Fungal biofilm formation and its regulatory mechanism.

Fungal biofilm is a microbial community composed of fungal cells and extracellular polymeric substances (EPS). In recent years, fungal biofilms have played an increasingly important role in many fields. However, there are few studies on fungal biofilms and their related applications and development are still far from enough. Therefore, this review summarizes the composition and function of EPS in fungal biofilms, and improves and refines the formation process of fungal biofilms according to the latest viewpoints. Moreover, based on the study of Saccharomyces cerevisiae and Candida albicans, this review summarizes the gene regulation network of fungal biofilm synthesis, which is crucial for systematically understanding the molecular mechanism of fungal biofilm formation. It is of great significance to further develop effective methods at the molecular level to control harmful biofilms or enhance and regulate the formation of beneficial biofilms. Finally, the quorum sensing factors and mixed biofilms formed by fungi in the current research of fungal biofilms are summarized. These results will help to deepen the understanding of the formation process and internal regulation mechanism of fungal biofilm, provide reference for the study of EPS composition and structure, formation, regulation, group behavior and mixed biofilm formation of other fungal biofilms, and provide strategies and theoretical basis for the control, development and utilization of fungal biofilms.

Global prevalence of Borrelia burgdorferi and Anaplasma phagocytophilum coinfection in Ixodes tick populations: protocol for a systematic review and meta-analysis.

INTRODUCTION: Ixodes ticks are pivotal in transmitting diseases like Lyme disease and human granulocytic anaplasmosis, caused by Borrelia burgdorferi and Anaplasma phagocytophilum, respectively. These pathogens not only affect humans through single or multiple tick bites but also pose risks to animal hosts, leading to potential coinfections. Despite regional studies indicating significant prevalence, their global coinfection data remain sparse. This study aims to bridge this gap through a systematic review and meta-analysis of B. burgdorferi and A. phagocytophilum coinfections in Ixodes ticks worldwide. Addressing data limitations and study variability, it seeks to provide a nuanced understanding of coinfection patterns, their epidemiological implications and inform targeted prevention strategies. METHODS AND ANALYSIS: Following Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015 guidelines and PROSPERO registration, this study will undertake a thorough database search without constraints on language or publication date, using standardised screening and data extraction protocols. The quality and bias of studies will be evaluated using Joanna Briggs Institute tools. In the statistical analysis phase, conducted in R, we will initially determine the use of fixed or random-effects models based on the assessment of data heterogeneity. This choice will guide the framework for subsequent analyses. Within the selected model's framework, we will perform subgroup analyses and meta-regression to investigate the effects of various factors, ensuring that each step is tailored to the initial model selection to maintain analytical consistency. ETHICS AND DISSEMINATION: As this study does not involve clinical research or data collection from subjects, ethical approval is not required. We will uphold ethical standards in synthesising and reporting data. Study outcomes will be published in peer-reviewed journals, communicating findings to the scientific community and contributing to the understanding of Ixodes tickborne diseases. PROSPERO REGISTRATION NUMBER: CRD42023449735.

A novel dual near-infrared fluorescent probe for bioimaging and visualization of viscosity in acute alcoholic liver injury.

A dual NIR fluorescent probe Cy-ND is developed for viscosity sensing with λex/em = 766/806 nm, making it apt for biological analysis, whose response is validated through DFT and TDDFT computations. Cy-ND successfully detected viscosity changes amidst acute alcohol-induced liver injury and liver ischemia-reperfusion injury.

Efficacy and safety of antibiotics for treatment of leptospirosis: a systematic review and network meta-analysis.

BACKGROUND: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. METHODS: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. RESULTS: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). CONCLUSIONS: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022354938.

The Property of a Key Amino Acid Determines the Function of Farnesyl Pyrophosphate Synthase in Sporobolomyces pararoseus NGR.

Farnesyl pyrophosphate synthase (FPPS) catalyzes the synthesis of C15 farnesyl diphosphate (FPP) from C5 dimethylallyl diphosphate (DMAPP) and two or three C5 isopentenyl diphosphates (IPPs). FPP is an important precursor for the synthesis of isoprenoids and is involved in multiple metabolic pathways. Here, farnesyl pyrophosphate synthase from Sporobolomyces pararoseus NGR (SpFPPS) was isolated and expressed by the prokaryotic expression system. The SpFPPS full-length genomic DNA and cDNA are 1566 bp and 1053 bp, respectively. This gene encodes a 350-amino acid protein with a predicted molecular mass of 40.33 kDa and a molecular weight of 58.03 kDa (40.33 kDa + 17.7 kDa), as detected by SDS-PAGE. The function of SpFPPS was identified by induction, purification, protein concentration and in vitro enzymatic activity experiments. Structural analysis showed that Y90 was essential for chain termination and changing the substrate scope. Site-directed mutation of Y90 to the smaller side-chain amino acids alanine (A) and lysine (K) showed in vitro that wt-SpFPPS catalyzed the condensation of the substrate DMAPP or geranyl diphosphate (GPP) with IPP at apparent saturation to synthesize FPP as the sole product and that the mutant protein SpFPPS-Y90A synthesized FPP and C20 geranylgeranyl diphosphate (GGPP), while SpFPPS-Y90K hydrolyzed the substrate GGPP. Our results showed that FPPS in S. pararoseus encodes the SpFPPS protein and that the amino acid substitution at Y90 changed the distribution of SpFPPS-catalyzed products. This provides a baseline for potentially regulating SpFPPS downstream products and improving the carotenoid biosynthesis pathway.

The inverted U-shaped relationship between epinephrine and pancreatic ductal adenocarcinoma patients' survival with compensation of lymphocyte.

BACKGROUND: The relationship between epinephrine and cancer can be dose-dependent in in vivo study. Whether it is the same in human body still needs verification. METHOD: We used frozen human pancreatic ductal adenocarcinoma (PDAC) tissues to detect epinephrine content and analyzed its relationship with survival using the K-M method and Cox regression. Disturbance of blood cell count and C-reactive protein and identification of related potent intermediary factors were also analyzed. RESULTS: K-M plot and Cox regression all showed the inverted U-shaped relationship between epinephrine and PDAC survival. Lymphocyte adjustment can increase the HRs of epinephrine for PDAC death by >10%. CONCLUSION: Epinephrine played an anti-tumor or pro-tumor effect depending on the specific concentration. Circulating lymphocyte count was elevated and might acted as a compensation pathway to reduce the pro-tumor effect of epinephrine to PDAC.

Nitrogen fertiliser-domesticated microbes change the persistence and metabolic profile of atrazine in soil.

Pesticides and fertilisers are frequently used and may co-exist on farmlands. The overfertilisation of soil may have a profound influence on pesticide residues, but the mechanism remains unclear. The effects of chemical fertilisers on the environmental behaviour of atrazine and their underlying mechanisms were investigated. The present outcomes indicated that the degradation of atrazine was inhibited and the half-life was prolonged 6.0 and 7.6 times by urea and compound fertilisers (NPK) at 1.0 mg/g (nitrogen content), respectively. This result, which was confirmed in both sterilised and transfected soils, was attributed to the inhibitory effect of nitrogen fertilisers on soil microorganisms. The abundance of soil bacteria was inhibited by nitrogen fertilisers, and five families of potential atrazine degraders (Micrococcaceae, Rhizobiaceae, Bryobacteraceae, Chitinophagaceae, and Sphingomonadaceae) were strongly and positively (R > 0.8, sig < 0.05) related to the decreased functional genes (atzA and trzN), which inhibited hydroxylation metabolism and ultimately increased the half-life of atrazine. In addition, nitrogen fertilisers decreased the sorption and vertical migration behaviour of atrazine in sandy loam might increase the in-situ residual and ecological risk. Our findings verified the weakened atrazine degradation with nitrogen fertilisers, providing new insights into the potential risks and mechanisms of atrazine in the context of overfertilisation.

Serological and molecular epidemiological investigation of Mediterranean spotted fever in Yunnan Province, China.

OBJECTIVES: Given the limited research and its potential hazards, the study aimed to determine the prevalence of Mediterranean spotted fever (MSF) caused by Rickettsia conorii (R. conorii), a tick-borne disease, in Yunnan Province, China. METHODS: Through stratified sampling across five distinct regions in Yunnan, 5358 blood samples were obtained from the general healthy population. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Polymerase chain reaction (PCR) were employed for analysis. RESULTS: IFA identified 27 (0.50%) subjects with immunoglobulin G (IgG) positivity; none were positive for immunoglobulin M (IgM) via ELISA. PCR detected one individual with R. conorii outer membrane protein A (ompA). Significant seroprevalence variation was observed, particularly in Southern Yunnan (P = 0.032), with R. conorii subsp. conorii confirmed in the PCR-positive sample. CONCLUSIONS: This research reveals a correlation between MSF prevalence, geography, and climate in Yunnan. The paucity of prior studies underscores MSF's potential diagnostic challenges in the region. Comprehensive understanding of the pathogen's distribution is pivotal for intervention. Given the study's scope and Yunnan's unique setting, additional research is advocated.

A key protein from Borrelia burgdorferi could stimulate cytokines in human microglial cells and inhibitory effects of Cucurbitacin IIa.

Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by Borrelia burgdorferi (Bb) infection. However, its pathogenesis is not fully understood. We used recombinant BmpA (rBmpA) to stimulate human microglia cell HMC3, then collected the culture supernatant and extracted total RNA from cells, and used the supernatant for cytokine chip, then ELISA and qPCR technology were used to validate the results from cytokine chip. After rBmpA stimulation of microglia, 24 inflammation-related cytokines showed elevated expression. Among them, six cytokines (IL-6, IL-8, CCL2, CCL5, CXCL1, and CXCL10) increased significantly in mRNA transcription, three cytokines (IL-6, IL-8, and CXCL10) concentrations in the cell supernatant increased significantly after the rBmpA stimulation, and CuIIa could inhibit expression of these cytokines. The BmpA can stimulate human microglia to produce large amounts of cytokines, leading to the occurrence of inflammation, which may be closely related to the development of LNB. CuIIa can inhibit BmpA-induced cytokine production in microglia, which may have potential therapeutic effects on LNB.

Regulation of cell differentiation to promote pullulan synthesis in Aureobasidium pullulans NG.

Pullulan is a polymer produced by Aureobasidium spp. The yield of pullulan production can be impacted by the cellular differentiation of Aureobasidium spp., which changes with alterations in the growth environment. To improve pullulan yield, identifying key factors that regulate cellular differentiation is crucial. In this study, the main form of pullulan synthesis in Aureobasidium pullulans NG was through swollen cells (SC). The results showed that citric acid (CA) can regulate the cellular differentiation of Aureobasidium pullulans NG by accumulating higher levels of CA in the cells to maintain growth in SC form and increase pullulan production. The addition of 1.0% CA to Aureobasidium pullulans NG for 96 h resulted in a significant increase in pullulan production, producing 18.32 g/l compared to the control group which produced 10.23 g/l. Our findings suggest that controlling cellular differentiation using CA is a promising approach for enhancing pullulan production in Aureobasidium pullulans. KEY POINTS: • The regulation of cell differentiation in Aureobasidium pullulans NG is demonstrated to be influenced by citric acid. • Intracellular citric acid levels in Aureobasidium pullulans NG have been shown to support the growth of swollen cells. • Citric acid has been found to increase pullulan production in Aureobasidium pullulans NG.

The intricate role of CCL5/CCR5 axis in Alzheimer disease.

The morbidity and mortality associated with Alzheimer disease (AD), one of the most common neurodegenerative diseases, are increasing each year. Although both amyloid ß and tau proteins are known to be involved in AD pathology, their detailed functions in the pathogenesis of the disease are not fully understood. There is increasing evidence that neuroinflammation contributes to the development and progression of AD, with astrocytes, microglia, and the cytokines and chemokines they secrete acting coordinately in these processes. Signaling involving chemokine (C-C motif) ligand 5 (CCL5) and its main receptor C-C chemokine receptor 5 (CCR5) plays an important role in normal physiologic processes as well as pathologic conditions such as neurodegeneration. In recent years, many studies have shown that the CCL5/CCR5 axis plays a major effect in the pathogenesis of AD, but there are also a few studies that contradict this. In short, the role of CCL5/CCR5 axis in the pathogenesis of AD is still intricate. This review summarizes the structure, distribution, physiologic functions of the CCL5/CCR5 axis, and the progress in understanding its involvement in the pathogenesis of AD.

Real-time airplane detection using multi-dimensional attention and feature fusion.

The remote sensing image airplane object detection tasks remain a challenge such as missed detection and misdetection, and that is due to the low resolution occupied by airplane objects and large background noise. To address the problems above, we propose an AE-YOLO (Accurate and Efficient Yolov4-tiny) algorithm and thus obtain higher detection precision for airplane detection in remote sensing images. A multi-dimensional channel and spatial attention module is designed to filter out background noise information, and we also adopt a local cross-channel interaction strategy without dimensionality reduction so as to reduce the loss of local information caused by the scaling of the fully connected layer. The weighted two-way feature pyramid operation is used to fuse features and the correlation between different channels is learned to improve the utilization of features. A lightweight convolution module is exploited to reconstruct the network, which effectively reduce the parameters and computations while improving the accuracy of the detection model. Extensive experiments validate that the proposed algorithm is more lightweight and efficient for airplane detection. Moreover, experimental results on the airplane dataset show that the proposed algorithm meets real-time requirements, and its detection accuracy is 7.76% higher than the original algorithm.

The analysis of the function, diversity, and evolution of the Bacillus phage genome.

BACKGROUND: Phages play a pivotal role in the evolution of microbial populations. The interactions between phages and their hosts are complex and may vary in response to host physiology and environmental conditions. Here, we have selected the genomes of some representative Bacillus prophages and lysosomes from the NCBI database for evolutionary analysis. We explored their evolutionary relationships and analyzed the protein information encoded by hundreds of Bacillus phages. RESULTS: We obtained the following conclusions: First, Bacillus phages carried some known functional gene fragments and a large number of unknown functional gene fragments, which might have an important impact on Bacillus populations, such as the formation of spores and biofilms and the transmission of virulence factors. Secondly, the Bacillus phage genome showed diversity, with a clear genome boundary between Bacillus prophages and Bacillus lytic phages. Furthermore, genetic mutations, sequence losses, duplications, and host-switching have occurred during the evolution of the Bacillus phage, resulting in low genome similarity between the Bacillus phages. Finally, the lysis module played an important influence on the process of Bacillus phage cross-species infestation. CONCLUSIONS: This study systematically described their protein function, diversity, and genome evolution, and the results of this study provide a basis for evolutionary diversity, horizontal gene transfer and co-evolution with the host in Bacillus phages.

Revision of the subgenus Stegana (Steganina) from China, with assessment of species delimitation using DNA barcodes (Diptera, Drosophilidae).

A total of 58 (eight known and 50 new) species of the subgenus Stegana (Steganina) from China were surveyed and (re)described: S. (S.) bacilla Chen & Aotsuka, 2004, S. (S.) belokobylskiji Sidorenko, 1997, S. (S.) hirticeps Wang, Gao, & Chen, 2013, S. (S.) izu Sidorenko, 1997, S. (S.) kanmiyai Okada & Sidorenko, 1992, S. (S.) masanoritodai Okada & Sidorenko, 1992, S. (S.) maymyo Sidorenko, 1997, stat. rev., S. (S.) nigripes Zhang & Chen, 2015, S. (S.) alafoliacea Zhang & Chen, sp. nov., S. (S.) baoxing Li & Chen, sp. nov., S. (S.) bibarbata Li & Chen, sp. nov., S. (S.) bimai Cui & Chen, sp. nov., S. (S.) cinereipecta Zhang & Chen, sp. nov., S. (S.) cardua Cui & Chen, sp. nov., S. (S.) cordhirsuta Wang & Chen, sp. nov., S. (S.) cornuta Li & Chen, sp. nov., S. (S.) cucullata Li & Chen, sp. nov., S. (S.) cultella Cui & Chen, sp. nov., S. (S.) curvitabulata Cui & Chen, sp. nov., S. (S.) daiya Cui & Chen, sp. nov., S. (S.) dendrophila Zhang & Chen, sp. nov., S. (S.) flabella Li & Chen, sp. nov., S. (S.) flavipes Li & Chen, sp. nov., S. (S.) formosa Zhang & Chen, sp. nov., S. (S.) fusca Li & Chen, sp. nov., S. (S.) fuscipes Li & Chen, sp. nov., S. (S.) glaucopalpula Cui & Chen, sp. nov., S. (S.) haba Zhang & Chen, sp. nov., S. (S.) hirticlavata Cui & Chen, sp. nov., S. (S.) iaspidea Zhang & Chen, sp. nov., S. (S.) idiasta Cui & Chen, sp. nov., S. (S.) kanda Cui & Chen, sp. nov., S. (S.) labao Li & Chen, sp. nov., S. (S.) lancang Li & Chen, sp. nov., S. (S.) latifoliacea Wang & Chen, sp. nov., S. (S.) liusanjieae Li & Chen, sp. nov., S. (S.) magniflava Cui & Chen, sp. nov., S. (S.) mailangang Li & Chen, sp. nov., S. (S.) marenubila Cui & Chen, sp. nov., S. (S.) menghai Zhang & Chen, sp. nov., S. (S.) menglian Li & Chen, sp. nov., S. (S.) minutiflava Li & Chen, sp. nov., S. (S.) multiprocera Li & Chen, sp. nov., S. (S.) nayun Li & Chen, sp. nov., S. (S.) nigridentata Wang & Chen, sp. nov., S. (S.) nigripalpula Cui & Chen, sp. nov., S. (S.) otphylla Cui & Chen, sp. nov., S. (S.) radiciflava Zhang & Chen, sp. nov., S. (S.) rava Cui & Chen, sp. nov., S. (S.) sciophila Li & Chen, sp. nov., S. (S.) septencolorata Li & Chen, sp. nov., S. (S.) serrata Zhang & Chen, sp. nov., S. (S.) silvestrella Zhang & Chen, sp. nov., S. (S.) simola Cui & Chen, sp. nov., S. (S.) yani Li & Chen, sp. nov., S. (S.) yixiang Zhang & Chen, sp. nov., S. (S.) zaduo Cui & Chen, sp. nov., and S. (S.) zhuoma Cui & Chen, sp. nov. We also provided a complete list of Chinese Steganina species together with their geographical distributions. In addition, the majority of currently available DNA barcode (partial sequence of the mitochondrial cytochrome c oxidase subunit I (COI) gene) sequences of this subgenus (435 sequences of 102 spp.) were employed in a molecular analysis for species delimitation. Taken together, morphology- and molecular-based species delimitation results reached a consensus for an overwhelming majority of these Steganina species (98 of 102 spp.).

Abiotic Synthetic Antibody Inhibitor with Broad-Spectrum Neutralization and Antiviral Efficacy against Escaping SARS-CoV-2 Variants.

The rapid emergence and spread of vaccine/antibody-escaping variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious challenges to our efforts in combating corona virus disease 2019 (COVID-19) pandemic. A potent and broad-spectrum neutralizing reagent against these escaping mutants is extremely important for the development of strategies for the prevention and treatment of SARS-CoV-2 infection. We herein report an abiotic synthetic antibody inhibitor as a potential anti-SARS-CoV-2 therapeutic agent. The inhibitor, Aphe-NP14, was selected from a synthetic hydrogel polymer nanoparticle library created by incorporating monomers with functionalities complementary to key residues of the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) involved in human angiotensin-converting enzyme 2 (ACE2) binding. It has high capacity, fast adsorption kinetics, strong affinity, and broad specificity in biologically relevant conditions to both the wild type and the current variants of concern, including Beta, Delta, and Omicron spike RBD. The Aphe-NP14 uptake of spike RBD results in strong blockage of spike RBD-ACE2 interaction and thus potent neutralization efficacy against these escaping spike protein variant pseudotyped viruses. It also inhibits live SARS-CoV-2 virus recognition, entry, replication, and infection in vitro and in vivo. The Aphe-NP14 intranasal administration is found to be safe due to its low in vitro and in vivo toxicity. These results establish a potential application of abiotic synthetic antibody inhibitors in the prevention and treatment of the infection of emerging or possibly future SARS-CoV-2 variants.

Integrative analysis of genomic and metabolomic data reveals key metabolic pathways involved in lipid and carotenoid biosynthesis in oleaginous red yeast Rhodosporidiobolus odoratus XQR.

Rhodosporidiobolus odoratus, one of the oleaginous red yeasts, is gaining biotechnological importance for their ability to produce microbial lipids and carotenoids. However, to date, the genomic resource underling lipid and carotenoid biosynthesis in R. odoratus has not been reported. Here, we reported the first genome assembly of R. odoratus using a combination of PacBio and Illumina techniques. The final genome assembly is 23.74 Mb in size, containing 52 scaffolds with a N50 length of 1200,460 bp and a GC content of 56.90%. Benchmarking Universal Single-Copy Orthologs (BUSCO) assessment showed that our assembly contains 94.23% of Basidiomycota universal single-copy orthologs. The genome was predicted to contain 4986 protein-coding genes, 4967 of which were functionally annotated. Metabolomic profiling identified 574 lipids, 3 carotenoids, and 208 volatile organic compounds synthesized by R. odoratus. Integrative analysis of genomics and metabolomics provides insights into the biosynthesis of lipid, carotenoid, and other bioactive compounds in R. odoratus. Collectively, the results presented herein greatly enhance our understanding of R. odoratus in lipids and carotenoids biosynthesis, and thus further accelerate its fundamental molecular investigations and biotechnological applications.

BCG-induced trained immunity: history, mechanisms and potential applications.

The Bacillus Calmette-Guérin (BCG) vaccine was discovered a century ago and has since been clinically applicable. BCG can not only be used for the prevention of tuberculosis, but also has a non-specific protective effect on the human body called trained immunity that is mediated by innate immune cells such as monocytes, macrophages, and natural killer cells. Mechanisms of trained immunity include epigenetic reprogramming, metabolic reprogramming, and long-term protection mediated by hematopoietic stem cells. Trained immunity has so far shown beneficial effects on cancer, viral-infections, autoimmune diseases, and a variety of other diseases, especially bladder cancer, respiratory viruses, and type 1 diabetes. The modulation of the immune response by BCG has led to the development of a variety of recombinant vaccines. Although the specific mechanism of BCG prevention on diseases has not been fully clarified, the potential role of BCG deserves further exploration, which is of great significance for prevention and treatment of diseases.

Seventy years of evidence on the efficacy and safety of drugs for treating leprosy: a network meta-analysis.

OBJECTIVE: The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations. METHOD: All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score. RESULTS: Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens. CONCLUSIONS: The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction. AVAILABILITY OF DATA AND MATERIALS: All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Bio-Fabrication of ZnONPs from Alkalescent Nucleoside Antibiotic to Control Rice Blast: Impact on Pathogen (Magnaporthe grisea) and Host (Rice).

In the traditional method of the bio-fabrication of zinc oxide nanoparticles (ZnONPs), bacterial strains face metal toxicity and antimicrobial action. In the current study, an alkalescent nucleoside antibiotic was mixed with zinc hexanitrate to fabricate the ZnONPs. An integrated approach of DIAION HP-20 macroporous resin and sephadex LH-20 column chromatography was adopted to separate and purify alkalescent nucleoside AN03 from Streptomyces koyanogensis. Alkalescent nucleoside was confirmed by the Doskochilova solvent system. The bio-fabricated ZnONPs were characterized by using Fourier transform infrared (FTIR), X-ray diffraction (XRD), and transmission electron microscopy (TEM) analyses. The XRD spectrum and the TEM images confirmed the crystallinity and the spherical shape of the ZnONPs with an average size of 22 nm. FTIR analysis showed the presence of functional groups, which confirmed the bio-fabrication of ZnONPs from alkalescent nucleoside ANO3. In-vitro studies showed that 75 µg/mL of ZnONPs had a strong inhibitory zone (28.39 mm) against the Magnaporthe grisea and significantly suppressed the spore germination. SEM and TEM observations respectively revealed that ZnONPs caused breakage in hyphae and could damage the cells of M. grisea. Greenhouse experiments revealed that the foliar spray of ZnONPs could control the rice blast disease by 98%. Results also revealed that ZnONPs had positive effects on the growth of the rice plant. The present study suggested that ZnONPs could be fabricated from microbe-derived nucleoside antibiotics without facing the problems of metal toxicity and antimicrobial action, thus overcoming the problem of pathogen resistance. This could be a potent biocontrol agent in rice blast disease management.

The Effect of Traditional Chinese Medicine on Postviral Olfactory Dysfunction: A Systematic Review and Meta-Analysis.

Objective: The aim of this study is to evaluate the efficacy and safety of traditional Chinese medicine (TCM) for postviral olfactory dysfunction (PVOD). Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical and Medical (CBM) Database, and Wanfang Database were electronically searched from their inception to July 25, 2022. Two authors independently performed study selection, data extraction, and quality assessment to ensure systematic quality evaluation. Randomized controlled trials (RCTs) comparing TCM with olfactory training and/or drug therapy (OTDT) were included. The outcomes were the effective rate, QOD-P, TDI score, UPSIT score, and adverse effects. Cochrane RoB was the guideline used to evaluate the methodological quality of the included trials. RevMan 5.3 software was used for statistical analysis. Results: A total of 6 RCTs involving 467 patients with PVOD were selected. Compared with OTDT, TCM plus OTDT decreased QOD-P (MD = -1.73, 95% CI (-2.40, -1.06), P < 0.0001) but did not increase the effective rate (T&T) (RR = 1.28, 95% CI (0.86, 1.90), P=0.22, I 2 = 61%). Compared with no treatment, TCM seemed to increase the treatment success rate (UPSIT) (RR = 3.17, 95% CI (1.78, 5.65), P < 0.0001, I 2 = 0%), but there was no statistically significant difference in improving the UPSIT score (MD = 3.44, 95% CI (-1.36, 8.24), P=0.16). Compared with drug therapy, TCM plus drug therapy appeared to increase the effective rate (ΔVAS) (RR = 2.36, 95% CI (1.41, 3.94), I 2 = 0%), but there was no statistically significant difference in improving the TDI score (MD = 2.10, 95% CI (-1.99, 6.19), P=0.31). No significant differences in adverse reactions were reported between TCM and OTDT. Conclusion: TCM may be an effective treatment for PVOD. With a lack of high-quality RCTs, further large-scale and high-quality RCTs are still warranted.