Burn-induced mitochondrial dysfunction in hepatocytes: The role of methylation-controlled J protein silencing.

Background: Burn injuries trigger a systemic hyperinflammatory response, leading to multiple organ dysfunction, including significant hepatic damage. The liver plays a crucial role in regulating immune responses and metabolism after burn injuries, making it critical to develop strategies to mitigate hepatic impairment. This study investigates the role of methylation-controlled J protein (MCJ), an inner mitochondrial protein that represses complex I in burn-induced oxidative stress and mitochondrial dysfunction, using an in vitro Alpha Mouse Liver 12 cell model.

Identification of cellular signatures associated with chinese hamster ovary cell adaptation for secretion of antibodies.

The secretory capacity of Chinese hamster ovary (CHO) cells remains a fundamental bottleneck in the manufacturing of protein-based therapeutics. Unconventional biological drugs with complex structures and processing requirements are particularly problematic. Although engineered vector DNA elements can achieve rapid and high-level therapeutic protein production, a high metabolic and protein folding burden is imposed on the host cell.

Short-term outcomes of robot-assisted versus conventional minimally invasive esophagectomy: A propensity score-matched study via a nationwide database.

Background: The advantages of robot-assisted minimally invasive esophagectomy (RA-MIE) over conventional minimally invasive esophagectomy (C-MIE) are unknown. This nationwide large-scale study aimed to compare surgical outcomes between RA-MIE and C-MIE using rigorous propensity score methods, including detailed covariates and relevant outcomes.

Methods: This Japanese nationwide retrospective cohort study included RA-MIE or C-MIE for esophageal malignant tumors performed between October 2018 and December 2019 and registered in the Japanese National Clinical Database.

Mycotic cyst: Case report.

Phaeohyphomycotic cyst is a common subcutaneous form of phaeohyphomycosis in which patients can present with subcutaneous plaques, nodules, etc., It is an infrequent presentation and is most reported in immunocompromised individuals. Diagnosis is confirmed by histopathological and mycological demonstration of the organism.

Heme regulates protein interactions and phosphorylation of BACH2 intrinsically disordered region in humoral response.

Heme is known to bind to the intrinsically disordered region (IDR) to regulate protein function. The binding of heme to the IDR of transcription factor BACH2 promotes plasma cell differentiation, but the molecular basis is unknown. Heme was found to increase BACH2 IDR interaction with TANK-binding kinase 1 (TBK1).

Molecular dynamics simulation studies on RbgA: insights into the RbgA-ribosome association and GTPase activity.

RbgA (ribosome biogenesis GTPase A) is involved in the maturation of later stages of the 50S ribosomal subunit by associating with the 45S ribosomal subunit. However, this binding relies on the specific nucleotide-bound state of RbgA-GTP-bound state is more favorable compared GDP-bound state, attributed to the conformational variations between those states. Therefore, to explore the conformational changes of RbgA, all-atom MD simulations of RbgA were carried out under various nucleotide bound states (GDP, GTP, GTP-Mg and GMPPNP-Mg).

International consensus guidelines on the implementation and monitoring of vosoritide therapy in individuals with achondroplasia.

Achondroplasia is the most common genetic form of short-limbed skeletal dysplasia (dwarfism). Clinical manifestations and complications can affect individuals across the lifespan, including the need for adaptations for activities of daily living, which can affect quality of life. Current international guidelines focus on symptomatic management, with little discussion regarding potential medication, as therapeutic options were limited at the time of their publication.

Comprehensive analysis of telomere and aging-related signature for predicting prognosis and immunotherapy response in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a high-risk malignancy. Telomeres- (TRGs) and aging-related genes (ARGs) play an important role in cancer progression and prognosis. This study aimed to develop a novel prognostic model combined TRGs and ARGs signatures to predict the prognosis of patients with LUAD.

Epidermal Growth Factor Receptors Unveiled: A Comprehensive Survey on Mutations, Clinical Insights of Global Inhibitors, and Emergence of Heterocyclic Derivatives as EGFR Inhibitors.

Mutations that overexpress the epidermal growth factor receptor (EGFR) are linked to cancers like breast (15-20%), head and neck (10-15%), colorectal (5-8%), and non-small cell lung cancer (10-50%), especially in East Asian populations. EGFR activation stimulates "RAS/RAF/MEK/ERK, PI3K/Akt, and MAPK" pathways, which enhance cell division, survival, angiogenesis, and tumor growth while inhibiting apoptosis and metastasis. Secondary mutations (e.

Statistical optimization of pectinases from thermophilic Aspergillus fumigatus BT-4 employing response surface methodology through submerged fermentation using agricultural wastes.

Background: In this study, thermophilic pectinase-producing strains were isolated. Among all the isolates, strain No. 4 was identified as Aspergillus fumigatus BT-4 based on its morphology and 18 S rDNA analysis.

Downregulation of serum miR-30c-5p serves as a biomarker to predict disease onset and short-term prognosis in acute coronary syndrome patients.

Background & Objective: Timely intervention for Acute coronary syndrome (ACS) could effectively reduce the mortality rate of ACS patients. This study aimed to investigate the clinical significance of miR-30c-5p for ACS and to provide a convenient biomarker for diagnosing of ACS.

Methods: Baseline information was collected from a total of 173 subjects (98 ACS subjects and 65 healthy subjects).

Systematic Review of Randomized Controlled Trials Evaluating the Use of Platelet-Rich Plasma for Knee Osteoarthritis: Adherence to Minimum Information for Studies Evaluating Biologics in Orthopaedics.

Background: The Minimum Information for Studies Evaluating Biologics in Orthopedics (MIBO) guidelines were developed in May 2017 to encourage improved reporting standards, promote increased transparency and reproducibility, and enhance clinical evaluation capabilities. The MIBO guidelines consist of 23 checklist items considered necessary to critically appraise clinical studies evaluating platelet-rich plasma (PRP).

Purpose: To assess randomized controlled trials that evaluated PRP for the treatment of knee osteoarthritis in order to systematically review their adherence to the MIBO guidelines.

Unravelling the outcome of L-glutaminase produced by Streptomyces sp. strain 5 M as an anti-neoplasm activity.

Background: Actinomycetes are a well-known example of a microbiological origin that may generate a wide variety of chemical structures. As excellent cell factories, these sources are able to manufacture medicines, agrochemicals, and enzymes that are crucial.

Results: In this study, about 34 randomly selected Streptomyces isolates were discovered in soil, sediment, sea water, and other environments.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

Structures and properties of α-amylase and glucoamylase immobilized by ZIF-8 via one-pot preparation.

The immobilization of α-amylase and glucoamylase using a metal-organic framework (enzyme@ZIF-8) was prepared in situ through a one-pot method. The morphology, crystal structure, and molecular characteristics of the free enzyme and enzyme@ZIF-8 were characterized. The enzyme@ZIF-8 exhibited the rhombic dodecahedron morphology, with a decrease in particle size.

Appreciating Appreciation: Residents' Experience Feeling Valued Differently as Learners, Physicians, and Employees.

Purpose: Cultures of wellness, defined as shared norms, values, attitudes, and behaviors that promote personal and professional growth and well-being, are robust determinants of professional fulfillment and professional performance. A major and largely overlooked aspect of a culture of wellness in medicine is residents' perceived appreciation or experience of feeling valued. Considering the pressing workforce and retention challenges that residency programs face, this study addressed the following research questions: How does appreciation at work manifest in the eyes of residents and how do residents perceive appreciation in relation to their professional fulfillment and performance?

Method: Guided by an interpretative phenomenological approach, this qualitative study purposively sampled 12 residents from different specialties, training years, regions in the Netherlands, and genders.

Comparative evaluation of pattern and distribution of stresses in single- and double-implant overdenture using ball-ring, positioner, and magnet-keeper attachment under different loading conditions: A finite element analysis.

Aim: The aim is to evaluate and compare stress distribution characteristics of ball, magnet, and positioned attachment systems in single and double implant-retained overdentures using the finite element method (FEM).

Setting And Design: In vitro (in silico study) finite element analysis (FEA).

Materials And Methods: A Styrofoam mandible with duplicated silicon mucosa was used to construct a mandibular complete denture.

Structural and kinetic characterization of DUSP5 with a Di-phosphorylated tripeptide substrate from the ERK activation loop.

Introduction: Dual specific phosphatases (DUSPs) are mitogen-activated protein kinase (MAPK) regulators, which also serve as drug targets for treating various vascular diseases. Previously, we have presented mechanistic characterizations of DUSP5 and its interaction with pERK, proposing a dual active site.

Methods: Herein, we characterize the interactions between the DUSP5 phosphatase domain and the pT-E-pY activation loop of ERK2, with specific active site assignments.

Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

Recombinant Fungal Aspartic Endopeptidases: Insights into Protein Hydrolysis and Combined Effect with Pepsin for Animal Feed Application.

Protein hydrolysis under acidic conditions can improve the product quality, nutrient availability, and cost efficiency, particularly when neutral or alkaline enzymes are ineffective. Six fungal aspartic endopeptidases (FAPs) were recombinantly expressed as active enzymes in , with peak activity between 30-50 °C and pH 3.0-4.

Rational engineering of minimally immunogenic nucleases for gene therapy.

Genome editing using CRISPR-Cas systems is a promising avenue for the treatment of genetic diseases. However, cellular and humoral immunogenicity of genome editing tools, which originate from bacteria, complicates their clinical use. Here we report reduced immunogenicity (Red)(i)-variants of two clinically relevant nucleases, SaCas9 and AsCas12a.

The spatially informed mFISHseq assay resolves biomarker discordance and predicts treatment response in breast cancer.

Current assays fail to address breast cancer's complex biology and accurately predict treatment response. On a retrospective cohort of 1082 female breast tissues, we develop and validate mFISHseq, which integrates multiplexed RNA fluorescent in situ hybridization with RNA-sequencing, guided by laser capture microdissection. This technique ensures tumor purity, unbiased whole transcriptome profiling, and explicitly quantifies intratumoral heterogeneity.

AI-based visualization of loose connective tissue as a dissectable layer in gastrointestinal surgery.

We aimed to develop an AI model that recognizes and displays loose connective tissue as a dissectable layer in real-time during gastrointestinal surgery and to evaluate its performance, including feasibility for clinical application. Training data were created under the supervision of gastrointestinal surgeons. Test images and videos were randomly sampled and model performance was evaluated visually by 10 external gastrointestinal surgeons.