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Background Steatotic livers tolerate ischemia–reperfusion injury (IRI) poorly, increasing the risk of organ dysfunction. Ferroptosis is considered the initiating factor of organ IRI. Heme oxygenase oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) (HO-1/BMMSCs) can reduce hepatic IRI; however, the role of ferroptosis in IRI of steatotic grafts and the effect of HO-1/BMMSCs-derived exosomes (HM-exos) on ferroptosis remain unknown. Methods A model of rat liver transplantation (LT) with a severe steatotic donor liver and a model of hypoxia and reoxygenation (H/R) of steatotic hepatocytes were established. Exosomes were obtained by differential centrifugation, and the differentially expressed genes (DEGs) in liver after HM-exo treatment were detected using RNA sequencing. The expression of ferroptosis markers was analyzed. microRNA (miRNA) sequencing was used to analyze the miRNA profiles in HM-exos. Results We verified the effect of a candidate miRNA on ferroptosis of H/R treated hepatocytes, and observed the effect of exosomes knockout of the candidate miRNA on hepatocytes ferroptosis. In vitro, HM-exo treatment reduced the IRI in steatotic grafts, and enrichment analysis of DEGs suggested that HM-exos were involved in the regulation of the ferroptosis pathway. In vitro, inhibition of ferroptosis by HM-exos reduced hepatocyte injury. HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis. Conclusion Ferroptosis is involved in the IRI during LT with a severe steatotic donor liver. miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft IRI, which might be a promising strategy to treat IRI in steatotic grafts. Graphical Abstract

Background Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR. Methods BMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells. Results NMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ. Conclusions NK cell and CD8 + T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.

Colistin resistance in bacteria has become a significant threat to food safety and public health, and its development was mainly attributed to the plasmid-mediated mcr genes. This study aimed to determine the global prevalence and molecular characteristics of mcr-producing Salmonella enterica isolates. A total of 2279 mcr-producing Salmonella genomes were obtained from the public database, which were disseminated in 37 countries from five continents worldwide, including Asia, Europe, America, Australia, and Africa. Human samples (39.5%; 900/2279) were the predominant sources of mcr-producing Salmonella isolates, followed by foods (32.6%), animals (13.7%), and environment (4.4%). Furthermore, 80 Salmonella serotypes were identified, and Typhimurium and 1,4,[5],12:i:- were the predominant serotypes, accounting for 18.3% and 18.7%, respectively. Twenty mcr variants were identified, and the most common ones were mcr-9.1 (65.2%) and mcr-1.1 (24.4%). Carbapenems-resistance gene blaNDM-1 and tigecycline-resistance gene tet(X4) were identified in one isolate, respectively. Phylogenetic results indicated that mcr-producing Salmonella fell into nine lineages (Lineages I-IX), and Salmonella Typhimurium, 1,4,[5],12:i:- and 4,[5],12:i:- isolates from different countries were mixed in Lineages I, II and III, suggesting that international spread occurred. These findings underline further challenges for the spread of Salmonella-bearing mcr genes.

Staphylococcus aureus, a major cause of foodborne illness globally, presents significant challenges due to its multidrug resistance and biofilm-forming capabilities. Pyruvate carboxylase (PycA), a metabolic master switch linking glycolysis and the tricarboxylic acid (TCA) cycle, is a potential target for controlling S. aureus. In this study, a pycA mutant was constructed and analyzed using phenotypic assays and proteomics to investigate its role in virulence and antimicrobial resistance. The results showed that deletion of pycA in the foodborne methicillin-resistant strain ATCC BAA1717 resulted in a 4- to 1024-fold reduction in resistance to β-lactams, aminoglycosides, and macrolides; a 23.24% impairment in biofilm formation; and a 22.32% decrease in staphyloxanthin production, a key antioxidant essential for survival in oxidative food environments. Proteomic analysis revealed downregulation of the TCA cycle, purine biosynthesis, surface adhesins (FnbA/B, SasG), and β-lactamase (BlaZ), linking PycA-mediated metabolism to phenotypes relevant to food safety. These findings underscore the importance of PycA as a metabolic regulator crucial for S. aureus resilience in food systems, suggesting novel strategies to combat foodborne staphylococcal infections through metabolic interference.

Enterotoxigenic (ETEC), an important intestinal pathogen, poses a significant threat to the intestinal health of piglets. (BC), a potential feed additive, can improve the intestinal function of piglets. However, the effects of BC on growth performance and intestinal function in ETEC-infected piglets are still unclear. In this study, 24 7-day-old piglets were randomly assigned to three treatment groups: control group (fed a basal diet), ETEC group (fed a basal diet and challenged with ETEC K88) and BC+ETEC group (fed a basal diet, orally administered BC, challenged with ETEC K88). During Days 1-6 of the trial, piglets in the BC+ETEC group were orally administered BC (1×10 CFU/kg). On Day 5 of the trial, piglets in the ETEC and BC+ETEC groups were orally administered ETEC K88 (5×10 CFU/piglet). Blood, intestinal tissue, and content samples were collected from the piglets on Day 7 of the trial. The average daily feed intake in the ETEC group was significantly reduced compared to that of the control group. Further research revealed that ETEC infection significantly damaged the structure of the small intestine. Compared to the control group, the villus height and surface area of the jejunum, the ratio of villus height to crypt depth in the duodenum and jejunum, and the activities of catalase and total superoxide dismutase in the jejunum were significantly reduced. Additionally, the levels of myeloperoxidase in the jejunum, malondialdehyde in the plasma and jejunum, and intestinal epithelial apoptosis were significantly increased in the ETEC group. However, BC supplementation had significantly mitigated these negative effects in the BC+ETEC group by Day 7 of the trial. Moreover, BC supplementation improved the gut microbiota imbalance by reversing the decreased numbers of , and in jejunum and , and in the colon, as well as the increased number of in the jejunum induced by ETEC K88. Overall, BC supplementation reduced the decline in average daily feed intake in ETEC K88-infected piglets by attenuating intestinal epithelial apoptosis and oxidative stress and regulating the gut microbiota. This suggests that BC may be used to prevent intestinal infections caused by ETEC in piglets.

Staphylococcus aureus biofilms are a serious problem in the food industry. Wall teichoic acid (WTA) is crucial in S. aureus biofilm formation. Overexpression of the WTA-hydrolyzing enzyme glycerophosphoryl diester phosphodiesterase (GlpQ), induced by lactobionic acid (LBA), may be related to biofilm formation. We investigated the relationship between the regulation on GlpQ degradation of WTA by LBA and S. aureus biofilm formation. LBA minimum inhibitory concentration for S. aureus was 12.5 mg/mL. Crystal violet staining revealed the LBA-mediated inhibition of S. aureus adhesion and biofilm formation. RT-qPCR revealed the repressed expression of adhesion-related genes by LBA. Scanning electron microscopy revealed the obvious disruption of S. aureus surface structure, confirming the repression of S. aureus adhesion and biofilm formation by LBA. Native-PAGE results suggested that the WTA content of S. aureus was reduced under the inhibition of LBA. Additionally, LBA induced the overexpression of glpQ. Combined with our previous work, these results suggest that glpQ is induced in S. aureus to function in WTA degradation with the addition of LBA, resulting in decreased WTA content and subsequent reduction of adhesion and biofilm formation. The findings provide new insight into the degradation mechanism of S. aureus WTA and indicate the potential of LBA as an anti-biofilm agent.

Background In diagnosing type 1 autoimmune pancreatitis (AIP), serum IgG4 (sIgG4) can be false-negative. EUS-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) pathology is key for diagnosis, but clinical features’ impact on pathologic confirmation is unclear. This study analyzed their link and factors improve diagnostic accuracy. Methods We analyzed data from a single-center retrospective study at Changhai Hospital (Jan 2009-Jan 2024). Type 1 AIP was diagnosed per International Consensus Diagnostic Criteria (ICDC). Patients with surgical diagnosis, no EUS, or incomplete biopsy data were excluded; eligible cases were grouped into “Confirmed”/“Unconfirmed” per ICDC. Baseline data, laboratory indicators, imaging, and EUS-FNA/FNB data were collected. Statistical analyses (ROC, χ² tests, multivariate logistic regression) were done with R 4.4.0. Results A total of 182 suspected type 1 AIP patients were enrolled; 84.07% were male, 88.46% middle-aged/elderly. Common symptoms: abdominal discomfort (65.93%), obstructive jaundice (43.41%). sIgG4 > 2×ULN (twice upper normal limit) occurred in 64.84%. Multivariate analysis: pathological confirmation rate 65.12% (EUS-FNB) vs. 18.75% (EUS-FNA) ( P  < .001, former higher). For IgG4-positive cells: 82.56% confirmation rate (> 10 cells/high-power field[HPF]) vs. 16.67% (< 10 cells/HPF) ( P  < .001). EUS-FNB (OR = 3.56, 95% CI: 1.55–8.18, P  = .003) and IgG4-positive cell count (> 10 cells/HPF) (OR = 15.71, 95% CI: 6.96–35.46, P  < .001) were independent confirmation predictors. Gender, age, sIgG4 had limited value; renal involvement, retroperitoneal fibrosis were auxiliary indicators. Conclusions Following systematic multi-dimensional factor screening, pathological confirmation of type 1 AIP relies on two key factors: EUS-FNB and histopathological detection of IgG4-positive cells (> 10 cells/HPF). Integrating these core diagnostic modalities with additional indicators—such as auxiliary markers of extrapancreatic involvement (e.g., renal involvement)—further enhances diagnostic precision, which facilitates the refinement of clinical diagnostic workflows for type 1 AIP.

Aim The main focus of this study is to explore the molecular mechanism of IRF7 regulation on RPS18 transcription in M1‐type macrophages in pancreatic adenocarcinoma (PAAD) tissue, as well as the transfer of RPS18 by IRF7 via exosomes to PAAD cells and the regulation of ILF3 expression. Methods By utilising single‐cell RNA sequencing (scRNA‐seq) data and spatial transcriptomics (ST) data from the Gene Expression Omnibus database, we identified distinct cell types with significant expression differences in PAAD tissue. Among these cell types, we identified those closely associated with lipid metabolism. The differentially expressed genes within these cell types were analysed, and target genes relevant to prognosis were identified. Flow cytometry was employed to assess the expression levels of target genes in M1 and M2 macrophages. Cell lines with target gene knockout were constructed using CRISPR/Cas9 editing technology, and cell lines with target gene knockdown and overexpression were established using lentiviral vectors. Additionally, a co‐culture model of exosomes derived from M1 macrophages with PAAD cells was developed. The impact of M1 macrophage‐derived exosomes on the lipid metabolism of PAAD cells in the model was evaluated through metabolomics analysis. The effects of M1 macrophage‐derived exosomes on the viability, proliferation, division, migration and apoptosis of PAAD cells were assessed using MTT assay, flow cytometry, EdU assay, wound healing assay, Transwell assay and TUNEL staining. Furthermore, a mouse PAAD orthotopic implantation model was established, and bioluminescence imaging was utilised to assess the influence of M1 macrophage‐derived exosomes on the intratumoural formation capacity of PAAD cells, as well as measuring tumour weight and volume. The expression of proliferation‐associated proteins in tumour tissues was examined using immunohistochemistry. Results Through combined analysis of scRNA‐seq and ST technologies, we discovered a close association between M1 macrophages in PAAD samples and lipid metabolism signals, as well as a negative correlation between M1 macrophages and cancer cells. The construction of a prognostic risk score model identified RPS18 and IRF7 as two prognostically relevant genes in M1 macrophages, exhibiting negative and positive correlations, respectively. Mechanistically, it was found that IRF7 in M1 macrophages can inhibit the transcription of RPS18, reducing the transfer of RPS18 to PAAD cells via exosomes, consequently affecting the expression of ILF3 in PAAD cells. IRF7/RPS18 in M1 macrophages can also suppress lipid metabolism, cell viability, proliferation, migration, invasion and intratumoural formation capacity of PAAD cells, while promoting cell apoptosis. Conclusion Overexpression of IRF7 in M1 macrophages may inhibit RPS18 transcription, reduce the transfer of RPS18 from M1 macrophage‐derived exosomes to PAAD cells, thereby suppressing ILF3 expression in PAAD cells, inhibiting the lipid metabolism pathway, and curtailing the viability, proliferation, migration, invasion of PAAD cells, as well as enhancing cell apoptosis, ultimately inhibiting tumour formation in PAAD cells in vivo. Targeting IRF7/RPS18 in M1 macrophages could represent a promising immunotherapeutic approach for PAAD in the future. This document is a detailed study on the role of IRF7 and RPS18 in regulating pancreatic cancer progression, specifically through the interactions between M1 macrophages and pancreatic cancer cells. The research utilises single‐cell RNA sequencing and spatial transcriptomics to identify the mechanisms by which IRF7 in M1 macrophages inhibits the occurrence of pancreatic cancer by regulating lipid metabolism‐related pathways. The study highlights the transfer of RPS18 via exosomes from M1 macrophages to pancreatic cancer cells, affecting the expression of ILF3 and thereby influencing the cancer cells' viability, migration, proliferation and apoptosis. Graphical Headlights This study utilised advanced single‐cell RNA sequencing technology. The study revealed the regulatory role of IRF7 in M1 macrophages. It identified the inhibitory effect of IRF7 on RPS18 transcription. The study uncovered the mechanism by which IRF7 suppresses the growth of pancreatic adenocarcinoma cells.

Nanodrug delivery systems (NDDS) have demonstrated broad application prospects in disease treatment, prevention, and diagnosis due to several advantages, including functionalization capability, high drug‐loading capacity, drug stability protection, and the enhanced permeability and retention (EPR) effect. However, their clinical translation still faces multiple challenges, including rapid clearance by the reticuloendothelial system (RES), poor targeting specificity, and insufficient efficiency in crossing biological barriers. To address these limitations, researchers have developed the biological carrier‐mediated nanomedicine hitchhiking strategy (BCM‐NHS), which leverages circulating cells, proteins, or bacteria as natural “mobile carriers” to enhance drug delivery. This approach enables nanocarriers to inherit the intrinsic biological properties, endowing them with immune evasion, prolonged circulation, dynamic targeting, biocompatibility, biodegradability, and naturally optimized biological interfaces. Here, a systematic overview of the BCM‐NHS is provided. First, the review delves into the methods of nanoparticles (NPs) binding and immobilization, encompassing both the surface‐attachment‐mediated “backpack” strategy and the encapsulation‐based “Trojan horse” strategy. Second, the classification of biological carriers, including both cell‐based and non‐cell‐based carriers, is elucidated. Third, the physical properties and release mechanisms of these nanomaterials are thoroughly described. Finally, the latest applications of BCM‐NHS in therapeutic and diagnostic contexts across various disease models including tumor, ischemic stroke, and pneumonia are highlighted. Diagram illustrating the binding methods of NPs and biological barriers. The biological carrier‐mediated nanomedicine hitchhiking strategy (BCM‐NHS) utilizes two distinct techniques: the surface‐based “Backpack” method, which relies on ligand‐receptor binding, covalent conjugation, and non‐covalent binding, and the encapsulated “Trojan horse” approach, which employs neutrophils and monocytes/macrophages as natural delivery vehicles. Created with Biorender (Agreement number: GW2854RTK7).

Quorum sensing (QS) is closely associated with the production of multiple virulence factors in bacterial pathogens. N-acyl homoserine lactones (AHLs) are important QS signal molecules that modulate the virulence of gram-negative pathogenic bacteria. Enzymatic degradation of AHLs to interrupt QS, termed quorum quenching (QQ), has been considered a novel strategy for reduction of pathogenicity and prevention of bacterial disease. However, the low expression levels of QQ proteins in the original host bacteria has affected the applications of these proteins. Previously, we identified a novel marine QQ enzyme, named MomL, with high activity and promising biocontrol function. In this study, we linked the target fragment momL to pNCMO2, which provided a basis for the first heterologous expression of MomL in the antifungal and anti-gram-positive-bacteria biocontrol strain Bacillus brevis, and obtaining the recombinant strain named BbMomL. The QQ activity of BbMomL was confirmed using a series of bioassays. BbMomL could not only degrade the exogenous signal molecule C6-HSL, but also the AHL signal molecules produced by the gram-negative pathogens Pectobacterium carotovorum subsp. carotovorum (Pcc) and Pseudomonas aeruginosa PAO1. In addition, BbMomL significantly reduced the secretion of pathogenic factors and the pathogenicity of Pcc and P. aeruginosa PAO1. We tested the biocontrol function of BbMomL for prevention of plant diseases in vitro. The result indicates that BbMomL has a broad antibacterial spectrum. Compared with wild-type B. brevis, BbMomL not only inhibited fungi and gram-positive bacterial pathogens but also considerably inhibited gram-negative bacterial pathogens. Moreover, the Bacillus brevis expression system has good application prospects and is an ideal host for expression and secretion of foreign proteins.