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Ventilator-associated pneumonia (VAP) and pyogenic liver abscess (PLA) due to Klebsiella pneumoniae infection can trigger life-threatening malignant consequences, however, there are few studies on the strain-associated clinical pathogenic mechanisms between VAP and PLA. A total of 266 patients consist of 129 VAP and 137 PLA were included for analysis in this study. We conducted a comprehensive survey for the two groups of K. pneumoniae isolates, including phenotypic experiments, clinical epidemiology, genomic analysis, and instrumental analysis, i.e., to obtain the genomic differential profile of K. pneumoniae strains responsible for two distinct infection outcomes. We found that PLA group had a propensity for specific underlying diseases, especially diabetes and cholelithiasis. The resistance level of VAP was significantly higher than that of PLA (78.57% vs. 36%, P < 0.001), while the virulence results were opposite. There were also some differences in key signaling pathways of biochemical processes between the two groups. The combination of iucA, rmpA, hypermucoviscous phenotype, and ST23 presented in K. pneumoniae infection is more important and highly prudent for timely treatment. The present study may contribute a benchmark for the K. pneumoniae clinical screening, epidemiological surveillance, and effective therapeutic strategies.
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Infecções por Klebsiella , Abscesso Hepático , Pneumonia Associada à Ventilação Mecânica , Humanos , Klebsiella pneumoniae , Fatores de Virulência/genética , Tipagem de Sequências Multilocus , Fenótipo , Infecções por Klebsiella/epidemiologiaRESUMO
BACKGROUND: The data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. This study aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/ALC/B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). RESULTS: Overall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates. CONCLUSIONS: MUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/classificação , Infecções Estafilocócicas/epidemiologia , Técnicas de Tipagem Bacteriana , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , China/epidemiologia , DNA Bacteriano/genética , Diterpenos/farmacologia , Eletroforese em Gel de Campo Pulsado , Ácido Fusídico/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Mupirocina/farmacologia , Mutação , Prevalência , Análise de Sequência de DNARESUMO
BACKGROUND: It has been reported that infectious agents contribute to the atherosclerotic process. However, it is unclear whether Staphylococcus aureus superantigen (SAg) toxic shock syndrome toxin-1 (TSST-1) has an effect on atherosclerosis progression. The present study was designed to investigate the pathogenic role of TSST-1 exposure in the atherosclerotic process in rabbits. METHODS: New Zealand White rabbits were exposed to TSST-1 through Alzet miniosmotic pumps with a constant pumping rate. Aortic atherosclerosis was evaluated by histological and morphometric methods. Using a biochemical analyzer/enzyme-linked immunosorbent assay/immunostaining, we further analyzed various atherosclerosis-related factors. RESULTS: The gross atherosclerotic lesion area in the aortic arch increased by 15.3% in high-fat-diet rabbits exposed to TSST-1 compared to that in the control group. In the atherosclerotic lesions, TSST-1 exposure increased the content of smooth muscle cells. Moreover, TSST-1 treatment up-regulated serum tumor necrosis factor alpha (TNF-α) level, but did not affect serum lipids (except for triglycerides) and endotoxin in the rabbits. CONCLUSIONS: Our data validated that chronic stimulation with TSST-1 facilitates the progression of atherosclerosis in rabbits independently of endotoxins, indicating that S. aureus and its SAgs may be targets to prevent and treat atherosclerosis.
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We have entered the post-antibiotic era. Phage therapy has recently been given renewed attention because bacteriophages are easily available and can kill bacteria. Many reports have demonstrated successful phage treatment of bacterial infection, whereas some studies have shown that phage therapy is not as effective as expected. In general, establishment of a standard operating procedure will ensure the success of phage therapy. In this paper, the whole operating procedure for phage therapy in clinical practice is explored and analyzed to comprehensively understand the success of using phage for the treatment of bacterial infectious disease in the future. The procedure includes the following: enrollment of patients for phage therapy; establishment of phage libraries; pathogenic bacterial isolation and identification; screening for effective phages against pathogenic bacteria; phage formulation preparation; phage preparation administration strategy and route; monitoring the efficacy of phage therapy; and detection of the emergence of phage-resistant strains. Finally, we outline the whole standard operating procedure for phage therapy in clinical practice. It is believed that phage therapy will be used successfully, especially in personalized medicine for the treatment of bacterial infectious diseases. Hopefully, this procedure will provide support for the entry of phage therapy into the clinic as soon as possible.
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Terapia por Fagos/normas , Padrões de Prática Médica/normas , Bactérias/isolamento & purificação , Bactérias/virologia , Humanos , Biblioteca de Peptídeos , Resultado do TratamentoRESUMO
Staphylococcus aureus is the main pathogen that causes skin and skin structure infections and is able to survive and persist in keratinocytes of the epidermis. Since the evolution of multidrug-resistant bacteria, the use of phages and their lysins has presented a promising alternative approach to treatment. In this study, a cell wall hydrolase (also called lysin) derived from Staphylococcus phage JD007 (JDlys) was identified. JDlys showed strong lytic activity against methicillin-resistant Staphylococcus aureus (MRSA) strains from different sources and of different multilocus sequence typing (MLST) types. Furthermore, a fusion protein consisting of a cell-penetrating peptide derived from the trans-activating transcription (Tat) factor fused to JDlys (CPPTat-JDlys) was used to kill MRSA bacteria causing intracellular infections. CPPTat-JDlys, in which the fusion of CPPTat to JDlys had almost no effect on the bacteriolytic activity of JDlys, was able to effectively eliminate intracellular MRSA bacteria and alleviate the inflammatory response and cell damage caused by MRSA. Specifically, CPPTat-JDlys was able to combat MRSA-induced murine skin infections and, consequently, expedite the healing of cutaneous abscesses. These data suggest that the novel antimicrobial CPP-JDlys may be a worthwhile candidate as a treatment for skin and skin structure infections caused by MRSA.IMPORTANCES. aureus is the main cause of skin and skin structure infections due to its ability to invade and survive in the epithelial barrier. Due to the overuse of antibiotics in humans and animals, S. aureus has shown a high capacity for acquiring and accumulating mechanisms of resistance to antibiotics. Moreover, most antibiotics are usually limited in their ability to overcome the intracellular persistence of bacteria causing skin and skin structure infections. So, it is critical to seek a novel antimicrobial agent to eradicate intracellular S. aureus In this study, a cell-penetrating peptide fused to lysin (CPP-JDlys) was engineered. Our results show that CPP-JDlys can enter keratinocytes and effectively eliminate intracellular MRSA. Meanwhile, experiments with mice revealed that CPP-JDlys efficiently inhibits the proliferation of MRSA in murine skin and thus shortens the course of wound healing. Our results indicate that the CPP-fused lysin has potential for use for the treatment of skin infections caused by MRSA.
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Peptídeos Penetradores de Células/farmacologia , Hidrolases/farmacologia , Queratinócitos/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Tipagem de Sequências Multilocus , Dermatopatias Bacterianas/tratamento farmacológico , Fagos de Staphylococcus/enzimologia , Fagos de Staphylococcus/genéticaRESUMO
BACKGROUND: The aim of the study was to establish reference intervals for 24-h urinary stone risk factors in the healthy Chinese Han population. METHODS: From May 2013 to July 2014, we collected and analyzed 24-h urine samples from healthy adult Han population during a cross-sectional study across China. The protocol for analysis of 24-h urine included volume, pH, oxalate, citrate, sodium, potassium, chloride, calcium, phosphorous, creatinine, urate, magnesium, the ion activity products of calcium oxalate (AP(CaOx) indexs) and calcium phosphate (AP(CaP) indexs). We calculated the reference intervals according to the Clinical and Laboratory Standards Institute (CLSI) 2008 guidelines and compared them with those recorded in other studies. RESULTS: A total of 132 male and 123 female healthy subjects with a mean (SD, range) age of 52.4 (15.2, 19-89) years were eligible in the final analysis. Men had higher 24-h excretion of creatinine, calcium, urate and phosphorus and lower levels of citrate, magnesium, chloride, sodium and potassium than women. AP(CaOx) indexs and AP(CaP) indexs were significantly higher among men than women. When urinary findings were compared with the reference intervals, most of our data showed a high abnormality rate, especially for creatinine, calcium, citrate, magnesium, chloride, sodium and potassium. CONCLUSIONS: The present study revealed the normal metabolic status for stone risk factors of the Chinese Han population. It is therefore necessary for each country or region to define their own reference intervals for comparison of stone risk factors between patients and healthy subjects.
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Povo Asiático , Etnicidade , Cálculos Urinários/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: The implementation of phage therapy is re-emerging with the increase in widespread antibiotic-resistant bacteria. METHODS: Staphylococcus phage JD007 was characterized and its complete genome sequence analysed. RESULTS: Staphylococcus phage JD007 was classified as belonging to the Myoviridae family based on its morphology, as observed by transmission electron microscopy. Its lytic activity was stable between pH 5-11 and below 42 °C; moreover, an absorbance curve showed that nearly 90% of the viral particles had adsorbed to its host after a 20 min co-incubation. The complete genome size is 141,836 bp, making JD007 one of the largest Staphylococcus phages of Myoviridae. No identifiable resistance or virulence genes were found in the JD007 genome. JD007 was able to lyse 95% of S. aureus isolates, including the prevalent ST239-MRSA and ST59-MRSA strains isolated from different hospitals in Shanghai, China, and inhibition assays showed that JD007 could inhibit S. aureus growth at a multiplicity of infection of 0.1. CONCLUSIONS: The results suggested that Staphylococcus phage JD007 can potentially be used in phage therapy or for the detection of S. aureus.
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Genoma Viral , Especificidade de Hospedeiro , Myoviridae/genética , Myoviridae/fisiologia , Fagos de Staphylococcus/genética , Fagos de Staphylococcus/fisiologia , Staphylococcus aureus/virologia , China , Infecção Hospitalar/microbiologia , DNA Viral/química , DNA Viral/genética , Humanos , Concentração de Íons de Hidrogênio , Viabilidade Microbiana/efeitos dos fármacos , Viabilidade Microbiana/efeitos da radiação , Microscopia Eletrônica de Transmissão , Myoviridae/classificação , Myoviridae/isolamento & purificação , Análise de Sequência de DNA , Infecções Estafilocócicas/microbiologia , Fagos de Staphylococcus/classificação , Fagos de Staphylococcus/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Temperatura , Vírion/ultraestruturaRESUMO
OBJECTIVES: To investigate the prevalence and associated factors of kidney stones among adults in China. SUBJECTS AND METHODS: A nationwide cross-sectional survey was conducted among individuals aged ≥18 years across China, from May 2013 to July 2014. Participants underwent urinary tract ultrasonographic examinations, completed pre-designed and standardised questionnaires, and provided blood and urine samples for analysis. Kidney stones were defined as particles of ≥4 mm. Prevalence was defined as the proportion of participants with kidney stones and binary logistic regression was used to estimate the associated factors. RESULTS: A total of 12 570 individuals (45.2% men) with a mean (sd, range) age of 48.8 (15.3, 18-96) years were selected and invited to participate in the study. In all, 9310 (40.7% men) participants completed the investigation, with a response rate of 74.1%. The prevalence of kidney stones was 6.4% [95% confidence interval (CI) 5.9, 6.9], and the age- and sex-adjusted prevalence was 5.8% (95% CI 5.3, 6.3; 6.5% in men and 5.1% in women). Binary logistic regression analysis showed that male gender, rural residency, age, family history of urinary stones, concurrent diabetes mellitus and hyperuricaemia, increased consumption of meat, and excessive sweating were all statistically significantly associated with a greater risk of kidney stones. By contrast, consumption of more tea, legumes, and fermented vinegar was statistically significantly associated with a lesser risk of kidney stone formation. CONCLUSION: Kidney stones are common among Chinese adults, with about one in 17 adults affected currently. Some Chinese dietary habits may lower the risk of kidney stone formation.
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Dieta/efeitos adversos , Cálculos Renais/diagnóstico por imagem , Ultrassonografia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos Epidemiológicos , Humanos , Cálculos Renais/epidemiologia , Cálculos Renais/prevenção & controle , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
A novel lytic Vibrio parahaemolyticus phage (SHOU24) belonging to the family Siphoviridae was isolated from aquatic market sewage. The phage is only able to infect V. parahaemolyticus containing a tdh gene. SHOU24 has a linear genome of 77,837 bp with a G+C content of 46.0 %. In total, 88 predicted proteins have homologues in databases, and the majority of the core genes share high sequence similarity with genes from unrelated viruses and bacteria. Genes related to lysogeny and host lysis were not detected. However, the detection method, the results of a one-step growth experiment and analysis using the Phage Classification Tool Set (PHACTS) indicate that SHOU24 is lytic. A bioinformatics analysis showed that SHOU24 is not closely related to other Vibrio phages.
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Bacteriófagos/genética , Siphoviridae/genética , Vibrio parahaemolyticus/virologia , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificação , Bacteriófagos/patogenicidade , Sequência de Bases , Genoma Viral , Dados de Sequência Molecular , Esgotos/virologia , Siphoviridae/classificação , Siphoviridae/isolamento & purificação , Siphoviridae/patogenicidade , VirulênciaAssuntos
Exossomos/imunologia , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Imunoglobulina E/imunologia , Mastócitos/imunologia , Receptores de IgE/imunologia , Animais , Exossomos/genética , Exossomos/patologia , Feminino , Hipersensibilidade/genética , Hipersensibilidade/patologia , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Receptores de IgE/genéticaRESUMO
The appropriate degradation characteristics of polydioxanone (PDO) are necessary for the safety and effectiveness of stents. This study aimed to investigate the degradation of PDO weaving tracheal stents (PW stents)in vitroandin vivo. The degradation solution ofS. aureus(SAU),E. coli(ECO),P. aeruginosa(PAE), and control (N) were prepared, and the PW stents were immersed for 12 weeks. Then, the radial support force, weight retention, pH, molecular structure, thermal performance, and morphology were determined. Furthermore, the PW stents were implanted into the abdominal cavity of rabbits, and omentum was embedded. At feeding for 16 weeks, the mechanical properties, and morphology were measured. During the first 8 weeks, the radial support force in all groups was progressively decreased. At week 2, the decline rate of radial support force in the experimental groups was significantly faster compared to the N group, and the difference was narrowed thereafter. The infrared spectrum showed that during the whole degradation process, SAU, ECO and PAE solution did not lead to the formation of new functional groups in PW stents.In vitroscanning electron microscope observation showed that SAU and ECO were more likely to gather and multiply at the weaving points of the PW stents, forming colonies.In vivoexperiments showed that the degradation in the concavity of weaving points of PW stents was more rapid and severe. The radial support loss rate reached more than 70% at week 4, and the radial support force was no longer measurable after week 8. In omentum, multinuclear giant cells and foreign giant cells were found to infiltrate. PW stents have good biocompatibility. The degradation rate of PW stents in the aseptic conditionsin vivowas faster than in the bacteriological environmentin vitro.
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Teste de Materiais , Polidioxanona , Stents , Traqueia , Animais , Polidioxanona/química , Coelhos , Materiais Biocompatíveis/química , Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , Concentração de Íons de Hidrogênio , OmentoRESUMO
Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.
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Klebsiella pneumoniae is a member of the family Enterobacteriaceae, opportunistic pathogens that are among the eight most prevalent infectious agents in hospitals. The emergence of multidrug-resistant strains of K. pneumoniae has became a public health problem globally. To develop an effective antimicrobial agent, we isolated a bacteriophage, named JD001, from seawater and sequenced its genome. Comparative genome analysis of phage JD001 with other K. pneumoniae bacteriophages revealed that phage JD001 has little similarity to previously published K. pneumoniae phages KP15, KP32, KP34, and phiKO2. Here we announce the complete genome sequence of JD001 and report major findings from the genomic analysis.
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Bacteriófagos/genética , Genoma Viral , Klebsiella pneumoniae/virologia , Dados de Sequência Molecular , Fases de Leitura AbertaRESUMO
Methicillin-resistant Staphylococcus aureus-related infections have become a serious problem worldwide. Bacteriophage therapy is an alternative approach against this threat. S. aureus phage JD007, which belongs to the Myoviridae family according to transmission electron microscopic imaging, could lyse nearly 30% of the S. aureus strains from Ruijin Hospital, Shanghai, China, and was isolated from chicken feces in Shanghai, China. The complete genome showed that JD007 is a linear, double-stranded DNA phage 141,836 bp in length with a GC content of 30.4% encoding 217 open reading frames. A BLAST search of the JD007 genome revealed that it was very similar to that of phage GH15.
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Genoma Viral , Fagos de Staphylococcus/genética , Staphylococcus aureus/virologia , DNA Viral/genética , Dados de Sequência MolecularRESUMO
Community-acquired pneumonia (CAP) is a major concern in hospitals and the bacterial community of which has not been systemically discussed yet. Sputum from patients in the acute stages is a kind of accessible sample reflecting its features. In our study, we analyzed 45 sputum samples from 45 patients with CAP. Eighteen sputum samples from healthy people were chosen as the controls. Pyrosequencing of the 16s rDNA V3 hypervariable regions of all the bacteria contained in the sputum was used as a culture-independent method to disclose the community constitution. Also, our published data for hospital-acquired pneumonia (HAP) in sputum was used for comparison. By pyrosequencing, >90,000 DNA reads were detected. After being analyzed by tools in the Ribosomal Database Project, the reads were classified into five main phyla and >100 genera. At the phyla level, the reads' distribution of CAP is similar to that of healthy people and at genera level, the occurrence of each genus possesses their feature in three categories. Genera such as Streptococcus and Neisseria showed stability in their percentages, indicating that such genera are rarely affected by exogenous bacteria or antibiotics. The role of other genera such as Moraxella and Rothia in CAP should be emphasized. According to our analysis, the bacterial communities of CAP are with slight change when compared with those of healthy people, but have a large gap between HAP. Meanwhile, Rothia might be an important endogenous pneumonia-causing factor.
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Infecções Comunitárias Adquiridas/microbiologia , Microbiota/genética , Pneumonia/microbiologia , Escarro/microbiologia , Adulto , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Análise por Conglomerados , Infecção Hospitalar/microbiologia , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying the initiation, propagation, and ultimate execution of cuproptosis in tumors remain unknown. Here, we show that copper content is significantly elevated in gastric cancer (GC), especially in malignant tumors. Screening reveals that METTL16, an atypical methyltransferase, is a critical mediator of cuproptosis through the m6A modification on FDX1 mRNA. Furthermore, copper stress promotes METTL16 lactylation at site K229 followed by cuproptosis. The process of METTL16 lactylation is inhibited by SIRT2. Elevated METTL16 lactylation significantly improves the therapeutic efficacy of the copper ionophore- elesclomol. Combining elesclomol with AGK2, a SIRT2-specific inhibitor, induce cuproptosis in gastric tumors in vitro and in vivo. These results reveal the significance of non-histone protein METTL16 lactylation on cuproptosis in tumors. Given the high copper and lactate concentrations in GC, cuproptosis induction becomes a promising therapeutic strategy for GC.
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Apoptose , Neoplasias Gástricas , Humanos , Cobre , Ácido Láctico , Metiltransferases/genética , RNA Mensageiro/genética , Sirtuína 2 , Neoplasias Gástricas/genéticaRESUMO
Enriched environment (EE) is an important animal experimental paradigm to decipher gene-environment interaction. It is thought to be efficient in aiding recovery from certain metabolism disorders or cognitive impairments. Recently, the effects of EE during adolescence in mice gradually draw much attention. We first established an EE model in adolescent mice, dissected lipid metabolism, and further examined baseline level of anxiety and depression by multiple behavioral tests, including open field test (OFT), elevated zero maze (EZM), tail suspension test (TST), and forced swimming test (FST). EE mice exhibited lower weights, lower cholesterol than standard housing (SH) mice. Behaviorally, EE mice traveled more distance and had higher velocity than SH mice in OFT and EZM. Besides, EE mice showed reduced anxiety levels in OFT and EZM. Furthermore, EE mice also had less immobility time than SH mice in TST and FST. Thus, these results suggest that EE during adolescence has metabolic and behavioral benefits in mice.
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Ansiedade , Metabolismo dos Lipídeos , Animais , Camundongos , Ansiedade/metabolismo , Ansiedade/psicologia , Natação , Comportamento AnimalRESUMO
BACKGROUND: An increasing number of studies have implicated the microbiome in certain diseases, especially chronic diseases. In this study, the bacterial communities in the sputum of pulmonary tuberculosis patients were explored. Total DNA was extracted from sputum samples from 31 pulmonary tuberculosis patients and respiratory secretions of 24 healthy participants. The 16S rRNA V3 hyper-variable regions were amplified using bar-coded primers and pyro-sequenced using Roche 454 FLX. RESULTS: The results showed that the microbiota in the sputum of pulmonary tuberculosis patients were more diverse than those of healthy participants (p<0.05). The sequences were classified into 24 phyla, all of which were found in pulmonary tuberculosis patients and 17 of which were found in healthy participants. Furthermore, many foreign bacteria, such as Stenotrophomonas, Cupriavidus, Pseudomonas, Thermus, Sphingomonas, Methylobacterium, Diaphorobacter, Comamonas, and Mobilicoccus, were unique to pulmonary tuberculosis patients. CONCLUSIONS: This study concluded that the microbial composition of the respiratory tract of pulmonary tuberculosis patients is more complicated than that of healthy participants, and many foreign bacteria were found in the sputum of pulmonary tuberculosis patients. The roles of these foreign bacteria in the onset or development of pulmonary tuberculosis should be considered by clinicians.
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Bactérias/classificação , Bactérias/genética , Biota , Metagenoma , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto , Idoso , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Adulto JovemRESUMO
A highly active and stable electrocatalyst based on Pd nanoparticles anchored on zeolitic imidazolate framework-derived Fe/Co/N co-doped carbon (Pd/FeCoNC) is prepared. FeCo alloy nanoparticles are uniformly dispersed and wrapped by graphene layers in Fe/Co/N co-doped carbon (FeCoNC). The influences of carbonization temperature on the structure and catalytic activity of FeCoNC toward oxygen reduction reaction (ORR) are investigated. The FeCoNC prepared at 800 °C (FeCoNC-800) has a favorable ORR catalytic activity as a consequence of the synergistic effect of Fe/Co/N co-doping and hierarchical pore structures of coexisting micropores and mesopores. Pyridinic N in FeCoNC is a preferential adsorption site for anchoring Pd nanoparticles. Pd/FeCoNC exhibits both superior activity and durability to 40 wt % Pt/C at the same level of metallic mass loading, which shows a 44 mV higher half-wave potential (0.88 V) than Pt/C and a 91% remaining current of the initial after 10,000 s. The Fe/Co/N co-doping and hierarchical pores of FeCoNC contribute a large diffusion current, and the introduction of Pd realizes more positive onset and half-wave potentials. This work provides an easy way for preparing low-cost and high-efficiency catalysts for ORR.
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Aim: Our previous proteomic analysis showed that small RNA SprC (one of the small pathogenicity island RNAs) of Staphylococcus aureus possesses the ability to regulate the expression of multiple bacterial proteins. In this study, our objective was to further provide insights into the regulatory role of SprC in gene transcription and metabolism of S. aureus. Methods: Gene expression profiles were obtained from S. aureus N315 wild-type and its sprC deletion mutant strains by RNA-sequencing (RNA-seq), and differentially expressed genes (DEGs) were screened by R language with a |log2(fold change)| ≥1 and a false discovery rate (FDR) ≤ 0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to understand the significance of the DEGs. The quality of RNA-seq was further verified by quantitative real-time PCR (qRT-PCR), mRNA target prediction, metabolomics analysis and transcript-level expression analysis of genes of sprC complementation strain. Results: A total of 2497 transcripts were identified, of which 60 transcripts expressions in sprC knockout strain were significantly different (37 up-regulated and 23 down-regulated DEGs). GO analysis showed that the functions of these DEGs were mainly concentrated in the biological process and molecular function related to metabolism and pathogenesis, and a higher number of genes were involved in the oxidation-reduction process, catalytic activity and binding. KEGG pathways enrichment analysis demonstrated that metabolism and pathogenesis were the most affected pathways, such as metabolic pathways, biosynthesis of secondary metabolites, purine metabolism, fructose and mannose metabolism and S. aureus infection. The qRT-PCR results of the DEGs with defined functions in the sprC deletion and complementation strains were in general agreement with those obtained by RNA-seq. Metabolomics analysis revealed 77 specific pathways involving metabolic pathways. Among them, many, such as metabolic pathways, biosynthesis of secondary metabolites and purine metabolism, were consistent with those enriched in the RNA-seq analysis. Conclusion: This study offered valuable and reliable information about the regulatory roles of SprC in S. aureus biology through transcriptomics and metabolomics analysis. These results may provide clues for new potential targets for anti-virulence adjuvant therapy on S. aureus infection.