BACKGROUND:Triptolide,a bioactive component of the traditional Chinese medicine Tripterygium wilfordii,has a certain protective effect on neurons.OBJECTIVE:To investigate the effect of triptolide on cerebral ischemia/reperfusion injury.METHODS:(1)Cell experiment:Hippocampal neurons(HT22 cells)were randomly divided into control group,glucose oxygen deprivation/reoxygenation(OGD/R)group,OGD/R+triptolide group,OGD/R+triptolide+si-TIGAR group,OGD/R+si-TIGAR group,and OGD/R+triptolide+rapamycin group.HT22 cell viability was detected by cell counting kit 8.Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,7 members of the solsolic vector family 11,sphingosine kinase 1(SPHK1)and(mTOR)were detected by western blot assay.Glutathione,malondialdehyde and iron level were detected using the biochemical kit.(2)Animal experiment:Rats were randomly divided into sham surgery group,model group,and triptolide group.Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups.Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days.Twenty-four hours after administration,LONGA method was used to evaluate the neurological impairment of rats,TTC method was used to observe the conditions of cerebral infarction,TUNEL staining was used to detect cell apoptosis,and western blot was performed to detect the expression level of related proteins.RESULTS AND CONCLUSION:(1)At the cellular level,triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R.Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,and 7 members of the solsolic vector family 11,activated the SPHK1/mTOR pathway,increased glutathione content,inhibited malondialdehyde content and iron levels.Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells.(2)At the animal level,triptolide significantly reduced neurological deficits,infarct volume,and cell apoptosis,and inhibited neuronal ferroptosis in brain tissue of rats.To conclude,triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling,and thereby reduced cerebral ischemia/reperfusion injury.These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.

BACKGROUND:Triptolide,a bioactive component of the traditional Chinese medicine Tripterygium wilfordii,has a certain protective effect on neurons.OBJECTIVE:To investigate the effect of triptolide on cerebral ischemia/reperfusion injury.METHODS:(1)Cell experiment:Hippocampal neurons(HT22 cells)were randomly divided into control group,glucose oxygen deprivation/reoxygenation(OGD/R)group,OGD/R+triptolide group,OGD/R+triptolide+si-TIGAR group,OGD/R+si-TIGAR group,and OGD/R+triptolide+rapamycin group.HT22 cell viability was detected by cell counting kit 8.Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,7 members of the solsolic vector family 11,sphingosine kinase 1(SPHK1)and(mTOR)were detected by western blot assay.Glutathione,malondialdehyde and iron level were detected using the biochemical kit.(2)Animal experiment:Rats were randomly divided into sham surgery group,model group,and triptolide group.Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups.Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days.Twenty-four hours after administration,LONGA method was used to evaluate the neurological impairment of rats,TTC method was used to observe the conditions of cerebral infarction,TUNEL staining was used to detect cell apoptosis,and western blot was performed to detect the expression level of related proteins.RESULTS AND CONCLUSION:(1)At the cellular level,triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R.Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,and 7 members of the solsolic vector family 11,activated the SPHK1/mTOR pathway,increased glutathione content,inhibited malondialdehyde content and iron levels.Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells.(2)At the animal level,triptolide significantly reduced neurological deficits,infarct volume,and cell apoptosis,and inhibited neuronal ferroptosis in brain tissue of rats.To conclude,triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling,and thereby reduced cerebral ischemia/reperfusion injury.These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.

Cross-linking mass spectrometry (XL-MS) technology has become a key tool for identifying protein-protein interactions (PPIs) and revealing the protein structures in living cells, tissues, or organelles. The XL-MS technology has demonstrated remarkable superiority compared with conventional methods for studying PPIs and protein structures. In the past few years, new cross-linker structures have been arising continuously. They have not only broadened the range of cross-linking reactions but also provided additional methods for the enrichment of cross-linking peptides. Moreover, owing to the advancement of computer software and artificial intelligence, cross - linking data search engines and visualization software have also been enhancing the speed and accuracy of cross-linking peptide identification. The evolution of cross-linkers and cross-linking peptide search engines has promoted the application of the XL-MS technology in the research on protein-protein interactions (PPIs) within organelles and even living cells and in the analysis of protein structures.

Objective To investigate the association between the variability of remnant cholesterol inflammatory index(RCII),a novel composite biomarker,and the risk of stroke,in order to provide a theoretical basis for stroke prevention.Methods A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006,2008,and 2010.These subjects were grouped based on the quartiles of RCII variability,which was represented by standard deviation(SD)and average real variability(ARV),and were followed up every 2 years,with the occurrence of stroke(including ischemic and hemorrhagic strokes),death,or the end of follow-up on December 31,2022 as the endpoints.Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups,and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group.Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.Results Among the 38 659 participants,a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years.After adjusting confounding factors,when the participants were grouped by the quartiles of RCII-SD,the hazard ratio(HR)for stroke was 1.034(95%CI:0.917～1.167,P=0.584),1.146(95%CI:1.018～1.290,P=0.025),and 1.209(95%CI:1.066～1.370,P=0.003),respectively in the Q2,Q3,and Q4 groups,when compared with the Q1 group(Ptrend<0.05).When they were grouped by the quartiles of RCII-ARV,the HR for stroke was 1.008(95%CI:0.894～1.136,P=0.901),1.109(95%CI:0.986～1.248,P=0.085),and 1.152(95%CI:1.018～1.303,P=0.025),respectively,in the Q2,Q3,and Q4 groups,when compared with the Q1 group.Furthermore,both sensitivity and stratified analyses yielded similar results.Conclusion RCII variability is significantly associated with stroke,and the risk of stroke is gradually increasing with increment of the variability.Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism,strengthening lifestyle interventions,and standardizing dietary,exercise,and weight management in order to suppress the index fluctuations.The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.

The rabies virus(RABV)that causes rabies mainly attacks the peripheral and central nervous systems.In the later stages of infection,it is scattered in the salivary glands and transmit-ted to other susceptible animals through infectious saliva.To study dispersion of the RABV in the three pairs of salivary gland tissues,the street strain PB4 of the RABV was inoculated into 21-day-old female mice through the hind limb muscles.During the moribund stage of the mice,the sublin-gual gland,submandibular gland and parotid gland were collected,respectively.The TCID50 titer of RABV in the three kinds of glands of the mice and the copy number of the RABV N gene were de-tected,and RABV in different salivary glands was observed by immunofluorescence.The results showed that PB4 was dispersed in all three kinds of salivary glands of the mice,with the largest a-mounts in the parotid gland,followed by the submandibular gland,and the lowest amount in the sublingual gland.Three-month-old dogs were inoculated with PB4 through the cranial cavity,and saliva were collected every 12 h after inoculation.The saliva samples were detected by TCID50 and RT-qPCR.And during the moribund stage of the dogs when the disease occurred,the three pairs of salivary glands were collected.Through the determination of the TCID50 titer,RT-qPCR and immu-nofluorescence detection,it was demonstrated that among the three different salivary glands of the dogs,the largest amount of PB4 was found in the parotid gland and the lowest in the sublingual gland.Our results in mice and dogs clearly proved that the parotid gland was consistently found to exhibit the highest content of street RABV among the three major salivary glands,which could en-rich experimental data for analyzing the dispersion of RABV in the salivary glands and interpreta-tion of the intermittent secretion of saliva in clinically rabid dogs.

Objective: To examine differences in depressive and anxiety symptoms between boarding and non boarding high school students and their associations with physical activity (PA) patterns, so as to provide evidence to inform adolescent mental health promotion. Methods: From October to December 2024, a convenience sample of 11 782 students aged 15-18 years was recruited from 36 schools in Nanchang, Ganzhou, and Shangrao of Jiangxi Province. Depressive and anxiety symptoms and PA were assessed using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and International Physical Activity Questionary Short Form (IPAQ-SF). Logistic regression model was used to examine associations between PA patterns, depressive and anxiety symptoms among boarding and non boarding students. Results: The detection rates of depressive symptoms were 45.7% and 46.4% among boarding and non boarding students, respectively; for anxiety symptoms, the corresponding rates were 43.0% and 46.7%. Boarding and non boarding students differed significantly in smoking status, screen time, sleep duration, sedentary time, daily vegetable intake, and napping ( χ 2=16.74-664.17, all P <0.01). Across PA pattern groups, the detection rates of depressive and anxiety symptoms differed significantly between boarding and non boarding students ( χ 2 depression = 23.85 , χ 2 anxiety = 22.78, both P <0.01). Adjusted for confounding factors, Logistic regression analysis of high school students showed that compared with the not meeting PA recommendations, both the concentrated and regular PA pattern were associated with lower odds of depressive symptoms [ OR (95% CI )=0.83(0.70-0.98), 0.90(0.83-0.98)]; and the concentrated pattern was also associated with lower odds of anxiety symptoms [ OR (95% CI )=0.78(0.65-0.92)], and the association of anxiety symptoms in concentrated boarding students was consistent with that of the overall group [ OR (95% CI )=0.71(0.52-0.98)] (all P <0.05). Conclusions There is a correlation of different physical activity patterns with depressive and anxiety symptoms among boarding and non boarding high school students. Schools should ensure students engage in regular physical activity and work to increase overall activity volume.

BACKGROUND:More and more scholars are investigating the mechanism of hypoxia-inducible factor-1α in regulating bone homeostasis and oral and maxillofacial diseases to provide new targets and strategies for the treatment of related disorders,but there is no relevant review.OBJECTIVE:To summarize the regulatory potential of hypoxia-inducible factor-1α in a variety of oral and maxillofacial diseases and bone homeostasis with the aim of providing a new research direction for oral and maxillofacial bone tissue engineering.METHODS:A literature review was conducted in databases such as PubMed,Web of Science and CNKI,for articles Published from 2003 to 2024.The keywords were"hypoxia inducible factor-1α,oral cavity,bone formation,osteoclast,angiogenesis,oxidative stress,tissue engineering,periodontitis,pulpitis,temporomandibular joint osteoarthritis"in Chinese and English.Finally,84 articles were included for review.RESULTS AND CONCLUSION:(1)Hypoxia-inducible factor-1α is essential in promoting bone tissue regeneration,facilitating osteogenic-angiogenic coupling,and mitigating damage from oxidative stress in bone tissue.(2)Increasing levels of hypoxia-inducible factor-1α in tissue cells reduces inflammation in periodontitis and promotes periodontal tissue remodeling,pulp regeneration,and involves in joint remodeling after temporomandibular joint osteoarthritis.(3)By stabilizing the level of hypoxia-inducible factor-1α in tissue cells,the micronutrient-carrying biomaterial promotes bone marrow mesenchymal stem cells to migrate and attach to the bone defect area,coupling angiogenesis and osteogenesis to achieve bone regeneration.(4)How to increase the level of hypoxia-inducible factor-1α in oral and maxillofacial tissues using bioactive materials to achieve bone regeneration at maxillofacial bone defects remains to be investigated.

Objective:To investigate the temporal expression of Growth Differentiation Factor-15 (GDF15) in the serum of patients with Acute Coronary Syndrome (ACS) and explore the clinical significance of GDF15 in protecting cardiomyocytes in ACS.Methods:A retrospective study was conducted on 289 ACS patients admitted to the emergency departments from February to October 2023. Data on gender, age, troponin T (TnT), creatine kinase isoenzyme (CK-MB), GDF15, and B-type natriuretic peptide (BNP) within 30 minutes of admission were recorded. Differences in these indicators among different groups were compared. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the diagnostic value of GDF15, TnT, and BNP for ACS. Among the patients, 15 exhibited a temporal expression pattern of GDF15, and their blood samples were re-measured using a GDF15 fluorescent quantitative immunochromatographic assay kit. Fifteen patients without temporal expression were randomly selected as controls, and their samples were also re-measured to exclude detection errors. Fifteen patients with temporal expression were included in the temporal expression group, and 15 without temporal expression were included in the non-temporal expression group. Laboratory indicators such as fasting blood glucose, glycated hemoglobin, triglycerides, creatinine, and uric acid were compared between the groups. Additionally, patient age, gender, body mass index (BMI), coronary angiography results, echocardiography, Gensini score, left ventricular ejection fraction (LVEF), and GRACE risk score were recorded to assess their correlation with GDF15 temporal expression. Statistical analysis was performed using SPSS 27 software, with continuous data expressed as mean ± standard deviation (Mean ± SD) and compared using t-tests and χ2 tests. Results:The overall trend in ACS patients showed a higher proportion of males than females (73.36% vs. 26.64%). The oldest group was the Unstable Angina (UA) group, with a mean age of (63.98 ± 15.19) years, while the youngest group was the non-ACS chest pain group, with a mean age of (54.29 ± 16.39) years. A higher proportion of patients in the UA, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation myocardial infarction (NSTEMI) groups had a history of smoking. The combination of GDF15 and TnT showed high diagnostic value for ACS, with an area under the ROC curve (AUC) of 0.843, consistent with previous studies. Among all ACS patients, 15 exhibited a temporal expression pattern of GDF15, where GDF15 levels peaked at 4 hours, gradually decreased, and peaked again at 24 hours. Patients in the temporal expression group had higher LVEF and left ventricular end-systolic diameter compared to the non-temporal expression group. The Gensini score was lower in the temporal expression group, and the GRACE risk score was significantly lower in the temporal expression group (00.7±14.72) compared to the non-temporal expression group (116.1±23.46), with a statistically significant difference ( P = 0.0115). There were no significant differences in general characteristics (age, gender, BMI) or clinical biochemical indicators (fasting blood glucose, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid) between the temporal and non-temporal expression groups ( P > 0.05). Conclusions:GDF15 demonstrates significant diagnostic and prognostic predictive value in ACS. Patients with temporally dynamic expression of serum GDF15 exhibit milder myocardial injury and a lower probability of mortality. These findings provide novel therapeutic targets and research directions for further exploring the role of GDF15 in ACS management.

Objective: To investigate the expression of ribosomal protein L26 ( RPL26) in gastric cancer cells (GC) and its effect on cell apoptosis and proliferation . Methods: The expression of RPL26 in GES-1 and GC cell lines was detected by Western blot. GC cell line HGC-27 was used to construct RPL26 overexpression cell line , and GC cell lines HGC-27 and AGS cells were used to construct RPL26 knockdown cell line . The overexpression and knockdown efficiency of RPL26 were detected by Western blot. Cell counting kit-8 (CCK-8) , colony formation assay and Transwell assay were used to detect the effects of the overexpression and knockdown of RPL26 on the pro- liferation and migration of GC cells . Western blot was used to detect the expression of Phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) signaling pathway related factors PI3K , AKT , phosphorylated phosphatidylinosi- tol-3-kinase (p-PI3K) , phosphorylated protein kinase B ( p-AKT) and downstream factors B-Cell lymphoma-2 (Bcl-2) , Bcl-2 associated X protein (Bax) and Cyclin A , G1 /S-specific Cyclin D1(Cyclin D1) , Cyclin-depend- ent kinases (CDK)4 and CDK2 in overexpression and knockdown of RPL26 stably transfected cell lines . Results: Compared with GES-1 , RPL26 was highly expressed in HGC-27 cells ( tHGC-27 = 4. 97 ; P < 0. 01) and elevated in AGS , but the difference was not statistically significant. In HGC-27 and AGS cells , CCK-8 and colony formation assays showed that the proliferation ability of cells decreased after the knockdown of RPL26. Transwell assay showed that the migration ability of cells decreased after the knockdown of RPL26. Western blot showed that Bcl-2 expression was decreased in HGC-27 , AGS cells after the knockdown of RPL26 ( tHGC-27 = 11 . 50 , tAGS = 4. 77 ; P < 0. 001 , P < 0. 01) , and Bax expression increased ( tHGC-27 = 9. 63 , tAGS = 4. 05 ; P < 0. 001 , P < 0. 05) . In HGC-27 cells , the ratios of p-PI3K/PI3K and p-AKT/AKT significantly decreased after the knockdown of RPL26 ( tp-PI3K/PI3K = 3 . 86 , tp-AKT/AKT = 8. 29 ; P < 0. 05 , P < 0. 01) . Cyclin A , Cyclin D1 , CDK4 , CDK2 protein expressions de- creased ( t = 9. 61 , 5 . 10 , 11 . 64 , 7. 81 ; P < 0. 01 or P < 0. 001) , while the overexpression of RPL26 in HGC-27 cells showed the opposite trend . Conclusion The knockdown of RPL26 may arrest the cell cycle in G1 /S phase by inhibiting the PI3K/AKT signaling pathway , thereby inhibiting cell proliferation and promoting apoptosis .

This study aims to inquire about the fluctuations of ubiquitin-specific protease 47 on neu-roblastoma cells(Neuro-2a,N2a)infected by rabies virus(RABV).USP47 expression levels were detected after RABV infection in N2a cells through RT-qPCR,protein immunoblotting,and virus titer determination.The levels of RABV nucleoprotein and phosphoprotein gene and protein,and RABV titers in supernatants were analyzed during overexpression and knockdown of USP47.The results showed that RABV infection increased USP47 gene level in N2a cells.When overexpression of USP47,the levels of RABV N and P were increased,and the virus titers were also improved.Mo-reover,the level of interleukin-6(IL-6)genes decreased.Knocking down USP47 expression reduced levels of RABV N and P genes and proteins,lowered the virus titer,and elevated the IL-6 gene lev-el.The results suggest that USP47 promotes RABV infection and suppresses IL-6 expression.This finding lays the foundation for further investigation into the molecular mechanisms by which USP47 regulates RABV infection.