Network Pharmacology and Experimental Validation Identify Paeoniflorin as a Novel SRC-Targeted Therapy for Castration-Resistant Prostate Cancer.

Despite advances in prostate cancer treatment, castration-resistant prostate cancer (CRPC) remains clinically challenging due to inherent therapy resistance and a lack of durable alternatives. Although traditional Chinese medicine offers untapped potential, the therapeutic role of paeoniflorin (Pae), a bioactive compound derived from Paeonia lactiflora, in prostate cancer has yet to be investigated. Using an integrative approach (network pharmacology, molecular docking, and experimental validation), we identified Pae key targets, constructed protein-protein interaction networks, and performed GO/KEGG pathway analyses.

Integrated Omics and Multi-Cohort Analyses Identify an Enhancer Variant Linking Ferroptosis to Precision Therapy in Prostate Cancer.

Prostate cancer is the most prevalent cancer among men worldwide and exhibits significant genetic heritability. In this study, we performed an integrative analysis combining chromatin accessibility profiling, transcriptomics, and two-stage case-control studies, alongside an unbiased phenome-wide exploration in the FinnGen cohort. This comprehensive approach identified the enhancer-associated single-nucleotide polymorphism rs7077830 at chromosome 10q11 as a critical modulator of prostate cancer susceptibility.

Digital infrastructure policies, local fiscal and financing constraints of Non-SOEs: Evidence from China.

Digital infrastructure serves as a cornerstone of urban digital transformation and smart city development, yet its implications for local fiscal systems and micro-level enterprises remain underexplored. This study empirically investigates the impact of digital infrastructure policies on the financing constraints of Non-SOEs in China. The contributions of this paper are as follows: (1) Theoretical innovation: It develops a comprehensive theoretical framework connecting macro-level digital policies, regional fiscal dynamics, and micro-enterprise financing constraints, offering a novel perspective on how macro policies influence micro-enterprises.

SUMO-activating enzyme subunit 1 (SAE1) promotes non-small cell lung cancer metastasis by promoting the epithelial-mesenchymal transition through the SUMOylation of N-cadherin.

Protein SUMOylation is a newly discovered process similar to protein ubiquitination and is crucial for protein stability and protein localization. SAE1 is an important enzyme that initiates protein SUMOylation, but its role in the progression of non-small cell lung cancer remains unknown. We analyzed the protein expression profiles of non-small cell lung cancer tissues and single-cell sequencing data and confirmed that SAE1 is highly expressed in non-small cell lung cancer cells and is associated with a malignant phenotype.

Pharmacokinetics, mass balance, and metabolism of [C]FCN-437c, a selective and potent CDK4/6 inhibitor in humans.

This study investigated the pharmacokinetics, mass balance, and metabolism of [C]FCN-437c, a selective and potent CDK4/6 inhibitor, in humans. Six healthy male Chinese subjects were administered a single oral dose of 200 mg [C]FCN-437c (120 µCi), and plasma, urine, and feces samples were collected up to 456 h post-dose. The geometric mean C of radioactivity in plasma and blood were 706 and 557 ng eq.

Mass balance and metabolite profiles in humans of tegoprazan, a novel potassium-competitive acid blocker, using C-radiolabelled techniques.

Background: Tegoprazan (LXI-15028), a novel potassium-competitive acid blocker, has shown great efficacy in treating acid-related disorders. However, its metabolic and excretion characteristics are not fully understood.

Research Design And Methods: A single oral dose of 50 mg/150 μCi [C]tegoprazan was administered to six healthy subjects.

Liquid biopsy-derived extracellular vesicle protein biomarkers for diagnosis and prognostic assessment of lung squamous cell carcinoma.

Background: For patients with nodules detected in imaging that are indeterminate for malignancy, achieving accurate, early, and non-invasive diagnosis of Lung Squamous Cell Carcinoma (LUSC) remains a significant challenge. Therefore, we aimed to establish diagnostic and prognostic models by identifying plasma extracellular vesicles (EVs) associated protein biomarkers specific to LUSC.

Methods: This study employed a novel nanomaterial, NaY, for the enrichment of EVs from plasma.

Enhancer transcription profiling reveals an enhancer RNA-driven ferroptosis and new therapeutic opportunities in prostate cancer.

Enhancer RNAs (eRNAs), a subclass of non-coding RNAs transcribed from enhancer regions, have emerged as critical regulators of gene expression; however, their functional roles in prostate cancer remain largely unexplored. In this study, we performed integrated chromatin accessibility and transcriptomic analyses using ATAC-seq and RNA-seq on twenty pairs of prostate cancer and matched benign tissues. By incorporating chromatin immunoprecipitation sequencing data, we identified a subset of differentially expressed eRNAs significantly associated with genes involved in prostate development and oncogenic signaling pathways.

Impact of parental myopia on myopia in schoolchildren and adolescents in China: A national cross-sectional survey.

Background: Parental myopia is an important risk factor for myopia in Chinese children and adolescents. This study aimed to assess the influence of parental myopia and the severity of myopia on offspring and to evaluate whether adopting healthy lifestyles can mitigate the effects of parental myopia on offspring.

Methods: This cross-sectional study analyzed data from children and adolescents aged 6-17 years with complete vision assessments and parental history of myopia from six provinces in China during 2013-2014.

Polydopamine-based nano-protectant for prolonged boar semen preservation by eliminating ROS and regulating protein phosphorylation via D2DR-mediated cAMP/PKA signaling pathway.

Preservation of porcine semen is essential for artificial insemination and genetic improvement in pig breeding programs. However, the overproduction of reactive oxygen species (ROS) and lower levels of protein phosphorylation emerge as two challenges during semen preservation. Inspired by the innate ligand-receptor binding biofunction of dopamine, herein, a dual-task nano-protectant that combines ROS-scavenging and protein phosphorylation-regulating properties via incorporating the natural antioxidant epigallocatechin gallate (EGCG) into polydopamine nanoparticles (EGCG@PDA NPs) was proposed to enhance the quality of pig semen during storage at 4 ℃.

Investigation of absorption, metabolism, and excretion of [C]pruxelutamide (GT0918), an androgen receptor antagonist in humans.

Aims: The primary objective of this study was to determine the pharmacokinetics, mass balance and biotransformation of [C]GT0918 in humans after the drug was administered to healthy Chinese male subjects.

Methods: The absorption, metabolism, and excretion (AME) of GT0918 was characterized via isotope labelling technology in six healthy Chinese male subjects after receiving a single 200 mg oral dose of [C]GT0918 (80 μCi), and the phenotype, together with the metabolic mechanism of GT0918, was confirmed in vitro.

Results: The medium T of total radioactivity was 6.

Ultrasound-laccase pre-treatment enhances agarwood essential oil extraction and bioactivity.

Agarwood essential oil is prized for its elegant aroma and pharmacological properties; however, the traditional hydrodistillation method suffers from inefficiencies, constraining the industrial potential of agarwood. We proposed an ultrasonic-assisted laccase synergistic pretreatment technique that enhanced extraction throughput by 70.90 % compared to the traditional method by facilitating pore formation in agarwood and expediting the release of essential oil.

Maternal Exposure to Polystyrene Nanoplastics Disrupts Spermatogenesis in Mouse Offspring by Inducing Overexpression in Undifferentiated Spermatogonia.

Undifferentiated spermatogonia (Undiff-SPG) plays a critical role in maintaining continual spermatogenesis. However, the toxic effects and molecular mechanisms of maternal exposure to nanoplastics on offspring Undiff-SPG remain elusive. Here, we utilized a multiomics combined cytomorphological approach to explore the reproductive toxicity and mechanisms of polystyrene nanoplastics (PS-NPs) on offspring Undiff-SPG in mice after maternal exposure.

Tuning Surface Valences of Nanoengagers to Enhance Their Structural Advantages for Efficiently Redirecting T Cells against Solid Tumors.

The nanoengager strategy, which enhances receptor signaling responsiveness through a multivalent ligand binding mode, offers a promising approach for improving immune cell redirecting therapy. Increasing nanomaterial platforms have been developed for constructing more flexible and multifunctional nanoengagers, but the different mediating mechanisms from their multivalent nanostructures, compared to original monomolecule engagers, have rarely been discussed. Here, we constructed dual-specificity T cell nanoengagers (TNEs) targeting CD3 and PDL1 receptors based on a polyethylene glycol--polylactic acid (PEG--PLA)-assembled nanoparticle and specifically studied the impact of surface antibody valences on their functional mechanisms, thereby enhancing the structural advantages of TNEs against solid tumors.

Beneficial effects of EGCG on boar sperm quality during liquid storage at 4 °C are mediated by DRD2 receptor.

Epigallocatechin gallate (EGCG), a natural antioxidant, plays a vital role in modulating sperm function, yet its protective impact on boar spermatozoa during liquid preservation at 4 °C remains elusive. This study aimed to investigate the beneficial effects of EGCG on boar semen preservation, and elucidate the potential mechanism. Multiple parameters including sperm quality, anti-oxidative status, protein phosphorylation levels, membrane receptor and cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathways were analyzed using computer-assisted semen analysis system, Western blot and molecular docking techniques.

Absorption, metabolism, and excretion of oral [C] radiolabeled donafenib: an open-label, phase I, single-dose study in humans.

Purpose: The study aims to investigate the absorption, metabolism, and excretion of donafenib, a deuterated derivative of sorafenib, in healthy Chinese male volunteers.

Methods: Six healthy Chinese male volunteers were administered a single oral dose of 300 mg donafenib containing 120 µCi of [14 C]-donafenib. The study involved collecting and analyzing plasma, urine, and feces samples to determine the recovery and distribution of total radioactivity, identify metabolites, and assess the metabolic pathways of donafenib.

Polymeric immunogel prevents tumor recurrence and metastasis by dual activation of innate and adaptive immunity.

Tumor recurrence and metastasis after surgery are important factors affecting patient survival. The immunosuppressed tumor microenvironment after surgery reduces the ability of the immune system to clear residual tumor cells, thus increasing the risk of recurrence and metastasis. Currently, immunotherapy-based adjuvant therapy can effectively inhibit tumor recurrence and metastasis after surgery, but simultaneous and efficient synergistic activation of adaptive and innate immunity is a challenge.

Development and validation of a comprehensive predictive model for surgical planning in patients with renal cell carcinoma and inferior vena cava tumor thrombus.

Objective: To investigate preoperative predictors for selecting different surgical approaches in patients with renal cell carcinoma with inferior vena cava (IVC) tumor thrombus (RCC-IVCTT), and to establish and validate corresponding predictive models.

Methods: Clinical data of 583 RCC-IVCTT patients were retrospectively analyzed. Of these, 465 cases were used to construct predictive models, and 118 cases were used for validation.

Clinical pharmacokinetic characteristics of Jaktinib in subjects with hepatic impairment in a phase I trial.

Jaktinib is a novel Janus kinase (JAK) inhibitor, and a phase I clinical trial of single-dose Jaktinib was conducted in a population of subjects with hepatic impairment to assess the safety, tolerability, and pharmacokinetic characteristics of Jaktinib. The patients were administered orally with 100 mg Jaktinib on day 1 in all the mild hepatic impairment group (mild group, n = 8), moderate hepatic impairment group (moderate group, n = 8) and normal hepatic function group (normal group, n = 8), and the blood samples were collected for later analysis. The mild to moderate hepatic impairment affected the metabolism of Jaktinib, which may lead to accumulation of original Jaktinib.

Estimating the global and regional burden of lower respiratory infections attributable to leading pathogens and the protective effectiveness of immunization programs.

Objectives: Reducing mortality from infectious diseases is an urgent global public health priority. Streptococcus pneumoniae, H. influenzae, and influenza virus are the three leading causes of lower respiratory infections (LRIs) death worldwide.

Trojan-Horse Strategy Targeting the Gut-Liver Axis Modulates Gut Microbiome and Reshapes Microenvironment for Orthotopic Hepatocellular Carcinoma Therapy.

Reversing the hepatic inflammatory and immunosuppressive microenvironment caused by gut microbiota-derived lipopolysaccharides (LPS), accumulating to the liver through the gut-liver axis, is crucial for suppressing hepatocellular carcinoma (HCC) and metastasis. However, synergistically manipulating LPS-induced inflammation and gut microbiota remains a daunting task. Herein, a Trojan-horse strategy is proposed using an oral dextran-carbenoxolone (DEX-CBX) conjugate, which combines prebiotic and glycyrrhetinic acid (GA) homologs, to targeted delivery GA to HCC through the gut-liver axis for simultaneous modulation of hepatic inflammation and gut microbiota.

ATF3 as a response factor to regulate Cd-induced reproductive damage by activating the NRF2/HO-1 ferroptosis pathway.

Cadmium (Cd) has garnered significant attention due to reproductive toxicity in inducing ferroptosis. However, the specific mechanisms underlying Cd-induced germ cell ferroptosis remain poorly understood. This study aimed to systematically explore the molecular mechanisms of germ cell ferroptosis by investigating differential changes in transcription factors and proteins in male mice treated orally with CdCl (0.

Analysis and functional validations of multiple cell death patterns for prognosis in prostate cancer.

Prostate cancer (PCa) has garnered significant attention due to its rising incidence, variable therapeutic outcomes, and the absence of reliable prognostic markers. The significance of different cell death patterns in tumor development underscores their potential as predictors of PCa prognosis. This study utilized The Cancer Genome Atlas (TCGA) datasets to evaluate the prognostic capabilities of 15 cell death patterns and established a Cell Death Index (CDI) signature based on necrosis and cuproptosis-related genes.

PDIA2 is associated with the prognosis of prostate cancer, and downregulation of PDIA2 delays the progression of prostate cancer cells.

Protein Disulfide-Isomerase A2 (PDIA2) is a gene that encodes proteins, responsible for protein folding and modification within cells. The development and course of many disorders are intimately linked to the aberrant expression of PDIA2. Nevertheless, more research is necessary to fully understand PDIA2's biological significance in pan-cancer, notably in prostate cancer (PCa).