Krishna Kistan Govender

किसी देश की संस्कृति, वहाँ के लोगों की पहचान जानने में एक महत्वपूर्ण मार्गदर्शक होती है। प्राचीन काल से भारत और श्री लंका के बीच मौजूद आपसी सांस्कृतिक संबंध इन देशों को चुनने का एक प्रमुख कारण था। इसलिए मैं उत्तर भारतीय क्षेत्रों और श्री लंकाई लोक गीतों के माध्यम से प्रकट होनेवाले दोनों देशों के ग्रामीण समाज की सांस्कृतिक पृष्ठभूमि के बारे में जानकारी का अध्ययन करना आशा करती हूँ। दोनों देशों के लोक गीतों में व्यक्त सांस्कृतिक सूचनाओं का अध्ययन करके नये तथ्य एकत्रित करना और ज्ञान प्राप्त करना है। उत्तर भारत और श्री लंका के ग्रामीण लोगों की संस्कृति, जन्म से लेकर मृत्यु तक कैसे संचालित होती थी, यह इसकी मुख्य समस्या है। यह शोध, गुणात्मक शोध प्रविधि के आगमनात्मक दृष्ठिकोण के आधार पर किया गया है। प्राथमिक स्रोतों के तहत, उत्तर भारतीय और श्री लंकाई लोक गीतों से संबंधित ग्रंथों का प्रयोग किया और द्वितीय स्रोतों के तहत, इससे संबंधित अन्य ग्रंथ, शोध आलेख तथा अंतरजाल का प्रयोग किया गया। इस शोध आलेख के आधार पर यह निष्कर्ष निकाला जा सकता है कि, दोनों देशों के लोक गीतों से प्राप्त जानकारियों में समानताओं के साथ-साथ...

Background/Objectives: Poly (ADP-ribose) polymerase (PARP1) has emerged as a promising therapeutic target in human breast cancer particularly in BRCA1/2 mutation carriers where a synthetic lethal interaction leads to massive tumor cell death upon specific inhibitors’ administration. Current clinically approved PARP inhibitors (Talazoparib and Olaparib) show outstanding therapeutic capabilities but suffer from severe side effects. Most importantly, some of them can cause life-threatening cardiotoxicity through hERG off-target effects. Here, we performed an extensive study to identify lead compounds with improved binding modes and favorable predicted pharmacokinetics using an integrated computational strategy. Methods: An artificial intelligence-driven drug design (AIDDISON™ v2023) workflow was employed to search ultra-large chemical space libraries for active compounds, which were then optimized via computer-aided methods to form a PARP-Tailored Database (PTD). This database was then analyzed through a virtual screening workflow, molecular docking studies, molecular dynamics (MD) simulations, MM/GBSA binding free energy calculations, DFT analysis and ADME/Tox predictions using the Schrödinger suite (v2023-2), MobaXterm v25.2, Gaussian 16.0, ProTox-3 and Pred-hERG v5.0 respectively. Results: Three compounds (1a–1c) were identified as promising candidates. Among them 1a appeared to be the most active compound with a favorable docking score (−9.488 kcal/mol) that is not only higher than 1b and 1c but also higher than that of Talazoparib (−6.778 kcal/mol). MD simulations of 1a–1c in the active site revealed an average RMSD of ~2.5–3.6 Å which is better compared to the parent Talazoparib (5.6 Å). Interestingly, on the 250 ns extended MD study, 1a exhibited a slightly reduced RMSD between 2.4 and 3.2 Å, whereas Talazoparib retained higher fluctuations of ~5 Å to 6 Å. MM/GBSA binding energy analysis indicated 1a to have better predicted binding affinity (−67.820 kcal/mol), which is also better than Talazoparib (−63.734 kcal/mol). DFT calculations showed good electronic properties and in silico ADMET studies also indicated 1a to have good drug-likeness and lower predicted hepatotoxicity and cardiotoxicity risk. Conclusions: These findings identify compound 1a as a promising lead, while compounds 1b and 1c remain viable candidates for further optimization. However, experimental validation is critical to confirm the predicted biological activity and safety profiles.

Perchlorate contamination in drinking water is an emerging environmental concern due to its persistence and adverse effects on thyroid function. However, the mechanisms governing its formation during water treatment processes remain poorly understood. This study investigates the formation pathways of perchlorate through chlorine–ozone interactions using a combined computational and experimental approach. Density functional theory (DFT) calculations were performed at the m06-2x/def2-svp level, with single-point energy corrections at the def2-tzvp level, and smd solvation was used to represent aqueous conditions. Reaction pathways, intermediates, and transition states were characterised to determine thermodynamic feasibility and kinetic barriers.The results show that perchlorate formation proceeds via stepwise oxidation of hypochlorite to chlorite and chlorate, with activation barriers below 30 kcal/mol, indicating feasibility under typical water treatment conditions. Experimental validation using ozonation of hypochlorite solutions confirmed that pH significantly influences reaction kinetics, with buffered systems exhibiting more stable reaction profiles. The overall process was found to be exergonic, supporting spontaneous formation once initiated. These findings provide new mechanistic insights into perchlorate formation and highlight ozonation as a potential source in water treatment systems, informing strategies to mitigate contamination.

A novel nanocomposite, diethylenetriamine functionalised zinc oxide-apricot stone shell (ZnO@Ap/DETA), has been synthesised for the efficient sequestration of 2,4-dichlorophenoxyacetic acid (2,4-D). The capacity and removal efficiency were evaluated using an artificial neural network (ANN). The characterisation of ZnO@Ap/DETA was performed to determine its physicochemical properties through various instrumental techniques. The nanocomposite displayed a more uniform mesoporous structure, having pores with an average size of 34.065 nm and a significantly enhanced surface area of 26.56 m² g⁻¹, approximately 13 times greater than that of the pristine apricot stone (AP) shells (2.076 m² g⁻¹). ZnO@Ap/DETA was utilised to adsorb 2,4-D from synthetic wastewater at pH 3, 50 mg adsorbent dose and 30 mg L⁻¹ initial 2,4-D concentration, and a real wastewater sample at 18.5 mg L⁻¹ 2,4-D concentration and 50 mg adsorbent dose, achieving performance efficiencies of 98.6% and 85.41%, respectively, after a 90-minute agitation period at 25 °C. The data on adsorption were consistent with the pseudo-second-order kinetic model and Langmuir isotherm, and thermodynamic investigations suggested that the process was spontaneous, favourable, and exothermic, as evidenced by a ΔH° value of −92.85 KJ mol⁻¹. To optimise the adsorption process, an ANN model was developed, comprising five input parameters, two hidden layers, and two output parameters. The developed model successfully predicted 2,4-D removal efficiency with a mean absolute error (MAE) of 0.2952, a mean squared error (MSE) of 0.4227, and a high R² of 0.9991. These results highlight the potential of ZnO@Ap/DETA for environmental remediation and for wastewater treatment.

Cutaneous squamous cell carcinoma (cSCC) poses a significant therapeutic challenge due to its aggressive nature and recurrence rates. The current treatment 5‐fluorouracil (5‐FU) is associated with adverse skin reactions. This study investigates cannabidiol (CBD) as a potential alternative therapy for cSCC through an integrated computational and experimental approach. Density functional theory (DFT) using the M06‐2X/6‐31+G(d,p) basis set revealed that CBD's smaller HOMO–LUMO gap (0.282 eV) compared to 5‐FU (0.288 eV) indicates a higher reactivity and potential biological interactions. Cannabidiol exhibits a higher binding affinity toward the CB1 receptor (−9.986 kcal/mol) than 5‐FU (−3.760 kcal/mol). Molecular dynamics simulations demonstrate that the CBD–CB1 complex remains stable through hydrogen bonding and hydrophobic interactions. Binding free energy calculations (MM‐GBSA) further confirmed CBD's enhanced affinity (−69.696 kcal/mol) over 5‐FU (−28.241 kcal/mol). Experimentally, CBD exhibited greater cytotoxicity against A431 cSCC cells with an IC ₅₀ of 2.76 μM compared to 5‐FU's IC ₅₀ of 5.61 μM. These integrated findings suggest that CBD is a promising alternative therapeutic candidate for cSCC, offering superior cytotoxicity and stable molecular interactions compared to 5‐FU.

Introduction: Rheumatoid arthritis (RA) arises from a complex inflammatory network involving cytokines, kinases, and matrix degrading enzymes. Methotrexate is the clinical standard but is limited by poor pharmacokinetics and a narrow mechanism. Methodology: This study evaluates six polyphenols sinapic acid, catechin, galangin, piceatannol, umbelliferone, and pinocembrin against fifteen validated RA targets and benchmarks them against methotrexate.An integrated in silico framework assessed ADME properties, molecular docking, and network pharmacology. ADME screening included Lipinski compliance, GI absorption, solubility, CYP450, and bioavailability. Results: All polyphenols fullfill Lipinski’s criteria and showed moderate lipophilicity, high predicted GI absorption, favourable solubility, minimal CYP450 interactions, and bioavailability scores of 0.55. Methotrexate displayed one rule violation, extreme hydrophilicity, poor permeability, low GI absorption, and a bioavailability score of 0.11. Docking confirmed methotrexate as the strongest single-target binder; however, catechin, piceatannol, galangin, and umbelliferone demonstrated strong affinities (–6.1 to –9.9 kcal/mol), particularly to iNOS, COX-2, and MMP-9. Network analysis highlighted modulation of TNF, IL-17, JAK–STAT, NF-κB, RA, and arachidonic-acid pathways and GO linked to inflammation and matrix degradation. Conclusion: The polyphenols, in combination with catechin, are pharmacokinetically robust multitarget modulators capable of suppressing cytokine signalling, kinase activation, NF-κB transcription, and matrix degradation, therefore positing these phytochemicals as promising for next-generation RA therapeutics.

Breast cancer, a leading cause of global mortality, necessitates novel therapies targeting key drivers like the epidermal growth factor receptor (EGFR). This computational study evaluates nine 4-phenyl-2H-[1,3]thiazino[3,2-a]benzimidazol-2-imine (H-thiazine) derivatives as potential EGFR inhibitors. Using molecular docking, ADMET profiling, molecular dynamics simulations, and binding energy calculations, we identified methyl- and bromine-substituted derivatives as probable candidates that outperform the reference drug Olmutinib in terms of binding affinity, pharmacokinetics, and stability. Although these compounds showed promising bioactivity, in silico toxicity screening indicated potential AMES mutagenicity and hERG-II inhibition, highlighting important safety liabilities. Overall, thiazine derivatives represent viable scaffolds for EGFR-targeted anti-cancer development; however, further optimization and experimental validation, including biochemical assays and genotoxicity testing, are required to confirm their therapeutic potential.

The RuClF/AlN vdWH shows a moderate Li-diffusion barrier of 0.33 eV, enabling fast ion transport and charge–discharge kinetics, and delivers a high theoretical capacity of ∼564.29 mAh g ⁻¹ , outperforming many 2D anodes.