ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

ObjectiveTo explore the vascular endothelial injury in male mice caused by exposure to polystyrene microplastics （PS-MPs） and the intervention effect of luteolin on vascular remodeling. Additionally， to investigate the mechanism through the oxidative system and metabolomics. MethodsThirty-two C57BL/6 mice （6-8 weeks old） were randomly divided into the saline group （saline group）， the 0.1 mg/kg PS-MPs exposure group （0.1PS-MPs group）， the 1 mg/kg PS-MPs exposure group （1PS-MPs group）， and the 1 mg/kg PS-MPs + luteolin treatment group （1PS-MPs + Lut group）， with 8 mice in each group. After 8 weeks of intervention， the body weight， blood pressure， aortic organ coefficient， and aortic histopathological changes of mice in each group were detected； the total cholesterol （TC）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C） lipid metabolism-related indicators in the aorta of mice were detected； the reactive oxygen species （ROS）， glutathione （GSH）， and malondialdehyde （MDA） oxidative stress-related indicators were detected； the endothelin （ET-1）， nitric oxide （NO）， vascular endothelial growth factor A （VEGF-A）， vascular cell adhesion molecule-1 （VCAM-1/CD106）， and intercellular adhesion molecule-1 （ICAM-1/CD54） endothelial function-related indicators and serum metabolomics were detected. ResultsCompared to the saline group， exposure to PS-MPs resulted in pathological thickening of the mouse aorta， increased aortic organ coefficient， and elevated blood pressure. Lipid metabolism-related indicators， including TC and TG， were elevated， while HDL-C was reduced， indicating lipid metabolism disorder in mice. Oxidative stress markers such as ROS and MDA increased， whereas GSH decreased， demonstrating oxidative damage. Vascular endothelial inflammation and injury markers， including ET-1， VEGF-A， VCAM-1， and ICAM-1， were upregulated， while the vasodilatory substance NO was downregulated， confirming endothelial injury. Furthermore， serum metabolomics results revealed that PS-MPs exposure induced endothelial damage by disrupting metabolic pathways such as the citrate cycle. Compared to the PS-MPs group， luteolin significantly reversed these effects， attenuating oxidative stress and lipid metabolism disorders， and effectively repairing endothelial injury. ConclusionPS-MPs induce vascular toxicity through oxidative stress and lipid metabolism. Luteolin effectively alleviates endothelial damage and vascular remodeling.

Objective To investigate the mechanism by which 4-week high-intensity interval training(HIIT)regulates the mitochondrial unfolded protein response(UPRmt)in skeletal muscle and improves mitochondrial function in a rat model of chronic unpredictable mild stress(CUMS).Methods Male SPF-grade SD rats(6～8 weeks old)were divided randomly into control(C),model(M),HIIT+control(HC),and HIIT+model(HM)groups.Rats in the M and HM groups were subjected to CUMS for 8 weeks to establish a depression model,while rats in the HC and HM groups received HIIT for 5 d a week for 4 weeks.The exercise regimen consisted of 3 min high-speed(85％～90％Smax)combined with 1 min low-speed(50％～55％Smax)uninterrupted repetitive training(Smax is maximum training speed).Behavioral changes were evaluated at weeks 4 and 8.Tissue samples were taken 24 h after the last behavioral test and skeletal muscle mitochondria were examined by transmission electron microscopy.The ATP and reactive oxygen species(ROS)contents were measured by enzyme-linked immunosorbent assays and protein expression levels of activating transcription factor(ATF)4,ATF5,C/EBP homologous protein(CHOP),and heat shock protein 60(HSP60)were detected by Western blot.Results(1)The body mass,number of crossing grids,number of upright positions,sugar-water preference rate,and ATP content were significantly decreased in group M compared with group C(P＜0.01),while the number of damaged mitochondria,ROS content,ATF4,ATF5,CHOP,and HSP60 protein expression were significantly increased(P＜0.01).(2)After 4-weeks of HIIT intervention,the ATP content and ATF4 and ATF5 protein expression levels were significantly increased in the HC group compared with C group(P＜0.05,P＜0.01).The number of crossing grids,number of upright positions,sugar-water preference rate,ATP content,and ATF4 protein expression were significantly increased in the HM group compared with M group(P＜0.01),while the number of damaged mitochondria,ROS content,and ATF5,CHOP,and HSP60 protein expression levels were significantly decreased(P＜0.01).(3)After 4 weeks of HIIT intervention,the number of crossing grids in CUMS rats was significantly positively correlated with ATF4 protein expression,and ROS content was correlated with CHOP protein expression,number of damaged mitochondria,and ATF5 protein expression(|r|＞0.75,P＜0.01;|r|＞0.75,P＜0.05).Upright frequency was significantly negatively correlated with ATF5 and HSP60 protein expression,the number of crossing grids,the sugar-water preference rate,and the expression of CHOP and HSP60 proteins(|r|＜0.75,P＜0.05).Conclusions 4-week HIIT intervention can improve mitochondrial dysfunction and alleviate depressive-like behavior in CUMS rats by regulating skeletal muscle UPRmt.

Objective To investigate the mechanism by which 4-week high-intensity interval training(HIIT)regulates the mitochondrial unfolded protein response(UPRmt)in skeletal muscle and improves mitochondrial function in a rat model of chronic unpredictable mild stress(CUMS).Methods Male SPF-grade SD rats(6～8 weeks old)were divided randomly into control(C),model(M),HIIT+control(HC),and HIIT+model(HM)groups.Rats in the M and HM groups were subjected to CUMS for 8 weeks to establish a depression model,while rats in the HC and HM groups received HIIT for 5 d a week for 4 weeks.The exercise regimen consisted of 3 min high-speed(85％～90％Smax)combined with 1 min low-speed(50％～55％Smax)uninterrupted repetitive training(Smax is maximum training speed).Behavioral changes were evaluated at weeks 4 and 8.Tissue samples were taken 24 h after the last behavioral test and skeletal muscle mitochondria were examined by transmission electron microscopy.The ATP and reactive oxygen species(ROS)contents were measured by enzyme-linked immunosorbent assays and protein expression levels of activating transcription factor(ATF)4,ATF5,C/EBP homologous protein(CHOP),and heat shock protein 60(HSP60)were detected by Western blot.Results(1)The body mass,number of crossing grids,number of upright positions,sugar-water preference rate,and ATP content were significantly decreased in group M compared with group C(P＜0.01),while the number of damaged mitochondria,ROS content,ATF4,ATF5,CHOP,and HSP60 protein expression were significantly increased(P＜0.01).(2)After 4-weeks of HIIT intervention,the ATP content and ATF4 and ATF5 protein expression levels were significantly increased in the HC group compared with C group(P＜0.05,P＜0.01).The number of crossing grids,number of upright positions,sugar-water preference rate,ATP content,and ATF4 protein expression were significantly increased in the HM group compared with M group(P＜0.01),while the number of damaged mitochondria,ROS content,and ATF5,CHOP,and HSP60 protein expression levels were significantly decreased(P＜0.01).(3)After 4 weeks of HIIT intervention,the number of crossing grids in CUMS rats was significantly positively correlated with ATF4 protein expression,and ROS content was correlated with CHOP protein expression,number of damaged mitochondria,and ATF5 protein expression(|r|＞0.75,P＜0.01;|r|＞0.75,P＜0.05).Upright frequency was significantly negatively correlated with ATF5 and HSP60 protein expression,the number of crossing grids,the sugar-water preference rate,and the expression of CHOP and HSP60 proteins(|r|＜0.75,P＜0.05).Conclusions 4-week HIIT intervention can improve mitochondrial dysfunction and alleviate depressive-like behavior in CUMS rats by regulating skeletal muscle UPRmt.

Objective:To observe the efficacy and safety of adrenocorticotropic hormone (ACTH) therapy in children with steroid dependent nephrotic syndrome (SDNS)/frequently relapsed nephrotic syndrome (FRNS).Methods:The clinical data of children with SDNS/FRNS who received treatment with prednisone acetate tablets were retrospectively collected from June 2019 to June 2023 in the Nephrology Department of Xi′an Children′s Hospital. The children were divided into glucocorticoid+ACTH group and glucocorticoid group, according to whether ACTH was used or not. The differences in cortisol, total cholesterol and 24 hour urinary protein quantity between 2 groups of children at baseline and follow-up endpoints were compared, and the effectiveness (the proportion of no recurrence and discontinuation of glucocorticoid) and occurrence of adverse reactions were evaluated.Results:A total of 39 patients with SDNS/FRNS were included in this study, with 21 cases in the glucocorticoid+ACTH group and 18 cases in the glucocorticoid group. Among the 39 children, there were 33 cases of SDNS and 6 cases of FRNS, respectively. The proportion of baseline low cortisol levels was 76.9% (30/39). The proportion of cortisol levels returning to normal after ACTH treatment in the glucocorticoid+ACTH group was 76.2% (16/21). The baseline and follow-up endpoint for cortisol levels in the glucocorticoid+ACTH group were 28.0(19.8, 51.5) μg/L and 79.9(58.9, 113.0) μg/L, respectively. The baseline and follow-up endpoint for cortisol levels in the glucocorticoid group were 21.0(15.8, 37.4) μg/L and 25.3(18.2, 51.4) μg/L, respectively. In the 2 groups of cortisol levels, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=11.595, P=0.001), there was a statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=19.462, P<0.001), and the difference was statistically significant in the time effect of the glucocorticoid+ACTH group ( Wald χ2=21.100, P<0.001). The baseline and follow-up endpoint for total cholesterol in the glucocorticoid+ACTH group were 4.95(4.23, 5.26) mmol/L and 4.38(4.04, 5.24) mmol/L, respectively. The baseline and follow-up endpoint for total cholesterol in the glucocorticoid group were 4.80 (4.17, 5.28) mmol/L and 5.74 (5.04, 6.88) mmol/L, respectively. In the 2 groups of total cholesterol, there was statistically significant difference in the interaction effect between time and group ( Wald χ 2=9.842, P=0.002), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ 2=12.187, P<0.001), the difference was statistically significant between the 2 groups in the time effect at baseline and the follow-up endpoint (glucocorticoid+ACTH group: Wald χ 2=6.488, glucocorticoid group: Wald χ2=7.112; all P<0.05). The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid+ACTH group were 115 (105, 128) mg/d and 121 (113, 128) mg/d, respectively. The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid group were 118 (113, 125) mg/d and 138 (119, 2 100) mg/d, respectively. In the 2 groups of 24 hour urinary protein quantity, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=7.743, P=0.005), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=7.779, P=0.005), and the difference was statistically significant in the time effect of the glucocorticoid group ( Wald χ2=13.331, P<0.001). The proportion of no recurrence (17/21) and discontinuation of oral glucocorticoid (16/21) in the glucocorticoid+ACTH group were higher than those in the glucocorticoid group (the proportion were both 6/18), and the differences between the 2 groups were statistically significant (the chi square values were 9.084 and 7.240, respectively; all P<0.01). No adverse reactions occurred in the glucocorticoid group. The incidence of adverse reactions in the glucocorticoid+ACTH group was 14.3% (3/21), of which 2 cases developed generalized urticaria and 1 case developed hypertension. Conclusions:ACTH has a good efficacy and safety in children with SDNS/FRNS. The results of this study need to be further validated by increasing the sample size and conducting multicenter studies.

Objective:To evaluate the improvement in the outcome of intracapsular condylar fractures(ICFs)treatment with pre-cise soft tissue reduction in combination with open reduction and internal fixation(PSTR-ORIF)by comparson with traditional open reduction and internal fixation(T-ORIF).Methods:40 patients with ICFs were treated by T-ORIF and PSTR-ORIF(n=20)re-spectively.Preoperative and 6-month postoperative whole-mouth panoramic tomography,CT and MRI imaging data were analyzed,the repositioning of the soft and hard tissues of temporomandibular joints(TMJs),the Helkimo index,clinical symptoms and subjec-tive symptoms were compared between the 2 groups.Results:In PSTR-ORIF(26 sides)and T-ORIF(27 sides)groups,the rate of complete anatomical restoration of fractured segments at 6 months after surgery was 96.15％and 81.48％,and the overall effective rate of ICF articular disc restoration was 96.15％and 74.07％respectively,the height of the ascending mandibular branch was bet-ter restored in patients with B-type fracture after surgery(P＜0.05).At 6 months postoperatively,patients in the PSTR-ORIF group showed significant improvement in mouth opening,mandibular anterior extension distance,and lateral movement compared with the T-ORIF group(P＜0.05).The Helkimo index showed that the PSTR-ORIF group got a significant improvement in the complaint symptom index score and the clinical symptom index score compared with the T-ORIF group(P＜0.05).Conclusion:PSTR-ORIF is more effective than T-ORIF in the treatment of ICFs for the healing of condylar fractures,restore postoperative TMJ mobility and reduce the postoperative joint discomfort through good repositioning of soft tissues.

Objective To investigate the effect of polystyrene microplastics(PS-MPs)on myocardial injury in mice and its molecular mechanism.Methods A total of 60 male C57BL/6 mice were randomly divided into normal sa-line group,0.1,1,10 mg/kg PS-MPs exposed group,and doxorubicin[5 mg/(kg·w)]group treated for 8 weeks.After treatment,we measured blood pressure,cardiac organ coefficient,cardiac histopathological changes,oxidative stress markers reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),4-hydroxynonenal(4-HNE)and nuclear factor E2-related factor 2(Nrf2),serum centroid injury markers creatine kinase MB(CK-MB)and troponin(cTnT),ferroptosis marker recombinant glutathione peroxidase 4(GPX4),Recombinant solute carrier family 7(SLC7 A11)as well as ferrous ions(Fe2+).Results Compared with the neg-ative control group,vacuolation,inflammatory infiltration and collagen fiber deposition were evident in the hearts of mice after PS exposure.The levels of myocardial injury markers CK-MB and cTnT significantly increased.Cardiac organ coefficient decreased,blood pressure increased,oxidative stress markers and ferroptosis markers increased.Conclusion PS-MPs exposure can induce oxidative stress and activate ferroptosis pathway,resulting in myocardial injury in mice.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

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.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*