TRα1 mutant suppresses KLF9 to cause endometrial metaplasia with ectopic IL-33 expression leading to uterine fibrosis and infertility.

Thyroid hormone receptors (TRs) mediate the genomic actions of thyroid hormone. Mutations of THRA gene cause a human disease known as resistance to thyroid hormone (RTHα). We created a mouse model expressing a dominant negative mutated TRα1 (Thra1 mice) that exhibits growth retardation, bone abnormalities, constipation, and anemia, as found in RTHα patients.

Nucleolin-targeted silicon-based nanoparticles for enhanced chemo-sonodynamic therapy of diffuse large B-cell lymphoma.

The limited selectivity and high systemic toxicity of traditional chemotherapy hinder its efficacy in treating diffuse large B-cell lymphoma (DLBCL). The combination of sonodynamic therapy (SDT) with chemotherapy has emerged as a novel strategy for cancer treatment, aiming to improve therapeutic outcomes and reduce systemic toxicity. However, challenges such as elevated drug clearance rates and non-selecitivity remain to be resolved.

Fiber length distribution characterizes the brain network maturation during early school-age.

Environmental and social changes during early school age have a profound impact on brain development. However, it remains unclear how the brains of typically-developing children adjust white matter to optimize network topology during this period. This study proposes fiber length distribution as a novel nodal metric to capture the continuous maturation of brain network.

Prenatal p25-activated Cdk5 induces pituitary tumorigenesis through MCM2 phosphorylation-mediated cell proliferation.

Aberrant expression of cyclin-dependent kinase 5 (Cdk5) has been reported in pituitary adenomas. However, the role of Cdk5 in the tumorigenesis remains unclear. We show that prenatal p25-activated Cdk5 phosphorylates minichromosome maintenance protein 2 (Mcm2), enhancing minichromosome maintenance (MCM) family proteins and driving intermediate lobe-located melanotrope-originated pituitary tumorigenesis.

Identifying and Validating Extracellular Matrix-Related Gene CTSH in Diabetic Foot Ulcer Using Bioinformatics and Machine Learning.

Background: Diabetic foot ulcer (DFU) is a serious clinical problem with high amputation and mortality rates, yet there is a lack of desirable therapy. While the extracellular matrix (ECM) contributes significantly to wound healing, ECM-related biomarker for DFU is still unknown. The study was designed to identify ECM-related biomarker in DFU using bioinformatics and machine learning and validate it in STZ-induced mice models.

Development of Personalized Strategies for Precisely Battling Malignant Melanoma.

Melanoma is the most severe and fatal form of skin cancer, resulting from multiple gene mutations with high intra-tumor and inter-tumor molecular heterogeneity. Treatment options for patients whose disease has progressed beyond the ability for surgical resection rely on currently accepted standard therapies, notably immune checkpoint inhibitors and targeted therapies. Acquired resistance to these therapies and treatment-associated toxicity necessitate exploring novel strategies, especially those that can be personalized for specific patients and/or populations.

Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1.

Introduction: The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remain uncertain, warranting further research.

Methods: A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group.

Mitochondria-Targeted Prodrug Nanoassemblies for Efficient Ferroptosis-Based Therapy via Devastating Ferroptosis Defense Systems.

Ferroptosis is a form of regulated cell death accompanied by lipid reactive oxygen species (ROS) accumulation in an iron-dependent manner. However, the efficiency of tumorous ferroptosis was seriously restricted by intracellular ferroptosis defense systems, the glutathione peroxidase 4 (GPX4) system, and the ubiquinol (CoQH) system. Inspired by the crucial role of mitochondria in the ferroptosis process, we reported a prodrug nanoassembly capable of unleashing potent mitochondrial lipid peroxidation and ferroptotic cell death.

The Function of NK Cells in Tumor Metastasis and NK Cell-Based Immunotherapy.

Metastatic tumors cause the most deaths in cancer patients. Treating metastasis remains the primary goal of current cancer research. Although the immune system prevents and kills the tumor cells, the function of the immune system in metastatic cancer has been unappreciated for decades because tumors are able to develop complex signaling pathways to suppress immune responses, leading them to escape detection and elimination.

PTEN phosphatase inhibits metastasis by negatively regulating the Entpd5/IGF1R pathway through ATF6.

encodes a tumor suppressor with lipid and protein phosphatase activities whose dysfunction has been implicated in melanomagenesis; less is known about how its phosphatases regulate melanoma metastasis. We demonstrate that PTEN expression negatively correlates with metastatic progression in human melanoma samples and a PTEN-deficient mouse melanoma model. Wildtype PTEN expression inhibited melanoma cell invasiveness and metastasis in a dose-dependent manner, behaviors that specifically required PTEN protein phosphatase activity.

Microbial Fertilization Improves Soil Health When Compared to Chemical Fumigation in Sweet Lily.

Lanzhou Lily( var. , which is also known as sweet lily in China, is used as a type of food. This lily is distributed in narrow regions, propagates asexually, cultivates perennially, and cultivates commonly in serious consecutive replant problems (CRPs).

PTEN Dual Lipid- and Protein-Phosphatase Function in Tumor Progression.

PTEN is the second most highly mutated tumor suppressor in cancer, following only p53. The PTEN protein functions as a phosphatase with lipid- and protein-phosphatase activity. PTEN-lipid-phosphatase activity dephosphorylates PIP3 to form PIP2, and it then antagonizes PI3K and blocks the activation of AKT, while its protein-phosphatase activity dephosphorylates different protein substrates and plays various roles in tumorigenesis.

Evaluation of the Safety and Immunogenicity of Duck-Plague Virus Mutants.

Duck plague (DP) is an acute infectious disease in the duck industry. The duck plague virus (DPV) is the pathogen, a subfamily of . gE is a type I membrane protein that contains three parts: an extracellular domain, a transmembrane domain, and a cytoplasmic domain.

UL11 Protein Is a Key Participant of the Duck Plague Virus in Its Life Cycle.

Tegument protein UL11 plays a critical role in the life cycle of herpesviruses. The UL11 protein of herpesviruses is important for viral particle entry, release, assembly, and secondary envelopment. Lipid raft is cholesterol-rich functional microdomains in cell membranes, which plays an important role in signal transduction and substance transport.

PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN.

Targeting mutant BRAF in patients with melanomas harboring this oncogene has been highly successful as a first-line treatment, but other mutations may affect its efficacy and alter the route of acquired resistance resulting in recurrence and poor prognosis. As an evolving strategy, melanoma treatment needs to be expanded to include targets based on newly discovered emerging molecules and pathways. We here show that PERK plays a critical role in BRAF inhibitor-acquired resistance in melanoma with impaired PTEN.

Targeting the SHP2 phosphatase promotes vascular damage and inhibition of tumor growth.

The tyrosine phosphatase SHP2 is oncogenic in cancers driven by receptor-tyrosine-kinases, and SHP2 inhibition reduces tumor growth. Here, we report that SHP2 is an essential promoter of endothelial cell survival and growth in the remodeling tumor vasculature. Using genetic and chemical approaches to inhibit SHP2 activity in endothelial cells, we show that SHP2 inhibits pro-apoptotic STAT3 and stimulates proliferative ERK1/2 signaling.

Clinicopathological features, risk factors, and outcomes of immunoglobulin A nephropathy associated with hepatitis B virus infection.

Background: Hepatitis B virus (HBV) infections are associated with an increased risk of kidney diseases. However, the effects of HBV infection on the prognosis of immunoglobulin A nephropathy (IgAN) are unclear.

Methods: A total of 838 patients with biopsy-confirmed IgAN were enrolled in this retrospective cohort study.

One-pot Synthesis of Pd/Azo-polymer as an Efficient Catalyst for 4-Nitrophenol Reduction and Suzuki-Miyaura Coupling Reaction.

The porous polymer matrix with good stability and confined microenvironment is considered as ideal support to stabilize isolated metal centers for catalysis. Herein, we report a "one-pot" method to prepare a kind of palladium complexed with azo porous organic polymer nanospheres (Pd-azo-POPs). The method combines the synthesis of azo-POPs with the reduction of the Pd ion, where azo serves as an anchoring group to limit the growth of Pd.

The association between platelet indices and cardiovascular events in chronic kidney disease patients without dialysis.

Purpose: Previous studies have indicated that platelet indices are related to the pathogenesis of cardiovascular diseases (CVD). However, it is unclear which platelet-related indicators are associated with CVD events in patients with chronic kidney disease (CKD) without dialysis.

Methods: We performed a single-center prospective cohort study involved 1391 CKD patients to explore the relationship between platelet indices and CVD events in CKD patients.

Heterologous prime-boost: an important candidate immunization strategy against Tembusu virus.

Background: Tembusu virus (TMUV), a newly emerging pathogenic flavivirus, spreads rapidly between ducks, causing massive economic losses in the Chinese duck industry. Vaccination is the most effective method to prevent TMUV. Therefore, it is urgent to look for an effective vaccine strategy against TMUV.

In situ surface-derivation of AgPdMo/MoS nanowires for synergistic hydrogen evolution catalysis in alkaline solution.

Metallic sulfides have emerged as highly active, durable, and robust electrocatalysts for the electrocatalytic hydrogen evolution reaction (HER) due to their intriguing electronic and catalytic properties. One of the important strategies to further enhance their HER performance is to build multimetallic nanostructures by tuning the electronic state. Here we combine multimetallic structures and metal sulfides, and report an efficient strategy for the in situ surface-derivation of molybdenum sulfide nanosheets (MoS NSs) on Ag-Pd-Mo alloy nanowires (AgPdMo NWs) to form AgPdMo/MoS NWs.