OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective To analyze the changing trends and epidemiological characteristics of the disease burden of blindness caused by type 2 diabetes mellitus(T2DM)in China from 1990 to 2021,and to predict the trends up to 2035.Methods Based on the standardized methodology of the Global Burden of Disease Study 2021,the age-standardized rates(ASRs)and their corresponding 95％uncertainty intervals(UI)for prevalence and years lived with disability(YLDs)rate were used to systematically describe the disease burden of blindness caused by T2DM in China.The temporal trends[esti-mated annual percentage change(EAPC)]and epidemiological characteristics were assessed,with attention to age and sex differences,to predict the trends in the disease burden up to 2035.Results From 1990 to 2021,the age-standardized prevalence rate increased from 6.03 per 100 000(95％UI:4.46-8.18)to 10.35 per 100 000(7.60-13.69),and the age-standardized YLDs rate increased from 1.09 per 100 000(95％UI:0.67-1.70)to 1.88 per 100 000(95％UI:1.21-2.90),with an EAPC of 2.18(95％CI:1.73-2.64).The disease burden was relatively heavier in females and the elderly population.Epidemiological changes,population growth,and aging collectively drove the increase in the burden of blind-ness caused by T2DM.The disease burden of blindness caused by T2DM is projected to continue rising by 2035.Conclu-sion The disease burden of blindness caused by T2DM in China continues to increase,with a relatively heavier burden on females and the elderly population.Future research should optimize the equity of medical resource allocation and conduct studies on the mechanisms of sex differences to enable precise interventions with evidence-based strategies.

Objective To compare the clinical outcomes of patients with coronary in-stent restenosis(ISR)who underwent drug-coated balloon(DCB)treatment,based on different clinical presentations.Methods This prospective study included 508 patients diagnosed with coronary ISR at Anzhen Hospital,Capital Medical University,between May 2020 and May 2022.All patients received DCB treatment.According to clinical presentation,the patients were divided into an acute coronary syndrome(ACS)group(185 patients)and a non-acute coronary syndrome(non-ACS)group(323 patients).All patients were followed for two years,primarily comparing the incidence of myocardial infarction(MI),target lesion revascularization(TLR),death,and major adverse cardiovascular events(MACE)between the two groups.Results Baseline data showed that the ACS group had a significantly higher proportion of hypertension,diabetes,and smoking compared to the non-ACS group(all P＜0.05).Additionally,the ACS group had a higher proportion of B2/C-type lesions,long lesions,and moderate to severe calcified lesions(all P＜0.05).The number,length,and diameter of stents implanted were also significantly larger in the ACS group(all P＞0.05).At the 1-year follow-up,the ACS group had a significantly higher incidence of TLR(8.1％vs.2.5％,P=0.007)and MACE(10.3％vs.5.3％,P=0.047)than the non-ACS group.By the end of the 2-year follow-up,the ACS group still had higher rates of TLR(18.9％vs.10.2％,P=0.007)and MACE(22.7％vs.14.9％,P=0.030).Conclusions ISR patients with ACS have higher cardiovascular risk and more complex lesions.They also experience a higher incidence of adverse events after DCB treatment.

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Aim To investigate the im-munomodulatory effects of Ononin on Th17/Treg bal-ance and inflammatory responses,and to evaluate its neuroinmune regulatory role in ischemic stroke.Methods A Foxp3 promoter-driven luciferase reporter assay was used to assess the effect of Ononin on Foxp3 transcriptional activity.The effect of Ononin on the dif-ferentiation of na?ve CD4+T cells into Th 17 and Treg subsets was evaluated by flow cytometry.A transient middle cerebral artery occlusion(tMCAO)model was established in mice to evaluate the effects of Ononin on infarct size,neurological recovery,body weight resto-ration,and survival rate.Flow cytometry and RT-PCR were conducted to elucidate the immunological mechanisms underlying Ononin's effects.Results On-onin significantly enhanced Foxp3 promoter activity,promoted the differentiation of na?ve CD4+T cells into Treg cells,and suppressed Th17 polarization.In the tMCAO model,Ononin significantly reduced acute in-farct size,improved survival,ameliorated long-term neurological deficits,and increased Treg cell propor-tions in ischemic brain tissue.Conclusions Ononin modulates peripheral and central inflammation by resto-ring the Th17/Treg immune balance,thereby exerting significant immunomodulatory effects.Its therapeutic benefit in ischemic stroke is closely linked to immune balance restoration.