Objective: To examine the relationship among physical education core literacy, exercise self efficacy, physical self esteem and subjective exercise experience among middle school students, and to analyze the latent classes of exercise self efficacy, so as to provide evidence for enhancing adolescents subjective exercise experience. Methods: Using stratified cluster random sampling, 2 569 students from 12 provinces, autonomous regions or municipality directly under the central govement (Jiangxi, Guangdong, Hunan, Guizhou, Henan, Guangxi, Yunnan, Chongqing, Sichuan, Shandong, Hubei, Hebei) were surveyed from September to November in 2024 with Core Competency Scale of Physical Education, Subjective Exercise Experiences Scale, Exercise Self Efficacy Scale, and Physical Self esteem Scale. Pearson correlation analysis was conducted to explore the relationships among physical education core literacy, exercise self efficacy, physical self esteem, and subjective exercise experience. Mediation models with Bootstrap testing were employed to examine the mediating roles of exercise self efficacy and physical self esteem in the relationship between physical education core literacy and subjective exercise experience. Latent profile analysis (LPA) of exercise self efficacy was performed using Mplus 8.3. Results: Pearson correlation analysis revealed positive associations between physical education core literacy and exercise self efficacy ( r =0.21), physical self esteem ( r =0.38), and subjective exercise experience ( r =0.40); exercise self efficacy was positively correlated with physical self esteem ( r =0.25) and subjective exercise experience ( r =0.45); and physical self esteem was positively correlated with subjective exercise experience ( r =0.34) (all P <0.01). Mediation analysis indicated that physical education core literacy positively predicted subjective exercise experience ( β =0.41, P <0.05), with exercise self efficacy and physical self esteem serving as partial mediators (effect size=0.14, P <0.01), accounting for 34% of the total effect. LPA identified three latent classes of exercise self efficacy:low (14.71%, n =378), moderate (65.51%, n =1 683), and high (19.78%, n =508) exercise self efficacy groups. Conclusion Adolescents exercise self efficacy demonstrates heterogeneity, and both exercise self efficacy and physical self esteem mediate the relationship between physical education core literacy and subjective exercise experience.

Objective: To understand the dynamic temporal evolution pathways of Internet addiction among university students and to identify the core driving nodes, so as to provide theoretical evidences for the precise implementation of targeted interventions. Methods: Using a convenient cluster sampling method, a total of 1 066 full time freshmen and sophomores were recruited from three universities in Guizhou, Jiangxi, and Guangdong Provinces for a follow up survey (T1:January-March 2024; T2:January-March 2025). The Revised Chen Internet Addiction Scale (CIAS-R) was employed to assess the status of Internet addiction among university students, and cross sectional as well as cross lagged panel network models were constructed to analyze Internet addiction and its multidimensional influencing factors. Results: The T1 network comprised 19 nodes and 114 non zero edges, while the T2 network comprised 19 nodes and 126 non zero edges. Cross sectional network analysis revealed the strongest association between "insufficient sleep" and "daytime fatigue"; the core nodes were "first thought upon waking for going online" and "feeling low after disconnection" (characteristics of psychological dependence) at T1, while the core nodes shifted to "impaired health" and "excitement when online" (characteristics of functional impairment and addictive psychodynamic features) at T2. Cross lagged network analysis further indicated that "reduced leisure" directly predicted "sleep compression", and a bidirectional relationship was observed between "needing more time to achieve satisfaction" and "academic decline". Conclusions Internet addiction among university students exhibits dynamic evolutionary characteristics. Stage specific targeted interventions focusing on core driving nodes are needed, integrating behavioral regulation and academic support to break the vicious cycle and enhancing the ability to cope with real life demands.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

In recent years,the field of nucleic acid therapeutics has been flourishing,progressively establishing itself as the third generation of drug modalities following small molecules and antibody-based drugs.Artificial intelligence technology based on machine learning is advancing rapidly,which can significantly accelerate the development process of nucleic acid therapeutics.This review provides an overview of the foundational aspects of artificial intelligence algorithms,databases,and characterizations in the field of nucleic acid drug development.It elucidates the advances in the application of artificial intelligence in nucleic acid structural prediction,small nucleic acid drug design,and other research and development phases of nucleic acid therapeutics,aiming to offer some reference for the interdisciplinary development of artificial intelligence and nucleic acid drugs.

Objective:To explore the expression level and clinical significance of serum Hsa_circ_0089761 in patients with cervical cancer.Methods:A total of 107 cervical cancer patients, 80 cervical intraepithelial neoplasia (CIN) patients, and 60 normal control group were selected and analyzed from January 2021 to March 2023 at the Ninth Affiliated People's Hospital of Shanghai Jiao Tong University School of Medicine. We compared the levels of serum Hsa_circ_0089761, squamous cell carcinoma antigen (SCCA), and carcinoembryonic antigen (CEA) among different groups, and analyzed the relationship between the expression level of serum Hsa_circ_0089761 and the clinical and pathological characteristics of cervical cancer. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of serum Hsa_circ_0089761, SCCA, and CEA levels for cervical cancer. Pearson correlation analysis was used to evaluate the correlation between serum Hsa_circ_0089761 expression levels and SCCA and CEA in cervical cancer patients.Results:The expression levels of serum Hsa_circ_0089761[(2.96±0.95) vs (1.83±0.74), (0.92±0.41)], SCCA[(9.63±1.84)ng/ml vs (2.28±0.65)ng/ml, (1.30±0.27)ng/ml], and CEA[(6.47±2.20)ng/ml vs (1.61±0.57)ng/ml, (1.15±0.12)ng/ml] in the cervical cancer group were significantly higher than those in the CIN group and the control group (all P<0.001), and the serum Hsa_circ_0089761 expression levels in the CIN group were significantly higher than those in the control group ( P<0.001). Cervical cancer patients in stages Ⅲ-Ⅳ, with low differentiation, lymph node metastasis, infiltration depth ≥1/2 of the muscle layer, positive SCCA, and positive CEA had significantly higher levels of serum Hsa_circ_0089761 expression (all P<0.05). The ROC curve analysis showed that the specificity of diagnosing cervical cancer was highest (85.00%) for Hsa_circ_0089761 ≥2.25, and the area under the ROC curve (AUC) for diagnosing cervical cancer in combination with SCCA was highest (0.932, 95% CI: 0.874-0.993), with the highest accuracy (89.30%). The sensitivity of the combination of Hsa_circ_0089761+ SCCA+ CEA in diagnosing cervical cancer was highest (96.26%). The correlation analysis results showed that the serum Hsa_circ_0089761 expression levels in cervical cancer patients were positively correlated with SCCA ( r=0.775, P<0.001) and CEA ( r=0.613, P<0.001). Conclusions:The expression level of serum Hsa_circ_0089761 in cervical cancer patients is significantly increased, which is related to clinical and pathological characteristics. The combination of Hsa_circ_0089761 and SCCA detection has high value in the diagnosis of cervical cancer.

Objective To explore the correlation between serum glycosylated hemoglobin(HbA1c),lym-phocyte activation gene-3(LAG-3)and thyroid nodules in patients with type 2 diabetes mellitus(T2DM).Methods A total of 120 T2DM patients with thyroid nodules admitted to the Third Hospital of Hebei Medi-cal University from July 2021 to July 2022 were included as the study group,and 100 simple T2DM patients(without thyroid nodules)were included as the control group during the same period.According to the patho-logical examination results of thyroid nodules,the study group was grouped into a benign nodule group(85 ca-ses)and a malignant nodule group(35 cases).Enzyme linked immunosorbent assay was applied to detect the serum LAG-3 level of all study subjects.Fully automated glycated hemoglobin analyzer was applied to detect HbA1c level in all study subjects.Spearman method was applied to analyze the correlation between serum HbA1c,LAG-3,and thyroid imaging report and data system(TI-RADS)scores in patients with T2DM and thyroid nodules.Multivariate Logistic regression was applied to analyze the influencing factors of T2DM with thyroid nodules.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of HbA1c and LAG-3 levels in T2DM with thyroid nodules.Results Compared with the control group,the level of HbA1c in the study group was obviously higher(P<0.05),while the level of LAG-3 was obviously lower(P<0.05).Compared with the benign nodule group,the serum LAG-3 level in the malignant nodule group was obviously lower(P<0.05),while the level of LAG-3 was obviously lower(P<0.05).Spearman analysis showed a positive correlation between HbA1c level and TI-RADS score in T2DM patients with thyroid nod-ules(r=0.378,P<0.001),while the serum LAG-3 level was negatively correlated with TI-RADS score(r=-0.472,P<0.001).The results of multivariate Logistic regression analysis showed that HbA1c was a risk factor for the occurrence of thyroid nodules in T2DM patients(P<0.05),and LAG-3 was a protective factor for the occurrence of thyroid nodules in T2DM patients(P<0.05).The combination of HbA1c and LAG-3 in the diagnosis of T2DM with thyroid nodules was superior to their individual diagnosis(Zcombination-HbA1c=2.542,P=0.011;Zcombination-LAG-3=3.098,P=0.002).Conclusion Patients with T2DM combined with thyroid nodules have obviously lower serum LAG-3 level and higher HbA1c level,and the two are related to the malignancy of thyroid nodules.

Objective: To explore the longitudinal relationship between regulatory emotional self-efficacy and the persistence of exercise, so as to provide a reference for promoting the development of exercise habits among college students. Methods: Using a cluster random sampling method, one undergraduate institution was selected from each of Jiangxi, Hunan, Guizhou, Yunnan, Guangdong, Anhui, and Fujian provinces. A total of 2 576 college students were recruited. The Regulatory Emotional Self-efficacy Scale and Exercise Persistence Scale were distributed to college students through the questionnaire star platform. Three rounds of questionnaire surveys were completed in September 2023 (T1), December 2023 (T2), and March 2024 (T3). Crosslagged analysis was employed to explore the relationship between regulatory emotional selfefficacy and the persistence of college students exercise. Results: Repeated measures analysis of variance indicated that the main effects of regulatory emotional self-efficacy on time and gender were statistically significant ( F =102.15, η 2=0.07; F =34.80, η 2=0.01), and the interaction effects between time and gender, as well as between time and academic stage, were also statistically significant ( F =3.81, η 2=0.00; F = 25.54 , η 2=0.02)( P ＜ 0.05). The main effect of exercise persistence on time was statistically significant ( F =111.28, η 2=0.05) and the interaction effect between time and academic stage was statistically significant ( F =27.13, η 2=0.02)( P <0.01). Cross lagged analysis revealed that regulatory emotional self-efficacy at T1 positively predicted exercise persistence at T2 ( β =0.068), and regulatory emotional self-efficacy at T2 positively predicted exercise persistence at T3 ( β =0.368)( P ＜0.01). Prior exercise persistence positively predicted subsequent exercise persistence, with path coefficients of 0.298 and 0.240 ( P <0.01). Exercise persistence at T1 negatively predicted regulatory emotional self-efficacy at T2 ( β =-0.068), and exercise persistence at T2 positively predicted regulatory emotional self-efficacy at T3 ( β =0.061) ( P <0.01). Prior regulatory emotional self-efficacy positively predicted subsequent regulatory emotional self-efficacy, with path coefficients of 0.271 and 0.639 ( P <0.01). Conclusions There is a longitudinal causal relationship between regulatory emotional self-efficacy and college students exercise persistence. In daily physical activities, the significant role of emotional factors in sports practices should be emphasized to promote exercise behaviors among college students.

ObjectiveTo investigate the molecular mechanism of the anti-inflammatory effect of Erchentang in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） via the heparin-binding factor （Midkine）/transmembrane receptor protein （Notch2）/Hey1 signaling pathway. MethodSixty SD rats were randomized into normal group， model group， modified Erchentang （5， 10， 20 g·kg^-1·d^-1） groups， and Notch1 pathway inhibitor （γ-secretase inhibitor， DAPT， 0.02 g·kg^-1） group， with 10 rats in each group. The rat model of COPD was established by cigarette smoke combined with lipopolysaccharide （LPS）. After the modeling， the rats were administrated with corresponding drugs by gavage， and those in the normal and model groups were administrated with normal saline by gavage for 21 days. The levels of Midkine， cytokine-induced neutrophil chemoattractant-1 （CINC-1）， macrophage-derived chemokine （MDC）， chemokine ligand 5 （CXCL5）， neutrophil elastase （NE）， and nuclear factor-kappa B （NF-κB） p65 in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and immunohistochemistry were respectively employed to determine the mRNA and protein levels of Midkine， Notch2， and Hey1 in the lung tissue. ResultCompared with the normal group， the modeling increased the levels of Midkine， CINC-1， MDC， CXCL5， NE， and NF-κB p65 in BALF （P<0.01） and up-regulated the mRNA and protein levels of Midkine， Notch2， and Hey1 in the lung tissue （P<0.01）. Compared with the model group， medium- and high-dose modified Erchentang and DAPT lowered the levels of Midkine， CINC-1， MDC， CXCL5， and NF-κB p65 in BALF （P<0.01） and down-regulated the mRNA levels of Midkine， Notch2， and Hey1 （P<0.01）. ConclusionModified Erchentang may inhibit the inflammation in COPD rats by down-regulating the expression of Midkine， Notch2， and Hey1 and reducing the content of Midkine， CINC-1， MDC， and CXCL5.

ObjectiveTo observe the effect of modified Erchentang on the expression of key molecules in the Jagged1/Notch1/Hes1 signaling pathway in lung tissues of rats with chronic obstructive pulmonary disease （COPD） and explore its anti-inflammatory effect and molecular mechanism on COPD through the Jagged1/Notch1/Hes1 signaling pathway. MethodSixty SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose modified Erchentang groups （5， 10， 20 g·kg^-1）， and γ-secretase inhibitor DAPT group （0.02 g·kg^-1）， with 10 rats in each group. The COPD model was induced in rats by cigarette smoking combined with intratracheal instillation of lipopolysaccharide （LPS）. Rats were treated with corresponding drugs by gavage， while those in the normal group and the model group were treated with the same amount of normal saline by gavage. The serum levels of Notch1， soluble intercellular adhesion molecule-1 （sICAM-1）， activated leukocyte cell adhesion molecule （ALCAM）， and soluble vascular adhesion molecule-1 （sVCAM-1） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of Jagged1， Notch1， and Hes1 was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression of Jagged1， Notch1， Notch1 intracellular domain （NICD1）， and Hes1 in lung tissues of rats was detected by immunohistochemistry （IHC）. ResultCompared with the normal group， the model group showed increased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.01）， increased mRNA expression of Jagged1， Notch1， and Hes1 in lung tissues （P<0.01）， and increased protein expression of Jagged1， Notch1， NICD1， and Hes1 （P<0.01）. Compared with the model group， the medium- and high-dose modified Erchentang groups and the DAPT group showed decreased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.05， P<0.05）， down-regulated mRNA expression of Jagged1， Notch1， and Hes1 （P<0.05， P<0.01）， and reduced protein expression of Jagged1， Notch1， NICD1， and Hes1（P<0.05， P<0.01）. ConclusionModified Erchentang may inhibit the inflammatory response in the lung of COPD rats， and its mechanism may be related to the resistance of inflammatory injury in the lung by decreasing the mRNA expression of Jagged1， Notch1， and Hes1 and inhibiting the release of Notch1， sICAM-1， ALCAM， and sVCAM-1.