Integrins identified as potential prognostic markers in osteosarcoma through multi-omics and multi-dataset analysis.

Osteosarcoma represents 20% of primary malignant bone tumors globally. Assessing its prognosis is challenging due to the complex roles of integrins in tumor development and metastasis. This study utilized 209,268 osteosarcoma cells from the GEO database to identify integrin-associated genes using advanced analysis methods.

Discovery of novel dual tubulin and MMPs inhibitors for the treatment of lung cancer and overcoming drug resistance.

Nowadays, hybrid molecule with dual targets activity or effect is regarded as an effective strategy for combating the drug resistance development in cancer therapy. Herein, novel of bifunctional conjugates targeting tubulin and MMPs inhibitors were synthesized. Among them, 15j exhibited robust anticancer activity in vitro and in vivo, with IC values of 0.

Nanosize Non-Viral Gene Therapy Reverses Senescence Reprograming Driven by PBRM1 Deficiency to Suppress iCCA Progression.

Polybromo-1 (PBRM1) serves as a crucial regulator of gene transcription in various tumors, including intrahepatic cholangiocarcinoma (iCCA). However, the exact role of PBRM1 in iCCA and the mechanism by which it regulates downstream target genes remain unclear. This research has revealed that PBRM1 is significantly downregulated in iCCA tissues, and this reduced expression is linked to aggressive clinicopathological features and a poor prognosis.

Intratumoral Collagen Deposition Supports Angiogenesis Suggesting Anti-angiogenic Therapy in Armored and Cold Tumors.

A previous study classifies solid tumors based on collagen deposition and immune infiltration abundance, identifying a refractory subtype termed armored & cold tumors, characterized by elevated collagen deposition and diminished immune infiltration. Beyond its impact on immune infiltration, collagen deposition also influences tumor angiogenesis. This study systematically analyzes the association between immuno-collagenic subtypes and angiogenesis across diverse cancer types.

An expanding universe of mutational signatures and its rapid evolution in single-stranded RNA viruses.

The study of mutational processes in somatic genomes has gained recent momentum, uncovering a wide array of endogenous and exogenous factors associated with somatic changes. However, the overall landscape of mutational processes in germline mutations across the tree of life and associated evolutionary driving forces are rather unclear. In this study, we analyzed mutational processes in single-stranded RNA (ssRNA) viruses which are known to jump between different hosts with divergent exogenous environments.

Comprehensive Cellular Senescence Evaluation to Aid Targeted Therapies.

Drug resistance to a single agent is common in cancer-targeted therapies, and rational drug combinations are a promising approach to overcome this challenge. Many Food and Drug Administration-approved drugs can induce cellular senescence, which possesses unique vulnerabilities and molecular signatures. However, there is limited analysis on the effect of the combination of cellular-senescence-inducing drugs and targeted therapy drugs.

Mutation Analysis of TMB-High Colorectal Cancer: Insights Into Molecular Pathways and Clinical Implications.

Colorectal cancer (CRC) is well characterized in terms of genetic mutations and the mechanisms by which they contribute to carcinogenesis. Mutations in APC, TP53, and KRAS are common in CRC, indicating key roles for these genes in tumor development and progression. However, for certain tumors with low frequencies of these mutations that are defined by tumor location and molecular phenotypes, a carcinogenic mechanism dependent on BRAF mutations has been proposed.

Single-atom nanozymes with intelligent response to pathological microenvironments for bacterially infected wound healing.

Wound healing is a complex and dynamic process often accompanied by bacterial infection, inflammation, and excessive oxidative stress. Single-atom nanozymes with multi-enzymatic activities show significant potential for promoting the healing of infected wounds by modulating their antibacterial and anti-inflammatory properties in response to the wound's physiological environment. In this study, we synthesized MN single-atom nanozymes with multi-enzymatic activities that intelligently respond to pH value changes in the wound healing process.

Targeting MXD1 sensitises pancreatic cancer to trametinib.

Background: The resistance of pancreatic ductal adenocarcinoma (PDAC) to trametinib therapy limits its clinical use. However, the molecular mechanisms underlying trametinib resistance in PDAC remain unclear.

Objective: We aimed to illustrate the mechanisms of resistance to trametinib in PDAC and identify trametinib resistance-associated druggable targets, thus improving the treatment efficacy of trametinib-resistant PDAC.

Nootkatone inhibits the progression of glioblastoma by activating the ATF4-CHOP-CHAC1 pathway.

Glioblastoma multiforme (GBM) represents a primary brain tumor that is widely prevalent, and clinical drugs available for its treatment exhibit varying degrees of resistance. Nootkatone (NKT) is a functional sesquiterpene sourced from traditional Chinese medicine --Alpinia Oxyphylla Miq and has been reported to have a diverse range of pharmacological properties. However, it remains unknown whether there are effects of NKT on GBM.

Hepatic adverse events associated with ketamine and esketamine: A population-based disproportionality analysis.

Background And Objective: To determine whether there is disproportionate reporting of hepatobiliary disorders in the United States (US) FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine.

Design: We identified Medical Dictionary for Regulatory Activities (MedDRA) terms in the FAERS related to hepatobiliary disorders.

Main Measures: Formulations of ketamine and esketamine were evaluated for the proportionality of reporting for each hepatobiliary disorder parameter using the reporting odds ratio (ROR).

Zinc nanoparticles from oral supplements accumulate in renal tumours and stimulate antitumour immune responses.

A successful therapeutic outcome in the treatment of solid tumours requires efficient intratumoural drug accumulation and retention. Here we demonstrate that zinc gluconate in oral supplements assembles with plasma proteins to form ZnO nanoparticles that selectively accumulate into papillary Caki-2 renal tumours and promote the recruitment of dendritic cells and cytotoxic CD8 T cells to tumour tissues. Renal tumour targeting is mediated by the preferential binding of zinc ions to metallothionein-1X proteins, which are constitutively overexpressed in Caki-2 renal tumour cells.

Exploring the use and usefulness of living guidelines for consumers: international online survey of patients' and carers' views.

Background: Living guidelines contain continually updated, and potentially changing, clinical recommendations. The implications of living guidelines for consumers (e.g.

Validation of the 9th edition of the TNM staging system for limited-stage small cell lung cancer after Resection: A multicenter study.

Objectives: The 9th edition of the tumor-node-metastasis (TNM) staging system for lung cancer was proposed at the 2023 World Conference on Lung Cancer in Singapore. This study aimed to externally validate and compare the latest staging of small-cell lung cancer (SCLC).

Methods: Four hundred and eight patients with limited-stage SCLC were collected after lung resection from four centers.

A reliable LC-MS/MS method for the quantification of natural amino acids in human plasma and its application in clinic.

A simple and fast LC-MS/MS method was developed and validated for simultaneous quantification of 20 L-amino acids (AAs) in human plasma. Chromatographic separation was achieved on an Agilent AdvanceBio Hilic column within 15 min via gradient elution with an aqueous solution containing 5 mM ammonium formate, 5 mM ammonium acetate and 0.1 % formic acid and an organic mobile phase containing 0.

Hypochlorous Acid-Activatable NIR Fluorescence/Photoacoustic Dual-Modal Probe with High Signal-to-Background Ratios for Imaging of Liver Injury and Plasma Diagnosis of Sepsis.

Hypochlorous acid can be employed as a biomarker for blood infection (such as sepsis) and tissue damage (such as drug-induced liver injury, DILI), and the diagnosis of tissue damage or blood infection can be achieved through the detection of hypochlorous acid in relevant biological samples. Considering the complex environment and the diverse interferences in living organisms and blood plasma, developing new detection methods for HClO with high signal-to-background ratios is particularly important, and it can improve the accuracy of detection and quality of imaging based on a higher contrast, which makes the detection of HClO clearer and more accurate. Here, based on the advantages of the NIR fluorescence/photoacoustic dual-modal probe, we reported a hypochlorous acid-activatable NIR fluorescence/photoacoustic dual-modal probe (NIRF-PA-HClO) based on the spirolactam ring-opening strategy in this paper.

Proximity Labeling and Genetic Screening Reveal that DSG2 is a Counter Receptor of Siglec-9 and Suppresses Macrophage Phagocytosis.

Cancer cells present sialylated glycoconjugates that modulate the activity of various immune cells within the tumor microenvironment through trans interaction with immunosuppressive Siglec receptors. Identifying counter receptors for Siglecs can provide valuable targets for cancer immunotherapy, but it presents significant challenges. Here, the identification of DSG2 (Desmoglein 2) as a dominant counter receptor of Siglec-9 in melanoma cells is reported, using a workflow that combines the strength of proximity labeling and the advantage of CRISPR knockout screening.

Bibliometric analysis of laryngeal cancer treatment literature (2003-2023).

Background: Despite advancements in medical science, the 5-year survival rate for laryngeal squamous cell carcinoma remains low, posing significant challenges in clinical management. This study explores the evolution of key topics and trends in laryngeal cancer research. Bibliometric and knowledge graph analysis are utilized to assess contributions in treating this carcinoma and to forecast emerging research hotspots that may enhance future clinical outcomes.

Construction of a prognostic model for gastric cancer based on immune infiltration and microenvironment, and exploration of MEF2C gene function.

Background: Advanced gastric cancer (GC) exhibits a high recurrence rate and a dismal prognosis. Myocyte enhancer factor 2c (MEF2C) was found to contribute to the development of various types of cancer. Therefore, our aim is to develop a prognostic model that predicts the prognosis of GC patients and initially explore the role of MEF2C in immunotherapy for GC.

IL-17 triggers PD-L1 gene transcription in NSCLC cells via TRIM31-dependent MEF2C K63-linked polyubiquitination.

Background: Non-small cell lung cancer (NSCLC) is a disease related to inflammation. Proinflammatory cytokines such as interleukin 17 (IL-17) can induce cancer cell proliferation, metastasis and immune escape. Although NSCLC immune escape is partly due to the interaction between PD-1 and PD-L1 and PD-L1 expression can be upregulated in cancer cells upon stimulation with IL-17, the underlying mechanism of IL-17-triggered PD-L1 gene transcription in NSCLC cells remains elusive.

Synergistic protection of nascent DNA at stalled forks by MSANTD4 and BRCA1/2-RAD51.

The regressed arms of reversed replication forks exhibit structural similarities to one-ended double-stranded breaks and need to be protected against uncontrolled nucleolytic degradation. Here, we identify MSANTD4 (Myb/SANT-like DNA-binding domain-containing protein 4), a functionally uncharacterized protein that uniquely counters the replication protein A (RPA)-Bloom (BLM)/Werner syndrome helicase (WRN)-DNA replication helicase/nuclease 2 (DNA2) complex to safeguard reversed replication forks from detrimental degradation, independently of the breast cancer susceptibility proteins (BRCA1/2)-DNA repair protein RAD51 pathway. MSANTD4 specifically interacts with the junctions between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in DNA substrates harboring a 3' overhang, which resemble the structural features of regressed arms processed by WRN-DNA2.

Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.

Alpha-1 antitrypsin (AAT) deficiency (AATD) is a monogenic disease caused by misfolding of AAT variants resulting in gain-of-toxic aggregation in the liver and loss of monomer activity in the lung leading to chronic obstructive pulmonary disease (COPD). Using high-throughput screening, we discovered a bioactive natural product, phenethyl isothiocyanate (PEITC), highly enriched in cruciferous vegetables, including watercress and broccoli, which improves the level of monomer secretion and neutrophil elastase (NE) inhibitory activity of AAT-Z through the endoplasmic reticulum (ER) redox sensor protein disulfide isomerase (PDI) A4 (PDIA4). The intracellular polymer burden of AAT-Z can be managed by combination treatment of PEITC and an autophagy activator.

Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS.

Background: The ovarian cancer (OC) preclinical detectable phase (PCDP), defined as the interval during which cancer is detectable prior to clinical diagnosis, remains poorly characterised. We report exploratory analyses from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Methods: In UKCTOCS between Apr-2001 and Sep-2005, 101,314 postmenopausal women were randomised to no screening (NS) and 50,625 to annual multimodal screening (MMS) (until Dec-2011) using serum CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA).