Directed Electrostatics Strategy Integrated as a Graph Neural Network Approach for Accelerated Cluster Structure Prediction.

We present a directed electrostatics strategy integrated as a graph neural network (DESIGNN) approach for predicting stable nanocluster structures on their potential energy surfaces (PESs). The DESIGNN approach is a graph neural network (GNN)-based model for building structures of large atomic clusters with specific sizes and point-group symmetry. This model assists in the structure building of atomic metal clusters by predicting molecular electrostatic potential (MESP) topography minima on their structural evolution paths.

Mid-term Outcomes of Patella Resurfacing During Total Knee Arthroplasty (TKA): Clinical, Functional, and Radiographic Insights.

Aim The primary objective of the study was to evaluate the mid-term implant survivability, rate of revisions, and clinical and functional outcomes following patella resurfacing during total knee arthroplasty (TKA) utilizing posterior stabilized (PS) total knee system (TKS). Methods A prospective, single-arm, multi-center, post-marketing surveillance encompassed patients with end-stage primary knee osteoarthritis (OA) or inflammatory arthritis. The time points of the study included baseline, six weeks, six months, one year, and three years post-operatively.

Optimizing Linezolid: Transforming It into a Selective MAO-B Inhibitor via a Toxicity-to-Activity Optimization Approach.

Linezolid, a widely used oxazolidinone antibiotic, exhibits potent activity against resistant bacterial infections but is associated with serotonergic toxicity, primarily due to its inhibition of monoamine oxidase (MAO). MAOs, consisting of MAO-A and MAO-B isoforms, play crucial roles in neurotransmitter metabolism, with implications for neurodegenerative disorders like Parkinson's and Alzheimer's diseases. This study aims to optimize Linezolid's structure to transform it into a selective MAO-B inhibitor.

Synthetic Strategies for the Development of Ibuprofen Derivatives: A Classified Study.

Ibuprofen, a widely used NSAID from the aryl propionic acid class, effectively relieves pain, fever, and inflammation. On prolonged use, it leads to gastrointestinal, hepatic, and renal toxicities, particularly gastrointestinal ulcers. These side effects are largely attributed to the carboxylic acid functional group common to NSAIDs.

Characterization and interactions between piperine and ezetimibe in their Anti-hyperlipidemic efficacy using Biopharmaceutics and Pharmacokinetics.

Background: Piperine, a secondary metabolite, affects the antihyperlipidemic effect of Ezetimibe (EZ). Hyperlipidemia is one of the independent risk factors for cardiovascular disorders such as atherosclerosis. Antihyperlipidemic drugs are essential for reducing cardiovascular events and patient mortality.

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.

Polyphenols as Wnt/β-catenin pathway modulators: A promising strategy in clinical neurodegeneration.

Polyphenols, a diverse group of naturally occurring compounds found in plants, have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases (NDs). The Wnt/β-catenin (WβC) signaling pathway, a crucial player in neurogenesis, neuronal survival, and synaptic plasticity, is involved in several cellular mechanisms related to NDs. Dysregulation of this pathway is a hallmark in the development of various NDs.

Organocatalytic [4+2] Benzannulation Between 1,4-Dithiane-Based Enal and Nitroolefins to Access 2-Nitrobiaryls.

A simple method for constructing unsymmetrical 2-nitrobiaryls has been developed between substituted 1,4-dithiine-2-carbaldehyde and nitroolefins under metal-free conditions. To gain the advantage of the HOMO-raising effect of temporary substitutions on in situ generated dienamine intermediate, the present protocol established [4+2] benzannulation of 1,4-dithiane-tethered enals with nitroolefin. Further, easy unmasking of 1,4-dithiine units results in a benzannulation product like that of unsubstituted enals, which are difficult to access.

CPAP Therapy for OSA and Its Impact on Various Cardiovascular Disorders.

Obstructive sleep apnea (OSA), a highly prevalent and serious disorder with significant complications, causes considerable daytime and nighttime symptoms as well as long-term consequences and is yet an underdiagnosed and inadequately treated condition. Patients with OSA undergo frequent awakenings during the sleep cycle and find it impossible to get restorative sleep. Individuals are extremely fatigued, sleepy, and irritable throughout the day.

Conservation agricultural practices promoted arbuscular mycorrhizal fungal colonization and glomalin content on sandy clay loam of southern India.

Arbuscular mycorrhizal Fungi (AMF) are essential in agriculture and are often inter-linked with glomalin-related soil protein (GRSP) production which supports binding of aggregates, enhanced SOC and biological attributes. However, conservation agricultural practices in agroecosystem may have significant impact on AMF diversity, GRSP and soil quality-related parameters (SQRPs). This current experiment was implemented to gauge AMF conization percentage (AMF-CP), GSRP and significant changes on critical SQRPs, and to investigate the linkages between AMF-CP, GRSP and SQRPs as influenced by synergistic tillage and weed management in CA.

Synthesis, Characterization, and Docking Studies of 1,4-dien as a Potential Impurity in Bimatoprost Drug.

Introduction: The origin, synthesis, characterization and docking studies of (Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((R,1E,4E)-3-hydroxy-5-phenylpenta-1,4-dien-1-yl)cyclopentyl)-N-ethylhept-5-enamide, an impurity generated in the preparation of an anti-glaucoma agent-Bimatoprost has been described.

Methods: This impurity was controlled by employing 30% Pd/C, and the impurity level was brought to the permissible level, i.e.

Silica Nanoparticles: A Promising Vehicle for Anti-Cancer Drugs Delivery.

The prevalence and death due to cancer have been rising over the past few decades, and eliminating tumour cells without sacrificing healthy cells remains a difficult task. Due to the low specificity and solubility of drug molecules, patients often require high dosages to achieve the desired therapeutic effects. Silica nanoparticles (SiNPs) can effectively deliver therapeutic agents to targeted sites in the body, addressing these challenges.

Investigating misclassification of type 1 diabetes in a population-based cohort of British Pakistanis and Bangladeshis using polygenic risk scores.

Correct classification of type 1 (T1D) and type 2 diabetes (T2D) is challenging due to overlapping clinical features and the increasingly early onset of T2D, particularly in South Asians. Polygenic risk scores (PRSs) for T1D and T2D have been shown to work relatively well in South Asians, despite being derived from largely European-ancestry samples. Here we used PRSs to investigate the rate of potential misclassification of diabetes amongst British Bangladeshis and Pakistanis.

Gymnema saponin-induced lipid flip-flop identifies rigid membrane phenotype of methicillin resistant S. aureus and enhances it's antibiotic susceptibility.

Our previous study revealed that lipid flip-flop inducing phytochemicals from Gymnema sylvestre increase membrane permeability of antimicrobials in S. aureus. However, their lipid flipping and membrane permeabilizing effect on methicillin resistant S.

Casein Kinases 2-dependent phosphorylation of the placental ligand VAR2CSA regulates Plasmodium falciparum-infected erythrocytes cytoadhesion.

Placental malaria is characterized by the massive accumulation and sequestration of infected erythrocytes in the placental intervillous blood spaces, causing severe birth outcomes. The variant surface antigen VAR2CSA is associated with Plasmodium falciparum sequestration in the placenta via its capacity to adhere to chondroitin sulfate A. We have previously shown that the extracellular region of VAR2CSA is phosphorylated on several residues and that the phosphorylation enhances the adhesive properties of CSA-binding infected erythrocytes.

Exploring the therapeutic potential of GLP-1 receptor agonists in the management of obstructive sleep apnea: a comprehensive review.

Obstructive Sleep Apnea (OSA) is a prevalent sleep disorder marked by repeated episodes of partial or complete upper airway obstruction during sleep, which leads to intermittent hypoxia and fragmented sleep. These disruptions negatively impact cardiovascular health, metabolic function, and overall quality of life. Obesity is a major modifiable risk factor for OSA, as it contributes to both anatomical and physiological mechanisms that increase the likelihood of airway collapse during sleep.

Novel combination therapy targeting oncogenic signaling kinase P21 activated Kinase-1 and chemotherapeutic drugs against triple negative breast cancer.

Most of the triple negative phenotype or basal-like molecular subtypes of breast cancers are associated with aggressive clinical behaviour and show poor disease prognosis. Current treatment options are constrained, emphasizing the need for novel combinatorial therapies for this particular tumor subtype. Our group has demonstrated that functionally active p21 activated kinase 1 (PAK1) exhibits significantly higher expression levels in clinical triple negative breast cancer (TNBC) samples compared to other subtypes, as well as adjacent normal tissues.

Vitrectomy for diabetic retinopathy: A review of indications, techniques, outcomes, and complications.

Diabetic retinopathy is one of the most severe forms of retinopathy and a leading cause of blindness all over the world. Of a greater concern is proliferative diabetic retinopathy which leads to vitreous haemorrhage and tractional retinal detachment in such cases. A majority of these cases require a surgical intervention to improve vision and prevent further vision loss.

Discovery of novel PDGFR inhibitors targeting non-small cell lung cancer using a multistep machine learning assisted hybrid virtual screening approach.

Non-Small Cell Lung Cancer (NSCLC) is a formidable global health challenge, responsible for the majority of cancer-related deaths worldwide. The Platelet-Derived Growth Factor Receptor (PDGFR) has emerged as a promising therapeutic target in NSCLC, given its crucial involvement in cell growth, proliferation, angiogenesis, and tumor progression. Among PDGFR inhibitors, avapritinib has garnered attention due to its selective activity against mutant forms of PDGFR, particularly PDGFRA D842V and KIT exon 17 D816V, linked to resistance against conventional tyrosine kinase inhibitors.

Rabies in rural northeast India: A case report emphasising the urgency of the One Health approach.

Dog-mediated rabies is endemic in India. The country records the highest mortality due to dog-bite-related rabies despite the availability of interventions to prevent deaths. We present a case study of the death of a 59-year-old man in a suburban town of Northeast India after a dog bite from an owned pup.

A leucine responsive small RNA AbcR200 regulates expression of the lactate utilization (lut) operon in Acinetobacter baumannii DS002.

Noncoding small RNAs are essential for modulating bacterial gene expression, especially under carbon and nutrient-limited conditions. In this study, by employing both in silico and molecular hybridization tools, we identified a carbon source responsive small RNA in A. baumannii DS002.

3D printed Aloe barbadensis loaded alginate-gelatin hydrogel for wound healing and scar reduction: In vitro and in vivo study.

Wounds are one of the most critical clinical issues in plastic surgery repair and restoration. Conventional wound dressing materials cannot absorb enough wound exudates and shield the site from microbial infection. Also, despite their healing prowess, bioactive molecules from medicinal plants are less bioavailable at the wound sites.

Emergence of ADM-mediated bioconjugate to enhance longevity and catalytic efficiency of urease.

The versatile nature of the urease enzyme makes it a valuable asset in biological and industrial contexts. The creation of bioconjugates using enzyme-polymer combinations has extended the shelf life and stability of urease. A triblock copolymer, PAM-co-PDPA-co-PMAA@urease (ADM@urease), was synthesized using acrylamide (AM), 2,5-dioxopyrrolidin-1-ylacrylate (DPA), methacrylic acid (MAA), and urease via the RAFT-Grafting-To polymerization method.

Molecular and phylogenetic analyses of the first complete genome sequence of Duck hepatitis A virus genotype 2 from India.

Duck viral hepatitis (DVH) caused by duck hepatitis A virus (DHAV) is a highly contagious and economically important disease of ducklings worldwide. In many parts of the globe, disease outbreaks are reported in spite of vaccinations, probably due to antigenic diversity among DHAV genotypes. We previously reported the first isolation of DHAV-2 (Genotype -2) from ducklings in Tamil Nadu, India.