Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives.

Lenvatinib is a multi-target tyrosine kinase inhibitor widely used in the treatment of hepatocellular carcinoma (HCC). Its primary mechanism of action involves inhibiting signal pathways such as vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptors (FGFR), thereby reducing tumor cell proliferation and angiogenesis and affecting the tumor's immune microenvironment. In the treatment of liver cancer, although lenvatinib monotherapy has shown good clinical effect, the problem of drug resistance is becoming more and more serious.

Melatonin mitigates intervertebral disc degeneration by suppressing NLRP3 inflammasome activation via the EGR1/DDX3X pathway.

Intervertebral disc degeneration (IVDD), is one of the leading causes of low back pain. Inflammation is considered to be the main pathophysiological process of IVDD. The nucleotide-binding domain and leucine-rich pyrin domain containing 3 (NLRP3) inflammasome-mediated inflammatory responses are critically involved in the progression of IVDD.

Knockout of hexokinase 2 regulates mitochondrial dysfunction and activates the NLRP3 signal pathway in the rumen epithelial cells of dairy cows.

Hexokinase 2 (HK2) plays a vital role in mitochondrial homeostasis; however, the molecular mechanisms underlying its involvement in high-concentrate diet-induced damage in the ruminal epithelium of dairy cows are poorly understood. This study aimed to explore the regulatory role of HK2 in mitochondrial function and responses to inflammation in the rumen of dairy cows fed a high-concentrate diet. Our results showed that, compared with a low-concentrate (LC) diet, feeding a high-concentrate (HC) diet increased oxidative stress and reduced relative antioxidant gene expression levels and enzyme activities in the ruminal epithelium.

Double-Layer Distributed and Integrated Fault Detection Strategy for Non-Gaussian Dynamic Industrial Systems.

Currently, with the increasing scale of industrial systems, multisensor monitoring data exhibit large-scale dynamic Gaussian and non-Gaussian concurrent complex characteristics. However, the traditional principal component analysis method is based on Gaussian distribution and uncorrelated assumptions, which are greatly limited in practice. Therefore, developing a new fault detection method for large-scale Gaussian and non-Gaussian concurrent dynamic systems is one of the urgent challenges to be addressed.

Causal relationship between Brugada syndrome and electrocardiogram traits: A bidirectional Mendelian randomization study.

Introduction: Observational studies have suggested associations between Brugada syndrome (BrS) and electrocardiograms traits. Nonetheless, the causal relationships remains uncertain in observational studies. This study aims to investigate the causal relationships between BrS phenotypic risk and electrocardiogram traits using Mendelian randomization (MR) analysis and colocalization analysis.

Multifaceted role of microRNA-301a in human cancer: from biomarker potential to therapeutic targeting.

With the growing data on microRNA (miRNA) expression in tissues and circulation, there is increasing evidence for the potential of microRNAs to serve as biomarkers in cancer diagnosis and prognosis, as well as novel therapeutic targets. The expression level of miRNA-301a (miR-301a) is altered in a wide range of human tumor types, and numerous studies have revealed the roles of miR-301a in tumorigenesis and tumor progression. Herein, we comprehensively summarize, compare, and contrast the research advancements on the role of miR-301a in different cancers.

Shear Anisotropy Domains on Graphene Revealed by In-Plane Elastic Imaging.

Anisotropic domains with 180° periodicity are known to be universally present on graphene as well as on other two-dimensional (2D) crystals. The physical origin of the domains and the mechanism of its anisotropy are, however, still unclear. Here, by employing in-plane elastic imaging by torsional resonance atomic force microscopy (TR-AFM), we demonstrate that the observed domains on graphene are of in-plane elastic (shear) anisotropy but not of friction anisotropy as commonly believed.

Anxiety and depression as risk factors for postoperative complications and pain in lumbar spine surgery: A national database study.

To investigate the potential association between anxiety and depression and surgical outcomes in patients undergoing LSS. By analyzing data from the Nationwide Inpatient Sample (NIS) database, we aim to identify whether anxiety and depression serve as predictors for postoperative complications and pain-related symptoms. A retrospective analysis was conducted via the NIS database.

Orbicular-Donor-Acceptor System in N-doped Nanographene for Highly Efficient NIR-II Photothermal Therapy.

Developing stable and efficient photothermal agents (PTAs) for the second near-infrared window (NIR-II, 1 000-1700 nm) photothermal therapy (PTT) is highly desirable but remains challenging. Herein, a facile strategy to prepare NIR-II nano-PTA based on the ionic N-doped nanographene hexapyrrolohexaazacoronene (HPHAC) is reported featuring a specific orbicular-donor-acceptor (O-D-A) structure. Oxidizing HPHAC 1 to dication 1 causes a substantial decrease in its band gap, leading to a shift in absorption from the confined UV region to a broad absorption range that reaches up to 1400 nm.

The role of cystathionine β-synthase in cancer.

Cystathionine β-synthase (CBS) occupies a key position as the initiating and rate-limiting enzyme in the sulfur transfer pathway and plays a vital role in health and disease. CBS is responsible for regulating the metabolism of cysteine, the precursor of glutathione (GSH), an important antioxidant in the body. Additionally, CBS is one of the three enzymes that produce hydrogen sulfide (HS) in mammals through a variety of mechanisms.

Analysis of risk factors for hospital-acquired pneumonia in schizophrenia.

Background: Hospital-acquired pneumonia is one of the most important causes of recurrent illness, disease progression, and even death during hospitalization. Patients with schizophrenia have the special characteristics of their disease, and at the same time, the occurrence of hospital-acquired pneumonia is more common among patients with schizophrenia due to the prolonged stay in closed wards, accompanied by various factors such as age, gender, and nutritional status.

Methods: The PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) databases were searched with a timeframe of build to February 2024 to collect studies on factors influencing hospital-acquired pneumonia in patients with schizophrenia.

Role of gasotransmitters in necroptosis.

Gasotransmitters are endogenous gaseous signaling molecules that can freely pass through cell membranes and transmit signals between cells, playing multiple roles in cell signal transduction. Due to extensive and ongoing research in this field, we have successfully identified many gasotransmitters so far, among which nitric oxide, carbon monoxide, and hydrogen sulfide are best studied. Gasotransmitters are implicated in various diseases related to necroptosis, such as cardiovascular diseases, inflammation, ischemia-reperfusion, infectious diseases, and neurological diseases.

Impaired degradation of PLCG1 by chaperone-mediated autophagy promotes cellular senescence and intervertebral disc degeneration.

Defects in chaperone-mediated autophagy (CMA) are associated with cellular senescence, but the mechanism remains poorly understood. Here, we found that CMA inhibition induced cellular senescence in a calcium-dependent manner and identified its role in TNF-induced senescence of nucleus pulposus cells (NPC) and intervertebral disc degeneration. Based on structural and functional proteomic screens, PLCG1 (phospholipase C gamma 1) was predicted as a potential substrate for CMA deficiency to affect calcium homeostasis.

Static magnetic field-modulated mesenchymal stem cell-derived mitochondria-containing microvesicles for enhanced intervertebral disc degeneration therapy.

Intervertebral disc degeneration (IVDD) is characterized by the senescence and declining vitality of nucleus pulposus cells (NPCs), often driven by mitochondrial dysfunction. This study elucidates that mesenchymal stem cells (MSCs) play a crucial role in attenuating NPC senescence by secreting mitochondria-containing microvesicles (mitoMVs). Moreover, it demonstrates that static magnetic fields (SMF) enhance the secretion of mitoMVs by MSCs.

Causal relationship between Alzheimer's disease and unstable angina: a bidirectional Mendelian randomization analysis.

Background: Research from observational studies has demonstrated a link between Alzheimer's disease (AD) and a higher risk of cardiovascular disease (CVD). Uncertainty surrounds the exact genetic cause of AD and coronary heart disease, particularly unstable angina (UA). Mendelian randomization (MR) analysis was used to examine the causal genetic link between AD and UA to evaluate the impact of AD on UA.

Association between surgical delays for femoral neck fractures and early postoperative complications in young and middle-aged adults: A study based on the national inpatient sample database.

Background: Femoral neck fractures (FNF) in young and middle-aged adults are primarily caused by high-energy injuries in traffic accidents. Surgical delays often occur due to transportation issues, preoperative evaluations, and economic burdens.

Methods: A retrospective analysis was conducted on young and middle-aged FNF patients undergoing reduction and internal fixation surgeries from 2010 to 2019 with the use of the National Inpatient Sample database.

Mechanistic insights into phosphoactivation of SLAC1 in guard cell signaling.

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases.

The role of hydrogen sulfide regulation of ferroptosis in different diseases.

Ferroptosis is a programmed cell death that relies on iron and lipid peroxidation. It differs from other forms of programmed cell death such as necrosis, apoptosis and autophagy. More and more evidence indicates that ferroptosis participates in many types of diseases, such as neurodegenerative diseases, ischemia-reperfusion injury, cardiovascular diseases and so on.