Objective: To explore the relationship between snack consumption and depressive symptoms in first year junior high school students with different left behind experiences in Yunnan Province, so as to provide a basis for improving depressive symptoms among first year junior high school students with different left behind experiences. Methods: From October to December 2022,a cluster random sampling method was used to select 8 500 first year junior high school students from 11 ethnic minority areas (Fugong County, Longling County, Longyang District, Luchun County, Mojiang County, Nanjian County, Qiaojia County, Shuangjiang County, Tengchong City, Yuanmou County, Zhenyuan County) in Yunnan Province for a questionnaire survey. The Chinese version of Depression Anxiety Stress Scale-21 was applied to assess depressive symptoms in first year junior high school students, and snack consumption was collected by employing food frequency questionnaire. The generalized linear model was used to analyze the association between first year junior high school students snack consumption and depressive symptoms, and the analysis was stratified according to left behind experience. Results: The detection rates of depressive symptoms among firstyear junior high school students with and without left behind experience were 36.25% and 26.91%, respectively. After controlling for confounding variables, the generalized linear model analysis showed that sweet snacks ( β=0.16, 95%CI =0.07-0.25), fast food ( β=0.14, 95%CI =0.04-0.23) and carbonated drinks ( β=0.09, 95%CI =0.01-0.17) of first year junior high school students with left behind experience (all P <0.05). Compared with those without such behavior, the risk of depressive symptoms was higher in consumption of fast food ( β=0.13, 95%CI =0.07-0.18) and carbonated drinks ( β=0.10, 95%CI =0.06-0.15)among first year junior high school students without left behind experience (both P <0.05). Conclusion Snack consumption among first year junior high school students in Yunnan may increase the risk of developing depressive symptoms, while first year junior high school students with left behind experience may have a greater risk of developing depressive symptoms.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Objective:To investigate the correlation between long-term statin use and Helicobacter pylori( Hp)infection in the elderly, and to compare the effects of rosuvastatin combined with bismuth-containing quadruple therapy for Hp eradication on lipid levels in elderly patients with mixed hyperlipidemia. Methods:A retrospective analysis was conducted on 1 181 elderly patients with hyperlipidemia, cardiovascular and cerebrovascular diseases, and peripheral arterial disease who were treated at the First Hospital of Lanzhou University between March 2019 and December 2023.According to the results of carbon 14 urea breath test(C 14-UBT), the subjects were divided into the Hp infection group and the non- Hp infection group.Multivariate logistic regression methods were used to analyze the correlation between Hp infection and statin use.A prospective case-control analysis was conducted on 109 patients with mixed hyperlipidemia and Hp infection treated during the same period, they were treated with rosuvastatin combined with bismuth-containing quadruple therapy for Hp eradication.The successful eradication people were selected as the eradication group (n=95). Patients with hyperlipidemia and Hp infection unwilling eradication was selected as the control group (n=109), and treated with rosuvastatin.Changes in lipid levels were compared over a consecutive 6-month period. Results:The overall Hp infection rate was 53.94%(637/1 181). Univariate analysis showed that the infection rate in women was higher than in men.Body mass index(BMI), low-density lipoprotein cholesterol(LDL-C), fasting blood glucose(FBG)levels in the Hp(+ )group were higher than in the Hp(-)group.Long-term low-dose aspirin users had a higher infection rate than non-users.The infection rate was lower in statin users than in non-users[42.65%(374/877) vs.55.59%(169/304), χ2=15.234, P<0.001]. Multivariate analysis showed that women had a higher infection risk than men ( OR=1.441, 95% CI: 1.102-1.729, P=0.011). Higher FBG and LDL-C levels increased the risk of Hp infection ( OR=1.406, 95% CI: 1.271-2.286, P<0.001, OR=1.118, 95% CI: 1.017-1.387, P=0.010). Aspirin use increased the risk of Hp infection( OR=1.162, 95% CI: 1.034-1.294, P=0.021), while statin use reduced the risk of Hp infection ( OR=0.177, 95% CI: 0.018-0.311, P<0.001). The Hp eradication rate was 87.16%(95/109). At 1-and 2-months post-eradication, statistically significant differences were observed between the eradication and control groups in LDL-C, total cholesterol(TC), changes from baseline, and target achievement rates(all P<0.05). At 1-month post-eradication, a statistically significant difference was observed in high-density lipoprotein cholesterol(HDL-C) levels between the two groups.Additionally, at both 1-and 2-months post-eradication, significant differences were found in the changes in HDL-C levels from baseline between the eradication group and the control group(all P<0.05). Conclusions:Long-term statin use in the elderly may reduce the risk of Hp infection.Rosuvastatin combined with a standard quadruple therapy does not improve the Hp eradication rates in elderly patients with mixed hyperlipidemia, but it facilitates short-term achievement of cholesterol targets.

Objective:To investigate the protective effect of N-acetylcysteine (NAC) against α-amanitin (α-AMA)-induced liver injury via regulation of mitochondrial dynamic imbalance.Methods:Thirty-two ICR mice were randomly (random number) assigned to four groups ( n = 8 per group): normal control, NAC control, α-AMA poisoning, and α-AMA + NAC treatment group. After modeling, behavioral changes were observed and survival curves were plotted. Liver function markers and oxidative stress indicators were measured using ELISA. Pathological damage in liver tissue was examined, and mitochondrial ultrastructural changes were observed via transmission electron microscopy, followed by mitochondrial injury scoring. Survival rates were analyzed using the Kaplan–Meier method. One-way ANOVA was used for intergroup comparisons, followed by pairwise comparisons. Results:Compared with the control group, α-AMA intoxication significantly reduced survival rates and increased serum ALT and AST levels ( P < 0.05). Liver tissues exhibited disordered hepatic cord arrangement, cytoplasmic loosening, and edema. Mitochondria showed moderate to severe swelling, cristae fragmentation, matrix dissolution, and vacuolation, along with increased injury scores ( P < 0.05). Oxidative markers MDA and ROS were elevated, while antioxidant enzymes SOD and CAT were decreased (all P < 0.05). Mitochondrial activity was impaired, expression of fusion proteins OPA1, MFN1, and MFN2 was downregulated, and fission protein DRP1 was upregulated (all P < 0.05). Compared with the α-AMA group, NAC treatment significantly improved survival, reduced ALT and AST levels ( P < 0.05), alleviated pathological and mitochondrial ultrastructural damage, decreased MDA and ROS, increased SOD and CAT (all P < 0.05), enhanced mitochondrial activity, upregulated OPA1, MFN1, and MFN2, and downregulated DRP1 (all P < 0.05). No significant differences were observed between the normal and NAC control groups. Conclusions:NAC may attenuate α-AMA-induced acute liver injury by maintaining mitochondrial dynamic homeostasis.

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This study explores the role and underlying molecular mechanisms of fucoidan sulfate(FPS) in regulating heme oxygenase-1(Hmox1)-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy(DCM) through in vivo and in vitro experiments and network pharmacology analysis. In vivo, a DCM rat model was established using a combination of "high-fat diet feeding + two low-dose streptozotocin(STZ) intraperitoneal injections". The rats were randomly divided into four groups: normal, model, FPS, and dapagliflozin(Dapa) groups. In vitro, a cellular model was created by inducing rat cardiomyocytes(H9c2 cells) with high glucose(HG), using zinc protoporphyrin(ZnPP), an Hmox1 inhibitor, as the positive control. An automatic biochemical analyzer was used to measure blood glucose(BG), serum aspartate aminotransferase(AST), serum lactate dehydrogenase(LDH), and serum creatine kinase-MB(CK-MB) levels. Echocardiography was used to assess rat cardiac function, including ejection fraction(EF) and fractional shortening(FS). Pathological staining was performed to observe myocardial morphology and fibrotic characteristics. DCFH-DA fluorescence probe was used to detect reactive oxygen species(ROS) levels in myocardial tissue. Specific assay kits were used to measure serum brain natriuretic peptide(BNP), myocardial Fe~(2+), and malondialdehyde(MDA) levels. Western blot(WB) was used to detect the expression levels of myosin heavy chain 7B(MYH7B), natriuretic peptide A(NPPA), collagens type Ⅰ(Col-Ⅰ), α-smooth muscle actin(α-SMA), ferritin heavy chain 1(FTH1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), 4-hydroxy-2-nonenal(4-HNE), and Hmox1. Immunohistochemistry(IHC) was used to examine Hmox1 protein expression patterns. FerroOrange and Highly Sensitive DCFH-DA fluorescence probes were used to detect intracellular Fe~(2+) and ROS levels. Transmission electron microscopy was used to observe changes in mitochondrial morphology. In network pharmacology, FPS targets were identified through the PubChem database and PharmMapper platform. DCM-related targets were integrated from OMIM, GeneCards, and DisGeNET databases, while ferroptosis-related targets were obtained from the FerrDb database. A protein-protein interaction(PPI) network was constructed for the intersection of these targets using STRING 11.0, and core targets were screened with Cytoscape 3.9.0. Molecular docking analysis was conducted using AutoDock and PyMOL 2.5. In vivo results showed that FPS significantly reduced AST, LDH, CK-MB, and BNP levels in DCM model rats, improved cardiac function, decreased the expression of myocardial injury proteins(MYH7B, NPPA, Col-Ⅰ, and α-SMA), alleviated myocardial hypertrophy and fibrosis, and reduced Fe~(2+), ROS, and MDA levels in myocardial tissue. Furthermore, FPS regulated the expression of ferroptosis-related markers(Hmox1, FTH1, SLC7A11, GPX4, and 4-HNE) to varying degrees. Network pharmacology results revealed 313 potential targets for FPS, 1 125 targets for DCM, and 14 common targets among FPS, DCM, and FerrDb. Hmox1 was identified as a key target, with FPS showing high docking activity with Hmox1. In vitro results demonstrated that FPS restored the expression levels of ferroptosis-related proteins, reduced intracellular Fe~(2+) and ROS levels, and alleviated mitochondrial structural damage in cardiomyocytes. In conclusion, FPS improves myocardial injury in DCM, with its underlying mechanism potentially involving the regulation of Hmox1 to inhibit ferroptosis. This study provides pharmacological evidence supporting the therapeutic potential of FPS for DCM-induced myocardial injury.
Animals ; Ferroptosis/drug effects* ; Rats ; Diabetic Cardiomyopathies/physiopathology* ; Male ; Rats, Sprague-Dawley ; Polysaccharides/pharmacology* ; Heme Oxygenase-1/genetics* ; Myocytes, Cardiac/metabolism* ; Myocardium/pathology* ; Humans ; Cell Line ; Heme Oxygenase (Decyclizing)

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective To elucidate the regulatory effects of titanium surface modification on the immune function of immature dendritic cells(imDCs),different crystalline nanomorphologies were constructed on titanium surface to investigate the mechanobiological response of imDCs to nanomorphologies with different crystalline phases.Methods Nanomorphologies with different crystalline phases were constructed on the titanium surface by anodic oxidation and calcination.The changes of the cytoskeleton F-actin,cell adhesion and morphology of imDCs cultured on nanomorphologies with different crystalline phases were observed by fluorescence staining.The relative gene expression of adhesion molecules was detected by quantitative real-time PCR.The migration behaviors of imDCs were observed using real-time live-cell imaging,and the membrane fluidity was detected by fluorescence polarization.Results Nanomorphologies with different crystalline phases,namely amorphous phase,anatase and rutile,were obtained on the titanium surface by anodic oxidation and calcination.The cytoskeleton of imDCs on nanomorphologies with different crystalline phases was remodeled.The spreading area of cells on anatase crystalline phase was relatively small,which was(353.3±148.5)μm2.The number of adherent cells was the largest,which was 587±132.The expression of adhesion molecules such as CD11a,integrin β2,ICAM1,and VCAM1 were also increased in cells which cultured on anatase crystalline phase.The imDCs cultured on anatase crystalline phase were equipped with strong migration ability.The accumulative migration distance was(383.6±177.7)μm,and the Euclidean migration distance was(51.82±50.13)μm.The membrane fluidity was relatively weak,and the fluorescence polarization was 0.348 5±0.041 8.Conclusions imDCs can respond to nanomorphologies with different crystalline phases on the titanium surface and exhibit different biomechanical behaviors.The results might provide a theoretical basis for the design of titanium biomaterials with immunomodulatory functions.