Restraint of TGFβ family signaling by SMAD7 is necessary for hematopoietic stem cell maturation in the embryo.

Hematopoietic stem cells (HSCs), defined as cells that can engraft an adult when transplanted, mature from precursors (pre-HSCs) that differentiate from hemogenic endothelial cells (HECs) in the embryo. Many signaling pathways required to generate the first hematopoietic stem and progenitor cells in the embryo are well-characterized, but how HSCs mature from pre-HSCs is poorly understood. Here we show that "mothers against decapentaplegic homolog 7" (SMAD7), a negative regulator of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) signaling, is required for pre-HSC to HSC maturation.

ABCDEF Bundle Implementation for Improved Respiratory Failure Outcomes.

Acute respiratory failure (ARF) is a severe condition frequently treated in intensive care units (ICUs) worldwide. ARF presents a spectrum of outcomes, from immediate complications to long-term impacts. This literature review examines the implementation of the ABCDEF bundle to address the complex pathophysiology of ARF.

Bromelain enhances nitric oxide bioavailability: Bradykinin's link to TRPV1/Ca /AMPK/autophagy signaling.

Bromelain, a protease enzyme extracted from the pineapple stem, is suggested to protect against atherosclerosis, non-alcohol fatty liver diseases, and coagulation dysfunction. However, the mechanism underlying the vascular protection of bromelain in the cardiovascular system is not fully understood. In this study, we explored the role of the kininogen-bradykinin system in bromelain-mediated nitric oxide (NO) bioavailability in endothelial cells (ECs).

Rac1 signaling mediates the protection of apigenin against hepatic lipid accumulation and insulin resistance.

Obesity-related metabolic disorders, including non-alcoholic fatty liver disease (NAFLD) and insulin resistance, are increasingly prevalent worldwide, yet effective therapeutic strategies remain limited. Recent research has highlighted the potential of natural compounds in mitigating metabolic dysfunction. Apigenin (Api), a plant-derived flavonoid, has been recognized for its anti-inflammatory, antioxidant, and anti-cancer properties; however, its role in regulating hepatic lipid metabolism and insulin sensitivity remains incompletely understood.

HMGB1 Regulates Adipocyte Lipolysis via Caveolin-1 Signaling: Implications for Metabolic and Cardiovascular Diseases.

High-mobility group box 1 (HMGB1) is a nuclear protein that can be secreted or released into the extracellular environment during cellular stress, functioning as a damage-associated molecular pattern molecule. This study investigates the role of HMGB1 in adipocyte development and metabolism, explicitly examining its interaction with β3-adrenergic receptor-mediated lipolysis and caveolin-1 (CAV1) regulation, which may influence cardiovascular risk factors. Using 3T3-L1 preadipocytes and mouse embryonic fibroblasts, we demonstrated that HMGB1 expression increases progressively during adipogenesis, reaching peak levels in mature adipocytes.

A Machine Learning Model for Predicting Breast Cancer Recurrence and Supporting Personalized Treatment Decisions Through Comprehensive Feature Selection and Explainable Ensemble Learning.

Purpose: This study investigates the efficiency of a machine learning model integrating least absolute shrinkage and selection operator (LASSO) feature selection with ensemble learning in predicting recurrence risk and supporting personalized treatment decisions in breast cancer patients.

Materials And Methods: Clinical data from 1,131 breast cancer patients (1,056 nonrecurrent and 75 recurrent) were collected from Kaohsiung Medical University Hospital's electronic health record system. After preprocessing and standardization, LASSO was applied for feature selection.

The neuronal GPCR OCTR-1 modulates longevity responses to both warm and cold temperatures.

Many animal species live longer in cold climates than in warm climates, which was traditionally explained using the rate of living theory, i.e., higher temperatures increase chemical reaction rates, thus speeding up the aging process.

Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring.

High-risk neuroblastoma, a leading cause of pediatric cancer mortality, exhibits substantial intratumoral heterogeneity, contributing to therapeutic resistance. To understand tumor microenvironment evolution during therapy, we longitudinally profiled 22 patients with high-risk neuroblastoma before and after induction chemotherapy using single-nucleus RNA and ATAC sequencing and whole-genome sequencing. This revealed profound shifts in tumor and immune cell subpopulations after therapy and identified enhancer-driven transcriptional regulators of neuroblastoma neoplastic states.

STAT1-mediated interferon signatures are associated with preclinical JAK inhibitor sensitivity in T-ALL.

We used single-cell genomics to characterize a patient with T-cell acute lymphoblastic leukemia treated in the Children's Oncology Group AALL0434 trial with poor clinical outcome despite favorable genomic features, identifying a STAT1-mediated interferon-related transcriptional signature and inflammatory microenvironment associated with sensitivity to small-molecule JAK inhibition.

Single-cell panleukemia signatures of HSPC-like blasts predict drug response and clinical outcome.

The critical role of leukemia-initiating cells as a therapy-resistant population in myeloid leukemia is well established. However, the molecular signatures of such cells in acute lymphoblastic leukemia remain underexplored. Moreover, their role in therapy response and patient prognosis is yet to be systematically investigated across various types of acute leukemia.

Atypical antipsychotics impair the lipid-lowering and pleiotropic effects of simvastatin via activation of the ADMA-NOX-ROS pathway.

Patients with schizophrenia receiving atypical antipsychotics have an increased risk of metabolic syndrome; however, the efficacy of statins in mitigating cardiovascular risks in these patients remains unclear. This study examined the effects of typical and atypical antipsychotics on the lipid-lowering efficacy of statins in schizophrenia patients and investigated the underlying mechanisms of simvastatin action in hepatocytes and endothelial cells (ECs). A retrospective analysis revealed that statins were less effective in lowering LDL levels in patients on atypical antipsychotics.

Reactive Axillary Lymphadenopathy Among Different COVID-19 Vaccines: A Retrospective Study in Breast Sonography.

During the coronavirus disease 2019 (COVID-19) outbreak, reactive lymphadenopathy after vaccination is a major concern in breast sonography, especially for patients with a history of breast cancer. The state-of-the-art literature on clinical and sonographic findings either examines a small volume of cases or limited types of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. This study is aimed at providing vast clinical information to facilitate breast sonographic examination for participants who underwent recent SARS-CoV-2 vaccination.

Targeting senescent stemlike subpopulations in Philadelphia chromosome-like acute lymphoblastic leukemia.

Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) is driven by genetic alterations that induce constitutive kinase signaling and is associated with chemoresistance and high relapse risk in children and adults. Preclinical studies in the most common CRLF2-rearranged/JAK pathway-activated Ph-like ALL subtype have revealed variable responses to JAK inhibitor-based therapies, suggesting incomplete oncogene addiction and highlighting a need to elucidate alternative biologic dependencies and therapeutic vulnerabilities, whereas the ABL-class Ph-like ALL subtype seems preferentially sensitive to SRC/ABL- or PDGFRB-targeting inhibitors. Which patients may be responsive vs resistant to tyrosine kinase inhibitor (TKI)-based precision medicine approaches remains a critical knowledge gap.

A multiomic atlas identifies a treatment-resistant, bone marrow progenitor-like cell population in T cell acute lymphoblastic leukemia.

Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to curing T cell acute lymphoblastic leukemia (T-ALL). While tumor heterogeneity has been implicated in treatment failure, the cellular and genetic factors contributing to resistance and relapse remain unknown. Here we linked tumor subpopulations with clinical outcome, created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic analysis to a diverse cohort of 40 T-ALL cases.

Identification and Characterization of Chemotherapy-Resistant High-Risk Neuroblastoma Persister Cells.

Relapse rates in high-risk neuroblastoma remain exceedingly high. The malignant cells that are responsible for relapse have not been identified, and mechanisms of therapy resistance remain poorly understood. In this study, we used single-nucleus RNA sequencing and bulk whole-genome sequencing to identify and characterize the residual malignant persister cells that survive chemotherapy from a cohort of 20 matched diagnosis and definitive surgery tumor samples from patients treated with high-risk neuroblastoma induction chemotherapy.

Correction: Chen et al. Bromelain Ameliorates Atherosclerosis by Activating the TFEB-Mediated Autophagy and Antioxidant Pathways. 2023, , 72.

In the original publication [...

Establishment and risk factor assessment of the abnormal body temperature probability prediction model (ABTP) for dairy cattle.

The study aims to develop an abnormal body temperature probability (ABTP) model for dairy cattle, utilizing environmental and physiological data. This model is designed to enhance the management of heat stress impacts, providing an early warning system for farm managers to improve dairy cattle welfare and farm productivity in response to climate change. The study employs the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to analyze environmental and physiological data from 320 dairy cattle, identifying key factors influencing body temperature anomalies.

Attributional styles are associated with care burden in geriatric depression: older adults and their caregivers in Taiwan.

Background: Given the rising prevalence of depression among older adults and the associated increase in caregiving responsibilities, understanding factors influencing caregiver burden is crucial. Previous research has not extensively explored the impact of caregivers' attributional styles, that is, how individuals interpret the causes of life events, on their care burden.

Aim: This study examined the relationship between caregivers' attributional styles and their care burden for older patients with depression.

Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging.

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes.

Transient receptor potential vanilloid 1 interacts with Toll-like receptor 4 (TLR4)/cluster of differentiation 14 (CD14) signaling pathway in lipopolysaccharide-mediated inflammation in macrophages.

Transient receptor potential vanilloid 1 (TRPV1), a ligand-gated cation channel, is a receptor for vanilloids on sensory neurons and is also activated by capsaicin, heat, protons, arachidonic acid metabolites, and inflammatory mediators on neuronal or non-neuronal cells. However, the role of the TRPV1 receptor in pro-inflammatory cytokine secretion and its potential regulatory mechanisms in lipopolysaccharide (LPS)-induced inflammation has yet to be entirely understood. To investigate the role and regulatory mechanism of the TRPV1 receptor in regulating LPS-induced inflammatory responses, bone marrow-derived macrophages (BMDMs) harvested from wild-type (WT) and TRPV1 deficient (Trpv1) mice were used as the cell model.

A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.

Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities to adult glioma, it is increasingly recognized as a molecularly distinct, yet highly heterogeneous disease. In this study, we longitudinally profiled a molecularly diverse cohort of 16 pHGG patients before and after standard therapy through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of the tumor microenvironment during progression following treatment.

Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance.

Fetuin-A, a hepatokine secreted by hepatocytes, binds to insulin receptors and consequently impairs the activation of the insulin signaling pathway, leading to insulin resistance. Apigenin, a flavonoid isolated from plants, has beneficial effects on insulin resistance; however, its regulatory mechanisms are not fully understood. In the present study, we investigated the molecular mechanisms underlying the protective effects of apigenin on insulin resistance.