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Klebsiella pneumoniae (Kp) is a human symbiotic opportunistic pathogen capable of causing severe hospital-based infections and community-acquired infections. The problem of antimicrobial resistance (AMR) has become increasing serious over time, posing a major threat to socio-economic and human development. In this study, we explored the global trend of AMR in 1786 strains of Kp isolated between 1982 and 2023. The number of antibiotic resistance genes (ARGs) in Kp increased significantly from 24.29 ± 5.44 to 32.42 ± 8.52 over time. Mobile genetic elements (MGEs) were responsible for the ARGs horizontal transfer of Kp strains. The results of structural equation modeling (SEM) indicated a strong association between the human development index and the increase of antibiotic consumption, which indirectly affected the occurrence and development of antibiotic resistance in Kp. The results of Generalized Linear Models (GLM) indicated that the influence of environmental factors such as temperature on the development of Kp resistance could not be ignored. Overall, this study monitored the longitudinal trend of antimicrobial resistance in Kp, explored the factors influencing antibiotic resistance, and provided insights for mitigating the threat of antimicrobial resistance.
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Antibacterianos , Farmacorresistência Bacteriana , Klebsiella pneumoniae , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologiaRESUMO
The confrontation between humans and bacteria is ongoing, with strategies for combating bacterial infections continually evolving. With the advancement of RNA sequencing technology, non-coding RNAs (ncRNAs) associated with bacterial infections have garnered significant attention. Recently, long ncRNAs (lncRNAs) have been identified as regulators of sterile inflammatory responses and cellular defense against live bacterial pathogens. They are involved in regulating host antimicrobial immunity in both the nucleus and cytoplasm. Increasing evidence indicates that lncRNAs are critical for the intricate interactions between host and pathogen during bacterial infections. This paper emphatically elaborates on the potential applications of lncRNAs in clinical hallmarks, cellular damage, immunity, virulence, and drug resistance in bacterial infections in greater detail. Additionally, we discuss the challenges and limitations of studying lncRNAs in the context of bacterial infections and highlight clear directions for this promising field.
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Background: Various prevalences of asthma in coronavirus disease 2019 (COVID-19) have been reported in different regions, and the association between asthma and COVID-19 subsequent mortality has been in debate. Thus, this study aimed to investigate whether there was a significant association between asthma and COVID-19 mortality in Spain through a meta-analysis. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were strictly complied with conducting this study. The pooled odds ratio (OR) with a corresponding 95% confidence interval (CI) was calculated by a random-effects model. The I 2 statistics for heterogeneity, sensitivity analysis for robustness, Begg's test, and Egger's test for publication bias, along with subgroup analyses for confounding bias, were also performed to support the foundation of this study. Results: The meta-analysis revealed that asthma was significantly associated with a lower risk of mortality among COVID-19 patients in Spain with a random-effects model (pooled OR = 0.78, 95% CI = 0.69-0.88, I 2 = 35%). Further subgroup analyses by male proportion and sample size also indicated that a statistically significant negative correlation did exist between asthma and COVID-19 mortality. Robustness and no publication on-bias were evidenced by sensitivity analysis, Egger's test, and Begg's test, respectively. Conclusion: In conclusion, patients with asthma were found to have a lower risk of mortality from COVID-19 in Spain, especially among elderly patients. In addition, asthmatic patients infected with COVID-19 may be at risk of death compared to non-asthmatic patients, which is not a cause for undue concern, thereby reducing the burden of medication.
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Tuberculosis (TB), which caused by Mycobacterium tuberculosis, is the leading cause of death from a single infectious agent and continues to be a major public health burden for the global community. Despite being the only globally licenced prophylactic vaccine, Bacillus Calmette-Guérin (BCG) has multiple deficiencies, and effective diagnostic and therapeutic options are limited. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is an adaptive immune system that is found in bacteria and has great potential for the development of novel antituberculosis drugs and vaccines. In addition, CRISPR-Cas is currently recognized as a prospective tool for the development of therapies for TB infection with potential diagnostic and therapeutic value, and CRISPR-Cas may become a viable tool for eliminating TB in the future. Herein, we systematically summarize the current applications of CRISPR-Cas-based technology for TB detection and its potential roles in drug discovery and vaccine development.
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Mycobacterium tuberculosis , Tuberculose , Humanos , Sistemas CRISPR-Cas/genética , Tuberculose/prevenção & controle , Tuberculose/microbiologia , Mycobacterium tuberculosis/genética , Descoberta de Drogas , Desenvolvimento de VacinasRESUMO
To determine that p38 MAPK activation contributes to the migration and invasion of lung cancer cells caused by cadmium (Cd). A549 lung cancer cell migration and invasion were assessed using a transwell plate system, and the role of p38 was determined by knocking down p38 activity with two different inhibitors of p38. The activity of p38 was measured by western blot analysis using phospho-specific p38 antibodies and normalized to blots using antibodies directed to total p38 proteins. Snail transcripts were measured using qRT-PCR. The inhibition of p38 blocked Cd-induced migration and invasion, which correlated with an increased activation of p38 as a function of dose and time. Furthermore, Cd-induced activation of p38 MAPK controlled the increase of snail mRNA expression. The p38 MAPK/snail signaling axis was involved in Cd-induced lung cancer cell migration and invasion.
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Cádmio , Neoplasias Pulmonares , Sistema de Sinalização das MAP Quinases , Humanos , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The association between peptic ulcer disease and the severity of coronavirus disease 2019 (COVID-19) is inconclusive across individual studies. Thus, this study aimed to investigate whether there was a significant association between peptic ulcer disease and COVID-19 severity through a meta-analysis. The electronic databases (Web of Science, Wiley, Springer, EMBASE, Elsevier, Cochrane Library, Scopus and PubMed) were retrieved for all eligible studies. The Stata 11.2 software was used for all statistical analyses. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated by a random-effects meta-analysis model. The heterogeneity was evaluated by the inconsistency index (I2) and Cochran's Q test. Egger's analysis and Begg's analysis were conducted to evaluate the publication bias. Meta-regression analysis and subgroup analysis were done to explore the potential source of heterogeneity. Totally, our findings based on confounding variables-adjusted data indicated that there was no significant association between peptic ulcer disease and the higher risk for COVID-19 severity (pooled OR = 1.17, 95% CI: 0.97-1.41) based on 15 eligible studies with 4,533,426 participants. When the subgroup analysis was performed by age (mean or median), there was a significant association between peptic ulcer disease and a higher risk for COVID-19 severity among studies with age ≥ 60 years old (pooled OR = 1.15, 95% CI: 1.01-1.32), but not among studies with age < 60 years old (pooled OR = 1.16, 95% CI: 0.89-1.50). Our meta-analysis showed that there was a significant association between peptic ulcer disease and a higher risk for COVID-19 severity among older patients but not among younger patients.
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The study aimed to investigate the influence of comorbid asthma on the risk for mortality among patients with coronavirus disease 2019 (COVID-19) in the United Kingdom (UK) by utilizing a quantitative meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was estimated by conducting a random-effects model. Sensitivity analysis, I2 statistic, meta-regression, subgroup analysis, Begg's analysis and Egger's analysis were all implemented. Our results presented that comorbid asthma was significantly related to a decreased risk for COVID-19 mortality in the UK based on 24 eligible studies with 1,209,675 COVID-19 patients (pooled OR = 0.81, 95% CI: 0.71-0.93; I2 = 89.2%, P < 0.01). Coming through further meta-regression to seek the possible cause of heterogeneity, none of elements might be responsible for heterogeneity. A sensitivity analysis proved the stability and reliability of the overall results. Both Begg's analysis (P = 1.000) and Egger's analysis (P = 0.271) manifested that publication bias did not exist. In conclusion, our data demonstrated that COVID-19 patients with comorbid asthma might bear a lower risk for mortality in the UK. Furthermore, routine intervention and treatment of asthma patients with severe acute respiratory syndrome coronavirus 2 infection should be continued in the UK.
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Asma , COVID-19 , Humanos , COVID-19/epidemiologia , Reprodutibilidade dos Testes , Comorbidade , Asma/epidemiologia , Reino Unido/epidemiologiaRESUMO
We aimed to explore the influence of comorbid asthma on the risk for mortality among patients with coronavirus disease 2019 (COVID-19) in Asia by using a meta-analysis. Electronic databases were systematically searched for eligible studies. The pooled odds ratio (OR) with 95% confidence interval (CI) was estimated by using a random-effect model. An inconsistency index (I2) was utilized to assess the statistical heterogeneity. A total of 103 eligible studies with 198,078 COVID-19 patients were enrolled in the meta-analysis; our results demonstrated that comorbid asthma was significantly related to an increased risk for COVID-19 mortality in Asia (pooled OR = 1.42, 95% CI: 1.20−1.68; I2 = 70%, p < 0.01). Subgroup analyses by the proportion of males, setting, and sample sizes generated consistent findings. Meta-regression indicated that male proportion might be the possible sources of heterogeneity. A sensitivity analysis exhibited the reliability and stability of the overall results. Both Begg's analysis (p = 0.835) and Egger's analysis (p = 0.847) revealed that publication bias might not exist. In conclusion, COVID-19 patients with comorbid asthma might bear a higher risk for mortality in Asia, at least among non-elderly individuals.
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The salt metathesis reaction of LnCl3 with 1 equivalent of arylamido lithium [2,6-(i)Pr2C6H3N(SiMe3)]Li followed by addition of 2 equivalents of LiN(SiHMe2)2 in THF at room temperature obtained neutral mono-arylamido-ligated rare-earth metal bis(silylamide) complexes [2,6-(i)Pr2C6H3N(SiMe3)]Ln[N(SiHMe2)2]2(THF) (Ln = Y (), Lu (), La ()) in good isolated yields. Treatment of with excess AlMe3 produced the mono(arylamido) Ln/Al heterotrinuclear methyl complexes [2,6-(i)Pr2C6H3N(SiMe3)]Ln[(µ-Me)2AlMe2]2 (Ln = Y (), Lu (), La ()) via amide-alkyl exchange. All these complexes were well-characterized by elemental analysis, NMR spectroscopy and FT-IR spectroscopy. , and were further structurally authenticated by X-ray crystallography. In the presence of [Ph3C][B(C6F5)4] and Al(i)Bu3, were highly active for cis-1,4-selective polymerization of isoprene, whereas /[Ph3C][B(C6F5)4]/Al(i)Bu3 promoted the polymerization in a living fashion.
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OBJECTIVE: To set up the drug lymphocyte stimulation test (DLST), as a diagnosis means for DILI which was immunity idiosyncrasy, improve the Diagnosis, level of DILI. METHOD: For the 59 patients who diagnosed as DILI, we separated their PBMC, exploring to the suspicious drug which caused DILI, then use the methods 3H-TdR to test, according to the mixed degree to clear the PBMC count which specific activated by drug.We also set up drug group, negative control and Positive control at the same time. Preliminary experiments was including the best dose of PHA and the best concentration of the drug. We set up 40 healthy group in our experiments as a control, and explore them on the same drug every time. We test the two groups at the same time. We handled the results use t-test. RESULTS: The methods 3H-TdR could be exactly reflect the PBMC's proliferation degree nearly the same when they were be stimulation by PHA or the sensitive drug. When the DILI patients were explore to the suspicious drug, their stimulation index (SI) Obviously higher than 1.8. Form this test, there were 28 in 59 patients of DILI's group were positive (47.46%), SI was from 1.9 to 43.08, the average was 22.49, the healthy group SI was lower than 1.8, the SI of DILI's group was significantly higher than healthy group (5.78+/-0.75/1.16+/-0.25, P less than 0.05). Our test suggested DLST has Higher specificity (94.92%) and sensitivity (47.46%). CONCLUSION: DLST was significance for the patients who diagnosed as immunity idiosyncrasy's DILI, it's reflected these patients' Proliferation of PBMC when explored to the suspicious drug for the second time.
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Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Ativação Linfocitária , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Recombinant human interferons (rhIFNs) are broadly used as effective therapeutic agents with antiviral, antitumor, and immune-modulating properties. Advances in protein biochip technology have benefited the medical community greatly, making true parallelism, miniaturization, and high throughput possible. In this study, 5 rhIFN proteins (IFN-alpha1b, IFN-alpha2a, IFN-alpha2b, IFN-beta, and IFN-gamma) were immobilized onto an N-hydroxysuccinimide (NHS)-modified gold-based biochip. The protein biochip was incubated with 6 specific mouse IgG antibodies (AK1, AK2, AK3, AK4, BK1, and CK1) against the human IFNs and then with Cy3-conjugated goat anti-mouse IgG antibody. The results showed that monoclonal antibody AK1 presented a unique binding characteristic to IFN-alpha1b. AK2 reacted in immunoassays equally with IFN-alpha2a and IFN-alpha2b. AK3 detected IFN-alpha1b, IFN-alpha2a, and IFN-alpha2b. AK4 had positive immunological responses directed to both IFN-alpha1b and IFN-alpha2b. Monoclonal antibodies BK1 and CK1 recognized epitope of IFN-beta and IFN-gamma, specifically. The assay specificity of the biochip was further confirmed by enzyme-linked immunosorbent assay (ELISA) and western blotting. Finally, 88 serum samples from patients treated with rhIFN-alpha2b were simultaneously tested on a single biochip. The result demonstrated that 6.8% (6 of 88 cases) presented positive reactions to anti-IFN-alpha2b antibodies, indicating that the patients under rhIFN-alpha2b therapy produced neutralized antibody against the IFN. The biochip format would offer a competitive alternative tool not only for facilitating characterization of IFN subtypes but also potentially for enabling clinical serum detection of corresponding antibodies directed against IFNs.