Objective: To investigate the prevalence levels and trends of overweight and obesity among adult residents in Zhejiang Province from 2015 to 2023, so as to provide a basis for developing regional weight management strategies. Methods: Permanent residents aged ≥18 years from Zhejiang Province who participated in the China Chronic Disease and Risk Factor Surveillance Project in 2015, 2018, and 2023 were selected as survey subjects. Data on sociodemographic information, height, weight and waist circumference were collected through questionnaire surveys and physical examinations. The prevalence of overweight, obesity, and central obesity were calculated and standardized using data from the Seventh National Population Census of Zhejiang Province in 2020. The Cochran-Armitage trend test was employed to analyze the trends in prevalence of overweight, obesity, and central obesity across different genders, ages and regions. Results: A total of 23 902 individuals were surveyed, comprising 10 985 males (45.96%) and 12 917 females (54.04%). Participants were aged ≥60 years, with 13 088 individuals accounting for 54.76%. There were 9 388 urban residents (39.28%) and 14 514 rural residents (60.72%). The standardized prevalence of overweight among residents increased from 30.05% in 2015 to 33.98% in 2023, the standardized prevalence of obesity increased from 7.67% to 15.22%, and the standardized prevalence of central obesity increased from 22.81% to 33.82%, all showed upward trends (all P<0.05). In 2015, 2018, and 2023, the standardized prevalence of overweight was higher in males than in females. In 2018 and 2023, the standardized prevalence of obesity and central obesity were higher in males than in females (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both males and females showed upward trends (all P<0.05). In 2015, 2018 and 2023, the prevalence of central obesity showed an increasing trend with age (all P<0.05). From 2015 to 2023, upward trends were observed in the prevalence of overweight, obesity, and central obesity among residents aged 18-<45 years and aged ≥60 years, as well as in the prevalence of obesity and central obesity among residents aged 45-<60 years (all P<0.05). In 2015, 2018 and 2023, the standardized prevalence of overweight obesity were higher in urban areas than in rural areas, while the standardized prevalence of central obesity was lower in urban areas (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both urban and rural areas showed upward trends (all P<0.05). Conclusion From 2015 to 2023, the prevalence of overweight, obesity, and central obesity among adult residents in Zhejiang Province showed increasing trends, with variations in prevalence levels and trends observed across genders, ages, and urban / rural areas.

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

OBJECTIVE: To explore the role of CDGSH iron-sulfur domain 2 (CISD2) in patients with sepsis-related myocardial injury (SMI) and its predictive value for 28-day prognosis and myocardial damage through clinical studies and cell experiments. METHODS: A retrospective study was conducted. Adult patients diagnosed with sepsis admitted to the critical care medicine of Third Affiliated Hospital of Qiqihar Medical University from January 2023 to January 2024 were enrolled. The clinical data, laboratory indicators, expression level of CISD2 mRNA in peripheral blood mononuclear cells (PBMC) 24 hours after admission, and 28 days prognosis were collected. Patients were divided into SMI group [left ventricular ejection fraction (LVEF) < 0.50 or LVEF decreased by ≥ 10% from baseline] and sepsis non-myocardial injury group based on LVEF. The expression levels of CISD2 mRNA were compared between the two groups, and the correlation between CISD2 and myocardial injury was analyzed. Patients were divided into the low-expression group (CISD2 mRNA < 0.5 copy/μL) and the high-expression group (CISD2 mRNA ≥ 0.5 copy/μL) based on the expression of CISD2 mRNA, and into the survival group and the death group based on the prognosis at 28 days. The clinical characteristics were analyzed between the groups. Multivariate Logistic regression was used to analyze the independent predictors of 28-day mortality in patients with sepsis. The predictive value of CISD2 for myocardial damage and 28-day prognosis in patients with sepsis were evaluated by using the receiver operator characteristic curve (ROC curve). In addition, in vitro experiments using human AC16 cardiomyocytes was conducted. The cells were divided into control group, lipopolysaccharide (LPS) group, the LPS+transfection group with overexpression of CISD2 plasmid (LPS+p-CISD2 group), and the LPS + transfection group with negative control plasmid (LPS+p-NC group). The mRNA expression of CISD2 in cells were detected by real-time quantitative polymerase chain reaction (RT-qPCR), the protein expression of CISD2 in cells were detected by Western blotting, and the cell viability was determined by cell counting kit-8 (CCK-8). RESULTS: A total of 85 sepsis patients were included, with 32 developing myocardial injury and 53 without myocardial injury. There were 40 cases of low expression of CISD2 and 45 cases of high expression of CISD2. At 28 days, 60 cases survived and 25 cases died. The mRNA expression of CISD2 in the SMI group was significantly lower than that in the sepsis non-myocardial injury group (copy/μL: 0.41±0.09 vs. 0.92±0.13, P < 0.05). CISD2 was significantly correlated with myocardial injury in patients with sepsis (r = 0.729, P < 0.05). The proportion of LVEF < 0.50 (67.50% vs. 11.11%), sequential organ failure score (SOFA: 15.63±2.15 vs. 11.12±1.52), and acute physiology and chronic health evaluation II (APACHEII: 29.49±3.51 vs. 22.41±2.61) in the CISD2 low-expression group were significantly higher than those in the CISD2 high-expression group (all P < 0.05), while there were no significantly differences in other indicators. The Kaplan-Meier survival curve showed that the 28-day survival time of sepsis patients with in the CISD2 low-expression group was significantly shorter than that in the CISD2 high-expression group (Log-rank test: χ ² = 5.601, P < 0.05). The proportion of CISD2 low-expression and the proportion of LVEF < 0.50 in the survival group were both higher than those in the death group (80.00% vs. 33.33%, 64.00% vs. 26.67%, both P < 0.05), while there were no significantly differences in other indicators. Multivariate Logistic regression analysis showed that CIDS2 and LVEF were independent predictive factors for 28-day mortality in patients with sepsis [CIDS2: odds ratio (OR) = 3.400, 95% confidence interval (95%CI) was 1.026-11.264, P = 0.045; LVEF: OR = 2.905, 95%CI was 1.029-8.199, P = 0.044]. ROC curve analysis showed that when CISD2 was expressed at a low level, patients with sepsis were at high risk of death within 28 days and myocardial injury. The sensitivity of CISD2 in predicting the 28-day mortality of patients with sepsis was 80.00%, and the specificity was 66.67%, and the area under the curve (AUC) was 0.733 (95%CI was 0.626-0.823). The sensitivity of CISD2 in predicting myocardial injury in patients with sepsis was 83.87%, the specificity was 74.07%, and the AUC was 0.790 (95%CI was 0.688-0.871). In addition, compared with the control group, the mRNA and protein expressions of CISD2 as well as the cell activity in the LPS group were significantly decreased. The mRNA and protein expressions of CISD2 and the activity of cardiomyocytes transfected with p-CISD2 were significantly increased. CONCLUSIONS CISD2 plays a protective role in sepsis-associated myocardial injury and has good predictive value for 28-day prognosis and myocardial injury.
Humans ; Sepsis/metabolism* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; RNA, Messenger/genetics* ; Aged ; Myocardium/metabolism*

Exercise fatigue is a complex physiological and psychological phenomenon that includes peripheral fatigue in the muscles and central fatigue in the brain. Peripheral fatigue refers to the loss of force caused at the distal end of the neuromuscular junction, whereas central fatigue involves decreased motor output from the primary motor cortex, which is associated with modulations at anatomical sites proximal to nerves that innervate skeletal muscle. The central regulatory failure reflects a progressive decline in the central nervous system’s capacity to recruit motor units during sustained physical activity. Emerging evidence highlights the critical involvement of central neurochemical regulation in fatigue development, particularly through neurotransmitter-mediated modulation. Alterations in neurotransmitter release and receptor activity could influence excitatory and inhibitory signal pathways, thus modulating the perception of fatigue and exercise performance. Increased serotonin (5-HT) could increase perception of effort and lethargy, reduce motor drive to continue exercising, and contribute to exercise fatigue. Decreased dopamine (DA) and noradrenaline (NE) neurotransmission can negatively impact arousal, mood, motivation, and reward mechanisms and impair exercise performance. Furthermore, the serotonergic and dopaminergic systems interact with each other; a low 5-HT/DA ratio enhances motor motivation and improves performance, and a high 5-HT/DA ratio heightens fatigue perception and leads to decreased performance. The expression and activity of neurotransmitter receptors would be changed during prolonged exercise to fatigue, affecting the transmission of nerve signals. Prolonged high-intensity exercise causes excess 5-HT to overflow from the synaptic cleft to the axonal initial segment and activates the 5-HT1A receptor, thereby inhibiting the action potential of motor neurons and affecting the recruitment of motor units. During exercise to fatigue, the DA secretion is decreased, which blocks the binding of DA to D1 receptor in the caudate putamen and inhibits the activation of the direct pathway of the basal ganglia to suppress movement, meanwhile the binding of DA to D2 receptor is restrained in the caudate putamen, which activates the indirect pathway of the basal ganglia to influence motivation. Furthermore, other neurotransmitters and their receptors, such as adenosine (ADO), glutamic acid (Glu), and γ‑aminobutyric acid (GABA) also play important roles in regulating neurotransmitter balance and fatigue. The occurrence of central fatigue is not the result of the action of a single neurotransmitter system, but a comprehensive manifestation of the interaction between multiple neurotransmitters. This review explores the important role of neurotransmitters and their receptors in central motor fatigue, reveals the dynamic changes of different neurotransmitters such as 5-HT, DA, NE, and ADO during exercise, and summarizes the mechanisms by which these neurotransmitters and their receptors regulate fatigue perception and exercise performance through complex interactions. Besides, this study presents pharmacological evidence that drugs such as agonists, antagonists, and reuptake inhibitors could affect exercise performance by regulating the metabolic changes of neurotransmitters. Recently, emerging interventions such as dietary bioactive components intake and transcranial electrical stimulation may provide new ideas and strategies for the prevention and alleviation of exercise fatigue by regulating neurotransmitter levels and receptor activity. Overall, this work offers new theoretical insights into the understanding of exercise central fatigue, and future research should further investigate the relationship between neurotransmitters and their receptors and exercise fatigue.

Liver diseases cannot be easily detected in the early stage， and although invasive diagnostic methods， such as liver biopsy， are relatively accurate， they tend to have a low degree of acceptance， which greatly limits the improvement in diagnosis and treatment techniques for liver diseases. Therefore， it is of great importance to search for new biomarkers and therapeutic targets. As an emerging biomarker for liquid biopsy， tRNA-derived small RNA （tsRNA） is abnormally expressed in various liver diseases including viral hepatitis， fatty liver disease， liver injury， and liver cancer， and it can affect the development and progression of liver diseases by regulating the biological functions such as gene expression， epigenetic regulation， and protein translation. This article reviews the origin， classification， and biological function of tsRNA， as well as the research advances in tsRNA as biomarkers and potential therapeutic targets for liver diseases， so as to provide ideas for the early diagnosis and treatment of liver diseases.

Intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has become the primary treatment for macular edema associated with retinal vascular disease such as diabetic retinopathy and retinal vein occlusion, but there are limitations such as variable treatment efficacy and insufficient durability of therapeutic effects. As the first bispecific antibody applied in ophthalmic treatment, Faricimab achieves favorable outcomes by simultaneously targeting both VEGF-A and angiopoietin-2(Ang-2)pathways. Based on evidence from recent clinical trials and real-world studies, this article reviews the research progress on Faricimab for the treatment of diabetic macular edema(DME), retinal vein occlusion-associated macular edema(RVO-ME)and refractory macular edema compared to the therapeutic effects of other agents. Additionally, based on Faricimab's safety characteristics and future potential, its therapeutic prospects for macular edema associated with retinal vascular diseases are discussed. This review aims to provide evidence-based references for optimizing clinical treatment strategies, thereby contributing to mitigating the risk of vision loss due to macular edema.

Transfer RNA-derived small RNAs(tsRNAs)are a novel class of non-coding small RNAs,which have various biological functions such as regulating gene expression,protein translation,epigenetic inheritance,cell proliferation and apoptosis,and communication.tsRNA is abnormally expressed in respiratory system cancers,lung injury,pulmonary hypertension,childhood obstructive sleep apnea-hypopnea syndrome and respiratory virus infections,affecting the occurrence and development of these diseases.However,the regulatory mechanism of tsRNAs in respiratory diseases has not been fully elucidated yet.Therefore,this review introduces the sources,classification and detection methods of tsRNA,summarizes the biological functions of tsRNA in respiratory diseases,related regulatory mechanisms,and its application prospects as biomarker in clinical diagnosis and prognosis evaluation,aiming to provide new ideas for the diagnosis and treatment of respiratory diseases,and to provide reference for in-depth research on tsRNA regulation of respiratory diseases.

Objective To investigate the effect of sal-like gene 2(Sall2)gene overexpression on the progression of disease in human superoxide dismutase 1(hSOD1)-G93A mutant amyotrophic lateral sclerosis(ALS)transgenic mice,with the aim of identifying potential therapeutic targets for ALS gene therapy.Methods Differential Sall2 gene were screened through bioinformatics analysis.Forty-eight ALS transgenic mice were selected for this study.AAV-PHP.eB-Sall2 adeno-associated virus with a neuron-specific promoter,human synapsin I(hSyn),was constructed and administered via tail vein injection to six-week-old mice.In parallel,the same litter of ALS mice received an injection of AAV-PHP.eB-GFP.The staining of Sall2 and neuron-specific nuclear protein(NeuN)/GFAP in the spinal cord and cerebral cortex of mice were detected through immunofluorescent double-label staining technology.The survival period,weight changes,exercise ability,and electromyographic changes of the gastrocnemius muscle were detected.The morphological changes in the spinal cord anterior horn neurons were detected through Nissl staining.The effect of Sall2 gene overexpression on the expression of the cell cycle protein E1(cyclin E1)was investigated through Western blotting.Results Bioinformatics analysis showed out that Sall2 was differentially expressed in ALS mice.Compared with ALS mice in the control group,the Sall2 protein expression of ALS mice in the overexpressing Sall2 gene group increased in both the spinal cord and cerebral cortex,and the Sall2 integral absorbance values of Sall2+/NeuN+double-positive cells were higher.The survival time of ALS mice in the Sall2 gene overexpressing group was prolonged,the rate of weight loss was slowed down,the performance in the rotarod and inverted grid tests was improved with longer times,and the positive sharp waves and fibrillation potentials in the gastrocnemius electromyography were reduced.The number of Nissl bodies labeled neurons increased in the spinal cord anterior horn of the Sall2 gene overexpressing mice,and the condition of neuronal damage was improved.Overexpression of the Sall2 gene also reduced the expression of cyclin E1 in both the spinal cord and cerebral cortex of ALS transgenic mice.Conclusion Overexpression of the Sall2 gene can delay disease progression and improve motor performance in ALS transgenic mice,affecting the expression of cyclin E1,thus exerting a therapeutic effect on these mice.

Objective To investigate the expression of myelin transcription factor 1-like(MYT1L)during amyotrophic lateral sclerosis(ALS)progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus(GEO)database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene(hSOD1G93A)compared to the wild-type(WT)mice.hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting.Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease.An ALS cellular model was established using hSOD1G93A mutant NSC34 cells,with hSOD1WT NSC34 cells as controls.MYT1L expression and distribution were assessed in these cells via Real-time PCR,Western blotting,and immunofluorescent staining.Based on the GSE76220 dataset from the GEO database,differentially expressed genes(DEGs)between MYT1L high-and low-expression groups in lumbar spinal motor neurons of ALS patients were identified,followed by Gene Ontology(GO)functional enrichment analysis.MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.Results In the GSE106803 dataset,MYT1L expression was significantly down-regulated in the spinal cord of ALS mice.Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid-and late-disease stages.Compared to the WT group,MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice,while it increased in astrocytes.In vitro,hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls,with MYT1L localized to both the cytoplasm and nucleus.DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients(GSE76220 dataset)were enriched in synaptic-related functions through GO analysis.Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis.Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons,suggesting its therapeutic potential.

Objective The aim of this study was to characterize the basic molecular and biochemical parameters for a cyclophilin protein in Cryptosporidium parvum called CpCyP1.Methods CpCyP1 expression patterns during the parasite life cycle were evaluated using qRT-PCR with total RNA isolated from different developmental stages of C.parvum.Native CpCyP1 protein in sporozoites was detected using western blot.The localization of CpCyP1 was performed using the immunofluorescence assay,with an affinity-purified rabbit polyclonal antibody against a synthetic peptide.The peptidyl-prolyl cis-trans isomerase(PPIase)activity of His-tagged recombinant CpCyP1 was evaluated using absorbance colorimetry,and the effect of cyclosporin A(CsA)on the activity of CpCyP1 was determined.Results CpCyP1 was expressed in all parasite developmental stages,whereas CpCyP1 was present mainly in the cytosol of sporozoites,meronts,and gamonts.CpCyP1 displayed Michaelis-Menten kinetics towards N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide for its PPIase activity(Km=456.4 μmol/L;Vmax=1.981 U).CsA inhibited PPIase activity,showing lower micromolar inhibitory activity and binding affinity(Kd=5.122 μmol/L;IC50=1.004 μmol/L).Conclusions These results imply that CpCyP1 in the parasite may be the target for the previously reported anti-cryptosporidial efficacy of CsA and suggest that C.parvum cyclophilins could be evaluated as candidate drug targets.