The zinc finger protein DHHC09 S-acylates the kinase STRK1 to regulate H2O2 homeostasis and promote salt tolerance in rice.

Soil salinity results in oxidative stress and heavy losses to crop production. The S-acylated protein SALT TOLERANCE RECEPTOR-LIKE CYTOPLASMIC KINASE 1 (STRK1) phosphorylates and activates CATALASE C (CatC) to improve rice (Oryza sativa L.) salt tolerance, but the molecular mechanism underlying its S-acylation involved in salt signal transduction awaits elucidation. Here, we show that the DHHC-type zinc finger protein DHHC09 S-acylates STRK1 at Cys5, Cys10, and Cys14 and promotes salt and oxidative stress tolerance by enhancing rice H2O2-scavenging capacity. This modification determines STRK1 targeting to the plasma membrane or lipid nanodomains and is required for its function. DHHC09 promotes salt signaling from STRK1 to CatC via transphosphorylation, and its deficiency impairs salt signal transduction. Our findings demonstrate that DHHC09 S-acylates and anchors STRK1 to the plasma membrane to promote salt signaling from STRK1 to CatC, thereby regulating H2O2 homeostasis and improving salt stress tolerance in rice. Moreover, overexpression of DHHC09 in rice mitigates grain yield loss under salt stress. Together, these results shed light on the mechanism underlying the role of S-acylation in RLK/RLCK-mediated salt signal transduction and provide a strategy for breeding highly salt-tolerant rice.

The protein phosphatase PC1 dephosphorylates and deactivates CatC to negatively regulate H2O2 homeostasis and salt tolerance in rice.

Catalase (CAT) is often phosphorylated and activated by protein kinases to maintain hydrogen peroxide (H2O2) homeostasis and protect cells against stresses, but whether and how CAT is switched off by protein phosphatases remains inconclusive. Here, we identified a manganese (Mn2+)-dependent protein phosphatase, which we named PHOSPHATASE OF CATALASE 1 (PC1), from rice (Oryza sativa L.) that negatively regulates salt and oxidative stress tolerance. PC1 specifically dephosphorylates CatC at Ser-9 to inhibit its tetramerization and thus activity in the peroxisome. PC1 overexpressing lines exhibited hypersensitivity to salt and oxidative stresses with a lower phospho-serine level of CATs. Phosphatase activity and seminal root growth assays indicated that PC1 promotes growth and plays a vital role during the transition from salt stress to normal growth conditions. Our findings demonstrate that PC1 acts as a molecular switch to dephosphorylate and deactivate CatC and negatively regulate H2O2 homeostasis and salt tolerance in rice. Moreover, knockout of PC1 not only improved H2O2-scavenging capacity and salt tolerance but also limited rice grain yield loss under salt stress conditions. Together, these results shed light on the mechanisms that switch off CAT and provide a strategy for breeding highly salt-tolerant rice.

Clinical presentation of early syphilis and genomic sequences of Treponema pallidum strains in patient specimens and isolates obtained by rabbit inoculation.

BACKGROUND: The global resurgence of syphilis necessitates vaccine development. METHODS: We collected ulcer exudates and blood from 17 primary syphilis (PS) participants and skin biopsies and blood from 51 secondary syphilis (SS) participants in Guangzhou, China for Treponema pallidum subsp. pallidum (TPA) qPCR, whole genome sequencing (WGS), and isolation of TPA in rabbits. RESULTS: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and two Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups. CONCLUSIONS: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

The incidence of new cases of syphilis has skyrocketed globally in the twenty-first century. This global resurgence requires new strategies, including vaccine development. As part of an NIH funded Cooperative Research Center to develop a syphilis vaccine, we established a clinical research site in Guangzhou, China to better define the local syphilis epidemic and obtain samples from patients with primary and secondary syphilis for whole genome sequencing (WGS) of circulating Treponema pallidum strains. Inoculation of rabbits enabled us to obtain T. pallidum genomic sequences from spirochetes disseminating in blood, a compartment of immense importance for syphilis pathogenesis. Collectively, our results further clarify the molecular epidemiology of syphilis in southern China, enrich our understanding of the manifestations of early syphilis, and demonstrate that the genomic sequences of spirochetes obtained by rabbit inoculation accurately represent those of the spirochetes infecting the corresponding patients.

Large-scale analysis of the N-terminal regulatory elements of the kinase domain in plant Receptor-like kinase family.

BACKGROUND: The N-terminal regulatory element (NRE) of Receptor-like kinases (RLKs), consisting of the juxtamembrane segment in receptor kinases (RKs) and the N-terminal extension segment in RLCKs, is a crucial component that regulates the activities of these proteins. However, the features and functions of the NRE have remained largely unexplored. Herein, we comprehensively analyze 510,233 NRE sequences in RLKs from 528 plant species, using information theory and data mining techniques to unravel their common characteristics and diversity. We also use recombinant RKs to investigate the function of the NRE in vitro. RESULTS: Our findings indicate that the majority of NRE segments are around 40-80 amino acids in length and feature a serine-rich region and a 14-amino-acid consensus sequence, 'FSYEELEKAT[D/N]NF[S/D]', which contains a characteristic α-helix and ST motif that connects to the core kinase domain. This conserved signature sequence is capable of suppressing FERONIA's kinase activity. A motif discovery algorithm identifies 29 motifs with highly conserved phosphorylation sites in RK and RLCK classes, especially the motif 'VGPWKpTGLpSGQLQKAFVTGVP' in LRR-VI-2 class. Phosphorylation of an NRE motif in an LRR-VI-2 member, MDIS1, modulates the auto-phosphorylation of its co-receptor, MIK1, indicating the potential role of NRE as a 'kinase switch' in RLK activation. Furthermore, the characterization of phosphorylatable NRE motifs improves the accuracy of predicting phosphorylatable sites. CONCLUSIONS: Our study provides a comprehensive dataset to investigate NRE segments from individual RLKs and enhances our understanding of the underlying mechanisms of RLK signal transduction and kinase activation processes in plant adaptation.

Identification and characterization of circRNAs encoded by MERS-CoV, SARS-CoV-1 and SARS-CoV-2.

The life-threatening coronaviruses MERS-CoV, SARS-CoV-1 and SARS-CoV-2 (SARS-CoV-1/2) have caused and will continue to cause enormous morbidity and mortality to humans. Virus-encoded noncoding RNAs are poorly understood in coronaviruses. Data mining of viral-infection-related RNA-sequencing data has resulted in the identification of 28 754, 720 and 3437 circRNAs encoded by MERS-CoV, SARS-CoV-1 and SARS-CoV-2, respectively. MERS-CoV exhibits much more prominent ability to encode circRNAs in all genomic regions than those of SARS-CoV-1/2. Viral circRNAs typically exhibit low expression levels. Moreover, majority of the viral circRNAs exhibit expressions only in the late stage of viral infection. Analysis of the competitive interactions of viral circRNAs, human miRNAs and mRNAs in MERS-CoV infections reveals that viral circRNAs up-regulated genes related to mRNA splicing and processing in the early stage of viral infection, and regulated genes involved in diverse functions including cancer, metabolism, autophagy, viral infection in the late stage of viral infection. Similar analysis in SARS-CoV-2 infections reveals that its viral circRNAs down-regulated genes associated with metabolic processes of cholesterol, alcohol, fatty acid and up-regulated genes associated with cellular responses to oxidative stress in the late stage of viral infection. A few genes regulated by viral circRNAs from both MERS-CoV and SARS-CoV-2 were enriched in several biological processes such as response to reactive oxygen and centrosome localization. This study provides the first glimpse into viral circRNAs in three deadly coronaviruses and would serve as a valuable resource for further studies of circRNAs in coronaviruses.

An atlas of human viruses provides new insights into diversity and tissue tropism of human viruses.

MOTIVATION: Viruses continue to threaten human health. Yet, the complete viral species carried by humans and their infection characteristics have not been fully revealed. RESULTS: This study curated an atlas of human viruses from public databases and literature, and built the Human Virus Database (HVD). The HVD contains 1131 virus species of 54 viral families which were more than twice the number of the human-infecting virus species reported in previous studies. These viruses were identified in human samples including 68 human tissues, the excreta and body fluid. The viral diversity in humans was age-dependent with a peak in the infant and a valley in the teenager. The tissue tropism of viruses was found to be associated with several factors including the viral group (DNA, RNA or reverse-transcribing viruses), enveloped or not, viral genome length and GC content, viral receptors and the virus-interacting proteins. Finally, the tissue tropism of DNA viruses was predicted using a random-forest algorithm with a middle performance. Overall, the study not only provides a valuable resource for further studies of human viruses but also deepens our understanding toward the diversity and tissue tropism of human viruses. AVAILABILITY AND IMPLEMENTATION: The HVD is available at http://computationalbiology.cn/humanVirusBase/#/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Inhibition of Astrocytic Carbohydrate Sulfotransferase 15 Promotes Nerve Repair After Spinal Cord Injury via Mitigation of CSPG Mediated Axonal Inhibition.

Nerve tissue regeneration is a significant problem. After neural diseases and damage such as spinal cord injury (SCI), the accumulation of chondroitin sulfate proteoglycans (CSPG) comprising axonal inhibitory glycosaminoglycan chains in the microenvironment is a major barrier that obstructs nerve repair. Interfering with the production of glycosaminoglycans, especially the critical inhibitory chains, could be a potential therapeutic strategy for SCI, which is, however, poorly defined. This study identifies Chst15, the chondroitin sulfotransferase controlling the generation of axonal inhibitory chondroitin sulfate-E, as a therapeutic target of SCI. Using a recently reported small molecular Chst15 inhibitor, this study investigates the effects of Chst15 inhibition on astrocyte behaviors and the associated consequences of in vivo disruption of the inhibitory microenvironment. Deposition of CSPGs in the extracellular matrix and migration of astrocytes are both significantly impaired by Chst15 inhibition. Administration of the inhibitor in transected spinal cord tissues of rats effectively promotes motor functional restoration and nerve tissue regeneration by a mechanism related to the attenuation of inhibitory CSPGs, glial scar formation and inflammatory responses. This study highlights the role of Chst15 in the CSPG-mediated inhibition of neural recovery after SCI and proposes an effective neuroregenerative therapeutic strategy that uses Chst15 as a potential target.

The relationship between the preference of mating type (MAT) and source in the opportunistic pathogen Talaromyces marneffei.

Genome-wide comparisons have shown Talaromyces marneffei possessed a stable mating type locus in its meiosis genes. But the function of the mating type locus in T. marneffei is not clear. The potential sex recombination might lead to problems in clinical, such as the evolution of increased resistance to antifungal drugs and virulence. To determine the mating type in a sample of 107 T. marneffei isolates and to explore the possible relationship between fungus virulence and mating type or source. We used PCR analysis to determine the distribution of mating type genes and also analyzed the relationship between mating type and isolated sources (including HIV-positive patients, HIV-negative patients, bamboo rats, and the environment). Further, the Drosophila melanogaster model of infection was used to compare the differences of virulence in mating type and sources. Our results showed the entire sample population of T. marneffei with an overabundance of MAT1-2 alleles, but with a higher ratio of MAT1-1 in the isolates from HIV-negative patients. However, no significant differences in the survival of the D. melanogaster infected neither with MAT1-1 (6.5 days) nor MAT1-2 (4 days) isolates. Similar results were also observed in virulence analysis tested with different sources of isolates. So, we found that all isolates bore single mating type idiomorphs and unequal distribution. The distribution of the MAT genes seems related to different sources. And the virulence differences are independent of mating type genotype and source.

Our work shows the entire sample population of 107 Talaromyces marneffei isolates with an overabundance of MAT1-2 alleles, but with a higher ratio of MAT1-1 in the isolates from HIV-negative patients. And fungus virulence is independent of mating type genotype and source in the Drosophila melanogaster model.

Dissemination of Neisseria gonorrhoeae with decreased susceptibility to extended-spectrum cephalosporins in Southern China, 2021: a genome-wide surveillance from 20 cities.

BACKGROUND: Antimicrobial resistance (AMR) of untreatable gonococcal infection is an emerging threat, especially in Guangdong, a prosperous province in Southern China. METHODS: N.gonorrhoeae was isolated from 20 cities in Guangdong and determined antimicrobial susceptibility. Through whole-genome sequencing (WGS), multilocus sequence typing (MLST), N.gonorrhoeae multiantigen sequence typing (NG-MAST), and N.gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were obtained based on the PubMLST database ( https://pubmlst.org/ ). Phylogenetic analysis was used for dissemination and tracking analysis. RESULTS: Antimicrobial susceptibility was performed on 347 isolates, and 50 isolates were identified as decreased susceptibility (DS) to cephalosporins. Of which 16.0% (8/50) were ceftriaxone DS, 38.0% (19/50) were cefixime DS, and 46.0% (23/50) were both ceftriaxone and cefixime DS. In all, the dual-resistant rate of the cephalosporin-DS isolates was 96.0% for penicillin and 98.0% for tetracycline-resistant, and 10.0% (5/50) were resistant to azithromycin. All cephalosporin-DS isolates were resistant to ciprofloxacin but sensitive to spectinomycin. The predominant MLSTs were ST7363 (16%, 8/50), ST1903 (14%, 7/50), ST1901 (12%, 6/50), and ST7365 (10%, 5/50). Besides some isolates that failed genotyping (NA), NG-STAR ST1143 (n = 6) and NG-MAST ST17748 (n = 4) were the most prevalent. Twelve isolates with mosaic penA-60.001 allele retained the most elevated cephalosporin MIC (Minimum Inhibitory Concentration). Phylogenetic analysis revealed that epidemic penA-60.001 clones, either domestic or foreign, had spread to nine cities in Guangdong, and 9/12 clones were from the Pearl River Delta region. CONCLUSIONS: N. gonorrhoeae with cephalosporins-DS was extensively disseminated in Guangdong, Southern China, requiring strict surveillance.

Pay-it-forward gonorrhea and chlamydia testing among men who have sex with men and male STD patients in China: the PIONEER pragmatic, cluster randomized controlled trial protocol.

BACKGROUND: Gonorrhea and chlamydia are the most common sexually transmitted diseases (STDs) among men who have sex with men (MSM) in China. Previous studies have shown pay-it-forward (PIF) interventions to be associated with a substantial increase in gonorrhea and chlamydia test uptake compared to standard-of-care. We propose a 'pay-it-forward' gonorrhea and chlamydia testing randomized controlled trial (PIONEER). The trial would evaluate the effectiveness of two pay-it-forward strategies in promoting testing uptake compared to the standard of care (in which men pay for their tests out-of-pocket) among MSM and male STD patients in China. METHODS: PIONEER will be a three-armed, pragmatic cluster randomized controlled trial (RCT), conducted across 12 clinics (six MSM-led and six public STD clinics) to compare the effectiveness of three implementation strategies. Each facility will be randomized to a standard pay-it-forward intervention of gonorrhea/ chlamydia testing with minimal encouragement for testing, a community-engaged pay-it-forward arm, or a control arm where men pay for their tests out-of-pockets. The primary outcome will be dual gonorrhea/chlamydia test uptake. Secondary outcomes will include syphilis testing, amount donated in pay-it-forward, number of positive gonorrhea and chlamydia tests, and measures of antimicrobial resistance. A sequential transformative mixed methods design will be used to evaluate the implementation process in type 2 effectiveness-implementation hybrid design. Data sources will include survey on acceptability, and feelings and attitudes towards the interventions among participants; testing and treatment uptake data from clinic records, WeChat records, and qualitative data to gain insights into men's perceptions and attitudes towards the pay-it-forward, mechanisms driving uptake, and donating behaviors. Implementers and organizers will be interviewed about fidelity and adherence to protocol, sustainability of pay-it-forward intervention, and barriers and facilitators of implementing the intervention. DISCUSSION: PIONEER will substantially increase gonorrhea/chlamydia testing among MSM in China, providing an innovative and new financial mechanism to sustain STD screening among sexual minorities in low- and middle-income countries. This study will answer compelling scientific questions about how best to implement pay-it-forward and the individual and organizational characteristics that moderate it. TRIAL REGISTRATION: The study with identification number NCT05723263 has been registered on clinicaltrials.gov/.

Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial.

BACKGROUND: Low syphilis testing uptake is a major public health issue among men who have sex with men (MSM) in many low- and middle-income countries. Syphilis self-testing (SST) may complement and extend facility-based testing. We aimed to evaluate the effectiveness and costs of providing SST on increasing syphilis testing uptake among MSM in China. METHODS AND FINDINGS: An open-label, parallel 3-arm randomized controlled trial (RCT) was conducted between January 7, 2020 and July 17, 2020. Men who were at least 18 years of age, had condomless anal sex with men in the past year, reported not testing for syphilis in the last 6 months, and had a stable residence with mailing addresses were recruited from 124 cities in 26 Chinese provinces. Using block randomization with blocks of size 12, enrolled participants were randomly assigned (1:1:1) into 3 arms: standard of care arm, standard SST arm, and lottery incentivized SST arm (1 in 10 chance to win US$15 if they had a syphilis test). The primary outcome was the proportion of participants who tested for syphilis during the trial period and confirmed with photo verification and between arm comparisons were estimated with risk differences (RDs). Analyses were performed on a modified intention-to-treat basis: Participants were included in the complete case analysis if they had initiated at least 1 follow-up survey. The Syphilis/HIV Duo rapid test kit was used. A total of 451 men were enrolled. In total, 136 (90·7%, 136/150) in the standard of care arm, 142 (94·0%, 142/151) in the standard of SST arm, and 137 (91·3%, 137/150) in the lottery incentivized SST arm were included in the final analysis. The proportion of men who had at least 1 syphilis test during the trial period was 63.4% (95% confidence interval [CI]: 55.5% to 71.3%, p = 0.001) in the standard SST arm, 65.7% (95% CI: 57.7% to 73.6%, p = 0.0002) in the lottery incentivized SST arm, and 14.7% (95% CI: 8.8% to 20.7%, p < 0.001) in the standard of care arm. The estimated RD between the standard SST and standard of care arm was 48.7% (95% CI: 37.8% to 58.4%, p < 0.001). The majority (78.5%, 95% CI: 72.7% to 84.4%, p < 0.001) of syphilis self-testers reported never testing for syphilis. The cost per person tested was US$26.55 for standard SST, US$28.09 for the lottery incentivized SST, and US$66.19 for the standard of care. No study-related adverse events were reported during the study duration. Limitation was that the impact of the Coronavirus Disease 2019 (COVID-19) restrictions may have accentuated demand for decentralized testing. CONCLUSIONS: Compared to standard of care, providing SST significantly increased the proportion of MSM testing for syphilis in China and was cheaper (per person tested). TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900022409.

Correction: Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pmed.1003930.].

Markedly Increasing Antibiotic Resistance and Dual Treatment of Neisseria gonorrhoeae Isolates in Guangdong, China, from 2013 to 2020.

The emergence of multidrug resistance in Neisseria gonorrhoeae is concerning, especially the cooccurrence of azithromycin resistance and decreased susceptibility to extended-spectrum cephalosporin. This study aimed to confirm the antibiotic resistance trends and provide a solution for N. gonorrhoeae treatment in Guangdong, China. A total of 5,808 strains were collected for assessment of antibiotic MICs. High resistance to penicillin (53.80 to 82%), tetracycline (88.30 to 100%), ciprofloxacin (96 to 99.8%), cefixime (6.81 to 46%), and azithromycin (8.60 to 20.03%) was observed. Remarkably, spectinomycin and ceftriaxone seemed to be the effective choices, with resistance rates of 0 to 7.63% and 2.00 to 16.18%, respectively. Moreover, the rates of azithromycin resistance combined with decreased susceptibility to ceftriaxone and cefixime reached 9.28% and 8.64%, respectively. Furthermore, genotyping identified NG-STAR-ST501, NG-MAST-ST2268, and MLST-ST7363 as the sequence types among representative multidrug-resistant isolates. Evolutionary analysis showed that FC428-related clones have spread to Guangdong, China, which might be a cause of the rapid increase in extended-spectrum cephalosporin resistance currently. Among these strains, the prevalence of N. gonorrhoeae was extremely high, and single-dose ceftriaxone treatment might be a challenge in the future. To partially relieve the treatment pressure, a susceptibility test for susceptibility to azithromycin plus extended-spectrum cephalosporin dual therapy was performed. The results showed that all the representative isolates could be effectively killed with the coadministration of less than 1 mg/liter azithromycin and 0.125 mg/liter extended-spectrum cephalosporin, with a synergistic effect according to a fractional inhibitory concentration (FIC) of <0.5. In conclusion, dual therapy might be a powerful measure to treat refractory N. gonorrhoeae in the context of increasing antibiotic resistance in Guangdong, China.

Development and application of Cas13a-based diagnostic assay for Neisseria gonorrhoeae detection and azithromycin resistance identification.

BACKGROUND: Gonorrhoea, caused by Neisseria gonorrhoeae, has spread worldwide. Strains resistant to most antibiotics, including ceftriaxone and azithromycin, have emerged to an alarming level. Rapid testing for N. gonorrhoeae and its antimicrobial resistance will therefore contribute to clinical decision making for early diagnosis and rational drug use. METHODS: A Cas13a-based assay (specific high-sensitivity enzymatic reporter unlocking; SHERLOCK) was developed for N. gonorrhoeae detection (porA gene) and azithromycin resistance identification (A2059G, C2611T). Assays were evaluated for sensitivity with purified dsDNA and specificity with 17 non-gonococcal strains. Performance of SHERLOCK (porA) was compared with Roche Cobas 4800 using 43 urine samples. Identification of azithromycin resistance mutations (A2059G, C2611T) was evaluated using a total of 84 clinical isolates and 18 urine samples. Lateral flow was tested for this assay as a readout tool. Moreover, we directly assayed 27 urethral swabs from patients with urethritis to evaluate their status in terms of N. gonorrhoeae infection and azithromycin resistance. RESULTS: The SHERLOCK assay was successfully developed with a sensitivity of 10 copies/reaction, except 100 copies/reaction for A2059G, and no cross-reaction with other species. Comparison of the SHERLOCK assay with the Cobas 4800 revealed 100% concordance within 18 positive and 25 negative urine samples. Of the 84 isolates, 21 strains with azithromycin resistance mutations were distinguished and further verified by sequencing and MIC determination. In addition, 62.96% (17/27) strains from swab samples were detected with no mutant strains confirmed by sequencing. CONCLUSIONS: The SHERLOCK assay for rapid N. gonorrhoeae detection combined with azithromycin resistance testing is a promising method for application in clinical practice.

Understanding the wetting discrepancy in calcium alumino silicate hydrate induced by Al/Si ratio.

The application of supplementary cementitious materials (SCMs) in concrete can improve its durability in the marine environment. Calcium alumino silicate hydrate (CASH) is the main hydration product of SCMs; however, to date, the mechanism of the wetting discrepancy in CASH with different Al/Si ratios has not been revealed at the molecular scale. Herein, the molecular dynamics simulation method was used to study the wettability of water nanodroplets on the surface of CASH substrates with different Al/Si ratios, aiming to reveal the influence of CASH gel with different Al contents on the wettability of water molecules. The simulation results suggested that the CASH interface with a high Al/Si ratio has better wettability for nanodroplets. The microcosmic analysis showed that the interaction between particles and the CASH substrate is affected by the Al content. The electronegativity of the CASH substrate increases due to the substitution of Al-O tetrahedrons, which makes it stronger to solidify Ca ions on its surface and easier to form hydrogen bonds with water molecules in a nanodroplet. The orientation distribution of water molecules further revealed the source of the force of the CASH substrate on nanodroplets at the atomic level. The analysis of the dynamic properties showed that the H-bonds between CASH substrate with a high Al/Si ratio and water molecules are more stable, and thus the nanodroplets have better stability on the surface of CASH.

Sexualized Drug Use Among Female Sex Workers from Eight Cities in China: A Cross-Sectional Study.

There is a rich literature on sexualized drug use (i.e., drug use before or during sex) for men who have sex with men but less data from female sex workers (FSW), particularly from low- and middle-income countries. We describe the sexual and reproductive health outcomes in FSW reporting sexualized drug use. In 2019, we conducted a cross-sectional study in eight cities from seven provinces in China. We recruited FSW through community organizations working with sex workers and included those aged 18 years or above, exchanged sex at least once for money or goods in the past three months, and had traded sex for longer than a year. Multivariable logistic regression models were used. In total, 650 women participated: average age was 38.8 years (SD 10.2), 57.1% reported a monthly income over 5000 RMB ($USD 707), and 12.8% completed high school or above. Among participants, 65 (10.0%, 95% confidence interval (CI) 7.8-12.6) reported a history of sexualized drug use. Compared to FSW who never reported a history of sexualized drug use, FSW who reported a history of sexualized drug use had greater odds of working for a manager compared to being self-employed (adjusted odds ratio (AOR) 4.04, 95% CI 2.12-7.69), work in a sauna (AOR 2.43, 95% CI 1.09-5.41), charging a higher price for vaginal sex (AOR 2.15, 95% CI 1.14-4.06), and ever diagnosed with STIs (AOR 4.51, 95% CI 2.61-7.80). One in ten FSW reported sexualized drug use. Although they had similar risk profiles in terms of consistency of condom use and reproductive health outcomes, these women were more likely to report past STIs than those who reported no sexualized drug use. Health workers who work with substance users should devote attention to the sexual practices of their clients to make sure that they have safer sex.

Prokaryotic virus host predictor: a Gaussian model for host prediction of prokaryotic viruses in metagenomics.

BACKGROUND: Viruses are ubiquitous biological entities, estimated to be the largest reservoirs of unexplored genetic diversity on Earth. Full functional characterization and annotation of newly discovered viruses requires tools to enable taxonomic assignment, the range of hosts, and biological properties of the virus. Here we focus on prokaryotic viruses, which include phages and archaeal viruses, and for which identifying the viral host is an essential step in characterizing the virus, as the virus relies on the host for survival. Currently, the method for determining the viral host is either to culture the virus, which is low-throughput, time-consuming, and expensive, or to computationally predict the viral hosts, which needs improvements at both accuracy and usability. Here we develop a Gaussian model to predict hosts for prokaryotic viruses with better performances than previous computational methods. RESULTS: We present here Prokaryotic virus Host Predictor (PHP), a software tool using a Gaussian model, to predict hosts for prokaryotic viruses using the differences of k-mer frequencies between viral and host genomic sequences as features. PHP gave a host prediction accuracy of 34% (genus level) on the VirHostMatcher benchmark dataset and a host prediction accuracy of 35% (genus level) on a new dataset containing 671 viruses and 60,105 prokaryotic genomes. The prediction accuracy exceeded that of two alignment-free methods (VirHostMatcher and WIsH, 28-34%, genus level). PHP also outperformed these two alignment-free methods much (24-38% vs 18-20%, genus level) when predicting hosts for prokaryotic viruses which cannot be predicted by the BLAST-based or the CRISPR-spacer-based methods alone. Requiring a minimal score for making predictions (thresholding) and taking the consensus of the top 30 predictions further improved the host prediction accuracy of PHP. CONCLUSIONS: The Prokaryotic virus Host Predictor software tool provides an intuitive and user-friendly API for the Gaussian model described herein. This work will facilitate the rapid identification of hosts for newly identified prokaryotic viruses in metagenomic studies.

Sequential posterior interosseous artery perforator flap for reconstruction of dorsal hand defects.

Dorsal hand defects accompanied by exposure of bones and tendons remain a huge challenge for plastic surgeons. The pedicled perforator flaps have unique advantages in resurfacing the defects. This study aimed to investigate the clinical efficacy of the sequential posterior interosseous artery perforator flap for repairing dorsal hand defects. This study was composed of an anatomical study and clinical application. Anatomically, 30 adult upper limb specimens injected with red latex were dissected, the perforators from the branches of the posterior interosseous artery were observed in the dorsal forearm, and the sequential flap based on them was designed based on the anatomical characteristics. Clinically, nine cases of soft tissue defects on the dorsum of the hand were treated by this flap. Anatomically, the posterior interosseous artery divided into an ascending branch and a descending branch, and the descending branch traveled 1.0 ± 0.3 cm down to divide into the ulnar and radial terminal branches. The ulnar terminal branch presented constantly, and the radial terminal branch had an occurrence rate of 93.33%. Clinically, all flaps survived completely and possessed a soft texture and satisfactory appearance, as well as a nonbloated pedicle, and the donor region had a natural color and appearance with only a linear scar left behind. The sequential posterior interosseous artery perforator flap could become a useful option for repairing dorsal hand defects, as it has the advantages of being easy to perform without sacrificing the main vessels and avoiding donor area skin grafting.

FERONIA is involved in phototropin 1-mediated blue light phototropic growth in Arabidopsis.

Plant shoot phototropism is triggered by the formation of a light-driven auxin gradient leading to bending growth. The blue light receptor phototropin 1 (phot1) senses light direction, but how this leads to auxin gradient formation and growth regulation remains poorly understood. Previous studies have suggested phot1's role for regulated apoplastic acidification, but its relation to phototropin and hypocotyl phototropism is unclear. Herein, we show that blue light can cause phot1 to interact with and phosphorylate FERONIA (FER), a known cell growth regulator, and trigger downstream phototropic bending growth in Arabidopsis hypocotyls. fer mutants showed defects in phototropic growth, similar to phot1/2 mutant. FER also interacts with and phosphorylates phytochrome kinase substrates, the phot1 downstream substrates. The phot1-FER pathway acts upstream of apoplastic acidification and the auxin gradient formation in hypocotyl under lateral blue light, both of which are critical for phototropic bending growth in hypocotyls. Our study highlights a pivotal role of FER in the phot1-mediated phototropic cell growth regulation in plants.

Analysis of Treponema pallidum Strains From China Using Improved Methods for Whole-Genome Sequencing From Primary Syphilis Chancres.

BACKGROUND: Whole-genome sequencing (WGS) of Treponema pallidum subspecies pallidum (TPA) has been constrained by the lack of in vitro cultivation methods for isolating spirochetes from patient samples. METHODS: We built upon recently developed enrichment methods to sequence TPA directly from primary syphilis chancre swabs collected in Guangzhou, China. RESULTS: By combining parallel, pooled whole-genome amplification with hybrid selection, we generated high-quality genomes from 4 of 8 chancre-swab samples and 2 of 2 rabbit-passaged isolates, all subjected to challenging storage conditions. CONCLUSIONS: This approach enabled the first WGS of Chinese samples without rabbit passage and provided insights into TPA genetic diversity in China.