Novel methyldithiocarbazate derivatives as NDM-1 inhibitors to combat multidrug-resistant bacterial infection with β-lactams.

Given the ever-evolving landscape of antimicrobial resistance, the emergence of New Delhi metallo-β-lactamase-1 (NDM-1) has introduced a formidable challenge to global public health. In previous research, we identified the Compound Zndm19 as an NDM-1 inhibitor and reported Zndm19 derivatives, which exhibited moderate antibacterial activity when combined with meropenem (MEM). This moderate activity may have been due to the inability of Zndm19 to efficiently penetrate the bacterial outer membrane or its susceptibility to hydrolysis, which prevented it from exerting strong enzyme inhibition in synergy with bacterial cells.

A proposed biomarker for human citric acid ester (CAE) exposure, and the potential disturbance on human lipid metabolism.

Citric acid esters (CAEs), as one class of important alternative plasticizers, have been proven to be ubiquitous in the environments, leading to an increasing concern regarding their potential health risk to humans. However, information regarding the biomarkers for human CAE biomonitoring is currently unknown. In the present study, we investigated the metabolism characteristics of CAEs by use of in vitro rat liver microsomes (RLMs) and in vivo mice.

[Application of chromatographic retention time correction in untargeted screening].

Objective: Chromatographic retention time correction is one of the important steps to effectively improve the accuracy of identification. This article proposed a strategy for untargeted screening of biological samples based on retention time correction.

Methods: A pre-treatment method for biological samples was established.

as a carbapenem synergist against KPC-2 positive .

The successful evolution of KPC-2 in bacteria has limited the clinical practice of carbapenems. This dilemma deteriorated the prognosis of associated infections and hence attracted increasing attention from researchers to explore alternative therapeutic options. Here, the enzyme inhibition assay was first performed to screen for a potent KPC-2 inhibitor.

Establishing and Validating Refractive Error Reference Values for Myopia Prediction Among Children Aged 6-12 Years - Jiangsu Province, China, 2018-2023.

What Is Already Known About This Topic?: Previously, it has been proved that a simplified model that uses refraction error value provides a robust and efficient means of predicting myopia for non-myopic students. Intervention targeting non-myopic children with alert refraction errors (or insufficient hyperopia reserve) holds significant importance in reducing the incidence rate of myopia.

What Is Added By This Report?: This study, comprising two phases (surveillance and cohort studies), was aiming to pinpoint the precise refractive error value for the onset of myopia prediction among non-myopic children in Jiangsu Province.

P-phenylenediamine antioxidants and their quinone derivatives: A review of their environmental occurrence, accessibility, potential toxicity, and human exposure.

Substituted p-phenylenediamines (PPDs), a class of antioxidants, have been widely used to extend the lifespan of rubber products, such as tires and pipes. During use, PPDs will generate their quinone derivatives (PPD-Qs). In recent years, PPDs and PPD-Qs have been detected in the global environment.

Laurocapram, a transdermal enhancer, boosts cephalosporin's antibacterial activity against Methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA), a notorious bacterium with high drug resistance and easy recurrence after surgery, has posed significant clinical treatment challenges. In the current scarcity of new antibiotics, the identification of adjuvants to existing antibiotics is a promising approach to combat infections caused by multidrug-resistant Gram-positive bacteria. The in vitro synergy test, which included a MIC assay, time-kill curve, antimicrobial susceptibility testing, and live/dead bacteria staining assay, revealed that laurocapram, a widely used chemical transdermal enhancer, could potentiate the antibacterial activity of cephalosporins against MRSA.

Enhancing the effectiveness of Polymyxin E with a Fisetin Nanoemulsion against a Colistin-resistant Salmonella typhimurium infection.

Background: Polymyxin E is widely recognized as a last resort for treating multidrug-resistant gram-negative bacteria. Unfortunately, the effectiveness of polymyxin E is significantly reduced when treating life-threatening bacterial infections due to plasmid-mediated polymyxin E resistance. The synergistic effect of applying a polymyxin E adjuvant is a promising strategy for overcoming the growing threat of antibiotic-resistant pathogens.

Repurposing harmaline as a novel approach to reverse tmexCD1-toprJ1-mediated tigecycline resistance against klebsiella pneumoniae infections.

Background: A novel plasmid-mediated resistance-nodulation-division (RND) efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae tremendously threatens the use of convenient therapeutic options in the post-antibiotic era, including the "last-resort" antibiotic tigecycline.

Results: In this work, the natural alkaloid harmaline was found to potentiate tigecycline efficacy (4- to 32-fold) against tmexCD1-toprJ1-positive K. pneumoniae, which also thwarted the evolution of tigecycline resistance.

Multi-omics Combined with Machine Learning Facilitating the Diagnosis of Gastric Cancer.

Gastric cancer (GC) is a highly intricate gastrointestinal malignancy. Early detection of gastric cancer forms the cornerstone of precision medicine. Several studies have been conducted to investigate early biomarkers of gastric cancer using genomics, transcriptomics, proteomics, and metabolomics, respectively.

The synbiotic combination of probiotics and inulin improves NAFLD though modulating gut microbiota.

Prebiotics can promote the growth of probiotics, cocombine of these is called synbiotics, and synbiotics is powerful regulators of gut microbiota. Intestinal microbiota plays an important role in nonalcoholic fatty liver disease (NAFLD), so synbiotics could be a therapeutic alternative. This study aims to investigate the effect of synbiotics combination of probiotics (Streptococcus Bifidobacterium and Streptococcus thermophilus) and prebiotics (Inulin) in vivo model of early NAFLD using yogurt as carrier.

A new function of thymol nanoemulsion for reversing colistin resistance in Salmonella enterica serovar Typhimurium infection.

Background: Adjuvant addition of approved drugs or foodborne additives to colistin might be a cost-effective strategy to overcome the challenge of plasmid-mediated mobile colistin resistance gene emergence, which poses a threat in the clinic and in livestock caused by infections with Gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae.

Methods: Chequerboard assay was applied to screen the colistin adjuvants from natural compounds. The killing-time curve, combined disc test and membrane permeation assay were conducted to identify the synergy efficacy of thymol and colistin in vitro.

Trend of blood pressure changes among children from 2012 to 2022: findings from student health surveillance in Eastern China.

Objectives: The primary objective of this study is to examine the secular trends in blood pressure levels from 2012 to 2022 in eastern China. Additionally, to compare two standards [International Blood Pressure Reference for Children and Adolescents (ICBP) and the National Blood Pressure Reference for Chinese Han Children and Adolescents (CCBP)], we calculate the 95th percentile of blood pressure levels for students in developed regions (ECCBP). Secondly, the study aims to investigate potential contributors to elevated blood pressure, including sex, age, behaviors, and mental health.

Discovery of isatin-β-methyldithiocarbazate derivatives as New Delhi metallo- β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates.

New Delhi metallo-β-lactamase-1 (NDM-1) poses a threat to public health due to its capability to hydrolyze nearly all β-lactam antibiotics, leaving limited treatment options for NDM-1 positive pathogens. Regrettably, there are presently no effective NDM-1 inhibitors in clinical use. This compels us to seek new compounds to combat multi-drug resistant bacterial infections (MDR).

Pattern of lifestyle behaviors and associated risk of being bullied at schools: A latent class analysis of 25,379 adolescents in Jiangsu Province of China.

School bullying is a worldwide problem. Although previous studies examined the association between different lifestyle behaviors and bullying victimization, the complex co-occurrence of these behaviors was not identified, and their association with the risk of being bullied remains unclear. We aimed to identify the behavioral patterns of adolescents and to explore their association with bullying victimization.

High-protein compound yogurt with quinoa improved clinical features and metabolism of high-fat diet-induced nonalcoholic fatty liver disease in mice.

Gut microbiota dysbiosis plays a crucial role in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD), which may be influenced by nutritional supplementation. Quinoa, a type of pseudocereal, has gained prominence due to its high nutritional value and diverse applications. This study aimed to determine whether yogurt containing quinoa can ameliorate NAFLD and alleviate metabolic disorders by protecting against the divergence of gut microbiota.

Urinary antibiotic concentrations in preschool children from eastern China and health risk assessment.

Despite limited biomonitoring studies suggesting extensive antibiotic exposure in general population, the body burden of antibiotics in young children and their potential health risks remain unclear. To assess the antibiotic exposure levels in young children, 508 preschoolers aged 3-6 years were recruited from eastern China in 2022, and a total of 50 representative antibiotics from 8 categories, including 17 human antibiotics (HAs), 4 antibiotics preferred as HAs (PHAs), 16 veterinary antibiotics (VAs), and 13 antibiotics preferred as VAs (PVAs), were analyzed by UPLC-MS/MS. Hazard quotient (HQ) and hazard index (HI) were calculated to evaluate the health risks, and multivariate logistic regression was applied to examine diet with antibiotic exposure.

Design, methodology, and baseline of eastern China student health and wellbeing cohort study.

Purpose: To describe the study design, methodology, and cohort profile of the Eastern China Student Health and Wellbeing Cohort Study. The cohort baseline includes (1) targeted disease (myopia, obesity, elevated blood pressure, and mental health) and (2) exposures (individual behaviors, environment, metabolomics, and gene and epigenetics).

Participants: Annual physical examination, questionnaire-based survey, and bio-sampling have been carried out in the study population.

Association between dietary approaches to stop hypertension (DASH) diet and hyperuricemia among Chinese adults: findings from a nationwide representative study.

Background: Certain foods and food groups could positively or negatively impact serum uric acid (SUA) levels. However, evidence on the holistic dietary strategy to prevent and control hyperuricemia (HUA) development remains limited.

Objective: The aim of this research work was to explore the association of dietary approaches to stop hypertension (DASH) diet with SUA levels and odds of HUA among Chinese adults.

The Application of Cinnamon Twig Extract as an Inhibitor of Listeriolysin O against Infection.

As a major virulence factor of (), listeriolysin O (LLO) can assist in the immune escape of , which is critical for the pathogen to evade host immune recognition, leading to various infectious diseases. Cinnamon twig (CT), as a traditional medicine, has been widely used in clinics for multiple functions and it has exhibited excellent safety, efficacy and stability. There are few reports on the effects of the extracts of traditional medicine on bacterial virulence factors.

Isoflavone glucoside genistin, an inhibitor targeting Sortase A and Listeriolysin O, attenuates the virulence of Listeria monocytogenes in vivo and in vitro.

As a common intracellular facultative anaerobic Gram-positive bacterium, Listeria monocytogenes (L. monocytogenes) exhibits strong resistance to extreme environments, such as low temperature and a wide range of pH values, causing contamination in food production and processing. Sortase A (SrtA) and listeriolysin O (LLO), two crucial virulence factors of L.

Naringenin Microsphere as a Novel Adjuvant Reverses Colistin Resistance via Various Strategies against Multidrug-Resistant Infection.

The efficacy of colistin, the last option against multidrug-resistant (MDR) Gram-negative bacteria, is severely threatened by the prevalence of plasmid- or chromosome-mediated colistin resistance genes. Herein, naringenin has dramatically restored colistin sensitivity against colistin-resistant infection without affecting bacterial viability, inducing resistance and causing obvious cell toxicity. Mechanism analysis reveals that naringenin potentiates colistin activity by multiple strategies including inhibition of mobilized colistin resistance gene activity, repression of two-component system regulation, and acceleration of reactive oxygen species-mediated oxidative damage.

Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating infection.

Background: (), as a pandemic foodborne pathogen, severely threatens food security and public health care worldwide, which evolves multiple bacterial virulence factors (such as listeriolysin O, LLO) for manipulating the immune response of -host interactions.

Methods: Hemolysis assay was employed to screen a potential LLO inhibitor and the underlying mechanisms were investigated using molecular dynamics (MD) simulation and oligomerization assay. The effects of candidates on immune response were examined by qRT-PCR and immunoblotting analysis.