Unveiling the impact of harvest time on Dioscorea opposita Thunb. cv. Tiegun maturity by NMR-based metabolomics and LC-MS/MS analysis.

Background: Dioscorea opposita Thunb. cv. Tiegun maturity (DM) is an important factor influencing its quality.

Comprehensive widely targeted metabolomics to decipher the molecular mechanisms of thunb. cv. Tiegun quality formation during harvest.

Thumb. cv. Tiegun is commonly consumed as both food and traditional Chinese medicine, which has a history of more than two thousand years.

Coronavirus Mask Protection Algorithm: A New Bio-inspired Optimization Algorithm and Its Applications.

Nowadays, meta-heuristic algorithms are attracting widespread interest in solving high-dimensional nonlinear optimization problems. In this paper, a COVID-19 prevention-inspired bionic optimization algorithm, named Coronavirus Mask Protection Algorithm (CMPA), is proposed based on the virus transmission of COVID-19. The main inspiration for the CMPA originated from human self-protection behavior against COVID-19.

The development of COVID-19 treatment.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic named coronavirus disease 2019 (COVID-19) that has become the greatest worldwide public health threat of this century. Recent studies have unraveled numerous mysteries of SARS-CoV-2 pathogenesis and thus largely improved the studies of COVID-19 vaccines and therapeutic strategies. However, important questions remain regarding its therapy.

Discovery of a potent and long-acting Xenopus GLP-1-based GLP-1/glucagon/Y receptor triple agonist.

The combination of incretin-based therapies and PYY analogue has shown great potential for the treatment of type 2 diabetes (T2DM) and obesity. In this study we developed the first example of a unimolecular triple agonist peptide to simultaneously target GLP-1, glucagon and Y receptors, aiming for superior weight loss and better glycemic control. The strategy for constructing such a unimolecular triple agonist peptide is the conjugation of the GLP-1R/GCGR dual-agonistic moiety and PYY moiety via maleimide-thiol specific reaction.

A tumor immune microenvironment-related integrated signature can predict the pathological response and prognosis of esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: A multicenter study in China.

Background: Currently, there are insufficient indicators for the reliable assessment of treatment response following neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal squamous cell carcinoma (ESCC). Considering the essential role of protein-coding and non-coding RNAs in gene regulation and cellular processes, we systematically explored the molecular features and clinical significance of mRNA and lncRNA in 249 pretreatment biopsies from four hospitals in three districts with a high incidence of ESCC patients in China.

Methods: During the discovery phrase, 13 differentially expressed genes were identified and validated between samples with a complete pathological response (pCR) and those with an incomplete pathological response ( View Article and Find Full Text PDF

Design of Xenopus GLP-1-Based Long-Acting Dual GLP-1/Y Receptor Agonists.

GLP-1 receptor (GLP-1R) and neuropeptide Y receptor (YR) dual agonists have shown great potential to treat obesity and type 2 diabetes (T2DM). We developed a multitarget strategy to design monomeric agonists based on GLP-1 (xGLP-1) and PYY analogues with dual activation activities on GLP-1R and YR. A novel peptide, , was obtained via stepwise structure optimization and receptor screens.

Discovery of METTL3 Small Molecule Inhibitors by Virtual Screening of Natural Products.

N-Methyladenosine (mA) is the most prevalent mRNA modification in mammalian cells that is mainly catalyzed by the methyltransferase complex of methyltransferase-like 3 and methyltransferase-like 14 (METTL3-METTL14). Many lines of evidence suggest that METTL3 plays important roles in several diseases such as cancers and viral infection. In the present study, 1,042 natural products from commercially available sources were chosen to establish a screening library, and docking-based high-throughput screening was performed to discover potential METTL3 inhibitors.

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.

Peptide-based long-acting co-agonists of GLP-1 and cholecystokinin 1 receptors as novel anti-diabesity agents.

The combined use of gastrointestinal hormones for treating metabolic diseases is gaining increasing attention. It was documented previously that co-administration of a cholecystokinin receptor-1 receptor (CCK-1R) agonist with a glucagon-like peptide-1 receptor (GLP-1R) agonist exerted improved effects on metabolic improvements in obese rodents. Here, we reported a series of novel GLP-1R/CCK-1R co-agonists constructed by linking the C-terminus of a GLP-1R agonist (native GLP-1 or Xenopus GLP-1) to the N-terminus of a CCK-1R selective agonist NN9056.

Identification of integrative molecular and clinical profiles of Fibrinogen-like protein 2 in gliomas using 1323 samples.

Background: Fibrinogen-like protein 2 (FGL2), a member of the fibrinogen superfamily, has been described to augment immunosuppression in gliomas. However, the precise clinical molecular features and the prognostic relevance of FGL2 in gliomas remain unclear. Therefore, a comprehensive analysis of the role of FGL2 in gliomas would provide insights into the therapeutic implications for this disease.

Hypoxia-induced GBE1 expression promotes tumor progression through metabolic reprogramming in lung adenocarcinoma.

Hypoxia mediates a metabolic switch from oxidative phosphorylation to glycolysis and increases glycogen synthesis. We previously found that glycogen branching enzyme (GBE1) is downstream of the hypoxia-inducible factor-1 (HIF1) signaling pathway in lung adenocarcinoma (LUAD) cells; however, the molecular mechanism underlying HIF1 regulation of GBE1 expression remains unknown. Herein, the effect of GBE1 on tumor progression via changes in metabolic signaling under hypoxia in vitro and in vivo was evaluated, and GBE1-related genes from human specimens and data sets were analyzed.

A comprehensive analysis of metabolomics and transcriptomics in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer death globally. More accurate and reliable diagnostic methods/biomarkers are urgently needed. Joint application of metabolomics and transcriptomics technologies possesses the high efficiency of identifying key metabolic pathways and functional genes in lung cancer patients.

Untargeted Metabolomics Analysis of Esophageal Squamous Cell Carcinoma Discovers Dysregulated Metabolic Pathways and Potential Diagnostic Biomarkers.

: Esophageal squamous cell carcinoma (ESCC) is one of the most fatal diseases worldwide. Because early diagnosis is difficult, ESCC is mostly diagnosed at an advanced stage, leading to a poor overall prognosis. The purpose of this study was to explore the differences between plasma metabolic profiles in ESCC patients and healthy controls and to establish a diagnostic model of ESCC.

Analysis of lncRNA, miRNA and mRNA-associated ceRNA networks and identification of potential drug targets for drug-resistant non-small cell lung cancer.

: Drug resistance to chemotherapeutic drugs or targeted medicines is an obstacle encountered in the treatment of non-small-cell lung cancer (NSCLC). However, the mechanisms of competing endogenous RNA (ceRNA) on the drug resistance in NSCLC are rarely reported. In this paper, the comprehensive expression profiles of lncRNAs and mRNAs in drug-resistant NSCLC cells were obtained by RNA sequencing.

Integrated quality evaluation strategy for multi-species resourced herb medicine of Qinjiao by metabolomics analysis and genetic comparation.

Background: Quality evaluation of multi-species resourced herb medicine (MSRHM) is a main problem for quality control of herb medicine. Current quality evaluation methodology lost consideration of species discrepancy. New quality evaluation strategy for MSRHM is in urgent need.

Polyphyllin VI induces apoptosis and autophagy in human osteosarcoma cells by modulation of ROS/JNK activation.

Purpose: Polyphyllin VI, a main active saponin isolated from traditional medicinal plant , has exhibited antitumor activities in several cancer cell lines. In the present study, we investigated the antitumor effect of Polyphyllin VI against human osteosarcoma cells (U2OS) and the underlying molecular mechanisms.

Methods: The U2OS cell lines were used to determine the antiproliferative effect of Polyphyllin VI by CCK8 assay.

An overview of recent progress in siderophore-antibiotic conjugates.

Multi-drug resistant infections caused by Gram-negative bacteria have become one of the most important reasons for the failure of clinical anti-infective treatment. Siderophore-antibiotic conjugates, which were designed based on a "Trojan horse" strategy wherein features enabled active uptake to bypass the Gram-negative cell wall, have been expected to be a weapon for anti-infective treatment in the clinic. Herein, we review antibiotic drug design strategies based on mimics of nature siderophores reported in recent years, we also focus our attention on the relationship between the type of linker and the corresponding antibacterial activity.

NMR-based metabolomics approach to investigate the distribution characteristics of metabolites in Dioscorea opposita Thunb. cv. Tiegun.

Dioscorea opposita Thunb. cv. Tiegun (DTT), a type of homologous medicinal plant, is commonly used as food in daily life.

Characterization of transcriptome profile and clinical features of a novel immunotherapy target CD204 in diffuse glioma.

CD204 is a specific marker of tumor-associated macrophages (TAMs) in glioma. However, the expression levels of CD204 and its involvement in glioma are not fully understood. In this large-scale study, we assessed the expression and function of CD204 in whole-grade glioma molecularly and clinically.

In vitro metabolic profiles of motolimod by using liquid chromatography tandem mass spectrometry: Metabolic stability, metabolite characterization and species comparison.

Motolimod (VTX-2337) is an agonist of toll-like receptor 8 (TLR8) with potential immune-stimulating and antineoplastic activities. The purpose of this study was to investigate the in vitro metabolic profiles of VTX-2337. The average in vitro T values were 6.

CDK11 plays a critical role in the tumorigenicity of esophageal squamous cell carcinoma cells and is a potential drug target.

Esophageal squamous cell carcinoma (ESCC) is a serious malignancy with limited options for targeted therapy. The exploration of novel targeted therapies for combating ESCC is urgently needed. Cyclin-dependent kinases (CDKs) play important roles in the progression of cancers; however, the function of CDK11 (cyclin-dependent kinase 11) in ESCC is still unknown.

Novel Strategy to Decipher the Regulatory Mechanism of 1-Naphthaleneacetic Acid in Strawberry Maturation.

1-Naphthaleneacetic acid (NAA) has long been used to regulate strawberry growth. However, its regulatory mechanisms are unclear. Here, a nuclear magnetic resonance (NMR)-based metabolomics approach was utilized to capture differential metabolites, then matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and transcriptomics as assisted methods to validate the significant findings of metabolomics.

Expression Profiles of microRNAs in Drug-Resistant Non-Small Cell Lung Cancer Cell Lines Using microRNA Sequencing.

Background/aims: Drug resistance remains a main obstacle to the treatment of non- small cell lung cancer (NSCLC). The aim of this study was to identify the expression profiles of microRNAs (miRNAs) in drug-resistant NSCLC cell lines.

Methods: The expression profiles of miRNAs in drug-resistant NSCLC cell lines were examined using miRNA sequencing, and the common dysregulated miRNAs in these cell lines were identified and analyzed by bioinformatics methods.

Large-scale analysis reveals a novel risk score to predict overall survival in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality and an increasing incidence worldwide; however, there are very few effective diagnostic approaches and prognostic biomarkers.

Materials And Methods: One hundred forty-nine pairs of HCC samples from Gene Expression Omnibus (GEO) were obtained to screen differentially expressed genes (DEGs) between HCC and normal samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene ontology enrichment analyses, and protein-protein interaction network were used.