A novel approach for target deconvolution from phenotype-based screening using knowledge graph.

Deconvoluting drug targets is crucial in modern drug development, yet both traditional and artificial intelligence (AI)-driven methods face challenges in terms of completeness, accuracy, and efficiency. Identifying drug targets, especially within complex systems such as the p53 pathway, remains a formidable task. The regulation of this pathway by myriad stress signals and regulatory elements adds layers of complexity to the discovery of effective p53 pathway activators.

Radical-Triggered Bicyclization and Aryl Migration of 1,7-Diynes with Diphenyl Diselenide for the Synthesis of Selenopheno[3,4-]quinolines.

The translocation of an aryl group from selenium into carbon enabled by the cleavage of the C-Se bond is reported by using nitrogen atom-linked 1,7-diynes and diaryl diselenides as starting materials, leading to various selenophene derivatives in a regioselective manner. This method enables the construction of two C-Se bonds and two C-C bonds through sequential radical bicyclization and 1,2-aryl migration under metal-free conditions. Control experiments and mechanistic studies suggest that this reaction proceeds through the cleavage of the inert C(Ph)-Se bond, facilitating the aryl translocation process.

A Single-Cell Atlas of Porcine Skeletal Muscle Reveals Mechanisms That Regulate Intramuscular Adipogenesis.

Porcine skeletal muscle development is closely linked to meat production efficiency and quality. The accumulation of porcine intramuscular fat is influenced by the hyperplasia and hypertrophy of adipocytes within the muscle. However, the cellular profiles corresponding to the two stages of muscle development remain undetermined.

[Professor 's clinical experience of acupuncture for subjective tinnitus].

This article introduces Professor 's clinical experience of acupuncture for treating subjective tinnitus. Professor advocates combining meridian differentiation, syndrome differentiation, and disease differentiation in clinical practice. For excess syndrome of subjective tinnitus, acupuncture aims to unblock the meridian and regulate and blood.

Dynll1-PI31 Interaction Enhances Proteolysis via the Proteasome, Representing a Novel Therapeutic Target for INF2-Related FSGS.

Background: The p.Arg218Gln (R218Q) mutation in the inverted formin 2 (INF2) gene causes podocytopathy prone to focal segmental glomerulosclerosis (FSGS). This mutation disrupts the ability of INF2 to sequester DYNLL1, thus promoting dynein-mediated mistrafficking of the slit diaphragm protein, nephrin, to proteolytic pathways.

Mechanisms of podocyte injury in genetic kidney disease.

Glomerular diseases are a leading cause of chronic kidney disease worldwide. Both acquired and hereditary glomerulopathies frequently share a common final disease mechanism: disruption of the glomerular filtration barrier, podocyte injury, and ultimately podocyte death and detachment. Over 70 monogenic causes of proteinuric kidney disease have been identified, and most of these genes are highly expressed in podocytes, regulating key processes such as maintenance of the slit diaphragm, regulation of actin cytoskeleton remodeling, and modulation of downstream transcriptional pathways.

[Effect and Influencing Factors of Peripheral Blood Hematopoietic Stem Cells Collection from Unrelated Donors].

Objective: To analyze the effect of peripheral blood hematopoietic stem cells (PBSC) collection from unrelated donors and its influencing factors.

Methods: A retrospective analysis was conducted on the mobilization and collection of PBSC from 113 unrelated donors at Yueyang Central Hospital from January 2021 to December 2023.

Results: 113 donors were successfully mobilized.

Construction and Optimization of a Yeast Cell Factory for Producing Active Unnatural Ginsenoside 3β--Glc-DM.

Ginsenosides are major active components of , which are generally glycosylated at C3-OH and/or C20-OH of protopanaxadiol (PPD) and C6-OH and/or C20-OH of protopanaxatriol. However, the glucosides of dammarenediol-II (DM), which is the direct precursor of PPD, have scarcely been separated from . Because different positions and numbers of the hydroxyl and glycosyl groups lead to a diversity of structure and function of the ginsenosides, it can be inferred that DM glucosides may have different pharmacological activities compared with natural ginsenosides.

Enhancing Adsorption Performance of Ce(III) by Amine-Thiourea and Aniline-Modified Magnetic Chitosan Nanocomposites.

To enhance the adsorption performance of chitosan for rare earth ions, two novel magnetic chitosan-based adsorbents were prepared by using chitosan-coated magnetic silica nanoparticles modified with amine-thiourea and aniline. The structure of copolymers was analyzed using characterization methods such as X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis, confirming the successful synthesis of modified magnetic chitosan nanocomposites. The investigation explored the influence of pH, contact time, dosage, initial concentration, and temperature on the adsorption performance.

Rapid Construction of Liquid-like Surfaces via Single-Cycle Polymer Brush Grafting for Enhanced Antifouling in Microfluidic Systems.

Liquid-like surfaces have demonstrated immense potential in their ability to resist cell adhesion, a critical requirement for numerous applications across various domains. However, the conventional methodologies for preparing liquid-like surfaces often entail a complex multi-step polymer brush modification process, which is not only time-consuming but also presents significant challenges. In this work, we developed a single-cycle polymer brush modification strategy to build liquid-like surfaces by leveraging high-molecular-weight bis(3-aminopropyl)-terminated polydimethylsiloxane, which significantly simplifies the preparation process.

Drought-Induced Alterations in Carbon and Water Dynamics of Chinese Fir Plantations at the Trunk Wood Stage.

Over the past three decades, China has implemented extensive reforestation programs, primarily utilizing Chinese fir ( (Lamb.) Hook) in southern China, to mitigate greenhouse gas emissions and counter extreme climate events. However, the effects of drought on the carbon sequestration capacity of these forests, particularly during the trunk wood stage, remain unclear.

Andrographolide sensitizes glioma to temozolomide by inhibiting DKK1 expression.

Background: Temozolomide (TMZ) is the first-line chemotherapeutic drug for gliomas treatment. However, the clinical efficacy of TMZ in glioma patients was very limited. Therefore, it is urgently needed to discover a novel approach to increase the sensitivity of glioma cells to TMZ.

Dominant Malignant Clones Leverage Lineage Restricted Epigenomic Programs to Drive Ependymoma Development.

Unlabelled: ZFTA-RELA is the most recurrent genetic alteration seen in pediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumors in mice. Despite ZFTA-RELA's potent oncogenic potential, gene fusions are observed exclusively in childhood EPN, with tumors located distinctly in the supratentorial region of the central nervous system (CNS). We hypothesized that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZFTA-RELA.

Comprehensive Analysis of Methylome and Transcriptome to Identify Potential Genes Regulating Porcine Testis Development.

DNA methylation plays a critical role in regulating gene expression during testicular development. However, few studies report on candidate genes related to the DNA methylation regulation of porcine testicular development. This study examined the differentially expressed genes (DEGs) and their methylation levels in testicular tissues from pigs at 60 days of age (60 d) and 180 days of age (180 d) using RNA-Seq and whole genome bisulfite sequencing (WGBS).

20S-O-Glc-DM treats metabolic syndrome-induced heart failure through regulating gut flora.

Heart failure is a multifactorial disease, the percentage of patients with heart failure caused by metabolic syndrome is increasing year by year. The effect of gut flora dysbiosis on metabolic syndrome and heart failure has received widespread attention in recent years. Drugs to treat the condition urgently need to be discovered.

Somatic mutation phasing and haplotype extension using linked-reads in multiple myeloma.

Somatic mutation phasing informs our understanding of cancer-related events, like driver mutations. We generated linked-read whole genome sequencing data for 23 samples across disease stages from 14 multiple myeloma (MM) patients and systematically assigned somatic mutations to haplotypes using linked-reads. Here, we report the reconstructed cancer haplotypes and phase blocks from several MM samples and show how phase block length can be extended by integrating samples from the same individual.

Engineered Microfibers for Tissue Engineering.

Hydrogel microfibers are hydrogel materials engineered into fiber structures. Techniques such as wet spinning, microfluidic spinning, and 3D bioprinting are often used to prepare microfibers due to their ability to precisely control the size, morphology, and structure of the microfibers. Microfibers with different structural morphologies have different functions; they provide a flow-through culture environment for cells to improve viability, and can also be used to induce the differentiation of cells such as skeletal muscle and cardiac muscle cells to eventually form functional organs in vitro through special morphologies.

Isomer engineering for deep understanding of aggregation-induced photothermal enhancement in conjugated systems.

Organic photothermal materials based on conjugated structures have significant potential applications in areas such as biomedical diagnosis, therapy, and energy conversion. Improving their photothermal conversion efficiency through molecular design is critical to promote their practical applications. Especially in similar structures, understanding how the position of heteroatoms affects the conversion efficiency is highly desirable.

Analysis of Medication Adherence Status and Influencing Factors in Adolescents with Major Depressive Episodes.

Background: By analyzing the current status and influencing factors of medication adherence in adolescent patients with major depressive episode, this study aimed to provide more evidence on clinical medication treatment of such patients.

Methods: This was a retrospective study. A total of 218 adolescents with major depressive disorder (MDD) admitted to the mental health center of the First Affiliated Hospital of Guangxi Medical University from June 2022 to June 2023 were selected as the study subjects.

A class of geranylquinol-derived polycyclic meroterpenoids from Arnebia euchroma against heart failure by reducing excessive autophagy and apoptosis in cardiomyocytes.

Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed.

20S-O-Glc-DM treats left ventricular diastolic dysfunction by modulating cardiomyocyte mitochondrial quality and excess autophagy.

Background: Left ventricular diastolic dysfunction (LVDD) is a manifestation of heart failure, with both its incidence and prevalence increasing annually. Currently, no pharmacological treatments are available for LVDD, highlighting the urgent need for new therapeutic discoveries. Ginsenosides are commonly used in cardiovascular therapy.