Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment.

Introduction: Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.

Nutritional, Nutraceutical, and Medicinal Potential of Fr.: A Comprehensive Review.

Mushrooms are considered as nutraceutical foods that can effectively prevent diseases such as cancer and other serious life-threatening conditions include neurodegeneration, hypertension, diabetes, and hypercholesterolemia. The , also known as the "Golden chanterelle" or "Golden girolle," is a significant wild edible ectomycorrhizal mushroom. It is renowned for its delicious, apricot-like aroma and is highly valued in various culinary traditions worldwide.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Adaptive Platform Trials in Stroke.

Clinical trials of treatments for stroke have generally utilized 2-arm, randomized designs to evaluate a single intervention against a control. Running separate clinical trials, with each addressing a single therapeutic question, is resource intensive and slows evidence generation, especially in a field with rapidly expanding treatment options and evolving practices. Platform trials-randomized clinical trials designed to evaluate multiple interventions that may enter and exit the ongoing platform based on a master protocol-accelerate the investigation of multiple therapeutic options within a single infrastructure.

Utilizing machine learning to optimize agricultural inputs for improved rice production benefits.

Lower efficiency of agricultural inputs in the four conventional rice planting methods limits productivity and environmental benefits in Southwest China. Thus, we developed a machine-learning-based decision-making system for achieving optimal comprehensive benefits during rice production. Based on conventional benefits for achieving optimal benefits, implemented strategies in these planting methods: reducing N fertilizer by 16% while increasing seed inputs by 9% in mechanical transplanting (MT) method improved yield and environmental benefits; reducing N fertilizer and seed inputs by 10-12% in mechanical direct seeding (MD) method decreased environmental impacts; increasing N-K fertilizers and seed inputs by 15-33% in manual transplanting (MAT) method improved its comprehensive benefits by 7-14%; applying N-P-K fertilizer ratio of 2:1:2 in manual direct seeding (MAD) method enhanced yield.

Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.

Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice.

Obesity is a chronic disease that contributes to the development of insulin resistance, type 2 diabetes (T2D), and cardiovascular risk. Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) co-agonism provide an improved therapeutic profile in individuals with T2D and obesity when compared with selective GLP-1R agonism. Although the metabolic benefits of GLP-1R agonism are established, whether GIPR activation impacts weight loss through peripheral mechanisms is yet to be fully defined.

Molecular Ultrasound Imaging With Clinically Translatable cRGD-Coated Microbubbles to Assess αvβ3-Integrin Expression in Inflammatory Bowel Disease.

Objectives: Inflammatory bowel disease (IBD) subdivides into Crohn disease (CD) and ulcerative colitis (UC), and is characterized by unpredictable periods of inflammation and results in significant patient suffering and even death. Conventional diagnostic methods, for example, colonoscopy, computed tomography, or magnetic resonance imaging, have limitations such as invasiveness, patient discomfort, and limited sensitivity and accuracy. Therefore, we propose ultrasound molecular imaging (USMI) to detect and characterize IBD.

Patient-Reported Outcomes after Surgery for Pigmented Villonodular Synovitis in the Knee: A Cohort Study.

Pigmented villonodular synovitis (PVNS) is a rare neoplastic proliferation of large joints, including the knee, with both localized PVNS (LPVNS) and diffuse PVNS (DPVNS) types. DPVNS is known to recur at a higher rate following resection; however, there is little evidence comparing patient-reported outcomes (PROs) between the two types. The purpose of this study was to compare PROs between patients with LPVNS and DPVNS involving the knee 2 years after surgical resection.

Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma.

Background: Subacute and chronic subdural hematomas are common and frequently recur after surgical evacuation. The effect of adjunctive middle meningeal artery embolization on the risk of reoperation remains unclear.

Methods: In a prospective, multicenter, interventional, adaptive-design trial, we randomly assigned patients with symptomatic subacute or chronic subdural hematoma with an indication for surgical evacuation to undergo middle meningeal artery embolization plus surgery (treatment group) or surgery alone (control group).

Endocisternal interfaces for minimally invasive neural stimulation and recording of the brain and spinal cord.

Minimally invasive neural interfaces can be used to diagnose, manage and treat many disorders, with reduced risks of surgical complications. However, endovascular probes lack access to key cortical, subcortical and spinal targets, and are not typically explantable after endothelialization. Here we report the development and testing, in sheep, of endocisternal neural interfaces that approach brain and spinal cord targets through inner and outer spaces filled with cerebrospinal fluid.

Elemental mapping in single-particle reconstructions by reconstructed electron energy-loss analysis.

For macromolecular structures determined by cryogenic electron microscopy, no technique currently exists for mapping elements to defined locations, leading to errors in the assignment of metals and other ions, cofactors, substrates, inhibitors and lipids that play essential roles in activity and regulation. Elemental mapping in the electron microscope is well established for dose-tolerant samples but is challenging for biological samples, especially in a cryo-preserved state. Here we combine electron energy-loss spectroscopy with single-particle image processing to allow elemental mapping in cryo-preserved macromolecular complexes.

Precise genetic control of ATOH1 enhances maturation of regenerated hair cells in the mature mouse utricle.

Vestibular hair cells are mechanoreceptors critical for detecting head position and motion. In mammals, hair cell loss causes vestibular dysfunction as spontaneous regeneration is nearly absent. Constitutive expression of exogenous ATOH1, a hair cell transcription factor, increases hair cell regeneration, however, these cells fail to fully mature.

Healing sequelae following tooth extraction and dental implant placement in an aged, ovariectomy model.

At present, a lack of consensus exists regarding the clinical impact of osteoporosis on alveolar bone metabolism during implant osseointegration. While limited preclinical and clinical evidence demonstrates a negative influence of osteoporosis on dental extraction socket healing, no preclinical studies offer data on the results of implant placement in 6-mo-old, ovariectomized (OVX) Sprague-Dawley rats. This study aimed to investigate the outcomes of dental tooth extraction socket healing and implant placement in a rodent model of osteoporosis following daily vehicle (VEH) or abaloparatide (ABL) administration.

Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages.

Macrophages exhibit diverse phenotypes and respond flexibly to environmental cues through metabolic remodeling. In this study, we present a comprehensive multi-omics dataset integrating intra- and extracellular metabolomes with transcriptomic data to investigate the metabolic impact on human macrophage function. Our analysis establishes a metabolite-gene correlation network that characterizes macrophage activation.

Nanoscale elemental and morphological imaging of nitrogen-fixing cyanobacteria.

Nitrogen-fixing cyanobacteria bind atmospheric nitrogen and carbon dioxide using sunlight. This experimental study focused on a laboratory-based model system, Anabaena sp., in nitrogen-depleted culture.

The Adverse Effects of Commonly Prescribed Antiseizure Medications in Adults With Newly Diagnosed Focal Epilepsy.

Background And Objectives: Systematic screening can help identify antiseizure medication (ASM)-associated adverse events (AEs) that may preclude patients from reaching effective doses or completing adequate trial periods. The Adverse Event Profile (AEP) is a self-completed instrument to identify the frequency of common AEs associated with ASM use. This study aimed to compare the AE profile of commonly used ASMs in adults with newly diagnosed focal epilepsy.

TGF-β and RAS jointly unmask primed enhancers to drive metastasis.

Epithelial-to-mesenchymal transitions (EMTs) and extracellular matrix (ECM) remodeling are distinct yet important processes during carcinoma invasion and metastasis. Transforming growth factor β (TGF-β) and RAS, signaling through SMAD and RAS-responsive element-binding protein 1 (RREB1), jointly trigger expression of EMT and fibrogenic factors as two discrete arms of a common transcriptional response in carcinoma cells. Here, we demonstrate that both arms come together to form a program for lung adenocarcinoma metastasis and identify chromatin determinants tying the expression of the constituent genes to TGF-β and RAS inputs.

Efficient reclamation of phosphorus from wetland biomass waste via liquid-recirculated hydrothermal carbonization and precipitation.

Hydrothermal carbonization (HTC) for the recovery of phosphorus (P) from biomass wastes has attracted considerable attention, while migration of P to the liquid phase greatly weakened P recovery efficiency and elevated the environmental risk. Therefore, a systematic scheme was proposed in this work to accomplish the complete reclamation of P from wetland plant (Ceratophyllum demersum) through coupling liquid-recirculated HTC mediated by HO or HSO with precipitation, and the migration and speciation of P during this process was determined by P K-edge X-ray absorption near edge structure, P nuclear magnetic resonance, and the modified sequential extraction. The P concentration in the liquid phase increased with the recirculation of HTC process water, and reached up to 550.

Synthesis of novel nanoflowers-like P, K co-doped graphitic carbon nitride for efficient HO photoproduction.

Photocatalytic oxygen reduction is considered an economical and green way to produce HO. Graphitic carbon nitride is a common photocatalyst, but its activity is limited by the low specific surface area and the high recombination rate of photogenerated electron-hole pairs. Herein, nanoflowers-like phosphorus (P) and potassium (K) co-doped graphitic carbon nitride (PKCN) is synthesized by co-polymerization of ammonium dihydrogen phosphate and melamine in the mixed molten salt (KCl/LiCl) medium.