ObjectiveTo explore the role and potential mechanism of circulating glutamate in enhancing insulin sensitivity by aerobic exercise. This research may provide a novel strategy for preventing metabolic diseases through precise exercise interventions. MethodsTo investigate the effects of elevated circulating glutamate on insulin sensitivity and its potential mechanisms, 18 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into 3 groups: a control group (C), a group receiving 500 mg/kg glutamate supplementation (M), and a group receiving 1 000 mg/kg glutamate supplementation (H). The intervention lasted for 12 weeks, with treatments administered 6 d per week. Following the intervention, an insulin tolerance test (ITT) and a glucose tolerance test (GTT) were conducted. Circulating glutamate levels were measured using a commercial kit, and the activity of the skeletal muscle InsR/IRS1/PI3K/AKT signaling pathway was analyzed via Western blot. To further investigate the role of circulating glutamate in enhancing insulin sensitivity through aerobic exercise, 30 male C57BL/6 mice were randomly assigned to 3 groups: a control group (CS), an exercise intervention group (ES), and an exercise combined with glutamate supplementation group (EG). The ES group underwent treadmill-based aerobic exercise, while the EG group received glutamate supplementation at a dosage of 1 000 mg/kg in addition to aerobic exercise. The intervention lasted for 10 weeks, with sessions occurring 6 d per week, and the same procedures were followed afterward. To further elucidate the mechanism by which glutamate modulates the InsR/IRS1/PI3K/AKT signaling pathway, C2C12 myotubes were initially subjected to graded glutamate treatment (0, 0.5, 1, 3, 5, 10 mmol/L) to determine the optimal concentration for cellular intervention. Subsequently, the cells were divided into 3 groups: a control group (C), a glutamate intervention group (G), and a glutamate combined with MK801 (an NMDA receptor antagonist) intervention group (GK). The G group was treated with 5 mmol/L glutamate, while the GK group received 50 μmol/L MK801 in addition to 5 mmol/L glutamate. After 24 h of intervention, the activity of the InsR/IRS1/PI3K/AKT signaling pathway was analyzed using Western blot. ResultsCompared to the mice in group C, the circulating glutamate levels, the area under curve (AUC) of ITT, and the AUC of GTT in the mice of group H were significantly increased. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle were significantly downregulated. Compared to the mice in group CS, the circulating glutamate levels, the AUC of ITT, and the AUC of GTT in the mice of group ES were significantly reduced. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle of group ES mice were significantly upregulated. There were no significant changes observed in the mice of group EG. Compared to the cells in group 0 mmol/L, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in cells of group 5 mmol/L were significantly downregulated. Compared to the cells in group C, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in the cells of group G were significantly downregulated. No significant changes were observed in the cells of group GK. ConclusionLong-term aerobic exercise can improve insulin sensitivity by lowering circulating levels of glutamate. This effect may be associated with the upregulation of the InsR/IRS1/AKT signaling pathway activity in skeletal muscle. Furthermore, glutamate can weaken the activity of the InsR/IRS1/PI3K/AKT signaling pathway in skeletal muscle, potentially by binding to NMDAR expressed in skeletal muscle.

Metabolic diseases characterized by an imbalance in energy homeostasis represent a significant global health challenge. Individuals with metabolic diseases often suffer from complications related to disorders in lipid metabolism, such as obesity and non-alcoholic fatty liver disease (NAFLD). Understanding core genes involved in lipid metabolism can advance strategies for the prevention and treatment of these conditions. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in lipid metabolism that converts saturated fatty acids into monounsaturated fatty acids. SCD1 plays a crucial regulatory role in numerous physiological and pathological processes, including energy homeostasis, glycolipid metabolism, autophagy, and inflammation. Abnormal transcription and epigenetic activation of Scd1 contribute to abnormal lipid accumulation by regulating multiple signaling axes, thereby promoting the development of obesity, NAFLD, diabetes, and cancer. This review comprehensively summarizes the key role of SCD1 as a metabolic hub gene in various (patho)physiological contexts. Further it explores potential translational avenues, focusing on the development of novel SCD1 inhibitors across interdisciplinary fields, aiming to provide new insights and approaches for targeting SCD1 in the prevention and treatment of metabolic diseases.
Stearoyl-CoA Desaturase/metabolism* ; Humans ; Metabolic Diseases/physiopathology* ; Lipid Metabolism/physiology* ; Animals ; Obesity/enzymology* ; Non-alcoholic Fatty Liver Disease

The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the in vitro metabolism and products of 2-MDCK. The results indicate that 2-MDCK undergoes various metabolic reactions, including dehydrogenation, deamination, hydroxylation, and demethylation, leading to the formation of eight metabolites. By conducting actual testing on hair samples from 2-MDCK abusers, the existence of six metabolites was confirmed. Comparing the metabolic products in the liver microsomal in vitro model, M3.1 and M4.1 were identified as biomarkers for 2-MDCK consumption. Five samples of abusers of 2-methyl-dechloroketamine were provided by the Anti-Drug Brigade of the Hangzhou Public Security Bureau. Negative hair samples were provided by laboratory volunteers, and all samples were obtained with the informed consent of the volunteers. These findings provide a scientific basis for the detection and identification of 2-MDCK and its metabolites, as well as crucial support for the study of the metabolic mechanisms of similar novel psychoactive substances in the phenylcyclohexylpyridine class. This research holds significant importance in addressing the issue of abuse of new psychoactive substances.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Foods can be contaminated with foodborne pathogens through a variety of pathways, including water, air and soil. Food safety events caused by foodborne pathogens show a serious impact on human health. However, due to the diversity of foodborne pathogens and the complexity of food matrices, the rapid detection of foodborne pathogens was difficult. The conventional microbial culture and physiological and biochemical identification can hardly meet the need of rapid detection of foodborne pathogens in the field. It is necessary to develop rapid detection technologies for foodborne pathogens. Clustered regularly interspaced short palindromic repeats (CRISPR) and associated protein (Cas) are an adaptive immune systems of prokaryotes with specific recognition and cleavage of nucleic acid sequences, which shows good potential for development of nucleic acid detection and biosensing in the field. According to different forms of application, paper-based analytical devices can be categorized into test paper, lateral flow assay and microfluidic paper-based chips, etc. As a good simplicity and low-cost analytical testing tools, they show good prospects in the field of rapid testing. Therefore, the rapid and sensitive detection of foodborne pathogens can be realized by combining the efficient recognition ability of CRISPR/Cas system and the simplicity of paper-based analytical devices. In this paper, we briefly introduce an overview of the CRISPR/Cas system for nucleic acid detection, and this section focuses on an overview of the features and principles of the class 2 system, including types II, V and VI, which uses a single effector. The application of CRISPR/Cas system based test paper analysis, lateral flow assay and microfluidic paper-based chips for the detection of foodborne pathogens are highlighted in the paper, and finally the advantages, current challenges and future prospects of CRISPR/Cas system in combination with paper-based analytical devices to establish detection methods are discussed.

Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.