EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes.

Myelodysplastic Syndromes (MDS) represent a group of heterogeneous myeloid clonal diseases derived from aberrant hematopoietic stem/progenitor cells. Enhancer of zeste homolog 2 (EZH2) is an important regulator in gene expression through methyltransferase-dependent or methyltransferase-independent mechanisms. Herein, we found EZH2 inhibition led to MDS cell pyroptosis through RNA Helicase A (RHA) down-regulation induced overexpression of S100A9, a key regulator of inflammasome activation and pyroptosis.

A novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome.

Background: The dynein cytoplasmic two heavy chain 1 (DYNC2H1) gene encodes a cytoplasmic dynein subunit. Cytoplasmic dyneins transport cargo towards the minus end of microtubules and are thus termed the "retrograde" cellular motor. Mutations in DYNC2H1 are the main causative mutations of short rib-thoracic dysplasia syndrome type III with or without polydactyly (SRTD3).

mHealth Incentivized Adherence Plus Patient Navigation (MIAPP): protocol for a pilot randomized controlled trial to improve linkage and retention on buprenorphine for hospitalized patients with methamphetamine use and opioid use disorder.

Background: Initiation of buprenorphine for treatment of opioid use disorder (OUD) in acute care settings improves access and outcomes, however patients who use methamphetamine are less likely to link to ongoing treatment. We describe the intervention and design from a pilot randomized controlled trial of an intervention to increase linkage to and retention in outpatient buprenorphine services for patients with OUD and methamphetamine use who initiate buprenorphine in the hospital.

Methods: The study is a two-arm pilot randomized controlled trial (N = 40) comparing the mHealth Incentivized Adherence Plus Patient Navigation (MIAPP) intervention to treatment as usual.

Trehalose enhances macrophage autophagy to promote myelin debris clearance after spinal cord injury.

Background: Myelin-laden foamy macrophages accumulate extensively in the lesion epicenter, exhibiting characteristics of autophagolysosomal dysfunction, which leads to prolonged inflammatory responses after spinal cord injury (SCI). Trehalose, known for its neuroprotective properties as an autophagy inducer, has yet to be fully explored for its potential to mitigate foamy macrophage formation and exert therapeutic effects in the context of SCI.

Results: We observed that trehalose significantly enhances macrophage phagocytosis and clearance of myelin in a dose-dependent manner in vitro.

Development and psychometric evaluation of the Brief Parenting Questionnaire.

Background: There is a paucity of brief self-report parenting measures validated for use in low- and middle-income countries (LMICs). We developed the Brief Parenting Questionnaire (BPQ), a 24-item self-report measure for use with parents of children ages 3-12.

Objective: We describe the development and evaluation of the psychometric properties of the BPQ, which was designed to include two subscales: warm and responsive parenting (WRP) and harsh parenting (HP).

Molecular and cellular characteristics of cerebrovascular cell types and their contribution to neurodegenerative diseases.

Many diseases and disorders of the nervous system suffer from a lack of adequate therapeutics to halt or slow disease progression, and to this day, no cure exists for any of the fatal neurodegenerative diseases. In part this is due to the incredible diversity of cell types that comprise the brain, knowledge gaps in understanding basic mechanisms of disease, as well as a lack of reliable strategies for delivering new therapeutic modalities to affected areas. With the advent of single cell genomics, it is now possible to interrogate the molecular characteristics of diverse cell populations and their alterations in diseased states.

Ambient air pollution and Alzheimer's disease and other dementias: a global study between 1990 and 2019.

Background: Emerging research found air pollution may be associated with incident Alzheimer's disease (AD) and other dementias. However, few studies have examined these associations at the global scale. This study aimed to assess the dynamic associations between ambient air pollution and the burden of AD and other dementias worldwide.

Prediction of pulmonary function decline in fibrous interstitial lung abnormalities based on quantitative chest CT parameters.

Background: Interstitial lung abnormalities (ILA) are a proposed imaging concept. Fibrous ILA have a higher risk of progression and death. Clinically, computed tomography (CT) examination is a frequently used and convenient method compared with pulmonary function tests.

The relationship between sarcopenia and mental health status in Chinese older adults: the mediating role of activities of daily living.

Background: Most existing studies focus on either the relationship between sarcopenia and depressive symptoms or sarcopenia and cognitive functions. Few studies have examined depressive symptoms and cognitive functions simultaneously. This study aimed to analyze the relationship between sarcopenia and both depressive symptoms and cognitive functions in the elderly by introducing activities of daily living to explore the mediating role of activities of daily living between sarcopenia and mental health.

Sub-micrometer scale synchrotron x-ray fluorescence measurements of trace elements in teeth compared with laser ablation inductively coupled plasma mass spectrometry.

Background: Elemental analysis of teeth allows for exposure assessment during critical windows of development and is increasingly used to link early life exposures and health. The measurement of inorganic elements in teeth is challenging; laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is the most widely used technique.

Objective: Both synchrotron x-ray fluorescence (SXRF) and LA-ICP-MS have the capability to measure elemental distributions in teeth with each having distinct advantages and disadvantages.

Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.

Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC resilience to inflammatory stress.

A deep learning analysis for dual healthcare system users and risk of opioid use disorder.

The opioid crisis has disproportionately affected U.S. veterans, leading the Veterans Health Administration to implement opioid prescribing guidelines.

Engaging Patients in Discussions About Medication Deprescribing.

Background: Deprescribing, intentional medication discontinuation or dose reduction, can reduce potentially inappropriate medication use and medication-related harms. Engaging patients in deprescribing discussions may increase likelihood of deprescribing and promote shared decision-making.

Objective: To examine the impact of patient-directed educational brochures on patient engagement and deprescribing discussions with primary care providers (PCPs).

pH-sensitive nano-drug delivery systems dual-target endothelial cells and macrophages for enhanced treatment of atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory disease characterized by vascular endothelial dysfunction. In the early stage of the disease, endothelial cell injury induces the infiltration of inflammatory macrophages, which secrete large amounts of inflammatory factors, further aggravating endothelial cell dysfunction and exacerbating the disease. Therefore, it is promising for co-targeting endothelial cells and macrophages further regulating the inflammatory microenvironment and endothelial cell function for effective treatment.

Racial and Ethnic Disparities in Hospital Breastfeeding Care in the US.

Objectives: This study examines the associations between race and ethnicity and receipt of Baby Friendly Hospital Initiative (BFHI) key clinical practices that support breastfeeding in US hospitals.

Methods: National data from 2016 to 2019 CDC PRAMS were analyzed. Our sample included 60,395 mothers who initiated breastfeeding with healthy, term newborns.

Determining the status of tertiary lymphoid structures in invasive pulmonary adenocarcinoma based on chest CT radiomic features.

Objectives: The aim of this study was to determine the status of tertiary lymphoid structures (TLSs) using radiomic features in patients with invasive pulmonary adenocarcinoma (IA).

Methods: In this retrospective study, patients with IA from November 2015 to March 2024 were recruited from two independent centers (center 1, training and internal test data set; center 2, external test data set). TLS was divided into two groups according to hematoxylin-eosin staining.

Medical management pathways for Cushing's disease in pituitary tumors centers of excellence (PTCOEs).

Purpose: A recent update of consensus guidelines for the management of Cushing's disease (CD) included indications for medical therapy. However, there is limited evidence regarding their implementation in clinical practice. This study aimed to evaluate current medical therapy approaches by expert pituitary centers through an audit conducted to validate the criteria of Pituitary Tumors Centers of Excellence (PTCOEs) and provide an initial standard of medical care for CD.

Hallmark discoveries in the biology of non-Wilms tumour childhood kidney cancers.

Approximately 20% of paediatric and adolescent/young adult patients with renal tumours are diagnosed with non-Wilms tumour, a broad heterogeneous group of tumours that includes clear-cell sarcoma of the kidney, congenital mesoblastic nephroma, malignant rhabdoid tumour of the kidney, renal-cell carcinoma, renal medullary carcinoma and other rare histologies. The differential diagnosis of these tumours dates back many decades, when these pathologies were identified initially through clinicopathological observation of entities with outcomes that diverged from Wilms tumour, corroborated with immunohistochemistry and molecular cytogenetics and, subsequently, through next-generation sequencing. These advances enabled near-definitive recognition of different tumours and risk stratification of patients.

Enhanced energy storage in antiferroelectrics via antipolar frustration.

Dielectric-based energy storage capacitors characterized with fast charging and discharging speed and reliability play a vital role in cutting-edge electrical and electronic equipment. In pursuit of capacitor miniaturization and integration, dielectrics must offer high energy density and efficiency. Antiferroelectrics with antiparallel dipole configurations have been of significant interest for high-performance energy storage due to their negligible remanent polarization and high maximum polarization in the field-induced ferroelectric state.

Generative AI as a tool to accelerate the field of ecology.

The emergence of generative artificial intelligence (AI) models specializing in the generation of new data with the statistical patterns and properties of the data upon which the models were trained has profoundly influenced a range of academic disciplines, industry and public discourse. Combined with the vast amounts of diverse data now available to ecologists, from genetic sequences to remotely sensed animal tracks, generative AI presents enormous potential applications within ecology. Here we draw upon a range of fields to discuss unique potential applications in which generative AI could accelerate the field of ecology, including augmenting data-scarce datasets, extending observations of ecological patterns and increasing the accessibility of ecological data.

Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway.

The inflammatory response of lung tissue and abnormal proliferation of pulmonary artery smooth muscle cells are involved in the pathogenesis of high-altitude pulmonary hypertension (HAPH). Halofuginone (HF), an active ingredient derivative of Chang Shan (Dichroa febrifuga Lour. [Hydrangeaceae]), has antiproliferative, antihypertrophic, antifibrotic, and other effects, but its protective effects on HAPH remains unclear.

Construction of a rodent neural network-skeletal muscle assembloid that simulate the postnatal development of spinal cord motor neuronal network.

Neuromuscular diseases usually manifest as abnormalities involving motor neurons, neuromuscular junctions, and skeletal muscle (SkM) in postnatal stage. Present in vitro models of neuromuscular interactions require a long time and lack neuroglia involvement. Our study aimed to construct rodent bioengineered spinal cord neural network-skeletal muscle (NN-SkM) assembloids to elucidate the interactions between spinal cord neural stem cells (SC-NSCs) and SkM cells and their biological effects on the development and maturation of postnatal spinal cord motor neural circuits.

CARD domains mediate anti-phage defence in bacterial gasdermin systems.

Caspase recruitment domains (CARDs) and pyrin domains are important facilitators of inflammasome activity and pyroptosis. Following pathogen recognition by nucleotide binding-domain, leucine-rich, repeat-containing (NLR) proteins, CARDs recruit and activate caspases, which, in turn, activate gasdermin pore-forming proteins to induce pyroptotic cell death. Here we show that CARD domains are present in defence systems that protect bacteria against phage.