Convergent Evolution of Armor: Thermal Resistance in Deep-Sea Hydrothermal Vent Crustaceans.

Organisms occupy diverse ecological niches worldwide, each with characteristics finely evolved for their environments. Crustaceans residing in deep-sea hydrothermal vents, recognized as one of Earth's extreme environments, may have adapted to withstand severe conditions, including elevated temperatures and pressure. This study compares the exoskeletons of two vent crustaceans (bythograeid crab sp.

Mutational Profiling of Korean Lymphomas and Diffuse Large B-Cell Lymphoma Subtype Classification Using Targeted Panel Sequencing.

Background: Lymphoma is a common hematological malignancy with diverse morphological and immunophenotypic characteristics that may affect treatment and outcomes. Thus, accurate differential diagnosis is crucial, and molecular genetic testing is valuable. We aimed to investigate the genetic characteristics of Korean patients with lymphoma using a next-generation sequencing (NGS)-based targeted panel.

Salivary exosomes exacerbate colitis by bridging the oral cavity and intestine.

Inflammatory bowel disease (IBD) presents a range of extraintestinal manifestations, notably including oral cavity involvement. The mechanisms underlying oral-gut crosstalk in IBD are not fully understood. Exosomes, found in various body fluids such as saliva, play an unclear role in IBD that requires further exploration.

A novel histone deacetylase inhibitor protects the blood-brain barrier by regulating NF-κB and Nrf2 signaling pathways in OGD/R injury.

Ischemic stroke, a severe cerebrovascular disease, is particularly prevalent among the elderly. Rsearch has indicated that histone deacetylases (HDACs) are pivotal in the pathogenesis of ischemic stroke. We introduce a novel HDACs inhibitor, HDI-1, as a potential therapeutic strategy for this condition.

Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method.

Gliomas are the most common brain tumor type in children and adolescents. To date, diagnosis and therapy monitoring for these tumors rely on magnetic resonance imaging (MRI) and histopathological as well as molecular analyses of tumor tissue. Recently, liquid biopsies (LB) have emerged as promising tool for diagnosis and longitudinal tumor assessment potentially allowing for a more precise therapeutic management.

Nuclear PD-L1 triggers tumour-associated inflammation upon DNA damage.

Immune checkpoint inhibitors against PD-1/PD-L1 are highly effective in immunologically hot tumours such as triple-negative breast cancer, wherein constitutive DNA damage promotes inflammation, while inducing PD-L1 expression to avoid attack by cytotoxic T cells. However, whether and how PD-L1 regulates the DNA damage response and inflammation remains unclear. Here, we show that nuclear PD-L1 activates the ATR-Chk1 pathway and induces proinflammatory chemocytokines upon genotoxic stress.

Updating probability of pathogenicity for RYR1 and CACNA1S exon variants in individuals without malignant hyperthermia after exposure to triggering anesthetics.

Objectives: We aimed to classify genetic variants in RYR1 and CACNA1S associated with malignant hyperthermia using biobank genotyping data in patients exposed to triggering anesthetics without malignant hyperthermia phenotype.

Methods: We identified individuals who underwent surgery and were exposed to triggering anesthetics without malignant hyperthermia phenotype and who had RYR1 or CACNA1S genotyping data available in our biobank. We classified all variants in the cohort using a Bayesian framework of the American College of Medical Genetics and Genomics and the Association of Molecular Pathologists guidelines for variant classification and updated the posterior probabilities from this model with the new information from our biobank cohort.

LIM kinases in cardiovascular health and disease.

The Lim Kinase (LIMK) family of serine/threonine kinases is comprised of LIMK1 and LIMK2, which are central regulators of cytoskeletal dynamics via their well-characterized roles in promoting actin polymerization and destabilizing the cellular microtubular network. The LIMKs have been demonstrated to modulate several fundamental physiological processes, including cell cycle progression, cell motility and migration, and cell differentiation. These processes play important roles in maintaining cardiovascular health.

Identification of a gene score related to antigen processing and presentation machinery for predicting prognosis in head and neck squamous cell carcinoma and its potential implications for immunotherapy.

Background: Despite its crucial role in immune surveillance and cell survival of tumors, the significance of MHC antigen processing and presentation machinery (APM) is still not fully understood in head and neck squamous cell carcinoma (HNSCC). We sought to develop an APM gene score (APMGS) to predict prognosis and reveal the molecular and immune traits of the APMGS-defined subgroups in HNSCC.

Methods: Based on the APM-related genes acquired from 6 databases, 117 combined machine learning algorithms were applied to develop APMGS with The Cancer Genome Atlas (TCGA)-HNSCC database and validated with the Gene Expression Omnibus (GEO) dataset.

Apolipoprotein E epsilon4 allele is associated with better performance language and visual memory in spinocerebellar ataxia type 3.

Background: The regulatory role of the apolipoprotein E (APOE) ε4 allele in the clinical manifestations of spinocerebellar ataxia type 3 (SCA3) remains unclear. This study aimed to evaluate the impact of the APOE ε4 allele on cognitive and motor functions in SCA3 patients.

Methods: This study included 281 unrelated SCA3 patients and 182 controls.

The role of sonic hedgehog signaling in the oropharyngeal epithelium during jaw development.

Sonic hedgehog (Shh) is expressed in the oropharyngeal epithelium, including the frontonasal ectodermal zone (FEZ), which is defined as the boundary between Shh and Fgf8 expression domains in the frontonasal epithelium. To investigate the role of SHH signaling from the oropharyngeal epithelium, we generated mice in which Shh expression is specifically deleted in the oropharyngeal epithelium (Isl1-Cre; Shh). In the mutant mouse, Shh expression was excised in the oropharyngeal epithelium as well as FEZ and ventral forebrain, consistent with the expression pattern of Isl1.

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

Permeation enhancer decorated nanoparticles for oral delivery of insulin: manipulating the surface density of borneol and PEG for absorption barriers.

Oral protein drugs' delivery faces challenges due to multiple absorption barriers for macromolecules. Co-administration with permeation enhancers and encapsulation in nano-carriers are two promising strategies to enhance their oral absorption. Herein, the poly(lactic--glycolic acid) nanoparticles (PLGA NPs) are decorated with polyethylene glycol (PEG) and a traditional Chinese medicine-derived permeation enhancer borneol (BO) for oral insulin delivery.

Single-Nucleus Atlas of Cell-Type Specific Genetic Regulation in the Human Brain.

Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. This study presents a comprehensive single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.

Docetaxel response in BRCA1,p53-deficient mammary tumor cells is affected by Huntingtin and BAP1.

Taxanes are frequently used anticancer drugs known to kill tumor cells by inducing mitotic aberrations and segregation defects. A defining feature of specific cancers, notably triple-negative breast cancer (TNBC) and particularly those deficient in BRCA1, is chromosomal instability (CIN). Here, we focused on understanding the mechanisms of docetaxel-induced cytotoxicity, especially in the context of BRCA1-deficient TNBC.

Single-cell atlas comparison across vertebrates reveals auditory cell evolution and mechanisms for hair cell regeneration.

Mammals suffer permanent hearing impairment from the loss of auditory hair cells due to their inability to regenerate. In contrast, lower vertebrates exhibit extraordinary capacity for hair cell regeneration and hearing restoration, but the mechanisms remain unclear. Here we characterize the single-cell atlas of Xenopus laevis inner ear and perform a comprehensive comparison with mouse model.

Polyethylene glycol loxenatide protects diabetic kidneys by inhibiting GRP78/PERK/eIF2α pathway, and improves cardiac injury by suppressing TLR4/NF-κB inflammatory pathway.

Background: Cardiovascular and renal complications of type 2 diabetes are the main causes of death in diabetic patients. Clinical studies have found that polyethylene glycol loxenatide (PEG-Loxe), a GLP-1 analog widely used to treat type 2 diabetes, boosts renal and cardiac functions in diabetic patients. However, its mechanism of action remains to be elucidated.

Analysis of mutations in precision oncology using the automated, accurate, and user-friendly web tool PredictONCO.

Next-generation sequencing technology has created many new opportunities for clinical diagnostics, but it faces the challenge of functional annotation of identified mutations. Various algorithms have been developed to predict the impact of missense variants that influence oncogenic drivers. However, computational pipelines that handle biological data must integrate multiple software tools, which can add complexity and hinder non-specialist users from accessing the pipeline.

Deep Saliva Proteomics Elucidating the Pathogenesis of Early Childhood Caries and Identifying Biomarkers for Early Prediction.

Early childhood caries (ECC) significantly impacts the physical and mental health of children. Saliva stands as a critical model for investigating the pathogenesis of caries disease since it reflects both host and microbial dynamics. However, the specific contributions of salivary host factors to ECC have not been fully understood.

Leveraging DNA methylation to create Epigenetic Biomarker Proxies that inform clinical care: A new framework for Precision Medicine.

The lack of accurate, cost-effective, and clinically relevant biomarkers remains a major barrier to incorporating omic data into clinical practice. Previous studies have shown that DNA methylation algorithms have utility as surrogate measures for selected proteins and metabolites. We expand upon this work by creating DNAm surrogates, termed epigenetic biomarker proxies (EBPs), across clinical laboratories, the metabolome, and the proteome.

circUBR5 promotes ribosome biogenesis and induces docetaxel resistance in triple-negative breast cancer cell lines via the miR-340-5p/CMTM6/c-MYC axis.

Objective: Docetaxel (DTX) represents an effective chemotherapeutic agent for treating triple-negative breast cancer (TNBC), but the efficacy is strongly limited by drug resistance. c-MYC-mediated ribosome biogenesis is considered a feasible strategy to confront chemoresistance in BC. We elucidated the impact of CMTM6 on TNBC DTX chemoresistance by governing c-MYC-mediated ribosome biogenesis, and its upstream ceRNA regulatory pathways.

Integration of genomics, clinical characteristics and baseline biological profiles to predict the risk of liver injury induced by high-dose methotrexate.

Background: High-dose methotrexate (HD-MTX) is commonly employed in the treatment of malignant tumors in children and young adults due to its distinctive therapeutic efficacy. Nonetheless, the systemic exposure to MTX often results in liver injury (drug induced liver injury, DILI), thereby imposing limitations on the sustained administration of HD-MTX. Additionally, individual variations including genetic underpinnings attributable to disparities in therapeutic effects and clinical toxicity remain to be elucidated.

Novel ionic chitosan derivatives based on pyridinium sulfonate: Synthesis, characterization, and studies on antimicrobial, antioxidant, and biocompatibility properties.

To improve the solubility, antimicrobial efficacy, antioxidant capacity, and biocompatibility of chitosan for broader applications, a series of novel ionic chitosan derivatives were synthesized in this study by amidating chitosan with carboxyl pyridinium sulfonate. These derivatives were characterized through various analytical techniques, including FTIR, H NMR, UV, TGA, and XRD. Proton NMR was particularly utilized to determine the degree of substitution.