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Tigecycline is a last-resort antibiotic that is used to treat severe infections caused by extensively drug-resistant bacteria. tet (X) has been shown to encode a flavin-dependent monooxygenase that modifies tigecycline 1 , 2 . Here, we report two unique mobile tigecycline-resistance genes, tet (X3) and tet (X4), in numerous Enterobacteriaceae and Acinetobacter that were isolated from animals, meat for consumption and humans. Tet(X3) and Tet(X4) inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline. Both tet (X3) and tet (X4) increase (by 64–128-fold) the tigecycline minimal inhibitory concentration values for Escherichia coli , Klebsiella pneumoniae and Acinetobacter baumannii . In addition, both Tet(X3) ( A. baumannii ) and Tet(X4) ( E. coli ) significantly compromise tigecycline in in vivo infection models. Both tet (X3) and tet (X4) are adjacent to insertion sequence IS Vsa3 on their respective conjugative plasmids and confer a mild fitness cost (relative fitness of >0.704). Database mining and retrospective screening analyses confirm that tet (X3) and tet (X4) are globally present in clinical bacteria—even in the same bacteria as bla NDM-1 , resulting in resistance to both tigecycline and carbapenems. Our findings suggest that both the surveillance of tet (X) variants in clinical and animal sectors and the use of tetracyclines in food production require urgent global attention. Mobile tet (X3) and tet (X4) genes are identified on conjugative plasmids in Enterobacteriaceae and Acinetobacter isolated from humans, meat for consumption and animals that confer resistance to tetracyclines, including tigecycline, eravacycline and omadacycline.

Plasmid-mediated colistin-resistance genes have been reported in human origin clinical samples worldwide which raises its threats to human infections. Notably, mcr-1 , mcr-3 , mcr-8 , and mcr-10 have been reported isolated directly from clinical samples which creates more seriously threaten to human health than other mcr gene types. A multiplex polymerase chain reaction (Multi-PCR) protocol was developed to detect and genotype mobile colistin-resistance genes ( mcr-1 , mcr-3 , mcr-8 , mcr-10 ) in Enterobacteria for clinical laboratory purposes. We first designed four pairs of new primers for the amplification of mcr -1, mcr -3, mcr -8, and mcr -10 gene respectively to achieve stepwise separation of amplicons between 216 and 241 bp, and complete this Multi-PCR system with the assistance of another pair of universal primer. Among which the forward primers for mcr-8 and mcr-10 amplicons were identical. The protocol was validated by testing 11 clinical isolates of Escherichia coli and 3 clinical isolates of Klebsiella from human origin, each well characterized and prospectively validated. The Multi-PCR assay showed full concordance with whole-genome sequence data and displayed higher sensitivity and 100% specificity. The assay could detect all variants of the various mcr alleles described. The Multi-PCR assay successfully genotyped of mcr alleles described in one test.

The 2022 global mpox outbreak highlighted the risk of sustained human-to-human transmission of monkeypox virus (MPXV) in non-endemic regions, yet genomic surveillance in Asia, particularly in China, remains limited. This study conducted horizontal genomic surveillance of MPXV in Shenzhen from 2023 to 2024 to characterize the phylogenetic structure, mutational patterns, and adaptive evolution of locally circulating strains. Phylogenetic analysis showed 95.2% of strains belonged to the dominant lineage C.1.1, with 4.8% in lineage E.3, forming three distinct genetic clusters that indicate multiple independent introductions and established local transmission chains. Whole-genome mutational analysis identified 146 single-nucleotide polymorphisms (SNPs), 81.5% of which carried APOBEC3-mediated mutation signatures (TC > TT and GA > AA), reflecting host-driven antiviral editing. Notably, dynamic changes in low-complexity regions (LCRs) were observed, implying potential roles in genome plasticity and adaptive evolution. Functional analysis revealed non-synonymous substitution biases in host-interacting proteins OPG064, OPG145, and OPG210, while replication protein OPG105 remained conserved. Structural modeling identified critical substitutions in OPG002 (S54F), OPG016 (R84K), and OPG036 (R48C) that may enhance immune evasion by modulating TNF-α signaling, NKG2D engagement, and Type I interferon antagonism. These findings illuminate unique MPXV evolutionary dynamics in Shenzhen, emphasizing continuous genomic surveillance for non-endemic outbreak preparedness.

Background Folpet is a nonspecific sulfonamide fungicide widely used to protect crops from mildew. However, the in vivo effects of folpet on glucose metabolism homeostasis, gut microbiota, and abundance of drug resistance genes remain unknown. The purpose of this study was to assess the effects of the pesticide, folpet, on glucose metabolism homeostasis, and folpet-induced changes in the intestinal microbiota and resistance genes in mice. Methods Mice were orally administered folpet at 0, 1, 10, and 100 mg/kg body weight/day for 5 weeks. Blood sugar levels in mice were measured after 5 weeks of folpet administration. Metagenomic sequencing and drug resistance gene analyses were performed to explore changes in the abundance of gut microbiota members and drug resistance genes in mice after folpet administration. Correlation analysis was performed using metabolomics to explore the relationship between intestinal microbiota, drug resistance genes, and glucose metabolism. Results Mice in the folpet group had significantly lower blood glucose levels than those in the control group. The abundance of Atopobium , Libanicoccus , Collinsella , and Parabacteroides in the intestinal microbiota of folpet-treated mice was significantly higher than that in the control group. However, the abundance of Mailhella , Bilophila , Roseburia , and Bacteroides were reduced in folpet-treated mice. Compared with the control group, the abundance of APH6-Ic and AAC6-Ie-APH2-Ia resistance genes in mice treated with folpet significantly increased. The abundance of tetQ , ermE , and BahA resistance genes was significantly reduced after folpet treatment. Conclusions Folpet is associated with changes in the abundance of gut microbiota in mice and may also affect the abundance of drug-resistance genes and the regulation of blood glucose levels.

Background: Hospital wastewater (HWW) is a critical reservoir for carbapenem-resistant Gram-negative bacteria. Methods: Between November 2024 and August 2025, sixty 24 h composite wastewater samples were collected from five tertiary hospitals. Of the 244 carbapenem-resistant isolates recovered, 34 blaNDM-1-positive Acinetobacter isolates were subjected to phenotypic, genotypic, and plasmid analyses. Results: Eleven species were identified among the 34 carbapenem-resistant Acinetobacter isolates, predominantly non-baumannii Acinetobacter (NBA). All isolates were carbapenem-resistant (34/34, 100%) with high-level MICs (meropenem MIC50/90, 32/64 mg/L; imipenem MIC50/90, >128/>128 mg/L); 21% (7/34) of isolates were resistant to colistin, and resistance to ceftazidime, cefepime, and trimethoprim-sulfamethoxazole was 100%, 94%, and 76%, respectively. Core-genome SNP analysis revealed highly similar isolates across hospitals within the same season (1-2 SNPs) or within the same hospital across seasons (19 SNPs). Genomic analysis showed that blaNDM-1 was present in all isolates (34/34, 100%), with plasmid carriage in 85.3% (29/34); blaOXA-58 co-occurred in 62.1% (18/29), mainly on Rep_3 plasmids (19/29), especially R3-T28 (15/29) that frequently carried blaOXA-58 (10/15). Two unclassified plasmids co-harboring blaNDM-1 and blaOXA-23 were detected in Acinetobacter tandoii isolates. The blaNDM-1 gene was embedded in a conserved Tn125-like structures with variable flanks. Conclusions: Overall, carbapenem-resistant Acinetobacter from hospital wastewater frequently carried Rep_3 plasmid-borne blaNDM-1, especially R3-T28 and often co-occurring with blaOXA-58, within a conserved Tn125-like core structures. These findings highlight HWW as a potential hotspot for dissemination of carbapenem resistance and support routine genomic surveillance under a One Health framework.

Background Climate change has raised scientific interest in examining the associations of weather conditions with adverse health effects, while most studies determined human thermal stress using ambient air temperature rather than the thermophysiological index. Objectives To evaluate the association between emergency ambulance dispatches (EADs) related to cardiovascular causes and heat/cold stress in Shenzhen, a city in southern China, with the aim of providing new insights for local policymakers. Methods A time series analysis using ambulance dispatch data of cardiovascular diseases in Shenzhen, China (2013–2019) was conducted. A quasi-Poisson nonlinear distributed lag model was applied to explore the relationship between emergency ambulance dispatches (EADs) due to cardiovascular causes and thermal stress (determined by Universal Thermal Climate Index, UTCI). Attributable fractions were estimated to identify which UTCI ranges have a greater health impact. Results The relationship between UTCI and EADs due to cardiovascular diseases exhibits a reverse J-shaped curve. The effects of cold stress were immediate and long-lasting, whereas the effects of heat stress were non-significant. Compared with the optimal equivalent temperature (71st percentile of UTCI, 29.22 °C), the relative risks for cumulative (0–21 days) exposures to cold stress (1st percentile, − 0.13 °C; 5th percentile, 7.68 °C) were 1.55 (95%CI:1.28,1.88) and 1.44 (95%CI:1.22,1.69), respectively. Thermal (cold and heat) stress was responsible for 10.81% (95%eCI: 5.67%,15.43%) of EADs for cardiovascular diseases, with 9.46% (95%eCI: 3.98%,14.40%) attributed to moderate cold stress (2.5th ~ 71st percentile). Greater susceptibility to cold stress was observed for males and the elderly. Heat stress showed harmful effects in the warm season. Conclusions Our results demonstrated that cold exposure elevates the risk of EADs for cardiovascular causes in Shenzhen, and moderate cold stress cause the highest burden of ambulance dispatches. Health authorities should consider effective adaptation strategies and interventions responding to cold stress to reduce the morbidity of cardiovascular diseases.

Current clinical strategies for Methicillin-resistant (MRSA)-induced acute lung injury (ALI) predominantly focus on single-approach interventions such as anti-inflammatory therapy. However, due to the complex, multi-pathway pathological network underlying the disease, targeting a single pathway often yields suboptimal therapeutic outcomes. Consequently, there is a pressing need to develop innovative drug delivery systems capable of systematically addressing this intricate pathological process. Geraniol, a naturally derived monoterpene alcohol, exhibits multiple pharmacological activities including antimicrobial, antioxidant, and organ-protective effects, while the antimicrobial peptide (AMP) FK13-a1 demonstrates broad-spectrum antibacterial, anti-inflammatory, and immunomodulatory functions. Recognizing their complementary mechanisms of action, we innovatively propose a synergistic therapeutic strategy combining geraniol with FK13-a1. To enhance targeting precision, we engineered a biomimetic delivery system by coating nanomaterials with macrophage membranes via tyramine linkage, enabling specific homing to pulmonary inflammatory sites. Guided by this design concept, we successfully fabricated the biomimetic nanodrug Tyr-MM@PLGA/G+F and conducted systematic characterization using multiple analytical techniques. Through established and infection models, we evaluated the therapeutic efficacy of this nanosystem. Results demonstrated that Tyr-MM@PLGA/G+F actively targets ALI lesion sites, achieving precise co-delivery and synergistic action of geraniol and FK13-a1 at the pathological foci, thereby significantly enhancing treatment outcomes. This study not only validates the remarkable efficacy of this composite nanosystem against ALI but also provides novel insights and experimental evidence for targeted therapy of this condition.

Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. Using a miRNA microarray, we previously showed that the whole blood level of let-7e-5p was significantly higher in ischemic stroke patients than in control subjects. However, the association between let-7e-5p expression and the occurrence of ischemic stroke remains unknown. In this study, we validated the expression levels of let-7e-5p in two case-control populations using miRNA TaqMan assays and further investigated the potential targets of let-7e-5p. The results suggest that the blood level of let-7e-5p was significantly higher in patients with ischemic stroke than in controls (p<0.05). Higher levels of let-7e-5p were associated with increased occurrence of ischemic stroke (adjusted OR, 1.89; 95% CI, 1.61~2.21, p<0.001) in the combined population. The addition of let-7e-5p to traditional risk factors led to an improvement in the area under the curve, which increased from 0.74 (95% CI, 0.70~0.78) to 0.82 (95% CI, 0.78~0.85), with a net reclassification improvement of 16.76% (p<0.0001) and an integrated discrimination improvement of 0.10 (p<0.0001) for patients with ischemic stroke. Bioinformatics prediction and cell experiments suggested that the expression levels of four genes enriched in the MAPK signaling pathway were down-regulated by let-7e-5p transfection. Specifically, the expression levels of the genes CASP3 and NLK were significantly lower in ischemic stroke patients than in controls and were negatively correlated with let-7e-5p expression. In summary, our study suggests the potential use of blood let-7e-5p as a biomarker for ischemic stroke and indicates its involvement in the related pathomechanism.

Fipronil (FPN), a widely used insecticide, poses health risks through environmental contamination. Although its toxicity is increasingly recognized, the impact of fipronil on glucose metabolism remains poorly understood. In this study, mice on a normal diet (ND) or high-fat diet (HFD) received a daily oral administration of fipronil (0, 0.25, 1, or 4 mg/kg) for 35 days. Blood glucose and insulin were measured, and glucose/insulin/pyruvate tolerance tests were performed. We found that fipronil compromised glucose tolerance in mice fed an ND. Gut microbiota composition was assessed by 16S rRNA sequencing and the expression of inflammatory factors was detected in the tissues. Serum fibroblast growth factor 15 (FGF15) and bile acid were determined. In HFD-fed mice, fipronil exacerbated glucose metabolic disorders and enhanced insulin resistance. These metabolic disturbances were associated with gut microbiota dysbiosis, particularly a marked reduction in Akkermansia muciniphila (A. muciniphila) abundance, and increased systemic inflammation. Fipronil exposure also decreased serum FGF15 and elevated serum bile acids. Our results suggest that fipronil disrupts glucose metabolism in association with gut microbiota alterations, impairment of the FGF15-bile acid axis, and induction of inflammation, highlighting its potential relevance to diabetes risk. Further studies are warranted to validate our findings.

Neonicotinoid insecticides (NEOs), one of the most widely used pesticide classes worldwide, have raised concerns due to potential neurotoxic effects. Yet evidence on human exposure and health outcomes, particularly in preschool children, remains limited. In this study, 506 children aged 3–6 years from Shenzhen, China, were assessed. Neurobehavioral development was evaluated with the Strengths and Difficulties Questionnaire (SDQ), and urinary concentrations of 11 NEOs were measured, including imidacloprid (IMI), clothianidin (CLO), thiamethoxam (THM), dinotefuran (DNT), nitenpyram (NIT), sulfoxaflor (SFX), acetamiprid (ACE), thiacloprid (THD), flonicamid (FLO), 6-chloronicotinic acid (6-CINA), N-desmethyl-acetamiprid (NACE), and N-desmethyl-thiamethoxam (NTHM). Seven compounds showed high detection rates, including IMI (97.4%), CLO (100%), THM (100%), DNT (99.8%), NIT (99.8%), NACE (100%), and NTHM (99.8%). The mean urinary concentration was 234.145 μg/g creatinine, exceeding levels in earlier studies and indicating widespread exposure. IMI, NTHM, and NACE showed significant positive dose–response relationships with emotional symptoms, hyperactivity, and total difficulties and were major contributors in mixture models; sex-stratified analyses suggested effect modification for NTHM and NACE. These findings provide new epidemiological evidence to inform public health risk assessment and regulatory action on NEOs.