Ishik University

A new symmetrical azine, 1,2-bis(1-(5-bromothiophen-2-yl)ethylidene)hydrazine (5BEH), was synthesized via a simple ionic-liquid-assisted protocol and fully characterized using FT-IR, NMR, and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic P21/c space group, and Hirshfeld surface analysis revealed that the Br & ctdot;H/H & ctdot;Br and S & ctdot;H/H & ctdot;S interactions dominated the supramolecular packing, supported by additional dispersion-driven H & ctdot;H contacts. Density functional theory (DFT) calculations at the B3LYP/6311++G(d,p) level reproduced the experimental geometry and vibrational features with high accuracy. Frontier molecular orbital and NBO analyses showed a moderately narrow HOMO-LUMO gap (3.58 eV), strong pi ->pi* and LP ->pi* charge-transfer pathways, and a bipolar electrostatic profile with electrophilic N-N/C=N regions and nucleophilic Br/S sites. Docking studies against meningitis-associated targets (4CVD and 4UMB) indicated that 5BEH binds more favourably than ceftriaxone, although with a weak absolute inhibitory affinity. ADME predictions further demonstrated good intestinal absorption, BBB penetration, low toxicity, and no hERG or carcinogenic risk, with CYP2D6 inhibition being a noted metabolic consideration. Overall, the structural, electronic, and in silico findings identify 5BEH as a stable, electronically versatile azine scaffold with in silico indicative potential for medicinal and materials-oriented applications.

Biofloc Technology (BFT) is recognized as an ecologically sustainable aquaculture method that improves water quality, enhances nutrient recycling, and increases disease resilience in cultured crustaceans, especially Litopenaeus vannamei. Initially designed to mitigate environmental impact and decrease reliance on water exchange, recent findings suggest that biofloc systems have significant immunomodulatory effects, driven by intricate interactions among host, microbes, and the environment. This review consolidates existing mechanistic insights regarding the influence of BFT on immune function in shrimps, focusing on microbiota modulation, innate immune activation, antioxidant enhancement, and exposure to bioactive microbial metabolites. Biofloc systems promote stable and diverse microbial communities that effectively exclude pathogens, enhance beneficial taxa, and provide immunostimulatory microbial-associated molecular patterns (MAMPs) that activate hemocyte and humoral responses. Furthermore, enhanced water quality and nutrient-dense microbial biomass jointly mitigate oxidative stress, promote physiological homeostasis, and bolster resistance to bacterial and viral pathogens, such as Vibrio spp. and white spot syndrome virus. Comparative analyses of biofloc and conventional systems demonstrate the enhanced immunological, nutritional, and environmental efficacy of BFT. However, they also identify significant limitations, such as inconsistent outcomes stemming from variable system management, insufficient long-term immune data, and a limited comprehension of the molecular pathways that regulate host responses. To address these knowledge gaps, standardized immune markers, integrated multiomics analyses, and farm-scale validation are necessary. This review presents a mechanistic framework for enhancing BFT as an immune-focused, climate-resilient approach to sustainable crustacean aquaculture.

This research introduces a comprehensive computational and experimental approach aimed at the systematic design of selective Histone Deacetylase 1 (HDAC1) inhibitors, which hold therapeutic promise for treating aggressive cancers. A comprehensive Quantitative Structure-Activity Relationship (QSAR) model was constructed utilizing 1168 experimentally validated HDAC1 inhibitors, incorporating molecular descriptors associated with hydrogen bonding, steric, and electronic properties. The validated model, with a R2 of 0.80 and a Q2 of 0.80, was utilized for the virtual screening of the ChemDiv HDAC library, successfully identifying high-potential hits. The leading compounds underwent receptor-based molecular docking with the HDAC1 crystal structure (PDB ID: 4BKX), which highlighted essential interactions such as zinc ion coordination and π-π stacking. Notably, compound 0356-0096 demonstrated a higher binding affinity than the reference inhibitor vorinostat. Molecular dynamics (MD) simulations conducted over a duration of 500 ns demonstrated the stability of the complex and a decrease in flexibility, as evidenced by analyses of Root Mean Square Deviation (RMSD) and Fluctuation (RMSF). The analysis of simulation trajectories through Principal Component Analysis (PCA) and the mapping of the Free Energy Landscape (FEL) revealed stable low-energy conformations that align with thermodynamically favorable binding conditions. The results of ADMET profiling demonstrated that the lead compounds exhibit good oral bioavailability, low toxicity, and favorable metabolic stability. Validation through in vitro methods using the MTT assay on MDA-MB-231 (triple-negative breast cancer) and A431 (epidermoid carcinoma) cell lines revealed significant, dose-dependent cytotoxic effects, with IC50 values of 2.7 μM and 91.6 nM, respectively. The computed Selectivity Index (SI) demonstrated a preferential cytotoxic effect on cancer cells in comparison to normal NRK kidney cells. This integrative QSAR-docking-MD-FEL-MTT approach effectively identified compound 0356-0096 as a potent and selective HDAC1 inhibitor. By combining predictive computational models with empirical validation, it provides a structured pathway for the preclinical development of targeted epigenetic cancer therapeutics.

The classical methods of disinfection such as UV, ozonation, and chlorination have some limitations, including low efficiency of pathogen destruction, high energy requirements, and the creation of disinfection by-products (DBPs). The availability of clean drinking water is one of the great challenges still faced by the world. The discovery of silver nanoparticles, also known as AgNPs, has proven them to be effective antibacterial agents for the long-term disinfection of water. This paper presents the primary mechanisms by which AgNPs inactive pathogens, including membrane disruption, induction of oxidative stress, and disruption of DNA and protein synthesis. AgNPs facilitate rapid and effective microbial inactivation when incorporated into a variety of scaffold systems, including carbon-based materials, hydrogels, foams, and ceramics. particle size, shape, particle concentration, substrate material, water chemistry, flow conditions, and other relevant variables that influence AgNPs efficacy are examined in greater detail. Various important limitations are highlighted, for example, cost, long-term stability, nanoparticle leaching, and potential environmental risks. Finally, recommendations are offered regarding priorities for future research, with attention directed to hybrid disinfection platforms, scalable point-of use technologies, improved immobilization strategies, reduced silver release, and biocompatible designs. In conclusion, silver-based nanoparticles offer a viable path for the development of energy-efficient, safe, and sustainable water disinfection solutions that align with sustainability and global health goals.

The metallic complexes with the pharmaceutical drugs have improved the mechanical strength, site action, enhanced stability and biological activities. In this research work, the controlled release from PVA/AgO nanobiocomposite hydrogel and biological potential of oxytetracycline (OTC) and Cu-OTC complex were compared. The OTC which is an antimicrobial class of tetracycline was altered chemically with the coordination complex of the copper ion. The OTC complex with copper (II) using copper chloride and OTC in one-pot synthesis was obtained to explore the biological activities and release kinetics. The OTC methanolic solution was mixed in copper chloride methanolic solution and then it was refluxed for three hours to get the fine crystals of Cu-OTC complex. The prepared complex was characterized using various techniques as measurement of melting points, UV-Vis spectrophotometer, FTIR spectroscopy, Surface-Enhanced Raman spectroscopy (SERS) along Principal Component analysis (PCA), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), NMR (1H 13C), SEM, EDX and X-ray Diffraction (XRD). The prepared complex and OTC were loaded on PVA/AgO hydrogel and controlled release in phosphate buffer solution of pH 7.4 at 37 °C for 33 h with the interval gap of 3 h was evaluated by using UV-Vis spectrophotometer. The Higuchi and Korsmeyer-Peppas models were employed to study the release kinetics. The antibacterial activity, MIC, and MBC against E. coli and S. aureus bacteria, hemolytic analysis and cytotoxicity against human colon cancer cells (SW480) were also performed to analyze the biological potential of the prepared complex. The molecular docking was also performed to compare the antibacterial and cytotoxicity of OTC and Cu-OTC complex. The stoichiometry determined by Job’s method proved the 1:1 Cu-OTC complex which is consistent with spectroscopic results. The Cu-OTC complex was found to have better antibacterial properties than free OTC based on increased yielding of broader zones of inhibition and reduced MIC/MBC. Diffusion controlled kinetics Studies of controlled release showed sustained release behavior at the PVA/AgO hydrogel. The cytotoxicity analysis showed that the Cu-OTC complex inhibited the growth of SW480 cells more than OTC did without causing significant hemocompatibility loss.