Bufalin alleviates inflammatory response and oxidative stress in experimental severe acute pancreatitis through activating Keap1-Nrf2/HO-1 and inhibiting NF-κB pathways.

Severe acute pancreatitis (SAP) is a prevalent acute inflammatory disease that is clinically manifested by systemic inflammation dysregulation, resulting in a significantly elevated mortality rate. Bufalin has been verified to have potent pharmacological properties, including analgesic, anti-tumor and anti-inflammatory effects. However, it remains unclear whether bufalin inhibits SAP.

Comparison of Injury Severity Score (ISS) and New Injury Severity Score (NISS) in the Evaluation of Thoracic Trauma Patients: A Retrospective Cohort Study.

Objective: To explore the value of the injury severity score (ISS) and the new injury severity score (NISS) for evaluating injuries and predicting complications (pneumonia and respiratory failure) and poor prognoses (in-hospital tracheal intubation, extended length of hospital stay, ICU admission, prolonged ICU stay, and death) in patients with thoracic trauma.

Methods: The data of consecutive patients with thoracic trauma who were admitted to the department of cardiothoracic surgery of a tertiary hospital between January 2018 and December 2021 were retrospectively collected. ISS and NISS were calculated for each patient.

An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG.

Background: Cyclic Nucleotide-Binding Domain (CNBD)-family channels display distinct voltage-sensing properties despite sharing sequence and structural similarity. For example, the human Ether-a-go-go Related Gene (hERG) channel and the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel share high amino acid sequence similarity and identical domain structures. hERG conducts outward current and is activated by positive membrane potentials (depolarization), whereas HCN conducts inward current and is activated by negative membrane potentials (hyperpolarization).

Effects of sodium-glucose cotransporter 2 inhibitors on renal risk factors in patients with abnormal glucose metabolism: a meta-analysis of randomized controlled trials.

Aims: Several trials have assessed the antihyperglycemic effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) in patients with type 2 diabetes mellitus (T2DM). We conducted a quantitative analysis to assess the effects of SGLT2Is on renal risk factors in patients with abnormal glucose metabolism.

Materials And Methods: Randomized controlled trials (RCTs) were identified by searching the PubMed, Embase, Scopus, and Web of Science databases published before September 30, 2022.

Functional characterization and in vitro pharmacological rescue of KCNQ2 pore mutations associated with epileptic encephalopathy.

Mutations in the KCNQ2 gene encoding K7.2 subunit that mediates neuronal M-current cause a severe form of developmental and epileptic encephalopathy (DEE). Electrophysiological evaluation of KCNQ2 mutations has been proved clinically useful in improving outcome prediction and choosing rational anti-seizure medications (ASMs).

Effects of Anterior Pituitary Adenomas' Hormones on Glucose Metabolism and Its Clinical Implications.

Pituitary adenomas have recently become more common and their incidence is increasing yearly. Functional pituitary tumors commonly secrete prolactin, growth hormones, and adrenocorticotropic hormones, which cause diseases such as prolactinoma, acromegaly, and Cushing's disease, but rarely secrete luteinizing, follicle-stimulating, thyroid-stimulating, and melanocyte-stimulating hormones. In addition to the typical clinical manifestations of functional pituitary tumors caused by excessive hormone levels, some pituitary tumors are also accompanied by abnormal glucose metabolism.

How Do Landscape Heterogeneity, Community Structure, and Topographical Factors Contribute to the Plant Diversity of Urban Remnant Vegetation at Different Scales?

In highly fragmented urban areas, plant diversity of remnant vegetation may depend not only on community structure and topographical factors, but also on landscape heterogeneity. Different buffer radius settings can affect the relative importance of these factors to plant diversity. The aim of this study was to examine the relative importance of landscape heterogeneity, community structure, and topographical factors on plant diversity under different buffer radii in biodiversity hotspots.

Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetes.

Owing to the increasing prevalence of type 2 diabetes, the development of novel hypoglycemic drugs has become a research hotspot, with the ultimate goal of developing therapeutic drugs that stimulate glucose-induced insulin secretion without inducing hypoglycemia. Vasoactive intestinal peptide (VIP), a 28-amino-acid peptide, can stimulate glucose-dependent insulin secretion, particularly by binding to VPAC2 receptors. VIP also promotes islet β-cell proliferation through the forkhead box M1 pathway, but the specific molecular mechanism remains to be studied.

Effects of the POMC System on Glucose Homeostasis and Potential Therapeutic Targets for Obesity and Diabetes.

The hypothalamus is indispensable in energy regulation and glucose homeostasis. Previous studies have shown that pro-opiomelanocortin neurons receive both central neuronal signals, such as α-melanocyte-stimulating hormone, β-endorphin, and adrenocorticotropic hormone, as well as sense peripheral signals such as leptin, insulin, adiponectin, glucagon-like peptide-1, and glucagon-like peptide-2, affecting glucose metabolism through their corresponding receptors and related signaling pathways. Abnormalities in these processes can lead to obesity, type 2 diabetes, and other metabolic diseases.

CTGF Promotes the Osteoblast Differentiation of Human Periodontal Ligament Stem Cells by Positively Regulating BMP2/Smad Signal Transduction.

Objective: This work is aimed at revealing the role and the molecular mechanism of connective tissue growth factor 2 (CTGF) in the osteoblast differentiation of periodontal ligament stem cells (PDLSCs).

Methods: The osteogenic differentiation of PDLSCs was induced by osteogenic induction medium (OM), and the expression level of osteogenic related proteins ALP, RUNX2, OCN, and CTGF was estimated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis. We constructed cell lines with CTGF overexpression or knockdown to verify the role of CTGF in the osteoblast differentiation of PDLSCs.

Discovery of SHR5133, a Highly Potent and Novel HBV Capsid Assembly Modulator.

Capsid assembly modulators (CpAMs) represent a new class of antivirals targeting hepatitis B virus (HBV) core protein to disrupt the assembly process. In this work, a novel chemotype featuring a fused heterocycle amide was discovered through pharmacophore exploration. Lead optimization resulted in compound with an EC value of 511 nM, and then methyl substitution on the piperazine was found to improve the potency remarkably.

IE86 Inhibits the apoptosis and promotes the cell proliferation of glioma cells via the hnRNP A2/B1-mediated alternative splicing of Bcl-x.

Human cytomegalovirus (HCMV), a ubiquitous pathogen, can cause severe illness in immunocompromised individuals. Typically, glioma is one of the most common malignant primary brain tumors and originates in the central nervous system. The IE86 gene of HCMV exerts a major role in regulating virus replication.

Discovery of SHR9352: A Highly Potent G Protein-Biased μ-Opioid Receptor Agonist.

Recently, targeting the G protein-biased signaling has emerged as an attractive therapeutic strategy for treating severe acute pain with the potential to reduce the side effect of the traditional opioid drug. Herein, we describe the discovery of a highly potent G protein-biased μ-opioid receptor (MOR) agonist, SHR9352. This novel molecule exhibited excellent MOR activity and limited β-arrestin recruitment, as well as a high selectivity over κ-opioid receptor and δ-opioid receptor demonstrated robust in vivo efficacy and displayed favorable pharmacokinetic properties across species.

Prevalence and distribution profiles of Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis responsible for superficial candidiasis in a Chinese university hospital.

The Candida parapsilosis complex consists of C. parapsilosis sensu stricto, C. orthopsilosis and C.

A synthetic multi-epitope antigen enhances hepatitis C virus-specific B- and T-cell responses.

Combining results from previous studies, a multi-epitope antigen PCXZ against the hepatitis C virus was synthesized in this study. The antigenic specificity of PCXZ was determined by recognizing antibodies in serum samples from hepatitis C virus patients, but not from healthy subjects or subjects who had the hepatitis B virus. The characteristics of PCXZ immunogenicity were evaluated in BALB/c mice.

Proliferating cells in suborbital tissue drive eye migration in flatfish.

The left/right asymmetry of adult flatfishes (Pleuronectiformes) is remarkable given the external body symmetry of the larval fish. The best-known change is the migration of their eyes: one eye migrates from one side to the other. Two extinct primitive pleuronectiformes with incomplete orbital migration have again attracted public attention to the mechanism of eye migration, a subject of speculation and research for over a century.

Generation and analysis of ESTs from the grass carp, Ctenopharyngodon idellus.

Grass carp, Ctenopharyngodon idellus (Valenciennes, 1844), is an economically important species widely cultured in the world, but its genome research resources are largely lacking. The objectives of this study were to construct normalized cDNA libraries for efficient EST analysis, to generate ESTs from these libraries, and to identify EST-related molecular markers such as microsatellites and single nucleotide polymorphisms (SNPs) for genetic analysis of this species. A total of 6,269 ESTs were generated representing 4,815 unique sequences, from which 105 putative microsatellites and 5,228 SNPs were identified.

Enzymatic synthesis of 2'-deoxyadenosine and 6-methylpurine-2'-deoxyriboside by Escherichia coli DH5alpha overexpressing nucleoside phosphorylases from Escherichia coli BL21.

Genes encoding purine nucleoside phosphorylase (deo D), uridine phosphorylase (udp) and thimidine phosphorylase (deo A) from Escherichia coli BL21 were cloned and overexpressed in E. coli DH5alpha. The recombinant strains were employed to synthesize 2'-deoxyadenosine (dAR) and 6-methylpurine-2'-deoxyriboside (MePdR).

A novel TTX-producing Aeromonas isolated from the ovary of Takifugu obscurus.

Puffer fish (Takifugu obscurus) from the Yangtze River of China were screened for tetrodotoxin-producing bacteria. An Aeromonas strain was isolated from the ovary of the puffer fish and was shown to produce tetrodotoxin; this strain was denoted Ne-1. The identity of tetrodotoxin produced by strain Ne-1 was confirmed by mouse bioassay, high performance liquid chromatography coupled with mass chromatography (LC-MS), and ELISA.

The intrabody targeting of hTERT attenuates the immortality of cancer cells.

hTERT (human telomerase reverse transcriptase) plays a key role in the process of cell immortalization. Overexpression of hTERT has been implicated in 85% of malignant tumors and offers a specific target for cancer therapy. In this paper, we describe an effective approach using a single-chain variable fragment (scFv) intrabody derived from monoclonal hybridoma directed against hTERT to attenuate the immortalization of human uterine cervix and hepatoma cells.

Isolation of SFRS3 gene and its differential expression during metamorphosis involving eye migration of Japanese flounder Paralichthys olivaceus.

Both eyes of flatfishes are located on one side of the body due to asymmetrical eye migration. The molecular mechanisms underlying such asymmetry is poorly understood. As an initial step, we have adopted suppression subtractive hybridization for the identification of upregulated genes during metamorphosis involving eye migration in Japanese flounder, Paralichthys olicaceus.