Fingerprint Stimulated Raman Scattering Imaging Unveils Ergosteryl Ester as a Metabolic Signature of Azole-Resistant Candida albicans.

Candida albicans (C. albicans), a major fungal pathogen, causes life-threatening infections in immunocompromised individuals. Fluconazole (FLC) is recommended as first-line therapy for treatment of invasive fungal infections. However, the widespread use of FLC has resulted in increased antifungal resistance among different strains of Candida, especially C. albicans, which is a leading source of hospital-acquired infections. Here, by hyperspectral stimulated Raman scattering imaging of single fungal cells in the fingerprint window and pixel-wise spectral unmixing, we report aberrant ergosteryl ester accumulation in azole-resistant C. albicans compared to azole-susceptible species. This accumulation was a consequence of de novo lipogenesis. Lipid profiling by mass spectroscopy identified ergosterol oleate to be the major species stored in azole-resistant C. albicans. Blocking ergosterol esterification by oleate and suppressing sterol synthesis by FLC synergistically suppressed the viability of C. albicans in vitro and limited the growth of biofilm on mouse skin in vivo. Our findings highlight a metabolic marker and a new therapeutic strategy for targeting azole-resistant C. albicans by interrupting the esterified ergosterol biosynthetic pathway.

Voluntary Medical Male Circumcision and Incident HIV Infection Among Men Who Have Sex With Men in China (The CoM Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Systematic reviews and meta-analyses based on observational studies have shown voluntary medical male circumcision (VMMC) may reduce HIV risk among men who have sex with men (MSM). There is a lack of randomized controlled trial (RCT) data assessing the efficacy of VMMC. OBJECTIVE: The primary objective of this study was to assess the efficacy of VMMC for preventing HIV acquisition among MSM who primarily engage in insertive anal sex. METHODS: A multicenter RCT will be conducted among MSM in 8 cities in China. Eligible participants are men aged 18-49 years who self-report ≥2 male sex partners in the past 6 months, predominantly practice insertive anal sex, and are willing to undergo circumcision. Interested men who satisfy inclusion criteria will be tested for HIV 1 month before enrollment and at enrollment, and only those who are HIV negative will be enrolled. At baseline, all enrolled participants will be asked to report sociodemographic characteristics and sexual behaviors; provide a blood sample for HIV, syphilis, and herpes simplex virus type 2 testing; and provide a penile swab for human papillomavirus testing. Participants will be randomly assigned to the intervention or control group. Those in the intervention group will receive VMMC and undergo a web-based weekly follow-up assessment of postsurgery healing for 6 consecutive weeks. All participants will be tested for HIV at 3-, 6-, 9-, and 12-month follow-ups. All participants will also be asked to report sexual behaviors and undergo repeat herpes simplex virus type 2 and human papillomavirus testing at 6- and 12-month follow-ups. The primary end point is HIV seroconversion. Secondary end points are the safety and satisfaction with VMMC and the changes in sexual behaviors after VMMC. The grouped censored data will be analyzed by intention-to-treat approach. RESULTS: Recruitment for the RCT began in August 2020 and continued through July 2022. Data collection is expected to be completed by July 2023, and full data analysis is going to be completed by September 2023. CONCLUSIONS: This study will be the first RCT to assess the efficacy of VMMC in preventing HIV infection among MSM. Results from this trial will provide preliminary evidence for the potential efficacy of VMMC to reduce incident HIV infection among MSM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000039436; https://www.chictr.org.cn/showproj.html?proj=63369. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47160.

Stakeholders' solutions to antiretroviral therapy interruption during the COVID-19 pandemic in China: a short report.

Obtaining antiretroviral therapy (ART) was a challenge for people living with HIV (PLHIV) in China during the COVID-19 outbreak. On 26 January 2020, the Chinese Center for AIDS/STD Control and Prevention issued a nationwide directive to relax restrictions on where and when PLHIV could refill ART. This qualitative study explored unexpected barriers under this directive and recommendations to improve future ART delivery. Between February 11 and February 15 2020, in-depth interviews of 4 groups of stake holders related to ART refilling (i.e., PLHIV, community-based organization employees, CDC staff, infectious disease physicians and nurses), were conducted via WeChat. Data were managed by NVivo 11.0 and transcripts were coded using thematic analysis. Sixty-two interviews were conducted. The main barriers to refilling ART included: (1) inconsistent documentation requirements to refill ART, (2) lack of specific protocols on ART refilling, (3) insufficient staffing, and (4) regimen verification and drug shortages. The most common recommendations to improve future ART delivery were: (1) to establish a nationwide system to distribute ART and (2) increase the number of pills delivered with each ART refill. Strengthening protocols and systems to refill ART and improving collaboration is key to preventing interruptions in ART among PLHIV during public health emergencies.

Blue Light Deactivation of Catalase Suppresses Candida Hyphae Development Through Lipogenesis Inhibition.

Hyphae formation is a key step for fungal penetration into epithelial cells and escaping from macrophages or neutrophils. We found that 405 nm light-induced catalase deactivation results in the inhibition of hyphae growth in Candida albicans. The treatment is capable of inhibiting hyphae growth across multiple hyphae-producing Candida species. Metabolic studies on light-treated C. albicans reveal that light treatment results in a strong reduction in both lipid and protein metabolism. A significant decrease in unsaturated and saturated fatty acids was detected through mass spectroscopy, indicating that the suppression of hyphae through light-induced catalase deactivation may occur through inhibition of lipid metabolism. Initial in vivo tests indicate that blue light treatment can suppress the hyphae forming capabilities of C. albicans within murine abrasion infections. Together, these findings open new avenues for the treatment of Candida fungal infections by targeting their dimorphism.

Bond-selective intensity diffraction tomography.

Recovering molecular information remains a grand challenge in the widely used holographic and computational imaging technologies. To address this challenge, we developed a computational mid-infrared photothermal microscope, termed Bond-selective Intensity Diffraction Tomography (BS-IDT). Based on a low-cost brightfield microscope with an add-on pulsed light source, BS-IDT recovers both infrared spectra and bond-selective 3D refractive index maps from intensity-only measurements. High-fidelity infrared fingerprint spectra extraction is validated. Volumetric chemical imaging of biological cells is demonstrated at a speed of ~20 s per volume, with a lateral and axial resolution of ~350 nm and ~1.1 µm, respectively. BS-IDT's application potential is investigated by chemically quantifying lipids stored in cancer cells and volumetric chemical imaging on Caenorhabditis elegans with a large field of view (~100 µm x 100 µm).

Optically-generated focused ultrasound for noninvasive brain stimulation with ultrahigh precision.

High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited precision at the millimeter level. Here, we report optically-generated focused ultrasound (OFUS) for non-invasive brain stimulation with ultrahigh precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with an ultrahigh lateral resolution of 83 µm, which is two orders of magnitude smaller than that of conventional transcranial-focused ultrasound (tFUS). Here, we show effective OFUS neurostimulation in vitro with a single ultrasound cycle. We demonstrate submillimeter transcranial stimulation of the mouse motor cortex in vivo. An acoustic energy of 0.6 mJ/cm2, four orders of magnitude less than that of tFUS, is sufficient for successful OFUS neurostimulation. OFUS offers new capabilities for neuroscience studies and disease treatments by delivering a focus with ultrahigh precision non-invasively.

The impact of COVID-19 non-pharmaceutical interventions on HIV care continuum in China: An interrupted time series analysis.

Background: China implemented strict non-pharmaceutical interventions to contain COVID-19 at the early stage. We aimed to evaluate the impact of COVID-19 on HIV care continuum in China. Methods: Aggregated data on HIV care continuum between 1 January 2017 and 31 December 2020 were collected from centers for disease control and prevention at different levels and major infectious disease hospitals in various regions in China. We used interrupted time series analysis to characterize temporal trend in weekly numbers of HIV post-exposure prophylaxis (PEP) prescriptions, HIV tests, HIV diagnoses, median time intervals between HIV diagnosis and antiretroviral therapy (ART) initiation (time intervals, days), ART initiations, mean CD4+ T cell counts at ART initiation (CD4 counts, cells/µL), ART collections, and missed visits for ART collection, before and after the implementation of massive NPIs (23 January to 7 April 2020). We used Poisson segmented regression models to estimate the immediate and long-term impact of NPIs on these outcomes. Findings: A total of 16,780 PEP prescriptions, 1,101,686 HIV tests, 69,659 HIV diagnoses, 63,409 time intervals and ART initiations, 61,518 CD4 counts, 1,528,802 ART collections, and 6656 missed visits were recorded during the study period. The majority of outcomes occurred in males (55·3-87·4%), 21-50 year olds (51·7-90·5%), Southwestern China (38·2-82·0%) and heterosexual transmission (47·9-66·1%). NPIs was associated with 71·5% decrease in PEP prescriptions (IRR 0·285; 95% CI 0·192-0·423), 36·1% decrease in HIV tests (0·639, 0·497-0·822), 32·0% decrease in HIV diagnoses (0·680, 0·511-0·904), 59·3% increase in time intervals (1·593, 1·270-1·997) and 17·4% decrease in CD4 counts (0·826, 0·746-0·915) in the first week during NPIs. There was no marked change in the number of ART initiations, ART collections and missed visits during the NPIs. By the end of 2020, the number of HIV tests, HIV diagnoses, time intervals, ART initiations, and CD4 counts reached expected levels, but the number of PEP prescriptions (0·523, 0·394-0·696), ART collections (0·720, 0·595-0·872), and missed visits (0·137, 0·086-0·220) were still below expected levels. With the ease of restrictions, PEP prescriptions (slope change 1·024/week, 1·012-1·037), HIV tests (1·016/week, 1·008-1·026), and CD4 counts (1·005/week, 1·001-1·009) showed a significant increasing trend. Interpretation: HIV care continuum in China was affected by the COVID-19 NPIs at various levels. Preparedness and efforts to maintain the HIV care continuum during public health emergencies should leverage collaborations between stakeholders. Funding: Natural Science Foundation of China.

Global Pattern and Trends in Penile Cancer Incidence: Population-Based Study.

BACKGROUND: Penile cancer is a relatively rare genital malignancy whose incidence and mortality are rising in many countries. OBJECTIVE: This study aims to assess the recent incidence and mortality patterns and incidence trends of penile cancer. METHODS: The age-standardized incidence and mortality rates (ASIR and ASMR, respectively) of penile cancer in 2020 were estimated from the Global Cancer Registries (GLOBOCAN) database. Incidence trends of penile cancer from 1973 to 2012 were assessed in 44 populations from 43 countries using the Cancer Incidence in Five Continents plus (CI5plus) and the Nordic Cancer Registries (NORDCAN) databases. Average annual percentage change was calculated to quantify trends in ASIR using joinpoint regression. RESULTS: Globally, the estimated ASIR and ASMR of penile cancer were 0.80 (per 100,000) and 0.29 (per 100,000) in 2020, equating to 36,068 new cases and 13,211 deaths in 2020, respectively. There was no significant correlation between the ASIR (P=.05) or ASMR (P=.90) and Human Development Index. In addition, 15 countries saw increasing ASIR for penile cancer, 13 of which were from Europe (United Kingdom, Lithuania, Norway, Estonia, Finland, Sweden, Cyprus, Netherlands, Italy, Croatia, Slovakia, Russia, and the Czech), and 2 from Asia (China and Israel). CONCLUSIONS: Although the developing countries still bear the higher incidence and mortality of penile cancer, the incidence is on the rise in most European countries. To mitigate the disease burden resulting from penile cancer, measures to lower the risk for penile cancers, including improving penile hygiene and male human papillomavirus vaccination, may be warranted.

Outness and its correlates among gay and bisexual men attending university in China: a cross-sectional study.

BACKGROUND: Disclosure of sexual orientation to others (outness) might be associated with sexual and mental health among gay and bisexual men (GBM) attending university. We aimed to characterise outness and investigate factors correlated with outness among GBM attending university in China. METHODS: Between September 2018 and March 2019, GBM attending university were recruited in six cities in China. Information on sociodemographic characteristics, outness and sexual behaviours were collected using a self-administered questionnaire. Each participant was tested for HIV/STIs. Correlates of outness were assessed using multivariable logistic regression. RESULTS: A total of 400 GBM attending university were recruited, of whom 251 (62.8%) had disclosed their sexual orientation. Men who served as student leaders (adjusted odds ratio [AOR]=2.28, 95% CI: 1.46-3.54) and donated blood (AOR 1.85, 95% CI: 1.05-3.24) were more likely to disclose their sexual orientation, whereas men who had sex with a female (AOR 0.19, 95% CI: 0.05-0.74) and had group sex (AOR 0.52, 95% CI: 0.30-0.89) were less likely to disclose their sexual orientation. Mental health status, HIV/STI infections were not associated with outness. CONCLUSIONS: GBM attending university who disclosed their sexual orientation were more likely to be involved with student work and less likely to engage in high-risk sexual behaviours. More attention and education could focus on non-disclosing GBM men attending university through peer education or other ways.

Photoinactivation of catalase sensitizes a wide range of bacteria to ROS-producing agents and immune cells.

Bacteria have evolved to cope with the detrimental effects of ROS using their essential molecular components. Catalase, a heme-containing tetramer protein expressed universally in most aerobic bacteria, plays an indispensable role in scavenging excess hydrogen peroxide (H2O2). Here, through use of wild-type and catalase-deficient mutants, we identified catalase as an endogenous therapeutic target of 400-420 nm blue light. Catalase residing inside bacteria could be effectively inactivated by blue light, subsequently rendering the pathogens extremely vulnerable to H2O2 and H2O2-producing agents. As a result, photoinactivation of catalase and H2O2 synergistically eliminated a wide range of catalase-positive planktonic bacteria and P. aeruginosa inside biofilms. In addition, photoinactivation of catalase was shown to facilitate macrophage defense against intracellular pathogens. The antimicrobial efficacy of catalase photoinactivation was validated using a Pseudomonas aeruginosa-induced mouse abrasion model. Taken together, our findings offer a catalase-targeting phototherapy approach against multidrug-resistant bacterial infections.

Incidence Trends of Five Common Sexually Transmitted Infections Excluding HIV From 1990 to 2019 at the Global, Regional, and National Levels: Results From the Global Burden of Disease Study 2019.

Objective: Sexually transmitted infections (STIs) are common worldwide and pose a challenge to public health. We conducted this study to assess the annual incidence of five common STIs, including syphilis, chlamydia, gonorrhea, trichomoniasis, and genital herpes at the global, regional, and national levels. Materials and Methods: We obtained detailed data on STIs excluding HIV from 1990 to 2019 from the Global Burden of Disease (GBD) 2019 database. Estimated annual percentage change (EAPC) was calculated to quantify trends in age-standardized incidence rates (ASR) of STIs, stratified by gender, sociodemographic index (SDI) region, and pathogenic microorganism. Results: Globally, incident cases of STIs increased by 58.15% from 486.77 million in 1990 to 769.85 million in 2019, but the annual change in ASR was only -0.04% (95% CI -0.09 to 0.01) per year. EAPC was 0.16 (0.06 to 0.26) for syphilis, 0.09 (0.05 to 0.13) for genital herpes, 0.06 (0.03 to 0.09) for trichomoniasis, -0.21 (-0.36 to -0.06) for chlamydia, and -0.14 (-0.19 to -0.08) for gonorrhea. High SDI regions reported significant increases in ASR of syphilis and chlamydia. Conclusions: The burden of disease from STIs remains large, though control of STIs has contributed to the decreasing incidence in most regions, especially in the low-SDI regions. Globally, over the past 20 years, the ASR has remained stable for trichomoniasis and genital herpes decreased for chlamydia and gonorrhea, and increased for syphilis.

Photoinactivation of Catalase Sensitizes Candida albicans and Candida auris to ROS-Producing Agents and Immune Cells.

Microbes have developed their own specific strategies to cope with reactive oxygen species (ROS). Catalase, a heme-containing tetramer expressed in a broad range of aerobic fungi, shows remarkable efficiency in degrading hydrogen peroxide (H2 O2 ) for fungal survival and host invasion. Here, it is demonstrated that catalase inactivation by blue light renders fungal cells highly susceptible to ROS attack. To confirm catalase as a major molecular target of blue light, wild type Candida albicans are systematically compared with a catalase-deficient mutant strain regarding their susceptibility to ROS through 410 nm treatment. Upon testing a wide range of fungal species, it is found that intracellular catalase can be effectively and universally inactivated by 410 nm blue light. It is also found that photoinactivation of catalase in combination with ROS-generating agents is highly effective in total eradication of various fungal species, including multiple Candida auris strains, the causative agent of the global fungal epidemic. In addition, photoinactivation of catalase is shown to facilitate macrophage killing of intracellular Candida albicans. The antifungal efficacy of catalase photoinactivation is further validated using a C. albicans-induced mouse model of skin abrasion. Taken together, the findings offer a novel catalase-photoinactivation approach to address multidrug-resistant Candida infections.

COVID-19 vaccine uptake and hesitancy among HIV-infected men who have sex with men in mainland China: a cross-sectional survey.

BACKGROUND: Men who have sex with men (MSM), a population bearing the greatest HIV burden in many countries, may also be vulnerable to COVID-19. COVID-19 vaccines are essential to containing the pandemic. However, vaccine hesitancy may compromise vaccine coverage. We aimed to understand the uptake of COVID-19 vaccine and factors associated with COVID-19 vaccine hesitancy among HIV-infected MSM in mainland China. METHODS: A cross-sectional online survey among HIV-infected MSM was conducted between 13 and 21 February 2021 in mainland China. Variables including demographics, mental health status, HIV characteristics, and knowledge of and attitudes toward COVID-19 pandemic and COVID-19 vaccine were collected. Chi-square tests and multivariable logistic regression were used to analyze factors associated with COVID-19 vaccine hesitancy. RESULTS: A total of 1295 participants were included. The median age was 29.3 years (interquartile range [IQR] 25.2-34.0 years). The uptake of COVID-19 vaccine was 8.7%. Two main reasons for receiving vaccines were "regarded vaccination as self-health protection" (67.3%) and "trust in domestic medical technology" (67.3%). Among participants who did not initiate vaccination, concern about side effects (46.4%) and disclosure of HIV infection (38.6%) were top two reasons, and 47.2% had higher vaccine hesitancy. Men who had with high antiretroviral therapy (ART) adherence (adjusted odds ratio [aOR] 0.53, 95% confidence interval [CI] 0.35-0.80), often (0.26, 0.17-0.40) or sometimes (0.46, 0.31-0.67) paid attention to information about the COVID-19 vaccine, preferred domestic vaccines (0.37, 0.24-0.59), thought the pandemic had moderate (0.58, 0.38-0.90) and moderately severe or severe impact (0.54, 0.38-0.78) on immunity, who were waiting for vaccination programs organized at workplace (0.60, 0.44-0.81) and who were unaware of where to get COVID-19 vaccine (0.61, 0.45-0.82) had lower degree of COVID-19 vaccine hesitancy. Men who were concerned about the efficacy (1.72, 1.16-2.54) and side effects (2.44, 1.78-3.35) had higher degree of COVID-19 vaccine hesitancy. CONCLUSION: COVID-19 vaccine uptake among HIV-infected MSM is still suboptimal. Understanding influencing factors of vaccine hesitancy among this group and making tailored measures to alleviate hesitancy would help improve the coverage of COVID-19 vaccination in this population.

Multiwindow SRS Imaging Using a Rapid Widely Tunable Fiber Laser.

Spectroscopic stimulated Raman scattering (SRS) imaging has become a useful tool finding a broad range of applications. Yet, wider adoption is hindered by the bulky and environmentally sensitive solid-state optical parametric oscillator (OPO) in a current SRS microscope. Moreover, chemically informative multiwindow SRS imaging across C-H, C-D, and fingerprint Raman regions is challenging due to the slow wavelength tuning speed of the solid-state OPO. In this work, we present a multiwindow SRS imaging system based on a compact and robust fiber laser with rapid and wide tuning capability. To address the relative intensity noise intrinsic to a fiber laser, we implemented autobalanced detection, which enhances the signal-to-noise ratio of stimulated Raman loss imaging by 23 times. We demonstrate high-quality SRS metabolic imaging of fungi, cancer cells, and Caenorhabditis elegans across the C-H, C-D, and fingerprint Raman windows. Our results showcase the potential of the compact multiwindow SRS system for a broad range of applications.

Stakeholder efforts to mitigate antiretroviral therapy interruption among people living with HIV during the COVID-19 pandemic in China: a qualitative study.

INTRODUCTION: The COVID-19 pandemic has affected antiretroviral therapy (ART) continuity among people living with HIV (PLHIV) worldwide. We conducted a qualitative study to explore barriers to ART maintenance and solutions to ART interruption when stringent COVID-19 control measures were implemented in China, from the perspective of PLHIV and relevant key stakeholders. METHODS: Between 11 February and 15 February 2020, we interviewed PLHIV, community-based organization (CBO) workers, staff from centres for disease control and prevention (CDC) at various levels whose work is relevant to HIV care (CDC staff), HIV doctors and nurses and drug vendors from various regions in China. Semi-structured interviews were conducted using a messaging and social media app. Challenges and responses relevant to ART continuity during the COVID-19 pandemic were discussed. Themes were identified by transcript coding and mindmaps. RESULTS: Sixty-four stakeholders were recruited, including 16 PLHIV, 17 CBO workers, 15 CDC staff, 14 HIV doctors and nurses and two drug vendors. Many CDC staff, HIV doctors and nurses responsible for ART delivery and HIV care were shifted to COVID-19 response efforts. Barriers to ART maintenance were (a) travel restrictions, (b) inadequate communication and bureaucratic obstacles, (c) shortage in personnel, (d) privacy concerns, and (e) insufficient ART reserve. CBO helped PLHIV maintain access to ART through five solutions identified from thematic analysis: (a) coordination to refill ART from local CDC clinics or hospitals, (b) delivery of ART by mail, (c) privacy protection measures, (d) mental health counselling, and (e) providing connections to alternative sources of ART. Drug vendors contributed to ART maintenance by selling out-of-pocket ART. CONCLUSIONS: Social and institutional disruption from COVID-19 contributed to increased risk of ART interruption among PLHIV in China. Collaboration among key stakeholders was needed to maintain access to ART, with CBO playing an important role. Other countries facing ART interruption during current or future public health emergencies may learn from the solutions employed in China.

Fluorescence-Detected Mid-Infrared Photothermal Microscopy.

Mid-infrared photothermal microscopy is a new chemical imaging technology in which a visible beam senses the photothermal effect induced by a pulsed infrared laser. This technology provides infrared spectroscopic information at submicrometer spatial resolution and enables infrared spectroscopy and imaging of living cells and organisms. Yet, current mid-infrared photothermal imaging sensitivity suffers from a weak dependence of scattering on the temperature, and the image quality is vulnerable to the speckles caused by scattering. Here, we present a novel version of mid-infrared photothermal microscopy in which thermosensitive fluorescent probes are harnessed to sense the mid-infrared photothermal effect. The fluorescence intensity can be modulated at the level of 1% per Kelvin, which is 100 times larger than the modulation of scattering intensity. In addition, fluorescence emission is free of interference, thus much improving the image quality. Moreover, fluorophores can target specific organelles or biomolecules, thus augmenting the specificity of photothermal imaging. Spectral fidelity is confirmed through fingerprinting a single bacterium. Finally, the photobleaching issue is successfully addressed through the development of a wide-field fluorescence-detected mid-infrared photothermal microscope which allows video rate bond-selective imaging of biological specimens.

Association between medical male circumcision and HIV risk compensation among heterosexual men: a systematic review and meta-analysis.

BACKGROUND: Medical male circumcision (MMC) reduces HIV infection among heterosexual men. There are concerns MMC might prompt higher-risk sexual behaviours because of lower self-perceived risk of HIV infection. We reviewed the published literature to examine associations between MMC and both condom use and number of sex partners among heterosexual men. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library for studies published before Nov 15, 2020. Interventional and observational studies were included if they contained original quantitative data describing the association between MMC and condom use or number of sex partners among heterosexual men. We excluded data from men whose circumcisions were ritual or religious and data from men who have sex with men. We extracted odds ratios (ORs) and 95% CIs for the associations between MMC and condomless sex and MMC and multiple sex partners directly from the publications if available, selecting adjusted ORs when provided; when necessary, we calculated ORs and 95% CIs using original study data provided in the publication. We used the Mantel-Haenszel random effects model to calculate pooled ORs and 95% CIs. FINDINGS: Our search yielded 3035 results, of which 471 were duplicates and 2537 did not meet the inclusion criteria. From the remaining 27 eligible studies, we identified 99 292 men from 31 independent population samples. 24 studies were done in Africa. We found no statistically significant associations between MMC and condomless sex (OR 0·91, 95% CI 0·80-1·05; k=30; I2=88·7%) or multiple sex partners (1·02, 0·88-1·18; k=27; I2=90·1%). No associations between MMC and condomless sex or multiple sexual partners were found in any subgroup analyses by study design, income of country, age, recruitment setting, circumcision assessment, circumcision prevalence, and risk of publication bias. INTERPRETATION: The promotion of circumcision as an HIV preventive measure does not appear to increase higher-risk sexual behaviours in heterosexual men. Ongoing sexual health education should be maintained as a vital component of effective MMC programmes. FUNDING: National Science and Technology Major Project of China, the Fundamental Research Funds for the Central Universities, and the Shenzhen Science and Technology Innovation Commission Basic Research Program.

Human papillomavirus prevalence among men who have sex with men in China: a systematic review and meta-analysis.

Human papillomavirus (HPV) infection among men who have sex with men (MSM) in China is underreported. We performed a systematic review and meta-analysis to clarify site-specific HPV prevalence among MSM in China. We searched both English and Chinese databases for all studies published before April 1, 2020, that reported HPV prevalence among MSM in China. Random-effects meta-analysis was used to calculate summary estimates. Thirty-four articles were eligible, where 32, 5, and 2 articles reported HPV prevalence at the anus, penis, and oral cavity, respectively. The estimated prevalence of anal HPV among MSM in China was 85.1% (HIV-positive), 53.6% (HIV-negative), and 59.2% (unknown HIV status), with HPV genotypes being predominated by HPV 6, 11, 16, 18, 52, and 58. Any HPV and high-risk (HR) HPV was more common in northern China, while low-risk HPV was more common in southern China. HPV prevalence increased with age among HIV-negative MSM, from 40.5% (aged < 20 years) to 57.2% (aged ≥ 40 years). High prevalence of any HPV (HIV+: 95.1%; HIV-: 97.7%) and multiple infections (HIV+: 75.9%; HIV-: 41.7%) was found in anogenital warts among MSM. HPV is common among MSM in China. MSM living with HIV and/or anogenital warts were at disproportionate risk for HR HPV. Younger MSM were found to have a lower HPV prevalence. HPV vaccines would have prevented the majority of infections if given before sex debut. HPV at anatomical sites other than the anus, incident HPV infection, and the cost-effectiveness of HPV vaccination in this population are worth further investigation.

Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane.

Ergosterol-targeting amphotericin B (AmB) is the first line of defense for life-threatening fungal infections. Two models have been proposed to illustrate AmB assembly in the cell membrane; one is the classical ion channel model in which AmB vertically forms transmembrane tunnel and the other is a recently proposed sterol sponge model where AmB is laterally adsorbed onto the membrane surface. To address this controversy, we use polarization-sensitive stimulated Raman scattering from fingerprint C═C stretching vibration to visualize AmB, ergosterol, and lipid in single fungal cells. Intracellular lipid droplet accumulation in response to AmB treatment is found. AmB is located in membrane and intracellular droplets. In the 16 strains studied, AmB residing inside cell membrane was highly ordered, and its orientation is primarily parallel to phospholipid acyl chains, supporting the ion channel model. Label-free imaging of AmB and chemical contents offers an analytical platform for developing low-toxicity, resistance-refractory antifungal agents.

Antiretroviral treatment interruption among people living with HIV during COVID-19 outbreak in China: a nationwide cross-sectional study.

INTRODUCTION: Social disruption associated with coronavirus disease 2019 (COVID-19) threatens to impede access to regular healthcare, including for people living with HIV (PLHIV), potentially resulting in antiretroviral therapy (ART) interruption (ATI). We aimed to explore the characteristics and factors associated with ATI during the COVID-19 outbreak in China. METHODS: We conducted an online survey among PLHIV by convenience sampling through social media between 5 and 17 February 2020. Respondents were asked to report whether they were at risk of ATI (i.e. experienced ATI, risk of imminent ATI, threatened but resolved risk of ATI [obtaining ART prior to interruption]) or were not at risk of ATI associated with the COVID-19 outbreak. PLHIV were also asked to report perceived risk factors for ATI and sources of additional ART. The factors associated with the risk of ATI were assessed using logistic regression. We also evaluated the factors associated with experienced ATI. RESULTS: A total of 5084 PLHIV from 31 provinces, autonomous regions and municipalities in mainland China completed the survey, with valid response rate of 99.4%. The median age was 31 years (IQR 27 to 37), 96.5% of participants were men, and 71.3% were men who had sex with men. Over one-third (35.1%, 1782/5084) reported any risk of ATI during the COVID-19 outbreak, including 2.7% (135/5084) who experienced ATI, 18.0% (917/5084) at risk of imminent ATI and 14.4% (730/5084) at threatened but resolved risk. PLHIV with ATI were more likely to have previous interruptions in ART (aOR 8.3, 95% CI 5.6 to 12.3), travelled away from where they typically receive HIV care (aOR 3.0, 95% CI 2.1 to 4.5), stayed in an area that implemented citywide lockdowns or travel restrictions to control COVID-19 (aOR 2.5, 95% CI 1.4 to 4.6), and be in permanent residence in a rural area (aOR 3.7, 95% CI 2.3 to 5.8). CONCLUSIONS: A significant proportion of PLHIV in China are at risk of ATI during the COVID-19 outbreak and some have already experienced ATI. Correlates of ATI and self-reported barriers to ART suggest that social disruptions from COVID-19 have contributed to ATI. Our findings demonstrate an urgent need for policies and interventions to maintain access to HIV care during public health emergencies.