Optimal fusion of genotype and drug embeddings in predicting cancer drug response.

Predicting cancer drug response using both genomics and drug features has shown some success compared to using genomics features alone. However, there has been limited research done on how best to combine or fuse the two types of features. Using a visible neural network with two deep learning branches for genes and drug features as the base architecture, we experimented with different fusion functions and fusion points. Our experiments show that injecting multiplicative relationships between gene and drug latent features into the original concatenation-based architecture DrugCell significantly improved the overall predictive performance and outperformed other baseline models. We also show that different fusion methods respond differently to different fusion points, indicating that the relationship between drug features and different hierarchical biological level of gene features is optimally captured using different methods. Considering both predictive performance and runtime speed, tensor product partial is the best-performing fusion function to combine late-stage representations of drug and gene features to predict cancer drug response.

Development of Multiplex Molecular Assays for Simultaneous Detection of Dengue Serotypes and Chikungunya Virus for Arbovirus Surveillance.

The major arboviruses mainly belong to the Bunyaviridae, Togaviridae, and Flaviviridae families, among which the chikungunya virus and dengue virus have emerged as global public health problems. The main objective of this study was to develop specific, sensitive, and cost-effective molecular multiplex RT-PCR and RT-qPCR assays for the rapid and simultaneous detection of CHIKV and the four serotypes of DENV for arbovirus surveillance. Specific primers for all viruses were designed, and one-step multiplex RT-PCR (mRT-PCR) and RT-qPCR (mRT-qPCR) were developed using reference strains of the CHIKV and DENV serotypes. The specificity of the test for all the viruses was confirmed through sequencing. The standard curves showed a high correlation coefficient, R2 = 0.99, for DENV-2 and DENV-3; R2 = 0.98, for DENV-4; and CHIKV; R2 = 0.93, for DENV-1. The limits of detection were calculated to be 4.1 × 10-1 copies/reaction for DENV-1, DENV-3, and CHIKV and 4.1 × 101 for DENV-2 and DENV-4. The specificity and sensitivity of the newly developed mRT-PCR and mRT-qPCR were validated using positive serum samples collected from India and Burkina Faso. The sensitivity of mRT-PCR and mRT-qPCR are 91%, and 100%, respectively. The specificity of both assays was 100%. mRT-PCR and mRT-qPCR assays are low-cost, and a combination of both will be a useful tool for arbovirus surveillance.

Extracellular mitochondrial components as new biomarkers for lupus nephritis.

Major reason for mortality among systemic lupus erythematosus patients is renal failure due to the deposition of immune complexes in the glomeruli. Being a chronic disease with multiple relapses and remissions across the lifespan, it's important to know the degree of nephritis for diagnosis as well as the long-term clinical management of the patients. Currently, renal biopsy is being used as the gold standard to diagnose and define the stages of the disease. However, renal biopsy being invasive only provides a localized picture of nephritis, and has the risk of bleeding. Additionally, it is also cost-intensive. Hence, a reliable, non-invasive biomarker is required for lupus nephritis. This study has evaluated extracellular mitochondrial components, including cell-free mitochondria, and cell-free mitochondrial DNA as probable biomarkers of the degree of nephritis. Both showed a significant correlation with proteinuria and protein-creatinine ratio. Our study substantiates their usage as clinical biomarkers of nephritis upon their validation in a larger cohort of lupus nephritis patients and other forms of nephritis. Although the current data suggest using cell-free mitochondria as a biomarker of lupus nephritis is better than the cell-free mitochondrial DNA.

Harnessing Therapeutic Potentials of Biochanin A in Neurological Disorders: Pharmacokinetic and Pharmacodynamic Overview.

Biochanin A, an isoflavone flavonoid with estrogenic activity, is naturally found in red clover and other legumes. It possesses a wide range of pharmacological properties, including antioxidant, anti-inflammatory, anti-apoptotic, neuroprotective, and anticancer effects. In recent years, a growing body of pre-clinical research has focused on exploring the therapeutic potential of biochanin A in various neurological disorders, such as Alzheimer's and Parkinson's disease, multiple sclerosis, epilepsy, ischemic brain injury, gliomas, and neurotoxicity. This comprehensive review aims to shed light on the underlying molecular mechanisms that contribute to the neuroprotective role of biochanin A based on previous pre-clinical studies. Furthermore, it provides a detailed overview of the protective effects of biochanin A in diverse neurological disorders. The review also addresses the limitations associated with biochanin A administration and discusses different approaches employed to overcome these challenges. Finally, it highlights the future opportunities for translating biochanin A from pre-clinical research to clinical studies while also considering its commercial viability as a dietary supplement or a potential treatment for various diseases.

Acaricide resistance status of deltamethrin and coumaphos in Hyalomma anatolicum ticks collected from different districts of Haryana.

To study the acaricide resistance status and possible mechanisms of action in conferring resistance to commonly used acaricides (deltamethrin and coumaphos), Hyalomma anatolicum ticks were collected from 6 dairy farms of Hisar and Charkhi Dadri districts of Haryana. By using standard larval packet test, H. anatolicum tick larvae of Charkhi Dadri isolates were found to be susceptible (100% mortality) to both the acaricides. Level-I resistance against coumaphos was recorded from four isolates, whereas, level-II was observed in only one isolate, collected from Hisar. One isolates (Kaimri) from Hisar also showed level-I resistance against deltamethrin. Biochemically, the ticks having higher values of resistance factor (RF) against coumaphos were found to possess increased enzymatic activity of α-esterase, ß-esterase, glutathione-S-transferase (GST) and mono-oxygenase enzymes, whereas, the monoamine oxidase did not show any constant trend. However, the RF showed a statistical significant correlation with GST only. Native PAGE analysis of H. anatolicum ticks revealed the presence of nine types of esterases (EST-1 h to EST-9 h) by using napthyl acetate as substrate. In the inhibitory assay, esterases were found to be inhibited by PMSF, indicating the presence of serine residue at catalytic triad. The partial cds of carboxylesterase and domain II of sodium channel genes were sequenced to determine any proposed mutations in resistant isolates of H. anatolicum ticks, however, no mutations were observed in either gene, indicating that increased expression of detoxification enzymes as a possible mechanism for resistance development, in the current study.

Formulation and Characterization of Silibinin Entrapped Nano-Liquid Crystals for Activity against Aß1-42 Neurotoxicity in In-Vivo Model.

Silibinin (SIL) Encapsulated Nanoliquid Crystalline (SIL-NLCs) particles were prepared to study neuroprotective effect against amyloid beta (Aß1-42) neurotoxicity in Balb/c mice model. Theses NLCs were prepared through hot emulsification and probe sonication technique. The pharmacodynamics was investigatigated on Aß1-42 intracerebroventricular (ICV) injected Balb/c mice. The particle size, zeta potential and drug loading were optimized to be 153 ± 2.5 nm, -21 mV, and 8.2%, respectively. Small angle X-ray (SAXS) and electron microscopy revealed to crystalline shape of SIL-NLCs. Thioflavin T (ThT) fluroscence and circular dichroism (CD) technique were employed to understand monomer inhibition effect of SIL-NLCs on Aß1-4. In neurobehavioral studies, SIL-NLCs exhibited enhanced mitigation of memory impairment induced on by Aß1-42 in T-maze and new object recognition test (NORT). Whereas biochemical and histopathological estimation of brain samples showed reduction in level of Aß1-42 aggregate, acetylcholine esterase (ACHE) and reactive oxygen species (ROS). SIL-NLCs treated animal group showed higher protection against Aß1-42 toxicity compared to free SIL and Donopezil (DPZ). Therefore SIL-NLCs promises great prospect in neurodegenerative diseases such as Alzheimer's disease.

Spatio-temporal distribution and source contributions of the ambient pollutants in Lucknow city, India.

Clean air is imperative to the survival of all life forms on the planet. However, recent times have witnessed enormous escalation in urban pollution levels. It is therefore, incumbent upon us to decipher measures to deal with it. In perspective, the present study was carried out to assess PM10 and PM2.5 loading, metallic constituents, gaseous pollutants, source contributions, health impact and noise level of nine-locations, grouped as residential, commercial, and industrial in Lucknow city for 2019-21. Mean concentrations during pre-monsoon for PM10, PM2.5, SO2 and NO2 were: 138.2 ± 35.2, 69.1 ± 13.6, 8.5 ± 3.3 and 32.3 ± 7.4 µg/m3, respectively, whereas post-monsoon concentrations were 143.0 ± 33.3, 74.6 ± 14.5, 12.5 ± 2.1, and 35.5 ± 6.3 µg/m3, respectively. Exceedance percentage of pre-monsoon PM10 over National Ambient Air Quality Standards (NAAQS) was 38.2% while that for post-monsoon was 43.0%; whereas corresponding values for PM2.5 were 15.2% and 24.3%. Post-monsoon season showed higher particulate loading owing to wintertime inversion and high humidity conditions. Order of elements associated with PM2.5 is Co < Cd < Cr < Ni < V < Be < Mo < Mn < Ti < Cu < Pb < Se < Sr < Li < B < As < Ba < Mg < Al < Zn < Ca < Fe < K < Na and that with PM10 is Co < Cd < Ni < Cr < V < Ti < Be < Mo < Cu < Pb < Se < Sr < Li < B < As < Mn < Ba < Mg < Al < Fe < Zn < K < Na < Ca. WHO AIRQ + ascertained 1654, 144 and 1100 attributable cases per 0.1 million of population to PM10 exposure in 2019-21. Source apportionment was carried out using USEPA-PMF and resolved 6 sources with highest percent contributions including road dust re-entrainment, biomass burning and vehicular emission. It is observed that residents of Lucknow city regularly face exposure to particulate pollutants and associated constituents making it imperative to develop pollution abetment strategies.

Atroposelective Synthesis of C-C Axially Chiral Compounds via Mono- and Dinuclear Vanadium Catalysis.

Axially chiral compounds with rotationally constrained σ-bonds that exhibit atropisomerism are lucrative synthetic targets because of their ubiquity in functional materials and natural products. The metal complex-catalyzed enantioselective fabrication of axially chiral scaffolds has been widely investigated, and thus far, considerable progress has been made. Over the past two decades, we have developed a highly efficient strategy for constructing axially chiral biarenol derivatives using chiral mono- and dinuclear vanadium complexes. These complexes are readily prepared from vanadium(IV) salts and Schiff base ligands (generated from the condensation of (S)-tert-leucine and di- or monoformyl-(R)-1,1'-bi-2-naphthol (BINOL) derivatives) under O2 and act as highly active catalysts for highly stereoselective C-C bond formation. In particular, the vanadium complex-catalyzed enantioselective oxidative coupling of 2-naphthols 1 under oxygen or in air, which is a green oxidant, affords the desired axially chiral molecules in high yields and high stereoselectivity (up to quantitative yield and 97% ee), along with water as the sole coproduct. This coupling reaction tolerated various functional groups (such as halogens, alkoxys, and boryls) and avoided overoxidation of coupling products.The key feature of dinuclear vanadium(V) catalysts such as (Ra,S,S)-5a is an outstanding mode of the homocoupling reaction, in which a single molecule of the catalyst activates two molecules of the starting material (e.g., 2-naphthols) simultaneously. With this "dual activation" mechanism, the oxidative coupling promoted by the dinuclear catalyst proceeds in an intramolecular manner. The homocoupling rate using 5 mol % of the dinuclear vanadium(V) complex (Ra,S,S)-5a was measured to be 111 times faster than that of the mononuclear vanadium(IV) complex (S)-4a bearing a half motif of the dinuclear vanadium complex.In the case of the heterocoupling reaction utilizing two different kinds of arenol derivatives, only a starting arenol having lower oxidation potential seems to be activated by the mononuclear vanadium complex. The reaction rate of the heterocoupling using either mono- or dinuclear vanadium complexes showed no difference to give the coupling product in high yields but with a different enantioselective manner; chiral mononuclear vanadium(V) complexes showed better enantioselectivites than that of the dinuclear vanadium(V) complexes. A competing heterocoupling study and a linear correlation between the ee of the mononucaler vanadium catalyst and ee of the heterocoupling suggested that the heterocoupling involves an intermolecular radical-anion coupling pathway.In this Account, we summarize the recent advances in vanadium-catalyzed coupling reactions that produced important chiral molecules, such as biresorcinols, polycyclic biphenols, oxa[9]helicenes, bihydroxycarbazoles, and C1-symmetrical biarenols, and their coupling reaction mechanisms. By pursuing vanadium catalysis, we believe numerous additional transformations as well as a renewed interest in catalytic and chemo-, regio-, and enantioselective aryl-aryl bond constructions will be manifested.

Generic ibrutinib a potential cost-effective strategy for the first-line treatment of chronic lymphocytic leukaemia.

Though the chronic lymphocytic leukaemia (CLL) management options in India are still limited compared to the novel drug options in resource-rich settings, the availability of less costly generics and the government health insurance scheme has enabled many patients to access the newer drugs in India. The current study compared the cost-effectiveness and cost-utility of existing initial management options for the progression-free survival (PFS) time horizon from the patient's perspective. A two-health-state, PFS and progressive disease, Markov model was assumed for three regimens (generics): ibrutinib monotherapy, bendamustine-rituximab (B-R), and rituximab-chlorambucil (RClb) used as the frontline treatment of CLL patients in India. All costs, utilization of services, and consequences data during the PFS period were collected from interviewing patients during follow-up visits. The transition probability (TP) and average PFS information were obtained from landmark published studies. EQ-5D-5L questionnaires were utilized to assess the quality of life (QoL). Quality-adjusted life years (QALY) were measured during the PFS period. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were studied. Upon analysis, the entire monetary expense during the PFS time was ₹1581964 with ibrutinib, ₹171434 with B-R, and ₹91997 with RClb treatment arm. Pooled PFS and QALY gain was 10.33 and 8.28 years for ibrutinib, 4.08 and 3.53 years for the B-R regimen, and 1.33 and 1.23 years in RClb arms, respectively. Ibrutinib's ICER and ICUR were ₹214587.32 per PFS year gain and ₹282384.86 per QALY gain when assessed against the B-R regimen. Ibrutinib also performed better in ICER and ICUR against the RClb arm with ₹157014.29 per PFS year gain and ₹200413.6 per QALY gain. In conclusion, generic ibrutinib is a cost-effective initial line of management compared to other commonly used treatment regimes in resource-limited settings.

Droperidol as a potential inhibitor of acyl-homoserine lactone synthase from A. baumannii: insights from virtual screening, MD simulations and MM/PBSA calculations.

Acinetobacter baumannii belongs to the ESKAPE family of pathogens and is a multi-drug resistant, gram-negative bacteria which follows the anaerobic form of respiration. A. baumannii is known to be the causative agent of hospital-related infections such as pneumonia, meningitis, endocarditis, septicaemia and a plethora of infections such as urinary tract infections found primarily in immunocompromised patients. These attributes of A. baumannii make it a priority pathogen against which potential therapeutic agents need to be developed. A. baumannii employs the formation of a biofilm to insulate its colonies from the outer environment, which allows it to grow under harsh environmental conditions and develop resistance against various drug molecules. Acyl-homoserine lactone synthase (AHLS) is an enzyme involved in the quorum-sensing pathway in A. baumannii, which is responsible for the synthesis of signal molecules known as acyl-homoserine lactones, which trigger the signalling pathway to regulate the factors involved in biofilm formation and regulation. The present study utilised a homology-modelled structure of AHLS to virtually screen it against the ZINC in trial/FDA-approved drug molecule library to find a subset of potential lead candidates. These molecules were then filtered based on Lipinski's, toxicological and ADME properties, binding affinity, and interaction patterns to delineate lead molecules. Finally, three promising molecules were selected, and their estimated binding affinity values were corroborated using AutoDock 4.2. The identified molecules and a control molecule were subsequently subjected to MD simulations to mimic the physiological conditions of protein ligand-binding interaction under the influence of a GROMOS forcefield. The global and essential dynamics analyses and MM/PBSA based binding free energy computations suggested Droperidol and Cipargamin as potential inhibitors against the binding site of AHLS from A. baumannii. The binding free energy calculations based on the MM/PBSA method showed excellent results for Droperidol (- 50.02 ± 4.67 kcal/mol) and Cipargamin (- 42.29 ± 4.05 kcal/mol).

Comparative evaluation of A1A2 and A2A2 cow milk-containing diets on biochemical and histological parameters of Wistar rats.

This Research Communication aims to compare the effect of A1A2 and A2A2 cow milk diets on the biochemical and histological parameters of rats. The rats were divided into four groups and fed with a normal diet, A2 milk powder, A1A2 or A2A2 cow milk diets for 90 d. Blood glucose, kidney function, liver function and lipid profile were examined during the experimental period. The study showed an increase in the body weight of the A1A2 group whereas a slight decrease in the A2A2 group, and blood glucose levels increased from d 0 to day 90 in all experimental groups. However, none of these changes were found to be statistically insignificant (P > 0.05). Moreover, no significant changes were recorded in other parameters (serum glutamic pyruvic transferase and serum glutamic-oxaloacetic transaminase for liver function, bilirubin direct, cholesterol, triglycerides, creatinine and uric acid). The histology of the liver, kidney and pancreas also showed no changes in all groups. Overall, this study revealed no significant difference in the nutritional values of A1A2 and A2A2 milk types and hence equally beneficial for health. Although the present study showed no significant difference in the effect of both milk types in 90 d, further studies might be conducted to evaluate their longer term effects.

Enhancing IoT Security through a Green and Sustainable Federated Learning Platform: Leveraging Efficient Encryption and the Quondam Signature Algorithm.

This research paper introduces a novel paradigm that synergizes innovative algorithms, namely efficient data encryption, the Quondam Signature Algorithm (QSA), and federated learning, to effectively counteract random attacks targeting Internet of Things (IoT) systems. The incorporation of federated learning not only fosters continuous learning but also upholds data privacy, bolsters security measures, and provides a robust defence mechanism against evolving threats. The Quondam Signature Algorithm (QSA) emerges as a formidable solution, adept at mitigating vulnerabilities linked to man-in-the-middle attacks. Remarkably, the QSA algorithm achieves noteworthy cost savings in IoT communication by optimizing communication bit requirements. By seamlessly integrating federated learning, IoT systems attain the ability to harmoniously aggregate and analyse data from an array of devices while zealously guarding data privacy. The decentralized approach of federated learning orchestrates local machine-learning model training on individual devices, subsequently amalgamating these models into a global one. Such a mechanism not only nurtures data privacy but also empowers the system to harness diverse data sources, enhancing its analytical capabilities. A thorough comparative analysis scrutinizes varied cost-in-communication schemes, meticulously weighing both encryption and federated learning facets. The proposed approach shines by virtue of its optimization of time complexity through the synergy of offline phase computations and online phase signature generation, hinged on an elliptic curve digital signature algorithm-based online/offline scheme. In contrast, the Slow Block Move (SBM) scheme lags behind, necessitating over 25 rounds, 1500 signature generations, and an equal number of verifications. The proposed scheme, fortified by its marriage of federated learning and efficient encryption techniques, emerges as an embodiment of improved efficiency and reduced communication costs. The culmination of this research underscores the intrinsic benefits of the proposed approach: marked reduction in communication costs, elevated analytical prowess, and heightened resilience against the spectrum of attacks that IoT systems confront.

Semi-Supervised Clustering-Based DANA Algorithm for Data Gathering and Disease Detection in Healthcare Wireless Sensor Networks (WSN).

Wireless sensor networks (WSNs) have emerged as a promising technology in healthcare, enabling continuous patient monitoring and early disease detection. This study introduces an innovative approach to WSN data collection tailored for disease detection through signal processing in healthcare scenarios. The proposed strategy leverages the DANA (data aggregation using neighborhood analysis) algorithm and a semi-supervised clustering-based model to enhance the precision and effectiveness of data collection in healthcare WSNs. The DANA algorithm optimizes energy consumption and prolongs sensor node lifetimes by dynamically adjusting communication routes based on the network's real-time conditions. Additionally, the semi-supervised clustering model utilizes both labeled and unlabeled data to create a more robust and adaptable clustering technique. Through extensive simulations and practical deployments, our experimental assessments demonstrate the remarkable efficacy of the proposed method and model. We conducted a comparative analysis of data collection efficiency, energy utilization, and disease detection accuracy against conventional techniques, revealing significant improvements in data quality, energy efficiency, and rapid disease diagnosis. This combined approach of the DANA algorithm and the semi-supervised clustering-based model offers healthcare WSNs a compelling solution to enhance responsiveness and reliability in disease diagnosis through signal processing. This research contributes to the advancement of healthcare monitoring systems by offering a promising avenue for early diagnosis and improved patient care, ultimately transforming the landscape of healthcare through enhanced signal processing capabilities.

Rationalizing the Use of COVID-19 Questionable Efficacy Drugs in a Low Middle-income Country: A Hospital Tocilizumab Committee Experience.

BACKGROUND: Only corticosteroids have confirmed mortality benefits in coronavirus disease of 2019 (COVID-19). Rational use of costlier drugs with questionable benefits poses a great concern to hospital pharmacies in low middle-income countriesAim: The present study aimed to assess the rational utilization of hospital supply tocilizumab and understand its clinical benefits in hospitalized COVID-19 pneumonia patientsMethods: The Hospital Tocilizumab Committee (HTC) decision support system framework was developed to make patients eligible or ineligible for tocilizumab procurement from the hospital pharmacy. A total of 33 consecutive patients receiving tocilizumab were analyzed retrospectively in the 3-month study period. The records of the inpatient stay of the patients were observed for pulse, blood pressure, respiratory rate (RR), oxygen saturation (SpO2), fraction of inspired oxygen (FiO2) laboratory work-up, hospital stay duration, and mortality benefit, if any. Patients were analyzed as "died," "survived," and "composite" subgroupsResults: The study observed death as a final outcome in 48% of patients. The study observed a significant effect of tocilizumab on C-reactive protein (CRP) (p = 0.02) and ferritin (p = 0.018) levels on a 10-day follow-up when all patients were analyzed together. Rising and declining trends of RR and FiO2 were observed among the "died" (RR, p = 0.02; FiO2, p = 0.03) and survived (RR, p = 0.03; FiO2, p = 0.05) subgroups. The second dose of tocilizumab was received by 88% of survivors as against 50% of patients who died (p = 0.04)Conclusion: Hospital Tocilizumab Committee (HTC) was successfully established to continue the assessment of the costlier drug with uncertain treatment benefits. A repeat dose of tocilizumab may provide a mortality benefit in Asian Indians.

Unknown presentation of a rare genetic disorder: Monogenic diabetes in young type 4 presenting with hepatic cysts and procoagulant state.

Maturity onset diabetes in young (MODY) is the most common form of monogenic diabetes, which characteristically presents in adolescents and young adults. Till date, pathogenic variations involving 14 different genes have been causally implicated with the development of MODY. Maturity onset diabetes in young type 4 (MODY-4) is a very rare form of MODY. We present here case of 28-year-old nonobese male patient with distinct family history of diabetes spanning two generations, incidentally, detected to have a rare form of diabetes on genetic analysis when he presented with recurrent thromboembolic manifestations: deep vein thrombosis and pulmonary thromboembolism. Our case highlights a previously unknown disease association of a rare genetic disorder. Increasing awareness about this genetic disorder and early identification of such cases will enhance our understanding of hitherto unknown disease associations and the pathophysiological role of genetic mutations. This may contribute to the improved treatment and prevention of debilitating diseases such as diabetes.

General Co-catalytic Hydrothiolation of gem-Difluoroalkenes.

Regioselective functionalization of gem-difluoroalkenes enables convergent late-stage access to fluorinated functional groups, though most functionalization reactions proceed through defluorinative functionalization processes that deliver mono-fluorovinyl products. In contrast, fewer reactions undergo net hydrofunctionalization to generate difluorinated products. Herein, we report a photocatalytic hydrothiolation of gem-difluoroalkenes that enables access to a broad spectrum of α,α-difluoroalkylthioethers. Notably, the reaction successfully couples nonactivated substrates, which expands the scope of accessible molecules relative to previously reported reactions involving organo- or photocatalytic strategies. Further, this reaction successfully couples biologically relevant molecules under aqueous conditions, highlighting potential applications in both late-stage and biorthogonal functionalizations.

Novel Nanostructured Lipid Carriers Co-Loaded with Mesalamine and Curcumin: Formulation, Optimization and In Vitro Evaluation.

PURPOSE: The aim of current study is to formulate, optimize and characterize the developed formulation of Mesalamine-Curcumin Nanostructured Lipid Carriers (Mes-Cur NLCs). METHODS: It was formulated using high pressure homogenization followed by probe sonication and formulation variables were optimized using Central Composite Design. The particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug release, cytotoxicity on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells and efficacy on RAW264.7 cells for optimized formulation was determined. RESULTS: The PS, ZP and EE were found to be 85.26 nm, -23.7 ± 7.45 mV, 99.2 ± 2.62 % (Mes) and 84 ± 1.51 % (Cur), respectively. The good correlation between predicted and obtained value indicated suitability and reproducibility of experimental design. NLCs showed spherical shape as confirmed by TEM. In vitro drug release profile of prepared formulation showed that Mes exhibited 100 % release at 48 h, whereas Cur exhibited 82.23 ± 2.97% release at 120 h. Both the drugs exhibited sustained release upon incorporation into the NLCs. The absence of any significant cell death during MTT assay performed on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells indicated that NLCs' were safe for use. Furthermore, significant reduction in nitric oxide level during anti-inflammatory evaluation of formulation on RAW264.7 cells showed excellent potential for the formulation to treat inflammation. The formulation was found stable as no significant difference between the PS, ZP and EE of the fresh and aged NLCs was observed. CONCLUSION: The outcomes of study deciphered successful formulation of Mes-Cur NLCs.

Hydrogen Production from Formaldehyde and Paraformaldehyde in Water under Additive-Free Conditions: Catalytic Reactions and Mechanistic Insights.

Efficient catalytic systems based on arene-Ru(II) complexes bearing bis-imidazole methane-based ligands were developed to achieve additive-free hydrogen generation from formaldehyde and paraformaldehyde in water. Our findings inferred the influential role of bis-imidazole methane ligands in the observed catalytic performance of the studied catalysts. Among the screened complexes, [(η6-p-cymene)RuCl(L)]+Cl- ([Ru]-2) (L = 4,4'-((2-methoxyphenyl)methylene)bis(2-ethyl-5-methyl-1H-imidazole) outperformed others to generate hydrogen gas from paraformaldehyde in water with an exceptionally high turnover number (TON) of >20,000. A detailed mechanistic pathway for hydrogen gas generation from formaldehyde has been proposed on the basis of identified several crucial catalytic intermediate species involved in the hydrogen production process.

BF3-etherate promoted facile access to vinyloxyimidazopyridines: a metal-free sustainable approach.

A convenient and metal-free synthesis of vinyloxyimidazopyridine derivatives has been attained via BF3.OEt2 promoted one-pot multicomponent approach. This procedure involves a facile coupling of 2-aminopyridine derivatives with arylglyoxal and alkyne derivatives. BF3.OEt2 complexation has successfully catalyzed the reaction at room temperature. Utilization of transition metal-free catalyst, mild reaction conditions, easy handling and operational simplicity are key features of developed process.

Spatial distribution of physicochemical-bacteriological parametric quality and water quality index of Gomti River, India.

Surface water bodies are vital source of water for human consumption, domestic needs, agriculture, industrial activities, and also for aquatic life and ecosystems. In this study, a stretch of river Gomti was studied at 5 sites in Lucknow for two consecutive seasons during 2019. The physicochemical-bacteriological parameters of water and sediment samples were analyzed, followed by multivariate statistics. Mean values of pH, turbidity, EC, TS, TDS, TSS, DO, BOD, COD, nitrate, phosphate, sulfate, total alkalinity, total hardness, chloride, and fluoride during the pre-monsoon period were 7.4 ± 0.2, 5.2 ± 3.3 (NTU), 444.4 ± 97.4 (µS/cm), 274.6 ± 61.6, 254.3 ± 50.2, 21.9 ± 11, 5.4 ± 1.6, 10.2 ± 5.9, 31.2 ± 13.3, 1.2 ± 0.5, 1.7 ± 1.1, 25.9 ± 3.7, 204 ± 41.8, 146.2 ± 11.5, 15.5 ± 8.7, and 0.5 ± 0.1 mg/l, respectively. The corresponding values during the post-monsoon season were 7.5 ± 0.2, 5.5 ± 3.2 (NTU), 436 ± 75.1 (µS/cm), 273.7 ± 124.2, 209.7 ± 82.5, 63.9 ± 43.4, 5.6 ± 1.6, 15.8 ± 8.9, 39.2 ± 23.5, 5.4 ± 4.6, 1.4 ± 0.9, 25.5 ± 5, 199.2 ± 36.6, 134 ± 8.6, 20.2 ± 8.9, and 1.7 ± 0.2 mg/l, respectively. Concentration of pollutants significantly increased by 5-15% from sampling station S1 (upstream) to S5 (downstream). Enumerations of fecal coliform and Escherichia coli bacteria were low at S1 but significantly higher at the S5 site. WQI ranged from 88 to 345 during pre-monsoon and 159 to 422 during post-monsoon period, indicating poor water quality which was unsuitable for drinking purposes. Strong positive correlations (≥ 0.9) were observed among pH, chloride, phosphate, sulfate, turbidity, conductivity, TS, TDS, BOD, and COD for water samples during both seasons. The data reveals that pollution load increases gradually from upstream to downstream due to the increasing discharge of raw sewage. Regulatory bodies should formulate strict regulations and ensure their implementation for the protection and management of river water quality.