Urolithin C Ameliorates Hyperuricemia by Mitigating Renal Dysfunction through ROS-p38/ERK MAPK Axis Suppression.

Hyperuricemia (HUA) is a prevalent metabolic disorder, with limited therapeutic options. This study investigated the effects and mechanisms of urolithin C (UroC), a gut-microbiota-derived bioactive metabolite from ellagitannin-rich foods, in the management of HUA. In HUA mice, UroC significantly reduced serum uric acid (SUA) levels, outperforming its analogs, UroA and UroB.

Navigating AKT-ivity across cellular compartments.

Phosphoinositide (PIP)-mediated AKT signaling is essential for cellular homeostasis because it orchestrates crucial processes such as metabolism, survival, proliferation, and motility. Dysregulation of this pathway drives various pathologies, particularly cancer. Although cytosolic activation of AKT has been extensively studied, its emerging roles in the nucleus have gained attention over the past decade.

Somato-Cognitive Action Network in Focal Dystonia.

Background: The central pathology causing idiopathic focal dystonia remains unclear. The recently identified somato-cognitive action network (SCAN) has been implicated.

Objective: We tested whether the effector-agnostic SCAN may constitute a central pathology shared across dystonia subtypes, whereas the effector-specific regions in the primary sensorimotor cortex may show distinct functional changes specific to the dystonic body part.

STN1 facilitates metastasis by promoting transcription of EMT-activator ZEB1 in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) poses a serious clinical challenge, demanding further exploration of its pathogenesis and therapeutic targets for metastasis, the main cause of mortality. Here, we identify STN1, a CST complex member crucial for maintaining telomere lengths and genome stability, as a key factor in promoting PDAC metastasis. Elevated STN1 levels correlate with poor patient survival, with oncogenic protein HOXB7 as an upstream transcription factor regulating STN1.

ALDH2 Ameliorates Acute Gouty Arthritis Through Inhibiting NLRP3 Inflammasome and Pyroptosis by Nrf2/ROS Pathway.

Background: Gouty arthritis is a common disease characterized by the deposition of monosodium urate (MSU) crystals in joint and non-joint structures. Nonetheless, the role of aldehyde dehydrogenase 2 (ALDH2) in the pathophysiology of acute gout remains unclear. This study aimed to evaluate the role of ALDH2 in MSU crystal-induced acute gout attacks and related mechanisms and to identify potential therapeutic strategies for gout management.

Case Report: Low-intensity transcranial focused ultrasound stimulation improves social interaction and stereotyped behavior in a boy with autism spectrum disorder.

Objectives: Presently, no biomedical therapies are available that specifically address the core symptoms of autism spectrum disorders. Given the evidence of cortical malfunction in ASD, low-intensity transcranial focused ultrasound stimulation has been discussed as a prospective therapeutic technique.

Methods: We describe the application of transcranial focused ultrasound to the left dorsolateral prefrontal cortex in a boy with ASD, which was applied for 30 minutes each consecutive weekday for four weeks (20 sessions in total).

Regulation of the MDM2-p53 nexus by a nuclear phosphoinositide and small heat shock protein complex.

The tumor suppressor p53 maintains genome stability in the setting of cellular stress and is frequently mutated in cancer. The stability of p53 is regulated by its interaction with the oncoprotein MDM2, a ubiquitin E3 ligase. Recently, nuclear phosphoinositides were reported to bind and stabilize p53.

Effects of mirror therapy combined with theta burst stimulation on motor recovery of upper limbs after stroke: a randomized controlled study.

Objective: This study aimed to explore the impacts of intermittent Theta burst stimulation (iTBS) and mirror image therapy (MT), both used separately and in combination with iTBS, on upper limb (UL) motor function, activities of daily living (ADL), and cortical excitability during the subacute phase of stroke.

Design: Randomized controlled study.

Setting: Inpatient rehabilitation centers of Tongji Hospital and Hubei Provincial Hospital of Integrated Chinese & Western Medicine.

Machine learning identification of key genes in cardioembolic stroke and atherosclerosis: their association with pan-cancer and immune cells.

Background: Cardioembolic stroke (CS) and atherosclerosis (AS) are closely related diseases. Ferroptosis, a novel form of programmed cell death, may play a key role in CS and AS. However, the pathophysiological mechanisms underlying their coexistence remain unclear.

TaCIPK19-3D Improves Photosynthetic Machinery, Growth, Yield, and Salt Tolerance in Transgenic Rice.

Calcineurin B-like interacting protein kinases (CIPKs) are central regulators of plant development and stress adaptation. However, the specific roles of individual CIPK family members remain largely unexplored in major crops like wheat and rice. In this study, we characterized the function of TaCIPK19-3D through overexpression in transgenic rice and CRISPR-Cas9-mediated oscipk19 knockout lines.

Effect of cognitive flexibility in mindfulness intervention for emotional distress: Two randomized controlled trials.

To examine the mechanistic role of cognitive flexibility in mindfulness intervention for emotional distress (MIED), we conducted two randomized controlled trials. In Study 1, 607 participants experiencing high emotional distress were randomly assigned to either an MIED program group ( = 304) or a waitlist control group ( = 303). Levels of cognitive flexibility, anxiety, depression, and general emotional distress were assessed at baseline (T0), Week 3 (T3), Week 5 (T5), and Week 7 (postintervention, T7).

DR1 activates histone gene expression to maintain pancreatic cancer cell survival through the ATAC complex.

Pancreatic ductal adenocarcinoma (PDAC) is the most malignant cancer and is characterized by short survival and limited treatment options. Epigenetic dysregulation is a defining feature of tumorigenesis but remains elusive in PDAC. Here, we identified DR1 as a vulnerability in PDAC.

Research on self-supervised super resolution restoration algorithm based on reflective micro-scanning optical system.

The features of infrared image such as less details and low SNR become bottleneck of infrared image application. This paper mainly focuses on research of super-resolution restoration algorithm of infrared image based on reflective infrared micro-scanning optical system. Aiming at solving super-resolution restoration problem of infrared image, self-supervised super resolution restoration algorithm is proposed and optimized.

Agonist- and stress-driven compartmentalized phosphoinositide signaling in cells.

Phosphoinositides (PIPs) are essential lipid messengers that regulate cellular responses to external stimuli and stress through spatially organized signaling pathways. In recent years, compartment-specific mechanisms by which PIP signaling integrates diverse cellular processes have been extensively expanded. This review discusses the distinct roles of PIP signaling across cellular compartments, including the plasma membrane, endosomes, lysosomes, protein scaffolds, and the nucleus.

A trend analysis of the burden of lower extremity peripheral arterial disease in China, 1990 to 2021: based on the Global Burden of Disease Study 2021.

The present study provides a thorough trend analysis of the burden of lower extremity peripheral arterial disease (PAD) in China during 1990-2021, based on data from the Global Burden of Disease Study 2021. Lower extremity PAD is an atherosclerotic disease that causes obstruction of blood vessels supplying the legs, presenting as intermittent claudication, rest pain, non - healing wounds, ulcers, or gangrene, and may lead to limb amputation or death due to critical limb ischemia. Our analysis covers prevalence, incidence, mortality, years lived with disability (YLDs), years of life lost (YLLs), and disability - adjusted life years (DALYs).

Cross-domain transformer spatial-temporal fusion network for traffic flow forecasting.

Accurate traffic forecasting is challenging due to the intricate inter-dependencies of road networks and congestion caused by unexpected accidents. Recent work has focused on dynamically changing traffic characteristics but has paid less attention to the global cross-spatial-temporal domain of modeling, which may limit their performance. In this paper, we propose a novel plug-and-play fusion unit to accurately express the spatial-temporal dependencies by cross-domain complementary information integration, named the Cross-Domain Transformer Spatial-Temporal Fusion Network (CDTSTFN).

Stigmatization and discrimination of female tuberculosis patients in Kyrgyzstan - a phenomenological study.

Introduction: The Republic of Kyrgyzstan is among the 30 countries with the highest burden of multidrug-resistant Tuberculosis worldwide. One of the reasons is widespread stigmatization and discrimination. As previous research has shown, particularly women experience stigma while its impact on their life and (mental) health is even greater than for men.

Probiotics and prebiotics in the treatment of functional constipation in the elderly individuals.

Functional constipation (FC) in elderly individuals is a significant health issue that adversely affects their quality of life, with recent studies indicating a close relationship between this condition and gut microbiota dysbiosis. This review aims to explore the role of the gut microbiota in FC in elderly individuals, analyze the mechanisms of the gut-brain axis, and evaluate the potential use of microecological agents, including probiotics and prebiotics, in modulating the gut microbiota and alleviating constipation symptoms. By integrating the latest research findings, this study seeks to provide new perspectives and intervention strategies for the management of FC in elderly individuals.

The poly(A) polymerase Star-PAP is regulated by stably associated phosphoinositide messengers.

Star-PAP is a noncanonical poly(A) polymerase that controls gene expression. Star-PAP was previously reported to bind PIPKI⍺ and its product PI(4,5)P, which regulate Star-PAP activity and expression of specific genes. Recent studies have revealed a nuclear p53-phosphoinositide signaling pathway in which the phosphatidylinositol transfer proteins (PITPs) and phosphoinositide kinases/phosphatases bind p53 to sequentially modify p53-linked phosphoinositides and regulate p53 function.

Nanoparticles-mediated intratumoral gene editing targeting PD-L1 and Galectin-9 for improved cancer immunotherapy.

PD-L1, a typical immune checkpoint expressed on tumor cells, reduces the effectiveness of T cell-mediated killing, which is further aggravated by Galectin-9 (Gal-9) co-expression through the TIM3/Gal-9 pathway. Although immune checkpoint inhibitors have shown promise in cancer therapy, limitations remain including low response rate, systemic toxicities, and the need of frequent treatments. Here, we described a dual knockout approach targeting PD-L1 and Gal-9 in tumor cells, achieved by nanoparticle-assisted CRISPR-Cas9 delivery, aimed at improved cancer immunotherapy.

Parkinson's disease-linked Kir4.2 mutation R28C leads to loss of ion channel function.

Parkinson's disease (PD) is a complex, progressive neurodegenerative disorder driven by multiple pathogenetic factors, including oxidative stress, mitochondria dysfunction, neuroinflammation and ion imbalance. Recent evidence highlights the significant role of potassium channels in the pathophysiology of PD. We recently identified a PD-linked genetic mutation in the KCNJ15 gene (KCNJ15), encoding the inwardly rectifying potassium channel Kir4.

Comparative analysis of epidermal gene expression in mice exposed to deionized water and groundwater.

In our daily life, our skin is frequently exposed to water, which can affect human health. Previous studies have demonstrated that water bathing improves skin conditions in individuals with dermatoses. However, whether groundwater bathing influences epidermal gene expression in normal skin is largely unknown.

Regulation of NRF2 by stably associated phosphoinositides and small heat shock proteins in response to stress.

Reactive oxygen species are generated by aerobic metabolism, and their deleterious effects are buffered by the cellular antioxidant response, which prevents oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of the antioxidant response. Basal levels of NRF2 are kept low by ubiquitin-dependent degradation of NRF2 by E3 ligases, including the Kelch-like ECH-associated protein 1 (KEAP1).

Metagenomic analysis deciphers airborne pathogens with enhanced antimicrobial resistance and virulence factors in composting facilities.

The composting process has been shown to effectively reduce antimicrobial resistance (AMR) in animal manure, but its influence on surrounding airborne AMR remains unknown, particularly with regard to human-pathogenic antibiotic-resistant bacteria (HPARB). In this study, air and paired compost samples were collected from a full-scale composting facility, and the antibiotic resistome, microbiome, and HPARB were systematically analyzed in both two habitats using metagenomic analysis. Current result uncovered the profiles of HPARB in air, showing that significantly more airborne HPARB were assembled than that in compost samples.