OBJECTIVE To explore the effects of isorhamnetin on the development of gastric cancer through up-regulation of solute carrier family 25 member 25 antisense RNA 1（SLC25A25-AS1）. METHODS Using BALB/c nude mice as the subjects， the xenograft tumor model was established by subcutaneously inoculating human gastric cancer MKN28 cells into the axillary region. The effects of low and high doses of isorhamnetin （20 and 40 mg/kg） on the tumor volume and mass in nude mice were investigated. MKN28 cells were selected and divided into control group， isorhamnetin group （70 μmol/L， similarly hereinafter）， isorhamnetin+knocking down negative control group， isorhamnetin+knocking down SLC25A25-AS1 group， isorhamnetin+ overexpression negative control group and isorhamnetin+overexpressing SLC25A25-AS1 group. Effects of knocking down/ overexpressing SLC25A25-AS1 on viability， apoptosis， migration and invasion ability of isorhamnetin-treated cells were detected. After verifying the targeting relationships between microRNA-212-3p （miR-212-3p） and SLC25A25-AS1， as well as phosphatase and tensin homologue deleted on chromosome 10 （PTEN）， the effects of knocking down/overexpressing SLC25A25-AS1 on the expression of miR-212-3p， PTEN mRNA， and PTEN protein in isorhamnetin-treated cells were investigated. RESULTS Compared with the model control group， tumor volume and mass of nude mice in the isorhamnetin low-dose and high-dose groups were reduced significantly， and the isorhamnetin high-dose group was significantly lower than the isorhamnetin low-dose group （P＜0.05）. miR-212-3p had targeting relationships with SLC25A25-AS1 and PTEN. Compared with the control group， the cell viability （intervened for 24， 48 h）， migration number， invasion number and miR-212-3p expression of cells in the isorhamnetin group， isorhamnetin+knocking down negative control group and isorhamnetin+overexpressing negative control group were significantly reduced or decreased or down-regulated， while the apoptosis rate， mRNA and protein expressions of PTEN were significantly increased or up-regulated （P＜0.05）. Compared with isorhamnetin group and isorhamnetin+knocking down negative control group， the cell viability， migration number， invasion number and miR-212-3p expression of cells in the isorhamnetin+knocking down SLC25A25-AS1 group were significantly increased or up- regulated， while the apoptosis rate， mRNA and protein expressions of PTEN were significantly reduced or down-regulated （P＜ 0.05）. Compared with isorhamnetin group and isorhamnetin+overexpressing negative control group， the cell viability， migration number， invasion number and miR-212-3p expression of cells in isorhamnetin+overexpressing SLC25A25-AS1 group were significantly reduced or decreased or down-regulated， while the apoptosis rate， PTEN mRNA and protein expressions were significantly increased or up-regulated （P＜0.05）. CONCLUSIONS Isorhamnetin may inhibit the development of gastric cancer by up-regulating the expression of SLC25A25-AS1， down-regulating miR-212-3p， and up-regulating the expression of PTEN， which is a downstream target of miR-212-3p.

Objective To explore the mechanism by which She-Ti-Zhi-Qiu decoction alleviates allergic rhinitis (AR) through gut microbiota-mediated regulation of T helper cell 17(Th17)/regulatory T cells(Treg) balance and related cytokines. Methods Twenty-eight female SD rats were randomly divided into four groups: the Control group, Model group, STZQ group, and Probiotics group. Except for the Control group, all other groups were sensitized with ovalbumin (OVA) to establish AR models. The Control and Model groups received intragastric administration of normal saline, while the STZQ group was administered She-Ti-Zhi-Qiu Decoction, and Probiotics group received probiotics. After two weeks of continuous intragastric administration, nasal mucosa, serum, peripheral blood, and colon contents were collected. The inflammation of nasal mucosal tissue was assessed via HE staining. 16S rDNA sequencing was used to detect and analyze the structure and content of bacteria in colon contents. Flow cytometry was used to detect the relative proportions of Treg and Th17 cells in peripheral blood. ELISA was used to measure the levels of Th17- and Treg-related cytokines in serum. Results Compared with the Control group, the Model group showed an inflammatory response in nasal mucosal tissue, along with increased IL-17A and IL-17E levels and decreased IL-10 levels. The percentage of Th17 cells in peripheral blood increased, while the percentage of Treg cells decreased. Beneficial bacteria in the intestine were decreased, while pathogenic bacteria were increased. Compared with the Model group, the STZQ group showed lower serum IL-17A and IL-17E levels and higher IL-10 levels. The percentage of Th17 in peripheral blood decreased, while the percentage of Treg increased. There was an increase in beneficial bacteria in the intestine and a decrease in pathogenic bacteria. The changes in the microbiota were correlated with IL-17A, IL-17E, and IL-10 levels. Conclusion She-Ti-Zhi-Qiu decoction can ameliorate the inflammation of AR by regulating gut microbiota and Th17/Treg immune balance.
Animals ; T-Lymphocytes, Regulatory/drug effects* ; Th17 Cells/drug effects* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Rhinitis, Allergic/microbiology* ; Rats ; Cytokines

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective To conduct a quantitative risk assessment of Listeria monocytogenes(LM)in prepackaged,non-vacuum sealed,short shelf-life,ready-to-eat meat products in Chengdu using the@Risk software.Methods Based on monitoring data of LM contamination in pre-packaged,non-vacuum sealed,refrigerated ready-to-eat meat products in Chengdu obtained from a previous study,a risk assessment model was established.The risk of LM infection caused by consuming cooked meat products in different groups of people was quantitatively assessed.In addition,the growth of LM in cooked meat products,from retail to consumption,was also taken into consideration in the assessment.Results In Chengdu,the numbers of potential cases of listeriosis caused by consumption of prepackaged,non-vacuum sealed,refrigerated ready-to-eat meat products were 0.01(95％confidence interval[CI]:0-1.71 × 10-2)per year per million in healthy individuals aged 5-＜65 years old,0.22(95％CI:0-2.67 × 10-1)in healthy individuals aged 65 and above,and 2.88(95％CI:3.85 × 10-8-4.35)in pregnant women.According to the results of the sensitivity analysis,the initial pollution level of LM in the retail stage was the most important factor affecting the prevalence(R=0.25),followed by retail temperature(R=0.08),retail time(R=0.07),and amount of consumption per meal(R=0.07).Conclusions For pre-packaged,non-vacuum sealed,cooked meat products,the most important measure to reduce the prevalence of listeriosis is to control the initial contamination level,which requires food processing plants to regularly clean and strictly disinfect the processing environment and equipment to minimize LM contamination at the source.Retail delicatessens should strictly maintain a storage temperature below 5.0℃ and strictly adhere to product shelf-life recommendations.As for consumers,they should consume these meat products as soon as possible after purchase or store them under refrigerated conditions and shorten the storage time.Pregnant women should thoroughly heat the meat products before eating to reduce the risk of listeriosis.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

Pulmonary fibrosis， chronic obstructive pulmonary disease， acute lung injury， asthma， and infectious pneumonia are common pulmonary inflammatory diseases worldwide. There is evidence that mitochondria produce a large amount of reactive oxygen species （ROS） when stimulated by inflammation， leading to oxidative stress that affects the onset and progression of pulmonary inflammatory diseases. With in-depth research， traditional Chinese medicine （TCM） has made significant progress in the treatment of pulmonary inflammatory diseases. An increasing amount of evidence indicates that single TCM and their active components， as well as TCM compound formulas， can improve mitochondrial oxidative stress status through multi-target and multi-pathway mechanisms， thereby effectively treating pulmonary inflammatory diseases. Currently， there is a lack of systematic review and summary of TCM research in this field both domestically and internationally. Therefore， this article aims to summarize and conclude the mechanisms by which TCM regulates mitochondrial oxidative stress to intervene in pulmonary inflammatory diseases， providing a scientific basis for its clinical application and offering new ideas and references for in-depth research on the prevention and treatment of pulmonary inflammatory diseases with TCM.

Objective To explore the research progress, research hotspot and development trend of tigecycline resistance based on the quantitative analysis and visualization function of CiteSpace. Methods The data were collected from 4,263 Chinese and English articles on tigecycline resistance in CNKI, Wanfang, VIP and Web of Science (WOS) databases from 2012 to 2022. CiteSpace 5.8.R3 software was used to analyze the cooperative network of authors, the cooperative network of countries and institutions, the total citation times of journals, and keywords included in the literature, to reveal the hotspots and trends of tigecycline resistance research. Results The number of articles published in English literature was higher than that in Chinese literature. China had the largest number of published documents, showing a significant international academic influence in this research field. Countries all over the world were concerned about the resistance of tigecycline, but Chinese literatures focused more on the clinical infection and prevention of tigecycline resistance, while English literatures placed special emphasis on the research about the drug resistance mechanism of tigecycline. Conclusion The research direction at home and abroad is basically the same, but the research focus has gradually shifted from the clinical treatment and monitoring of tigecycline to the molecular level of drug resistance mechanism.

Objective:To explore brain network properties and their relationship with cognitive function in children with spastic cerebral palsy (SCP) using diffusion tensor imaging (DTI) based graph theory analysis.Methods:The study was a cross-sectional study. Clinical and imaging data of 21 children with SCP (SCP group) and 32 healthy children (control group) who underwent cranial MRI at the Affiliated Hospital of Zunyi Medical University from August 2020 to April 2022 were analyzed retrospectively. 3D-T 1WI, DTI and Wechsler Intelligence Scale were assessed for all subjects. The Wechsler Intelligence Scale included the verbal comprehension index (VCI), the processing speed index (PSI), the work memory index (WMI), and the perceptual reasoning index (PRI), etc., and ultimately the full scale intelligence quotient (FSIQ) scores were obtained based on the indices of each subscale. Independent samples t-test was used to analyze the differences in the small world attributes [small-world index (σ), normalized shortest path length (λ), normalized clustering coefficients (γ)], global attributes [global efficiency (Eglob), local efficiency (Eloc), characteristic path length (Lp), clustering efficiency (Cp)] and node attributes [degree centrality(DC), nodal efficiency (Ne), betweeness centrality (Bc), nodal shortest path length (NLp), nodal clustering efficiency, nodal local efficiency] between two groups of children′s brain networks. Brain network indicators with statistically significant differences between the 2 groups were correlated with Wechsler Intelligence Scale scores using Spearman. Results:The FSIQ scores on the Wechsler Intelligence Scale and the VCI, WMI, PSI, and PRI were lower in the SCP group than in the control group, and the differences were all statistically significant (all P<0.05). Both groups of children′s brain networks had small world properties. Compared with the control group, Eglob decreased, Lp and λ increased in the SCP group (all P<0.05). Compared with the control group, DC and Ne in multiple brain regions decreased, NLp increased in the SCP group (all P<0.05, FDR corrected). Correlation analysis showed that DC in the right parsopercularis was positively correlated with FSIQ, VCI, WMI and PRI( r=0.53, 0.47, 0.47, 0.60, P=0.019, 0.045, 0.044, 0.020, respectively); NLp in the right parsopercularis was negatively correlated with PRI( r=-0.56, P=0.030); Ne in left paracentral, the right parsopercularis, right precentral, right postcentra were positively correlated with PRI( r=0.62, 0.56, 0.53, 0.54, P=0.015, 0.031, 0.044, 0.039, respectively); Ne in the right precentral was positively correlated with WMI ( r=0.48, P=0.039) in the SCP group. Conclusions:There are changes in the topological attributes of global and multiple regional brain networks in SCP. The changes in the attributes of nodes in the right parsopercularis, right precentral, right postcentral, and left paracentral could reflect cognitive dysfunction in children with SCP.

Objective To analyze the research status and trend of scarlet fever literature in China, and to provide reference for subsequent research. Methods Three major Chinese databases, CNKI, Wanfang, and VIP, as well as Web of Science English database, were used to search for literature related to scarlet fever from 2000 to 2023. Citespace6.2.R2 software was used to statistically analyze the number of publications, authors, institutions and journals, co-cited literature, keyword clustering, and other literature characteristics of the literature. Results From 2000 to 2023, a total of 1 011 Chinese literature were included in the three major Chinese databases. Since 2011, the number of publications had gradually increased, but in recent years, the number of publications had decreased. The organization with the most publications was the Shenyang Center for Disease Control and Prevention. The cluster analysis of key words mainly formed 9 cluster tags, and the high-frequency keywords mainly included epidemic characteristics, epidemiology, incidence rate, etc. A total of 84 English literature were included in the WOS database, with an overall upward trend in publication volume. The institution with the most publications was the China Center for Disease Control and Prevention, and the most frequently cited journal was ^“LANCET INFECT DIS^”.《Resurgence of scarlet fever in China: a 13-year population-based surveillance study》 was the most cited journal. After keyword cluster analysis, 9 cluster labels were mainly formed, and the keywords were mainly outbreak，Hong Kong, and Group A streptococcus. Conclusion Compared with the English literature, which mainly focuses on spatiotemporal aggregation, etiology and strain resistance, Chinese literature focuses more on epidemic surveillance, clinical features and quality nursing.