Discovery of 4,5-dihydro-benzo[g]indazole-based hydroxamic acids as HDAC3/BRD4 dual inhibitors and anti-tumor agents.

Concurrent inhibition of HDAC and BRD4, two well-established epigenetic targets for anti-tumor therapy, demonstrates the potential to enhance anti-tumor effects synergistically. The present study involves the development of a series of novel HDAC3/BRD4 dual inhibitors, followed by evaluation of their antitumor efficacy against several tumor models. Guided by scaffold hopping strategy, key pharmacophore of BRD4 inhibitor I-BET-151 was incorporated into an in-house developed HDAC3-selective inhibitor 17h.

The Association Between Anthropometric Indices and Overactive Bladder (OAB): A Cross-Sectional Study From the NHANES 2005-2018.

Background: The association between different anthropometric indices, including body mass index (BMI), a body shape index (ABSI), lipid accumulation product (LAP), visceral adiposity index (VAI), waist circumference-triglyceride index (WTI), weight-adjusted waist index (WWI), body roundness index (BRI) and the prevalence of overactive bladder (OAB) is unclear. This investigation aims to explore the association among different anthropometric indices and overactive bladder as well as confounding variables.

Methods: Data were obtained from the USA National Health and Nutrition Examination Survey (NHANES) data set between 2005 and 2018, and 15231 participants were included in the study.

Major adverse events associated with lipid reduction in inclisiran:a pharmacovigilance research of the FAERS database.

Objective: The effectiveness and safety of the short-interfering RNA drug inclisiran in lowering patients' lipoprotein cholesterol levels to lower their risk of cardiovascular disease are presently being investigated. Based on the real-world adverse event report record in the FDA Adverse Event Reporting System, this article explores the occurrence and risk of adverse events during inclisiran treatment.

Research Design And Methods: We retrieved and screened all available data from the Food and Drug Administration website for the period from 2009 to the third quarter of 2023.

Associations between ethylene oxide exposure and chronic bronchitis: results from the NHANES 2013-2018.

Introduction: Ethylene oxide (EtO) is a reactive gas commonly used in the production of various chemical compounds. Research has linked EtO exposure to respiratory conditions, including chronic obstructive pulmonary disease (COPD) and asthma. However, its potential effects on chronic bronchitis (CB) remain unclear, highlighting the need for further study to understand its role in respiratory health.

Toripalimab plus chemotherapy for first line treatment of advanced non-small cell lung cancer (CHOICE-01): final OS and biomarker exploration of a randomized, double-blind, phase 3 trial.

A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.

Comparative analysis of community composition and network structure between phyllosphere endophytic and epiphytic fungal communities of .

The phyllosphere constitutes a critical habitat for microorganisms, exerting profound influences on host vitality, developmental dynamics, reproductive functions, and stress resilience. However, the diversity and network structure of endophytic and epiphytic fungal communities within this microecosystem have not been thoroughly explored. In this investigation, high-throughput sequencing technologies were employed to assess the diversity, community composition, and network structure of endophytic and epiphytic fungal communities associated with across six geographically distinct locations in Southeast China.

Value of metagenomic next-generation sequencing in the diagnosis of native pyogenic spinal infections: a multicenter, retrospective observational study.

Background Context: The etiological diagnosis of pyogenic spinal infection is crucial for its precise antibiotic treatment. Traditional methods of detection are often slow and ineffective. In recent times, metagenomic next-generation sequencing (mNGS) has revolutionized pathogen detection, offering a more effective approach to disease management.

Pharmacokinetics and Bioequivalence Evaluation of Trazodone Hydrochloride Sustained-Release Tablets in Healthy Chinese Volunteers.

The aim of this study was to investigate the pharmacokinetics, bioequivalence, and safety of generic trazodone hydrochloride sustained-release tablet and its reference listed product in healthy Chinese subjects. An open, randomized, single-dose, and 2-period crossover study was involved under fasting and fed conditions, with a 7-day washout period. A single oral dose of 150 mg of 2 trazodone hydrochloride sustained-release tablets was administered to 84 healthy volunteers, with 36 in the fasting group and 48 consuming a high-fat diet, respectively.

Immune regulation: a new strategy for traditional Chinese medicine-based treatment of granulomatous lobular mastitis.

Granulomatous lobular mastitis (GLM) presents significant challenges, including high rates of morbidity, recurrence, and disability, ultimately impacting women's health and quality of life. Local autoimmune imbalance involving dysregulated cytokines and immune cells has been recognized to play a key role in the pathology of GLM. Traditional Chinese medicine (TCM), with its multi-component, multi-pathway and multi-target characteristics, offers unique advantages and broad prospects in the treatment of GLM.

Living photosynthetic microneedle patches for in situ oxygenation and postsurgical melanoma therapy.

Surgical excision remains the principal treatment for melanoma, while tumor recurrence and delayed wound healing often occur due to the residual tumor cells and hypoxic microenvironment in the postoperative skin wounds. Herein, we present a living photosynthetic microneedle (MN) patch (namely MA/CM@MN) loaded with microalgae (MA) and cuttlefish melanin (CM) for postsurgical melanoma therapy and skin wound healing. Benefiting from the oxygenic photosynthesis of the alive MA in the MN base, the MA/CM@MN can generate oxygen under light exposure, thus facilitating skin cell proliferation and protecting cells against hypoxia-induced cell death.

A Comparative Study of Neutron Shielding Performance in Al-Based Composites Reinforced with Various Boron-Containing Particles for Radiotherapy: A Monte Carlo Simulation.

This study aimed to assess and compare the shielding performance of boron-containing materials for neutrons generated in proton therapy and used in boron neutron capture therapy (BNCT). Five composites, including AlB, Al-BC, Al-TiB, Al-BN, and Al-TiB-BN, were selected as shielding materials, with concrete used as a benchmark. The mass fraction of boron compounds in these materials ranged from 10% to 50%.

Long non-coding RNAs: regulators of autophagy and potential biomarkers in therapy resistance and urological cancers.

The non-coding RNAs (ncRNAs) comprise a large part of human genome that mainly do not code for proteins. Although ncRNAs were first believed to be non-functional, the more investigations highlighted tthe possibility of ncRNAs in controlling vital biological processes. The length of long non-coding RNAs (lncRNAs) exceeds 200 nucleotidesand can be present in nucleus and cytoplasm.

A Portable Zn Fluorescence Sensor for Information Storage and Bio-Imaging in Living Cells.

A fluorescence probe (Probe-ITR) was designed and synthesized for the rapid detection of Zn based on the excited state intramolecular proton transfer (ESIPT) mechanism. The specific recognition ability of Probe-ITR to Zn was tested using UV-VIS and fluorescence emission spectroscopy. The results demonstrated a rapid response within 40s upon addition of an appropriate amount of Zn into the mixed solution of the target probe molecules (DMSO/PBS = 5/5).

Retraction Note: MiR-522-3p inhibits proliferation and activation by regulating the expression of SLC31A1 in T cells.

[This retracts the article DOI: 10.1007/s10616-021-00472-5.].

OpenDock: a pytorch-based open-source framework for protein-ligand docking and modelling.

Motivation: Molecular docking is an invaluable computational tool with broad applications in computer-aided drug design and enzyme engineering. However, current molecular docking tools are typically implemented in languages such as C++ for calculation speed, which lack flexibility and user-friendliness for further development. Moreover, validating the effectiveness of external scoring functions for molecular docking and screening within these frameworks is challenging, and implementing more efficient sampling strategies is not straightforward.

C1-FDX is required for the assembly of mitochondrial complex I and subcomplexes of complex V in Arabidopsis.

C1-FDX (Complex I-ferredoxin) has been defined as a component of CI in a ferredoxin bridge in Arabidopsis mitochondria. However, its full function remains to be addressed. We created two c1-fdx mutants in Arabidopsis using the CRISPR-Cas9 methodology.