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.

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.

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

Objective To explore the research hotspots and development trends of Ziziphi Spinosae Semen in the past 20 years,and to provide reference for related research.Methods Literatures on Ziziphi Spinosae Semen were searched from January 1,2000 to December 31,2022 in CNKI,Web of Science Core Collection Database.VOS viewer software was used to visually analyze the citation frequency,research institutions and keyword hotspots of English literatures.CiteSpace software was used to visually analyze research institutions,authors,emergence keywords and keyword overlap time of Chinese literatures,and Microsoft Excel 2021 software was used to analyze of annual publication trends and publication volume of Chinese and English literatures,and download frequency of Chinese literatures.Results A total of 4 872 Chinese and 128 English literatures were included,with an overall upward trend in the number of annual publications.The research institutions with the highest number of publications in Chinese and English were Shandong University of Traditional Chinese Medicine and Tianjin University of Commerce,and the authors with the highest number of publications were DU Chenhui and XIE Junbo,respectively.The most frequent keywords in Chinese literatures were"Ziziphi Spinosae Semen","composed"and"application of compound therapy",and in English literatures were"performance","oxidative stress".Conclusion From 2000 to 2022,the research hotspots of Ziziphi Spinosae Semen mainly focused on the chemical composition,pharmacological effects and clinical application analysis,compatibility research,formulation and preparation.Quality control and evaluation of Ziziphi Spinosae Semen,and the research on the mechanism of preventing and treating insomnia with Ziziphi Spinosae Semen may become future research directions.

Objectives:To analyze the consistency of evaluating left ventricular hemodynamics (HDF) based on single plane and multi plane cine sequences of magnetic resonance mitral valve orifice.Methods:A prospective study was conducted on 48 healthy adults, and two methods were used to measure the mitral valve diameter and calculate HDF parameters. The first method was to measure the diameter of the mitral valve opening in the left ventricular three chamber cine sequence; The second method is to measure the mitral valve diameter using cine sequences of two chamber, three chamber, and four chamber hearts, and then take the average value. Paired t-tests were used to compare the differences in HDF measured by two methods, and Pearson correlation coefficient ( r), intra group correlation coefficient ( ICC), and Bland-Altman analysis were used to test the consistency and reproducibility of the two methods. Results:The root mean square (RMS) of longitudinal HDF calculated using single plane and multi plane mitral valve diameters were [(17.28±4.41)% vs (17.21±4.61)%] ( P=0.379) for the entire cardiac cycle, [(21.45±5.54)% vs (21.49±5.68)%] ( P=0.646) for systolic phase, and [(12.78±4.10)% vs (12.54±4.24)%] ( P=0.106) for diastolic phase, respectively. The difference in the calculation results of HDF parameters related to ventricular function was not statistically significant (all P>0.05), and there was good consistency ( r=0.924-0.996, ICC=0.924-0.995). The two HDF parameters related to atrial function were sensitive to the measurement method of mitral valve orifice diameter [RMS of longitudinal HDF during active atrial emptying: (3.26±1.51)% vs (3.32±1.55)%, P=0.006; longitudinal HDF pulse during active atrial emptying: (-2.60±1.28)% vs (-2.76±1.30)%, P<0.001]. Conclusions:The ventricular function related HDF parameters obtained from the analysis of mitral valve orifice diameter using single plane and multi plane methods have good consistency, and can be evaluated using relatively simple single plane methods for left ventricular HDF.

Objective:To explore the value of dual-layer detector spectral CT quantitative parameters in evaluating the treatment response of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The study was a cross-sectional study. From May 2021 to March 2023, a total of 52 patients with LARC who received complete nCRT and were pathologically confirmed rectal adenocarcinoma at the Guangdong Province Hospital of Traditional Chinese Medicine were retrospectively enrolled. Each patient underwent spectral CT examination before and after nCRT, including plain scan, arterial phase (AP), and venous phase (VP) scans. According to the tumor regression grade, the patients were divided into the good response ( n=20) and the poor response group ( n=32). Measurements of the primary tumor′s spectral CT parameters, including effective atomic number (Z eff) at plain scan, iodine concentration (IC), CT values of 40 keV and 100 keV virtual monochromatic image (VMI) at dual-enhanced phases, were taken before and after nCRT. Additionally, the normalized iodine concentration (NIC), spectral curve slope (λHU), and the change rate of the above parameters before and after nCRT were calculated. The independent sample t-test or Mann-Whitney U test was used to compare the differences between the two groups. The receiver operating characteristic (ROC) curve was used to assess the efficacy of various metrics in evaluating the tumor treatment response of nCRT. A binary logistic regression analysis of combined parameter results was performed for the parameters with the areas under curve (AUC)>0.75, and the AUC of the combined parameter was evaluated. Results:There were significant differences in NIC AP and λHU VP before nCRT, NIC VP and λHU VP after nCRT, and the change rates of Z eff, NIC AP, NIC VP and λHU AP between the good response group and the poor response group ( P<0.05). The remaining parameters showed no statistically significant difference ( P>0.05). The ROC curve results showed that the AUCs of the above 8 parameters for evaluating tumor treatment response of nCRT were 0.702, 0.655, 0.695, 0.769, 0.738, 0.807, 0.791, and 0.677, respectively. The AUC of the combined model of the three parameters with AUC>0.75 (λHU VP after nCRT, the change rate of NIC AP and NIC VP) was 0.869, with 80.0% sensitivity and 84.4% specificity. Conclusion:The quantitative parameters derived from spectral CT may provide new markers for evaluating the response to nCRT treatment in patients with LARC. The multi-parameter combined model can improve diagnostic efficacy.

Background Quartz dust cannot be degraded in the lungs, and inhalation of a large amount of quartz dust in the occupational production process will lead to the occurrence of pulmonary fibrosis, and then develop into silicosis. In recent years, studies have found that exosomes may be involved in the pathogenesis of fibrotic diseases by carrying microribonucleic acid (miRNA), but the mechanism of their actions in silicosis still needs to be studied. Objective To investigate the role of exosome-derived miRNA-21-5p/mothers against decapentaplegic homolog 7 (Smad7) in quartz dust-induced pulmonary fibrosis in rats. Methods Twenty-four healthy male SD rats were randomly divided into four groups (six rats in each group): control 4-week group, control 16-week group, quartz 4-week group, and quartz 16-week group. At the beginning of the experiment, 1 mL of quartz suspension (50 mg·mL⁻¹) and 1 mL of normal saline were injected into the trachea of rats in the quartz group and the control group, respectively, by means of one-time non-exposure intratracheal dust staining. Alveolar lavage was performed at the 4th and 16th weeks after dust staining, the exosomes in lavage solution were extracted by polyethylene glycol (PEG) precipitation, morphological identification was conducted by transmission electron microscopy (TEM), particle size of exosomes was detected by nano-tracking analysis (NTA), and the marker proteins CD9 and CD63 of exosomes were detected by Western blotting (WB). The expression of miRNA-21-5p in exosomes was determined by reverse transcription polymerase chain reaction (RT-PCR). The degree of lung tissue injury and fibrosis was observed by hematoxylin-eosin staining (HE) and Masson staining. The collagen content of lung tissue was detected by hydroxyproline (HYP) method. The expression of Smad7 protein in lung tissue was detected by WB. Results The results of pathological staining showed that compared with the control group, lung inflammatory cell infiltration, alveolar wall thickening, and collagen increase were observed after 4 weeks of dusting, and collagen deposition and silicon nodules appeared after 16 weeks of dusting. Compared with the control group, the expression level of HYP in the lung tissue of the quartz group was increased after 4 weeks and 16 weeks of dust staining (P<0.05). Transmission electron microscopy showed that exosomes were saucer-shaped, and the average particle size of exosomes was 95.8 nm by NTA. Positive expression of exosome marker proteins CD9 and CD81 was found by WB. Compared with the control group, the expression of exosome-derived miRNA-21-5p in alveolar lavage fluid in the quartz group increased in the 4th week and the 16th week (P<0.05), and the expression of Smad7 protein in lung tissue decreased (P<0.05). Conclusion Exosome-derived miRNA-21-5p and Smad7 may be involved in the mechanism of quartz dust-induced pulmonary fibrosis in rats.