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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.

Ni-based catalysts are the most promising catalysts for CO 2 methanation. The development of catalysts with low-temperature activity could bring significant energy and environmental benefits. In this work, the hydrogenation of CO 2 to methane was studied on Ni-M/γ-Al 2 O 3 (M = Fe, Co, or Mn) bimetallic catalysts. The optimum reaction was obtained using Ni-Mn/γ-Al 2 O 3 (CO 2 conversion: 85%, CH 4 selectivity: 99%, 280 °C). In situ FTIR studies revealed the excellent performance of Ni-Mn/γ-Al 2 O 3 , which lowers the required reaction temperature. Based on in situ FTIR studies, CO 2 methanation proceeded over three intermediates on the catalysts: bicarbonate → carbonate → formate → methane. The second metal (Co or Mn) promoted the dispersion of both Ni and itself and improved the ability of Ni to crack H 2 . And introduced more oxygen vacancies to strengthen the basicity of surrounding O 2− on the surface of the catalysts. In effect, the number of carbonate active sites could be increased accordingly, thereby improving the adsorption capacity for CO 2 . Graphic Abstract

The performance of commonly used assays for diagnosis of syphilis varies considerably depending on stage of infection and sample type. In response to the need for improved syphilis diagnostics, we develop assays that pair PCR pre-amplification of the tpp47 gene of Treponema pallidum subsp. pallidum with CRISPR-LwCas13a. The PCR-LwCas13a assay achieves an order of magnitude better analytical sensitivity than real-time PCR with equivalent specificity. When applied to a panel of 216 biological specimens, including 135 clinically confirmed primary and secondary syphilis samples, the PCR-LwCas13a assay demonstrates 93.3% clinical sensitivity and 100% specificity, outperforming tpp47 real-time PCR and rabbit-infectivity testing. We further adapt this approach to distinguish Treponema pallidum subsp. pallidum lineages and identify genetic markers of macrolide resistance. Our study demonstrates the potential of CRISPR-based approaches to improve diagnosis and epidemiological surveillance of syphilis. Clinical diagnosis of Treponema pallidum subspecies pallidum ( TPA ), the causative agent of syphilis, depends upon serological testing, which has reduced sensitivity for some stages of the disease. Accompanying methods to complement serological testing also have distinct limitations. In this work, authors develop an assay that combines PCR with CRISPR-LwCas13a, and demonstrate sensitivity and specificity on clinically confirmed syphilis samples.

Metal ions are vital components in many proteins for the inference and engineering of protein function, with coordination complexity linked to structural, catalytic, or regulatory roles. Modeling transition metal ions, especially in transient, reversible, and concentration-dependent regulatory sites, remains challenging. We present PinMyMetal (PMM), a hybrid machine learning system designed to accurately predict transition metal localization and environment in macromolecules, tailored to tetrahedral and octahedral geometries. PMM outperforms other predictors, achieving high accuracy in ligand and coordinate predictions. It excels in predicting regulatory sites (median deviation 0.36 Å), demonstrating superior accuracy in locating catalytic sites (0.33 Å) and structural sites (0.19 Å). Each predicted site is assigned a certainty score based on local structural and physicochemical features, independent of homologs. Interactive validation through our server, CheckMyMetal, expands PMM’s scope, enabling it to pinpoint and validate diverse functional metal sites from different structure sources (predicted structures, cryo-EM, and crystallography). This facilitates residue-wise assessment and robust metal binding site design. The lightweight PMM system demands minimal computing resources and is available at https://PMM.biocloud.top . The PMM workflow can interrogate with protein sequence to characterize the localization of the most probable transition metals, which is often interchangeable and hard to differentiate by nature. PinMyMetal (PMM) is an accurate tool for predicting transition metal binding sites in proteins. It integrates geometric and chemical features, outperforms existing methods, and supports large-scale genome analysis and drug design.

The conversion of CO2 into light olefins over bifunctional catalysts is a promising route for producing high-value-added products. This approach not only mitigates excessive CO2 emissions but also reduces the chemical industry’s reliance on fossil fuels. Among bifunctional catalysts, ZnZrOx is widely used due to its favorable oxide composition. In this work, ZnZrOx solid solution was synthesized by calcining an MOF precursor, resulting in a large specific surface area and a small particle size. Characterization studies revealed that ZnZrOx prepared via MOF calcination exhibited an enhanced CO2 activation and H2 dissociation capacity compared to that synthesized using the co-precipitation method. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) showed that CO2 adsorption on ZnZrOx led to the formation of carbonate species, while HCOO* and CH3O* intermediates were generated upon exposure to the reaction gas. When ZnZrOx was combined with SAPO-34 molecular sieves under reaction conditions of 380 °C, 3 MPa, and 6000 mL·g_cat−1·h−1, the CO2 conversion reached 34.37%, with a light olefin yield of 15.13%, demonstrating a superior catalytic performance compared to that of the co-precipitation method.

HIV testing rates are suboptimal among at-risk men. Crowdsourcing may be a useful tool for designing innovative, community-based HIV testing strategies to increase HIV testing. The purpose of this study was to use a stepped wedge cluster randomized controlled trial (RCT) to evaluate the effect of a crowdsourced HIV intervention on HIV testing uptake among men who have sex with men (MSM) in eight Chinese cities. An HIV testing intervention was developed through a national image contest, a regional strategy designathon, and local message contests. The final intervention included a multimedia HIV testing campaign, an online HIV testing service, and local testing promotion campaigns tailored for MSM. This intervention was evaluated using a closed cohort stepped wedge cluster RCT in eight Chinese cities (Guangzhou, Shenzhen, Zhuhai, and Jiangmen in Guangdong province; Jinan, Qingdao, Yantai, and Jining in Shandong province) from August 2016 to August 2017. MSM were recruited through Blued, a social networking mobile application for MSM, from July 29 to August 21 of 2016. The primary outcome was self-reported HIV testing in the past 3 months. Secondary outcomes included HIV self-testing, facility-based HIV testing, condom use, and syphilis testing. Generalized linear mixed models (GLMMs) were used to analyze primary and secondary outcomes. We enrolled a total of 1,381 MSM. Most were ≤30 years old (82%), unmarried (86%), and had a college degree or higher (65%). The proportion of individuals receiving an HIV test during the intervention periods within a city was 8.9% (95% confidence interval [CI] 2.2-15.5) greater than during the control periods. In addition, the intention-to-treat analysis showed a higher probability of receiving an HIV test during the intervention periods as compared to the control periods (estimated risk ratio [RR] = 1.43, 95% CI 1.19-1.73). The intervention also increased HIV self-testing (RR = 1.89, 95% CI 1.50-2.38). There was no effect on facility-based HIV testing (RR = 1.00, 95% CI 0.79-1.26), condom use (RR = 1.00, 95% CI 0.86-1.17), or syphilis testing (RR = 0.92, 95% CI 0.70-1.21). A total of 48.6% (593/1,219) of participants reported that they received HIV self-testing. Among men who received two HIV tests, 32 individuals seroconverted during the 1-year study period. Study limitations include the use of self-reported HIV testing data among a subset of men and non-completion of the final survey by 23% of participants. Our study population was a young online group in urban China and the relevance of our findings to other populations will require further investigation. In this setting, crowdsourcing was effective for developing and strengthening community-based HIV testing services for MSM. Crowdsourced interventions may be an important tool for the scale-up of HIV testing services among MSM in low- and middle-income countries (LMIC). ClinicalTrials.gov NCT02796963.

Identifying and characterizing metal-binding sites (MBS) within macromolecular structures is imperative for elucidating their biological functions. CheckMyMetal ( CMM ) is a web based tool that facilitates the interactive validation of MBS in structures determined through X-ray crystallography and cryo-electron microscopy (cryo-EM). Recent updates to CMM have significantly enhanced its capability to efficiently handle large datasets generated from cryo-EM structural analyses. In this study, we address various challenges inherent in validating MBS within both X-ray and cryo-EM structures. Specifically, we examine the difficulties associated with accurately identifying metals and modeling their coordination environments by considering the ongoing reproducibility challenges in structural biology and the critical importance of well annotated, high-quality experimental data. CMM employs a sophisticated framework of rules rooted in the valence bond theory for MBS validation. We explore how CMM validation parameters correlate with the resolution of experimentally derived structures of macromolecules and their complexes. Additionally, we showcase the practical utility of CMM by analyzing a representative cryo-EM structure. Through a comprehensive examination of experimental data, we demonstrate the capability of CMM to advance MBS characterization and identify potential instances of metal misassignment.

Background: After Neisseria gonorrhoeae FC428 was first found in Japan, ceftriaxone-resistant strains disseminated globally, and the gonococcal resistance rate increased remarkably. Epidemiological investigations are greatly significant for the analysis of antimicrobial resistance (AMR) trends, molecular features and evolution. Objectives: To clarify the AMR trend from 2016-2019 and reveal the molecular characteristics and evolution of ceftriaxone-resistant penA 60.001 isolates. Methods: The minimum inhibitory concentrations (MICs) of antibiotics against 4113 isolates were detected by the agar dilution method. N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST) and N.gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were used to identify the sequence types. Genome analysis was conducted to analyze resistance genes, virulence factors, and evolutionary sources. Results: Isolates with decreased ceftriaxone susceptibility have increased from 2.05% (2016) to 16.18% (2019). Six ceftriaxone-resistant isolates possessing penA 60.001 appeared in Guangdong Province, and were resistant to ceftriaxone, penicillin, tetracycline, ciprofloxacin and cefixime, but susceptible to azithromycin and spectinomycin. Single-nucleotide polymorphisms (SNPs) in the porB gene were the major cause of different NG-MAST types. ST1903 was the main NG-STAR genotype and only strain-ZH545 was ST7365, with molecular features consistent with the MICs. Furthermore, different MLSTs suggested diverse evolutionary sources. Genome analysis revealed a set of virulence factors along with the resistance genes \"penA\" and \"blaTEM-1B\". Half of penA 60.001 strains were fully mixed with global FC428-related strains. Conclusions: Global FC428-related clones have disseminated across Guangdong, possibly causing decreased ceftriaxone susceptibility. Enhanced gonococcal surveillance will help elucidate the trajectory of transmission and curb further dissemination.

BackgroundThe indiscriminate use of antibiotics has accelerated antimicrobial resistance (AMR) in Neisseria gonorrhoeae (NG), emphasising the need to follow treatment guidelines. This study aimed to assess the rate of adherence to standard treatment among patients with gonorrhoea and identify influencing factors.MethodsA survey was conducted in Guangdong province, China, involving uncomplicated gonorrhoea cases registered in the Chinese Information System for Disease Control and Prevention. Data on demographic characteristics and medical information were collected to determine the standard treatment rate, defined as the proportion of patients receiving treatment according to national guidelines (ie, a single dose of ceftriaxone 250 mg, spectinomycin 2 g, cefotaxime 1 g or other third-generation cephalosporins). Medication choices were documented. χ² tests and multilevel logistic regression were used to analyse factors associated with standard treatment.ResultsThe survey included 2424 patients with gonorrhoea from 59 hospitals. The standard treatment rate was 30.7% (743/2424), with 36.2% for females and 29.6% for males. Common reasons for substandard treatment included the use of non-guideline medications (42.3%, 710/1681) and incorrect dosing (36.2%, 605/1681). Factors associated with the standard treatment rate included gender, address, educational level, department, physicians’ training, number of diagnosed gonorrhoea cases and hospital level.ConclusionThe standard treatment rate for gonorrhoea in Guangdong province, China, is below expectations. Comprehensive measures, such as establishing a goal-directed monitoring system and implementing promotional activities, are needed to improve adherence to treatment guidelines.

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.