Development and verification of a manganese metabolism- and immune-related genes signature for prediction of prognosis and immune landscape in gastric cancer.

Background: Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body's anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors. Methods: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of NPR3 in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments. Results: GC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. NPR3 expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of NPR3 was distributed in endothelial cells. Cellular experiments demonstrated that NPR3 facilitated the proliferation of GC cells. Conclusion: This is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.

ß1 integrins regulate cellular behavior and cardiomyocyte organization during ventricular wall formation.

AIMS: The mechanisms regulating the cellular behavior and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how ß1 integrins regulate cardiomyocyte behavior and organization during ventricular wall morphogenesis in the mouse. METHODS AND RESULTS: We applied mRNA deep sequencing and immunostaining to determine the expression repertoires of α/ß integrins and their ligands in the embryonic heart. Integrin ß1 subunit (ß1) and some of its ECM ligands are asymmetrically distributed and enriched in the luminal side of cardiomyocytes, and fibronectin surrounds cardiomyocytes, creating a network for them. Itgb1, which encodes the ß1, was deleted via Nkx2.5Cre/+ to generate myocardial-specific Itgb1 knockout (B1KO) mice. B1KO hearts display an absence of a trabecular zone but a thicker compact zone. The levels of hyaluronic acid and versican, essential for trabecular initiation, were not significantly different between control and B1KO. Instead, fibronectin, a ligand of ß1, was absent in the myocardium of B1KO hearts. Furthermore, B1KO cardiomyocytes display a random cellular orientation and fail to undergo perpendicular cell division, be organized properly, and establish the proper tissue architecture to form trabeculae. Mosaic clonal lineage tracing showed that Itgb1 regulates cardiomyocyte transmural migration and proliferation autonomously. CONCLUSIONS: ß1 is asymmetrically localized in the cardiomyocytes, and some of its ECM ligands are enriched along the luminal side of the myocardium, and fibronectin surrounds cardiomyocytes. ß1 integrins are required for cardiomyocytes to attach to the ECM network. This engagement provides structural support for cardiomyocytes to maintain shape, undergo perpendicular division, and establish cellular organization. Deletion of Itgb1 leads to loss of ß1 and fibronectin and prevents cardiomyocytes from engaging the ECM network, resulting in failure to establish tissue architecture to form trabeculae.

Sleep deprivation boosts O2·- levels in the brains of mice as visualized by a Golgi apparatus-targeted ratiometric fluorescence nanosensor.

Sleep deprivation (SD) is highly prevalent in the modern technological world. Emerging evidence shows that sleep deprivation is associated with oxidative stress. At the organelle level, the Golgi apparatus actively participates in the stress response. In this study, to determine whether SD and Golgi apparatus stress are correlated, we rationally designed and fabricated a novel Golgi apparatus-targeted ratiometric nanoprobe called Golgi dots for O2·- detection. This probe exhibits high sensitivity and selectivity in cells and brain slices of sleep-deprived mice. Golgi dots can be readily synthesized by coprecipitation of Golgi-F127, an amphiphilic polymer F127 modified with a Golgi apparatus targeting moiety, caffeic acid (CA), the responsive unit for O2·-, and red emissive carbon nanodots (CDs), which act as the reference signal. The fluorescence emission spectrum of the developed nanoprobe showed an intense peak at 674 nm, accompanied by a shoulder peak at 485 nm. As O2·- was gradually added, the fluorescence at 485 nm continuously increased; in contrast, the emission intensity at 674 nm assigned to the CDs remained constant, resulting in the ratiometric sensing of O2·-. The present ratiometric nanoprobe showed high selectivity for O2·- monitoring due to the specific recognition of O2·- by CA. Moreover, the Golgi dots exhibited good linearity with respect to the O2·- concentration within 5 to 40 µM, and the limit of detection (LOD) was ~ 0.13 µM. Additionally, the Golgi dots showed low cytotoxicity and an ability to target the Golgi apparatus. Inspired by these excellent properties, we then applied the Golgi dots to successfully monitor exogenous and endogenous O2·- levels within the Golgi apparatus. Importantly, with the help of Golgi dots, we determined that SD substantially elevated O2·- levels in the brain.

Constructing and validating a risk model based on neutrophil-related genes for evaluating prognosis and guiding immunotherapy in colon cancer.

BACKGROUND: Colon cancer is one of the most common digestive tract malignancies. Although immunotherapy has brought new hope to colon cancer patients, there is still a large proportion of patients who do not benefit from immunotherapy. Studies have shown that neutrophils can interact with immune cells and immune factors to affect the prognosis of patients. METHODS: We first determined the infiltration level of neutrophils in tumors using the CIBERSORT algorithm and identified key genes in the final risk model by Spearman correlation analysis and subsequent Cox analysis. The risk score of each patient was obtained by multiplying the Cox regression coefficient and the gene expression level, and patients were divided into two groups based on the median of risk score. Differences in overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier survival analysis, and model accuracy was validated in independent dataset. Differences in immune infiltration and immunotherapy were evaluated by immunoassay. Finally, immunohistochemistry and western blotting were performed to verify the expression of the three genes in the colon normal and tumor tissues. RESULTS: We established and validated a risk scoring model based on neutrophil-related genes in two independent datasets, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, with SLC11A1 and SLC2A3 as risk factors and MMP3 as a protective factor. A new nomogram was constructed and validated by combining clinical characteristics and the risk score model to better predict patients OS and PFS. Immune analysis showed that patients in the high-risk group had immune cell infiltration level, immune checkpoint level and tumor mutational burden, and were more likely to benefit from immunotherapy. CONCLUSIONS: The low-risk group showed better OS and PFS than the high-risk group in the neutrophil-related gene-based risk model. Patients in the high-risk group presented higher immune infiltration levels and tumor mutational burden and thus may be more responsive to immunotherapy.

Assessing Seasonal Effects on Identification of Cultivation Methods of Short-Growth Cycle Brassica chinensis L. Using IRMS and NIRS.

Seasonal (temporal) variations can influence the δ13C, δ2H, δ18O, and δ15N values and nutrient composition of organic (ORG), green (GRE), and conventional (CON) vegetables with a short growth cycle. Stable isotope ratio mass spectrometry (IRMS) and near-infrared spectroscopy (NIRS) combined with the partial least squares-discriminant analysis (PLS-DA) method were used to investigate seasonal effects on the identification of ORG, GRE, and CON Brassica chinensis L. samples (BCs). The results showed that δ15N values had significant differences among the three cultivation methods and that δ13C, δ2H, and δ18O values were significantly higher in winter and spring and lower in summer. The NIR spectra were relatively clustered across seasons. Neither IRMS-PLS-DA nor NIRS-PLS-DA could effectively identify all BC cultivation methods due to seasonal effects, while IRMS-NIRS-PLS-DA combined with Norris smoothing and derivative pretreatment had better predictive abilities, with an 89.80% accuracy for ORG and BCs, 88.89% for ORG and GRE BCs, and 75.00% for GRE and CON BCs. The IRMS-NIRS-PLS-DA provided an effective and robust method to identify BC cultivation methods, integrating multi-seasonal differences.

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway.

Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)-NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.

Ecosystem health evaluation based on land use change-case study of the riparian zone of the Yangtze River in Jiangsu Province, China.

Evaluating the ecosystem health of riparian zones is helpful for decision-makers to formulate appropriate management measures. However, there are few methods for such evaluation which account for both the human requirements and ecological aspects of riparian zones. To address this, we created a Pressure-State(Vigor-Organization-Resilience)-Response framework for evaluating the ecosystem health of the riparian zone of the Yangtze River in Jiangsu Province, a region experiencing intense land use changes. Evaluation indicators, including land use change and ecosystem services, were selected. The comprehensive index method was used to calculate the evaluation indicators of ecosystem health, namely pressure, state, and response, and the comprehensive evaluation indicator itself. Using the cold and hot spot analysis, we also analyzed the spatial heterogeneity of ecosystem health in the riparian zone, constructed an ecological management pattern, and proposed corresponding management and protection measures. The results show that (1) from 2010 to 2020, construction land in the study area increased by more than 20%, and all studied land types underwent some degree of conversion to construction land, with cultivated land and water bodies being the main focus of conversion. (2) In 2020, the average ecosystem health in the riparian zone was normal, with a spatial distribution characterized by "high dispersion and low clustering"; and (3) according to the results of the ecosystem health evaluation and cold and hot spot analysis, key areas for stronger ecological protection were identified and, based on this, a number of management recommendations were proposed.

Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway.

Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata, is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.

Role of Kinetochore Scaffold 1 (KNL1) in Tumorigenesis and Tumor Immune Microenvironment in Pan-Cancer: Bioinformatics Analyses and Validation of Expression.

Purpose: Kinetochore scaffold 1 (KNL1), a crucial protein during cell mitosis participating in cell division, was widely expressed in multiple kinds of cancers. However, the expression profile, the effect on cell biological function, tumor immune microenvironment, and predictive value of clinical prognosis in pan-cancer of KNL1 still require a comprehensive inquiry. Methods: The mRNA and protein expression profile of KNL1 was validated in pan-cancer using different databases. Six algorithms were used to explore the correlation between KNL1 and immune infiltration and the relationship between KNL1 and tumor mutation burden (TMB), microsatellite instability (MSI), and TIDE score were calculated. The diagnostic and clinical prognostic predictive ability of KNL1 was assessed. Differentially expressed genes (DEGs) of KNL1 were screened out and function enrichment analyses were performed in pancreatic adenocarcinoma (PAAD), stomach adenocarcinoma (STAD), and bladder urothelial carcinoma (BLCA). Finally, 8 cases of pancreatic adenocarcinoma tissues and paired adjacent tissues were collected for immunohistochemical (IHC) staining and the histological score (H-score) was calculated. Real-time PCR was performed in gastric cancer and bladder cancer cell lines. Results: KNL1 was abnormally upregulated in more than half of cancers across different databases. IHC and real-time PCR verified the up-regulated expression in cancer tissues in PAAD, gastric cancer, and BLCA. The satisfactory diagnostic value of KNL1 was indicated in 30 cancers and high KNL1 expression was associated with poorer overall survival (OS) in 12 cancers. The prognostic role of KNL1 as a predictive biomarker of PAAD was clarified. KNL1 played an active part in the cell cycle and cell proliferation. Moreover, KNL1 was likely to mold the Th2-dominant suppressive tumor immune microenvironment and was associated with TMB, MSI, and immune checkpoint-related genes in pan-cancer. Conclusion: Our study elucidated the anomalous expression of KNL1 and revealed that KNL1 was a promising prognostic biomarker in pan-cancer.

Effect of anti-inflammatory drugs on the storm of inflammatory factors in respiratory tract infection caused by SARS-CoV-2: an updated meta-analysis.

Background: New reports suggest that anti-inflammatory drugs are widely used to treat respiratory tract infections caused by SARS-CoV-2. Anti-inflammatory drugs were the most frequently used treatment for the COVID-19-related cytokine storm in China. However, the efficacy of anti-inflammatory drugs has yet to be systematically analyzed, and clinicians are often uncertain which class of anti-inflammatory drug is the most effective in treating patients with respiratory tract infections caused by SARS-CoV-2, especially those with severe disease. Methods: From 1 October 2022, relevant studies were searched in the PubMed, Embase, Medline, Cochrane Library, and Web of Science databases. A total of 16,268 publications were retrieved and collated according to inclusion and exclusion criteria, and sensitivity analyses were performed using STATA 14 software. Publication bias was assessed using funnel plots and Egger's test. Study quality was assessed using the PEDro scale, and the combined advantage ratio was expressed as a 95% confidence interval (CI). In total, 19 randomized controlled trials were included in the study. STATA 14 software was used for all random effects model analyses, and the results are expressed as relative risk ratios (RR) with 95% CI. Results: Quantitative analyses were performed on 14,514 patients from 19 relevant randomized controlled clinical trials. Pooled estimates (RR = 0.59, 95% CI 0.44-0.80) revealed that the use of anti-inflammatory drugs resulted in a significant reduction in mortality in patients with respiratory tract infection caused by SARS-CoV-2 compared with controls, and methylprednisolone (RR = 0.14, 95% CI 0.03-0.56) was more effective than other anti-inflammatory drugs. Anti-inflammatory drugs were effective in reducing mortality in critically ill patients (RR = 0.67, 95% CI 0.45-0.98) compared with non-critically ill patients (RR = 0.50, 95% CI 0.34-0.76); however, more clinical evidence is needed to confirm these findings. Conclusion: The use of anti-inflammatory drugs in patients with respiratory infections caused by SARS-CoV-2 reduces patient mortality, especially in severe cases. In individual studies, methylprednisolone was more effective than other drugs.

Application of omics in Sjögren's syndrome.

OBJECTIVE: The pathogenesis, diagnosis, and treatment of Sjögren's syndrome (SS) face many challenges, and there is an urgent need to develop new technologies to improve our understanding of SS. METHODS: By searching the literature published domestically and internationally in the past 20 years, this artical reviewed the research of various omics techniques in SS. RESULTS: Omics technology provided valuable insights into the pathogenesis, early diagnosis, condition and efficacy evaluation of SS. It is helpful to reveal the pathogenesis of the disease and explore new treatment schemes, which will open a new era for the study of SS. CONCLUSION: At present, omics research has made some gratifying achievements, but there are still many uncertainties. Therefore, in the future, we should improve research techniques, standardize the collection of samples, and adopt a combination of multi-omics techniques to jointly study the pathogenesis of SS and provide new schemes for its treatment.

Nanoscale Wear Triggered by Stress-Driven Electron Transfer.

Wear of sliding contacts causes device failure and energy costs; however, the microscopic principle in activating wear of the interfaces under stress is still open. Here, the typical nanoscale wear, in the case of silicon against silicon dioxide, is investigated by single-asperity wear experiments and density functional theory calculations. The tests demonstrate that the wear rate of silicon in ambient air increases exponentially with stress and does not obey classical Archard's law. Series calculations of atomistic wear reactions generally reveal that the mechanical stress linearly drives the electron transfer to activate the sequential formation and rupture of interfacial bonds in the atomistic wear process. The atomistic wear model is thus resolved by combining the present stress-driven electron transfer model with Maxwell-Boltzmann statistics. This work may advance electronic insights into the law of nanoscale wear for understanding and controlling wear and manufacturing of material surfaces.

ß1 integrins regulate cellular behaviors and cardiomyocyte organization during ventricular wall formation.

Aims: The mechanisms regulating the cellular behavior and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how ß1 integrins regulate cardiomyocyte behavior and organization during ventricular wall morphogenesis in the mouse. Methods and Results: We applied mRNA deep sequencing and immunostaining to determine the expression repertoires of α/ß integrins and their ligands in the embryonic heart. Integrin ß1 subunit (ß1) and some of its ECM ligands are asymmetrically distributed and enriched in the luminal side of cardiomyocytes, while fibronectin surrounds cardiomyocytes, creating a network for them. Itgb1 , which encodes the ß1 integrin subunit, was deleted via Nkx2.5 Cre/+ to generate myocardial-specific Itgb1 knockout (B1KO) mice. B1KO hearts display an absence of trabecular zone but a thicker compact zone. The abundances of hyaluronic acid and versican are not significantly different. Instead, fibronectin, a ligand of ß1, was absent in B1KO. We examined cellular behaviors and organization via various tools. B1KO cardiomyocytes display a random cellular orientation and fail to undergo perpendicular cell division, be organized properly, and establish the proper tissue architecture to form trabeculae. The reduction of Notch1 activation was not the cause of the abnormal cellular organization in B1KO hearts. Mosaic clonal lineage tracing shows that Itgb1 regulates cardiomyocyte transmural migration and proliferation autonomously. Conclusions: ß1 is asymmetrically localized in the cardiomyocytes, and its ECM ligands are enriched in the luminal side of the myocardium and surrounding cardiomyocytes. ß1 integrins are required for cardiomyocytes to attach to the ECM network. This engagement provides structural support for cardiomyocytes to maintain shape, undergo perpendicular division, and establish cellular organization. Deletion of Itgb1 , leading to ablation of ß1 integrins, causes the dissociation of cardiomyocytes from the ECM network and failure to establish tissue architecture to form trabeculae.

Comparative Analysis of Physical Examination, CT Scan, and Three-Dimensional Gait Analysis in Evaluating Lower Extremity Torsion Deformities in Children with Cerebral Palsy.

BACKGROUND The aim of this study was to analyze the correlation and the accuracy of lower-extremity torsion deformities measured by physical examination, CT scan, and three-dimensional gait analysis in children with CP. MATERIAL AND METHODS The study group included 72 children with CP with lower-extremity torsion deformities. All subjects were assessed by: 1. physical examination: maximum internal rotation (MIR), maximum external rotation (MER) for hip joint torsion, and transmalleolar axis (TMA) for tibial torsion; 2. CT scanning: femoral anteversion (FAV) and tibial torsion (TT); 3. three-dimensional gait analysis kinematic parameters: single-support phase of femoral rotation, double-support phase of femoral rotation, swing phase of femoral rotation and single-support phase of tibial rotation, double-support phase of tibial rotation, and swing phase of tibial rotation. Statistical analysis was performed using the Pearson correlation test. A significance level of P<0.05 was set. RESULTS In femurs, MIR and MER were correlated with FAV, and the correlation of MER was higher, while physical examination and FAV were not correlated with any kinematic data in gait analysis. In tibias, there was no correlation between TMA and TT, but both TMA and TT were correlated with the gait analysis kinematic data, and the correlation of TT was higher. TMA was more correlated with tibial rotation during swing phase, while TT was more correlated with tibial rotation in single-support phase. CONCLUSIONS Three-dimensional gait analysis can analyze the tibial rotation of children with cerebral palsy, which is highly correlated with CT and physical examination. However, femoral rotation was not associated with CT and physical examination.

Effects of Thiamethoxam and Fenvalerate Residue Levels on Light-Stable Isotopes of Leafy Vegetables.

Accurate identification of the rational and standardized use of pesticides is important for the sustainable development of agriculture while maintaining a high quality. The insecticides thiamethoxam and fenvalerate and the vegetables spinach, cabbage, and lettuce were used here as study objects. Descriptive analysis and primary reaction kinetic equations were used to analyze the changes in metabolic residues of the two insecticides after different numbers of application in three vegetables. The effects of pesticide residue levels on the δ13C, δ15N, δ2H, and δ18O values of vegetables were analyzed by one-way analysis of variance and correlation analysis. Partial least squares discriminant analysis (PLS-DA) was applied to build discrimination models of the vegetables with different pesticide residues based on stable isotopes. The results showed that the first degradation residues of thiamethoxam and fenvalerate in spinach, cabbage, and lettuce conformed to primary reaction kinetic equations, but the degradation half-lives were long, and accumulation occurred in the second application. The differences in the four stable isotope ratios in the control group of the three vegetables were statistically significant, and two-thirds of the stable isotope ratios in the three vegetables with different numbers of pesticide applications were significantly different. The δ13C and δ15N values of spinach, the δ13C, δ15N, and δ2H values of cabbage, and the δ13C, δ15N, δ2H, and δ18O values of lettuce were significantly correlated with different residues of thiamethoxam and/or fenvalerate applications. The control groups of the three vegetables, spinach-thiamethoxam-first, spinach-thiamethoxam-second, cabbage-thiamethoxam-second, cabbage-fenvalerate-first, and lettuce-thiamethoxam-first, were fully identified by PLS-DA models, while the identification models of other vegetables containing pesticide residues still need to be further improved. The results provide technical support for identifying the rational use of pesticides in vegetables and provide a reference method for guaranteeing the authenticity of green and organic vegetables.

The engagement of autophagy in maniac disease.

AIMS: Mania is a prevalent psychiatric disorder with undefined pathological mechanism. Here, we reviewed current knowledge indicating the potential involvement of autophagy dysregulation in mania and further discussed whether targeting autophagy could be a promising strategy for mania therapy. DISCUSSIONS: Accumulating evidence indicated the involvement of autophagy in the pathology of mania. One of the most well-accepted mechanisms underlying mania, circadian dysregulation, showed mutual interaction with autophagy dysfunction. In addition, several first-line drugs for mania therapy were found to regulate neuronal autophagy. Besides, deficiencies in mitochondrial quality control, neurotransmission, and ion channel, which showed causal links to mania, were intimately associated with autophagy dysfunction. CONCLUSIONS: Although more efforts should be made to either identify the key pathology of mania, the current evidence supported that autophagy dysregulation may act as a possible mechanism involved in the onset of mania-like symptoms. It is therefore a potential strategy to treat manic disorder by correting autophagy.

Targeting neuronal mitophagy in ischemic stroke: an update.

Cerebral ischemia is a neurological disorder associated with complex pathological mechanisms, including autophagic degradation of neuronal mitochondria, or termed mitophagy, following ischemic events. Despite being well-documented, the cellular and molecular mechanisms underlying the regulation of neuronal mitophagy remain unknown. So far, the evidence suggests neuronal autophagy and mitophagy are separately regulated in ischemic neurons, the latter being more likely activated by reperfusional injury. Specifically, given the polarized morphology of neurons, mitophagy is regulated by different neuronal compartments, with axonal mitochondria being degraded by autophagy in the cell body following ischemia-reperfusion insult. A variety of molecules have been associated with neuronal adaptation to ischemia, including PTEN-induced kinase 1, Parkin, BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (Bnip3), Bnip3-like (Bnip3l) and FUN14 domain-containing 1. Moreover, it is still controversial whether mitophagy protects against or instead aggravates ischemic brain injury. Here, we review recent studies on this topic and provide an updated overview of the role and regulation of mitophagy during ischemic events.

[Effect of Systematic Graded Rewarming Pattern on All-Cause Mortality of Hypothermic Trauma Patients in Different Time Periods].

Objective To investigate the effect of systematic graded rewarming pattern on all-cause mortality of hypothermic trauma patients in different time periods. Methods A prospective case-control study was carried out for 236 hypothermic trauma patients with modified trauma score<12 in the Emergency Department of the Second Affiliated Hospital of Wenzhou Medical University from January 2020 to December 2021.The patients were randomly assigned into a systematic graded rewarming group (n=118) and a traditional rewarming group (n=118).The main outcome event was all-cause death within 15 days after trauma,and the secondary outcome event was all-cause death within 3,7,and 30 days after trauma. Results Overall,13.98%(33/236) and 14.83%(35/236) of the patients died within 15 and 30 days after trauma,respectively,and the median survival time of all dead patients was 6 (4,10) days.The systematic graded rewarming group had higher temperature after rewarming for 2 h (P=0.001) and larger temperature change after rewarming intervention (P=0.047) than the traditional rewarming group.The all-cause mortality within 15 days (27.3%vs.72.7%,P=0.005) and 30 days (25.7%vs.74.3%,P=0.002) in the systematic graded rewarming group was lower than that in the traditional rewarming group.Kaplan-Meier analysis showed that the survival time of the patients in the systematic graded rewarming group was longer than that in the traditional rewarming group (P=0.003).Multivariate cox regression analysis indicated that systematic graded rewarming was a strong protective factor for survival time after trauma (HR=0.450, P=0.042).Further Logistic regression analysis for the occurrence of all-cause death in each time period showed that the OR of systematic graded rewarming pattern to all-cause death within 15 days and 30 days after trauma were 0.289 and 0.286,respectively,after adjusting the covariates(P=0.008,P=0.005).The temperature after rewarming for 2 h had a negative correlation with all-cause mortality within 30 days after trauma (OR=0.670, P=0.049). Conclusions Systematic graded rewarming is a protective factor for the survival time of patients with traumatic hypothermia and an independent factor affecting the risk of all-cause death within 15 days and 30 days after trauma.The temperature after rewarming for 2 h is expected to be an independent predictor of all-cause mortality of 30 days after trauma in the patients with hypothermia.The systematic graded rewarming pattern could reduce the mortality of hypothermic trauma patients.

Association between triglyceride glucose index and sleep disorders: results from the NHANES 2005-2008.

BACKGROUND: To determine the association between sleep disorders and Triglyceride glucose index. METHODS: A cross-sectional analysis of the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES) was performed. The 2005 to 2008 NHANES national household survey for adults ≥ 20 years was examined for the sleep disorders.TyG index: ln [triglyceride (mg/ dL) × fasting blood glucose (mg/dL)/2].Multivariable logistic and linear regression models were used to explore the association between the TyG index and sleep disorders. RESULTS: A total of 4,029 patients were included. Higher TyG index is significantly associated with elevated sleep disorders in U.S. adults. TyG was moderately correlated with HOMA-IR (Spearman r = 0.51). TyG was associated with higher odds of sleep disorders(adjusted OR [aOR],1.896; 95% CI, 1.260 2.854), Sleep apnea (aOR, 1.559; 95% CI, 0.660 3.683), Insomnia(aOR, 1.914;95% CI, 0.531 6.896), and Restless legs (aOR, 7.759; 95% CI,1.446 41.634). CONCLUSIONS: In this study, our result shown that population with higher TyG index are significantly more likely to have sleep disorders in U.S. adults.

Sanwei DouKou Decoction ameliorate Alzheimer disease by increasing endogenous neural stem cells proliferation through the Wnt/ß-catenin signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanwei DouKou decoction (SDKD) is a traditional Chinese medicine (TCM) prescription derived from the Tibetan medical book "Si Bu Yi Dian" and is clinically used for the treatment of Alzheimer's disease (AD). However, the potential mechanism of SDKD treatment for AD remains elusive. AIM OF THE STUDY: This study aims to explore the potential mechanism by which SDKD alleviates AD. MATERIALS AND METHODS: Extracts of SDKD were identified with Gas chromatograph-mass spectrometer (GC-MS). 5 × FAD mice were treated with SDKD for 8 weeks. The efficacy of SDKD against AD was evaluated by in-vivo experiments. Morris water maze and contextual fear conditioning tests were used to detect the learning and memory ability of mice. Hematoxylin-eosin staining (H&E) staining was used to observe the pathological changes of brain tissue. Immunohistochemistry was used to detect the positive expression of Nestin in hippocampus. In in-vitro experiments, the Cell Counting Kit 8 (CCK-8) technique was used to detect cell viability, the proliferation of neural stem cells was detected by immunofluorescence staining, the intracellular protein expression was detected by Western Blot. RESULTS: The results of this study suggested that SDKD may ameliorate AD. SDKD significantly shortened the escape latency of mice in the Morris water maze experiment, increased the number of times the mice crossed the target quadrant, and prolonged freezing time in the contextual fear memory experiment. SDKD also improved neuronal pathology in the hippocampus, decreased neuronal loss, and increased Nestin protein levels. Furthermore, in in-vitro experiments, SDKD could significantly increase Neural stem cells (NSCs) viability, promoted NSCs proliferation, and also effectively activated the Wnt/ß-catenin signalling pathway, increased Wnt family member 3A (Wnt3a), ß-catenin and CyclinD1 protein levels, activated the NSCs proliferation pathways in AD model mouse brain tissue. CONCLUSIONS: The present study demonstrated that sanwei doukou decoction can ameliorate AD by increasing endogenous neural stem cells proliferation through the Wnt/ß-catenin signalling pathway. Our observations justify the traditional use of SDKD for a treatment of AD in nervous system.