Increased COX6A2 promotes pancreatic β-cell apoptosis and is suppressed in diabetic GK rats after Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) has been shown to inhibit β-cell apoptosis, but the underlying mechanisms are not yet fully understood. Cytochrome c oxidase subunit 6A2 (COX6A2) is expressed in β-cells. Here, we sought to investigate the role of COX6A2 in β-cell apoptosis, especially following RYGB.

Enhancing Force Absorption, Stress-Strain and Thermal Properties of Weft-Knitted Inlay Spacer Fabric Structures for Apparel Applications.

The pursuit of materials that offer both wear comfort and protection for functional and protective clothing has led to the exploration of weft-knitted spacer structures. Traditional cushioning materials such as spacer fabrics and laminated foam often suffer from deformation under compression stresses, thus compromising their protective properties This study investigates the enhancement of the force absorption, stress-strain, and thermal properties of weft-knitted spacer fabrics with inlays. Surface yarns with superior stretchability and thermal properties are used and combined with elastic yarns in various patterns to fabricate nine different inlay samples.

A Systematic Review of AI-Driven Prediction of Fabric Properties and Handfeel.

Artificial intelligence (AI) is revolutionizing the textile industry by improving the prediction of fabric properties and handfeel, which are essential for assessing textile quality and performance. However, the practical application and translation of AI-predicted results into real-world textile production remain unclear, posing challenges for widespread adoption. This paper systematically reviews AI-driven techniques for predicting these characteristics by focusing on model mechanisms, dataset diversity, and prediction accuracy.

Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes.

cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes.

Study of individual domains contributing to MALT1 dimerization in BCL10-independent and dependent assembly.

The CARMA-BCL10-MALT1 (CBM) signalosome functions as a pivotal supramolecular module, integrating diverse receptor-induced signaling pathways to regulate BCL10-dependent NF-kB activation in innate and adaptive immunity. Conversely, the API2-MALT1 fusion protein in t(11; 18)(q21; q21) MALT lymphoma constitutively induces BCL10-independent NF-kB activation. MALT1 dimer formation is indispensable for the requisite proteolytic activity and is critical for NF-kB activation regulation in both scenarios.

Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis.

Fas-associated protein with death domain (FADD), procaspase-8, and cellular FLICE-inhibitory proteins (cFLIP) assemble through death-effector domains (DEDs), directing death receptor signaling towards cell survival or apoptosis. Understanding their three-dimensional regulatory mechanism has been limited by the absence of atomic coordinates for their ternary DED complex. By employing X-ray crystallography and cryogenic electron microscopy (cryo-EM), we present the atomic coordinates of human FADD-procaspase-8-cFLIP complexes, revealing structural insights into these critical interactions.

Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes.

Background: This study was designed to assess the associations between emerging cardiometabolic indices-the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)-and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients.

Methods: We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters.

Synergistic anti-tumor effect of dual drug co-assembled nanoparticles based on ursolic acid and sorafenib.

Both ursolic acid (UA) and sorafenib (Sora) have been generally utilized in cancer treatment, and the combination of the two has also shown a good anti-tumor effect. However, single-agent therapy for Hepatocellular carcinoma (HCC) has the disadvantages of multi-drug resistance, poor water solubility and low bioavailability, and the application of traditional nanocarrier materials is limited due to their low drug loading and low carrier-related toxicity. Therefore, we prepared US NPs with different proportions of UA and Sora by solvent exchange method for achieving synergistic HCC therapy.

Dual-drug controllable co-assembly nanosystem for targeted and synergistic treatment of hepatocellular carcinoma.

The effectiveness of chemotherapeutic agents for hepatocellular carcinoma (HCC) is unsatisfactory because of tumor heterogeneity, multidrug resistance, and poor target accumulation. Therefore, multimodality-treatment with accurate drug delivery has become increasingly popular. Herein, a cell penetrating peptide-aptamer dual modified-nanocomposite (USILA NPs) was successfully constructed by coating a cell penetrating peptide and aptamer onto the surface of sorafenib (Sora), ursolic acid (UA) and indocyanine green (ICG) condensed nanodrug (USI NPs) via one-pot assembly for targeted and synergistic HCC treatment.

Lysine Deprivation Suppresses Adipogenesis in 3T3-L1 Cells: A Transcriptome Analysis.

Growing evidence proves that amino acid restriction can reverse obesity by reducing adipose tissue mass. Amino acids are not only the building blocks of proteins but also serve as signaling molecules in multiple biological pathways. The study of adipocytes' response to amino acid level changes is crucial.

Imperatorin inhibits LPS-induced bone marrow-derived macrophages activation by decreased NF-κB p65 phosphorylation.

Background: Imperatorin (IMP) is a secondary metabolite of plants and is the most abundant in Angelica dahurica. Previous studies showed that IMP exhibited anti-inflammatory activity in RAW264.7 cell line.

Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide.

Isocorydine (ICD) is a type of isoquinoline alkaloid originating from , which has been used to relieve spasm, dilate blood vessels, and treat malaria as well as hypoxia in clinic. However, its effect on inflammation and underlying mechanisms remains unclear. The aim of our study was to determine the potential effects and mechanisms of ICD on pro-inflammatory interleukin-6 (IL-6) expression in bone marrow-derived macrophages (BMDMs) and acute lung injury mouse model.

Experimental and computational models to investigate intestinal drug permeability and metabolism.

Oral administration is the preferred route for drug administration that leads to better therapy compliance. The intestine plays a key role in the absorption and metabolism of oral drugs, therefore, new intestinal models are being continuously proposed, which contribute to the study of intestinal physiology, drug screening, drug side effects, and drug-drug interactions.Advances in pharmaceutical processes have produced more drug formulations, causing challenges for intestinal models.

Ultrasonographic evaluation of diaphragm function in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Background: Some studies have reported using ultrasonic evaluations to assess diaphragm function in patients with chronic obstructive pulmonary disease (COPD). However, they have limitations and thus cannot provide strong evidence to support ultrasound evaluations for diaphragm function and dysfunction severity assessments in this patient population. Additionally, quantitative studies on the relationship between ultrasound evaluations and diaphragm function do not exist.

Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats.

Many orally administered phenolic drugs undergo enterohepatic recycling (EHR), presumably mediated by the hepatic phase II enzymes. However, the disposition of extrahepatically generated phase II metabolites is unclear. This paper aims to determine the new roles of liver and intestine in the disposition of oral phenolics.

Ibrutinib and venetoclax target distinct subpopulations of CLL cells: implication for residual disease eradication.

Ibrutinib inhibits Bruton tyrosine kinase while venetoclax is a specific inhibitor of the anti-apoptotic protein BCL2. Both drugs are highly effective as monotherapy against chronic lymphocytic leukemia (CLL), and clinical trials using the combination therapy have produced remarkable results in terms of rate of complete remission and frequency of undetectable minimal residual disease. However, the laboratory rationale behind the success of the drug combination is still lacking.

Development and Validation of a Radiomic-Based Model for Prediction of Intrahepatic Cholangiocarcinoma in Patients With Intrahepatic Lithiasis Complicated by Imagologically Diagnosed Mass.

Background: This study was conducted with the intent to develop and validate a radiomic model capable of predicting intrahepatic cholangiocarcinoma (ICC) in patients with intrahepatic lithiasis (IHL) complicated by imagologically diagnosed mass (IM).

Methods: A radiomic model was developed in a training cohort of 96 patients with IHL-IM from January 2005 to July 2019. Radiomic characteristics were obtained from arterial-phase computed tomography (CT) scans.

Rapid intestinal glucuronidation and hepatic glucuronide recycling contributes significantly to the enterohepatic circulation of icaritin and its glucuronides in vivo.

Icaritin (ICT), a prenylflavonoid derivative extracted from the Epimedium genus, has exhibited antitumor effects in hepatocellular carcinoma (HCC) cells and safety and tolerance in clinical settings. However, ICT exhibits low blood concentration and the in vivo dominant plasma species of ICT is glucuronides [icaritin-3-glucuronide (G1), icaritin-7-glucuronide (G2) and icaritin-3, 7-diglucuronide (DIG)]. Therefore, how ICT reaches the liver and exerts its effect with low toxicity remains unknown.

Development and validation of an LC-MS/MS method for the quantification of flavonoid glucuronides (wogonoside, baicalin, and apigenin-glucuronide) in the bile and blood samples: Application to a portal vein infusion study.

Glucuronidation is one of the major metabolic pathways for flavonoids. However, quantification of flavonoid glucuronides in biological samples, especially in the bile, is sometimes challenging due to signal suppression by bile acids. The purpose of this study is to establish a robust LC-MS/MS method for directly measuring flavonoid glucuronides in bile and blood.

Roux-en-Y gastric bypass enhances insulin secretion in type 2 diabetes via FXR-mediated TRPA1 expression.

Objective: Roux-en-Y gastric bypass surgery (RYGB) improves the first phase of glucose-stimulated insulin secretion (GSIS) in patients with type 2 diabetes. How it does so remains unclear. Farnesoid X receptor (FXR), the nuclear receptor of bile acids (BAs), is implicated in bariatric surgery.

Myeloid translocation gene CBFA2T3 directs a relapse gene program and determines patient-specific outcomes in AML.

CBFA2T3 is a master transcriptional coregulator in hematopoiesis. In this study, we report novel functions of CBFA2T3 in acute myeloid leukemia (AML) relapse. CBFA2T3 regulates cell-fate genes to establish gene expression signatures associated with leukemia stem cell (LSC) transformation and relapse.