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Abstract. The present study aimed to examine the chemoprotective effect of Hydroethanolic Murraya koenigii leaves extract (HEMKLE) on murine skin carcinogenesis model. For the study, male LACA mice divided into four groups (n = 15 per group). Group I (Control), Group II (DMBA/TPA), Group III (HEMKLE), and Group IV (HEMKLE + DMBA/TPA). Skin tumors were induced in Group II (DMBA/TPA) and Group IV (HEMKLE + DMBA/TPA) by topical application of 7, 12 dimethylbenz[a]anthracene (DMBA) [500 nmol/100 μL of acetone, twice a week for two weeks] and 12-O-tetradecanoyl phorbol-13-acetate (TPA) [1.7 nmol/100 μL of acetone, twice a week for eighteen weeks] and HEMKLE (200 mg/kg b. w.) was administered orally (instilled by oral gavage). The chemoprotective response of HEMKLE was evident by inhibition in tumor incidence, mean tumor volume, mean tumor burden, total number of tumors, and tumor size in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA). HEMKLE administration also decreased the reactive oxygen species (ROS) and lipid peroxidation (LPO) levels and increased the antioxidants enzyme activities in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA) that suggests its antioxidant potential. HEMKLE administration also increased the mRNA and protein expression of caspase-9 and caspase-3 and decreased the mRNA and protein expression of Bcl-2 in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA) that suggest its apoptosis-inducing effect on DMBA/TPA induced skin carcinogenesis.

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM. Published version The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) supported the meta-analysis—Project-ID 387509280—SFB1350 (Subproject C6 to I.M.H.). A.M.H., B.R., and R.T. were supported by VACSR&D MVP grant CX001897. This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by VACSR&D MVP grant CX001897 (A.M.H.). This publication does not represent the views of the Department of Veteran Affairs or the United States Government. We conducted this research using the UK Biobank resource under the application number 20272.

The recent outbreak of SARS CoV-2 has changed the global scenario of human lives/economy. A significant number of the non-survivors showed cardiac-renal-vasculature dysfunction. A 'cytokine storm' namely, interleukin IL6-IL1 receptors i.e. IL6R-IL1R over-functioning was reported. Here, nigellidine, an indazole-alkaloid and key-component of Nigella Sativa L. (NS) commonly known as black-cumin-seed was analyzed for COVID-19 protein-targeting and IL1R-IL6R inhibition through molecular-docking-study and biochemical-study in experimental-rat to evaluate antioxidative-capacity. The NMR/X-ray-crystallographic/Electron-microscopic structures of COVID-19 Main-protease (6LU7)/Spike-glycoprotein(6vsb)/NSP2(QHD43415_2)/Nucleocapsid(QHD43423), Human IL1R(1itb)-IL6R(1pm9) from PDB were retrieved-analyzed for receptor-ligand interaction. Then those structures were docked with nigellidine using Autodock and Patchdock-server. A brief comparison was made with nigellicine-thymoquinone from N. sativa. Where nigellidine showed highest binding-energy of -6.6 (kcal/mol), ligand-efficiency of -0.3 with COVID19 Nsp2 forming bonds with amino acid CYS240 present in binding-pocket. Nigellidine showed strong interaction with main-protease (BE:-6.38/LE:-0.29). Nigellidine showed affinity to IL1R (-6.23). The NS treated rat showed marked decline in ALP-SGPT-SGOT-malondialdehyde(MDA) than the basal-levels. From the Western-blot and activity-analysis it was observed that Nigellidine (sulfuryl-group-drug) showed no impact on Phenol-catalyzing ASTIV and Steroid-catalyzing estrogen-sulfotransferase expressions and activities in liver-tissue and thus has no influence in sulfation-mediated adverse metabolic-processes. Conclusively, nigellidine has hepato-reno-protective/antioxidant-immunomodulatory/anti-inflammatory activities with inhibit-potentials of COVID-19 proteins. Further validation is necessary.

STAT3 signaling has been shown to regulate cellular function and cytokine production in the tumor microenvironment (TME). Within the head and neck squamous cell carcinoma (HNSCC) TME, we previously showed that therapeutic targeting of STAT3 in combination with radiation resulted in improved tumor growth delay. However, given the independent regulatory effects STAT3 has on anti-tumor immunity, we aimed to decipher the effects of individually targeting STAT3 in the cancer cell, regulatory T cells (Tregs), and natural killer (NK) cell compartments in driving tumor growth and resistance to therapy in HNSCCs. We utilized a CRISPR knockout system for genetic deletion of STAT3 within the cancer cell as well as two genetic knockout mouse models, FoxP3-Cre/STAT3 fl and NKp46-Cre/STAT3 fl, for Tregs and NK cell targeting, respectively. Our data revealed differences in development of resistance to treatment with STAT3 CRISPR knockout in the cancer cell, driven by differential recruitment of immune cells. Knockout of STAT3 in Tregs overcomes this resistance and results in Treg reprogramming and recruitment and activation of antigen-presenting cells. In contrast, knockout of STAT3 in the NK cell compartment results in NK cell inactivation and acceleration of tumor growth. These data underscore the complex interplay between the cancer cell and the immune TME and carry significant implications for drug targeting and design of combination approaches in HNSCCs.

Co-composting of invasive aquatic weeds with pond sediment can be a cost-effective way to manage the problem of invasion and eutrophication in aquatic systems and improvement of soil fertility in agricultural systems. Nevertheless, preparation of good quality compost is a challenge because of the variations in the physico-chemical properties of the plant material and the bulking agent. Mixing the plant biomass and the bulking agent in an appropriate proportion is crucial to make good quality compost, which requires a systematic empirical study. We standardized a protocol for composting Eichhornia crassipes and Ipomoea carnea biomass using pond sediment as a bulking agent. For each species, we used a randomized block design with 3 treatments × 3 replicates. The study revealed that mixing pond sediment and the weed biomass in 1:5 ratio yielded better quality compost in both the species compared to other treatments. The study emphasizes that composting aquatic weeds with pond sediment should help in managing the problem of weed invasion, sedimentation, eutrophication, and loss of soil fertility in agricultural fields.

Key Points HMB is associated with rare and common variants in genes related to anemias and bleeding disorders.These are the first exome-sequencing results from patients with HMB, as well as their comparison with control exomes., Visual Abstract, Adolescents with low von Willebrand factor (VWF) levels and heavy menstrual bleeding (HMB) experience significant morbidity. There is a need to better characterize these patients genetically and improve our understanding of the pathophysiology of bleeding. We performed whole-exome sequencing on 86 postmenarchal patients diagnosed with low VWF levels (30-50 IU/dL) and HMB and compared them with 660 in-house controls. We compared the number of rare stop-gain/stop-loss and rare ClinVar “pathogenic” variants between cases and controls, as well as performed gene burden and gene-set burden analyses. We found an enrichment in cases of rare stop-gain/stop-loss variants in genes involved in bleeding disorders and an enrichment of rare ClinVar “pathogenic” variants in genes involved in anemias. The 2 most significant genes in the gene burden analysis, CFB and DNASE2, are associated with atypical hemolytic uremia and severe anemia, respectively. VWF also surpassed exome-wide significance in the gene burden analysis (P = 7.31 × 10−6). Gene-set burden analysis revealed an enrichment of rare nonsynonymous variants in cases in several hematologically relevant pathways. Further, common variants in FERMT2, a gene involved in the regulation of hemostasis and angiogenesis, surpassed genome-wide significance. We demonstrate that adolescents with HMB and low VWF have an excess of rare nonsynonymous and pathogenic variants in genes involved in bleeding disorders and anemia. Variants of variable penetrance in these genes may contribute to the spectrum of phenotypes observed in patients with HMB and could partially explain the bleeding phenotype. By identifying patients with HMB who possess these variants, we may be able to improve risk stratification and patient outcomes.

The choice of active site and support matrix decides the activity of catalyst. Any modifications on these will have a significant impact on its reactivity and selectivity. Here we have synthesised WO3 loaded boehmite and applied them for acetalization of biomass derived bulk chemical, glycerol. The well-characterized acid catalyst, exhibit a selective acetalization of glycerol with good conversions to five-membered dioxolane product. The cyclability of catalyst up to six times with retention of catalytic activity ensures the heterogeneity of the material.

Alzheimer's disease (AD) is a multifactorial progressive and irreversible neurodegenerative disorder characterized by severe memory impairment and cognitive disability in the middle and old-aged human population. There are no proven drugs for AD treatment and prevention. In Ayurveda, medhya plants are used to prepare Rasayana, and its consumption improves memory and cognition. Nardostachys jatamansi (D.Don) DC is a medhya plant used in traditional medicine to treat neurological disorders, and its unique pyranocoumarins can be a potential drug candidate for AD. Given its traditional claims, this study aims to find the multi-target potential efficacy of the ligands (drug molecules) against the AD from N. jatamansi pyranocoumarins using computational drug discovery techniques. Drug likeliness analysis confirms that pyranocoumarins of N. jatamansi, such as seselin, jatamansinol, jatamansine, jatamansinone, and dihydrojatamansin are probable drug candidates for AD. Molecular docking, molecular dynamic simulations, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis confirm that dihydrojatamansin inhibits acetylcholinesterase (AChE), and jatamansinol inhibits butyrylcholinesterase (BuChE), glycogen synthase kinase 3β (GSK3β), and kelch-like ECH-associating protein 1 (Keap1) AD therapeutic targets. Therefore, this study provides potential multi-target inhibitors that would further validate experimental studies, leading to new treatments for AD.Communicated by Ramaswamy H. Sarma.

Iron is an essential element due to its role in a wide variety of physiological processes. Iron homeostasis is crucial to prevent iron overload disorders as well as iron deficiency anemia. The liver synthesized peptide hormone hepcidin is a master regulator of systemic iron metabolism. Given its role in overall health, measurement of hepcidin can be used as a predictive marker in disease states. In addition, hepcidin-targeting drugs appear beneficial as therapeutic agents. This review emphasizes recent development on analytical techniques (immunochemical, mass spectrometry and biosensors) and therapeutic approaches (hepcidin agonists, stimulators and antagonists). These insights highlight hepcidin as a potential biomarker as well as an aid in the development of new drugs for iron disorders.

Lipase is one of the promising biocatalyst in field of Enzymatic Biodiesel production. Screening of lipase producing bacteria and its media optimization facilitates enhanced lipase production. Considering the advantages of enzymatic biodiesel production using lipases the objective of present work was to isolate lipase producing bacteria and its media optimization. Bacterial strain were isolated from oil rich sample showing maximum zone of hydrolysis on TBA Media was selected and identified as Lysinibacillus macroides FS1 by 16SrDNA gene sequence analysis. Lipase production was carried out in production media and lipase activity of 3.1U/ ml was assayed by titrimetric method. Various media parameters were optimized and maximal lipase activity of 16.75U/ml were observed at 48 hr of incubation in optimized media with Honge oil as inducer, Galactose as carbon source , Ammonium Chloride and Beef extract as source of nitrogen, pH 7 and 37oC temperature with agitation speed of 120 rpm. Under optimized condition 5.4 fold increases in the lipase activity than innate activity was observed. 50.74% yield was observed with specific activity of 21.25U/mg after purification with 30% ammonium sulphate. Purified lipase was stable in presence of methanol at 37°C. Results obtained shows that Lipase from Lysinibacillus macroides FS1 was promising biocatalyst for Biodiesel production.

Urinary tract infection (UTI) has been reported most often in recent days. In a clinical aspect there are various reasons for this cause. Out of 100 samples tested (Clinical samples from Rashi Diagnostic Center- Bangalore NABL laboratory), under the analytical aspect several comparative analysis was done. Urine was tested within half an hour of the collection. Physical characteristics of Urine sample were studied initially. Laura M is the device used to analyses the Uro-dip. Sugar and the presence of albumin was also found. Sediment of the centrifuged sample was subjected to gram staining and direct microscopic analysis. Pus cells, epithelial cells, yeast cells and rod shaped bacteria. It was found that epithelial cells are visualized in female samples and very less or not visualized in male samples. Bilirubin content, Bile salt content and ketone bodies were analyzed and compared in each of the samples. Sample is then subjected to culturing were the T streak is done on the Mac Conkey agar and Blood agar. This will differentiate between the lactose and Non-Lactose fermenting bacteria. Each of the colony is subjected to Gram staining. Yeast cells are also reported often. Though the yeast cells are the commensals they are considered non- pathogenic. But it was found that the yeast with pseudo-hyphae are pathogenic in nature. Both Lactose and Non-Lactose fermenting bacterial colonies from Blood agar is subjected to various biochemical methods to identify the organism. The most commonly noticed non-lactose fermenting organism was Pseudomonas spp. And Lactose fermenting organisms were Escherichia coli, Enterobacteria spp and Klebsiella spp. Each Colony from the culture plate was picked and streaked on the MHA agar and Kirby Bauer method has been performed (Disc diffusion method) under the McFerland standard. Zone of inhibition of each organism towards the antibiotic in the disc was recorded.

Objectives Monitoring the antibody responses to SARS-CoV-2 infection and its correlation to clinical spectrum of disease is critical in understanding the disease progression and protection against re-infection. We assessed the nucleocapsid (N) and receptor-binding-domain of spike (SRBD) protein specific IgG and neutralizing antibody (NAb) responses in COVID-19 patients up to 8 months and its correlation with diverse disease spectrum. Methods During the first wave of the SARS-CoV-2 pandemic, from 284 COVID-19 patients, 608 samples were collected up to 8 months post infection. The patients were categorized as asymptomatic, symptomatic and severe. The N and SRBD IgG and NAb titers were evaluated and correlated with clinical data. Results A steep increase in antigen specific antibody titers was observed till 40 days post onset of the disease (POD), followed by a partial decline till 240 days. Severe disease was associated with a stronger SRBD IgG response and higher NAb titers. The persistence of antibody response was observed in 76% against N, 80% against SRBD and 80% for NAbs of cases up to 8 months POD. Conclusion RBD and N protein specific IgG persisted till 240 days POD which correlated with NAb response, irrespective of individual`s symptomatic status indicating overall robust protection against re-infection.

Since 2005, the Pathogen–Host Interactions Database (PHI-base) has manually curated experimentally verified pathogenicity, virulence and effector genes from fungal, bacterial and protist pathogens, which infect animal, plant, fish, insect and/or fungal hosts. PHI-base (www.phi-base.org) is devoted to the identification and presentation of phenotype information on pathogenicity and effector genes and their host interactions. Specific gene alterations that did not alter the in host interaction phenotype are also presented. PHI-base is invaluable for comparative analyses and for the discovery of candidate targets in medically and agronomically important species for intervention. Version 4.12 (September 2021) contains 4387 references, and provides information on 8411 genes from 279 pathogens, tested on 228 hosts in 18, 190 interactions. This provides a 24% increase in gene content since Version 4.8 (September 2019). Bacterial and fungal pathogens represent the majority of the interaction data, with a 54:46 split of entries, whilst protists, protozoa, nematodes and insects represent 3.6% of entries. Host species consist of approximately 54% plants and 46% others of medical, veterinary and/or environmental importance. PHI-base data is disseminated to UniProtKB, FungiDB and Ensembl Genomes. PHI-base will migrate to a new gene-centric version (version 5.0) in early 2022. This major development is briefly described.

(3E,7Z)-Tetradecadienyl acetate, the major sex pheromone component of the potato pest Symmetrischema tangolias (Gyen), was stereoselectively synthesized from the commercially available 3-bromo-1-propanol via the stereospecific reduction of alkyne with lithium aluminum hydride (LAH) and the Wittig reaction.

In recent times, fused azaheterocycles emerged as impressive therapeutic agents. Binding studies of such azaheterocycles with biomolecules is an important subject for pharmaceutical and biochemical studies aiming at the design and development of new drugs. Fused heterocyclic scaffolds, such as thiazolopyrmidines have long been used in the pharmaceutical industry for the treatment of various diseases. In this study, we have accomplished a regioselective synthesis of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines by the reaction of tetrahydropyrimidine-2(H)-thione with α-bromo-1,3-diketones, generated in situ from 1,3-diketones and NBS, using visible light as an inexpensive, green and renewable energy source under mild reaction conditions with wide-ranging substrate scope. The regioisomer was characterized unambiguously by 2D-NMR [1H-13C] HMBC and [1H-13C] HMQC spectroscopy. In silico toxicity data analysis showed the low toxicity risks of the synthesized compounds. Computational molecular docking studies were carried out to examine the interaction of thiazolo[3,2-a]pyrimidines with calf-thymus DNA (ct-DNA) and Bovine Serum Albumin (BSA). Moreover, different spectroscopic approaches viz. steady-state fluorescence, competitive displacement assay, UV–visible and circular dichroism (CD) along with viscosity measurements were employed to investigate the binding mechanisms of thiazolo[3,2-a]pyrimidines with DNA and BSA. The results thus obtained revealed that thiazolo[3,2-a]pyrimidines offer groove bindings with DNA and showed moderate bindings with BSA.

A codon optimized cellobiohydrolase (CBH) encoding synthetic gene of 1188 bp from a thermophilic mold Myceliophthora thermophila (MtCel6A) was cloned and heterologously expressed in Escherichia coli for the first time. In silico analysis suggested that MtCel6A is a GH6 CBH and belongs to CBHII family, which is structurally similar to Cel6A of Humicola insolens. The recombinant MtCel6A is expressed as active inclusion bodies, and the molecular mass of the purified enzyme is ~ 45 kDa. The rMtCel6A is active in a wide range of pH (4–12) and temperatures (40–100 °C) with optima at pH 10.0 and 60 °C. It exhibits T1/2 of 6.0 and 1.0 h at 60 and 90 °C, respectively. The rMtCel6A is an extremozyme with organic solvent, salt and alkali tolerance. The Km, Vmax, kcat and kcat/Km values of the enzyme are 3.2 mg mL−1, 222.2 μmol mg−1 min−1, 2492 s−1 and 778.7 s−1 mg−1 mL−1, respectively. The product analysis of rMtCel6A confirmed that it is an exoenzyme that acts from the non-reducing end of cellulose. The addition of rMtCel6A to the commercial cellulase mix (Cellic CTec2) led to 1.9-fold increase in saccharification of the pre-treated sugarcane bagasse. The rMtCel6A is a potential CBH that finds utility in industrial processes such as in bioethanol, paper pulp and textile industries. Graphical Abstract

Natural fibers are very flexible materials; their properties vary with physical structure and chemical composition. Chemical treatment of fiber can chemically modify, clean the fiber surface, incre...

This study describes the clinical, biochemical, and molecular characteristics of Indian children with 46,XY DSD and suspected androgen insensitivity syndrome (AIS). Fifty children (median age 3.0 years, range 0–16.5 years) with 46,XY DSD and a suspected diagnosis of AIS were enrolled. Sanger sequencing was performed to identify pathogenic variants in the androgen receptor (AR) gene and to study genotype-phenotype correlations. All 5 (100%) patients with CAIS and 14/45 (31%) patients with PAIS had pathogenic/likely pathogenic variants in the AR gene (overall, 14 different variants in 19 patients; 38.8%). There was no significant difference in clinical (cryptorchidism, hypospadias, or external masculinizing score) or biochemical parameters (gonadotropins and testosterone) between patients with or without pathogenic variants. However, patients with AIS were more likely to have a positive family history, be assigned female gender at birth, and present with gynaecomastia at puberty. Three novel pathogenic/likely pathogenic variants, including one splice donor site variant c.2318+1G>A, one frameshift variant p.H790Lfs*40, and one missense variant p.G821E, were identified in 3 patients with CAIS. The missense variant p.G821E was predicted as deleterious, damaging, disease-causing, and likely functionally inactive by in silico analysis and protein modelling study. Two previously not reported pathogenic/likely pathogenic variants, including p.R386H and p.G396R, were identified in patients with PAIS. This study contributes in expanding the spectrum of pathogenic variants in the AR gene in patients with AIS. Only 31% patients with a provisional diagnosis of PAIS had pathogenic variants in the AR gene, suggesting other possible mechanisms or candidate genes may be responsible for such a phenotypic presentation.

Cocaine abuse is known to cause inflammation, oxidative injury and alterations in the gut microbiota. Although emerging studies have demonstrated the role of gut microbiota in modulating neurological complications and behavior, the mechanism(s) underlying these processes remain unclear. In the present study, we investigated the protective effect of Lactobacillus rhamnosus probiotic on cocaine-induced oxidative stress, glial activation, and locomotion in mice. In this study, groups of male C56BL6 mice were administered gut-resident commensal bacteria L. rhamnosus probiotic (oral gavage) concurrently with cocaine (20 mg/kg, i.p.) or saline for 28 days and assessed for oxidative stress and cellular activation in both the gut and brain as well as alterations in locomotion behavior. Cocaine-induced gut dysregulation was associated with increased formation of 4-hydroxynonenal (4-HNE) adducts, increased expression of pERK-1/2, pNF-kB-p65 and antioxidant mediators (SOD1, GPx1). In cocaine administered mice, there was increased activation of both microglia and astrocytes in the striatum and cortex of the brain as shown by enhanced expression of CD11b and GFAP, respectively. Cocaine administration also resulted in increased locomotor activity in the open field test in these mice. Administration of L. rhamnosus attenuated cocaine-induced gut oxidative stress and inflammation as well as glial activation and locomotion. These results suggest the potential of microbial-based interventions to attenuate cocaine-mediated behavioral responses and neuroinflammation, in addition to systemic inflammation and oxidative damage.

Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive embryonal neoplasms of the central nervous system that correspond to WHO grade IV and have a dismal prognosis. The latest Central Brain Tumor Registry of the United States data shows that AT/RT constitutes 16.6% of all embryonal tumors in children. The molecular hallmark of this tumor is pathogenic SMARCB1 genetic alterations resulting in the loss of INI-1 immunopositivity, with fewer tumors harboring SMARCA4 (BRG1) variants. Maternal embryonal leucine zipper kinase (MELK) is a member of the Snf1/AMPK family of serine/threonine-protein kinases involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis, and splicing regulation. Recent studies have highlighted the involvement of MELK in AT/RT and its possible therapeutic role. The purpose of this study was to review the histological and immunohistochemical profile of AT/RT with special reference to MELK staining. In this retrospective study conducted over 6 years, all diagnosed cases of AT/RT, defined by loss of INI-1 immunopositivity, were retrieved and studied. Demographic details of patients and microscopic findings were analyzed, with special attention to histological patterns and immunohistochemistry profile including MELK immunoreactivity. There were 50 cases of AT/RT diagnosed in the specified period. Of the cases operated at our institute during this period, embryonal tumors constituted 20.6% of all pediatric brain tumors with AT/RT representing 12.6% of this subset. The median age at presentation was 3.5 years (range: 8 months-22 years) and there were three adult cases. Males outnumbered females by a ratio of 1.94:1. Tumor location was distributed equally between the supratentorial and infratentorial compartments. Characteristic rhabdoid cells were identified in 70% of cases. Areas with epithelial, mesenchymal, and undifferentiated tumor cells were seen in 8%, 20%, and 52% of cases, respectively. Cells with vacuolated cytoplasm were noted in 28% of cases. Immunohistochemistry (IHC) showed a polyimmunophenotypic profile with immunopositivity for GFAP in 70%, Vimentin in 100%, SMA in 68%, and EMA in 88% of cases, indicating the remarkable heterogeneity of the tumor cells. MELK immunopositivity was noted in 83.33% of cases. Thus, atypical teratoid/rhabdoid tumors are rare neoplasms. In line with other studies, we show that these tumors occur predominantly in very young children and display marked variability on histology and IHC with loss of INI-1. MELK is presumed to be an important molecule involved in cell cycle regulation, proliferation, and other critical functions. High expression of MELK in AT/RT may suggest its plausible role in neoplastic transformation of embryonic and postnatal multipotent neural progenitors which in turn could explain the diverse morphological and immunohistochemical characteristics observed in these tumors.

The present research was done to analyse the physico-chemical, Nutritional, Mineral, functional and phytochemical analysis in Functional cereals; oats, pearl millet, sorghum and finger millet. The protein content of the analyzed cereals varied from 7.45% to 14.69% with oats having higher concentration of protein content. The higher fibre content in oats accounted for its highest WAC while as the lowest fibre content in sorghum (2.35%) masked its WAC despite containing the highest carbohydrate content. Neutral detergent fiber that gives the measurement insoluble fibre was found highest in sorghum (11.29%) and lowest in pearl millet (5.56%). Total sugars comprising of reducing and non reducing sugars were found highest in pearl millet (2.88%) followed by sorghum (2.14%) and the least content was found in finger millet (1.69%). Oats were found to possess highest content of phosphorus (381.02mg/100g) and finger millet the lowest (8.21mg/100g). Resistant starch that is inaccessible to enzymes was found highest in oats (2.69g/100g) and lowest in sorghum (1.74g/100g).

Mitochondria are dynamic organelles that differ significantly in their morphologies across cell types, reflecting specific cellular needs and stages in development. Despite the wide biological significance in disease and in health, delineating mitochondrial morphologies in complex systems remains challenging. Here, we present the Mitochondrial Cellular Phenotype (MitoCellPhe) tool developed for quantifying mitochondrial morphologies and demonstrate its utility in delineating differences in mitochondrial morphologies in a human fibroblast and human induced pluripotent stem cell (hiPSC) line. MitoCellPhe generates 24 parameters, allowing for a comprehensive analysis of mitochondrial structures and importantly allows for quantification to be performed on mitochondria in images containing single cells or clusters of cells. With this tool, we were able to validate previous findings that show networks of mitochondria in healthy fibroblast cell lines and a more fragmented morphology in hiPSCs. Using images generated from control and diseased fibroblasts and hiPSCs, we also demonstrate the efficacy of the toolset in delineating differences in morphologies between healthy and the diseased state in both stem cell (hiPSC) and differentiated fibroblast cells. Our results demonstrate that MitoCellPhe enables high-throughput, sensitive, detailed, and quantitative mitochondrial morphological assessment and thus enables better biological insights into mitochondrial dynamics in health and disease.

The activity of 137Cs was measured in different terrestrial samples around Kakrapar Gujarat site. Transfer Factor and Ecological half-life of 137Cs was evaluated. 137Cs activity observed in these matrices are comparable with pre-operational baseline activity and there is no build up of activity. Transfer Factor of soil to grass, leaf, cereals, pulses, fruits and vegetables for 137Cs was observed to be in the range of 0.01–1.49, 0.06–0.64, 0.03–0.92, 0.03–3.99, 0.01–0.34 and 0.01–0.20, respectively. Ecological half-life (years) of 137Cs for soil, grass, leaf, cereals, pulses, fruits, vegetables and milk was found to be 11.8, 5.9, 5.9, 5.7, 3.9, 7.7, 9.0 and 7.2 respectively.

Purpose:Natural killer (NK) cells are type I innate lymphoid cells that are known for their role in killing virally infected cells or cancer cells through direct cytotoxicity. In addition to direct tumor cell killing, NK cells are known to play fundamental roles in the tumor microenvironment through secretion of key cytokines, such as FMS-like tyrosine kinase 3 ligand (FLT3L). Although radiotherapy is the mainstay treatment in most cancers, the role of radiotherapy on NK cells is not well characterized.Experimental Design:This study combines radiation, immunotherapies, genetic mouse models, and antibody depletion experiments to identify the role of NK cells in overcoming resistance to radiotherapy in orthotopic models of head and neck squamous cell carcinoma.Results:We have found that NK cells are a crucial component in the development of an antitumor response, as depleting them removes efficacy of the previously successful combination treatment of radiotherapy, anti-CD25, and anti-CD137. However, in the absence of NK cells, the effect can be rescued through treatment with FLT3L. But neither radiotherapy with FLT3L therapy alone nor radiotherapy with anti-NKG2A yields any meaningful tumor growth delay. We also identify a role for IL2 in activating NK cells to secrete FLT3L. This activity, we show, is mediated through CD122, the intermediate affinity IL2 receptor, and can be targeted with anti-CD25 therapy.Conclusions:These findings highlight the complexity of using radio-immunotherapies to activate NK cells within the tumor microenvironment, and the importance of NK cells in activating dendritic cells for increased tumor surveillance.

Biodiesel a fatty acid alkyl esteris one of the promising biofuel and a clean energy source as an alternative to petroleum-based diesel fuels. The Enzymatic transesterification reaction is influenced by many factors such as amount of biocatalyst, molar ratio of oil to alcohol, temperature, pH, rpm, time etc. Effective variables for transesterification may vary based on the type of feedstock and catalyst used, therefore it is essential to optimise the process suitable for each type of feedstock to achieve higher yield of biodiesel. The statistically-based Plackett-Burman experimental design was adopted in this study to identify effective factors for transesterification reaction of Pongamiapinnata seed oil using immobilized lipase. The factors used in the present study for Plackett-Burman design are molar ratio, amount of immobilized lipase, temperature, time, pH, agitation and water content. The result showed that among seven variables, pH (p-value0.003), agitation speed(p-value 0.024) and amount of immobilized lipase(p-value 0.041) having p

Background We observe the emergence of several promoter-variant viral strains in India during recent years. The variant viral promoters contain additional copies of transcription factor binding sites present in the viral modulatory region or enhancer, including RBEIII, LEF-1, Ap-1 and/or NF-κB. These sites are crucial for governing viral gene expression and latency. Here, we infer that one variant viral promoter R2N3-LTR containing two copies of RBF-2 binding sites (an RBEIII site duplication) and three copies of NF-κB motifs may demonstrate low levels of gene expression noise as compared to the canonical RN3-LTR or a different variant R2N4-LTR (a duplication of an RBEIII site and an NF-κB motif). To demonstrate this, we constructed a panel of sub-genomic viral vectors of promoter-variant LTRs co-expressing two reporter proteins (mScarlet and Gaussia luciferase) under the dual-control of Tat and Rev. We established stable pools of CEM.NKR-CCR5 cells (CEM-CCR5RL reporter cells) and evaluated reporter gene expression under different conditions of cell activation. Results The R2N3-LTR established stringent latency that was highly resistant to reversal by potent cell activators such as TNF-α or PMA, or even to a cocktail of activators, compared to the canonical RN3- or the variant R2N4-LTR. The R2N3-LTR exhibited low-level basal gene expression in the absence of cell activation that enhanced marginally but significantly when activated. In the presence of Tat and Rev, trans-complemented in the form of an infectious virus, the R2N3-LTR demonstrated gene expression at levels comparable to the wild-type viral promoter. The R2N3-LTR is responsive to Tat and Rev factors derived from viral strains representing diverse genetic subtypes. Conclusion With extremely low-level transcriptional noise, the R2N3-LTR can serve as an excellent model to examine the establishment, maintenance, and reversal of HIV-1 latency. The R2N3-LTR would also be an ideal viral promoter to develop high-throughput screening assays to identify potent latency-reversing agents since the LTR is not affected by the usual background noise of the cell.

α-amylase, an enzyme of industrial importance is used extensively in food, pharmaceutical, textile and detergent industries. Since, a substantial quantity of α-amylase isderived from microbial sources, manipulation of bacterial strain, fermentation conditions and media composition has a major effect on yield of enzyme. Bacillus amyloliqifaciens, obtained from MTCC culture collection was used to study the enhancement of α-amylase production using media concentration manipulation. Taguchi’s orthogonal array was designed for maximization of α-amylase output. The different media components selected as parameters to be optimized were calcium chloride, starch, tryptone, ammonium sulphate and glucose. The concentration of starch and tryptone demonstrated to have maximum effect on amylase production. The optimization strategy was successful in obtaining substantial increase in amylase production of about 2 folds as compared to the unoptimized medium.

Axon degeneration is a prominent feature of the injured nervous system, occurs across neurological diseases, and drives functional loss in neural circuits. We have seen a paradigm shift in the last decade with the realization that injured axons are capable of actively driving their own destruction through the sterile-alpha and TIR motif containing 1 (SARM1) protein. Early studies of Wallerian degeneration highlighted a central role for NAD+ metabolites in axon survival, and this association has grown even stronger in recent years with a deeper understanding of SARM1 biology. Here, we review our current knowledge of SARM1 function in vivo and our evolving understanding of its complex architecture and regulation by injury-dependent changes in the local metabolic environment. The field is converging on a model whereby SARM1 acts as a sensor for metabolic changes that occur after injury and then drives catastrophic NAD+ loss to promote degeneration. However, a number of observations suggest that SARM1 biology is more complicated, and there remains much to learn about how SARM1 governs nervous system responses to injury or disease.

The vast majority of the industrial use of enzymes is covered from microorganisms. Microorganisms are favoured in industry because of their several advantages for example rapid growth, short life expectancy and simplicity in doing genetic alterations. Microbial enzymes are thus amply provided, very much standardized and promoted by many companies. Among various enzymes, Pectinases hold an exceptional place because of its different uses in various sectors like food, textile and biofuel industries.A total of 25% of total enzyme market is being shared by Pectinase alone.The current study was carried out to evaluate the pectinase activity of the pectinolytic bacteria. 40 Bacterial strains were isolated from different soil samples and screened for Pectinase production. Primary and Secondary screening showed 3 potential isolates I38 , I39 and I40 showing pectin degradation on Vincent’s media. Further, extracellular pectinase was partially purified by ammonium sulphate precipitation and dialysis. Sequential ammonium sulphate saturations from 20-80% i.e. (20, 40, 60 and 80%) showed 60% ammonium sulphate was optimum for precipitation of intracellular enzyme whereas 80% was optimum for extracellular enzyme.

Frailty is defined as “a clinically recognizable state of increased vulnerability, resulting from aging associated decline in reserve and function across multiple A Hospital based descriptive cross-sectional study in tertiary care hospital. Atotal of 294 patients admitted in the Medicine/Geriatric Ward, were included in stressors is compromised”. It is a robust and powerful risk factor for disability. With this background, study was conducted at a tertiary centre with objectives to assess the frailty in elderly patients and to assess the correlation of frailty with Serum Albumin and CRP physiologic systems, such that the ability to cope with every day or acute and evaluate the clinical outcome in terms of length of hospital stay. The study. Demographic details and details of known comorbidities were recorded. Cognition score of all patients were assessed using mini mental scale examination. Investigations like Serum Albumin and CRP were done. The data was analyzed using statistical software.Our results show that in hospitalized patients frailty is seen in both gender. The presence of co-morbidities worsens the frailty. 30 second chair test is very good indicator for frailty and risk of fall and we observed reduced duration in the Pre-Frail group. The cognition score decreased along with the increase in age groups. When compared with the Frailty index, it was more in the Pre-Frail group. The duration of hospital stay was more in Frail group. The mean serum albumin level is important marker to identify early frailty.Assessment of frailty in elderly patients is necessary and identifying Pre-Frailgroup is very important. 30 second chair stand test and serum albumin are very important early markers in the assessment of frailty. Cognitive function is also very important to identify early frailty. Our study shows that the length of hospital stay is more in the Frail group. Frailty is important aspect of elderly. It should be included in routine clinical assessment of all elderly patients.

In the search for potential anticancer agents from fruits, the present research work was carried out to examine the in vitro cytotoxic potential of kernel part of Prunus armeniaca (apricot) against eight distinct human cancer cell lines from six different tissues: lung (A-549), colon (HCT-116), breast (MCF-7, MDAMB-231), pancreatic (MIAPaCa-2, Panc-1), prostrate (PC- 3) and CNS (N2A). Methanolic extract and subsequent fractions (n-hexane, chloroform, ethyl acetate, acetone and methanol) were used as test material and anticancer activity was determined via SRB assay at 100g/mL. Results revealed that chloroform fraction of kernel suppressed the proliferation of human breast cancer cellline with growth inhibition of 89%. The fraction of kernel was then evaluated at lower concentrations of 50, 40, 30, 20 and 10g/mL. Further IC50 value was calculated and it was observed that the fraction showed IC5038.66. To conclude, kernel part of Prunus armeniaca possesses certain constituents with cytotoxic properties that can be used to develop anticancer agents especially for breast cancer therapy and to provide a great service to cancer patients.Further studies are required for the isolation of active ingredients from the kernel part.

Bacterial strain identified as Klebsiella pneumoniae SK1, based on 16S rDNA sequence study, was isolated from a textile mill discharge point at Dada Nagar industrial area in Kanpur, India in media containing 100 µg/ml each of disulfonated azo dye Acid Red 249 (AR) and hexavalent chromium [Cr(VI)]. SK1 is efficient in the concomitant decolorization and reduction of 100 µg/ml toxic AR and Cr(VI) respectively in 48 h under microaerophilic conditions. The efficacy of AR decolorization was found to be preeminent in static conditions, 37°C, 2-4% salinity and 7-9 pH range. 99% decolorization for initial AR concentration of 100 µg/ml in 48 h, and 91% for 250 µg/ml and 77% for 500 µg/ml was recorded in 72 h respectively in the presence of 100 µg/ml Cr(VI). Significant reductive changes in spectroscopic absorption spectra were observed for SK1 treated AR+Cr(VI) amended media with respect to controls. FITR spectroscopy was used to ascertain the breakage of the azo dye bond and the formation of biodegradative metabolites. Additionally, SK1 was found to be positive for indole acetic acid, ammonia, phosphate and potassium solubilization and biofilm formation. In plant bioassay, in vitro SK1 treated AR+Cr(VI) TSB media was used to treat Triticum aestivum in the soil environment. In comparison to untreated control, plants treated with bioremediation media shows increased percent germination, root and shoot length with a complete reversal of phytotoxic effects of the AR+Cr(VI) treated plants. In this study, environmental K. pneumoniae SK1 shows concomitant azo dye and Cr(VI) remediation with plant growth-promoting activity.

Introduction: The increase in contagious diseases like nosocomial infections, urinary tract infections, and meningitis has led to the emergence of antimicrobial resistance urgently needs new antimicrobial medication with new modes of action. Some of the antibiotics present in the market have been obtained from terrestrial plants, or extracted semisynthetically from materials which can be fermented. Methods: Marine microorganisms account for approximately 80% of sea biomass and they are essential for the survival and well-being of aquatic habitats owing to their indispensable contribution to biogeochemical cycles and biological processes. In marine ecosystems, microorganisms live as microbial communities in seawater, where symbiotic relationships are formed, and their ecological functions are fulfilled. Results: Marine microorganisms remain the largest, most diverse and most exciting source of structurally and functionally complex antimicrobial agents. They are extremely involved in their structure and functions. Enormous biological wealth lies in marine habitats. These microorganisms are potential sources of novel antimicrobial compounds to combat the most infectious diseases like nosocomial infections, urinary tract infections. Conclusion: This study deals with biologically active antimicrobial compounds taken from marine microorganism source which was reported between the years 2005 and 2019. This review highlights their chemical groups, their bioactivities and sources. Marine microorganism exploitation techniques have also been reported by the authors.

Objective To estimate the burden of active infection and anti-SARS-CoV-2 IgG antibodies in Karnataka, India, and to assess variation across geographical regions and risk groups. Methods A cross-sectional survey of 16,416 people covering three risk groups was conducted between 3–16 September 2020 using the state of Karnataka’s infrastructure of 290 healthcare facilities across all 30 districts. Participants were further classified into risk subgroups and sampled using stratified sampling. All participants were subjected to simultaneous detection of SARS-CoV-2 IgG using a commercial ELISA kit, SARS-CoV-2 antigen using a rapid antigen detection test (RAT) and reverse transcription-polymerase chain reaction (RT-PCR) for RNA detection. Maximum-likelihood estimation was used for joint estimation of the adjusted IgG, active and total prevalence (either IgG or active or both), while multinomial regression identified predictors. Results The overall adjusted total prevalence of COVID-19 in Karnataka was 27.7% (95% CI 26.1–29.3), IgG 16.8% (15.5–18.1) and active infection fraction 12.6% (11.5–13.8). The case-to-infection ratio was 1:40 and the infection fatality rate was 0.05%. Influenza-like symptoms or contact with a COVID-19-positive patient were good predictors of active infection. RAT kits had higher sensitivity (68%) in symptomatic people compared with 47% in asymptomatic people. Conclusion This sentinel-based population survey was the first comprehensive survey in India to provide accurate estimates of the COVID-19 burden. The findings provide a reasonable approximation of the population immunity threshold levels. Using existing surveillance platforms coupled with a syndromic approach and sampling framework enabled this model to be replicable.

All India coordinated Research Project on linseed conducted a field experiment on Agriculture Farm, College of Agriculture, Nagpur under Dr. PDKV, Akola, Maharashtra during Rabi Season of 2019-20 in Factorial Randomized Block Design with three replication. Three genotypes NL – 356, JLS-95, T-397 were tested with three nutrient levels i.e. 50 % RDF, 100% RDF and 150 % RDF. The result revealed yield potential of the entry NL-356 was 26% highest over JLS-95 and 13% more on T-397 under rainfed condition. However, the increase in nutrient level from 50 % RDF to 150 % RDF influence the growth and yield attributes which favours the increase in yield. Therefore, it is concluded that genotype NL 356 with 100 % RDF achieve higher growth rate i.e. plant height, number of branches as well as yield attributes number of capsules per plant, number of seed per capsule and highest NMR and B:C ratio.

A field experiment was conducted under All India coordinated Research Project on linseed at Agriculture Farm, College of Agriculture, Nagpur in Rabi Season 2019-20. The experiment was laid out in Factorial Randomized Block Design with three replication in which effect of three seed rate i.e. 30, 40 and 50 Kg/ha was tested on three genotypes i.e. BRLS-106, Shekhar and T- 397. The results revealed that among the genotype BRLS -106 was found superior over Shekhar and T-397 genotypes under utera condition with respect to growth, yield and yield attributes. However, the seed rate 50 kg-1 found superior in yield, GMR and NMR. The interaction of BRLS-106 with seed rate 40kg/ha has recorded the highest seed yield and net monetary returns also.

The commercial importance of linseed (Linum usitatissimum L.) has attracted Agronomist to increase its seed yield using various agronomical and breeding approaches. Plant growth regulators (PGRs) have a significant role in enhancing yield and its related traits in linseed. Hence, to find out effect of different growth regulators on growth, yield attributes, yield and economics of linseed, the present experiment was conducted under AICRP on Linseed, College of Agriculture, Nagpur. Growth regulator shows significant effect on growth, yield attributes and yield of linseed. Plant height and number of capsules per plant was observed highest and significantly superior after application of 400 ppm Gibberellic acid (GA) and application of 0.1 % Tebuconazole which was at par with T7 i.e. 1.0 ppm Auxin + 200 ppm GA and T5 i.e. 75 ppm salicylic acid. Number of branches and number of capsules per plant were also observed at par in the treatment T3 i.e. 200 ppm GA. The seed yield of linseed was recorded significantly higher in T4 i.e. 400 ppm GA which was at par with T7 i.e. 1.0 ppm Auxin + 200 ppm GA and treatment T3 i.e. 200 ppm GA and treatment T5 i.e. 75 ppm salicylic acid. The gross monetary return was found maximum in the treatment T4 i.e. 400 ppm GA, this might be due the maximum seed yield after application of 400 ppm GA, but net monetary return and B:C ratio resulted minimum due to the high market cost of GA (Rs. 9000/- for 400 ppm). Net monetary return and B:C ratio was found maximum in treatment T5 i.e. 75 ppm salicylic acid, this might be due to the low cost of Salicylic acid.

Viruses rely on the host translation machinery to synthesize their own proteins. Consequently, they have evolved varied mechanisms to co-opt host translation for their survival. SARS-CoV-2 relies on a non-structural protein, Nsp1, for shutting down host translation. However, it is currently unknown how viral proteins and host factors critical for viral replication can escape a global shutdown of host translation. Here, using a novel FACS-based assay called MeTAFlow, we report a dose-dependent reduction in both nascent protein synthesis and mRNA abundance in cells expressing Nsp1. We perform RNA-Seq and matched ribosome profiling experiments to identify gene-specific changes both at the mRNA expression and translation level. We discover a functionally-coherent subset of human genes are preferentially translated in the context of Nsp1 expression. These genes include the translation machinery components, RNA binding proteins, and others important for viral pathogenicity. Importantly, we uncovered a remarkable enrichment of 5′ terminal oligo-pyrimidine (TOP) tracts among preferentially translated genes. Using reporter assays, we validated that 5’ UTRs from TOP transcripts can drive preferential expression in the presence of NSP1. Finally, we found that LARP1, a key effector protein in the mTOR pathway may contribute to preferential translation of TOP transcripts in response to Nsp1 expression. Collectively, our study suggests fine tuning of host gene expression and translation by Nsp1 despite its global repressive effect on host protein synthesis.

Aquaculture is an important agriculture sector in Dhanusha district with the involvement of large number of farming community. An interview-based questionnaire survey of 45 randomly selected fish farmers and 13 fish traders in fish block area of Dhanusha district, Nepal was carried out to appraise current situation of Production and marketing system of fish farming during the period of February to April, 2020. Majority of the farmers (86.76%) had done fish farming as main occupation and was found to be profitable with the average productivity of 5.53 Mt/ha/year and B/C ratio of 1.37. Most of the farmers were practicing carp polyculture however, monoculture and integrated fish farming was also found to be done by few respondents. Fish produced were sold in local market, adjacent districts and also to distant markets. The findings showed that traders were involved in marketing system of fish of which 59.65% of the total was sold to the wholesalers, 30.49% to the retailers and 9.87% was sold directly to the consumers. Commonly used means of transportation were bicycle, motorbike and pickup vans. The study also revealed that farmers were facing several problems like lack of technical knowhow, untimely availability of feed and other inputs, disease and water quality problem, lack of well managed commodity market, poor storage facilities etc. which needs to be addressed to enhance the fish production and marketing efficiency in the study area.

Telomere length (TL) is a marker of biological aging associated with several health outcomes. High throughput reproducible TL measurements are needed for large epidemiological studies. We compared the novel DNA methylation-based estimator (DNAmTL) with the high-throughput quantitative PCR (qPCR) and the highly accurate flow cytometry with fluorescent in situ hybridization (flow FISH) methods using blood samples from healthy adults. We used Pearson’s correlation coefficient, Bland Altman plots and linear regression models for statistical analysis. Shorter DNAmTL was associated with older age, male sex, white race, and cytomegalovirus seropositivity (p70% of TL categorized above or below the median, but the accuracy dropped with increasing TL categories. The ability of DNAmTL to detect associations with age and other TL-related factors in the absence of strong correlation with measured TL may indicate its capture of aspects of telomere maintenance mechanisms and not necessarily TL. The inaccuracy of DNAmTL prediction should be considered during data interpretation and across-study comparisons.

Background MYL-1501D is a proposed biosimilar to insulin glargine. The noninferiority of MYL-1501D was demonstrated in patients with type 1 diabetes and type 2 diabetes in 2 phase 3 trials. Immunogenicity of MYL-1501D and reference insulin glargine was examined in both studies. Methods INSTRIDE 1 and INSTRIDE 2 were multicenter, open-label, randomized, parallel-group studies. In INSTRIDE 1, patients with type 1 diabetes received MYL-1501D or insulin glargine over a 52-week period. In INSTRIDE 2, patients with type 2 diabetes treated with oral antidiabetic drugs, insulin naive or not, received MYL-1501D or reference insulin glargine over a 24-week period. Incidence rates and change from baseline in relative levels of antidrug antibodies (ADA) and anti–host cell protein (anti-HCP) antibodies in both treatment groups were determined by a radioimmunoprecipitation assay and a bridging immunoassay, respectively. Results were analyzed using a mixed-effects model (INSTRIDE 1) or a nonparametric Wilcoxon rank sum test (INSTRIDE 2). Results Total enrollment was 558 patients in INSTRIDE 1 and 560 patients in INSTRIDE 2. The incidence of total and cross-reactive ADA was comparable between treatment groups in INSTRIDE 1 and INSTRIDE 2 (P > 0.05 for both). A similar proportion of patients had anti-HCP antibodies in both treatment groups in INSTRIDE 1 at week 52 (MYL-1501D, 93.9 %; reference insulin glargine, 89.6 %; P = 0.213) and in INSTRIDE 2 at week 24 (MYL-1501D, 87.3 %; reference insulin glargine, 86.9 %; P > 0.999). Conclusions In INSTRIDE 1 and INSTRIDE 2, similar immunogenicity profiles were observed for MYL-1501D and reference insulin glargine in patients with type 1 diabetes and type 2 diabetes, respectively. Trial registration ClinicalTrials.gov, INSTRIDE 1 (NCT02227862; date of registration, August 28, 2014); INSTRIDE 2 (NCT02227875; date of registration, August 28, 2014).

Several factors influence an individual’s susceptibility in inter-individual lipid changes and its role in the onset of type-2 diabetes mellitus (T2DM). Considering the above fact, the present investigation focuses on determining the association between fatty acid desaturase 2 (FADS2) rs174575 (C/G) polymorphism, circulating lipid levels and susceptibility to type-2 diabetes mellitus. As per the inclusion and exclusion criteria a total of 429 subjects (non-diabetic-216; diabetic-213) were recruited for the study. Glycemic and lipid profile status were assessed using commercially available kits. Based on the previous reports SNP rs174575 of fatty acid desaturase gene (FADS2) was selected and identified using the dbSNP database. The amplified products were sequenced by means of Sanger sequencing method. Lipid profile status and apolipoprotein levels revealed statistically significant difference between the groups. Three models were assessed namely, recessive model (CC vs CG + GG), dominant model (CC + CG vs GG) and additive model (CC vs CG vs GG). The recessive model, displayed a statistically significant variations between the circulating lipid levels in T2DM. The multivariate model with genotype (G allele carriers), triglyceride (TG) and insulin served as a predictive model. The study results potentiate the functional link between FADS2 gene polymorphism, lipid levels and type-2 diabetes mellitus.

Background: The development and spread of pathogenic antibiotic resistance to many antibiotics have been growing worldwide. This concept is of enormous importance, and it is crucial to identify appropriate therapeutic drugs to fight against these antibiotic-resistant microbes. Plant species can make a valuable contribution to new antibiotics to replace or improve existing treatment potential. Methods: In this work, we conducted a molecular modelling study of three phytochemicals (Peperomin A, Peperomin E, Peperomin F) with bacterial targets penicillin-binding protein (2C6W) from Streptococcus pneumoniae and kdpFABC complex (5MRW) of Escherichia coli. Peperomia pellucida methanolic extract was conducted antimicrobial activity against clinical Streptococcus pneumoniae and Escherichia coli. Results: Three phytochemicals (Peperomin A, Peperomin E, Peperomin F) showed the best docking results with target antimicrobial-resistant targets. Peperomia pellucida methanolic extract showed good antibacterial activity against clinical Streptococcus pneumoniae and Escherichia coli. Conclusion: In-vitro and In silico bactericidal studies conducted, Peperomia pellucida phytochemical has significance antibacterial activity against clinical Streptococcus pneumoniae, Escherichia coli.

Epigenetic mechanisms are central to understanding the molecular basis underlying tumorigenesis. Aberrations in epigenetic modifiers alter epigenomic landscapes and play a critical role in tumorigenesis. Notably, the histone lysine methyltransferase KMT2D (a COMPASS/ Set1 family member; also known as MLL4, ALR, and MLL2) is among the most frequently mutated genes in many different types of cancer. Recent studies have demonstrated how KMT2D loss induces abnormal epigenomic reprograming and rewires molecular pathways during tumorigenesis. These findings also have clinical and therapeutic implications for cancer treatment. In this review, we summarize recent advances in understanding the role of KMT2D in regulating tumorigenesis and discuss therapeutic opportunities for the treatment of KMT2D-deficient tumors.

Streptokinase is a well-established cost-effective therapeutic molecule for thrombo-embolic complications. In the current study, a tag-free variant of streptokinase with a native N-terminus (N-rSK) was developed using the Pichia expression system. A three-copy clone was screened that secreted 1062 mg/L of N-rSK in the complex medium at shake flask level. The biologically active (67,552.61 IU/mg) N-rSK recovered by anion exchange chromatography was predicted to contain 15.43% α-helices, 26.43% β-sheets. The fermentation run in a complex medium yielded a poor quality product due to excessive N-rSK degradation. Therefore, modified basal salt medium was also employed during fermentation operations to reduce the proteolytic processing of the recombinant product. The concomitant feeding of 1 g/L/h soya flour hydrolysate with methanol during the protein synthesis phase reduced the proteolysis and yielded 2.29 g/L of N-rSK. The fermentation medium was also supplemented with urea during growth and induction phases. The combined feeding approach of nitrogen-rich soya flour hydrolysate and urea during bioreactor operations showed significant improvement in protein stability and resulted in a 4-fold increase in N-rSK concentration to a level of 4.03 g/L over shake flask. Under optimized conditions, the volumetric productivity and specific product yield were 52.33 mg/L/h and 33.24 mg/g DCW, respectively.

Background Emerging insights from numerous laboratories have revealed important roles for nonneoplastic cells in the development and progression of brain tumors. One of these nonneoplastic cellular constituents, glioma-associated microglia (GAM), represents a unique population of brain monocytes within the tumor microenvironment that have been reported to both promote and inhibit glioma proliferation. To elucidate the role of GAM in the setting of low-grade glioma (LGG), we leveraged RNA sequencing meta-analysis, genetically engineered mouse strains, and human biospecimens. Methods Publicly available disease-associated microglia (DAM) RNA-seq datasets were used, followed by immunohistochemistry and RNAScope validation. CD11a-deficient mouse microglia were used for in vitro functional studies, while LGG growth in mice was assessed using anti-CD11a neutralizing antibody treatment of Neurofibromatosis type 1 (Nf1) optic glioma mice in vivo. Results We identified Itgal/CD11a enrichment in GAM relative to other DAM populations, which was confirmed in several independently generated murine models of Nf1 optic glioma. Moreover, ITGAL/CD11A expression was similarly increased in human LGG (pilocytic astrocytoma) specimens from several different datasets, specifically in microglia from these tumors. Using CD11a-knockout mice, CD11a expression was shown to be critical for murine microglia CX3CL1 receptor (Cx3cr1) expression and CX3CL1-directed motility, as well as glioma mitogen (Ccl5) production. Consistent with an instructive role for CD11a+ microglia in stromal control of LGG growth, antibody-mediated CD11a inhibition reduced mouse Nf1 LGG growth in vivo. Conclusions Collectively, these findings establish ITGAL/CD11A as a critical microglia regulator of LGG biology relevant to future stroma-targeted brain tumor treatment strategies.

India is a global epicenter of oral cancer patients and the magnitude of the problem is ever increasing day by day. There is excess burden of oral malignancies all over the country and the risk factors associated with the disease are at its peak. Addressing the disease which is quite like an epidemic is a great challenge and major public health issue in India. This review paper discusses the burden of the disease, its top risk factors in India including the use of tobacco, alcohol, areca nut and HPV infections; and methods for prevention and control of oral cancer in India. Keywords: Oral cancer, Burden, Risk factors, Tobacco, Alcohol, Areca nut, HPV, Prevention.

Theranostic nanoparticles (NPs) can reach their target tissue only by passing through blood. However, the influence of NPs on blood is still not well understood. Understanding the effects of NPs on the functioning of blood is critical for successful translation of this novel drug delivery paradigm. In this article, we examined the potential effect of NPs on blood components using four physically and chemically diverse NPs such as carbon nanotube (CNT), magnesium (Mg), silver (Ag), and copper oxide (CuO) NPs. The interaction of different NPs on blood was studied under similar conditions and the effect was assessed by determining the total protein, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cholesterol, and electrolytes such as Na+, K+, and Cl- concentrations in blood. The concentration of total protein, AST, Na+, and Cl- did not show any significant change in blood when exposed to the NPs. On the other hand, the concentration of ALT and ALP declined for Ag and CuO NPs. Cholesterol levels declined significantly when exposed to CNT, Mg, and CuO NPs. K+ in blood increased over 24 h for Mg NPs but remained consistent for other NPs. Such an increase in K+ induced by Mg NPs can be attributed to the direct interaction of the NPs with the RBCs and other components in blood, resulting in hemolysis. Overall, the results suggest that physical and chemical natures of NPs are critical factors influencing the interaction between NPs and blood components.

A field experiment was conducted during rabi season of 2019-20 at College Farm, S. D. Agricultural University, Jagudan. The treatments included of best combinations consisting of physical and chemical methods as well as alone. The studies signified the importance of hand weeding at 25 and 40 DAS or application of post emergence herbicides which could benefit the crops in reducing the different weed density and ultimately reduced the weed dry matter which resulted in increase in the crop yield. Keeping the crop weed free up tharvest recorded higher weed control efficiency (100 %) and lower weed index (0%). Higher growth and yield attributes under physical method alone and their integration with herbicide treatments might be due to effective control of weeds, significantly reduced crop–weed competition resulting in better congenial condition for growth and development of the crop. The maximum seed yield was recorded with weed free up to harvest and was at par with the treatments in which adoption of physical and chemical methods alone and their combinations. The maximum net realization and benefit cost ratio (BCR) were recorded with treatment T2 i.e. Two interculture followed by hand weed at 25 and 40 DAS.