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Certain trace inequalities for positive definite matrices are generalized for positive semidefinite matrices using the notion of the group generalized inverse.

Targeting exhausted CD8+ T-cell (TEX)-induced aggravated cancer stem cells (CSC) holds immense therapeutic potential. In this regard, immunomodulation via Neem Leaf Glycoprotein (NLGP), a plant-derived glycoprotein immunomodulator is explored. Since former reports have proven immune dependent-tumor restriction of NLGP across multiple tumor models, we hypothesized that NLGP might reprogram and rectify TEX to target CSCs successfully. In this study, we report that NLGP's therapeutic administration significantly reduced TEX-associated CSC virulence in in vivo B16-F10 melanoma tumor model. A similar trend was observed in in vitro generated TEX and B16-F10/MCF7 coculture setups. NLGP rewired CSCs by downregulating clonogenicity, multidrug resistance phenotypes and PDL1, OCT4, and SOX2 expression. Cell cycle analysis revealed that NLGP educated-TEX efficiently pushed CSCs out of quiescent phase (G0G1) into synthesis phase (S), supported by hyper-phosphorylation of G0G1-S transitory cyclins and Rb proteins. This rendered quiescent CSCs susceptible to S-phase-targeting chemotherapeutic drugs like 5-fluorouracil (5FU). Consequently, combinatorial treatment of NLGP and 5FU brought optimal CSC-targeting efficiency with an increase in apoptotic bodies and proapoptotic BID expression. Notably a strong nephron-protective effect of NLGP was also observed, which prevented 5FU-associated toxicity. Furthermore, Dectin-1-mediated NLGP uptake and subsequent alteration of Notch1 and mTOR axis were deciphered as the involved signaling network. This observation unveiled Dectin-1 as a potent immunotherapeutic drug target to counter T-cell exhaustion. Cumulatively, NLGP immunotherapy alleviated exhausted CD8+ T-cell-induced CSC aggravation. Implications: Our study recommends that NLGP immunotherapy can be utilized to counter ramifications of T-cell exhaustion and to target therapy elusive aggressive CSCs without evoking toxicity., (©2024 American Association for Cancer Research.)

Throughout the process of evolution, DNA undergoes the accumulation of distinct mutations, which can often result in highly organized patterns that serve various essential biological functions. These patterns encompass various genomic elements and provide valuable insights into the regulatory and functional aspects of DNA. The physicochemical, mechanical, thermodynamic, and structural properties of DNA sequences play a crucial role in the formation of specific patterns. These properties contribute to the three-dimensional structure of DNA and influence their interactions with proteins, regulatory elements, and other molecules. In this study, we introduce DNASCANNER v2, an advanced version of our previously published algorithm DNASCANNER for analyzing DNA properties. The current tool is built using the FLASK framework in Python language. Featuring a user-friendly interface tailored for nonspecialized researchers, it offers an extensive analysis of 158 DNA properties, including mono/di/trinucleotide frequencies, structural, physicochemical, thermodynamics, and mechanical properties of DNA sequences. The tool provides downloadable results and offers interactive plots for easy interpretation and comparison between different features. We also demonstrate the utility of DNASCANNER v2 in analyzing splice-site junctions, casposon insertion sequences, and transposon insertion sites (TIS) within the bacterial and human genomes, respectively. We also developed a deep learning module for the prediction of potential TIS in a given nucleotide sequence. In the future, we aim to optimize the performance of this prediction model through extensive training on larger data sets.

Breast cancer (BC) is globally one of the leading killers among women. Within a breast tumor, a minor population of transformed cells accountable for drug resistance, survival, and metastasis is known as breast cancer stem cells (BCSCs). Several experimental lines of evidence have indicated that BCSCs influence the functionality of immune cells. They evade immune surveillance by altering the characteristics of immune cells and modulate the tumor landscape to an immune-suppressive type. They are proficient in switching from a quiescent phase (slowly cycling) to an actively proliferating phenotype with a high degree of plasticity. This review confers the relevance and impact of crosstalk between immune cells and BCSCs as a fate determinant for BC prognosis. It also focuses on current strategies for targeting these aberrant BCSCs that could open avenues for the treatment of breast carcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guha, Goswami, Sultana, Ganguly, Choudhury, Chakravarti, Bhuniya, Sarkar, Bera, Dhar, Das, Das, Baral, Bose and Banerjee.)

Vaccine development is a complex and long process. It involves several steps, including computational studies, experimental analyses, animal model system studies, and clinical trials. This process can be accelerated by using in silico antigen screening to identify potential vaccine candidates. In this chapter, we describe a deep learning-based technique which utilizes 18 biological and 9154 physicochemical properties of proteins for finding potential vaccine candidates. Using this technique, a new web-based system, named Vaxi-DL, was developed which helped in finding new vaccine candidates from bacteria, protozoa, viruses, and fungi. Vaxi-DL is available at: https://vac.kamalrawal.in/vaxidl/ ., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Extent of metastasis influences activation of platelets in tumor-microenvironment. Activated platelets potentiate mesenchymal-stem-cells (MSCs) to migrate in secondary metastatic sites without participation in process of invasion. Presence of higher percentage of MSCs along with activated-platelets induces formation of vascular-mimicry (VM). The pathophysiology, VM, has already been reported in multiple types of cancer including lung, ovary, melanoma etc. and related to poor-prognosis. Interaction of MSCs with platelets in cell-to-cell contact dependent manner is essential for their migration, thereby, VM. Evidences are obtained suggesting that under influence of tumor-associated-activated-platelets, expressions of vimentin, ve-cadherin are increased, along with decrease in e-cadherin on CD105 + MSCs in both mRNA and protein levels that may help in formation of vessel like structure in VM. Adoptive transfer of MSCs along with tumor-activated-platelets causes greater B16 melanoma metastasis at lungs in comparison to MSCs with non-activated platelets. Presence of CD105 + Vimentin + MSCs in vessel like structure in the metastatic lung confirms the involvement of platelet-activated-MSCs in VM, thereby, in metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The majority of pandemics are known to be a result of either bacteria or viruses out of which viruses seem to be an entity of growing concern due to the sheer number of yet unidentified and potentially threatening viruses, their ability to quickly evolve and transform, their ability to transfer and change from one host organism to another and the difficulty in creating safe vaccines on time., Main Body: The present review attempts to bring forth the potential risks, prevention and its impact on the global society in terms of sociological and economic parameters. Taking hindsight from previously as well as ongoing current viral epidemics, this article aims to draw a concrete correlation between these viruses in terms of their origin, spread and attempts to compare how much they can affect the population. The study also assesses the worst-case scenarios and the amount of preparedness, required to fight against such pandemics and compares the required amount of preparedness to the current precautions and measures by different governments all across the world., Short Conclusion: Learning from the current pandemic, we can implement certain measures to prevent the adverse effects of pandemics in the future and through severe preparedness can combat the challenges brought about by the pandemic., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

Paracetamol is a popular and safe drug preferred by victims of pain or pyrexia; however, its overdose or abuse is a growing concern worldwide. Here the hepatoprotective effect of an ethnomedicinal plant Drynaria quercifolia against paracetamol‑induced toxicity in murine model is demonstrated. This fern, native to tropical countries including the Northeast India, is used by local tribes to treat inflammatory conditions. Paracetamol 500 mg/kg body weight was orally administered on alternate days for a period of 21days to mimic a chronic overdose. Drynaria quercifolia acetone extract (DQA) treatment interspaced with paracetamol significantly decreased serum biomarkers of hepatotoxicity (ALT, AST and ALP) renal toxicity (urea, creatinine), lipid peroxidation level, histological damage in liver and kidney. The protein and mRNA expressions of the transcription factor, Nrf2, and its target antioxidant genes (SOD1, CAT and GST) as well as activities of these antioxidant enzymes were downregulated by paracetamol administration but significantly recovered following the DQA treatment (Tab. 3, Fig. 5, Ref. 31). Keywords: acetaminophen/paracetamol, Drynaria quercifolia, renal toxicity, hepatotoxicity, Nrf-2.

This data deals with the optimization of microprojectile bombardment particles for efficient genetic transformation in an indica rice involving AmSOD gene for development of salinity tolerant transgenic lines [1]. In this study, various parameters such as effect of genotypes, helium pressure, osmoticum, explants, flight distance, particle size, particle volume, vacuum, carrier DNA and stopping screen properties have been evaluated to determine their role in transformation of indica rice involving AmSOD gene for development of salinity tolerant Pusa Basmati 1 rice variety. To perform the transformation process, plasmid vector pCAMBIA 1305.2 was used, which harbours GUS Plus™ gene, intron from the castor bean catalase gene, pBR322 ori, kanamycin resistant gene and Xho I site. The transformants have been confirmed using slot blot, polymerase chain reaction and Southern hybridization techniques., (© 2020 The Authors.)

We present the first observation of dynamically modulated quantum phase transition between two distinct charge density wave (CDW) phases in two-dimensional 2H-NbSe_{2}. There is recent spectroscopic evidence for the presence of these two quantum phases, but its evidence in bulk measurements remained elusive. We studied suspended, ultrathin 2H-NbSe_{2} devices fabricated on piezoelectric substrates-with tunable flakes thickness, disorder level, and strain. We find a surprising evolution of the conductance fluctuation spectra across the CDW temperature: the conductance fluctuates between two precise values, separated by a quantum of conductance. These quantized fluctuations disappear for disordered and on-substrate devices. With the help of mean-field calculations, these observations can be explained as to arise from dynamical phase transition between the two CDW states. To affirm this idea, we vary the lateral strain across the device via piezoelectric medium and map out the phase diagram near the quantum critical point. The results resolve a long-standing mystery of the anomalously large spectroscopic gap in NbSe_{2}.

Introduction: Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AChE) inhibitory, anti-cholinergic, anti-inflammatory, anti-microbial, anti-oxidant, anti-proliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer's disease., Objective: The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease., Methodology: Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method., Results: In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC 50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC 50 was predicted as 6.025 nM., Conclusion: Results indicated that flavonoids could be efficient inhibitors of AChE and thus, could be useful in the management of Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

The objective of the present study is to detect genetic impurity in the seed lots of CMS lines, restorers and hybrids and to identify signature markers to differentiate parents and hybrids through DNA-based assays. Furthermore, attempts have been made to find out an alternative to Grow-Out-Test, which is very tedious, time consuming and used conventionally for seed genetic purity testing since beginning of quality seed multiplication chain. Fifty-one rice-specific sequence tagged microsatellite (STMS) primer pairs distributed throughout the rice genome were employed for fingerprinting of eight rice hybrids and their parental lines with a view to assess variation within parental lines and to test the genetic purity of the commercial seed lots. Among those, 51 markers, 28 microsatellite markers showed polymorphism (54.90 %). A total of 98 alleles were obtained with an average of 1.92 alleles per primer pair and number of alleles amplified for each primer pair ranged from 1 to 4. A set of markers were identified to differentiate parental lines of the hybrids and which emphasizes the immense scope of those molecular markers for their use in the unambiguous identification of hybrid, which would be of great benefit to farmers that depend on the hybrids.

Ethnopharmacological Relevance: Being one of the most common types of life threatening diseases in Southern Assam, India, the digestive system disorders (DSD) have gained much attention in recent decades. Traditional beliefs and inadequate income of mass population result in the use of alternative phytotherapies to treat the diseases., Aim of the Study: The present paper documents the medicinal knowledge and utilization of plants for treatment of digestive system disorders in Southern Assam, India by Disease Consensus Index (DCI). It also determines the most suitable plant species used to treat digestive system disorders in the study area., Materials and Methods: The study was based on ethnomedicinal field survey covering a period of 1 year from 2014-2015. The ethnomedicinal information was collected by using semi-structured questionnaires from different traditional Bengali people having knowledge on medicinal plants. Collected data were analyzed by calculating DCI., Results: During the survey, 29 informants were interviewed and a total of 49 plants under 46 genera belonging to 33 families were listed. Data analysis revealed that Litsea glutinosa, Momordica charantia, Andrographis paniculata, Lawsonia inermis, Cleome viscosa, Psidium guajava, Ageratum conyzoides, Cuscuta reflexa, Cynodon dactylon and Carica papaya are the most prominent plants among the people of Southern Assam for treating DSD., Conclusion: This explorative survey emphasizes the need to preserve and document the traditional healing practices for managing DSD inviting for more imminent scientific research on the plants to determine their efficacy as well as safety. With the help of statistical analysis (DCI), we propose 10 priority plants for DSD in present work. Systematic pharmacological study with these plants may contribute significant result., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Worldwide, several studies have shown that adaptation to different host plants in phytophagous insects can promote speciation. The cotton aphid, Aphis gossypii Glover (Homoptera: Aphididae: Aphidini), is a highly polyphagous species, but its populations increase by parthenogenetic reproduction alone in Indian subcontinent. This study showed that genotypes living in wild plants of taro, Colocasia esculenta var. esculenta (L.) Schott (Alismatales: Araceae), and brinjal, Solanum torvum Swartz (Solanales: Solanaceae), behave as distinct host races. Success rates of colonization after reciprocal host transfers were very poor. Clones of A. gossypii from wild taro partly survived in the first generation when transferred to wild brinjal, but nymph mortality was 100% in the second generation. In contrast, brinjal clones, when transferred to taro, could not survive even in the first generation. Significant differences between the clones from two host species were also recorded in development time, generation time, fecundity, intrinsic rate of increase, net reproductive rate, and mean relative growth rate. Morphologically, aphids of wild taro clones possessed longer proboscis and fore-femora than the aphids of the brinjal clones. The results showed that A. gossypii exists as distinct host races with different abilities of colonizing host plants, and its populations appear to have more potential of sympatic evolution than previously regarded.

Autism spectrum disorder (ASD) is a childhood neurodevelopmental disorder. During fetal and neonatal brain development, the cues for neurodevelopment are regulated in a well orchestrated manner. Generally, neurotransmitters play a major role in the formation of central nervous system (CNS) and peripheral nervous system (PNS). Glutamate, the excitatory neurotransmitter actively participates in various neurodevelopmental processes through complex regulatory events. Excitatory neurotransmitter signaling via glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in ASD. Therefore, glutamate and its regulatory molecules are considered as potential targets for these disorders. Pharmacological, biochemical and behavioral studies reveal possible involvement of glutamatergic system in ASD pathology. An abnormal increase in electrical activity resulting from excessive glutamate signaling causes prolonged alterations in behavior, as commonly seen in ASDs. On the contrary, reports on animal models of hypoglutamatergia demonstrate phenotypes that overlap with features seen in autism. So controversies prevail whether to regard autism as hyper- or hypo-glutamatergic disorder. This paper reviews the role of glutamate and its regulatory proteins such as different receptors, transporters and metabolizing enzymes in the pathophysiology of ASD based on evidences gathered through multidisciplinary approaches. All these information raise the possibility of exploiting glutamatergic neurotransmitter system for future therapeutic interventions for ASD., (Copyright © 2011. Published by Elsevier Inc.)

Interaction between cell surface integrin receptors with extracellular matrix (ECM) plays an important role in cell survival, proliferation, and migration including tumor development and invasion. Binding of ECM to integrins initiates intracellular signaling cascades, modulating expression and activity of different matrix metalloproteinases (MMPs) which is important in ECM degradation. The present study investigates fibronectin-integrin-mediated signaling and thereby modulation of MMPs expression and activity in human breast cancer cell line, MDA-MB-231. Culture of MDA-MB-231 cells on fibronectin (FN) induced expression and activity of pro-matrixmetalloproteinase-9 (MMP-9). Appreciable reduction of FN-induced pro-MMP-9 activity was observed in anti-α5 antibody treated cells. Inhibitor studies revealed that inhibitors of phosphatidyl inositiol-3-kinase (PI-3K), and nuclear factor kappa B (NF-κB) inhibited FN-induced pro-MMP-9 activity. FN increased tyrosine phosphorylation of focal adhesion kinase (FAK), integrin linked kinase (ILK), and PI-3K in MDA-MB-231 cells. FN-induced the transactivation of MMP-9 promoter by enhancing DNA binding activity of NF-κB and Sp1. Wound healing assay showed faster migration of MDA-MB-231cells grown on fibronectin-coated as surface as compared to control. Our findings indicated that culture of MDA-MB-231 on fibronectin perhaps send signals via fibronectin-integrin-mediated signaling pathways recruiting FAK, PI-3K, ILK, NF-κB, and modulate expression and activation of pro-MMP-9. These observations may enrich fundamental aspects of cancer biology especially role of α5β1 integrin in regulation of MMPs expression and activity.

Aims: The tumor inhibiting property of green tea polyphenol epigallocatechin-3-gallate (EGCG) is well documented. Studies reveal that matrix-metalloproteinases (MMPs) play pivotal roles in tumor invasion through degradation of basement membranes and extracellular matrix (ECM). We studied the effect of EGCG on matrixmetalloproteinases-2 (MMP-2), the factors involved in activation, secretion and signaling molecules that might be involved in the regulation of MMP-2 in human breast cancer cell line, MCF-7., Main Methods: MCF-7 was treated with EGCG (20 muM, 24 h), the effect of EGCG on MMP-2 expression, activity and its regulatory molecules were studied by gelatin zymography, Western blot, quantitative and semi-quantitative real time RT-PCR, immunoflourescence and cell adhesion assay., Key Findings: EGCG treatment reduced the activity, protein expression and mRNA expression level of MMP-2. EGCG treatment reduced the expression of focal adhesion kinase (FAK), membrane type-1-matrix metalloproteinase (MT1-MMP), nuclear factor-kappa B (NF-kB), vascular endothelial growth factor (VEGF) and reduced the adhesion of MCF-7 cells to ECM, fibronectin and vitronectin. Real time RT-PCR revealed a reduced expression of integrin receptors alpha5, beta1, alphav and beta3 due to EGCG treatment., Significance: Down regulation of expression of MT1-MMP, NF-kB, VEGF and disruption of functional status of integrin receptors may indicate decreased MMP-2 activation; low levels of FAK expression might indicate disruption in FAK-induced MMP-2 secretion and decrease in activation of phosphatidyl-inositol-3-kinase (PI-3K), extracellular regulated kinase (ERK) indicates probable hindrance in MMP-2 regulation and induction. We propose EGCG as potential inhibitor of expression and activity of pro-MMP-2 by a process involving multiple regulatory molecules in MCF-7.

Among the cool season legume crops grown in India and the Indian sub-continent, peas are very popular and preferred by the growers as well as consumers for various uses. The third largest area in pea cultivation is occupied by India after Canada and Russia. Among the important and popular varieties of peas that are grown in India, several are from exotic background. But very little work has been done to carry out the genetic diversity present in the widely adapted Indian pea varieties using DNA markers. Twenty-four most popular and widely adapted varieties were subjected to RAPD analysis to find out the genetic relatedness among them using 60 decamer primers. All the primers used in our study were found to be polymorphic and seven of them showed 100% polymorphism. Out of 579 amplified products, 433 showed polymorphism (74.8%). On an average, 9.65 bands were amplified per primer. Cluster analysis based on Jaccard's similarity coefficient using UPGMA grouped all the tall type varieties together, whereas, dwarf types formed two different clusters based upon their pedigree. The arithmetic mean heterozygosity (Hav) value and marker index (MI) was found to be 0.496 and 4.787, respectively, thus this indicated the efficiency of RAPD as a marker system. Moreover, the calculated value of probability of identical match by chance suggested that about 10(53) genotypes can be unambiguously distinguish by employing 60 RAPD primers.

In contrast to normal subjects diabetic patients and very low plasma ascorbic acid and significantly high (p less than 0.001) dehydroascorbic acid irrespective of age, sex, duration of the disease, type of treatment, and glycemic control. However, there was no significant difference between the mean leukocyte ascorbate concentrations of the two populations. The in vitro rates of dehydroascorbate reduction in the hemolysate and the erythrocyte reduced glutathione levels and the glucose-6-phosphate dehydrogenase activities, which regulate the dehydroascorbate reduction, were similar in normal and diabetic subjects. The turnover of ascorbic acid was higher in the diabetics than that in the normal volunteers. Experiments with diabetic rats indicated that the increased turnover of ascorbic acid was probably due to increased oxidation of ascorbate to dehydroascorbate in tissue mitochondria. Ascorbic acid supplementation at a dose of 500 mg per day for a brief period of 15 days resulted in an increase in the plasma ascorbate level temporarily, but it did not lower the blood glucose level of the diabetic patients.