A combinatorial screening protocol for identifying novel and highly potent dual-target inhibitor of BRD4 and STAT3 for kidney cancer therapy.

Concurrent inhibition of bromodomain-containing protein 4 ( signal transductor and activator of transcription 3 (STAT3) could potentially be an effective strategy against renal cell carcinoma (RCC). Here, we successfully identified five dual-targeted BRD4/STAT3 inhibitors (BSTs 1-5) using a combinatorial screening protocol. Particularly, BST-4 was the most potent inhibitor simultaneously targeting BRD4 (IC = 2.

GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis.

Sarcoidosis is a complex inflammatory disease with a strong genetic component. Here, we perform a genome-wide association study in 9755 sarcoidosis cases to identify risk loci and map associated genes. We then use transcriptome-wide association studies and enrichment analyses to explore pathways involved in sarcoidosis and use Mendelian randomization to examine associations with modifiable factors and circulating biomarkers.

Highly Active Oxygen Evolution Integrating with Highly Selective CO-to-CO Reduction.

Artificial carbon fixation is a promising pathway for achieving the carbon cycle and environment remediation. However, the sluggish kinetics of oxygen evolution reaction (OER) and poor selectivity of CO reduction seriously limited the overall conversion efficiencies of solar energy to chemical fuels. Herein, we demonstrated a facile and feasible strategy to rationally regulate the coordination environment and electronic structure of surface-active sites on both photoanode and cathode.

Pharmacokinetics, Pharmacodynamics, and Safety Evaluation of the Novel HIF-PH Inhibitor Enarodustat: An Open-Label Phase I Study in Healthy Chinese Participants.

Background And Objectives: Enarodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor. We evaluated the pharmacokinetics, pharmacodynamics, and safety profile of domestic enarodustat (SAL-0951) and analyzed the influence of ethnic factors.

Methods: In this phase I study, healthy Chinese participants received single and multiple oral doses (1, 5, and 15 mg) of SAL-0951 while in a fasted state.

Hepatic stellate cells control liver zonation, size and functions via R-spondin 3.

Hepatic stellate cells (HSCs) have a central pathogenetic role in the development of liver fibrosis. However, their fibrosis-independent and homeostatic functions remain poorly understood. Here we demonstrate that genetic depletion of HSCs changes WNT activity and zonation of hepatocytes, leading to marked alterations in liver regeneration, cytochrome P450 metabolism and injury.

Exploration of crucial stromal risk genes associated with prognostic significance and chemotherapeutic opportunities in invasive ductal breast carcinoma.

Background: Few studies revealed that stromal genes regulate the tumor microenvironment (TME). However, identification of key-risk genes in the invasive ductal breast carcinoma-associated stroma (IDBCS) and their associations with the prediction of risk group remains lacking.

Methods: This study used the GSE9014, GSE10797, GSE8977, GSE33692, and TGGA BRCA datasets.

Zhizichi decoction alleviates depressive-like behaviors through modulating mitochondria-associated membrane via the IP3R3-GRP75-VDAC1 complex.

Ethnopharmacological Relevance: Zhizichi Decoction (ZZCD), a traditional Chinese medicine (TCM), is derived from the combination of Gardenia jasminoides J.Ellis [Rubiaceae] and Semen Sojae Praeparatum, a fermented derivative of Glycine max (L.) Merr.

Innovative Construction and Application of Bile Duct Organoids: Unraveling the Complexity of Bile Duct Diseases and Potential Therapeutic Strategies.

The biliary system is crucial for liver function, regulating bile production, secretion, and transport. Dysfunctions within this system can lead to various diseases, such as cholangiopathies and biliary fibrosis, which may progress from benign to malignant states like cholangiocarcinoma. While liver organoid research is well-established and technologically advanced, bile duct organoids (BDOs) offer significant potential.

Preparation of the conjugated hypercrosslinked polymers containing phenylenediamine and phenylenetriamine derivatives for fluorescent sensing of three nitrophenols.

Hypercrosslinked polymers (HCPs) are the most promising porous organic polymers for large-scale production due to their easy preparation, extensive raw material source, good stability, and large specific surface area. However, due to the lack of extended conjugability, their application in fluorescence sensing is limited. Herein, three conjugated hypercrosslinked polymers (the conjugated HCPs: TPPDA-DMB, TDPAB-DMB, and MTDAB-DMB) were easily prepared by the Friedel-Craft arylation reactions with phenylenediamine or phenylenetriamine derivatives and p-dimethoxybenzene (DMB).

Optimized microwave absorption and thermal properties for TiB@BN/PDMS composites via TiB@BN heterogeneous interface engineering.

The single electromagnetic (EM) wave loss mechanism leads to suboptimal microwave absorption in dielectric materials, whereas, introducing different materials and constructing distinctive microstructures can significantly improve microwave absorption. In this study, TiB and TiB@BN powders were synthesized using boron thermal reduction and chemical solution methods. Their microwave absorption and thermal properties were systematically analyzed.

A review-based estimation of GHG emissions of China's wastewater management system.

Under China's "Dual Carbon Goal", the wastewater treatment system plays a crucial role in the country's efforts to reduce greenhouse gas (GHG) emissions. However, a lack of baseline emissions data poses challenges for decarbonization efforts. This study aims to profile and diagnose the GHG emissions of China's entire wastewater system and identify key contributing factors.

A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis.

Interstitial lung disease (ILD) consists of a group of immune-mediated disorders that can cause inflammation and progressive fibrosis of the lungs, representing an area of unmet medical need given the lack of disease-modifying therapies and toxicities associated with current treatment options. Tissue-specific splice variants (SVs) of human aminoacyl-tRNA synthetases (aaRSs) are catalytic nulls thought to confer regulatory functions. One example from human histidyl-tRNA synthetase (HARS), termed HARS because the splicing event resulted in a protein encompassing the WHEP-TRS domain of HARS (a structurally conserved domain found in multiple aaRSs), is enriched in human lung and up-regulated by inflammatory cytokines in lung and immune cells.

Fish requires FasL to facilitate CD8+ T-cell function and antimicrobial immunity.

Although bony fish have CD8+ T cells, the mechanisms by which these early-evolved cytotoxic cells combat intracellular pathogens remain unclear. In the present study, using Nile tilapia as a model, we investigated the detailed function, mechanism, and evolutionary pattern concerning CD8+ T cells. By depleting CD8+ T cells, they are found essential in combating Edwardsiella piscicida infection.

Comparing oncologic outcomes of partial and radical nephrectomy for T2 renal cell carcinoma: a propensity score matching cohort study and an external multicenter validation.

Purpose: There is very limited evidence on the optimal surgical treatment for patients with larger T2 renal tumors. This study aims to evaluate the oncologic outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) in T2 renal cell carcinoma (RCC).

Methods: A retrospective data analysis was conducted on T2 RCC patients who underwent PN or RN between 2004 and 2019 using the SEER database, and validated with data from multiple centers in China from 2014 to 2019.

A General Strategy for Exceptionally Robust Conducting Polymer-Based Bioelectrodes with Multimodal Capabilities Through Decoupled Charge Transport Mechanisms.

Bioelectrodes function as a critical interface for signal transduction between living organisms and electronics. Conducting polymers (CPs), particularly poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate), are among the most promising materials for bioelectrodes, due to their electrical performance, high compactness, and ease of processing, but often suffer from degradation or de-doping even in some common environments (e.g.

Design Strategies of S Molecule Cathodes for Room-Temperature Na-S Batteries.

Sodium-sulfur batteries have been provided as a highly attractive solution for large-scale energy storage, benefiting from their substantial storage capacity, the abundance of raw materials, and cost-effectiveness. Nevertheless, conventional sodium-sulfur batteries have been the subject of critique due to their high operating temperature and costly maintenance. In contrast, room-temperature sodium-sulfur batteries exhibit significant advantages in these regards.

Tryptophan Metabolic Enzyme IL4I1 Inhibits Ferroptosis by Decreasing Ubiquitination of Nrf2 via I3P in Glioblastoma.

Glioblastoma multiforme (GBM) is the deadliest brain tumour with an extremely poor prognosis. Tryptophan catabolism could enhance an array of protumour-genic signals and promoted tumour progression in GBM. However, the mechanisms of oncogenic signalling under tryptophan catabolism and potential therapy targeting this pathway have not been completely understood.

Geniposidic acid inhibits OVA-induced asthma by suppressing allergic airway inflammation and regulating gut microbiota.

Asthma is a serious chronic inflammatory disease of the respiratory system. In this study, we aimed to explore the role of geniposidic acid (GPA) in ovalbumin (OVA)-induced asthma in mice and to clarify its underlying mechanism. The mice were divided into control group, OVA group, OVA+GPA (12.

Nomograms of risk prediction and prognosis for the T1-T2 stage gastric cancer with lymph node metastasis: a population-based study.

Background And Aims: Lymph node metastasis plays a crucial role in determining the appropriate treatment approach for patients with gastric cancer (GC), particularly those in the T1-T2 stage. Currently available diagnostic strategies for GC with lymph nodes have limited accuracy. The present research aimed to create and validate diagnostic and prognostic nomograms specifically tailored for the T1-T2 stage GC patients with LNM.

Intracranial vessel wall enhancement scoring system for monitoring disease activity and neuropsychiatric impairment in systemic lupus erythematosus.

Objectives: To establish an intracranial vessel wall enhancement (VWE) scoring system and evaluate its potential as a protocol for monitoring systemic lupus erythematosus (SLE) disease activity and neuropsychiatric impairment.

Materials And Methods: In this retrospective study, fifty patients with SLE underwent conventional MRI and high-resolution magnetic resonance vascular wall imaging (HR-VWI) at three tertiary hospitals between August 2022 and December 2023. We analyzed VWE distribution in intracranial arteries, developed a scoring system based on enhancement patterns, and examined the relationship between VWE scores, disease activity, and cognitive function.

Mitochondria-targeted nanovesicles for ursodeoxycholic acid delivery to combat neurodegeneration by ameliorating mitochondrial dysfunction.

Mitochondria are pivotal in sustaining oxidative balance and metabolic activity within neurons. It is well-established that mitochondrial dysfunction constitutes a fundamental pathogenic mechanism in neurodegeneration, especially in the context of Parkinson's disease (PD), this represents a promising target for therapeutic intervention. Ursodeoxycholic acid (UDCA), a clinical drug used for liver disease, possesses antioxidant and mitochondrial repair properties.

Clinical and functional significance of SPATA2 in cancer particularly in LIHC.

Spermatogenesis-associated protein 2 (SPATA2) is primarily named for its important role in spermatogenesis. Its function in tumorigenesis remains elusive. Here, we used various bioinformatic tools to systematically analyze the expression patterns of SPATA2 in cancers, the correlation of SPATA2 expression with clinical parameters, genetic variation, methylation, phosphorylation, immune infiltration and immune therapy.

Clinical features and outcomes of congenital anterior urethrocutaneous fistula: A case series study.

Objective: To evaluate the clinical features and prognosis of congenital anterior urethrocutaneous fistulas (CAUF) patients.

Methods: This is a retrospective chart review of patients diagnosed with CAUF and underwent surgical repair by the author between October 2017 and December 2021 that was performed at a single tertiary-care institution. The medical records of CAUF patients were reviewed to evaluate their clinical characteristics and outcomes.