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This study addresses the distribution and antimicrobial resistance of Acinetobacter baumannii (A. baumannii) in a medical facility in Haikou City, aiming to provide essential insights for enhancing in-hospital treatment and prevention strategies. We conducted a retrospective analysis of 513 A. baumannii isolates collected from a tertiary care hospital in Haikou between January 2018 and December 2020, focusing on their antimicrobial resistance patterns. Random Amplified Polymorphic DNA (RAPD) analysis was performed on 48 randomly selected A. baumannii strains. Using Gel-pro4.0 and NTSYSspc2.10 software, we constructed dendrograms to assess the genetic diversity of these strains. Our results indicate that males between 60 and 70 years old are particularly vulnerable to A. baumannii infections, which are most frequently detected in sputum samples, with a detection rate exceeding 70%. Alarmingly, over 50% of the isolates were identified as multi-drug resistant. The RAPD-PCR fingerprinting cluster analysis demonstrated substantial genetic diversity among the strains. Using primer OPA-02 at a 45% similarity coefficient, the strains were categorized into four groups (A-D), with group A being predominant (39 strains). high-prevalence areas like the Neurosurgery and Intensive Care Medicine Wards require enhanced surveillance and targeted interventions to manage Group C infections effectively. Additionally, the varied presence of other groups necessitates customized strategies to address the specific risks in each ward. Similarly, primer 270 at a 52% similarity coefficient classified the strains into five groups (E-I), with group E being most common (36 strains). The study highlights a concerning prevalence of antimicrobial resistance, particularly multi-drug resistance, among A. baumannii strains in the Haikou hospital. The significant genetic diversity, especially within groups A and E, underscores the need for tailored hospital treatment protocols and prevention measures. These findings contribute to the growing body of research on antimicrobial resistance, emphasizing the urgent need for effective management strategies in healthcare settings.
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Infecções por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Variação Genética , Centros de Atenção Terciária , Acinetobacter baumannii/genética , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/tratamento farmacológico , Estudos Retrospectivos , Antibacterianos/farmacologia , Adulto , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Idoso de 80 Anos ou mais , Técnica de Amplificação ao Acaso de DNA Polimórfico , Adolescente , Adulto Jovem , Criança , Pré-Escolar , Lactente , Farmacorresistência Bacteriana/genéticaRESUMO
The mechanical properties of polymer gels devote to emerging devices and machines in fields such as biomedical engineering, flexible bioelectronics, biomimetic actuators, and energy harvesters. Coupling network architectures and interactions has been explored to regulate supportive mechanical characteristics of polymer gels; however, systematic reviews correlating mechanics to interaction forces at the molecular and structural levels remain absent in the field. This review highlights the molecular engineering and structural engineering of polymer gel mechanics and a comprehensive mechanistic understanding of mechanical regulation. Molecular engineering alters molecular architecture and manipulates functional groups/moieties at the molecular level, introducing various interactions and permanent or reversible dynamic bonds as the dissipative energy. Molecular engineering usually uses monomers, cross-linkers, chains, and other additives. Structural engineering utilizes casting methods, solvent phase regulation, mechanochemistry, macromolecule chemical reactions, and biomanufacturing technology to construct and tailor the topological network structures, or heterogeneous modulus compositions. We envision that the perfect combination of molecular and structural engineering may provide a fresh view to extend exciting new perspectives of this burgeoning field. This review also summarizes recent representative applications of polymer gels with excellent mechanical properties. Conclusions and perspectives are also provided from five aspects of concise summary, mechanical mechanism, biofabrication methods, upgraded applications, and synergistic methodology.
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Marine microorganisms like Tistrella are essential for producing bioactive compounds, including didemnins with antitumor and antiviral properties. However, our understanding of Tistrella's ecological features and didemnin production in natural environments is limited. In this study, we used genomics and metagenomics to show that Tistrella is widely distributed across natural habitats, especially in marine environments from the surface to 5000 m deep, with distinct non-random distribution patterns revealed by co-occurrence analysis. Importantly, transcriptional profiling of didemnin biosynthetic gene clusters indicates active in situ production of this compound within marine ecosystems. These findings enhance our understanding of Tistrella's ecology and secondary metabolite production in natural environments. Further research is needed to explore the ecological dynamics and functional impacts of Tistrella in these ecosystems.
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Ecossistema , Microbiota , Organismos Aquáticos , Metagenômica , Água do Mar/microbiologia , Água do Mar/químicaRESUMO
Didemnins are a class of cyclic depsipeptides derived from sea tunicates that exhibit potent anticancer, antiviral, and immunosuppressive properties. Although certain Tistrella species can produce didemnins, their complete biosynthetic potential remains largely unexplored. In this study, we utilize feature-based molecular networking to analyze the metabolomics of Tistrella mobilis and Tistrella bauzanensis, focusing on the production of didemnin natural products. In addition to didemnin B, we identify nordidemnin B and [hysp2]didemnin B, as well as several minor didemnin analogs. Heterologous expression of the didemnin biosynthetic gene cluster in a Streptomyces host results in the production of only didemnin B and nordidemnin B in limited quantities. Isotope-labeling studies reveal that the substrate promiscuity of the adenylation domains during biosynthesis leads to the accumulation of nordidemnin B and [hysp2]didemnin B. Additionally, precursor-directed biosynthesis is applied to generate eight novel didemnin derivatives by supplementing the culture with structurally related amino acids. Furthermore, we increased the titers of nordidemnin B and [hysp2]didemnin B by supplementing the fermentation medium with l-valine and l-isoleucine, respectively. Finally, both compounds undergo side-chain oxidation to enhance their biological activity, with their anticancer properties found to be as potent as plitidepsin.
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Antineoplásicos , Depsipeptídeos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Depsipeptídeos/biossíntese , Depsipeptídeos/química , Depsipeptídeos/farmacologia , Depsipeptídeos/metabolismo , Humanos , Animais , Família Multigênica , Streptomyces/metabolismo , Streptomyces/genética , Urocordados/metabolismo , Linhagem Celular Tumoral , Vias Biossintéticas , Produtos Biológicos/metabolismo , Produtos Biológicos/química , Produtos Biológicos/farmacologiaRESUMO
Cuticle proteins (CPs) are the vital components of the cuticle and chitin lining covering the digestive tract of crustaceans. In this study, four new CP genes (designated as EsCP3, EsCP4, EsCP5, and EsCP8) were initially cloned and identified from the Chinese mitten crab Eriocheir sinensis. EsCP3/4/5/8 included 375, 411, 381, and 570 bp open reading frame encoding 124, 136, 126, and 189 amino acid proteins, respectively. Except for EsCP8, EsCP3/4/5 all contained a Chitin_bind_4 domain. EsCP3/4/5/8 were clustered into different groups in the phylogenetic tree. Quantitative real-time PCR results indicated that four EsCP genes have different patterns of tissue distribution. Changes in the expression levels of these four EsCP genes were observed in the intestine of crabs under Vibrio parahaemolyticus challenge. RNA interference assay showed that the knockdown of EsCPs in the intestine could inhibit the expression of antimicrobial peptides (AMPs), including crustins and anti-lipopolysaccharide factors. In addition, the knockdown of EsRelish in the intestine decreased the expression levels of these four EsCP genes. These results indicated that EsCPs were involved in regulating the expression of AMPs, and EsCPs were regulated by EsRelish.
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Proteínas de Artrópodes , Braquiúros , Regulação da Expressão Gênica , Vibrio parahaemolyticus , Animais , Sequência de Aminoácidos , Peptídeos Antimicrobianos/genética , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/imunologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/química , Sequência de Bases , Braquiúros/genética , Braquiúros/imunologia , Braquiúros/microbiologia , Clonagem Molecular , DNA Complementar/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Filogenia , Alinhamento de Sequência/veterinária , Vibrio parahaemolyticus/fisiologiaRESUMO
Understanding the factors that drive PM2.5 concentrations in cities with varying population and land areas is crucial for promoting sustainable urban population health. This knowledge is particularly important for countries where air pollution is a significant challenge. Most existing studies have investigated either anthropogenic or environmental factors in isolation, often in limited geographic contexts; however, this study fills this knowledge gap. We employed a multimethodological approach, using both multiple linear regression models and geographically weighted regression (GWR), to assess the combined and individual effects of these factors across different cities in China. The variables considered were urban built-up area, land consumption rate (LCR), population size, population growth rate (PGR), longitude, and latitude. Compared with other studies, this study provides a more comprehensive understanding of PM2.5 drivers. The findings of this study showed that PGR and population size are key factors affecting PM2.5 concentrations in smaller cities. In addition, the extent of urban built-up areas exerts significant influence in medium and large cities. Latitude was found to be a positive predictor for PM2.5 concentrations across all city sizes. Interestingly, the northeast, south, and southwest regions demonstrated lower PM2.5 levels than the central, east, north, and northwest regions. The GWR model underscored the importance of considering spatial heterogeneity in policy interventions. However, this research is not without limitations. For instance, international pollution transfers were not considered. Despite the limitation, this study advances the existing literature by providing an understanding of how both anthropogenic and environmental factors, in conjunction with city scale, shape PM2.5 concentrations. This integrated approach offers invaluable insights for tailoring more effective air pollution management strategies across cities of different sizes and characteristics.
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PURPOSE OF REVIEW: There are significant differences in the transmission rate and mortality rate of COVID-19 under environmental conditions such as seasons and climates. However, the impact of environmental factors on the role of the COVID-19 pandemic and the transmission mechanism of the SARS-CoV-2 is unclear. Therefore, a comprehensive understanding of the impact of environmental factors on COVID-19 can provide innovative insights for global epidemic prevention and control policies and COVID-19 related research. This review summarizes the evidence of the impact of different natural and social environmental factors on the transmission of COVID-19 through a comprehensive analysis of epidemiology and mechanism research. This will provide innovative inspiration for global epidemic prevention and control policies and provide reference for similar infectious diseases that may emerge in the future. RECENT FINDINGS: Evidence reveals mechanisms by which natural environmental factors influence the transmission of COVID-19, including (i) virus survival and transport, (ii) immune system damage, (iii) inflammation, oxidative stress, and cell death, and (iiii) increasing risk of complications. All of these measures appear to be effective in controlling the spread or mortality of COVID-19: (1) reducing air pollution levels, (2) rational use of ozone disinfection and medical ozone therapy, (3) rational exposure to sunlight, (4) scientific ventilation and maintenance of indoor temperature and humidity, (5) control of population density, and (6) control of population movement. Our review indicates that with the continuous mutation of SARS-CoV-2, high temperature, high humidity, low air pollution levels, and low population density more likely to slow down the spread of the virus.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/transmissão , COVID-19/prevenção & controle , Humanos , Poluição do Ar/efeitos adversos , PandemiasRESUMO
BACKGROUND: Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear. METHODS: A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35-0.60) and PFS (0.49, 95% CI, 0.35-0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%). CONCLUSIONS: The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone. TRIAL REGISTRATION: International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).
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Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de ProgressãoRESUMO
To evaluate the efficacy of the 18F-AlF-NOTA-RGD2 positron emission tomography (PET)/computed tomography (CT) molecular probe for the noninvasive staging of liver fibrosis in mini pigs, a potential alternative to invasive diagnostic methods was revealed. This study used 18F-AlF-NOTA-RGD2 PET/CT imaging of mini pigs to assess liver fibrosis. The methods included synthesis and quality control of the molecular probe, establishment of an animal model of liver fibrosis, blood serum enzymatic tests, histopathological examination, PET/CT imaging, collagen content and expression, and mitochondrial reserve function assessment. The 18F-AlF-NOTA-RGD2 PET/CT molecular probe effectively differentiated various stages of liver fibrosis in mini pigs. Blood serum enzymatic tests revealed distinct stages of liver fibrosis, revealing significant increases in AST, ALT, TBIL, and DBIL levels as fibrosis advanced. Notably, ALT levels increased markedly in severe fibrosis patients. A gradual increase in collagen deposition and increasing α-SMA RNA expression and protein levels effectively differentiated between mild and severe fibrosis stages. Pathological examinations and Sirius Red staining confirmed these findings, highlighting substantial increases in collagen accumulation. PET/CT imaging results aligned with histopathological findings, showing that increased radiotracer uptake correlated with fibrosis severity. Assessments of mitochondrial function revealed a decrease in total liver glutathione content and mitochondrial reserve capacity, especially in patients with severe fibrosis. The 18F-AlF-NOTA-RGD2 PET/CT molecular probe is a promising tool for the noninvasive assessment of liver fibrosis, offering potential benefits over traditional diagnostic methods in hepatology.
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BACKGROUND AND AIM: There is a pressing need for non-invasive preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This study investigates the potential of exosome-derived mRNA in plasma as a biomarker for diagnosing MVI. METHODS: Patients with suspected HCC undergoing hepatectomy were prospectively recruited for preoperative peripheral blood collection. Exosomal RNA profiling was conducted using RNA sequencing in the discovery cohort, followed by differential expression analysis to identify candidate targets. We employed multiplexed droplet digital PCR technology to efficiently validate them in a larger sample size cohort. RESULTS: A total of 131 HCC patients were ultimately enrolled, with 37 in the discovery cohort and 94 in the validation cohort. In the validation cohort, the expression levels of RSAD2, PRPSAP1, and HOXA2 were slightly elevated while CHMP4A showed a slight decrease in patients with MVI compared with those without MVI. These trends were consistent with the findings in the discovery cohort, although they did not reach statistical significance (P > 0.05). Notably, the expression level of exosomal PRPSAP1 in plasma was significantly higher in patients with more than 5 MVI than in those without MVI (0.147 vs 0.070, P = 0.035). CONCLUSION: This study unveils the potential of exosome-derived PRPSAP1 in plasma as a promising indicator for predicting MVI status preoperatively.
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Biomarcadores Tumorais , Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , Invasividade Neoplásica , RNA Mensageiro , Humanos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Exossomos/genética , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , RNA Mensageiro/sangue , Microvasos/patologia , Idoso , Valor Preditivo dos Testes , Estudos Prospectivos , HepatectomiaRESUMO
The microbial synthesis of sulfonolipids within the human body is likely involved in maintaining human health or causing diseases. However, the enzymes responsible for their biosynthesis remain largely unknown. In this study, we identified and verified the role of 3-ketocapnine reductase, the third-step enzyme, in the four-step conversion of l-phosphoserine into sulfobacin B both in vivo and in vitro. This finding builds upon our previous research into sulfonolipid biosynthesis, which focused on the vaginal bacterium Chryseobacterium gleum DSM 16776 and the gut bacterium Alistipes finegoldii DSM 17242. Through comprehensive gene mapping, we demonstrate the widespread presence of potential sulfonolipid biosynthetic genes across diverse bacterial species inhabiting various regions of the human body. These findings shed light on the prevalence of sulfonolipid-like metabolites within the human microbiota, suggesting a potential role for these lipid molecules in influencing the intricate biointeractions within the complex microbial ecosystem of the human body.
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The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.
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Galinhas , Infecções por Coronavirus , Vírus da Bronquite Infecciosa , Doenças das Aves Domésticas , Vírus da Bronquite Infecciosa/genética , Vírus da Bronquite Infecciosa/patogenicidade , Vírus da Bronquite Infecciosa/fisiologia , Animais , Glicosilação , Doenças das Aves Domésticas/virologia , Virulência , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Replicação Viral , Substituição de AminoácidosRESUMO
This review delves into the burgeoning field of explainable artificial intelligence (XAI) in the detection and analysis of lung diseases through vocal biomarkers. Lung diseases, often elusive in their early stages, pose a significant public health challenge. Recent advancements in AI have ushered in innovative methods for early detection, yet the black-box nature of many AI models limits their clinical applicability. XAI emerges as a pivotal tool, enhancing transparency and interpretability in AI-driven diagnostics. This review synthesizes current research on the application of XAI in analyzing vocal biomarkers for lung diseases, highlighting how these techniques elucidate the connections between specific vocal features and lung pathology. We critically examine the methodologies employed, the types of lung diseases studied, and the performance of various XAI models. The potential for XAI to aid in early detection, monitor disease progression, and personalize treatment strategies in pulmonary medicine is emphasized. Furthermore, this review identifies current challenges, including data heterogeneity and model generalizability, and proposes future directions for research. By offering a comprehensive analysis of explainable AI features in the context of lung disease detection, this review aims to bridge the gap between advanced computational approaches and clinical practice, paving the way for more transparent, reliable, and effective diagnostic tools.
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Inteligência Artificial , Biomarcadores , Pneumopatias , Humanos , Pneumopatias/diagnóstico , Biomarcadores/metabolismoRESUMO
Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 µg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.
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Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/química , Humanos , Família Multigênica , Camundongos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/genética , Peptídeos Antimicrobianos/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Genoma Bacteriano/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Biologia Computacional/métodos , Cisteína/metabolismo , Cisteína/químicaRESUMO
Rabies is a zoonotic infection with the potential to infect all mammals and poses a significant threat to mortality. Although enzyme-linked immunosorbent tests and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) have been established for rabies virus (RABV) detection, they require skilled staff. Here, we introduce a personal glucose meter (PGM)-based nucleic acid (NA-PGM) detection method to diagnose RABV. This method ensures sensitive and convenient RABV diagnosis through hybridization of reverse transcription-recombinase aided amplification (RT-RAA) amplicons with probes labeled with sucrose-converting enzymes, reaching a detection level as low as 6.3 copies/µL equivalent to 12.26 copies. NA-PGM allows for the differentiation of RABV from other closely related viruses. In addition, NA-PGM showed excellent performance on 65 clinical samples with a 100% accuracy rate compared with the widely adopted RT-qPCR method. Thus, our developed NA-PGM method stands out as sensitive, semiquantitative, and portable for RABV detection, showcasing promise as a versatile platform for a wide range of pathogens.
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The rapid emergence of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) variants, coupled with severe immune evasion and imprinting, has jeopardized the vaccine efficacy, necessitating urgent development of broad protective vaccines. Here, we propose a strategy employing recombinant rabies viruses (RABV) to create a universal SARS-CoV-2 vaccine expressing heterologous tandem receptor-binding domain (RBD) trimer from the SARS-CoV-2 Prototype, Delta, and Omicron strains (SRV-PDO). The results of mouse immunization indicated that SRV-PDO effectively induced cellular and humoral immune responses, and demonstrated higher immunogenicity and broader SARS-CoV-2 neutralization compared to the recombinant RABVs that only expressed RBD monomers. Moreover, SRV-PDO exhibited full protection against SARS-CoV-2 in the challenge assay. This study demonstrates that recombinant RABV expressing tandem RBD-heterotrimer as a multivalent immunogen could elicit a broad-spectrum immune response and potent protection against SARS-CoV-2, making it a promising candidate for future human or veterinary vaccines and offering a novel perspective in other vaccine design.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Camundongos Endogâmicos BALB C , Vírus da Raiva , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Animais , Vírus da Raiva/imunologia , Vírus da Raiva/genética , Vacinas contra COVID-19/imunologia , Camundongos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/prevenção & controle , COVID-19/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Feminino , Humanos , Imunidade Humoral , Vetores Genéticos , Eficácia de Vacinas , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/administração & dosagemRESUMO
Research on the chemoselective metal-catalyzed hydrogenation of conjugated π-systems has mostly been focussed on enones. Herein, we communicate the understudied asymmetric hydrogenation of enimines catalyzed by N,P-iridium complexes and chemoselective toward the alkene. A number of enoxime ethers underwent hydrogenation smoothly to yield the desired products in high yield and stereopurity (up to 99 % yield, up to 99 % ee). No hydrogenation of the C=N π-bond was observed under the applied reaction conditions (20â bar H2, rt, DCM). It was demonstrated that the chiral oxime ether could be hydrolyzed into the ketone with complete preservation of the installed stereogenity at the α-carbon. At last, a binding mode of the substrate to the active iridium catalyst and the consequence for the stereoselective outcome was proposed.
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Methanotrophs of the genus Methylocystis are frequently found in rice paddies. Although more than ten facultative methanotrophs have been reported since 2005, none of these strains was isolated from paddy soil. Here, a facultative methane-oxidizing bacterium, Methylocystis iwaonis SD4, was isolated and characterized from rhizosphere samples of rice plants in Nanjing, China. This strain grew well on methane or methanol but was able to grow slowly using acetate or ethanol. Moreover, strain SD4 showed sustained growth at low concentrations of methane (100 and 500 ppmv). M. iwaonis SD4 could utilize diverse nitrogen sources, including nitrate, urea, ammonium as well as dinitrogen. Strain SD4 possessed genes encoding both the particulate methane monooxygenase and the soluble methane monooxygenase. Simple and rapid genetic manipulation methods were established for this strain, enabling vector transformation and unmarked genetic manipulation. Fast growth rate and efficient genetic tools make M. iwaonis SD4 an ideal model to study facultative methanotrophs, and the ability to grow on low concentration of methane implies its potential in methane removal.
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Metano , Methylocystaceae , Oryza , Rizosfera , Microbiologia do Solo , Oryza/microbiologia , Methylocystaceae/genética , Methylocystaceae/metabolismo , Methylocystaceae/isolamento & purificação , Metano/metabolismo , Oxigenases/genética , Oxigenases/metabolismo , China , Metanol/metabolismoRESUMO
Nanotechnology has emerged as a transformative force in modern agriculture, offering innovative solutions to address challenges related to fungal plant diseases and overall agricultural productivity. Specifically, the antifungal activities of metal, metal oxide, bio-nanoparticles, and polymer nanoparticles were examined, highlighting their unique mechanisms of action against fungal pathogens. Nanoparticles can be used as carriers for fungicides, offering advantages in controlled release, targeted delivery, and reduced environmental toxicity. Nano-pesticides and nano-fertilizers can enhance nutrient uptake, plant health, and disease resistance were explored. The development of nanosensors, especially those utilizing quantum dots and plasmonic nanoparticles, promises early and accurate detection of fungal pathogens, a crucial step in timely disease management. However, concerns about their potential toxic effects on non-target organisms, environmental impacts, and regulatory hurdles underscore the importance of rigorous research and impact assessments. The review concludes by emphasizing the significant prospects of nanotechnology in reshaping the future of agriculture but advocates for a balanced approach that prioritizes safety, sustainability, and environmental stewardship.