JAK activity regulates mesoderm cell fate by controlling MESP1 expression.

Cardiac development requires precise gene expression programs at each developmental stage guided by multiple signaling pathways and transcription factors (TFs). MESP1 is transiently expressed in mesoderm, and is essential for subsequent cardiac development, while the precise mechanism regulating its own transcription and mesoderm cell fate is not fully understood. Therefore, we developed a high content screen assay to identify regulators of MESP1 expression in mesodermal cells differentiated from human pluripotent stem cells (hPSCs).

Role of GDF-15 in diabetic nephropathy: mechanisms, diagnosis, and therapeutic potential.

Purpose: Growth differentiation factor 15 (GDF-15) is a cytokine involved in regulating homeostasis, and its expression is up-regulated in response to injury, stress, and inflammation. This study explored the role of GDF-15 in diabetic nephropathy (DN), a severe complication of diabetes mellitus, and its potential as a biomarker for disease progression.

Methods: As a member of the transforming growth factor-β superfamily, GDF-15 exhibits its renal protective functions primarily through its anti-inflammatory effects and the up-regulation of other renal protective factors.

Obstructive Tracheobronchitis in Influenza-Associated Pulmonary Aspergillosis.

We report a bronchoscopic image of a 36-year-old with significant airway obstruction from obstructive tracheobronchitis secondary to invasive pulmonary aspergillosis. It is rare to see such a severe form of obstructive tracheobronchitis, likely caused by the patient'sp immunocompromised status and rapid progression nature of influenza-associated pulmonary aspergillosis.

Porous Photocrosslinkable Hydrogel Functionalized with USC Derived Small Extracellular Vesicles for Corpus Spongiosum Repair.

Reconstruction of a full-thickness spongy urethra is difficult because a corpus spongiosum (CS) defect cannot be repaired using self-healing or substitution urethroplasty. Small extracellular vesicles (sEVs) secreted by urine-derived stem cells (USC-sEVs) strongly promote vascular regeneration. In this study, it is aimed to explore whether USC-sEVs promote the repair of CS defects.

Hydrogen sulfide produced by the gut microbiota impairs host metabolism via reducing GLP-1 levels in male mice.

Dysbiosis of the gut microbiota has been implicated in the pathogenesis of metabolic syndrome (MetS) and may impair host metabolism through harmful metabolites. Here, we show that Desulfovibrio, an intestinal symbiont enriched in patients with MetS, suppresses the production of the gut hormone glucagon-like peptide 1 (GLP-1) through the production of hydrogen sulfide (HS) in male mice. Desulfovibrio-derived HS is found to inhibit mitochondrial respiration and induce the unfolded protein response in intestinal L cells, thereby hindering GLP-1 secretion and gene expression.

NAD metabolism-related genes provide prognostic value and potential therapeutic insights for acute myeloid leukemia.

Introduction: Acute myeloid leukemia (AML) is an aggressive blood cancer with high heterogeneity and poor prognosis. Although the metabolic reprogramming of nicotinamide adenine dinucleotide (NAD) has been reported to play a pivotal role in the pathogenesis of acute myeloid leukemia (AML), the prognostic value of NAD metabolism and its correlation with the immune microenvironment in AML remains unclear.

Methods: We utilized our large-scale RNA-seq data on 655 patients with AML and the NAD metabolism-related genes to establish a prognostic NAD metabolism score based on the sparse regression analysis.

GPRC5A promotes gallbladder cancer metastasis by upregulating TNS4 via the JAK2-STAT3 pathway.

Aberrant expression of G protein-coupled receptor class C group 5 member A (GPRC5A) has been reported in multiple cancers and is closely related to patient prognosis. However, the mechanistic role of GPRC5A in gallbladder cancer (GBC) remains unclear. Here, we determined tumor expression levels of GPRC5A and the molecular mechanisms by which GPRC5A regulates gallbladder cancer metastasis.

Sensory ASIC3 channel exacerbates psoriatic inflammation via a neurogenic pathway in female mice.

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

Background: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.

Methods: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.

Early Diagnosis of Colorectal Cancer Based on Bisulfite-free Site-specific Methylation Identification PCR Strategy: High-Sensitivity, Accuracy, and Primary Medical Accessibility.

Due to its decade-long progression, colorectal cancer (CRC) is most suitable for population screening to achieve a significant reduction in its incidence and mortality. DNA methylation has emerged as a potential marker for the early detection of CRC. However, the current mainstream methylation detection method represented by bisulfite conversion has issues such as tedious operation, DNA damage, and unsatisfactory sensitivity.

A dual-energy computed tomography-based radiomics nomogram for predicting time since stroke onset: a multicenter study.

Objectives: We aimed to develop and validate a radiomics nomogram based on dual-energy computed tomography (DECT) images and clinical features to classify the time since stroke (TSS), which could facilitate stroke decision-making.

Materials And Methods: This retrospective three-center study consecutively included 488 stroke patients who underwent DECT between August 2016 and August 2022. The eligible patients were divided into training, test, and validation cohorts according to the center.

Effects of the "AI-TA" Mobile App With Intelligent Design on Psychological and Related Symptoms of Young Survivors of Breast Cancer: Randomized Controlled Trial.

Background: Young women often face substantial psychological challenges in the initial years following cancer diagnosis, leading to a comparatively lower quality of life than older survivors. While mobile apps have emerged as potential interventions, their effectiveness remains inconclusive due to the diversity in intervention types and variation in follow-up periods. Furthermore, there is a particular dearth of evidence regarding the efficacy of these apps' intelligent features in addressing psychological distress with these apps.

The associations between nutritional status and physical frailty and Alzheimer's disease plasma biomarkers in older cognitively unimpaired adults with positive of amyloid-β PET.

Background & Aims: It has been revealed good nutritional status and no physical frailty, which are modifiable lifestyle factors, are linked to less cognitive decline and a lower risk of Alzheimer's disease (AD). We aimed to investigate the associations between nutritional status and physical frailty and plasma AD biomarkers, especially the Tau-associated biomarkers in older cognitively unimpaired (CU) adults with higher β-amyloid (Aβ) burden.

Methods: The nutritional status and physical frailty were assessed via Mini-Nutritional Assessment Short-Form (MNA-SF) and Fried frailty index.

Cannabinoid receptor 2 selective agonist alleviates systemic sclerosis by inhibiting Th2 differentiation through JAK/SOCS3 signaling.

Systemic sclerosis (SSc) poses a significant challenge in autoimmunology, characterized by the development of debilitating fibrosis of skin and internal organs. The pivotal role of dysregulated T cells, notably the skewed polarization toward Th2 cells, has been implicated in the vascular damage and progressive fibrosis observed in SSc. In this study, we explored the underlying mechanisms by which cannabinoid receptor 2 (CB2) highly selective agonist HU-308 restores the imbalance of T cells to alleviate SSc.

The prognostic impact of tumor location in nonmuscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing Chinese multicenter and SEER registries.

Objective: Most bladder cancers are nonmuscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach.

Targeting Super-Enhancer-Driven Transcriptional Dependencies Suppresses Aberrant Hedgehog Pathway Activation and Overcomes Smoothened Inhibitor Resistance.

Aberrant activation of the Hedgehog (Hh) signaling pathway plays important roles in oncogenesis and therapeutic resistance in several types of cancer. The clinical application of FDA-approved Hh-targeted smoothened inhibitors (SMOi) is hindered by the emergence of primary or acquired drug resistance. Epigenetic and transcriptional-targeted therapies represent a promising direction for developing improved anti-Hh therapies.

Amino acids-based deep eutectic solvents as additives for improved enantioseparation in capillary electrophoresis.

In this study, several amino acids deep eutectic solvents were prepared using L-valine and L-leucine as hydrogen bond acceptors, and L-lactic acid and glycerol as hydrogen bond donors. These amino acids' deep eutectic solvents were first used as buffer additives to construct several synergistic systems along with maltodextrin in capillary electrophoresis for the enantioseparations of four racemic drugs. Compared with single maltodextrin system, the separations of model drugs in the synergistic systems were significantly improved.