Absence of PNET formation and normal longevity in a mouse model of Mahvash disease.

Mahvash disease, a rare autosomal recessive metabolic disorder characterized by biallelic loss-of-function mutations in the glucagon receptor gene (), induces significant pancreatic hyperglucagonemia, resulting in α-cell hyperplasia and occasional hypoglycemia. Utilizing CRISPR-Cas9 technology, we engineered a mouse model, designated as , harboring a homozygous V369M substitution in the glucagon receptor (GCGR). Although wild-type (WT) and mice exhibited no discernible difference in appearance or weight, adult mice, approximately 12 months of age, displayed a notable decrease in fasting blood glucose levels and elevated the levels of cholesterol and low-density lipoprotein-cholesterol.

A novel variation of increases grain weight without penalty in grain protein content in wheat ( L.).

Unlabelled: Yield and quality are two crucial breeding objects of wheat therein grain weight and grain protein content (GPC) are two key relevant factors correspondingly. Investigations of their genetic mechanisms represent special significance for breeding. In this study, 199 F plants and corresponding F families derived from Nongda3753 (ND3753) and its EMS-generated mutant 564 (M564) were used to investigate the genetic basis of larger grain and higher GPC of M564.

Distinct roles of the extracellular surface residues of glucagon-like peptide-1 receptor in β-arrestin 1/2 signaling.

Glucagon-like peptide-1 receptor (GLP-1R) is a prime drug target for type 2 diabetes and obesity. The ligand initiated GLP-1R interaction with G protein has been well studied, but not with β-arrestin 1/2. Therefore, bioluminescence resonance energy transfer (BRET), mutagenesis and an operational model were used to evaluate the roles of 85 extracellular surface residues on GLP-1R in β-arrestin 1/2 recruitment triggered by three representative GLP-1R agonists (GLP-1, exendin-4 and oxyntomodulin).

Research on Resource Allocation and Optimization of Community Intelligent Sports Service for the Elderly Based on Group Intelligence.

The mainstream development trend in the era of intelligent sports. At present, with the rapid development of science and technology, it is absolutely wise to combine group intelligence with community intelligent sports services for the elderly. Group intelligence has opened a new era of intelligent sports service.

Constitutive signal bias mediated by the human GHRHR splice variant 1.

Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone-releasing hormone receptor (GHRHR) is capable of transducing biased signal. Differing only at the receptor N terminus, GHRHR predominantly activates G while SV1 selectively couples to β-arrestins.

Allosteric Modulators Enhancing GLP-1 Binding to GLP-1R via a Transmembrane Site.

The glucagon-like peptide-1 receptor (GLP-1R) is a well-established drug target for the treatment of type II diabetes. The development of small-molecule positive allosteric modulators (PAMs) of GLP-1R is a promising therapeutic strategy. Here, we report the discovery and characterization of PAMs with distinct chemotypes, binding to a cryptic pocket formed by the cytoplasmic half of TM3, TM5, and TM6.

Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver-α-cell axis.

Glucagon plays an important role in glucose homeostasis and amino acid metabolism. It regulates plasma amino acid levels which in turn modulate glucagon secretion from the pancreatic α-cell, thereby establishing a liver-α-cell axis described recently. We reported previously that the knock-in mice bearing homozygous V369M substitution (equivalent to a naturally occurring mutation V368M in the human glucagon receptor, GCGR) led to hypoglycemia with improved glucose tolerance.

BCL9/BCL9L promotes tumorigenicity through immune-dependent and independent mechanisms in triple negative breast cancer.

Treatment of patients with triple-negative breast cancer (TNBC) has been challenging due to a lack of well-defined molecular targets. The Wnt/β-catenin pathway is known to be activated in many TNBC patients and BCL9 and BCL9L are important transcriptional co-activators of β-catenin, but whether inhibition of BCL9/BCL9L can suppress TNBC growth and the underlying mechanism are not fully understood. Here we demonstrate that the expression of BCL9 and BCL9L is directly correlated with malignancy in TNBC patient tumors and that BCL9 and BCL9L promote tumor cell growth, cell migration and metastasis in TNBC models.

Characterization and phylogenetic analysis of the complete mitochondrial genome of pathogen (Trichosporonales: Trichosporonaceae).

In the present study, the complete mitochondrial genome of was sequenced and assembled. The complete mitochondrial genome of contained 22 protein-coding genes (PCG), 2 ribosomal RNA (rRNA) genes, and 24 transfer RNA (tRNA) genes. The total size of the mitochondrial genome is 39,466 bp, with the GC content of 27.

Minocycline alleviates the symptoms of morphine withdrawal via the CaMKII-Ras-ERK signaling pathway.

Objective: To investigate the effect of minocycline on morphine withdrawal symptoms.

Methods: We established a rat model of morphine dependence, then injected the animals with naloxone to induce withdrawal symptoms. Minocycline was injected into the midbrain periaqueductal gray and its effect on withdrawal symptoms and Ca-dependent protein kinase (CaMKII), Ras, and phospho-extracellular signal-regulated kinase (p-ERK) expression was observed.

W2476 represses TXNIP transcription via dephosphorylation of FOXO1 at Ser319.

Thioredoxin-interacting protein (TXNIP) overexpression is implicated in the pathogenesis of type 2 diabetes. Previous studies have shown that a small molecule compound (W2476) was able to improve β-cell dysfunction and exert therapeutic effects in diabetic mice via repression of TXNIP signaling pathway. The impact of W2476 on TXNIP transcription was thus investigated using the chromatin immunoprecipitation method.

Characterization and phylogenetic analysis of the complete mitochondrial genome of a basidiomycetous yeast sp. (Cystobasidiales: Cystobasidiaceae).

In the present study, the complete mitochondrial genome of a basidiomycetous yeast sp. was assembled and obtained. The mitochondrial genome of sp.

Injection of minocycline into the periaqueductal gray attenuates morphine withdrawal signs.

This study investigated the effects of minocycline microinjections, into the midbrain periaqueductal gray (PAG), on morphine withdrawal and the expression of pannexin-1 (panx1), phosphorylated mammalian target of rapamycin (p-mTOR), protein kinase A (PKA), and cAMP response element-binding protein (CREB). Rats were injected with morphine, intraperitoneally, at increasing doses, twice per day, to establish animal models of morphine exposure. Minocycline was administered into the PAG before the first intraperitoneal (i.

Characterization of a naturally occurring mutation V368M in the human glucagon receptor and its association with metabolic disorders.

Glucagon is a peptide hormone secreted by islet α cells. It plays crucial roles in glucose homeostasis and metabolism by activating its cognate glucagon receptor (GCGR). A naturally occurring deleterious mutation V368M in the human GCGR leads to reduced ligand binding and down-regulation of glucagon signaling.

Injection of D1 receptor antagonist SCH23390 into the periaqueductal gray attenuates morphine withdrawal symptoms in rats.

The aim of this study was to investigate the relationship of dopamine D1 receptor (D1R) and its downstream factors with morphine withdrawal symptoms in rats. Rats were injected intraperitoneally with morphine in a dose-escalating manner. The midbrain periaqueductal gray (PAG) area was microinjected with D1R antagonist SCH23390 or D1R agonist SKF38393.

Early detection of Alzheimer's disease by peptides from phage display screening.

Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective treatment so far. As clinical trials show that early-stage patients are more likely to respond to potential interventions, various technologies have been used to search blood biomarkers for the early diagnosis of AD. Phage display could be used to select specific peptides against desired target and here, we established a peptide binding assay based on phage display peptide library to detect early-stage AD patients.

Dopamine D1 receptor agonist treatment alleviates morphine-exposure-induced learning and memory impairments.

We investigated the mechanisms by which the dopamine D1 receptor alleviates morphine-exposure-induced cognitive impairments. Rats were intraperitoneally injected with morphine in a dose-escalating manner over 10 days, and 15 min before the morphine injection on days 1, 3, 5, 7, and 9, the rats were administered the D1 receptor agonist SKF81297 or the D1 receptor antagonist SCH38933 into the midbrain periaqueductal gray (PAG). The Morris water maze was used to examine learning- and memory-related behavioral changes.

Characterization and comparative analysis of six complete mitochondrial genomes from ectomycorrhizal fungi of the Lactarius genus and phylogenetic analysis of the Agaricomycetes.

Lactarius is one of the most prominent genera of mushroom-forming fungi in the world. In the present study, complete mitochondrial genomes (mitogenomes) from six Lactarius species were sequenced and assembled. The six mitogenomes were all composed of circular DNA molecules, with total lengths ranging from 38,445 bp to 60,843 bp.

A dopamine D1 receptor agonist improved learning and memory in morphine-treated rats.

Objective: The objective of this article is to study the role of the dopamine (DA) D1 receptor in the midbrain periaqueductal grey (PAG) on learning and memory in morphine-addicted rats.

Methods: DA D1 receptor agonist SKF81297 and D1 receptor antagonist SCH SCH23390 were administrated into the PAG, respectively, and the learning and memory behavioral changes of morphine addicted rats were detected by water maze. Western blot and immunohistochemistry were used to detect glutamate decarboxylase 67 (GAD67) and tyrosine receptor kinase B (TrkB) in PAG.

Combinatorial antitumor effects of indoleamine 2,3-dioxygenase inhibitor NLG919 and paclitaxel in a murine B16-F10 melanoma model.

Indoleamine 2,3-dioxygenase (IDO) is involved in tumor immune escape and resistance to chemotherapy, and is clinically correlated with tumor progression. IDO inhibitors show marginal efficacy as single agents; therefore, combinations of these inhibitors with other therapies hold promise for cancer therapy. The aim of this study was to investigate the synergistic antitumor effects of IDO inhibitor NLG919 in combination with different regimens of paclitaxel in a murine B16-F10 melanoma model.

Protective Effect of RA on Myocardial Infarction-Induced Cardiac Fibrosis via AT1R/p38 MAPK Pathway Signaling and Modulation of the ACE2/ACE Ratio.

Rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyllactic acid, RA) is a major active constituent of Rosmarinus officinalis Linn. (rosemary) having significant anti-inflammatory, anti-apoptotic, and antioxidant effects. However, the cardioprotection of RA is still not understood.

Antidepressant-like Effects of LPM580153, A Novel Potent Triple Reuptake Inhibitor.

The purpose of this study was to characterize a novel compound, 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl) ethyl] phenyl 3-nitrophenyl ether, designated LPM580153. We used several well-validated animal models of depression to assess the antidepressant-like activity of LPM580153, followed by a neurotransmitter uptake assay and a corticosterone-induced cell injury model to explore its mechanism of action. In mice, LPM580153 reduced immobility time in the tail suspension test, and in rats subjected to chronic unpredictable mild stress it reversed reductions in body weight gain and ameliorated anhedonia.

RACK1 inhibits morphine re-exposure via inhibition of Src.

Objective: We previously demonstrated that receptor for activated C kinase 1 (RACK1) inhibited phosphorylated extracellular signal-regulated kinase (p-ERK) during morphine reward in mice. In the present study, we examined the role of Src in regulating the inhibition of p-ERK in the brain following RACK1 over-expression during morphine reward.

Methods: Mice were subcutaneously injected with morphine on days 2, 4, 6, and 8 after pre-test (day 1), and saline was delivered the following day.

Production and immunoanalytical application of 32 monoclonal antibodies against metacestode somatic antigens of Echinococcus multilocularis.

Alveolar echinococcosis is a rare but potentially fatal disease. Immunodiagnosis based on antibodies or antigens plays an important role in its diagnosis. In this study, metacestode somatic antigens of Echinococcus multilocularis were used to immunize BALB/c mice, and hybridomas were formed by cell fusion.