Design, Synthesis, and Biological Evaluation of 3,4-Dihydroisoquinolin-1()-one Derivatives as Protein Arginine Methyltransferase 5 Inhibitors for the Treatment of Non-Hodgkin's Lymphoma.

Through catalyzing the transfer of methyl groups onto the guanidinium of arginine, protein arginine methyltransferase 5 (PRMT5) was essential to the cell growth of cancer cells. By utilizing a scaffold hopping strategy, a novel series of 3,4-dihydroisoquinolin-1()-one derivatives were designed and synthesized. Through a systematic SAR study, demonstrated excellent PRMT5 inhibitory activity, potent antiproliferative activity against Z-138, favorable pharmacokinetic profiles, and low hERG toxicity.

Design, Synthesis, and Biological Activities Evaluation of Type I FLT3 Inhibitors for the Treatment of Acute Myeloid Leukemia.

The abnormal overexpression of FLT3 kinase is intimately associated with pathogenesis of acute myeloid leukemia (AML), positioning FLT3 inhibitors as pivotal therapeutic agents. Despite the availability of three FDA-approved FLT3 inhibitors, their clinical utility is hampered by resistance stemming from tyrosine kinase domain (TKD) mutations. Through an integrative analysis of case studies, we identified a potential advantage of type I FLT3 inhibitors in overcoming TKD mutation-induced resistance.

Consumption of plant sterols-enriched soy milk with a healthy dietary pattern diet lowers blood pressure in adults with metabolic syndrome: A randomized controlled trial.

Background & Aims: Plant sterols (PS) have been shown to lower blood lipid-lipoproteins concentrations and may serve as a potential functional ingredient for cardiovascular disease (CVD) risk management. However, there are limited studies examining this effect in individuals with metabolic syndrome (MetS). The aim of this study was to evaluate the effects of PS-enriched food consumption as part of a healthy dietary pattern (HDP) on blood pressure and endothelial function in Singaporean adults with MetS.

Exploring observed and instructed mHealth use in the middle-aged and elderly people (MAEP): A social learning perspective.

Objective: Based on social learning theory, this study aimed to explore the intention of middle-aged and elderly people (MAEP) to engage with mobile health (mHealth) and the underlying effects of usability and utility. The goal was to garner insights that could enhance the advancement of mHealth and improve the scope of benefits of mHealth use among MAEP in the future.

Methods: We employed a survey-based approach to delve into the mHealth use intentions among MAEP individuals aged 45 and above.

Identification of novel PHGDH inhibitors based on computational investigation: an all-in-one combination strategy to develop potential anti-cancer candidates.

Objective: Biological studies have elucidated that phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in the serine synthesis pathway in humans that is abnormally expressed in numerous cancers. Inhibition of the PHGDH activity is thought to be an attractive approach for novel anti-cancer therapy. The development of structurally diverse novel PHGDH inhibitors with high efficiency and low toxicity is a promising drug discovery strategy.

Automation and machine learning augmented by large language models in a catalysis study.

Recent advancements in artificial intelligence and automation are transforming catalyst discovery and design from traditional trial-and-error manual mode into intelligent, high-throughput digital methodologies. This transformation is driven by four key components, including high-throughput information extraction, automated robotic experimentation, real-time feedback for iterative optimization, and interpretable machine learning for generating new knowledge. These innovations have given rise to the development of self-driving labs and significantly accelerated materials research.

Active substance and mechanisms of Actinidia chinensis Planch for the treatment of breast cancer was explored based on network pharmacology and in silico study.

In this paper, our objective was to investigate the potential mechanisms of Actinidia chinensis Planch (ACP) for breast cancer treatment with the application of network pharmacology, molecular docking, and molecular dynamics. "Mihoutaogen" was used as a key word to query the Traditional Chinese Medicine Systems Pharmacology database for putative ingredients of ACP and its related targets. DrugBank, GeneCards, Online Mendelian Inheritance in Man, and therapeutic target databases were used to search for genes associated with "breast cancer.

Impact of Brewers' Spent Grain-Containing Biscuit on Postprandial Glycaemic Response in Individuals with Metabolic Syndrome: A Crossover Randomised Controlled Trial.

Brewers' spent grain (BSG) is a fibre and protein-rich by-product of beer-brewing. Fermenting BSG with can further increase its content of soluble fibre, protein and certain antioxidants. Since nutrients rich in BSG can improve postprandial glycaemic response, this study assessed the postprandial glucose response (PPGR) and postprandial insulin response (PPIR) controlling effect of consuming 30% wheat flour substituted biscuits with autoclaved BSG (ABSG) or fermented BSG (FBSG) in individuals with metabolic syndrome (MetS).

Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging.

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor (), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes.

Breaking-Down Tumoral Physical Barrier by Remotely Unwrapping Metal-Polyphenol-Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy-Induced Immune Response.

The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here a remotely unwrapping strategy is proposed of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO).

A biomimetic phototherapeutic nanoagent based on bacterial double-layered membrane vesicles for comprehensive treatment of oral squamous cell carcinoma.

As one of the most common malignancies, oral squamous cell carcinoma (OSCC) with high rates of invasiveness and metastasis threatens people's health worldwide, while traditional therapeutic approaches have not met the requirement of its cure. Phototherapies including photothermal therapy (PTT) and photodynamic therapy (PDT) have shown great potential for OSCC treatment due to their noninvasiveness or minimal invasiveness, high selectivity and little tolerance. However, PTT or PDT alone makes it difficult to eradicate OSCC and prevent its metastasis and recurrence.

Analysis of Zinc and Stromal Immunity in Disuse Osteoporosis: Mendelian Randomization and Transcriptomic Analysis.

Objective: Disuse osteoporosis is known to be primarily caused by a lack of exercise. However, the causal relationships between zinc and immunity and disuse osteoporosis remain unknown. This study investigated these relationships and their potential mechanisms.

Understanding older adults' smartphone addiction in the digital age: empirical evidence from China.

Background: Despite the fact that an increasing number of older adults are addicted to smartphones, the existing addiction literature still focuses primarily on adolescents. To address this issue, this study draws from the perspectives of subjective cognitive decline and family relationship conflict to examine older adults' smartphone addiction based on their key characteristics.

Methods: This study investigates the effects of subjective cognitive decline and family relationship conflict on older adults' smartphone addiction through a survey of 371 subjects in China.

Risk prediction of placenta previa based on the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy.

Objectives: To explore the relationship between the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy and placenta previa.

Material And Methods: A prospective cohort study of women who underwent pregnancy examination in Weifang People's Hospital or Sunshine Union Hospital from January 2020 to June 2021. The distance from the lower edge of the gestational sac to the internal cervical os was measured at 5-6 weeks' gestation.

A geomagnetic vector compensation method compatible with nonlinear interferences based on back propagation network and 3D Helmholtz coil.

Magnetic interferential compensation plays a vital role in geomagnetic vector measurement applications. Traditional compensation accounts for only the permanent interferences, induced field interferences, and eddy-current interferences. However, nonlinear magnetic interferences are found, which also have a great impact on measurement, and it cannot be fully characterized by a linear compensation model.

Enhanced β-glucosidase in Western flower thrips affects its interaction with the redox-based strategies of kidney beans under elevated CO.

β-Glucosidase is validated as an elicitor for early immune responses in plants and it was detected in the salivary glands of Frankliniella occidentalis in previous research. Seven differentially expressed genes encoding β-glucosidase were obtained by comparing the transcriptomes of F. occidentalis adults grown under two different CO concentrations (800 vs.

Wide-Range Linear Iontronic Pressure Sensor with Two-Scale Random Microstructured Film for Underwater Detection.

A broad linear range of ionic flexible sensors (IFSs) with high sensitivity is vital to guarantee accurate pressure acquisition and simplify back-end circuits. However, the issue that sensitivity gradually decreases as the applied pressure increases hinders the linearity over the whole working range and limits its wide-ranging application. Herein, we design a two-scale random microstructure ionic gel film with rich porosity and a rough surface.

Engineering mitochondrial uncoupler synergistic photodynamic nanoplatform to harness immunostimulatory pro-death autophagy/mitophagy.

Generally, autophagy/mitophagy, as a highly conserved lysosomal-based catabolic pathway, compromises the photodynamic therapy (PDT) efficiency by increasing the adaptation of tumor cells toward reactive oxygen species (ROS)-triggered protein damages and mitochondrial destruction. On the other hand, excessively activated autophagy/mitophagy cascades can provoke autophagic cell death and promote the endogenous antigens release of dying cells, thus playing a vital role in initiating the antitumor immune responses. To harness the exquisite immunomodulating effect of pro-death autophagy/mitophagy, we rationally constructed a MnO shell-coated multifunctional porphyrinic metal-organic framework (MOF) to load carbonyl cyanide 3-chlorophenylhydrazone (CCCP).

Prediction of 2D IV-VI semiconductors: auxetic materials with direct bandgap and strong optical absorption.

Auxetic materials are highly desirable for advanced applications because of their negative Poisson's ratios, which are rather scarce in two-dimensional materials. Motivated by the elemental mutation method, we predict a new class of monolayer IV-VI semiconductors, namely, δ-IV-VI monolayers (GeS, GeSe, SiS and SiSe). Distinctly different from the previously predicted IV-VI monolayers, the newly predicted δ-MX (X = Ge and Si; M = S and Se) monolayers exhibit a puckered unit cell with a space group of 2.

Exploring the Association between Glutathione Metabolism and Ferroptosis in Osteoblasts with Disuse Osteoporosis and the Key Genes Connecting them.

Disused osteoporosis is a kind of osteoporosis, a common age-related disease. Neurological disorders are major risk factors for osteoporosis. Though there are many studies on disuse osteoporosis, the genetic mechanisms for the association between glutathione metabolism and ferroptosis in osteoblasts with disuse osteoporosis are still unclear.