Targeting ADAR1 with a small molecule for the treatment of prostate cancer.

Despite the initial response to androgen signaling therapy, most cases of prostate cancer (PCa) eventually relapse and remain incurable. The specific function of ADAR1 that governs PCa progression and specific inhibitors of ADAR are underexplored. In this study, we demonstrate that highly expressed ADAR1 is a crucial oncogenic target in PCa and develop an effective small-molecule ADAR1 inhibitor, ZYS-1, with marked antitumor efficacy and a favorable safety profile.

Tumor-associated-fibrosis and active collagen-CD44 axis characterize a poor-prognosis subtype of gastric cancer and contribute to tumor immunosuppression.

Background: Tumor-associated fibrosis modifies the tumor microenvironment (TME), hinders the infiltration and activity of cytotoxic immune cells, and is a critical pathological process leading to the ineffectiveness of tumor immunotherapy in gastric cancer (GC). However, the specific mechanisms and interventions are yet to be fully explored.

Methods: Our study included 375 gastric cancer samples from TCGA, 1 single-cell RNA sequencing (scRNA-seq) dataset comprising of 15 gastric cancer samples from GEO, 19 cohorts of immunotherapy and 2 GWAS datasets.

Identification and validation of CDK1 as a promising therapeutic target for Eriocitrin in colorectal cancer: a combined bioinformatics and experimental approach.

Background: Colorectal cancer (CRC) is a prevalent malignancy worldwide, associated with significant morbidity and mortality. Cyclin-dependent kinase 1 (CDK1) plays a crucial role in cell cycle regulation and has been implicated in various cancers. This study aimed to evaluate the prognostic value of CDK1 in CRC and to identify traditional Chinese medicines (TCM) that can target CDK1 as potential treatments for CRC.

Washed microbiota transplantation stopped recurrent sepsis in a patient with myelofibrosis: a case report.

Background: Sepsis represents the most prevalent infectious complication and the primary cause of mortality in myeloproliferative neoplasms (MPN). The risk of sepsis and the difficulty of treatment are significantly increased in MPN patients due to the need for immunomodulators and antibiotics.

Case Presentation: On June 9, 2023, a 69-year-old male was admitted to the hospital.

Design, Synthesis, and Antitumor Activity Evaluation of 2-Phenylthiazole-5-Carboxylic Acid Derivatives Targeting Transactivation Response RNA-Binding Protein 2.

Transactivation response (TAR) RNA-binding protein 2 (TRBP) plays a critical role in microRNA (miRNA) biosynthesis, with aberrant expression linked to various cancers. Previously, we identified , a phenyloxazole derivative that disrupts the TRBP-Dicer interaction in hepatocellular carcinoma (HCC). In this study, we optimized this scaffold and substituent, leading to the discovery of , a 2-phenylthiazole-5-carboxylic acid derivative with nanomolar inhibitory activity (EC = 0.

A minimal transcription template-based amplification-free CRISPR-Cas13a strategy for DNA detection.

CRISPR-Cas13a has shown great potential for the rapid and accurate detection of pathogen nucleic acids. However, conventional CRISPR-Cas13a-based assays typically require pre-amplification, which can introduce aerosol contamination and operational complexities. In this study, we developed a Minimalist transcription template-based Amplification-free CRISPR-Cas13a strategy for DNA detection (MAD).

New insights into the function and therapeutic potential of RNA-binding protein TRBP in viral infection, chronic metabolic diseases, brain disorders and cancer.

RNA-binding proteins (RBPs) and non-coding RNAs are crucial trans-acting factors that bind to specific cis-acting elements in mRNAs, thereby regulating their stability and translation. The trans-activation response (TAR) RNA-binding protein (TRBP) recognizes precursor microRNAs (pre-miRNAs), modulates miRNA maturation, and influences miRNA interference (mi-RNAi) mediated by the RNA-induced silencing complex (RISC). TRBP also directly binds and mediates the degradation of certain mRNAs.

Novel plasma protein biomarkers: A time-dependent predictive model for Alzheimer's disease.

Background: The accurate prediction of Alzheimer's disease (AD) is crucial for the efficient management of its progression. The objective of this research was to construct a new risk predictive model utilizing novel plasma protein biomarkers for predicting AD incidence in the future and analyze their potential biological correlation with AD incidence.

Methods: A cohort of 440 participants aged 60 years and older from the Alzheimer's Disease Neuroimaging Initiative (ADNI) longitudinal cohort was utilized.

Cancer cell-derived exosome based dual-targeted drug delivery system for non-small cell lung cancer therapy.

Lung cancer is among most prevalent cancers in the world, in which non-small cell lung cancer (NSCLC) accounts for more than 85 % of all subtypes of lung cancers. NSCLC is often diagnosed at an advanced stage with a high mortality rate. Despite the demonstrated efficacy of chemotherapy in the treatment of NSCLC, the main drawback of current therapy is the lack of an effective drug-targeted delivery system, which may result in undesirable side effects during the clinical treatment.

Analysis of key targets for 5-hydroxymethyl-2-furfural-induced lung cancer based on network toxicology, network informatics, and experiments.

5-hydroxymethyl-2-furfural (5-HMF) is a by-product of Maillard reaction and widely exists in food and environment, which may lead to lung cancer. However, the relevant mechanism is unknown. This study aims to predict the key targets of 5-HMF-induced lung cancer through network toxicology, analyze the relationship between the key targets and lung cancer through network informatics, and further validate them through experiments.

Effect of long-term in-row branch covering on soil microorganisms in pear orchards.

Branches covering (BC) is a way to reuse the pruned branches and save the cost of ground cloth. This study investigated the effects of BC and ground-cloth covering on the soil microcosm environment by measuring the chemical properties and microbial communities at different soil depths for 6 years. The results revealed that BC significantly improved soil chemical properties, increased the abundance of bacterial microbial communities and the diversity and homogeneity of bacteria and fungi, while decreased the abundance of fungal microbial communities.

Encapsulating Antibiotic and Protein-Stabilized Nanosilver into Sandwich-Structured Electrospun Nanofibrous Scaffolds for -Infected Wound Treatment.

With the increasing prevalence of microbial infections, which results in prolonged inflammation and delayed wound healing, the development of effective and safe antimicrobial wound dressings of multiple properties remains challenging for public health. Despite their various formats, the available developed dressings with limited functions may not fulfill the diverse demands involved in the complex wound healing process. In this study, multifunctional sandwich-structured electrospinning nanofiber membranes (ENMs) were fabricated.

The cause and effect of gut microbiota in development of inflammatory disorders of the breast.

Background: Inflammatory disorders of the breast (IDB) damages the interests of women and children and hinders the progress of global health seriously. Several studies had offered clues between gut microbiota (GM) and inflammatory disorders of the breast (IDB). The gut-mammary gland axis also implied a possible contribution of the GM to IDB.

Discovery of Potent and Wild-Type-Sparing Fourth-Generation EGFR Inhibitors for Treatment of Osimertinib-Resistance NSCLC.

Osimertinib resistance is an unmet clinical need for the treatment of non-small cell lung cancer (NSCLC), and the main mechanism is tertiary C797S mutation of epidermal growth factor receptor (EGFR). To date, there is no inhibitor approved for the treatment of Osimertinib-resistant NSCLC. Herein, we reported a series of Osimertinib derivatives as fourth-generation inhibitors which were rationally designed.

Discovery of Potent DYRK2 Inhibitors with High Selectivity, Great Solubility, and Excellent Safety Properties for the Treatment of Prostate Cancer.

Prostate cancer (PCa) is a common male cancer with high incidence and mortality, and hormonal therapy as the major treatment for PCa patients is troubled by the inevitable resistance that makes us identify novel targets for PCa. Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) was found to be an effective target for the treatment of PCa, but the research on its inhibitors is rather little. In this work, a potent DYRK2 inhibitor (IC = 0.

5-Hydroxymethylfurfural induces mice frailty through cell senescence-associated sarcopenia caused by chronic inflammation.

Objective: 5-Hydroxymethylfurfural (5-HMF) is an important component of air pollution, confirmed to be a risk factor for pulmonary inflammation. However, its association with general health is unknown. This article aimed to clarify the effect and mechanism of 5-HMF in the occurrence and aggravation of frailty in mice by investigating whether exposure to 5-HMF was linked to the occurrence and aggravation of mice frailty.

Evaluation of the gut microbiome alterations in healthy rats after dietary exposure to different synthetic ZnO nanoparticles.

Aims: Although synthetic ZnO nanoparticles (Nano-ZnO) as an alternative of ZnO compounds have been extensively used such as in livestock production, the increased consuming of Nano-ZnO has raised considerable concerns in environmental pollution and public health. Because of the low digestion of Nano-ZnO, the systematic studies on their interactions with gut microbiota remain to be clarified.

Materials And Methods: Nano-ZnOs were prepared by co-precipitation (ZnO-cp) and high temperature thermal decomposition (ZnO-td) as well as the commercial type (ZnO-s).

Comparison of Phytochemical Constituents and Pharmacological Activities of Various Solvent Extracts Obtained from Stem Powder.

is a plant extensively used as an important component in Chinese herbal medicine and food-based medicines. The present study was carried out to determine the total flavonoid content (TFC), volatile phytoconstituents, and pharmacological activities, i.e.

Discovery, Optimization, and Evaluation of Selective CDK4/6 Inhibitors for the Treatment of Breast Cancer.

Breast cancer is the most common tumor in women, and selective cyclin-dependent kinase (CDK) 4/6 inhibitors played an important role in the treatment of breast cancer. Therefore, discovering selective CDK4/6 inhibitors with great safety and potent efficacy is beneficial for the breast cancer treatment. In our work, the lead compound was identified through virtual screening; then, systematic structural optimization was conducted to afford , which exhibited strong inhibition on CDK4/6 and showed high selectivity among 205 kinases.

Clinical significance of potential drug-drug interactions in older adults with psychiatric disorders: a retrospective study.

Background: Polypharmacy increases the risk of potential drug-drug interactions (pDDIs). This retrospective analysis was conducted to detect pDDIs and adverse drug reactions (ADRs) among older adults with psychiatric disorder, and identify pDDIs with clinical significance.

Methods: A retrospective analysis was carried out based on the medical records of older adults with psychiatric disorders.

SP1-Induced Upregulation of lncRNA LINC00659 Promotes Tumour Progression in Gastric Cancer by Regulating miR-370/AQP3 Axis.

Growing evidence demonstrates that long noncoding RNAs (lncRNAs) play critical roles in various human tumors. LncRNA LINC00659 (LINC00659) is a newly identified lncRNA and its roles in tumors remain largely unclear. In this study, we elucidated the potential functions and molecular mechanisms of LINC00659 on the biological behaviors of gastric cancer (GC), and also explored its clinical significance.

Systematic Identification of the RNA-Binding Protein STAU2 as a Key Regulator of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer. RNA-binding proteins (RBPs) regulate highly dynamic post-transcriptional processes and perform very important biological functions. Although over 1900 RBPs have been identified, most are considered markers of tumor progression, and further information on their general role in PAAD is not known.