BackgroundIn recent years， the incidence of non-suicidal self-injury （NSSI） behaviors among adolescents has been increasing annually. Self-esteem and alexithymia are strongly associated with NSSI behaviors， and alienation is closely linked to both self-esteem and alexithymia. However， there is limited research on the relationship between alienation and NSSI behaviors among adolescents in China. ObjectiveTo analyze the relationship between alienation and NSSI behaviors among adolescents， and to explore the factors influencing NSSI behaviors in this population， so as to provide insights for the prevention and treatment of NSSI behaviors in adolescents. MethodsAdolescents admitted to the Department of Psychiatry and Psychology at the 923^rd Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from September 1， 2021 to March 1， 2023， who met the diagnostic criteria for NSSI in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were selected as the study group （n=60）. Concurrently， middle school students from Nanning were recruited as the control group （n=60）. Participants were assessed using Adolescent Self Harm Scale （ASHS）， Rosenberg Self-Esteem Scale （RSES）， Toronto Alexithymia Scale （TAS） and Adolescent Students′ Alienation Scale （ASAS）. Pearson correlation analysis was employed to examine the relationships between scale scores in the study group， and Logistic regression analysis was used to identify the influencing factors of NSSI behaviors among adolescents. ResultsThe RSES score of the study group was significantly lower than that of the control group （t=-7.033， P<0.01）. The TAS and ASAS scores of the study group were significantly higher than those of the control group （t=5.591， 8.124， P<0.01）. The ASHS score was negatively correlated with RSES score （r=-0.410， P<0.01） and positively correlated with ASAS score （r=0.555， P<0.01）. The RSES scores of the study group were negatively correlated with TAS and ASAS scores （r=-0.317， -0.590， P<0.05 or 0.01）. Logistic regression analysis showed that being female （OR=0.714， 95% CI： 0.042~0.709） was a protective factor for NSSI behaviors among adolescents， while high alienation （OR=1.028， 95% CI： 1.013~1.043） and residing in rural areas （OR=6.692， 95% CI： 2.038~21.967） were risk factors for NSSI behaviors among adolescents. ConclusionAlienation was positively correlated with NSSI behaviors in adolescents. Female adolescents had a lower risk of NSSI behaviors， while those with higher levels of alienation or residing in rural areas were more prone to NSSI behaviors. ［Funded by Self-financed Scientific Research Project of the Health Commission of Guangxi Zhuang Autonomous Region （number， Z20210656）； Self-financed Scientific Research Project of the Health Commission of Guangxi Zhuang Autonomous Region （number， Z-A20231057）］

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

ObjectiveTo investigate the effect and mechanism of Bukan Yilidan on perimenopausal psycho-cardiac disease by mitochondrial autophagy mediated by dynamin-related protein 1（Drp1）/phosphatase and tensin homolog（PTEN） induced putative kinase 1（PINK1）/Parkin pathway. MethodsSixty rats were randomly divided into the blank group， model group， western medicine group（isosorbide mononitrate 7.2 mg·kg^-1+sertraline hydrochloride tablets 18 mg·kg^-1）， Bukan Yilidan low， medium and high dose groups（2.59， 5.18， 10.35 g·kg^-1）， with 10 rats in each group. Except for the blank group， the rat model of perimenopausal psycho-cardiac disease was prepared by ovariectomy（OVX） combined with high-fat feeding， chronic unpredictable mild stress（CUMS） and subcutaneous multi-point injection of isoproterenol hydrochloride. After successful modeling， the general state and tongue image of rats were observed. The depression status of rats in vivo was evaluated by open field test， sucrose preference test， forced swimming immobility time and grip strength value， and the cardiac function of rats was evaluated by electrocardiogram and echocardiography. The levels of serum norepinephrine（NE）， dopamine（DA） and 5-hydroxytryptamine（5-HT） were detected by enzyme-linked immunosorbent assay（ELISA）， and biochemical detection was used to assess myocardial injury by measuring serum levels of high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， triglyceride（TG）， total cholesterol（TC）， aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， lactate dehydrogenase（LDH） and creatine kinase isoenzyme（CK-MB）. Hematoxylin-eosin（HE） and Nissl staining were used to observe the pathological status of hippocampus and myocardial tissue in rats， the status of mitophagosomes in hippocampus and myocardium was observed by transmission electron microscope（TEM）， and Western blot was used to detect the contents of Drp1， mitochondrial fusion protein 2（Mfn2）， optic atrophy protein 1（OPA1）， PINK1， Parkin， p62 and microtubule-associated protein light chain 3B（LC3B） in hippocampus and myocardium. ResultsCompared with the blank group， the food intake and water intake of rats in the model group decreased， the hair was dark yellow， the gloss and smoothness decreased， the spirit was depressed， the tongue was light purple or dark purple， accompanied by petechiae or ecchymosis， the sublingual collaterals were purple and black， and the tongue coating was white and smooth. The indexes of open field test， grip strength and sucrose preference of rats decreased significantly， and the immobility time of forced swimming increased significantly（P<0.01）. Electrocardiogram and echocardiography showed that ST segment was significantly depressed， and left ventricular fractional shortening（LVFS） and left ventricular ejection fraction（LVEF） were significantly decreased（P<0.05， P<0.01）. Pathological observation showed that the number of hippocampal neurons and myocardial cells decreased， and the structural damage was obvious. The levels of serum TC， TG， LDL-C， CK-MB， LDH， AST and ALT increased， while the levels of HDL-C， 5-HT， DA and NE decreased（P<0.05， P<0.01）. TEM showed obvious mitochondrial damage in hippocampus and myocardial tissue. The protein expressions of Drp1， PINK1， Parkin and p62 in hippocampus and myocardium were increased， while the protein expressions of OPA1， Mfn2 and LC3BⅡ/Ⅰ were decreased（P<0.05， P<0.01）. Compared with the model group， the mental state， body curling up， fear of cold and other symptoms of rats in each administration group were improved， and the degree of pale purple or dark purple tongue was reduced. The scores of open field test， grip strength， sucrose preference， LVFS and LVEF were increased， and the immobility time of forced swimming was shortened（P<0.05， P<0.01）. The ST segment of electrocardiogram had a significant recovery（P<0.01）， pathological observation showed that the damage of nerve cells and myocardial tissue was improved. The levels of serum TC， TG， LDL-C， CK-MB， LDH， AST and ALT decreased， while the levels of HDL-C， 5-HT， DA and NE increased（P<0.05， P<0.01）. TEM showed that mitochondrial damage was reduced in hippocampal neurons and cardiomyocytes with visible mitochondrial autophagosomes. The protein expressions of Drp1， PINK1， Parkin and p62 in hippocampus and myocardium were decreased， while the protein expressions of OPA1， Mfn2 and LC3BⅡ/Ⅰ were increased（P<0.05， P<0.01）. ConclusionBukan Yilidan can alleviate depression， lipid metabolism disorder and myocardial ischemia injury in rats with perimenopausal psycho-cardiac disease， and its mechanism may be related to inhibiting Drp1/PINK1/Parkin signaling pathway and enhancing mitochondrial autophagy.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

Synthetic biology, recognized as one of the most revolutionary interdisciplinary fields in the 21st century, has established innovative strategies for the genetic improvement of rice through the integration of multidisciplinary technologies including genome editing, genetic circuit design, metabolic engineering, and artificial intelligence. This review systematically summarizes recent research advancements and breakthrough achievements in the application of synthetic biology in the genetic improvement of rice, focusing on three critical domains: yield improvement, nutritional quality fortification, and reinforcement of disease resistance and abiotic stress tolerance. It elucidates that synthetic biology enables precise genomic and metabolic pathway engineering through modular, standard, and systematic approaches, effectively overcoming the limitations of conventional breeding methods characterized by prolonged cycles and restricted trait modification capabilities. The implementation of synthetic biology has facilitated synergistic improvement of multi-traits, thereby providing critical technical references for developing elite rice cultivars with superior productivity and nutritional value. These technological breakthroughs hold significant implications for ensuring global food security and promoting green and sustainable development of agriculture.
Oryza/growth & development* ; Synthetic Biology/methods* ; Metabolic Engineering ; Plant Breeding/methods* ; Gene Editing ; Genetic Engineering/methods* ; Plants, Genetically Modified/genetics* ; Disease Resistance/genetics*

Genetically modified (GM) crops, as a pivotal innovation in modern agriculture, exhibit significant advantages such as pest and disease resistance, herbicide tolerance, stress tolerance, and yield enhancement. However, their widespread adoption has been associated with potential ecological risks, including weediness of transgenic plants, gene flow, emergence of novel viral strains in virus-resistant crops, impacts on non-target organisms and soil ecosystems, and evolution of target pest resistance. This review focuses on the dual characteristics of GM crops, systematically examining their agronomic benefits and the underlying mechanisms of ecological risks. This review provides a theoretical foundation for optimizing the development of GM crops and ecological risk management, facilitating sustainable agricultural practices.
Plants, Genetically Modified/growth & development* ; Crops, Agricultural/growth & development* ; Ecosystem ; Ecology

Enterococcus faecalis is the main pathogen causing refractory apical periodontitis(RAP).This bacterium can tolerate harsh environments and trigger periapical immune inflammatory responses that result in persistent infection inside and outside the root canal.Adhesion to the dentin wall of root canals and the subsequent formation of biofilms significantly enhances the drug resistance and anti-erosion ability of Enterococcus faecalis,which is the key factor medi-ating its pathogenesis.The adhesion of Enterococcus faecalis to dentin involves non-specific adhesion and specific adhe-sion,and the latter is mediated by adhesion-related virulence factors,mainly including the adhesin of collagen from en-terococci(Ace),extracellular surface protein(Esp),gelatinase(GelE),serine protease(SprE),endocarditis and biofilm associated pilus(Ebp)and aggregation substance(AS),which is regulated by multiple two-component systems.The two-component system Fsr can promote the expression of gelE and sprE when the cell population density increases.GelE can further reduce Ace,while the two-component system GrvRS directly downregulates ace expression in response to the serum environment.The two-component systems CroRS and WalRK may also promote and inhibit the expression of vari-ous virulence factors,including ace and gelE,thus affecting the adhesion of Enterococcus faecalis.In addition,the mech-anochemical preparation and the internal environment of the root canal can also influence the adhesion of Enterococcus faecalis to dentin.Avoiding the introduction of Enterococcus faecalis and using adhesion-interfering medications during root canal treatment can effectively prevent the adhesion of Enterococcus faecalis,and a variety of activated irrigation protocols can also be effective at increasing the clearance of Enterococcus faecalis from the root canal.The design of ra-tional drugs targeting key factors involved in and regulators of the adhesion of Enterococcus faecalis to dentin is expected to provide new ideas and strategies for root canal infection control.The present paper reviews the adhesion of Enterococ-cus faecalis to dentin and its influencing factors.