Targeting the NLRP3 inflammasome abrogates cardiotoxicity of immune checkpoint blockers.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many malignant tumors. However, ICI-induced hyper-immune activation causes cardiotoxicity. Traditional treatments such as glucocorticoids and immunosuppressants have limited effectiveness and may even accelerate tumor growth.

Inhibition of Glycolysis Alleviates Chronic Unpredictable Mild Stress Induced Neuroinflammation and Depression-like Behavior.

Background: Growing evidence suggests that glucose metabolism plays a crucial role in activated immune cells, significantly contributing to the occurrence and development of neuroinflammation and depression-like behaviors. Chronic stress has been reported to induce microglia activation and disturbances in glucose metabolism in the hippocampus.

Aims: This study aims to investigate how chronic stress-mediated glycolysis promotes neuroinflammation and to assess the therapeutic potential of the glycolysis inhibitor, 2-deoxy-D-glucose (2-DG), in a model of chronic stress-induced neuroinflammation and depression-like behavior.

Establishment a nomogram model for preoperative prediction of the risk of cholangiocarcinoma with microvascular invasion.

Objectives: The research aimed to create and verify a nomogram model that can predict the likelihood of cholangiocarcinoma with microvascular invasion (MVI).

Methods: The clinical data of 476 patients with surgically confirmed cholangiocarcinoma were collected retrospectively. This included 240 cases of intrahepatic cholangiocarcinoma (iCCA), 85 cases of perihilar cholangiocarcinoma (pCCA), and 151 cases of extrahepatic cholangiocarcinoma (eCCA).

Chronic stress disturbed the metabolism of homocysteine in mouse hippocampus and prefrontal cortex.

Stress is an independent risk factor for cognitive impairment, with elevated plasma homocysteine (HCY) levels playing a crucial role in stress-induced cognitive decline. While the rise in plasma HCY levels is linked to abnormal peripheral catabolism, the impact of stress on HCY catabolism in the brain remains unclear. This study investigated the effect of stress on HCY metabolism in the brain by analyzing HCY and its metabolic enzymes in the hippocampus and prefrontal cortex.

Functional Ginger-Derived Extracellular Vesicles-Coated ZIF-8 Containing TNF-α siRNA for Ulcerative Colitis Therapy by Modulating Gut Microbiota.

Tumor necrosis factor-α (TNF-α) plays a causal role in the pathogenesis of ulcerative colitis (UC), and anti-TNF-α siRNA shows great promise in UC therapy. However, delivering siRNA with site-targeted stability and therapeutic efficacy is still challenging due to the complex and dynamic intestinal microenvironment. Here, based on the functional plant-derived ginger extracellular vesicles (EVs) and porous ZIF-8 nanoparticles, we propose a novel TNF-α siRNA delivery strategy (EVs@ZIF-8@siRNA) for UC targeted therapy.

Bioderived Nanoparticles for Cardiac Repair.

Biobased therapy represents a promising strategy for myocardial repair. However, the limitations of using live cells, including the risk of immunogenicity of allogeneic cells and inconsistent therapeutic efficacy of autologous cells together with low stability, result in an unsatisfactory clinical outcomes. Therefore, cell-free strategies for cardiac tissue repair have been proposed as alternative strategies.

GLUT1-mediated microglial proinflammatory activation contributes to the development of stress-induced spatial learning and memory dysfunction in mice.

Background: Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear.

Methods: The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment.

Non-insulin-based insulin resistance indexes in predicting atrial fibrillation recurrence following ablation: a retrospective study.

Background: Insulin resistance (IR) is involved in the pathophysiological processes of arrhythmias. Increasing evidence suggests triglyceride and glucose (TyG) index, metabolic score for insulin resistance (METS-IR), triglyceride glucose-body mass index (TyG-BMI), and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio are simple and reliable surrogates for IR. Although they have been associated with atrial fibrillation (AF), evidence supporting this is limited.

A novel experimental setup for axial-torsional coupled vibration impact-assisted PDC drill bit drilling.

The geological conditions of hot dry rock (HDR) reservoirs are complex. The geothermal mining of HDR faces major challenges in the drilling and construction of wells, fracturing to create storage, and flowing to extract heat. Vibration impacts help improve the rock-breaking efficiency, where the axial-torsional coupled vibration impact technology can increase the bit penetration depth and reduce the stick-slip effect.

Establishment and validation of a nomogram model for preoperative prediction of the risk of cholangiocarcinoma with perineural invasion.

Objective: To establish and validate a nomogram model for predicting the risk of cholangiocarcinoma with perineural invasion.

Methods: We retrospectively collected the clinical data of 356 patients with surgically confirmed cholangiocarcinoma, including 98 cases of extrahepatic cholangiocarcinoma (eCCA), 197 cases of intrahepatic cholangiocarcinoma (iCCA), and 61 cases of perihilar cholangiocarcinoma (pCCA).

Results: Based on these data, we determined the influencing factors of preoperative perineural invasion risk in patients with cholangiocarcinoma by forward multivariate regression analysis.

Blood-brain barrier dysfunction mediated by the EZH2-Claudin-5 axis drives stress-induced TNF-α infiltration and depression-like behaviors.

Growing evidence suggests that neurovascular dysfunction characterized by blood-brain barrier (BBB) breakdown underlies the development of psychiatric disorders, such as major depressive disorder (MDD). Tight junction (TJ) proteins are critical modulators of homeostasis and BBB integrity. TJ protein Claudin-5 is the most dominant BBB component and is downregulated in numerous depression models; however, the underlying mechanisms remain elusive.

ROR1-AS1 might promote in vivo and in vitro proliferation and invasion of cholangiocarcinoma cells.

Long non-coding RNAs (lncRNAs) play important roles in many pathophysiological processes, including cancer progression. Namely, lncRNA Receptor-tyrosine-kinase-like orphan receptor-1 antisense 1 (ROR1-AS1) is crucial for cancer occurrence and progression in organs such as the liver or bladder. However, its expression and role in cholangiocarcinoma (CCA) have not been thoroughly explored.

FEN1 promotes cancer progression of cholangiocarcinoma by regulating the Wnt/β-catenin signaling pathway.

Purpose: Cholangiocarcinoma (CHOL) comprises a cluster of highly heterogeneous malignant biliary tumors. Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. This study aimed to explore the biological functions and mechanisms of FEN1 in CHOL.

Norepinephrine promotes neuronal apoptosis of hippocampal HT22 cells by up-regulating the expression of long non-coding RNA MALAT1.

Stress is ever present in our modern, performance-oriented and demanding society, which causes adverse stress reactions of the body and affects health seriously. Chronic stress has been recognized as a significant risk factor leading to cognitive impairment, but the underlying mechanism is far from fully understood. Norepinephrine (NE), a pivotal stress-induced hormone, has been found to induce cell apoptosis.

Targeted miR-34a delivery with PD1 displayed bacterial outer membrane vesicles-coated zeolitic imidazolate framework nanoparticles for enhanced tumor therapy.

MicroRNA (miRNA) has been widely used as an effective gene drug for tumor therapy, but its chemical instability limited its therapeutic application in vivo. In this research, we fabricate an efficient miRNA nano-delivery system using zeolitic imidazolate framework-8 (ZIF-8) coated with bacterial outer membrane vesicles (OMVs), aimed for cancer treatment. The acid-sensitive ZIF-8 core enables this system to encapsulate miRNA and release them from lysosome quickly and efficiently in the target cells.

Atherosclerosis: The Involvement of Immunity, Cytokines and Cells in Pathogenesis, and Potential Novel Therapeutics.

As a leading contributor to coronary artery disease (CAD) and stroke, atherosclerosis has become one of the major cardiovascular diseases (CVD) negatively impacting patients worldwide. The endothelial injury is considered to be the initial step of the development of atherosclerosis, resulting in immune cell migration and activation as well as inflammatory factor secretion, which further leads to acute and chronic inflammation. In addition, the inflammation and lipid accumulation at the lesions stimulate specific responses from different types of cells, contributing to the pathological progression of atherosclerosis.

Biomarkers for predicting the prognosis of intrahepatic cholangiocarcinoma: A retrospective single-center study.

The aim of this retrospective study was to investigate the association between preoperative serological and clinical indicators and postoperative recovery in patients who had undergone resection of intrahepatic cholangiocarcinoma (ICC). We collected data form the medical records of patients who underwent operations for the treatment of ICC at Qingdao University Affiliated Hospital from 2015 to 2021. We analyzed the data to explore the independent predictors of disease prognosis after surgery for ICC.

[The role of semaphorin 4D in the mechanism of bisphosphonate-related osteonecrosis of the jaw in rats].

Purpose: To study the expression level of semaphorin 4D (Sema4D) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to explore its possible role in the occurrence of BRONJ.

Methods: BRONJ-like rat model was established by intraperitoneal injection of zoledronic acid assisted with tooth extraction. The maxillary specimens were extracted for imaging and histological examination, and bone marrow mononuclear cells(BMMs) and bone marrow mesenchymal stem cells(BMSCs) of each group were obtained in vitro for co-culture.

Leucine mediates cognitive dysfunction in early life stress-induced mental disorders by activating autophagy.

Objectives: To explore the relationship between leucine in cerebrospinal fluid (CSF) and cognitive dysfunction in rats with early life stress (ELS) induced mental illness, and pathophysiological mechanism involved.

Methods: The maternal separation (MS), an animal paradigm used widely as a preclinical model of ELS which is one of the important risk factors for mental disorders. Behavioral experiments including open-field test, sucrose preference, object recognition and Morris water maze tests, Nissl staining, transmission electron microscopy and WES were employed in the present study.

Prognostic influence for hilar cholangiocarcinoma and comparisons of prognostic values of Mayo staging and TNM staging systems.

The study was designed to discuss the effect of stratification factors in the Mayo staging on the prognosis of hilar cholangiocarcinoma (HCCA) patients, and to evaluate the predictive value of the Mayo staging on the prognosis. The Kaplan-Meier survival curve and Log-rank test were used to perform univariate analysis on each index and obtain statistically significant influencing factors. The Kaplan-Meier survival curve and Log-rank test were used to analyze the correlation between the two staging systems and the survival period.

Forkhead box M1 recruits FoxP3 Treg cells to induce immune escape in hilar cholangiocarcinoma.

Objective: Hilar cholangiocarcinoma (HCCA) is a malignancy related to chronic biliary tract inflammation. Tumor immune escape is a necessary process of tumorigenesis. Forkhead box M1 (FoxM1) could affect the progression of various carcinomas.

COL17A1 facilitates tumor growth and predicts poor prognosis in pancreatic cancer.

Objective: This study aimed to determine the role of COL17A1 in tumor progression and predict the prognosis of pancreatic cancer (PC).

Methods: RNA-seq data from The Cancer Genome Atlas and Genotype-Tissue Expression were analyzed using bioinformatics methods. "Limma" package was used to screen differentially expressed genes (DEGs).