AgNOx as Nitrogen Source for [1+1+3] Cycloaddition of Isocyanides with Isocyanates: Selective Synthesis of 1,2,4-Triazoles.

A novel [1+1+3] annulation of AgNOx, isocyanides, and isocyanates for the selective synthesis of 1,2,4-triazoles is presented herein. In this transformation, AgNOx and isocyanates are used as nitrogen sources instead of the traditional hydrazine or diazonium reagents. This process also involves N-O/C-H/C═N bond cleavage and the construction of new N-N/C-N bonds with a good substrate scope and functional group tolerance.

Serum Anion Gap at Admission Predicts All-Cause Mortality in Critically Ill Patients With Cirrhosis: A Retrospective Cohort Study.

Introduction: The primary objective of this study was to evaluate admission serum anion gap (AG) as a predictor of all-cause mortality in critically ill patients with cirrhosis.

Methods: A total of 3,084 cirrhotic patients were included and randomly divided into training and validation cohorts (n = 2,159 and 925, respectively). Patients were categorized into high and normal AG groups based on their AG values.

Inhibition of ACOX1 enhances the therapeutic efficacy of obeticholic acid in treating non-alcoholic fatty liver disease and mitigates its lipotoxicity.

Background And Aims: High-dose Obeticholic acid exhibits promise for non-alcoholic fatty liver disease (NAFLD) treatment but can induce lipotoxicity. Our study sought to understand this mechanism and propose a solution.

Approach And Results: In a non-alcoholic fatty liver disease (NAFLD) model induced by a high-fat diet in FXR mice, we pinpointed that FXR regulated the expression of ACOX1 through RNA-Seq analysis.

Ligand-controlled regiodivergent Ni-catalyzed -hydroboration/carboboration of internal alkynes with Bpin.

Unprecedented regioselective -hydroboration and carboboration of unbiased electronically internal alkynes were realized a nickel catalysis system with the aid of the directing group strategy. Furthermore, the excellent α- and β-regioselectivity could be accurately switched by the nitrogen ligand (terpy) and phosphine ligand (Xantphos). Mechanistic studies provided an insight into the rational reaction process, that underwent the -to- isomerization of alkenyl nickel species.

Risk factors for the development of sepsis in patients with cirrhosis in intensive care units.

Sepsis is a serious complication of liver cirrhosis. This study aimed to develop a risk prediction model for sepsis among patients with liver cirrhosis. A total of 3130 patients with liver cirrhosis were enrolled from the Medical Information Mart for Intensive Care IV database, and randomly assigned into training and validation cohorts in a 7:3 ratio.

Prognostic-Related Biomarkers in Pancreatic Ductal Adenocarcinoma Correlating with Immune Infiltrates Based on Proteomics.

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) accounts for 85% of pancreatic carcinoma cases. Patients with PDAC have a poor prognosis. The lack of reliable prognostic biomarkers makes treatment challenging for patients with PDAC.

Identification of potential feature genes in non-alcoholic fatty liver disease using bioinformatics analysis and machine learning strategies.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and NAFLD-associated hepatocellular carcinoma (HCC) has continuously increased in recent years. Machine learning is an effective method for screening the feature genes of a disease for prediction, prevention and personalized treatment. Here, we used the "limma" package and weighted gene co-expression network analysis (WGCNA) to screen 219 NAFLD-related genes and found that they were mainly enriched in inflammation-related pathways.

Perivascular epithelioid cell tumors of the liver misdiagnosed as hepatocellular carcinoma: Three case reports.

Background: Hepatic perivascular epithelioid cell neoplasms (PEComas) are rare. Diagnostic and treatment experience with hepatic PEComa remains insufficient.

Case Summary: Three hepatic PEComa cases are reported in this paper: One case of primary malignant hepatic PEComa, one case of benign hepatic PEComa, and one case of hepatic PEComa with an ovarian mature cystic teratoma.

Deciphering Nonbioavailable Substructures Improves the Bioavailability of Antidepressants by Serotonin Transporter.

Inadequate bioavailability is one of the most critical reasons for the failure of oral drug development. However, the way that substructures affect bioavailability remains largely unknown. Serotonin transporter (SERT) inhibitors are first-line drugs for major depression disorder, and improving their bioavailability may be able to decrease side-effects by reducing daily dose.

Prolonged activated partial thromboplastin time predicts poor short-term prognosis in patients with acute pancreatitis: A retrospective cohort study.

It is unclear whether activated partial thromboplastin time (APTT) is predictive of survival in patients with acute pancreatitis (AP). Our study aimed to investigate the relationship between APTT and short-term prognosis in AP. From the Medical Information Mart for Intensive Care (MIMIC)-IV database, a total of 844 patients with AP were randomly divided into the training cohort (n = 591) and the validation cohort (n = 253) at a ratio of 7:3.

Obeticholic Acid Induces Hepatoxicity Via FXR in the NAFLD Mice.

Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, is a promising drug for nonalcoholic fatty liver disease (NAFLD); however, it can cause liver injury, especially at high doses. Here, we investigated the role of FXR in the high-dose OCA-induced hepatoxicity in the condition of the NAFLD mouse model. Wild-type (WT) mice and FXR mice were administered with over-dose OCA (0.

Decaprenyl Diphosphate Synthase Subunit 1 (PDSS1): A Potential Prognostic Biomarker and Immunotherapy-Target for Hepatocellular Carcinoma.

Purpose: PDSS1 (decaprenyl diphosphate synthase subunit 1) plays an important role in the progression of several types of tumor. However, the biological functions of PDSS1 remain unclear in patients with hepatocellular carcinoma (HCC). In this study, We attempted to determine the role of PDSS1 in predicting the survival and efficacy of immunotherapy for HCC patients.

Obeticholic acid inhibits hepatic fatty acid uptake independent of FXR in mouse.

Objective: Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, is believed to alleviate nonalcoholic fatty liver disease (NAFLD) by decreasing hepatic lipogenesis in an FXR-dependent manner. Here, we revealed a novel mechanism by which OCA improves NAFLD by affecting hepatic long-chain fatty acids (LCFAs) uptake.

Methods: Stably transfected HEK-293 cells expressing fatty acid transport protein 5 (FATP5) were established to examine fatty acid uptake; FXR, human (h) FATP5, and FXR/hFATP5 mouse models were incorporated to explore the effects of OCA on FATP5 ex vivo and in vivo.

Pd(II)-Catalyzed Synthesis of Alicyclic[]-Fused Pyridines via C(sp)-H Activation of -Unsaturated -Acetyl Hydrazones with Vinyl Azides.

A new synthetic protocol for alicyclic[]-fused pyridines with complete regioselectivity from unsaturated -acetyl hydrazones and vinyl azides via Pd(II)-catalyzed C-H activation/cyclization/aromatization strategy has been described. A series of five- to eight-membered alicyclic[]-fused pyridines were prepared in a one-step manner with wide substrate scope and good functional group tolerance.

Access to Cycloalkeno[]-Fused Pyridines via Pd-Catalyzed C(sp)-H Activation and Cyclization of -Acetyl Hydrazones of Acylcycloalkenes with Vinyl Azides.

A novel Pd(II)-catalyzed vinylic C-H activation and cyclization has been developed, reacting a series of small, medium, and large -acetyl hydrazones of acylcycloalkenes with vinyl azides to access diverse cycloalkeno[]-fused pyridine scaffolds. This protocol provides progress in C(sp)-H bond activation of medium to large cycloalkenes, and the target products can be obtained in a specific regioselectivity with good functional group tolerance and a broad substrate scope.

Real-time monitoring of γ-Glutamyltranspeptidase in living cells and in vivo by near-infrared fluorescent probe with large Stokes shift.

γ-Glutamyltranspeptidase (GGT) is a cell surface-bound enzyme that is closely implicated in various physiological disorders such as tumor. Thus, an efficient method for monitoring GGT is extremely important for biological studies and disease diagnosis. Herein, a near-infrared fluorescent probe (TMN-Glu) has been developed for turn-on trapping of GGT activity in vitro and in vivo based on conjugating a dicyanoisophorone derivative fluorophore with a GGT activatable γ-glutamyl amide moiety.

Cytotoxic withanolides from the aerial parts of Tubocapsicum anomalum.

Ten new withanolides (1-10) and three artificial withanolides (11-13) were isolated from the aerial parts of Tubocapsicum anomalum, together with five known analogues (14-18). Their structures were determined on the basis of extensive spectroscopic and chemical methods. They include seven acnistin-type (1-4, 11, 14 and 15), three withajardin-type (5-7), and eight normal-type (8-10, 12, 13 and 16-18) withanolides.

Downregulation of hepatic lipase is associated with decreased CD133 expression and clone formation in HepG2 cells.

The drug resistance of cancer remains a major obstacle to successful chemotherapy. New strategies for improving chemotherapeutic efficacy are urgently required. Recent studies have indicated that LIPC plays a role in promoting the liver metastasis of colorectal cancer.

3-((R)-4-(((R)-6-(2-Bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholin-2-yl)propanoic Acid (HEC72702), a Novel Hepatitis B Virus Capsid Inhibitor Based on Clinical Candidate GLS4.

The inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. On the basis of the preclinical properties and clinical results of GLS4, we carried out further investigation to seek a better candidate compound with appropriate anti-HBV potency, reduced hERG activity, decreased CYP enzyme induction, and improved pharmacokinetic (PK) properties. To this end, we have successfully found that morpholine carboxyl analogues with comparable anti-HBV activities to that of GLS4 showed decreased hERG activities, but they displayed strong CYP3A4 induction in a concentration-dependent manner, except for morpholine propionic acid analogues.

Efficacy of noninvasive evaluations in monitoring inflammatory bowel disease activity: A prospective study in China.

Aim: To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease (IBD).

Methods: Fecal calprotectin (FC), clinical activity index (CDAI or CAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome (IBS) patients that served as controls.

Use of confocal laser endomicroscopy with a fluorescently labeled fatty acid to diagnose colorectal neoplasms.

Endoscopic treatment for early colorectal cancer closely correlates with patient prognosis. However, endoscopic differentiation between carcinomas and non-neoplastic lesions remains difficult. Here, we topically stained colorectal neoplasms with a fatty acid analogue (BODIPY-FA) and quantified the fluorescent signals using confocal laser endomicroscopy (CLE) and fluorescence microscopy.

Low-temperature fabrication of brown TiO2 with enhanced photocatalytic activities under visible light.

Here we report a facile one-step low-temperature solution-based method to treat native TiO2 with NaH. The NaH treatment effectively induces the Ti(iii) species and oxygen vacancies into the TiO2 host lattice, and enables the absorption edge of TiO2 to be conveniently adjusted from the UV region to the red end of the visible spectrum.

Dependence of brown adipose tissue function on CD36-mediated coenzyme Q uptake.

Brown adipose tissue (BAT) possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ). While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency.

Statin use and risk of liver cancer: an update meta-analysis.

Objective: Statins are commonly prescribed cholesterol-lowering drugs. Preclinical studies suggest that statins may possess cancer preventive properties. The primary objective of this meta-analysis was to determine the association between statin use and risk of liver cancer.