Understanding the effects of adduct functionalization on C nanocages for the hydrogen evolution reaction.

In this work, we use experimental and theoretical techniques to study the origin of the boosted hydrogen evolution reaction (HER) catalytic activity of two pyridyl-pyrrolidine functionalized C fullerenes. Notably, the mono-(pyridyl-pyrrolidine) penta-adduct of C has exhibited a remarkable HER catalytic activity as a metal-free catalyst, delivering an overpotential () of 75 mV RHE and a very low onset potential of -45 mV RHE. This work addresses fundamental questions about how functionalization on C changes the electron density on fullerene cages for high-performance HER electrocatalysis.

Machine perfusion strategies in Liver Transplantation: A systematic review, pairwise, and network meta-analysis of randomized controlled trials.

Background: Machine perfusion (MP), including hypothermic oxygenated machine perfusion (HOPE), dual HOPE, normothermic machine perfusion (NMP), NMP ischemia-free liver transplantation (NMP-ILT), and controlled oxygenated rewarming (COR), is increasingly being investigated to improve liver graft quality from extended criteria donors and donors after circulatory death and expand the donor pool. This network meta-analysis investigates the comparative efficacy and safety of various liver MP strategies versus traditional static cold storage (SCS).

Methods: We searched PubMed, Scopus, Web of Science, and Cochrane Controlled Register of Trials for randomized controlled trials (RCTs) comparing liver transplantation (LT) outcomes between SCS and MP techniques.

FAM43A coordinates mtDNA replication and mitochondrial biogenesis in response to mtDNA depletion.

Mitochondrial retrograde signaling (MRS) pathways relay the functional status of mitochondria to elicit homeostatic or adaptive changes in nuclear gene expression. Budding yeast have "intergenomic signaling" pathways that sense the amount of mitochondrial DNA (mtDNA) independently of oxidative phosphorylation (OXPHOS), the primary function of genes encoded by mtDNA. However, MRS pathways that sense the amount of mtDNA in mammalian cells remain poorly understood.

Proteomic Profiling of Medullary Thyroid Cancer Identifies CAPN1 as a Key Regulator of NF1 and RET Fueled Growth.

Medullary thyroid cancer (MTC) is a frequently metastatic tumor of the thyroid that develops from the malignant transformation of C-cells. These tumors most commonly have activating mutations within the RET or RAS proto-oncogenes. Germline mutations within RET result in C-cell hyperplasia, and cause the MTC pre-disposition disorder, multiple endocrine neoplasia, type 2A (MEN2A).

"It's Like You're Feeding Your Child Twice": Barriers and Facilitators to Human Milk Feeding Children With Cystic Fibrosis.

Background: Cystic Fibrosis Foundation guidelines recommend human milk (HM) as the ideal source of nutrition for children with CF (cwCF). Despite known pulmonary and nutritional benefits, fewer cwCF ever receive HM compared to the general population. Early nutrition choices are preference-sensitive, yet little is known about the factors that impede or sustain HM feeding among parents of cwCF.

Rationalizing protein-ligand interactions via the effective fragment potential method and structural data from classical molecular dynamics.

The Effective Fragment Potential (EFP) method, a polarizable quantum mechanics-based force field for describing non-covalent interactions, is utilized to calculate protein-ligand interactions in seven inactive cyclin-dependent kinase 2-ligand complexes, employing structural data from molecular dynamics simulations to assess dynamic and solvent effects. Our results reveal high correlations between experimental binding affinities and EFP interaction energies across all the structural data considered. Using representative structures found by clustering analysis and excluding water molecules yields the highest correlation (R2 of 0.

Extending Badger's rule. I. The relationship between energy and structure in hydrogen bonds.

We derive a new expression for the strength of a hydrogen bond (VHB) in terms of the elongation of the covalent bond of the donor fragment participating in the hydrogen bond (ΔrHB) and the intermolecular coordinates R (separation between the heavy atoms) and θ (deviation of the hydrogen bond from linearity). The expression includes components describing the covalent D-H bond of the hydrogen bond donor via a Morse potential, the Pauli repulsion, and electrostatic interactions between the constituent fragments using a linear expansion of their dipole moment and a quadratic expansion of their polarizability tensor. We fitted the parameters of the model using ab initio electronic structure results for six hydrogen bonded dimers, namely, NH3-NH3, H2O-H2O, HF-HF, H2O-NH3, HF-H2O, and HF-NH3, and validated its performance for extended parts of their potential energy surfaces, resulting in a mean absolute error ranging from 0.

The ketamine chameleon: history, pharmacology, and the contested value of experience.

Introduction: Since its synthesis in 1962, ketamine has been widely used in diverse medical contexts, from anesthesia to treatment-resistant depression. However, interpretations of ketamine's subjective effects remain polarized. Biomedical frameworks typically construe the drug's experiential effects as dissociative or psychotomimetic, while psychedelic paradigms emphasize the potential therapeutic merits of these non-ordinary states.

Immune-Mediated Liver Injury From Checkpoint Inhibitor: An Evolving Frontier With Emerging Challenges.

Over the past decade, immune checkpoint inhibitors (ICIs) have transformed the treatment of cancer, though they come with the risk of immune-related adverse (irAEs) events such as hepatotoxicity or Immune-mediated Liver Injury from Checkpoint Inhibitors (ILICI). ILICI is a serious irAE that, when severe, requires cessation of ICI and initiation of immunosuppression. Cytotoxic T Lymphocytes (CTLs) play a central role in ILICI; however, they are just part of the picture as immunotherapy broadly impacts all aspects of the immune microenvironment and can directly and indirectly activate innate and adaptive immune cells.

Draft genome assemblies of 35 bacteria isolated from hibernating arctic ground squirrels.

Arctic ground squirrels () hibernate for several months without eating or drinking yet suffer no disuse atrophy. We are investigating the potential contributions of gut microorganisms to host nitrogen homeostasis, and here, we describe the genome assemblies of 35 isolated bacteria collected from gastrointestinal material and sequenced using Nanopore technology.

Cross-Sectional Comparison of Structural MRI Markers of Impairment in a Diverse Cohort of Older Adults.

Neurodegeneration is presumed to be the pathological process measure most proximal to clinical symptom onset in Alzheimer Disease (AD). Structural MRI is routinely collected in research and clinical trial settings. Several quantitative MRI-based measures of atrophy have been proposed, but their low correspondence with each other has been previously documented.

Opportunistic assessment of steatotic liver disease in lung cancer screening eligible individuals.

Background: Steatotic liver disease (SLD) is a potentially reversible condition but often goes unnoticed with the risk for end-stage liver disease.

Purpose: To opportunistically estimate SLD on lung screening chest computed tomography (CT) and investigate its prognostic value in heavy smokers participating in the National Lung Screening Trial (NLST).

Material And Methods: We used a deep learning model to segment the liver on non-contrast-enhanced chest CT scans of 19,774 NLST participants (age 61.

Long-day induced flowering requires DNA hypermethylation in orchardgrass.

Flowering, a pivotal plant lifecycle event, is intricately regulated by environmental and endogenous signals via genetic and epigenetic mechanisms. Photoperiod is a crucial environmental cue that induces flowering by activating integrators through genetic and epigenetic pathways. However, the specific role of DNA methylation, a conserved epigenetic marker, in photoperiodic flowering remains unclear.

Fluorofurimazine, a novel NanoLuc substrate, enhances real-time tracking of influenza A virus infection without altering pathogenicity in mice.

Unlabelled: Bioluminescence imaging (BLI) using engineered bioluminescent viruses has emerged as a powerful tool for real-time, noninvasive monitoring of viral replication in living animals. While traditional luciferase-based systems, such as firefly luciferase, have been widely used, the NanoLuc luciferase system offers distinct advantages, including its significantly smaller gene size, increased brightness, and independence from ATP as a cofactor, allowing for extracellular detection. However, the utility of NanoLuc has been limited by its traditional substrate, furimazine, which exhibits poor water solubility and potential cytotoxicity.

Hypothermic machine perfusion in uterus transplantation in a porcine model: A proof of concept and the first results in graft preservation.

Introduction: Graft optimization is a necessity in order to develop uterus transplantation from brain-dead donors, as a complement to living donors, as these grafts are rare and the last organs retrieved in multiple organ donation. The aim of this study was to assess the feasibility and interest of hypothermic machine perfusion (HMP) in uterus transplantation using a porcine model; secondary outcomes were the evaluation of the graft's tolerance to a prolonged cold ischaemia time and to find new biomarkers of uterus viability.

Material And Methods: Fifteen uterus allotransplantations were performed in a porcine model, after 18 h of cold ischaemia, divided in three groups: Static cold storage in a HTK solution, HMP (with the VitaSmart (™) machine Bridge to Life Ltd.

Sodium-glucose cotransporter 2 inhibitors and outcomes in transthyretin amyloid cardiomyopathy: Systematic review and meta-analysis.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) commonly leads to heart failure but has traditionally been an exclusion criterion in randomized clinical trials (RCTs) of sodium-glucose cotransporter 2 inhibitors (SGLT2i); therefore, the effects of these drugs in this population remain undocumented. In light of recent studies, this meta-analysis aimed to investigate the effect of SGLT2i on the prognosis of patients with ATTR-CM.

Methods: A comprehensive search of Medline, Scopus, and the Cochrane Library was conducted up to November 17, 2024.

Multicenter validation of secondary hemophagocytic lymphohistiocytosis diagnostic criteria.

Background: Five fulfilled hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, and the HScore are widely used and recommended by international expert consensus to diagnose secondary HLH. Both diagnostic scores have never been validated in heterogeneous patient cohorts of secondary HLH patients. We aimed to systematically optimize and validate diagnostic criteria of secondary HLH using a multicenter approach.

Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP.

Triple-negative breast cancer (TNBC) in obese patients remains challenging. Recent studies have linked obesity to an increased risk of TNBC and malignancies. Through multiomic analysis and experimental validation, a dysfunctional Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3H)/Yes-associated protein (YAP) proteolytic axis is identified as a pivotal junction mediating the interplay between cancer-associated adipocytes and the response to anti-cancer drugs in TNBC.

Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium.

This proceedings article summarizes the inaugural "T Cells in the Brain" symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia-T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau.

Phytochemical-Based Drug Discovery for Breast Cancer: Combining Virtual Screening and Molecular Dynamics to Identify Novel Therapeutics.

Maternal Embryonic Leucine Zipper Kinase (MELK), a pivotal signaling protein, plays a crucial role in various physiological processes such as cell growth, survival, and differentiation. There is currently a growing interest in MELK as a promising therapeutic target for multiple cancers, including triple-negative breast cancer (TNBC). Exploring MELK as a target offers a prospective strategy to impede cancer progression and enhance the efficacy of conventional anticancer therapies.

Cardiovascular, cancer, and infection risks of Janus kinase inhibitors in rheumatoid arthritis and ulcerative colitis: A nationwide cohort study.

Background: Evolving evidence suggests that patients undergoing treatment with Janus kinase inhibitors (JAKi) may face an increased risk of cardiovascular events, malignancies, and serious infections.

Objectives: We assessed cardiovascular, malignancy, and serious infection risks associated with JAKi use compared to tumor necrosis factor inhibitor (TNFi) use, which served as the active comparator, in patients with rheumatoid arthritis (RA) or ulcerative colitis (UC).

Methods: This study emulated a target trial using South Korea's nationwide claims database (2013-2023).