ObjectiveTo investigate the relationship between mitochondrial DNA copy number (mtDNAcn) and cognitive dysfunction, and its mediating role between type 2 diabetes mellitus (T2DM) and cognitive dysfunction. MethodsA case-control study was conducted from May 2019 to April 2021 at the Shanghai Yangpu District Central Hospital, China. A total of 193 subjects were recruited and divided into two groups based on the Montreal Cognitive Assessment (MoCA): normal control (NC) group (n=95) and cognitive impairment group (n=98). The prevalence of T2DM was determined on the basis of medical history, while mtDNAcn in peripheral blood samples was quantified using realtime fluorescent quantitative polymerase chain reaction. ResultsUnivariate analyses revealed that the mean mtDNAcn in the cognitive impairment group was 0.76±0.37, significantly lower than that in the NC group (1.06±0.45) (P<0.05). Logistic regression analyses showed that higher mtDNAcn was associated with a reduced risk of cognitive impairment (OR=0.315, 95%CI: 0.125‒0.795). Additionaly, a statistically significant positive correlation was observed between mtDNAcn and the total MoCA score (r=0.381, P<0.01). Morever, T2DM history (OR=2.741, 95%CI: 1.002‒7.497) and elevated glycosylated hemoglobin (HbA1c) levels (OR=1.796, 95%CI: 1.190‒2.711) were identified as risk factors for cognitive impairment. Mediation analyses indicated that mtDNAcn served as a mediator between T2DM/HbA1c and the risk of cognitive impairment, with proportions of mediating effect of 9.04% and 9.18%, respectively. ConclusionPatients with mild and moderate cognitive impairment have significantly lower mtDNAcn than those with normal cognitive function. Reduced mtDNAcn is an influencing factor for cognitive dysfunction and may play a mediating role in the association between T2DM and mild to moderate cognitive impairment.

Objective: To investigate the influencing factors for cognitive function among aluminum workers, so as to provide the basis for intervention and prevention of cognitive function among aluminum-exposed populations. Methods: From July to August 2019, male aluminum workers in the electrolytic aluminum workshop of an aluminum factory in Shanxi Province were selected using the cluster sampling method. Demographic information, prevalence of chronic diseases, lifestyle behaviors, night shifts, and sleep quality were collected through questionnaire surveys. Blood aluminum levels were measured using inductively coupled plasma-mass spectrometry. Cognitive function was investigated using the Montreal Cognitive Assessment. Factors affecting cognitive function among aluminum workers were analyzed by a quantile regression model. Results: A total of 142 aluminum workers were surveyed, including 57 workers aged 20 to <40 years (40.14%) and 85 workers aged 40 to 60 years (59.86%). The median blood aluminum level was 38.23 (interquartile range, 21.82) μg/L. The median cognitive function score was 24.00 (interquartile range, 3.00) points. Quantile regression analysis revealed that older age (βQ5=-0.186, 95%CI: -0.269 to -0.102), lower educational level (βQ5=1.933, 95%CI: 1.029 to 2.838; βQ10=1.743, 95%CI: 0.480 to 3.006; βQ50=1.038, 95%CI: 0.141 to 1.935; βQ75=1.006, 95%CI: 0.437 to 1.575; βQ90=1.111, 95%CI: 0.291 to 1.930), smoking (βQ5=-2.056, 95%CI: -3.264 to -0.849), alcohol consumption (βQ5=-1.821, 95%CI: -3.247 to -0.396) and higher blood aluminum level (βQ5=-0.075, 95%CI: -0.110 to -0.040; βQ10=-0.078, 95%CI: -0.127 to -0.029; βQ50=-0.075, 95%CI: -0.110 to -0.040; βQ75=-0.057, 95%CI: -0.079 to -0.035; βQ90=-0.067, 95%CI: -0.099 to -0.035) were associated with cognitive function decline among aluminum workers. Conclusions Educational level and blood aluminum level are the main factors affecting the cognitive function among aluminum workers. Among those with lower cognitive function scores, age, smoking and alcohol consumption are also associated with cognitive function.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

S-methyl-L-cysteine sulfoxide (SMCO) is a non-protein sulfur-containing amino acid with a variety of functions. There are few reports on the enzymes catalyzing the biosynthesis of SMCO from S-methyl-L-cysteine (SMC). In this study, the flavin-containing monooxygenase gene derived from Schizosaccharomyces pombe (spfmo) was heterologously expressed in Escherichia coli BL21(DE3) and the enzymatic properties of the expressed protein were analyzed. The optimum catalytic conditions of the recombinant SpFMO were 30 ℃ and pH 8.0, under which the enzyme activity reached 72.77 U/g. An appropriate amount of Mg²⁺ improved the enzyme activity. The enzyme kinetic analysis showed that the K_m and k_cat/K_m of SpFMO on the substrate SMC were 23.89 μmol/L and 61.71 L/(min·mmol), respectively. Under the optimal reaction conditions, the yield of SMCO synthesized from SMC catalyzed by SpFMO was 12.31% within 9 h. This study provides reference for the enzymatic synthesis of SMCO.
Schizosaccharomyces/genetics* ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Cysteine/biosynthesis* ; Mixed Function Oxygenases/metabolism* ; Schizosaccharomyces pombe Proteins/metabolism* ; Oxygenases/metabolism* ; Kinetics

Bacillus velezensis DJ1 exhibits broad-spectrum antagonistic activity against diverse phytopathogenic fungi, while its biocontrol mechanisms against Fusarium graminearum, the causal agent of maize stalk rot, remain poorly characterized. In this study, we integrated genomics and transcriptomics to elucidate the antifungal mechanisms of strain DJ1. The results demonstrated that DJ1 inhibited F. graminearum with the efficacy of 64.4%, while its polyketide crude extract achieved the control efficacy of 55% in pot experiments against this disease. Whole-genome sequencing revealed a single circular chromosome (3 929 792 bp, GC content of 47%) harboring 12 biosynthetic gene clusters for secondary metabolites, six of which encoded known antimicrobial compounds (macrolactin H, bacillaene, difficidin, surfactin, fengycin, and bacilysin). Transcriptomic analysis identified 243 differentially expressed genes (152 upregulated and 91 downregulated, P < 0.05), which were potentially associated with the antagonistic activity against F. graminearum. KEGG enrichment analysis highlighted activation (P < 0.05) of cysteine/methionine metabolism, pentose phosphate pathway, and polyketide biosynthesis pathways, indicating that DJ1 employed synergistic strategies involving antimicrobial compound synthesis, energy metabolism enhancement, and nutrient competition to suppress pathogens. This study provides a theoretical foundation for developing novel microbial resources and application technologies to combat phytopathogenic fungi.
Fusarium/drug effects* ; Bacillus/metabolism* ; Plant Diseases/prevention & control* ; Antifungal Agents/pharmacology* ; Genomics ; Zea mays/microbiology* ; Transcriptome ; Gene Expression Profiling ; Antibiosis ; Multigene Family ; Multiomics

To detect interleukin-33(IL-33)level and investigate the effect of IL-33 signaling pathway on monocytes in patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),total of 31 HBV-HCC patients,33 chronic hepatitis B(CHB)patients and 21 normal controls were enrolled in the study.Peripheral blood was collected to isolate plasma and peripheral blood mononuclear cells(PBMC),then CD14+monocytes were purified by magnetic-activated cell sorting.Intrahepatic lymphocytes(IHL)were isolated from para-tumor tissues and tumor tissues of 11 HBV-HCC patients.IL-33 and soluble suppressor of tumorigenicity 2(sST2)levels in plasma were measured by enzyme-linked immunosorbent assay;ST2 expression in CD14+monocytes was investigated by flow cytometry.Recombinant human IL-33 was used to stimulate CD14+monocytes,then the cytokine secretion and HLA-DR proportion in CD14+monocytes were assessed.Furthermore,cytotoxicity of monocytes was also investigated.Data showed that plasma IL-33 level in CHB patients and HBV-HCC patients were lower than that in controls(P<0.01).Plasma sST2 level of HBV-HCC patients was higher than those of CHB patients and controls(P<0.01).ST2+CD14+proportion in PBMC from HBV-HCC patients was lower than those of from CHB patients and controls(P<0.000 1).ST2 mean fluorescence intensity(MFI)in PBC from HBV-HCC patients was lower than those from CHB patients and controls(P<0.0001).ST2+CD14+proportion in IHL was also lower in tumor tissues than that in para-tumor tissues(P<0.05);ST2 MFI in IHL was lower in tumor tissues than that in para-tumor tissues(P<0.05).As compared with controls,monocytes activity of HBV-HCC and CHB patients were lower,especially in tumor tissues,which was presented as downregulation of HLA-DR proportion,TNF-α,IL-6,IL-1β and granzyme B secretion(P<0.05).IL-33 stimulation did not affect ST2 level in CD14+monocytes(P>0.05).Both 0.1 ng/ml and 1 ng/ml of IL-33 stimulation elevated cytokine production and HLA-DR+CD14+monocytes percentage in CD14+monocytes from HBV-HCC patients(P<0.05).However,only 1 ng/ml of IL-33 stimulation promoted monocytes-induced target cell death(P<0.000 1).Taken together,monocytes activity is down-regulated in HBV-HCC patients,and IL-33 signaling pathway could enhance monocytes function in HBV-HCC patients.

The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.

Objective:To analyze the hepatobiliary phase (HBP) image manifestation classification and pathological features of nodules in nodules accompanied by hepatocellular carcinoma (NIN-HCC).Methods:Twenty-five cases cases (27 lesions) with cirrhosis who were confirmed as NIN-HCC by surgical pathology and underwent gadoxetate disodium-enhanced MRI examination before surgery at Nantong Third Hospital affiliated with Nantong University from July 2015 to November 2022 were retrospectively enrolled. The size, signal intensity, enhancement pattern, and pathological features of internal and external nodules were analyzed in NIN-HCC. The lesions score were recorded according to the 2018 version of the Liver Imaging Reporting and Data Systems (LI-RADS) classification criteria. NIN-HCCs were grouped and typed according to the different HBP signal intensities of the inner and outer nodules. The independent-samples t-test, Mann-Whitney U test or Fisher's exact probability method were used to compare the differences in imaging features and LI-RADS scores between the groups. The Spearman correlation coefficient was used to evaluate the correlation between the pathological differentiation degree of internal and external nodules and the HBP signal intensity. The Kaplan-Meier curve was used to analyze recurrence-free survival (RFS) following NIN-HCC surgery. Results:The internal nodules of the 27 NIN-HCCs showed altered hypervascularity with a maximum diameter of (13.2±5.5) mm during the arterial phase. 51.9% (14/27) and 48.1% (13/27) showed "fast in and fast out" and fast in and slow out"enhancement patterns. The external nodules showed altered hypovascularity with a maximum diameter of (25.7±7.3) mm, and 13 (48.1%) of them were accompanied to manifest during the arterial phase. NIN-HCC was divided into two groups according to the signal intensity of HBP of the outer nodules with the background liver parenchyma signal intensity as a reference: the hyposignal group ( n=17, 63.0%) and the isosignal group ( n=10, 37.0%). The hyposignal group and the isosignal group were divided into A~C type and D~F type, a total of six types, according to the hypo, iso, and hyper signals of the inner nodules and the signal intensity of the outer nodules as a reference. Within the hyposignal group, 7.4% (2/27) of the inner nodules showed hyposignal (type A), 37.0% (10/27) showed isosignal (type B), and 18.5% (5/27) showed hypersignal (type C). Within the isosignal group, 29.6% (8/27) of the inner nodules showed hyposignal (type D), 7.4% (2/27) showed isosignal (type E), and there was no hypersignal (type F). 40.7% (11/27) of the lesions were LR-4 in LI-RADS score, and 59.3% (16/27) were LR-5. There was no statistically significant difference ( P>0.05) in the maximum diameter, enhancement pattern, and LI-RADS score of internal and external nodules between the hypo and iso signal group. Histologically, NIN-HCC showed fine trabecular/pseudoglandular duct type without microvascular invasion, among which the inner nodules were mainly moderately differentiated HCC, and the outer nodules were mainly well-differentiated HCC. The degree of differentiation between the inner and outer nodules and the HBP signal intensity had no statistically significant difference ( r=0.290, P=0.143; r=0.079, P=0.697). The median RFS follow-up time after NIN-HCC radical resection was 31.7 months, and the cumulative RFS rates at 1, 3, and 5 years were 96.0%, 76.0%, and 64.0%, respectively. Conclusions:NIN-HCC can serve as a morphological marker for early-stage diagnosis of multi-step cancer evolution in HCC, with certain imaging and pathological features. HBP imaging classification is helpful to enhance the diagnostic recognition of this disease.

Objective:To analyze the concentration of formic acid,propionic acid and butyric acid in gingival crevicular fluid(GCF)of patients with stages Ⅲ and Ⅳ periodontitis,and their relationship with periodontitis.Methods:The study enrolled 37 systemically healthy patients with periodontitis and 19 healthy controls who visited Department of Periodontology,Peking University School and Hospital of Sto-matology from February 2008 to May 2011.Their GCFs were collected from the mesial-buccal site of one molar or incisor in each quadrant.Periodontal clinical parameters,including plaque index(PLI),probing depth(PD),bleeding index(BI),and attachment loss(AL).Concentrations of formic acid,propionic acid and butyric acid in the supernatant of the GCFs were analyzed by high-performance capil-lary electrophoresis(HPCE).The prediction ability of formic acid,propionic acid and butyric acid with the risk of periodontitis and the differences between grade B and grade C periodontitis were analyzed.Results:In this study,32 patients with stage Ⅲ and 5 patients with stage Ⅳ were enrolled,including 9 patients with grade B and 28 patients with grade C.Clinical periodontal variables in the patients with pe-riodontitis were significantly higher than those in the control group(P＜0.001).Formic acid was signifi-cantly lower in periodontitis than that in the control group[5.37(3.39,8.49)mmol/L vs.12.29(8.35,16.57)mmol/L,P＜0.001].Propionic acid and butyric acid in periodontitis were significantly higher than those in the control group:Propionic acid,10.23(4.28,14.90)mmol/L vs.2.71(0.00,4.25)mmol/L,P＜0.001;butyric acid,2.63(0.47,3.81)mmol/L vs.0.00(0.00,0.24)mmol/L,P＜0.001.There was no significant difference in formic acid,propionic acid and butyric acid concentrations between grade B and grade C periodontitis(P＞0.05).Propionic acid and butyric acid in the deep pocket were significantly higher than in the shallow pocket,while the concentration of formic acid decreased with the increase of PD.Propionic acid(OR=1.51,95％CI:1.29-1.75)and butyric acid(OR=3.72,95％CI:1.93-7.17)were risk factors for periodontitis,while formic acid(OR=0.87,95％CI:0.81-0.93)might be a protective factor for periodontitis.Propionic acid(AUC=0.852,95％CI:0.805-0.900),butyric acid(AUC=0.889,95％CI:0.841-0.937),f(formic acid,AUC=0.844,95％CI:0.793-0.895)demonstrated a good predictive capacity for the risk of periodontitis.Conclusion:The concentration of formic acid decrease in the GCF of periodontitis patients,which is a protective factor for periodontitis,its reciprocal have good predictive capacity.However,propionic acid and butyric acid increase,which are risk factors for periodontitis and have good predictive capacity.The concentration of formic acid,propionic acid,and butyric acid vary with probing depth,but there is no significant difference between grade B and grade C periodontitis.