Objective To analyze the epidemiological characteristics of poisonous mushroom-related foodborne disease incidents in Chongqing from 2010 to 2024, and to provide a scientific basis for effective prevention and control of mushroom-related foodborne diseases. Methods Data of poisonous mushroom related foodborne disease incidents reported by the CDCs of 39 districts and counties in Chongqing from 2010 to 2024 were collected, and their epidemic characteristics were analyzed. Results A total of 264 poisonous mushroom poisoning outbreaks were reported in Chongqing from 2010 to 2024, resulting in 1 046 cases of illness, 543 hospitalizations, and 15 deaths, with a mortality rate of 1.43%. The peak of poisoning incidents was from June to October, accounting for 89.02% of the total number of incidents. The top three high-incidence areas were Pengshui Miao Tujia Autonomous County, Dianjiang County, and Nanchuan District. Poisonous mushroom poisoning incidents occurring in household settings, accidental picking and ingestion, and cases involving unidentified mushroom species accounted for 89.02%, 83.33%, and 90.15% of all foodborne disease outbreak incidents, respectively. Conclusion Foodborne disease incidents related to poisonous mushrooms in Chongqing City show an upward trend, and the effectiveness of prevention and control needs to be improved. Based on their seasonal, regional and household clustering characteristics, efforts should be made before the peak season of mushroom poisoning in high-risk areas, targeting key populations with health education, monitoring and early warning, food safety supervision, and medical treatment.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.

Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

A portable molecularly imprinted(MIP)surface-enhanced Raman scattering(SERS)chip was fabricated via a green electrochemical approach for highly selective detection of bisphenol A(BPA).This MIP-AuNP/UIO-66/SPE sensor was fabricated through a single-step co-deposition process.The process involved electropolymerization onto a UIO-66 modified screen-printed electrode(SPE),by usingo-phenylenediamine(OPD)as functional monomer and BPA as template,and simultaneously electro-reduction generated gold nanoparticles(AuNPs),which served as the SERS-active substrate.Ultimately,this one-step method formed a three-dimensional porous architecture on the electrode surface.Under 785 nm laser excitation,the sensing chip exhibited a highly sensitive SERS response towards BPA.The intensity of its characteristic peak at 850 cm-1 showed a good linear relationship with logarithm of BPA concentration in the range of 1.0×10-10 to 1.0×10-6 mol/L,with a detection limit of 1.0×10-12 mol/L.More importantly,the fabricated chips maintained highly selective binding affinity for BPA in water samples even in the presence of structural analogs bisphenol F(BPF)and bisphenol S(BPS).When the chip was applied to detection of BPA in water samples from plastic bottle and paper cup,the recovery rates ranged from 94.0%to 103.0%with relative standard deviations(RSD)less than 4.7%.The developed chip offered a highly sensitive and selective solution for detection of trace BPA in complex water samples.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective:To evaluate whether the mechanism by which mesenchymal stem cell-derived exosomes (MSC-exo) mitigated endotoxin-induced lung injury was related to the heme oxygenase-1 (HO-1)/mitochondrial signaling pathway in alveolar macrophages of mice.Methods:In vivo experiment Eighteen C57BL/6 wild-type (WT) mice were divided into 3 groups ( n=6 each) using a random number table method: control group (C group), lipopolysaccharide (LPS) group (L group) and LPS + MSC-exo group (LM group). Six HO-1 conditional knockout mice (HO-1 -/-) were selected and served as HO-1 -/- + MSC-exo + LPS group (HML group). The model of endotoxin-induced lung injury was prepared by injection of LPS 15 mg/kg. MSC-exo (2×10 11 particles) was intravenously injected at 1 h before injection of LPS in LM group. MSC-exo (2×10 11 particles) was intravenously injected and 1 h later LPS was injected in HML group. The expression of HO-1 in macrophages was detected using immunofluorescence, lung injury was assessed following hematoxylin-eosin staining, the wet/dry weight ratio (W/D ratio) was determined, and the mitochondrial morphology was observed with a transmission electron microscope. Cell experiment Alveolar macrophages (MH-S) were divided into 4 groups ( n=20 each) using a random number table method: control group (C group), LPS+ phosphate buffer solution group (LP group), LPS+ MSC-exo group (LM group), and LPS+ MSC-exo+ HO-1 small-interfering RNA group (LMS group). Cells were incubated for 12 h with LPS 10 μg/ml in LP, LM and LMS groups. In addition, LM group was incubated with MSC-exo 100 μg/ml, LP group was incubated with the equal volume of phosphate buffer solution, and the alveolar macrophages were transfected with HO-1 small interfering RNA and incubated with MSC-exo 100 μg/ml in LMS group at the same time. The concentrations of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in supernatant were measured by enzyme-linked immunosorbent assay, HO-1 expression was detected by Western blot, the mitochondrial membrane potential was measured using JC-1 staining, and the expression of reactive oxygen species (ROS) was detected by fluorescence. Results:In vivo experiment Compared to C group, the lung injury score and W/D ratio were significantly increased ( P<0.05), the fluorescence signal of HO-1 in macrophages was enhanced, and the damage to mitochondria was aggravated in L group. Compared to L group, the lung injury score and W/D ratio were significantly decreased ( P<0.05), the fluorescence signal of HO-1 in macrophages was enhanced, and the damage to mitochondria was reduced in LM group. Compared to LM group, the lung injury score and W/D ratio were significantly increased ( P<0.05), macrophages had no HO-1 fluorescence signal, and the damage to mitochondria was aggravated in HML group. Cell experiment Compared to C group, the concentrations of IL-1β and TNF-α in supernatant were significantly increased, the expression of HO-1 was up-regulated ( P<0.05), and the mitochondria predominantly exhibited green JC-1 fluorescence, accompanied by an enhanced ROS fluorescence signal in LP group. Compared to LP group, the concentrations of IL-1β and TNF-α in supernatant were significantly decreased, the expression of HO-1 was up-regulated ( P<0.05), and the mitochondria predominantly exhibited red JC-1 fluorescence, accompanied by a weakened ROS fluorescence signal in LM group. Compared to LM group, the concentrations of IL-1β and TNF-α in supernatant were significantly increased, the expression of HO-1 was down-regulated ( P<0.05), and the mitochondria predominantly exhibited green JC-1 fluorescence, accompanied by an enhanced ROS fluorescence signal in LMS group. Conclusions:The mechanism by which MSC-exo attenuates endotoxin-induced lung injury may be related to up-regulation of HO-1 expression in alveolar macrophages and reduction of mitochondrial damage in mice.