Sino-Vietnam border FSWs in Guangxi, China was low, which may be an important reason for the high HIV-1 prevalence among FSWs in the region. A number of factors were identified to be associated with HIV-1 testing uptake, suggesting that HIV testing prevention strategies in this region could include accelerating AIDS education training, raising personal awareness of HIV testing, and improving accessibility of HIV testing.

Effect and Mechanism of Cotrimoxazole Against Talaromyces marneffei in vitro.

BACKGROUND: Talaromyces marneffei (formerly Penicillium marneffei) is an important thermally dimorphic fungus endemic which is characterized by one of the most frequent opportunistic infections in HIV/AIDS patients, mainly prevalent in Southeast Asia, southern China, and northeastern India. Cotrimoxazole(CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi, thereby commonly used to prevent several opportunistic infections among HIV/AIDS patients. In addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis are considered to have the potential to prevent T. marneffei infection in HIV/AIDS patients receiving antiretroviral therapy (ART). However, the effect of cotrimoxazole towards T. marneffei fungus in vitro remains unclear. METHODS: Human THP-1 macrophages were used as cell model in vitro to explore the effect and mechanism of cotrimoxazole resistance towards T. marneffei. Cell viability assay and drug sensitivity colony forming units (CFU) experiments were conducted to determine the minimum inhibitory concentration (MIC) of cotrimoxazole inside and outside THP-1 macrophages respectively. Enzyme-linked immunosorbent assay (Elisa) was used to measure the concentration of Dihydropteroic acid synthetase (DHPS), Dihydrofolate synthetase (DHFS) and Dihydrofolate reductase (DHFR) between T. marneffei adding TMP/SMX and without adding TMP/SMX group respectively. Real-time fluorescence quantitative PCR(qPCR) was performed to detect the mRNA expression levels in Dectin-1 mediated signaling pathway and downstream inflammatory cytokines including IL-6, IL-10, IL-23A, CXCL8 and TNF-α released by T. marneffei-infected macrophages between adding TMP/SMX and without adding TMP/SMX group respectively. RESULTS: Cotrimoxazole can inhibit the proliferation of T. marneffei within safe concentration inside and outside THP-1 macrophages. Drug susceptibility results showed the minimal inhibit concentration(MIC) of 1:5 TMP/SMX was ranging from 14/70 to 68/340 µg/ml. The MIC of SMX was ranging from 100 to 360 µg/ml. The MIC of TMP was ranging from 240 to 400 µg/ml outside macrophages. The MIC of TMP/SMX was ranging from 36/180 to 68/340 µg/ml. The MIC of SMX was ranging from 340 to 360 µg/ml. The MIC of TMP was ranging from 320 to 400 µg/ml inside macrophages. The synergistic interaction of 1:5 TMP/SMX was more effective in inhibiting T. marneffei than separate SMX and TMP. DHPS, DHFS and DHFR can be inhibited by cotrimoxazole within safe and effective concentration. Dectin-1 expression is increased following T. marneffei infection, leading to the increase of IL-6, IL-10, IL-23A and the decrease of CXCL8 and TNF-α. Conversely, cotrimoxazole decrease the levels of Dectin-1, IL-6, IL-10, IL-23A and increase the levels of CXCL8 and TNF-α, thereby enhancing the intracellular killing-T. marneffei capacity of macrophages. CONCLUSIONS: Our findings indicated that cotrimoxazole directly inhibited T. marneffei growth by blocking DHPS, DHFS and DHFR and indirectly inhibited T. marneffei growth perhaps by regulating the Dectin-1 signaling pathway, which may effectively interfere with the defense ability of the host against T. marneffei infection.

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.

Temporal variability of free-living microbial culturability and community composition after an Akashiwo sanguinea bloom in Shenzhen, China.

Dinoflagellate blooms currently caused serious environmental problems in different areas of the world. Recent studies revealed close relationship between dinoflagellate blooms and microbial community dynamics, while less attention has been paid on the bacterial culturability change associated with the bloom. Here, we investigated the temporal variation of microbial community composition and culturability during the decline stage of an Akashiwo sanguinea bloom occurred in Shenzhen, China. The daily microbial community phylogenetic structures in water samples collected during a four-day period after the bloom peak were assessed through 16S rRNA gene amplicons sequencing on the MiSeq (Illumina) platform. The environmental parameters, Chlorophyll a concentrations, and total viable and culturable bacterial densities were also measured. Our results showed that Gamma-proteobacteria comprising mostly of Pseudoalteromonadaceae and Vibrionaceae was the predominant microbial class in the post-bloom samples, except for the second day. During that day, the represented groups switched to Alpha-proteobacteria (Rhizobiales) and Beta-proteobacteria (Comamonadaceae), with the microbial culturability decreased. Total viable bacterial densities reached the maximum value on the third day, with Gamma-proteobacteria regained the dominance till the fourth day. The dramatic microbial community succession and culturability variation observed in this study indicated the complication of algae-bacteria interactions during dinoflagellate bloom.