Network pharmacology and experimental analysis reveal Ethyl caffeate delays osimertinib resistance in lung cancer by suppression of MET.

Background: Fei Yanning Formula (FYN) is extensively applied in clinical lung cancer treatment. However, the specific active constituents and targets of its therapeutic effects remain unclear.

Objective: The study aims to explore the active constituents and mechanism of FYN in delaying osimertinib resistance by network pharmacology analysis and experimental verification.

Switchable Divergent Photocatalytic C-Glycosylation of Glycosyl Benzoates.

Metabolically robust C-glycosides are crucial in various biological and medical applications, underscoring the need for efficient synthesis methods. While radical C-glycosylation reactions are known for their reliability and functional group tolerance, challenges such as glycosyl donor stability and atom economy persist. In this study, we investigate the underexplored potential of condition-controlled divergent synthesis of C-glycosides through a switchable photocatalytic C-glycosylation strategy, involving reductive anomeric C-O bond cleavage.

Trimethylamine-N-oxide enhances drought tolerance in Eucalyptus by increasing photosynthesis.

Drought stress significantly reduces agricultural productivity, threatening global food security and timber production. Although trimethylamine-N-oxide (TMAO) has been shown to enhance drought tolerance in plants such as Arabidopsis thaliana and tomato, the physiological and molecular mechanisms by which it regulates drought tolerance in plants remain unclear. In this study, we investigated the physiological and transcriptomic changes in Eucalyptus under drought stress following exogenous TMAO treatment.

DNA Origami Scaffold-Based Peptide-Major Histocompatibility Complex Multimers for Spatial Imaging of T Cells.

Visualizing the spatial distribution of antigen-specific T cells is essential for understanding immune responses and improving therapeutic strategies. However, detecting low-affinity antigen-specific T cells and enhancing signals from low-abundance populations remain challenging due to limitations in sensitivity. Here, we report DNA origami scaffold-based peptide-major histocompatibility complex multimers (DOS-pMHCs) with precise spatial organization of pMHC and signaling molecules on the nanoscale for enhanced in situ visualization of antigen-specific T cells.

Fatty acid metabolism shapes immune responses in chronic lymphocytic leukemia.

Background: Fatty acids serve as a crucial energy source for tumor cells during the progression of chronic lymphocytic leukemia (CLL). The present study aims to elucidate the characteristics of fatty acid metabolism (FAM) in CLL, construct a related prognostic score, and investigate the regulatory role and mechanisms of FAM in CLL development.

Methods: Bulk RNA sequencing data from CLL patients and healthy controls were analyzed to identify differentially expressed fatty acid metabolic genes.

Identification of sex-biased and gonadal developmental miRNAs during critical windows of early gonadal differentiation in the Chinese giant salamander (Andrias davidianus).

The Chinese giant salamander (CGS), Andrias davidianus, the largest living amphibian, is of significant conservation importance for its wild populations and serves as a valuable economic species in aquaculture. Given that male CGS are larger than female, understanding the mechanisms behind gonadal differentiation and development is critical for optimizing production in aquaculture. This study conducted small RNA-seq on male and female gonads during two key differentiation windows in CGS.

Optical Nonreciprocity Based on the Four-Wave Mixing Effect in Semiconductor Quantum Dots.

Optical nonreciprocity and nonreciprocal devices such as optical diodes have broad and promising applications in various fields, ranging from optical communication to signal process. Here, we propose a magnet-free nonreciprocal scheme based on the four-wave mixing (FWM) effect in semiconductor quantum dots (SQDs). Via controlling the directions of the coupling fields, the probe field can achieve high transmission in the forward direction within a certain frequency range due to the FWM effect.

Topology Identification of Weighted Complex Networks Under Intermittent Control and Its Application in Neural Networks.

Topology identification of stochastic complex networks is an important topic in network science. In modern identification techniques under a continuous framework, the controller has a negative dynamic gain (feedback gain), such that stochastic LaSalle's invariance principle (SLIP) is directly satisfied. In this article, the topology identification of stochastic complex networks is studied under aperiodic intermittent control (AIC).

piRNA28846 has the potential to be a novel RNA nucleic acid drug for ovarian cancer.

Conventional targeted therapies primarily rely on small molecules and proteins. However, they often struggle to enter specific protein conformations, which limits their therapeutic effectiveness. In contrast, RNA therapy is emerging as a more precise and effective targeting strategy.

High-frequency ultrasound induced the preparation of oxidized low density lipoprotein.

Foam cells have been frequently used in studies related to atherosclerosis. Traditional methods for inducing oxidized low-density lipoprotein (oxLDL) involve copper ion (Cu) treatment, which has inherent limitations such as prolonged oxidation times and residual copper ions. This study explored high-frequency ultrasound (400 kHz) as an alternative method for LDL oxidization.

Predictive Modeling of Endograft Limb Occlusion After Endovascular Aneurysm Repair: A Propensity Score Matching Analysis.

Background: Endovascular aneurysm repair (EVAR) is widely used to treat abdominal aortic aneurysm (AAA). However, it carries the risk of complications that often require further interventions. Endograft limb occlusion (ELO), though relatively rare, significantly affects patient outcomes.

Stacking-Dependent Correlated Gap and Kondo Peak in the Heterophase Bilayer with Picometer-Level Interlayer Shift.

Two-dimensional heterojunctions provide a versatile platform for exploring various quantum properties. Here, we create bilayer 1T/2H-NbSe heterophase junctions and realize two types of stacking configurations with picometer-level lattice shifts. By high-resolution scanning tunneling microscopy/spectroscopy, we found that the electronic states are highly dependent on the stacking configurations of the 1T layer on the 2H one.

Differential regulation of reproduction and molting by juvenile hormone in aphids.

Insects rely on juvenile hormones to regulate various physiological processes, including reproduction and molting; currently eight forms of this hormone are known. In most insects, only JH Ⅲ is synthesized. Meanwhile, aphids produce JH Ⅲ and JH Ⅲ skipped bisepoxide (JHSB).

Use quercetin for pulmonary fibrosis: a preclinical systematic review and meta-analysis.

Background: Pulmonary fibrosis (PF) is an age-related interstitial lung disease, which lacks effective drug treatment at present. Quercetin has been shown to have favorable anti-inflammatory and anti-fibrotic properties, and preliminary evidence suggests its potential efficacy and tolerability in PF patients. However, a comprehensive systematic review and evaluation of the protective effects and potential mechanisms of quercetin in PF models remains to be completed.

Functional identification of the diterpene synthases exploring the landscape of diterpene structural diversity in Isodon.

The genus Isodon is recognized as a primary source for the production of ent-kaurane-type diterpenes and previous studies predominantly focused on ent-kaurene and miltiradiene as the most extensively investigated diterpenes in Isodon. The diversity of diterpene synthases within this genus has recently been acknowledged, while such studies have been largely restricted to single species. In this study, we systematically mined and functionally validated diterpene synthases from three Isodon species using transcriptomic and metabolomic analyses.

Global spatio-temporal distribution of coronavirus disease 2019 vaccine hesitancy between 2020 and 2022: A meta-analysis.

Objective: Vaccine hesitancy is a major barrier to high coronavirus disease 2019 (COVID-19) vaccine coverage. To synthesize global research on COVID-19 vaccine hesitancy, a meta-analysis was conducted to provide scientific evidence for understanding its spatial and temporal variations and influencing factors.

Methods: We searched the PubMed, Web of Science, and Embase databases for studies published in English between January 2020 and December 2023 and included cross-sectional and cohort studies with study populations that included the general adult population aged ≥18 years and provided quantitative data on COVID-19 vaccine acceptance or hesitancy.

Nanoassemblies of the redox paclitaxel prodrug with the natural active ingredient dihydroartemisinin for therapy of breast cancer.

Natural products have attracted attention owing to their multiple antitumor effects, improved chemotherapy sensitivity, and few side effects. The combination of natural active ingredients and chemotherapy drugs could be an effective strategy for synergistic antitumor therapy by preserving their activity to inhibit the growth of tumors, while reducing the side effects of chemotherapy drugs at relatively low doses. Although the feasibility of the delivery of natural products and chemotherapy drugs has been proven, most current carriers cannot be efficiently loaded, thus leading to a discrepancy in the drug release ratio compared to the predefined loading ratio.

Exploring a digital music teaching model integrated with recurrent neural networks under artificial intelligence.

This study proposes an intelligent digital music teaching model based on Artificial Intelligence (AI) and Long Short-Term Memory (LSTM) networks to enhance personalized assessment and feedback in music education. Within this teaching model, the music evaluation module employs a three-layer Bidirectional LSTM (Bi-LSTM) combined with an attention mechanism, effectively capturing the long-term sequential features of Musical Instrument Digital Interface (MIDI) music to support the assessment of students' musical performances. In comparative experiments with multiple models, the three-layer Bi-LSTM achieved a final accuracy of 91.

Isomeric 1,4-Dihydropentalene-Containing Building Blocks for High Mobility Ladder-Type Conjugated Polymers.

Nearly amorphous conjugated polymers, though lacking long-range order, can exhibit high charge carrier mobility and enhanced flexibility, making them ideal for flexible or stretchable OFET applications. However, research on novel structural blocks for this class of materials remains limited. We report the synthesis of two derivatives of the 5,10-dihydroindeno[2,1-a]indene (DHI) core, where two thieno groups are appended to each end to reduce torsional disorder with adjacent comonomers.

Structure-Based Design of New LSD1/EGFR Dual Inhibitors for Treating EGFR Mutant NSCLC Cancers.

Epigenetic changes, such as LSD1 dysregulation, contribute to acquired resistance in EGFR mutant NSCLCs and reduce the effectiveness of current therapeutics. To address the challenges, we herein reported the structure-based design of new LSD1/EGFR dual inhibitors, of which represents the shortlisted lead compound with high potency, selectivity, and unique dual modes of action (namely irreversibly binding to EGFR but reversibly binding to LSD1). effectively inhibited growth in both parent- and TKI-resistant NSCLC cells.

Comparative characterization of human accelerated regions in neurons.

Human accelerated regions (HARs) are conserved genomic loci that have experienced rapid nucleotide substitutions following the divergence from chimpanzees. HARs are enriched in candidate regulatory regions near neurodevelopmental genes, suggesting their roles in gene regulation. However, their target genes and functional contributions to human brain development remain largely uncharacterized.

Inter-protomer opening cooperativity of envelope trimers positively correlates with HIV-1 entry stoichiometry.

HIV-1 entry to host cells is fulfilled by fusion, mediated by surface glycoprotein envelope (Env) trimers upon interaction with host receptors. The entry stoichiometry (T) defining the number of Env trimers required for fusion remains elusive. Stoichiometry was previously estimated using mathematical modeling of infectivity curves of pseudoviruses surface-decorated with heterotrimers containing wild-type and entry-deficient Env.

RNA Editing Analysis Reveals Methyl Jasmonic Acid Regulation of Fucoxanthin and Fatty Acid Metabolism in .

is a marine diatom with significant biotechnological potential, particularly in producing high-value bioactive compounds such as fucoxanthin and unsaturated fatty acids, which possess significant pharmaceutical and nutraceutical properties. However, the naturally low yields of these compounds present a major challenge for large-scale production. Methyl jasmonic acid (MeJA), a plant-derived signaling molecule, has been shown to enhance the biosynthesis of these metabolites in .

Atomistic Understanding of Dislocation Climb in Nitride Semiconductors: Role of Asymmetric Jogs.

Effective control of dislocation climb is of fundamental interest and practical importance in tuning the mechanical and electronic properties of semiconductors. However, it remains a big challenge due to the lack of a clear understanding of its inherent mechanism, in particular, in the nitride semiconductors. In this Letter, the atomic-scale climb process of a single dislocation in GaN is observed for the first time, which undergoes an alternating five- and nine-atomic-ring transformation.

Multiple interactions mediate the localization of BLTP2 at ER-PM contacts to control plasma membrane dynamics.

BLTP2/KIAA0100, a bridge-like lipid transfer protein, was reported to localize at contacts of the endoplasmic reticulum (ER) with either the plasma membrane (PM) or recycling tubular endosomes depending on the cell type. Our findings suggest that mediating bulk lipid transport between the ER and the PM is a key function of this protein as BLTP2 tethers the ER to tubular endosomes only after they become continuous with the PM and that it also tethers the ER to macropinosomes in the process of fusing with the PM. We further identify interactions underlying binding of BLTP2 to the PM, including phosphoinositides, the adaptor proteins FAM102A and FAM102B, and also N-BAR domain proteins at membrane-connected tubules.