TRPML1 agonist ML-SA5 mitigates uranium-induced nephrotoxicity via promoting lysosomal exocytosis.

Uranium (U) released from U mining and spent nuclear fuel reprocessing in the nuclear industry, nuclear accidents and military activities as a primary environmental pollutant (e.g., drinking water pollution) is a threat to human health.

Efficacy and Safety of Combined Bedaquiline and Delamanid Use among Patients with Multidrug-Resistant Tuberculosis in Beijing, China.

Objectives: The combined use of bedaquiline and delamanid (BDQ-DLM) is limited by an increased risk of prolonging the QTc interval. We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital. We aimed to present clinical efficacy and safety data for Chinese patients.

Surveillance of close contacts of patients with infectious tuberculosis: a prospective cohort study.

Background: A long-term follow-up of close contacts to monitor their infection status is essential to formulate a promising screening strategy. The study aimed to assess the dynamics of tuberculosis (TB) infection using Interferon-γ release assay (IGRA) and determine risk factors associated with TB infection.

Methods: Definite TB patients were interviewed and their household contacts were screened for TB infection by IGRA during 12-month longitudinal investigation.

Diagnostic accuracy of oral swab for detection of pulmonary tuberculosis: a systematic review and meta-analysis.

Objectives: Tuberculosis (TB) remains a significant concern in terms of public health, necessitating the timely and accurate diagnosis to impede its advancement. The utilization of oral swab analysis (OSA) presents a promising approach for diagnosing pulmonary TB by identifying (MTB) within oral epithelial cells. Due to disparities in the diagnostic performance of OSA reported in the original studies, we conducted a meticulous meta-analysis to comprehensively assess the diagnostic efficacy of OSA in pulmonary TB.

Antigen-specific chemokine profiles as biomarkers for detecting infection.

Background: Latent tuberculosis (TB) infection can progress to active TB, which perpetuates community transmission that undermines global TB control efforts. Clinically, interferon-γ release assays (IGRAs) are commonly used for active TB case detection. However, low IGRA sensitivity rates lead to false-negative results for a high proportion of active TB cases, thus highlighting IGRA ineffectiveness in differentiating MTB-infected individuals from healthy individuals.

Prolonged Dual Antiplatelet Therapy in Acute Myocardial Infarction Patients Without Revascularization: China Acute Myocardial Infarction Registry Study.

At least 12 months of dual antiplatelet therapy (DAPT) is 1 of the standards of care following percutaneous coronary intervention in patients with acute coronary syndrome. However, study on prolonged DAPT for patients with acute myocardial infarction (AMI) without revascularization is limited. We studied 1,744 patients with AMI without revascularization from the China Acute Myocardial Infarction registry between January 2013 and September 2014.

In vitro susceptibility of nontuberculous mycobacteria in China.

Objectives: This study aimed to measure the prevalence of resistance to antimicrobial agents, and explore the risk factors associated with drug resistance by using nontuberculous Mycobacteria (NTM) isolates from China.

Methods: A total of 335 NTM isolates were included in our analysis. Broth dilution method was used to determine in vitro drug susceptibility of NTM isolates.

The emerging threat of fluroquinolone-, bedaquiline-, and linezolid-resistant Mycobacterium tuberculosis in China: Observations on surveillance data.

Background: Drug-resistant tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB), constitutes a major obstacle to fulfill end TB strategy globally. Although fluoroquinolones (FQs), linezolid (LZD) and bedaquiline (BDQ) were classified as Group A drugs for MDR-TB treatment, our knowledge of the prevalence of TB which were resistant to Group A drugs in China is quite limited.

Methods: In this study, we conducted a prospective multicenter surveillance study in China to determine the proportion of TB patients that were resistant to Group A drugs.

Induction of lysosomal exocytosis and biogenesis via TRPML1 activation for the treatment of uranium-induced nephrotoxicity.

Uranium (U) is a well-known nephrotoxicant which forms precipitates in the lysosomes of renal proximal tubular epithelial cells (PTECs) after U-exposure at a cytotoxic dose. However, the roles of lysosomes in U decorporation and detoxification remain to be elucidated. Mucolipin transient receptor potential channel 1 (TRPML1) is a major lysosomal Ca channel regulating lysosomal exocytosis.

Real-time recombinase-aided amplification assay for rapid amplification of the IS1081 gene of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (MTB), the etiological agent of tuberculosis (TB), is the leading cause of death due to a single infectious agent worldwide. Rapid and accurate diagnosis of MTB is critical for controlling TB especially in resource-limited countries, since any diagnosis delay increases the chances of transmission. Here, a real-time recombinase-aided amplification (RAA) assay targeting conserved positions in IS1081 gene of MTB, is successfully established to detect MTB.

Serum Cytokine Biomarkers for Use in Diagnosing Pulmonary Tuberculosis versus Chronic Pulmonary Aspergillosis.

Background: -induced chronic pulmonary aspergillosis (CPA), the most common pulmonary tuberculosis (TB) sequela, tends to occur after pulmonary infection with the intracellular pathogen (). Timely and accurate detection of infection of pulmonary TB patients would undoubtedly greatly improve patient prognosis. Currently, the galactomannan (GM) antigen test is commonly used to detect infection but has poor sensitivity that renders this assay inadequate for use in clinical practice.

Analysis of Xpert MTB/RIF results in retested patients with very low initial bacterial loads: A retrospective study in China.

Background: The Xpert MTB/RIF (Xpert) assay has been widely used to diagnose suspected active tuberculosis (TB) and rifampicin-resistant TB cases. Despite its excellent performance record, false-positive Xpert rifampicin (RIF) resistance results are obtained for specimens with extremely low bacterial loads.

Objective: We aimed to study the feasibility of repeat Xpert testing as a strategy for reducing the odds of obtaining false-positive results when testing paucibacillary TB patients.

Development and clinical evaluation of a CRISPR/Cas13a-based diagnostic test to detect in clinical specimens.

Objective: Tuberculosis diagnosis requires rapid, simple and highly sensitive methods. Clustered regularly interspaced short palindromic repeats (CRISPRs) and associated protein (Cas) systems are increasingly being used for clinical diagnostic applications, due to their high flexibility, sensitivity and specificity. We developed a sensitive (MTB) complex polymerase chain reaction (PCR)-CRISPR/Cas13a detection method (CRISPR-MTB) and then evaluated its performance in detecting MTB in clinical specimens.

Clinical isolates of with different genotypes exhibit distinct host macrophage responses .

. (), the causative agent of tuberculosis, can survive as an intracellular parasite after entering macrophages via phagocytosis. strains are genotypically distinct and engage in diverse pathogen-host interactions, with different host immune responses triggered by different strains.

Antimicrobial Effect of Oxazolidinones and Its Synergistic Effect with Bedaquiline Against Complex.

Purpose: Unsatisfactory efficacies of currently recommended anti- complex (MABC) treatment regimens have led to development of novel drugs to combat MABC infections. In this study, we evaluated in vitro antimicrobial activities of bedaquiline (BDQ) and four oxazolidinones against MABC isolates.

Methods: The resazurin microplate assay was performed to determine minimum inhibitory concentrations (MICs) of BDQ and four oxazolidinones, including tedizolid (TZD), sutezolid (SZD), delpazolid (DZD), and linezolid (LZD), against 65 MABC isolates.

Predominance of Escherichia-Shigella in Gut Microbiome and Its Potential Correlation with Elevated Level of Plasma Tumor Necrosis Factor Alpha in Patients with Tuberculous Meningitis.

Tuberculous meningitis (TBM), the most lethal and disabling form of tuberculosis (TB), may be related to gut microbiota composition, warranting further study. Here we systematically compared gut microbiota compositions and blood cytokine profiles of TBM patients, pulmonary TB patients, and healthy controls. Notably, the significant gut microbiota dysbiosis observed in TBM patients was associated with markedly high proportions of Escherichia-Shigella species as well as increased blood levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6).

A Complete Method for Evaluating the Performance of Photocatalysts for the Degradation of Antibiotics in Environmental Remediation.

Various antibiotics such as tetracycline, aureomycin, amoxicillin, and levofloxacin are found in large quantities in groundwater and soil systems, potentially leading to the development of resistant and multi-drug resistant bacteria, posing a threat to humans, animals, and environmental systems. Photocatalytic technology has attracted keen interest due to its rapid and stable treatment and direct use of solar energy. However, most studies evaluating the performance of semiconductor catalysts for the photocatalytic degradation of organic pollutants in water are currently incomplete.

Transition between Mycobacterium tuberculosis and nontuberculous mycobacteria in recurrent "tuberculosis" patients.

Recurrence of tuberculosis (TB) is still a key issue in the control of tuberculosis. The presence of nontuberculous mycobacteria (NTM) complicates the diagnosis of recurrent TB due to similarity in clinical presentation. Herein, we have used molecular genotyping methods to identify mycobacteria species, and analyzed the characteristics of patients with transition between MTB and NTM.

Highly Discriminative Genotyping of Complex Using a Set of Variable Number Tandem Repeats in China.

In this study, our aims were to comparatively analyze the power of variable number tandem repeat (VNTR) typing to discriminate isolates within subspecies and to identify a potential genetic marker for better molecular typing of complex (MABC) strains. A total of 103 clinical MABC isolates were collected from a nationwide cross-sectional study in China. Eighteen VNTR loci were chosen to genotype the MABC isolates.

Reevaluating Rifampicin Breakpoint Concentrations for Mycobacterium tuberculosis Isolates with Disputed Mutations and Discordant Susceptibility Phenotypes.

In this study, rifampicin resistance breakpoints based on MICs of disrupted mutants of Mycobacterium tuberculosis (MTB) were explored using the Mycobacteria Growth Indicator Tube (MGIT) system and microplate alamarBlue assay (MABA). Sixty-one MTB isolates with disputed low-level rifampicin resistance-associated mutations and 40 RIF-susceptible wild-type isolates were included. Among the 61 resistant isolates, 25 (41.

Prevalence and Risk Factors of Subclinical Tuberculosis in a Low-Incidence Setting in China.

Subclinical tuberculosis (TB) represents a substantial proportion of individuals with TB disease, although limited evidence is available to understand the epidemiological characteristics of these cases. We aimed to explore the prevalence of subclinical patients with TB and identify the underlying association between the subclinical TB cases in the study setting and the Beijing genotype. A retrospective study was conducted among patients with incident TB at the Fifth People's Hospital of Suzhou between January and December 2018.

Effect of Mixed Infections with and Nontuberculous Mycobacteria on Diagnosis of Multidrug-Resistant Tuberculosis: A Retrospective Multicentre Study in China.

Background: Correct species identification is essential before initiation of TB treatment, due to substantial drug susceptibility profile differences among mycobacterial species. Given that nontuberculous mycobacteria (NTM) are frequently resistant to first-line anti-tuberculosis drugs, cases with mixed infections with (MTB) and NTM tend to be diagnosed as multidrug-resistant tuberculosis (MDR-TB) cases. Here we report results of a retrospective multicentre study that was conducted to determine the prevalence of TB-NTM infections in previously diagnosed laboratory-confirmed multidrug-resistant tuberculosis (MDR-TB) patients using phenotypic drug susceptibility testing.

Distinguishing Relapse From Reinfection With Whole-Genome Sequencing in Recurrent Pulmonary Tuberculosis: A Retrospective Cohort Study in Beijing, China.

Tuberculosis recurrence is still a major problem for the control of tuberculosis, and the cause of the recurrence is still unclear. We retrospectively recruited 68 pairs of samples of (MTB) from recurrent TB cases in Beijing Chest Hospital between January 2008 and December 2019. The whole-genome sequencing was conducted to analyze single-nucleotide polymorphism (SNP) and to identify whether recurrent disease was due to relapse or reinfection.