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Nanofluids have a wide range of applications in biological research. They are employed in targeted medication administration, hyperthermia (for cancer treatment) and differential diagnostics like magnetic resonance image (MRI). In light of these medical applications, the impact of an external magnetic field and an exponential heat source on the dynamics of [Formula: see text]–[Formula: see text] over a nonlinearly stretched surface has been investigated. A realistic modified Buongiorno model has been used which includes the effects of reaction rate, Biot number and activation energy. The boundary value problem governing the model is solved on MATLAB R2022a using the solver, BVP5C. Further, the consequences of different parameters on rate of heat transfer coefficient (Nusselt number), rate of mass transfer coefficient (Sherwood number), drag coefficient, velocity, temperature and volume fraction profile are observed graphically. It is noted that volume fraction and uniform heat source intensity have a positive effect on the Nusselt number and negative effect on Sherwood number. The effects of thermal radiation and magnetic field on volume fraction profile are, respectively, positive and negative. The current physics of flow across a vertical stretching surface is expected to serve as the foundation for various medical science, engineering and technology applications.

BackgroundChromobacteriumspecies, through their bioactive molecules, help in combating biotic and abiotic stresses in plants and humans. The present study was aimed to identify, characterize and preserve in natural gums the violet-pigmented bacterial isolate TRFM-24 recovered from the rhizosphere soil of rice collected from Tripura state.ResultsBased on morphological, biochemical and 16S rRNA gene sequencing, the isolate TFRM-24 was identified asChromobacterium violaceum(NAIMCC-B-02276; MCC 4212). The bacterium is saprophytic, free living and Gram negative. The strain was found positive for production of IAA, cellulase, xylanase and protease, and showed tolerance to salt (2.5%) and drought (-1.2 MPa). However, it showed poor biocontrol activity against soil-borne phytopathogens and nutrient-solubilizing abilitiets.C. violaceumstrain TRFM-24 did not survive on tryptic soya agar (TSA) beyond 12 days between 4 and 32 °C temperature hence a method of preservation of this bacterium was attempted using different natural gums namelyAcacia nilotica(babul),Anogeissus latifolia(dhavda),Boswellia serrata(salai) andButea monosperma(palash) under different temperature regime (6–32 °C). The bacterium survived inbabulgum (gum acacia),dhavdaandsalaisolution at room temperature beyond a year.ConclusionBased on polyphasic approach, a violet-pigmented isolate TRFM-24 was identified asChromobacterim violaceumwhich possessed some attributes of plant and human importance. Further, a simple and low-cost preservation method of strain TRFM-24 at room temperature was developed using natural gums such asbabul,dhavdaandsalaigums which may be the first report to our knowledge.

Inhibition of human carbonic anhydrase (hCA) isoform IX with concurrent induction of apoptosis is a promising approach for targeting cancer in humans. Prompted by the scope, novel benzenesulfonamides containing the 1,2,3-triazolylthiazolotriazole tail were synthesized and screened as inhibitors of hCA isoforms I, II, IV, and IX. The tumor-associated isoform hCA IX was strongly inhibited by the sulfonamides reported here with K

Diacylglycerol kinase (DGK), a lipid kinase, catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid, thereby terminating DAG-mediated signaling by Gq-coupled receptors that regulate contraction of airway smooth muscle (ASM). A previous study from our laboratory demonstrated that DGK inhibition or genetic ablation leads to reduced ASM contraction and provides protection for allergen-induced airway hyperresponsiveness. However, the mechanism by which DGK regulates contractile signaling in ASM is not well established. Herein, we investigated the role of prorelaxant cAMP-protein kinase A (PKA) signaling in DGK-mediated regulation of ASM contraction. Pretreatment of human ASM cells with DGK inhibitor I activated PKA as demonstrated by the phosphorylation of PKA substrates, VASP, Hsp20, and CREB, which was abrogated when PKA was inhibited pharmacologically or molecularly using overexpression of the PKA inhibitor peptide, PKI. Furthermore, inhibition of DGK resulted in induction of cyclooxygenase (COX) and generation of prostaglandin E2 (PGE2 ) with concomitant activation of Gs-cAMP-PKA signaling in ASM cells in an autocrine/paracrine fashion. Inhibition of protein kinase C (PKC) or extracellular-signal-regulated kinase (ERK) attenuated DGK-mediated production of PGE2 and activation of cAMP-PKA signaling in human ASM cells, suggesting that inhibition of DGK activates the COX-PGE2 pathway in a PKC-ERK-dependent manner. Finally, DGK inhibition-mediated attenuation of contractile agonist-induced phosphorylation of myosin light chain 20 (MLC-20), a marker of ASM contraction, involves COX-mediated cAMP production and PKA activation in ASM cells. Collectively these findings establish a novel mechanism by which DGK regulates ASM contraction and further advances DGK as a potential therapeutic target to provide effective bronchoprotection in asthma.

The identification of x-ray crystal structure of cathepsin B (CTSB) in the early 90's enabled researchers to embark on a journey to understand and demystify its multiple catalytic mechanisms (endopeptidase/carboxypeptidase/peptidyl-dipeptidase) in diverse physiological processes and their switching into one another under different conditions. The engagement of CTSB in different pathological conditions due to its over-expression further highlighted the enhanced research interest around the domain. The occurrence of over-expressed CTSB in various diseases like Alzheimer's, cancer, arthritis, cardiovascular, etc., and the use of CTSB inhibitors for the treatment of these diseases have established its involvement in different pathological conditions. Such an understanding tempted researchers to design, synthesize, and screen diverse classes of compounds against CTSB. This in turn, helped in understanding their interactions with the active sites of the enzyme. Heterocyclic compounds comprise a very rich and broad class of medicinally important compounds that also hold great potential for CTSB inhibition. This review covers the CTSB inhibition potential of various natural and synthetic heterocyclic scaffolds. Researchers working in the fields of molecular modeling, drug design and development, and enzyme inhibitors can benefit significantly from this review.

Spiders are one of the most fascinating and diverse invertebrates and also potential bio-control agents in agro-ecosystems. Field surveys were carried out at Sundernagar, Jogindernagar, Nurpur and Palampur areas of Himachal Pradesh by two methods namely visual count and sweep net to assess seasonal abundance and diversity of spider, in the rice ecosystems during kharif, 2015 and 2016. It was found that the population trend was well represented by visual count method as compared to sweep net method. Maximum numbers of spiders were recorded from Palampur area followed by Sundernagar, Jogindernagar and Nurpur. Eleven families viz., Oxyopidae, Tetragnathidae, Salticidae, Lycosidae, Pisauridae, Araneidae, Theridiidae, Clubionidae, Sparassidae, Thomisidae and Pholcidae were recorded from the fields with majority belonging to Araneidae and Tetragnathidae. The pre-dominant spider genus from all the locations were Tetragnatha and Neoscona while Araneus pseudosturmii and Runcinia ghorpadei Tikader were confined only to Nurpur and Sundernagar, respectively. A. pseudosturmii and Micropholcus fauroti Simon seem to be the first records from India while R. ghorpadei to be the hitherto unknown male morph.

This article explores the effects of two temperatures on the combined problem of wave propagation and thermomechanical loading in a homogeneous isotropic plate. The governing equations are converte...

Lung cells are constantly exposed to various internal and external stressors that disrupt protein homeostasis. To cope with these stimuli, cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR). UPR stressors can impose greater protein secretory demands on the endoplasmic reticulum (ER), resulting in the development, differentiation, and survival of these cell types to meet these increasing functional needs. Dysregulation of the UPR leads to the development of the disease. The UPR and ER stress are involved in several human conditions, such as chronic inflammation, neurodegeneration, metabolic syndrome, and cancer. Furthermore, potent and specific compounds that target the UPR pathway are under development as future therapies. The focus of this review is to thoroughly describe the effects of both internal and external stressors on the ER in asthma. Furthermore, we discuss how the UPR signaling pathway is activated in the lungs to overcome cellular damage. We also present an overview of the pathogenic mechanisms, with a brief focus on potential strategies for pharmacological interventions.

Nucleotide monomers that hold two nucleobases each, i.e. double-headed nucleotides, have been shown to form two sets of functional Watson–Crick base pairs when incorporated into dsDNA, and they hereby behave as dinucleotides. To form the basis for fully modified double-headed nucleic acids (DhNA), we have prepared three new DhNA monomers and can now demonstrate that the molecular information of 10 Watson–Crick base pairs can be condensed to highly stable 5-mer DhNA duplexes.

A library of twenty-two arylthiazolylhydrazono-1,2,3-triazoles incorporating sulfanilamide and metanilamide moieties have been synthesized by utilizing tail-approach and characterized by their IR

In this work, Cu-Ag core-shell nanoparticles were synthesized via a chemical reduction method. Subsequently, Cu-Ag core-shell nanoparticles were dispersed into polyvinyl alcohol (PVA) and films wer...

Human carbonic anhydrase (hCA) isoforms hCA IX and hCA XII are well established anticancer drug targets and their selective inhibition is highly desired for the proper treatment of cancer. Lack of isoform-selectivity in current clinically used CA inhibitors (CAIs) is a major concern as it leads to undesired side effects, associated with off-target inhibition. Thus, there is need to explore alternative approaches for the design of isoform-selective inhibitors and the leading promising approach for the design of isoform-selective CAIs is "the tail-approach". Virtually, most drug design studies in the last decade were done by considering the tail-approach reported in 1999. The past decade of 2010-2020 witnessed progressive maturation of this approach as a large number of CAIs have been designed and synthesised based on it, many of which turned out to be effective as well as selective hCA IX and hCA XII inhibitors. This review covers the past decade (2010-2020) research, considering selective as well as potent inhibitors of tumor associated isoforms, hCA IX and hCA XII, which include newer generation inhibitors containing sulfonamides or their bioisosteres, non-classical inhibitors (including carboxylic acid/ester, coumarin and sulfocoumarin classes) and various other novel classes of inhibitors belonging to newly identified chemotypes/scaffolds.

Efficacy of seven insecticides buprofezin (0.04%), chlorantraniliprole (0.005%), fenazaquin (0.025%), imidacloprid (0.004%), spiromesifen (0.02%), thiamethoxam (0.05%) and cypermethrin (0.014%) was evaluated against sucking pests infesting okra at CSK HPKV Palampur during kharif 2018. Imidacloprid (0.004%) was found to be most effective treatment against Aphis gossypii Glover and Amrasca biguttula biguttula Ishida amongst all the insecticides followed by thiamethoxam (0.05%). For the remaining treatments, the decreasing order of efficacy based on the % reduction in aphid incidence was buprofezin, chlorantraniliprole, cypermethrin, fenazaquin and spriromesifen whereas in case of jassids the decreasing order of efficacy was cypermethrin, buprofezin, chlorantraniliprole, spiromesifen and fenazaquin. Imidacloprid treated plots resulted in maximum fruit yield and incremental cost benefit ratio followed by thiamethoxam, buprofezin, chlorantraniliprole, cypermethrin, spiromesifen and fenazaquin.

Efficacy of a biopesticide and five natural products comprising azadirachtin, cow urine, darekastra, jeevamrit, vermiwash and tamarlassi were evaluated against sucking pests in okra at the CSK HPKV, Palampur during kharif, 2018. The aphid and jassid incidence was observed to undergo reduction with sprays and reached to 61.55 and 62.95%, respectively in azadirachtin after fifth spray. Darekastra, jeevamrit and vermiwash were moderately effective, with the least effective one being cow urine. The fruit yield and incremental cost benefit ratio was 1: 5.72 in azadirachtin (59.63 q/ ha).

Twenty novel 1,2,3-triazole benzenesulfonamides featuring nitrile 8a-g, carbothioamide 9a-f, and N'-hydroxycarboximidamide 10a-g functionalities were designed and synthesized to improve potency and selectivity as carbonic anhydrase inhibitors (CAIs). The synthesized 1,2,3-triazole compounds were tested in vitro as CAIs against four physiologically and pharmacologically relevant isoforms of human carbonic anhydrase (hCA I, II, IV, and IX). Compounds 8a-g, 9a-f, and 10a-g displayed variable inhibition constants ranging from 8.1 nM to 3.22 μM for hCA I, 4.7 nM to 0.50 μM for hCA II, 15.0 nM to 3.7 μM for hCA IV, and 29.6 nM to 0.27 μM for hCA IX. As per the inhibition data profile, compounds 9a-e exhibited strong efficacy for hCA IV, whereas the inhibition was found to be somewhat diminished in the case of hCA IX by nearly all the compounds. A computational protocol based on docking and MM-GBSA was conducted to reveal the plausible interactions of the targeted sulfonamides within the hCA II and IX binding sites. The outcomes of appending various functionalities at the C-4 position of the 1,2,3-triazole motif over the inhibition potential and selectivity of the designed sulfonamides were examined with a potential for the discovery of new isoform selective CAIs. The CAI and SAR data established the significance of the synthesized 1,2,3-triazoles as building blocks for developing CAI drugs.

Exaggerated airway smooth muscle (ASM) contraction regulated by the Gq family of G protein-coupled receptors causes airway hyperresponsiveness in asthma. Activation of Gq-coupled G protein-coupled receptors leads to phospholipase C (PLC)-mediated generation of inositol triphosphate (IP

Autophagy, apoptosis, and the unfolded protein response (UPR) are fundamental biological processes essential for manifold cellular functions in health and disease. Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disorder associated with aging that has limited therapies, reflecting our incomplete understanding. We conducted an observational study linking molecular markers of cell stress response pathways (UPR: BiP, XBP1; apoptosis: cleaved caspase-3; autophagy: LC3β) in lung tissues from IPF patients and correlated the expression of these protein markers to each subject’s lung function measures. We hypothesized that changes in lung tissue expression of apoptosis, autophagy, and UPR markers correlate with lung function deficits in IPF. The cell stress markers BiP, XBP1, LC3β puncta, and cleaved caspase-3 were found to be elevated in IPF lungs compared to non-IPF lungs, and, further, BiP and cleaved caspase-3 co-localized in IPF lungs. Considering lung function independently, we observed that increased XBP1, BiP, and cleaved caspase-3 were each associated with reduced lung function (FEV1, FVC, TLC, RV). However, increased lung tissue expression of LC3β puncta was significantly associated with increased diffusion capacity (DLCO), an indicator of alveolar–capillary membrane function. Similarly, the co-localization of UPR (XBP1, BiP) and autophagy (LC3β puncta) markers was positively correlated with increased lung function (FEV1, FVC, TLC, DLCO). However, the presence of LC3β puncta can indicate either autophagy flux inhibition or activation. While the nature of our observational cross-sectional study design does not allow conclusions regarding causal links between increased expression of these cell stress markers, lung fibrosis, and lung function decline, it does provide some insights that are hypothesis-generating and suggests that within the milieu of active UPR, changes in autophagy flux may play an important role in determining lung function. Further research is necessary to investigate the mechanisms linking UPR and autophagy in IPF and how an imbalance in these cell stress pathways can lead to progressive fibrosis and loss of lung function. We conclude by presenting five testable hypotheses that build on the research presented here. Such an understanding could eventually lead to the development of much-needed therapies for IPF.

Normally speech-disabled people use sign gestures to communicate with another person but for a normal person, it’s very hard to understand sign language. So, our aim is to develop a device capable of translating sign language in order to make it easy for disabled people to communicate with the general public. For this, a smart hand gesture recognition system is proposed to reduce the communication gap between disabled and normal people (Hubbell 2014). The system is in the form of a glove, which consists of five flex sensors, one for each finger and a 3-axis accelerometer, on the back of the palm, connected to an Arduino MEGA device. Flex sensors measure the bend of each finger and the accelerometer measures the slope of the palm. Data from these sensors is for each gesture collected to create a dataset (Deller et al. 2006). The system is based on American Sign Language. Machine Learning Algorithms train over these datasets to predict what gesture the user is making. The goal of this smart system is to minimize the communication gap and make day to day communication for disabled easy.

COPD is a common and highly destructive disease with huge impacts on people and health services throughout the world. It is mainly caused by cigarette smoking though environmental pollution is also significant. There are no current treatments that affect the overall course of COPD; current drugs focus on symptomatic relief and to some extent reducing exacerbation rates. There is an urgent need for in-depth studies of the fundamental pathogenic mechanisms that underpin COPD. This is vital, given the fact that nearly 40%–60% of the small airway and alveolar damage occurs in COPD well before the first measurable changes in lung function are detected. These individuals are also at a high risk of lung cancer. Current COPD research is mostly centered around late disease and/or innate immune activation within the airway lumen, but the actual damage to the airway wall has early onset. COPD is the end result of complex mechanisms, possibly triggered through initial epithelial activation. To change the disease trajectory, it is crucial to understand the mechanisms in the epithelium that are switched on early in smokers. One such mechanism we believe is the process of epithelial to mesenchymal transition. This article highlights the importance of this profound epithelial cell plasticity in COPD and also its regulation. We consider that understanding early changes in COPD will open new windows for therapy.

Current asthma therapies fail to target airway remodeling that correlates with asthma severity driving disease progression that ultimately leads to loss of lung function. Macroautophagy (hereinafte...

Deficiency of vitamin-E or tocopherol causes neurological disorders in humans. α-tocopherol possessing the highest vitamin-E activity is present in low concentration in maize kernel. Nine lines and four testers possessing favourable allele of ZmVTE4 that significantly enhances vitamin-E activity were used to generate 36 hybrid combinations. Significant variation was observed for α- (5.95–39.03 μg/g), γ- (11.69–50.82 μg/g), δ- (4.09–10.76 μg/g) and total-tocopherol (33.18–90.53 μg/g). α-, γ- and δ-tocopherol constituted 36%, 53% and 11% of the total tocopherol, respectively. Majority of the experimental hybrids possessed significantly higher α-tocopherol (mean: 21.37 μg/g) than the check hybrids (mean: 11.16 μg/g). AMMI analysis revealed that across tocopherols, genotype and interaction effect accounted 35–77% and 23–45% of variation, respectively. The environmental effects were of minor magnitude. Non-additive gene action was predominant for α-, γ-, and total-tocopherol, while δ-tocopherol was conditioned predominantly by additive gene action. The information generated here assumes great significance in biofortification programme. This is the first report of variability, G × E interactions and combining ability for kernel tocopherol using maize hybrids possessing novel allele of ZmVTE4.

Salt stress hampers plant growth and development. It is now becoming one of the most important threats to agricultural productivity. Rhizosphere microorganisms play key roles in modulating cellular responses and enable plant tolerant to salt stress, but the detailed mechanisms of how this occurs need in-depth investigation. The present study elucidated that the microbe-mediated restructuring of the cellular responses leads to ecological fitness and adaptiveness to the maize (Zea mays L.) grown in saline–sodic soil. In the present study, effects of seed biopriming with B. safensis MF-01, B. altitudinis MF-15, and B. velezensis MF-08 singly and in consortium on different growth parameters were recorded. Soil biochemical and enzymatic analyses were performed. The activity and gene expression of High-Affinity K+ Transporter (ZmHKT-1), Sodium/Hydrogen exchanger 1 (zmNHX1), and antioxidant enzymes (ZmAPX1.2, ZmBADH-1, ZmCAT, ZmMPK5, ZmMPK7, and ZmCPK11) were studied. The expression of genes related to lateral root development (ZmHO-1, ZmGSL-1, and ZmGSL-3) and root architecture were also carried out. Seeds bioprimed with consortium of all three strains have been shown to confer increased seed germination (23.34–26.31%) and vigor indices (vigor index I: 38.71–53.68% and vigor index II: 74.11–82.43%) as compared to untreated control plant grown in saline–sodic soil at 30 days of sowing. Results indicated that plants treated with consortium of three strains induced early production of adventitious roots (tips: 4889.29, forks: 7951.57, and crossings: 2296.45) in maize compared to plants primed with single strains and untreated control (tips: 2019.25, forks: 3021.45, and crossings: 388.36), which was further confirmed by assessing the transcript level of ZmHO-1 (7.20 folds), ZmGSL-1 (4.50 folds), and ZmGSL-3 (12.00 folds) genes using the qPCR approach. The uptake and translocation of Na+, K+, and Ca2+ significantly varied in the plants treated with bioagents alone or in consortium. qRT-PCR analysis also revealed that the ZmHKT-1 and zmNHX1 expression levels varied significantly in the maize root upon inoculation and showed a 6- to 11-fold increase in the plants bioprimed with all the three strains in combination. Further, the activity and gene expression levels of antioxidant enzymes were significantly higher in the leaves of maize subjected seed biopriming with bioagents individually or in combination (3.50- to 12.00-fold). Our research indicated that ZmHKT-1 and zmNHX1 expression could effectively enhance salt tolerance by maintaining an optimal Na+/K+ balance and increasing the antioxidant activity that keeps reactive oxygen species at a low accumulation level. Interestingly, up-regulation of ZmHKT-1, NHX1, ZmHO-1, ZmGSL-1, and ZmGSL-3 and genes encoding antioxidants regulates the cellular responses that could effectively enhance the adaptiveness and ultimately leads to better plant growth and grain production in the maize crop grown in saline–sodic soil.

Background The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. Results After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), P = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), P = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61–2.99), P = 0.942] and patients on statins showed a more normal computed tomography (CT) scan result [OR = 0.41, 95% CI = (0.07–2.33), P = 0.312]. Conclusions Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19, we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to further evaluate and validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

A one pot synthesis of β-ketonitriles from readily accessible 3-chloropropenals using economically benign iodine, aqueous ammonia and sodium hydroxide solution, employing mild reaction conditions have been described. This report presents a convenient, inexpensive, highly toxic-matter-free and eco-friendly approach for β-ketonitriles.