Computer-aided discovery of triazolothiadiazoles as DYRK1A-targeted neuroprotective agents.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a promising target for drug discovery against neurological diseases. So far, no DYRK1A inhibitor has been approved for clinical use, partly due to the lack of effective and safe chemotypes. In this study, by using a computer-aided drug design strategy and DYRK1A inhibition assay, we were able to identify a novel DYRK1A inhibitor, , compound Y16-5 (Specs ID: ) with an IC value of 0.

A scoping review of advancements in machine learning for glaucoma: current trends and future direction.

Introduction: Machine learning technology has demonstrated significant potential in glaucoma research, particularly in early diagnosis, predicting disease progression, evaluating treatment responses, and developing personalized treatment strategies. The application of machine learning not only enhances the understanding of the pathological mechanism of glaucoma and optimizes the diagnostic process but also provides patients with accurate medical services.

Methods: This study aimed to describe the current state of research, highlight directions for further development, and identify potential trends for improvement.

Machine Learning-Based Discovery of a Novel Noncovalent MurA Inhibitor as an Antibacterial Agent.

The bacterial cell wall is crucial for maintaining the integrity of bacterial cells. UDP-N-acetylglucosamine 1-carboxyethylene transferase (MurA) is an important enzyme involved in bacterial cell wall synthesis. Therefore, it is an important target for antibacterial drug research.

Identification of ETFDH gene c. 487 + 2 T > A pathogenic variant and mechanisms for polycystic kidney in neonatal onset MADD.

Background: Multiple acyl-coenzyme A (CoA) dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from mutations in the ETFDH gene. It is characterized by a wide spectrum of clinical symptoms, of which polycystic kidney disease is a specific phenotype of early-onset MADD. This study aims to broaden the genetic mutation spectrum of ETFDH gene.

Development of a vitrified CRISPR/Cas12b-based assay for rapid genotyping of SNPs without DNA amplification.

Two single nucleotide polymorphisms (SNPs) in the human gene, c.388A>G (rs2306283) and c.521T>C (rs4149056), are independent determinants of the efficacy and side effects of statin drugs.

Discovery of Novel FtsZ Inhibitors With Antimicrobial Activity by Virtual Screening and In Vitro Biological Evaluation.

The filamentous temperature-sensitive protein Z (FtsZ) plays a vital role in bacterial division, making it an important antibacterial target. The inhibitor activity targeting the cleft between the H7 helix and the C-terminal substructural domain exhibited superior binding compared to the GTP binding site. This highlights the potential of the cleft as a promising target for further inhibitor discovery.

Discovery of Metabolic Reprogramming 2-Quinolones as Effective Antimicrobials for MRSA-Infected Wound Therapy.

To date, the abuse of antibiotics and a gradual decline in novel antibiotic discovery enlarge the threat of drug-resistant bacterial infections, especially methicillin-resistant (MRSA). Herein, inspired by the unique structures and antibacterial activities of 2-quinolones, a class of novel 2-quinolones with substituted pyridines was synthesized. Notably, compound , the derivative with a methylpyridine fragment, showed potent antibacterial and antibiofilm activities, especially for MRSA strains (MIC = 0.

Expression of ALG8 in hepatocellular carcinoma and its diagnostic and prognostic significance.

Background: Alpha-1,3-glucosyltransferase (ALG8), a key enzyme in protein glycosylation, is implicated in the oncogenesis and progression of several human malignancies. This study aimed to define the role of ALG8 in hepatocellular carcinoma (HCC) and uncover its mechanisms of action.

Methods: ALG8 expression in HCC and normal tissues was analyzed using the TCGA and GEO databases, validated by RT-qPCR and western blot.

Multi-omic characterization of air pollution effects: Applications of AirSigOmniTWP Hub.

Air pollution, particularly fine particulate matter and gaseous pollutants including NO and NO, presents significant public health challenges. While the harmful effects of these pollutants are well-documented, the molecular mechanisms underlying their impact on health remain incompletely understood. In this study, we utilized genome-wide association study (GWAS) data from the UK Biobank, expression quantitative trait loci (eQTL) data from the Genotype-Tissue Expression (GTEx) project, and protein quantitative trait loci (pQTL) data from the Atherosclerosis Risk in Communities (ARIC) study to conduct comprehensive analyses using the Unified Test for Molecular Signatures (UTMOST), Transcriptome-wide Association Studies (TWAS), and Proteome-wide Association Studies (PWAS).

Discovery of a novel DYRK1A inhibitor with neuroprotective activity by virtual screening and in vitro biological evaluation.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is implicated in accumulation of amyloid β-protein (Aβ) and phosphorylation of Tau proteins, and thus represents an important therapeutic target for neurodegenerative diseases. Though many DYRK1A inhibitors have been discovered, there is still no marketed drug targeting DYRK1A. This is partly due to the lack of effective and safe chemotypes.

Integrated analysis identified the role of three family members of ARHGAP in pancreatic adenocarcinoma.

The Rho GTPase activating protein family (ARHGAPs) is expressed in pancreatic adenocarcinoma (PAAD) but its function is unclear. The aim of this study was to explore the role and potential clinical value of ARHGAPs in PAAD. Using TCGA and GEO databases to analyze expression of ARHGAPs in PAAD and normal tissues.

Identification of SMC2 and SMC4 as prognostic markers in breast cancer through bioinformatics analysis.

Background: Breast cancer (BRCA) is one of the most common malignant tumors. The structural maintenance of chromosome (SMC) gene family has been shown to play an important role in human cancers. However, the role of SMC families in BRCA is unclear.

Combined transcriptome and proteome analysis reveals MSN and ARFIP2 as biomarkers for trastuzumab resistance of breast cancer.

Purpose: HER2-positive breast cancer (BC) accounts for 20-30% of all BC subtypes and is linked to poor prognosis. Trastuzumab (Tz), a humanized anti-HER2 monoclonal antibody, is a first-line treatment for HER2-positive breast cancer which faces resistance challenges. This study aimed to identify the biomarkers driving trastuzumab resistance.

Discovery of a novel chemotype as DYRK1A inhibitors against Alzheimer's disease: Computational modeling and biological evaluation.

Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) plays an essential role in Tau and Aβ pathology closely related to Alzheimer's disease (AD). Accumulative evidence has demonstrated DYRK1A inhibition is able to reduce the pathological features of AD. Nevertheless, there is no approved DYRK1A inhibitor for clinical use as anti-AD therapy.

A landscape of metabolic variation among clinical outcomes of peritoneal dialysis in end-stage renal disease.

Background: Peritoneal dialysis (PD) helps prevent lethal complications of end-stage renal disease (ESRD). However, the clinical outcomes are affected by PD-related complications. We investigated metabolic biomarkers to estimate the clinical outcomes of PD and identify patients at high risk of downstream complications and recurrent/relapsing infections.

AutoMolDesigner for Antibiotic Discovery: An AI-Based Open-Source Software for Automated Design of Small-Molecule Antibiotics.

Discovery of small-molecule antibiotics with novel chemotypes serves as one of the essential strategies to address antibiotic resistance. Although a considerable number of computational tools committed to molecular design have been reported, there is a deficit in holistic and efficient tools specifically developed for small-molecule antibiotic discovery. To address this issue, we report AutoMolDesigner, a computational modeling software dedicated to small-molecule antibiotic design.

Identification of a 2-phenylthiazole derivative acetylcholinesterase modulator with in vitro antitumor activity in breast cancer cells.

Acetylcholinesterase (AchE) is a serine hydrolase with classical function to degrade acetylcholine and terminate neurotransmission. While "nonclassical" functions of AchE were involved in cell growth, death, invasion, etc. The expression and activity of AchE is changed in tumors, suggesting AChE inhibitors (AchEIs) may serve as potential antitumor drugs.

Discovery of isatin-β-methyldithiocarbazate derivatives as New Delhi metallo- β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates.

New Delhi metallo-β-lactamase-1 (NDM-1) poses a threat to public health due to its capability to hydrolyze nearly all β-lactam antibiotics, leaving limited treatment options for NDM-1 positive pathogens. Regrettably, there are presently no effective NDM-1 inhibitors in clinical use. This compels us to seek new compounds to combat multi-drug resistant bacterial infections (MDR).

Rapid and accurate genotyping of human SNP rs671 in aldehyde dehydrogenase 2 gene using one-step CRISPR/Cas12b assay without DNA amplification.

Background: The SNP rs671 of Human aldehyde dehydrogenase (ALDH) is G-A transition at 1510th nucleotides, which is an important clinical indicator of alcoholic liver disease, digestive tract cancer and some drug efficiency. The commonly used genotyping assay of this polymorphism is relatively time-consuming and costly.

Finding: This study develops a rapid and accurate one-step CRISPR/Cas12b assay to distinguish the G1510A polymorphism of human ALDH2 free of DNA amplification.

Biomaterial-assisted tumor therapy: A brief review of hydroxyapatite nanoparticles and its composites used in bone tumors therapy.

Malignant bone tumors can inflict significant damage to affected bones, leaving patients to contend with issues like residual tumor cells, bone defects, and bacterial infections post-surgery. However, hydroxyapatite nanoparticles (nHAp), the principal inorganic constituent of natural bone, possess numerous advantages such as high biocompatibility, bone conduction ability, and a large surface area. Moreover, nHAp's nanoscale particle size enables it to impede the growth of various tumor cells diverse pathways.

Comprehensive bioinformatics analysis reveals the significance of forkhead box family members in pancreatic adenocarcinoma.

Background: Forkhead box proteins (FOXs) play important roles in multiple biological processes; while little is known regarding the role of FOX members in pancreatic adenocarcinoma (PAAD). This study aimed to comprehensively investigate the function of FOX family members in PAAD.

Methods: Expression and prognostic value of FOXs were analyzed by R language and GEPIA.

LncRNA DDX11-AS1 Promotes Chemoresistance through LIN28A-Mediated ATG12 mRNA Stabilization in Breast Cancer.

Introduction: During breast cancer chemotherapy, the chemoresistance that frequently accompanies the treatment has become a big challenge. Long noncoding RNAs (LncRNAs) have been related to the development of chemoresistance in multiple cancer types. LncRNA DDX11-AS1 has shown a carcinogenic role in lung and colorectal cancer and was reported to enhance oxaliplatin resistance in gastric cancer and Taxol insensitivity in esophageal cancer.

Expedient Discovery for Novel Antifungal Leads Inhibiting : 3-(Phenylamino)quinazolin-4(3)-ones Deriving from Systematic Optimizations on a Tryptanthrin Structure.

The ever-increasing resistance of has emerged as a pressing agricultural issue that could be settled by developing novel fungicides owning inimitable action mechanisms. With the aim of discovering novel antifungal leads inhibiting , a tryptanthrin structure was dexterously optimized to generate 30 novel quinazolin-4(3)-one derivatives. The aforementioned optimization generated the molecule that owned exhilarating anti- effect (EC value = 0.

A Novel ATM Antisense Transcript ATM-AS Positively Regulates ATM Expression in Normal and Breast Cancer Cells.

Objective: The ataxia telangiectasia mutated (ATM) gene is a master regulator in cellular DNA damage response. The dysregulation of ATM expression is frequent in breast cancer, and is known to be involved in the carcinogenesis and prognosis of cancer. However, the underlying mechanism remains unclear.