Two-Dimensional Square Lattice of Colloidal Particles Formed by Electrostatic Adsorption in Confined Space.

In this study, we demonstrate a novel and efficient fabrication methodology for nonclose-packed, two-dimensional (2D) colloidal crystals exhibiting square lattice structures. In our recent work, we detailed the formation of 2D colloidal crystals via the electrostatic adsorption of three-dimensional (3D) charged colloidal crystals onto oppositely charged substrates. These 3D colloidal crystals possessed a face-centered cubic (FCC) lattice structure with their (111) planes aligned parallel to the substrate, facilitating the formation of 2D crystals with triangular lattice arrangements upon adsorption.

Comparative evaluation of cellular senescence in naturally aged and stress-induced murine macrophages for identifying optimum senescent macrophage study systems.

Background: The role and relevance of macrophages both as causes and therapeutics of cellular senescence is rapidly emerging. However, current knowledge regarding the extent and depth of senescence in macrophages in vivo is limited and controversial. Further, acute models of stress-induced senescence in transformed/cancerous macrophage cell lines are being used although their efficacy and relevance are not characterized.

Multifunctional Nanomedicine for Targeted Atherosclerosis Therapy: Activating Plaque Clearance Cascade and Suppressing Inflammation.

Atherosclerosis (AS) is a prevalent inflammatory vascular disease characterized by plaque formation, primarily composed of foam cells laden with lipids. Despite lipid-lowering therapies, effective plaque clearance remains challenging due to the overexpression of the CD47 molecule on apoptotic foam cells, inhibiting macrophage-mediated cellular efferocytosis and plaque resolution. Moreover, AS lesions are often associated with severe inflammation and oxidative stress, exacerbating disease progression.

High GRWD1 expression may predict clinically aggressive lower grade glioma, skin cutaneous melanoma, and kidney renal clear cell carcinoma carrying wild-type p53: a systematic study based on TCGA data analysis.

Glutamate-rich WD40 repeat containing 1 (GRWD1) is a novel oncogene/oncoprotein that downregulates the p53 tumor suppressor protein through several mechanisms. One important mechanism involves binding of GRWD1 to RPL11, which competitively inhibits the RPL11-MDM2 interaction and releases RPL11-mediated suppression of MDM2 ubiquitin ligase activity toward p53. Here, we mined the TCGA (The Cancer Genome Atlas) database to gain in-depth insight into the clinical relevance of GRWD1.

Early Evaluation of the Interaction and Gender Differences in Combination of Apatinib and Metoprolol Using Humanized CYP2D6 Model.

Apatinib, a commonly used tyrosine kinase inhibitor in cancer treatment, can cause adverse reactions such as hypertension. Hypertension, in turn, can increase the risk of certain cancers. The coexistence of these diseases makes the use of combination drugs more common in clinical practice, but the potential interactions and regulatory mechanisms in these drug combinations are poorly understood.

Yip1 interacting factor homolog B mediates the unconventional secretion of ORF8 during SARS-CoV-2 infection.

Severe cases of COVID-19 are associated with immune responses that lead to a surge in inflammatory molecules, resulting in multi-organ failure and death. This significant increase in inflammatory factors is triggered by viral proteins. Open reading frame 8 (ORF8) has received particular attention as a unique accessory protein of SARS-CoV-2.

Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patients.

Introduction: Severe cutaneous adverse reactions (SCARs) are life-threatening and often linked to antiepileptic drugs (AEDs). Common types of SCARs include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Immune-mediated mechanisms involving human leukocyte antigen () alleles have been implicated in the pathogenesis of this reaction.

Ligand Design with Accelerated Disulfide Formation with Serum Albumin to Extend Blood Retention.

We proposed a novel ligand for the interaction with human serum albumin (HSA) to extend the blood half-life of small molecular weight therapeutics. The ligand features an alkyl chain and an activated disulfide to allow binding to the hydrophobic pockets of HSA and the formation of disulfide to Cys34 of HSA, thereby minimizing the initial renal clearance. The dual nature of the ligand-HSA bonding was expected to give the ligand long blood retention.

A versatile entry to unnatural, disulfide-linked amino acids and peptides through the disulfuration of azlactones.

Despite the evident demand and promising potential of disulfide-functionalized amino acids and peptides in linker chemistry and peptide drug discovery, those disulfurated specifically at the α-position constitute a unique yet rather highly underexplored chemical space. In this study, we have developed a method for preparing -linked amino acid/peptide derivatives through a base-catalyzed disulfuration reaction of azlactones, followed by the ring-opening functionalization. The disulfuration reaction proceeds under mild conditions, yielding disulfurated azlactones in excellent yields across a variety of -dithiophthalimides and diverse azlactones derived from various amino acids and peptides.

Advances in VEGFR Inhibitors: A Comprehensive Review of Novel Anticancer Agents.

Cancer, characterized by aberrant cell growth, presents a formidable health challenge, impacting millions of individuals worldwide each year. Among the myriad mechanisms facilitating tumor progression, Vascular Endothelial Growth Factor receptors (VEGFR) play a pivotal role in driving angiogenesis the process by which tumors develop their own blood supply. This vascularization not only supports tumor nourishment and growth but also facilitates metastasis, enabling cancer to spread to distant sites.

Single-cell multi-omics deciphers hepatocyte dedifferentiation and illuminates maintenance strategies.

Due to the similarity to human hepatocytes, porcine hepatocytes play an important role in hepatic research and drug evaluation. However, once hepatocytes were cultured in vitro, it was often prone to dedifferentiate, resulting in the loss of their characteristic features and normal functions, which impede their application in liver transplantation and hepatotoxic drugs evaluation. Up to now, this process has yet to be thoroughly investigated from the single-cell resolution and multi-omics perspective.

Importance of Computer-Aided Drug Design in Modern Pharmaceutical Research.

Background: Computer-Aided Drug Design (CADD) approaches are essential in the drug discovery and development process. Both academic institutions and pharmaceutical and biotechnology corporations utilize them to enhance the efficacy of bioactive compounds.

Objective: This study aims to entice researchers by investigating the benefits of Computer-Aided Drug and Design (CADD) and its fundamental principles.

Potential of Nanoparticle Based Antimicrobial Drug Repurposing to Efficiently Target Alzheimer's: A Concise Update on Evidence-based Research and Challenges Ahead.

Repurposing of drugs through nanocarriers (NCs) based platforms has been a recent trend in drug delivery research. Various routine drugs are now being repurposed to treat challenging neurodegenerative disorders including Alzheimer disease (AD). AD, at present is one of the challenging neurodegenerative disorders characterized by extracellular accumulation of amyloid-β and intracellular accumulations of neurofibrillary tangles.

Synaptic Targets and Cellular Sources of CB1 Cannabinoid Receptor and Vesicular Glutamate Transporter-3 Expressing Nerve Terminals in Relation to GABAergic Neurons in the Human Cerebral Cortex.

Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunoreactive axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3.

Integrating the ADS Score with 24-Hour ASPECTS and red cell distribution width for enhanced prediction of stroke-associated pneumonia following intravenous thrombolysis: model development and internal validation.

Introduction: Stroke-associated pneumonia (SAP) is a major cause of mortality during the acute phase of stroke. The ADS score is widely used to predict SAP risk but does not include 24-h non-contrast computed tomography-Alberta Stroke Program Early CT Score (NCCT-ASPECTS) or red cell distribution width (RDW). We aim to evaluate the added prognostic value of incorporating 24-h NCCT-ASPECTS and RDW into the ADS score and to develop a novel prediction model for SAP following thrombolysis.

Citrullinated IGF2BP1 promotes rheumatoid synovial aggression via increasing the mRNA stability of SEMA3D.

Protein citrullination modification plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA), and anti-citrullinated protein antibodies (ACPAs) are extensively employed for clinical diagnosis of RA. However, there remains limited understanding regarding specific citrullinated proteins and their implications in the progression of RA. In this study, we screen and verify insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) as a novel citrullinated protein with significantly elevated citrullinated level in RA.

Saturated F2-rings from Alkenes.

A general method to convert simple exocyclic alkenes (no Ar-substituents) into saturated F2-rings has been developed. The reaction involves the IIII-reagent C6F5I(OAc)2 (F5-PIDA). The reaction efficiently works on the mg-, g-, and even multigram scale.

Discovery of Brain-Penetrative Negative Allosteric Modulators of NMDA Receptors Using FEP-Guided Structure Optimization and Membrane Permeability Prediction.

-Methyl-d-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptors in the central nervous system (CNS), have garnered attention for their role in brain disorders. Specifically, GluN2A-containing NMDA receptors have emerged as a potential therapeutic target for the treatment of depressive disorders and epilepsy. However, the development of GluN2A-containing NMDA receptor-selective antagonists, represented by -(4-(2-benzoylhydrazine-1-carbonyl)benzyl)-3-chloro-4-fluorobenzenesulfonamide (TCN-201) and its derivatives, faces a significant challenge due to their limited ability to penetrate the blood-brain barrier (BBB), hampering their characterization and further advancement.

High cellular plasticity state of medulloblastoma local recurrence and distant dissemination.

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets.

Assessment of Osteoprotegerin and Receptor Activator of Nf-Κb Ligand in Malaysian Male Patients with Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

Background: Limited information exists regarding the pathophysiological interactions between osteoporosis and chronic obstructive pulmonary disease (COPD). Objective: To study the association of Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL) in male COPD patients. Methods: An observational clinical study was conducted at Penang General Hospital in Malaysia.

Synthesis and biological evaluation of 4-((3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)oxy)quinoline derivatives as novel potential transforming growth factor-β type 1 receptor inhibitors for hepatocellular carcinoma.

The transforming growth factor β (TGF-β) type 1 receptor (ALK5) plays a key role in tumor microenvironment. Small-molecule inhibitors of TGFβR1 provides a prospective approach for the treatment of malignant tumors. In this study, a series of 4-((3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)oxy)quinoline derivatives were identified as novel, potential TGFβR1 inhibitors.

Schisandrol B alleviates depression-like behavior in mice by regulating bile acid homeostasis in the brain-liver-gut axis via the pregnane X receptor.

Background: Depression is a widely recognized neuropsychiatric disorder. Recent studies have shown a potential correlation between bile acid disorders and depression, highlighting the importance of maintaining bile acid balance for effective antidepressant treatment. Schisandrol B (SolB), a primary bioactive compound from Schisandra chinensis (Turcz.

Biocatalytic Hydrogenation of Biomass-Derived Furan Aldehydes to Alcohols.

The biomass-derived furan aldehydes furfural (FF) and 5-hydroxymethylfurfural (HMF) are versatile platform chemicals used to produce various value-added chemicals through further valorization processes. Selectively reducing C═O in FF and HMF molecules to form furfuryl alcohol (FAL) and 2,5-bis(hydroxymethyl)furan (BHMF), represents an important research field in upgrading biomass-based furan compounds. Currently, the reduction of furan aldehydes to furan alcohols through chemical transformation often leads to unavoidable environmental issues and the formation of potential byproducts.

Assembly and functional mechanisms of plant NLR resistosomes.

Nucleotide-binding and leucine-rich repeat (NLR) proteins are essential intracellular immune receptors in both animal and plant kingdoms. Sensing of pathogen-derived signals induces oligomerization of NLR proteins, culminating in the formation of higher-order protein complexes known as resistosomes in plants. The NLR resistosomes play a pivotal role in mediating the plant immune response against invading pathogens.

Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents.

The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.