Epigenetic regulations, including DNA methylation, are critical to the development and progression of kidney fibrosis, but the underlying mechanisms remain elusive. Here, we show that fibrosis of the mouse kidney was associated with the induction of DNA methyltransferases and increases in global DNA methylation and was alleviated by the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza). Genome wide analysis demonstrated the hypermethylation of 94 genes in mouse unilateral ureteral obstruction kidneys, which was markedly reduced by 5-Aza. Among these genes, Hoxa5 was hypermethylated at its gene promoter and this hypermethylation was associated with reduced HOXA5 expression in fibrotic mouse kidneys after ureteral obstruction or unilateral ischemia-reperfusion injury. 5-Aza prevented Hoxa5 hypermethylation, restored HOXA5 expression, and suppressed kidney fibrosis. Down-regulation of HOXA5 was verified in human kidney biopsies from patients with chronic kidney disease and correlated with the increased kidney fibrosis and DNA methylation. Kidney fibrosis was aggravated by conditional knockout of Hoxa5 and alleviated by conditional knockin of Hoxa5 in kidney proximal tubules of mice. Mechanistically, we found that HOXA5 repressed Jag1 transcription by directly binding to its gene promoter, resulting in the suppression of JAG1-NOTCH signaling during kidney fibrosis. Thus, our results indicate that loss of HOXA5 via DNA methylation contributes to fibrogenesis in kidney diseases by inducing JAG1 and consequent activation of the NOTCH signaling pathway.

The purpose of this study was to explore the effect and mechanism responsible for how curcumin affects the biofilm formation by Streptococcus mutans (S. mutans). The antibacterial activity of curcumin was evaluated by measuring the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). The mass of the biofilm was measured by crystal violet staining. Transcriptome sequencing was used to obtain all the transcript information associated with the biological activity of curcumin-treated S. mutans. Real-time quantitative PCR (qRT-PCR) was performed to examine the expression levels of related biofilm formation genes. The MIC value for curcumin was 64 μM. Curcumin inhibited the formation of a biofilm by S. mutans and degraded mature biofilms. A gene ontology enrichment analysis showed that the DEGs were significantly relevant to biofilm formation. In addition, 17 significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways (p ≤ 0.01) were identified and were potentially associated with the biochemical metabolic processes of S. mutans. DEGs associated with the biofilm formation of S. mutants, including gtfB, gtfC, rgpG, spaP, spxA1, spxA2, bacA, lrgB, and gshAB. The qRT-PCR results were consistent with transcriptome sequencing that the expression levels of gtfB, gtfC, rgpG, and spaP significantly decreased in the curcumin-treated group, whereas the expression levels of spx1, spx2, bacA, lrgB, and gshAB were up-regulated. Curcumin showed marked inhibitory effects against the formation of biofilms by S. mutans and degradation of formed biofilms.

Pandoraea species are emerging multidrug-resistant pathogens with inconsistent carbapenem susceptibility, being resistant to meropenem but susceptible to imipenem, which complicates treatment. Here, we identified a previously uncharacterized oxacillinase gene, bla_OXA-1152, in 12 Pandoraea sputorum strains from Wuhan, China. Deleting bla_OXA-1152 reduced meropenem and imipenem minimal inhibitory concentrations (MICs) by 64- and 4-fold, respectively, while reintroducing it into P. sputorum and E. coli DH5α restored resistance. Mechanistically, OXA-1152 exhibited stronger binding and hydrolysis efficiency for meropenem than imipenem. Combining avibactam with carbapenems restored susceptibility to meropenem and further reduced imipenem MICs, highlighting OXA-1152’s role in resistance variation. These findings reveal the molecular basis of carbapenem resistance discrepancy in Pandoraea and suggest avibactam-carbapenem combinations as a promising therapeutic strategy, offering broader implications for treating multidrug-resistant infections.

Metastasis remains the primary cause of mortality in gastric cancer patients; however, the underlying mechanisms driving this process remain incompletely understood. Here, we performed an integrated single‐cell analysis of gastric cancer primary tumours and their corresponding liver and lymph node metastases to identify critical intercellular communication networks driving the metastatic process. Notably, gene expression analysis of metastatic tissues showed significant upregulation of cholesterol metabolism and PPAR signalling pathway (a nuclear receptor–mediated regulatory system that orchestrates lipid metabolism, adipogenesis and energy homeostasis) genes compared to primary tumours. Our analysis revealed that myeloid cell–derived Galectin‐9 (LGALS9) and its receptor beta‐subunit of prolyl 4‐hydroxylase (P4HB) on epithelial cells constitute a previously uncharacterized ligand–receptor interaction involved in gastric cancer metastasis. Functional experiments confirmed that the activation of P4HB by LGALS9 significantly enhanced proliferation, epithelial‐mesenchymal transition (EMT) and lipid metabolism in gastric cancer cells, while pharmacological inhibition of P4HB reversed these effects. Collectively, our findings establish the myeloid‐derived LGALS9‐P4HB interaction as a crucial mediator of gastric cancer metastatic colonisation through modulation of lipid metabolism, suggesting a potential therapeutic target for metastatic gastric cancer.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been successfully applied to identify microorganisms. However, unlike bacteria and yeast where identification results can be obtained rapidly and accurately by using a simple direct-coating pretreatment method, the traditional pretreatment methods for filamentous fungi are more complex, involving ethanol, formic acid, acetonitrile, and a protein extraction process by centrifugation, i.e., the EtOH-FA full extraction. This cumbersome pretreatment for filamentous fungi is a major reason for the lack of widespread use of MALDI-TOF MS for the identification of filamentous fungi in clinical settings. The present study describes an alternative method, the FA-sandwich, and demonstrates that the approach is efficient and effective. 148 clinical filamentous fungal isolates collected from three large general hospitals in Hubei Province, China, were processed by the FA-sandwich method and identified by two MALDI-TOF MS platforms, Autof ms and Vitek MS. The FA-sandwich allowed a 93.9% species-level identification with Autof ms, and 97.3% species-level identification rates were found for Vitek MS when the IVD, the RUO and in-house databases are used in combination. Further comparison of the ease of FA-sandwich with the EtOH-FA full extraction showed that the FA-sandwich is a more convenient, time- and reagent-saving, and sensitive pretreatment method. These findings indicate that the FA-sandwich method is suitable for pretreating filamentous fungi followed by MALDI-TOF MS identification in clinical microbiology laboratories. Lay summary: The FA-sandwich method improves the efficiency of identification of filamentous fungi using MALDI-TOF MS while ensuring identification accuracy. The method is easy to perform and very suitable for detecting mold in the microbiology laboratory with the goal of promoting timely and accurate therapies.

Within the complex system of gastric cancer, the tumour microenvironment mediates a complex network of cellular interactions, yet its tissue‐specific intracellular communication patterns have remained poorly understood. Leveraging cutting‐edge single‐cell RNA sequencing, we investigated two independent research studies (GSE183904 and GSE184198), creating an unprecedented map of cellular crosstalk across gastric cancer tissues, their adjacent normal tissue and gastric mucosa (GM). Our systematic analysis revealed two distinct patterns: 7557 distinct interactions from normal tissue to tumour cells, while gastric mucosa engaged in 7320 unique interactions with malignant conditions. Within this cellular network, the endothelin pathway emerged as a key regulator, specifically increased in gastric mucosa‐to‐tumour interaction. The Cancer Genome Atlas data demonstrated that patients harbouring elevated EDNRA expression faced significantly poorer outcomes. EDNRA, previously underexplored in this context, showed remarkable upregulation across diverse gastric cancer cell lines. Through experimental validation, we demonstrated that EDNRA overexpression, when stimulated by endothelin‐1, dramatically accelerated the proliferation of human gastric epithelial GSE‐1 cells. Conversely, pharmacological inhibition of EDNRA using ABT‐627 suppressed both NCI‐N87 and MKN‐28 gastric cancer cells proliferation. Further mechanistic investigation revealed the molecular mechanism of ABT‐627: simultaneously triggering both extrinsic and intrinsic apoptotic cascades. TISIDB analysis revealed significant positive correlations between EDNRA and multiple immunostimulators, suggesting the role of EDNRA in immunomodulation networks. These findings reveal a previously unidentified connection between gastric mucosa and tumour progression, positioning EDNRA not only as a molecular target, but also as a critical mediator of tissue‐specific cancer communication. In conclusion, EDNRA functions as both a regulatory factor and therapeutic target, offering a promising therapeutic avenue for gastric cancer intervention.