Identification of the metabolites of nimbolide in rat by liquid chromatography combined with quadrupole/orbitrap mass spectrometry.

Nimbolide is a major furanoid compound isolated from Azadirachta indica. The aim of this study was to characterize the metabolites of nimbolide in rats and to propose the metabolic pathways. The metabolites were generated by incubating nimbolide (10 μM) with rat liver microsomes, nicotinamide adenine dinucleotide phosphate (NADPH), and nucleophiles (glutathione [GSH] or N-acetyl-lysine [NAL]) at 37°C for 60 min.

Integrated serum metabolomics, 16S rRNA sequencing and bile acid profiling to reveal the potential mechanism of gentiopicroside against nonalcoholic steatohepatitis in lean mice.

Ethnopharmacological Relevance: Lean nonalcoholic steatohepatitis (NASH) poses a serious threat to public health worldwide. Herbs of the genus Gentiana have been used for centuries to treat hepatic disease or have been consumed for hepatic protection efficiency. Gentiopicroside (GPS), the main bioactive component of Gentiana herbs, has been shown to be beneficial for protecting the liver, improving intestinal disorders, modulating bile acid profiles, ameliorating alcoholic hepatosteatosis, and so on.

IMPACT OF CLIMATE CHANGE ON COASTAL ECOSYSTEM AND OUTDOOR ACTIVITIES: A COMPARATIVE ANALYSIS AMONG FOUR LARGEST COASTLINE COVERING COUNTRIES.

Climate change and coastal ecosystems have become challenging subjects for world sustainability. Humans, animals, and other ocean habitats are primarily affected by the harmful changes in climate. Coastal ecosystems support biodiversity and a wide range of species that serve as habitats for many commercially important fish species and enhance human activities in coastal areas.

Investigating the efficacy and mechanisms of Jinfu'an decoction in treating non-small cell lung cancer using network pharmacology and in vitro and in vivo experiments.

Ethnopharmacological Relevance: Jinfu'an Decoction (JFAD) is a traditional Chinese decoction used in lung cancer treatment to improve patient quality of life and survival. Previous research has established that JFAD has a significant therapeutic effect on non-small cell lung cancer (NSCLC), although the underlying molecular mechanisms have not been largely underexplored.

Aim Of The Study: We used network pharmacology to identify the putative active ingredients of JFAD and conducted experimental studies to determine the potential molecular mechanism of JFAD in NSCLC treatment.

Endothelial progenitor cells in pregnancy-related diseases.

Placental neovascularization plays a crucial role in fetomaternal circulation throughout pregnancy and is dysregulated in several pregnancy-related diseases, including preeclampsia, gestational diabetes mellitus, and fetal growth restriction. Endothelial progenitor cells (EPCs) are a heterogeneous population of cells that differentiate into mature endothelial cells, which influence vascular homeostasis, neovascularization, and endothelial repair. Since their discovery in 1997 by Asahara et al.

Modeling the protein binding non-linearity in population pharmacokinetic model of valproic acid in children with epilepsy: a systematic evaluation study.

Several studies have investigated the population pharmacokinetics (popPK) of valproic acid (VPA) in children with epilepsy. However, the predictive performance of these models in the extrapolation to other clinical environments has not been studied. Hence, this study evaluated the predictive abilities of pediatric popPK models of VPA and identified the potential effects of protein binding modeling strategies.

Lipid metabolism as a target for cancer drug resistance: progress and prospects.

Cancer is the world's leading cause of human death today, and the treatment process of cancer is highly complex. Chemotherapy and targeted therapy are commonly used in cancer treatment, and the emergence of drug resistance is a significant problem in cancer treatment. Therefore, the mechanism of drug resistance during cancer treatment has become a hot issue in current research.

Salvianolic acid F suppresses KRAS-dependent lung cancer cell growth through the PI3K/AKT signaling pathway.

Background: KRAS mutation is a common driver of NSCLC, and there is a high proportion of lung cancer patients with KRAS G12C and G12D mutation. KRAS was previously considered an "undruggable" target, but the first KRAS G12C mutation-targeted drug AMG510, entered the market in 2021. However, treatments for G12D mutant tumors remain to be discovered.

Multi-omics analysis reveals the prognostic and tumor micro-environmental value of lumican in multiple cancer types.

Lumican (LUM), a proteoglycan of the extracellular matrix, has been reported to be involved in the regulation of immune escape processes, but the data supporting this phenomenon are not sufficient. In this study, we aimed to explore the links among LUM expression, survival, tumor microenvironment (TME), and immunotherapy in 33 cancer types. Data from several databases, such as UCSC Xena, GTEx, UALCAN, HPA, GEPIA2, TISIDB, PrognoScan, TIMER2, and GEO, as well as published studies, were used to determine the relationship between LUM expression and clinical features, TME, heterogeneity, and tumor stemness.

Clinical diagnostic value of amino acids in laryngeal squamous cell carcinomas.

Background: Early diagnosis and treatment can improve the survival rates of patients with laryngeal squamous cell carcinoma (LSCC). Therefore, it is necessary to discover new biomarkers for laryngeal cancer screening and early diagnosis.

Methods: We collected fasting plasma from LSCC patients and healthy volunteers, as well as cancer and para-carcinoma tissues from LSCC patients, and performed quantitative detection of amino acid levels using liquid chromatography-mass spectrometry.

RBFOX2 confers tumor growth by PI3K/AKT and MAPK signaling in gastric cancer.

RNA-binding Fox (RBFOX)2, a member of a family of RNA-binding proteins, is well known as a regulator of alternative pre-mRNA splicing. However, its possible role in gastric cancer is unknown. In this study, we investigated the biologic role and clinical significance of RBFOX2 in gastric cancer growth and elucidated its underlying molecular mechanisms.

Clip-SP1 cleavage activates downstream prophenoloxidase activating protease (PAP) in Plutella xylostella.

Melanization is a component of the humoral immune defense of insects and is induced by serine protease-mediated phenoloxidase (PO) catalysis. Prophenoloxidase (PPO) in the midgut of Plutella xylostella is activated by the CLIP domain serine protease (clip-SP) in response to Bacillus thuringiensis (Bt) infection, but the detailed signaling cascade following this activation is unknown. Here, we report that activation of clip-SP enhances PO activity in the P.

Enhanced resistance to Bacillus thuringiensis Cry1Ac toxin mediated by the activation of prophenoloxidase in a cosmopolitan pest.

Plutella xylostella has evolved resistance to Bacillus thuringiensis Cry1Ac toxin over a long evolutionary period. Enhanced immune response is an important factor in insect resistance to a variety of insecticides, and whether phenoloxidase (PO), an immune protein, is involved in resistance to Cry1Ac toxin in P. xylostella remains unclear.

Analysis of the Effect of and Transporter on Cry1Ac Susceptibility by CRISPR/Cas9-Mediated Knockout.

Many insects, including the (L.), have developed varying degrees of resistance to many insecticides, including () toxins, the bioinsecticides derived from . The polycalin protein is one of the potential receptors for toxins, and previous studies have confirmed that the Cry1Ac toxin can bind to the polycalin protein of , but whether polycalin is associated with the resistance of toxins remains controversial.

Correlation of endocrine disrupting chemicals with essential elements in biological samples of children (1-5 years) with different infectious diseases and impact on sustainable outdoor activities.

Endocrine disrupting chemicals (EDCs) have been extensively explored due to their harmful effects on individual health and the environment by interfering with hormone activity and disrupting the endocrine system. However, their relationship with essential trace elements remains uncertain. This research aimed to investigate the possible correlation between essential trace elements and toxic metals, including cadmium (Cd), and lead (Pb) in children aged 1-5 years with various infectious diseases, including gastrointestinal disorders, typhoid fever, and pneumonia.

Development and validation of an immune-related gene signature for prognosis in Lung adenocarcinoma.

The most common type of lung cancer tissue is lung adenocarcinoma. The TCGA-LUAD cohort retrieved from the TCGA dataset was considered the internal training cohort, while GSE68465 and GSE13213 datasets from the GEO database were used as the external test cohort. The TCGA-LUAD cohort was classified into two immune subtypes using single-sample gene set enrichment analysis of the immune gene set and unsupervised clustering analysis.

Pre- and post-COVID-19: The impact of the pandemic and stock market psychology on the growth and sustainability of consumer goods industries.

The objective of this study is to investigate the impact of the COVID-19 pandemic and stock market psychology on investor investment decisions in different business units operating in the Shandong stock market. The sample size of the study consists of 5,000 individuals from six different business units. The study used the event study statistical technique to analyze the market reaction to newly released information from the stock market perspective to assess whether the number of COVID-19 positive cases impacted it.

Do oil, gold and metallic price volatilities prove gold as a safe haven during COVID-19 pandemic? Novel evidence from COVID-19 data.

The spreading COVID-19 outbreak has wreaked havoc on the world's financial system that raises an urgent need for the re-evaluation of the gold as safe haven for their money because of the unprecedented challenges faced by markets during this period. Therefore, the current study investigates whether different asset class volatility indices affect desirability of gold as a safe-haven commodity during COVID-19 pandemic. Long run and the short run relationship of gold prices with gold price volatility, oil price volatility, silver price volatility and COVID-19 (measured by the number of deaths due to COVID) has been analyzed in the current study by applying ARDL Bound testing cointegration and non linear ARDL approach on daily time series data ranging from January 2020 to Dec 2021.

The Potential Role of the Methionine Aminopeptidase Gene in a Cosmopolitan Pest for Toxin Tolerance.

Methionine aminopeptidases (MetAPs) catalyze the cleavage of the N-terminal initiator methionine (iMet) in new peptide chains and arylamides, which is essential for protein and peptide synthesis. MetAP is differentially expressed in two diamondback moth (DBM; ) strains: the G88 susceptible strain and the Cry1S1000 strain, which are resistant to the Bt toxin Cry1Ac, implicating that MetAP expression might be associated with Bt resistance. In this study, we identified and cloned a MetAP gene from DBMs, named , which has a CDS of 1140 bp and encodes a 379 amino acid protein.

Post-COVID-19 investor psychology and individual investment decision: A moderating role of information availability.

This study aims to investigate the influence of psychological biases on the investment decision of Chinese individual investors after the pandemic of COVID-19 with a moderating role of information availability. A cross-sectional method with a quantitative research approach was employed to investigate the hypothesized relationships among variables. The snowball sampling technique was applied to collect the data through a survey questionnaire from individual investors investing in the Chinese stock market.

A GLP-1/glucagon (GCG)/CCK receptors tri-agonist provides new therapy for obesity and diabetes.

Background And Purpose: Glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptor dual agonist have promising therapeutic effects in the treatment of obesity and diabetes. Moreover, GLP-1 and cholecystokinin 2 (CCK ) dual agonists have been shown to restore pancreas function and improve glycaemic control in preclinical studies. We describe, for the first time, the beneficial effects of GLP-1/glucagon receptor and GLP-1/CCK dual agonists, which can be integrated into one peptide, resulting in significant anti-diabetes and anti-obesity effectiveness.

Theory of Mind Among Swedish Children with ASD, Down Syndrome and Typically Developing Group.

The present study examined the role of IQ and the Theory of Mind understanding in children with an autism spectrum disorder and down syndrome. Sixty-six Swedish children with ASD (n = 26), DS (n = 18), and typically developed group (n = 22) ranged between 6 and 12 years old were compared on ToM tasks consisted of standard ToM and IQ tasks. SPSS 25 program was used to analyze data.

A Novel Reference for Bt-Resistance Mechanism in Based on Analysis of the Midgut Transcriptomes.

The diamondback moth, , is a lepidopteran insect that mainly harms cruciferous vegetables, with strong resistance to a variety of agrochemicals, including (Bt) toxins. This study intended to screen genes associated with Bt resistance in by comparing the midgut transcriptome of Cry1Ac-susceptible and -resistant strains together with two toxin-treated strains 24 h before sampling. A total of 12 samples were analyzed by BGISEQ-500, and each sample obtained an average of 6.

UPLC-MS/MS method for simultaneously determining nucleosides and methyl-nucleosides in liver mRNA of Epimedin C-induced liver injury mouse model.

Background: Epimedin C, one of the main active ingredients of Epimedium, has been reported to have potential hepatotoxicity. However, the mechanism of Epimedin C-induced liver injury has not been studied. mRNA methylation, mainly including N6-methyladenosine and N5-methylcytidine, is implicated in the regulation of many biological processes and diseases.

The effectiveness of traditional Chinese medicine-based exercise on physical performance, balance and muscle strength among older adults: a systematic review with meta-analysis.

Background: Traditional Chinese medicine (TCM) based exercises have been widely used in the prevention and treatment of balance, cardiopulmonary, and other related diseases in older adults. However, there seems to be no consensus on the improvement and comparison of physical performance, balance, and muscle strength in the elderly population.

Objectives: To systematically examine the impact of different TCM-based exercises on physical performance, balance, and muscle strength outcomes in the elderly.