Enhancement of nutritional quality of chickpea flour by solid-state fermentation for improvement of in vitro antioxidant activity and protein digestibility.

The nutritional properties, anti-nutritional factors, and in vitro digestion characteristics of chickpeas after solid-state fermentation (SSF) with autochthonous microorganisms were investigated. Two strains (P.pentosaceus LFSBB12 & P.

Intrinsic Capacity and Instrumental Activity of Daily Living Among Community Dwelling Elderly in China: The Mediating Effect of Two-Way Social Support and Sense of Coherence.

Objectives: To explore the influence of intrinsic capacity (IC) on instrumental activities of daily living (IADL) among community-dwelling elderly and to analyze the chain-mediated effects of two-way social support, and sense of coherence (SOC).

Design: This study was a cross-sectional research design. Participants were recruited from September 2023 to December 2023 from Hangzhou City, Zhejiang Province, China, using a multistage sampling method.

Discovery of the First BRD4 Second Bromodomain (BD2)-Selective Inhibitors.

Pan-BD2 inhibitors have been shown to retain an antileukemia effect and display less dose-limiting toxicities than pan-BET inhibitors. However, it is necessary to consider the potential off-target toxicity associated with the inhibition of four BET BD2 proteins. To date, no BRD4 BD2 domain selective inhibitor has been reported.

Micheliolide ameliorates severe acute pancreatitis in mice through potentiating Nrf2-mediated anti-inflammation and anti-oxidation effects.

Severe acute pancreatitis (SAP) is an acute inflammatory injury disease with significant mortality rate and currently without effective strategy being available. Inflammation and oxidative stress play central roles in the etiology of SAP. Micheliolide (MCL), an active monomeric component isolated from Michelia champaca, has been proved its multiple therapeutic properties including anti-inflammatory, antioxidant and anti-cancer.

A 3'UTR-derived small RNA represses pneumolysin synthesis and facilitates pneumococcal brain invasion.

Pneumolysin (Ply) of Streptococcus pneumoniae (pneumococcus) at relatively high and low levels facilitates pneumococcal invasion into the lung and brain, respectively; however, the regulatory mechanisms of Ply expression are poorly understood. Here, we find that a small RNA plyT, processed from the 3'UTR of the ply operon, is expressed higher in anaerobically- than in statically-cultured pneumococcus D39. Using bioinformatic, biochemical and genetic approaches, we reveal that PlyT inhibits Ply synthesis and hemolytic activities by pairing with an RBS-embedded intergenic region of the ply operon.

Copper overload exacerbates testicular aging mediated by lncRNA:CR43306 deficiency through ferroptosis in Drosophila.

Testicular aging manifests as impaired spermatogenesis and morphological alterations in Drosophila. Nonetheless, the comprehensive molecular regulatory framework remains largely undisclosed. This investigation illustrates the impact of copper overload on testicular aging and underscores the interplay between copper overload and lncRNA.

Regulation mechanism of endoplasmic reticulum stress on metabolic enzymes in liver diseases.

The endoplasmic reticulum (ER) plays a pivotal role in protein folding and secretion, Ca storage, and lipid synthesis in eukaryotic cells. When the burden of protein synthesis and folding required to be handled exceeds the processing capacity of the ER, the accumulation of misfolded/unfolded proteins triggers ER stress. In response to short-term ER stress, the unfolded protein response (UPR) is activated to allow cells to survive.

Cellular Senescence in Acute Liver Injury: What Happens to the Young Liver?

Cellular senescence, characterized by irreversible cell cycle arrest, not only exists in age-related physiological states, but has been found to exist in various diseases. It plays a crucial role in both physiological and pathological processes and has become a trending topic in global research in recent years. Acute liver injury (ALI) has a high incidence worldwide, and recent studies have shown that hepatic senescence can be induced following ALI.

Glutathione Modified silicon-doped Carbon Quantum dots as a Sensitive Fluorescent Probe for ClO Detection.

A selective and sensitive fluorescence method for hypochlorite (ClO) was designed using glutathione (GSH) modified silicon-doped carbon quantum dots (GSH@Si-CDs). Then a dual emission ratio fluorescence probe (RF-probe) was obtained based on carbodiimide-activated coupling reaction between GSH and Si-CDs. i.

Discovery of a Promising CBP/p300 Degrader XYD129 for the Treatment of Acute Myeloid Leukemia.

The epigenetic target CREB (cyclic-AMP responsive element binding protein) binding protein (CBP) and its homologue p300 were promising therapeutic targets for the treatment of acute myeloid leukemia (AML). Herein, we report the design, synthesis, and evaluation of a class of CBP/p300 PROTAC degraders based on our previously reported highly potent and selective CBP/p300 inhibitor . Among the compounds synthesized, (XYD129) demonstrated high potency and formed a ternary complex between CBP/p300 and CRBN (AlphaScreen).

Small diameter vascular grafts: progress on electrospinning matrix/stem cell blending approach.

The exploration of the next-generation small diameter vascular grafts (SDVGs) will never stop until they possess high biocompatibility and patency comparable to autologous native blood vessels. Integrating biocompatible electrospinning (ES) matrices with highly bioactive stem cells (SCs) provides a rational and promising solution. ES is a simple, fast, flexible and universal technology to prepare extracellular matrix-like fibrous scaffolds in large scale, while SCs are valuable, multifunctional and favorable seed cells with special characteristics for the emerging field of cell therapy and regenerative medicine.

Construction of an Exercise Intervention Program for Patients with Sarcopenic Obesity: A Delphi Method Study.

Purpose: Construct an exercise intervention program for patients with sarcopenic obesity.

Material And Methods: Based on the COM-B theoretical model and evidence-based principles, the program was constructed using qualitative methods of literature analysis and Delphi method. The Delphi panel consisted of 15 experts from the fields of clinical medicine, rehabilitation medicine, medical technology, and nursing.

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes.

Discovery of Highly Potent and Efficient CBP/p300 Degraders with Strong Antitumor Activity.

The transcriptional coactivator cAMP response element binding protein (CREB)-binding protein (CBP) and its homologue p300 have emerged as attractive therapeutic targets for human cancers such as acute myeloid leukemia (AML). Herein, we report the design, synthesis, and biological evaluation of a series of cereblon (CRBN)-recruiting CBP/p300 proteolysis targeting chimeras (PROTACs) based on the inhibitor CCS1477. The representative compounds (XYD190) and (XYD198) potently inhibited the growth of AML cells with low nanomolar IC values and effectively degraded CBP and p300 proteins in a concentration- and time-dependent manner.

JAK3/STAT5 signaling-triggered upregulation of PIK3CD contributes to gastric carcinoma development.

Gastric cancer (GC) is one of the most common solid cancers with high incidence and mortality worldwide. Chronic gastritis and consequent inflammatory microenvironment is known as a major cause leading to gastric carcinogenesis. Here we report that PIK3CD that encodes p110δ, a catalytic subunit of the class IA PI3Ks, is overexpressed and tumorigenic in GC and associated with tumor inflammatory microenvironment.

SP1 Mediated PIK3CB Upregulation Promotes Gastric Carcinogenesis.

PIK3CB, one of catalytic subunits of PI3Ks kinase family, is implicated in several cellular processes such as cell growth, proliferation, mobility and neoplastic transformation. Its abnormal expression has been found in several human cancer types. However, the regulation pattern and function of PIK3CB in gastric cancer (GC) are still unclear.

The Fibrosis-5 Index Predicts Major Adverse Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

This study aimed to evaluate the fibrosis-5 (FIB-5) index as a marker of liver fibrosis for major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A total of 406 STEMI patients were enrolled in the study. Over an average follow-up of 27 months, 143 of the patients developed MACE.

A Ratio Fluorescence Method Based on Dual Emissive Copper Nanoclusters for the Detection of Vanillin.

In this study, a novel double-emission fluorescence probe at 340 and 400 nm was synthesized by one-pot method using phenylalanine (Phe) and ascorbic acid (AA) as stabilizing and reducing agents. It was found that the fluorescence intensity of the probe at 400 nm could be controlled by controlling the temperature within a certain range, and the ratio of double-emission fluorescence probe could be further regulated. Under the optimal conditions, the fluorescence intensity at 340 nm decreased significantly, while it only showed a slight decrease at 400 nm, which constituted the ratio fluorescence probe.

Optimization of the synthesis of BET BD2 selective inhibitor XY153.

XY153 is a promising BET BD2 inhibitor with an IC value of 0.79 nM against BRD4 BD2. It shows 354-fold selectivity over BRD4-BD1 and 6-fold selectivity over other BET BD2 domains.

Alterations in urinary microbiota composition in urolithiasis patients: insights from 16S rRNA gene sequencing.

Objectives: To investigate the urinary microbiota composition in urolithiasis patients compared to healthy controls and to identify potential microbial markers and their association with clinical parameters.

Methods: A total of 66 samples, comprising 45 from urolithiasis patients and 21 from healthy controls, were analyzed. 16S rRNA gene sequencing was employed to determine the microbiota composition.

The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition.

Background: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility.

Discovery of a potent and selective CBP bromodomain inhibitor (Y08262) for treating acute myeloid leukemia.

The bromodomain of CREB (cyclic-AMP response element binding protein) binding protein (CBP) is an epigenetic "reader" and plays a key role in transcriptional regulation. CBP bromodomain is considered to be a promising therapeutic target for acute myeloid leukemia (AML). Herein, we report the discovery of a series of 1-(indolizin-3-yl)ethan-1-one derivatives as potent, and selective CBP bromodomain inhibitors focused on improving cellular potency.

Sensitive Detections of Sodium Dichloroisocyanurate and Rosmarinic Acid by Polyvinylpyrrolidone Coated Copper Nanoclusters.

In this article, the water-soluble blue-light-emitting copper nanoclusters (CuNCs) were prepared by polyvinylpyrrolidone (PVP) and ascorbic acid as templating and reducing agents, respectively. The optimization of synthesis conditions of PVP-CuNCs were studied and analyzed. And the quantum yield of the PVP-CuNCs was calculated to be 14.

Characteristics and risk of interstitial lung disease in dermatomyositis and polymyositis: a retrospective cohort study in Japan.

Dermatomyositis and polymyositis are rare, idiopathic inflammatory myopathies. Interstitial lung disease is one of the most common and potentially severe extra-muscular manifestations of dermatomyositis and polymyositis and is strongly linked to poor prognosis and early mortality. We aimed to characterise the demographic and clinical characteristics, incidence, and treatment of interstitial lung disease in patients with dermatomyositis or polymyositis.