A novel peptide encoded by circSRCAP confers resistance to enzalutamide by inhibiting the ubiquitin-dependent degradation of AR-V7 in castration-resistant prostate cancer.

Background: The sustained activation of androgen receptor splice variant-7 (AR-V7) is a key factor in the resistance of castration-resistant prostate cancer (CRPC) to second-generation anti-androgens such as enzalutamide (ENZ). The AR/AR-V7 protein is regulated by the E3 ubiquitin ligase STUB1 and a complex involving HSP70, but the precise mechanism remains unclear.

Methods: High-throughput RNA sequencing was used to identify differentially expressed circular RNAs (circRNAs) in ENZ-resistant and control CRPC cells.

m1A-regulated DIAPH3 promotes the invasiveness of colorectal cancer via stabilization of KRT19.

Background: In recent years, the emphasis has shifted to understanding the role of N1-methyladenosine (m1A) in tumor progression as little is known about its regulatory effect on mRNA and its role in the metastasis of colorectal cancer (CRC).

Methods: We performed methylated RNA immunoprecipitation sequencing of tumor tissues and tumor-adjacent normal tissues from three patients with CRC to determine the m1A profile of mRNA in CRC. The expression of diaphanous-related formin 3 (DIAPH3) and its correlation with clinicopathological characteristics of CRC were evaluated using immunohistochemistry and online datasets.

FTO Suppresses Proliferation and Induces Apoptosis of T98G Glioblastoma Cells via N6-methyladenosine Modification of GSTO1.

Glioblastoma (GBM) is the most malignant type of glioma with a very poor prognosis. N6-methyladenosine (m6A) is well-documented to be involved in GBM progression, and FTO is a demethylase. GSTO1 is also associated with tumor progression.

Health state assessment method for complex system based on multiexpert joint belief rule base.

The health of complex systems continues to decline as they operate over long periods of time, so it is important to assess the health state of complex systems. Belief rule base (BRB) is widely used in the field of health state assessment of complex systems as a semi-quantitative method that can address uncertainty effectively and with interpretability. In practical engineering, BRB still has problems: the incompleteness of expert knowledge and the inconsistency of the cognitive abilities of each expert have an effect on the construction of the model and interpretability.

Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity.

Understanding the heterogeneity of epigenetic modifications within single cells is pivotal for unraveling the nature of the complexity of gene expression and cellular function. In this study, we have developed a strategy based on multichrome encoding and "AND" Boolean logic recognition for multiplexed, spatially resolved imaging of single-cell RNA epigenetic modifications, termed as PRoximity Exchange-assisted Encoding of Multichrome (PREEM). Through the implementation of this strategy, we can now map the expression and nuclear distribution of multiple site-specific RNA N6-methyladenosine (mA) modifications at the single-molecule resolution level in single-cells, and reveal the previously unknown heterogeneity.

Regulating the macroscopic and microscopic self-assembly behavior of hydroxybutyl chitosan based on alkyl distribution.

Hydroxybutyl chitosan (HBC), a derivative of chitosan, exhibits biocompatibility and temperature-sensitive properties, rendering it utilized in tissue engineering, and biomedical science. Currently, HBC is mainly prepared based on heterogeneous and homogeneous reactions. However, the impact of reactions on structure of derivatives and their mechanisms for self-assembly remains to be elucidated.

Integrating the modified amphiphilic Eleocharis tuberosa starch to stabilize curcuminoid-enriched Pickering emulsions for enhanced bioavailability, thermal stability, and retention of the hydrophobic bioactive compound.

The study involves the modification of a non-conventional starch isolated from the under-utilized variety of Chinese water chestnut (CWC (Eleocharis tuberosa) and integrating it to fabricate stabilized and curcumin-enriched Pickering emulsions with enhanced bioavailability, thermal stability, and retention of encapsulated curcumin. A time-efficient, semi-dried esterification method was used to prepare modified amphiphilic starches using 3, 6, or 9 % (w/v) octenyl succinic anhydride (OSA) and characterized through degree of substitution (DS), contact angle, particle size, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and in-vitro digestibility. Moreover, Pickering emulsions were formulated using CWCS-OSA at 3 %, 6 %, or 9 % concentrations to serve as a carrier for curcumin to improve its water solubility and storage stability.

Quaternary ammonium chitosan-functionalized mesoporous silica nanoparticles: A promising targeted drug delivery system for the treatment of intracellular MRSA infection.

The limited membrane permeability and bacterial resistance pose significant challenges in the management of intracellular drug-resistant bacterial infections. To overcome this issue, we developed a bacterial-targeted drug delivery system based on quaternary ammonium chitosan-modified mesoporous silica nanoparticles (MSN-NH-CFP@HACC) for the treatment of intracellular Methicillin-resistant Staphylococcus aureus (MRSA) infections. This system utilizes amino-functionalized mesoporous silica nanoparticles to efficiently load cefoperazone (CFP), and the nanoparticles' surface is coated with 2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) to target bacteria and enhance macrophage uptake.

Review on bioproduction of sialylated human milk oligosaccharides: Synthesis methods, physiologic functions, and applications.

Human milk oligosaccharides (HMOs) are crucial for promoting neonatal health, with sialylated oligosaccharides, a significant subclass, offering a variety of health benefits such as prebiotic effects, anti-inflammatory and antimicrobial properties, antiviral defense, and cognitive development support. Among these, 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) have received "GRAS" status from the U.S.

Effects of ascorbic acid treatment on starch metabolism during wound healing in fresh-cut potatoes.

Starch degradation and wound healing occur in potato tubers following fresh-cut processing, and ascorbic acid (AA) treatment can suppress these processes, though the underlying regulatory mechanisms remain unclear. This study investigated the effects of 5 g L AA treatment on the multiscale structural changes and metabolic responses of starch during wound healing in fresh-cut potatoes. The results revealed that AA treatment delayed starch degradation and reducing sugar accumulation while promoting sucrose and fructose accumulation.

Glutathione-scavenging natural-derived ferroptotic nano-amplifiers strengthen tumor therapy through aggravating iron overload and lipid peroxidation.

Nanomedicine-driven ferroptosis has emerged as a promising tumor treatment strategy through delivering exogenous iron and aggravating the lethal accumulation of lipid peroxides (LPO). However, the compensatory mechanisms of ferroptosis defense systems in cancer cells compromise the therapeutic efficacy and lead to potential side effects. Herein, a highly effective ferroptotic nano-amplifier is designed to synergistically promote ferroptosis via increasing intracellular labile iron, exacerbating lipid peroxidation and overcoming the defense system.

Identification of a novel butenolide signal system to regulate high production of tylosin in Streptomyces fradiae.

Identifying hormone-like quorum sensing (QS) molecules in streptomycetes is challenging due to low production levels but is essential for understanding secondary metabolite biosynthesis and morphological differentiation. This work reports the discovery of a novel γ-butenolide-type signaling molecule (SFB1) via overexpressing its biosynthetic gene (orf18) in Streptomyces fradiae. SFB1 was found to be essential for production of tylosin through dissociating the binding of its receptor TylP (a transcriptional repressor) to target genes, thus activating the expression of tylosin biosynthetic gene cluster (tyl).

Bioactive glass 45S5 promotes odontogenic differentiation of apical papilla cells through autophagy.

Objectives: The mechanism of the odontogenic differentiation of apical papillary cells (APCs) stimulated by bioactive glass 45S5 is still unclear. This study aims to investigate the effect of autophagy on the odontogenic differentiation of APCs stimulated by bioactive glass 45S5.

Methods: APCs were isolated and cultured , and the cell origin was identified by flow cytometry.

The safety, tolerability, pharmacokinetics and pharmacodynamics of an optimized dual GLP-1/GIP receptor agonist (BGM0504) in healthy volunteers: A dose-escalation Phase I study.

Objective: Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers.

Methods: A randomized, double-blind, placebo-controlled and dose-escalation Phase I study was conducted as follows: a single dose (2.

Backbone Engineering of Bithiophene Imide Dimer-Based Polymeric Mixed Ionic-Electronic Conductors for High-Performance n-Type Organic Electrochemical Transistors.

Polymeric mixed ionic-electronic conductors (PMIECs) are gaining significant attention due to their potential applications in organic electrochemical transistors (OECTs). However, the performance of n-type OECTs still lags behind that of their p-type counterparts. Here, the structure-performance correlation of fused bithiophene imide dimer (BTI2)-based PMIECs is systematically investigated with the backbone evaluation from acceptor-strong donor (A-SD) to acceptor-donor (A-D), to acceptor-weak donor (A-WD), to acceptor-weak acceptor (A-WA), and finally to A-A structures.

TET2-mediated 5-hydroxymethylcytosine of TXNIP promotes cell cycle arrest in systemic anaplastic large cell lymphoma.

Background: 5-Hydroxymethylcytosine (5hmC) modification represents a significant epigenetic modification within DNA, playing a pivotal role in a range of biological processes associated with various types of cancer. The role of 5hmC in systemic anaplastic large cell lymphoma (ALCL) has not been thoroughly investigated. This study aims to examine the function of 5hmC in the advancement of ALCL.

A beneficial levels of 25-hydroxyvitamin D for a decrease in thyrotropin receptor antibody (TRAB) in patients with Graves' disease: a real-world study.

Objective: This study aimed to determine whether a relationship exist between pre-therapy 25-hydroxyvitamin D levels and the remission/negative conversion rates of thyrotropin receptor antibody (TRAB) during treatment in patients with newly diagnosed Graves' disease (GD).

Methods: 171 patients were included from the Endocrinology Department of the First Affiliated Hospital of Fujian Medical University in March 2013 to April 2016. Ninety-five patients of them were diagnosed at our hospital but transferred to local hospitals for treatment.

Psychotropic Polypharmacy in Dementia: A Retrospective Analysis for People with Neuropsychiatric Symptoms Referred to an Australian Dementia Support Service.

Background And Objectives: Despite their limited benefits and serious adverse effects, psychotropics remain frequently prescribed for neuropsychiatric symptoms (NPS) of dementia. Psychotropic polypharmacy, the use of two or more concomitant psychotropic medications, is therefore not recommended for people with dementia. The objectives of this study were to investigate the prevalence of psychotropic polypharmacy in Australians living with dementia whose caregivers sought external NPS support from Dementia Support Australia (DSA; the national provider of NPS support) and the association of psychotropic polypharmacy with their demographics and NPS characteristics.

A multicenter, randomized, open label, two formulation, crossover bioequivalence trial of doxorubicin hydrochloride liposomal injection in Chinese patients with metastatic breast cancer.

Purpose: The primary objectives of this trial were aimed at exploring the pharmacokinetic profiles and the human bioequivalence of an intravenous liposomal injection of doxorubicin hydrochloride in comparison with a reference formulation in Chinese patients diagnosed with metastatic breast cancer.

Methods: To achieve these goals, the trial employed a randomized, open-label, two-formulation crossover dosing strategy among Chinese patients with metastatic breast cancer. Pharmacokinetic (PK) evaluation was conducted through the collection of blood samples, and the liquid chromatography tandem mass spectrometry (LC/MS/MS) method was leveraged to quantify plasma concentrations of both liposome-encapsulated doxorubicin and non-encapsulated doxorubicin in patients.

Fabrication and mechanical properties of porous tantalum carbon composites by chemical vapor deposition.

This study investigates the deposition of tantalum (Ta) coatings on carbon foams using the chemical vapor deposition (CVD) method to enhance their compressive strength. Two types of open-cell carbon foams, CF-1 and CF-2, with different strut diameters, were examined. The morphology and uniformity of the coatings were characterized, and the effect of coating thickness on the compressive strength of the foams was systematically analyzed.

Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides.

Echinacoside (ECH), one of the most representative phenylethanoid glycosides (PhGs), has considerable neuroprotective effects and is an effective ingredient in numerous commercial drugs. Here, we elucidate the complete ECH biosynthetic pathway in the medicinal plant Cistanche tubulosa. In total, 14 related genes are cloned and functionally characterized.

Proton Exchange Membrane with Dual-Active-Center Surpasses the Conventional Temperature Limitations of Fuel Cells.

High temperature-proton exchange membrane fuel cells (HT-PEMFC) call for ionomers with low humidity dependence and elevated-temperature resistance. Traditional perfluorosulfonic acid (PFSA) ionomers encounter challenges in meeting these stringent requirements. Herein, this study reports a perfluoroimide multi-acid (PFMA) ionomer with dual active centers achieved through the incorporation of sulfonimide and phosphonic acid groups into the side chain.

Injured Myocardium-Targeted Theranostic Nanoplatform for Multi-Dimensional Immune-Inflammation Regulation in Acute Myocardial Infarction.

Pyroptosis is a key mode of programmed cell death during the early stages following acute myocardial infarction (AMI), driving immune-inflammatory responses. Cardiac resident macrophages (CRMs) are the primary mediators of cardiac immunity, and they serve a dual role through their shaping of both myocardial injury and post-AMI myocardial repair. To appropriately regulate AMI-associated inflammation, HM4oRL is herein designed, an innovative bifunctional therapeutic nanoplatform capable of inhibiting cardiomyocyte pyroptosis while reprogramming inflammatory signaling.

Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.

Sepsis is a severe systemic inflammatory syndrome characterized by a dysregulated immune response to infection, often leading to high mortality rates. The intestine, owing to its distinct structure and physiological environment, plays a pivotal role in the pathophysiology of sepsis. It functions as the "central organ" or "engine" in the progression of sepsis, with intestinal injury exacerbating the condition.

Facile synthesis of plasmonic BP@Au nanomatrix for sensitive detection of irinotecan and its active SN-38 metabolite via laser desorption/ionization mass spectrometry.

A new methodology is presented for the rapid, specific, and sensitive detection of irinotecan (CPT-11), a chemotherapeutic agent utilized in the treatment of cancer, along with its metabolically active derivative, SN-38, via laser desorption/ionization mass spectrometry (LDI MS). The method includes the detection of camptothecin (CPT), which can be utilized as an internal standard for the quantitative assessment of both CPT-11 and SN-38 in mouse serum. The approach utilizes a plasmonic two-dimensional (2D) black phosphorus nanosheet (BPN)-gold nanomatrix (BP@Au) in LDI MS.