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ABSTRACTIntroductionIschemic stroke is a significant global health challenge with limited treatment options. Neuroinflammation, driven by microglial activation, plays a critical role in stroke pathophysiology. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has emerged as a key player in microglial activation, sterile neuroinflammation, and cell death following stroke. Understanding the interplay between this pathway and stroke pathophysiology is crucial for exploring newer therapeutics for stroke patients.Areas CoveredThis review discusses the pivotal role of the cGAS-STING pathway in ischemic stroke. It explores the interplay between cGAS-STING activation, neuroinflammation, microglia activation, M2 polarization, neutrophil infiltration, and cytokine release. Additionally, the authors examine its contributions to various cell death programs (pyroptosis, apoptosis, necroptosis, lysosomal cell death, autophagy, and ferroptosis). The review summarizes recent studies on targeting cGAS-STING signaling in stroke, highlighting the therapeutic potential of small molecule inhibitors and RNA-based approaches in mitigating neuroinflammation, preventing cell death, and improving patient outcomes.Expert opinionUnderstanding cGAS-STING signaling in ischemic stroke offers an exciting avenue for drug discovery. Targeting this pathway holds promise for developing novel therapeutics that effectively mitigate neuroinflammation, prevent cell death, and enhance patient outcomes. Further research and development of therapeutic strategies are warranted to fully exploit the potential of this pathway as a therapeutic target for stroke.

Salinity stands as a critical abiotic stress factor, posing significant challenges to global agricultural productivity. However, there is no comprehensive study that simultaneously investigates multiple spinach genotypes; integrates assessments of various parameters like biomass yield, ion uptake, and partitioning; and conducts genetic characterization of salinity tolerance mechanisms. To address this gap, we conducted a greenhouse experiment with 16 spinach genotypes, from diverse geographical regions, irrigated with saline waters of 1.87 and 23.3 dS m–1. The salt tolerance index for shoot biomass exhibited significant variability among the genotypes, with 'Dikenli', 'Victoria', and 'Cornell ID #148' being the top performers and 'Cornell ID #87', 'Gazelle', and 'Polag Benaresi' being the bottom performers. Under high salinity, on average, plants accumulated 25-fold higher Na and 8.5-fold higher Cl in leaves compared to the control. Leaves accumulated 2.4-fold more Na and Cl than roots under salinity compared to the control. Expression analyses of specific genes in roots and leaves provided insights into Na+/Cl–efflux, vacuolar sequestration, root-to-shoot movement, ion homeostasis, and scavenging of reactive oxygen species. Our results demonstrate the importance of screening geographically diverse genotypes and considering multiple traits when selecting genotypes for salt tolerance.

Nanocomposites based on graphene oxide have shown significant potential in various applications, including solar devices. In this paper, hydrothermally synthesized cadmium sulfide (CdS)-embedded graphene oxide (GO–CdS) nanocomposites were reported. The resulting powder was black and was filtered and washed with distilled water. The samples were then characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, optical transmission and photoluminescence studies. The samples demonstrated a polycrystalline phase with a rutile structure and high luminescence peaks. As the amount of cadmium sulfide in the graphene oxide increased, the particle size of the nanocomposites also increased. FTIR analysis confirmed the formation of GO–CdS nanocomposites. Furthermore, the samples exhibited excellent photoluminescence, which made these composites highly suitable for optoelectronic applications.

This study reports the photocatalytic degradation of Methyl Red dye at various pH values under white LED light using highly efficient ZnO/CdS Hierarchical Heterostructures grown by a two-step ultrasonicated hydrothermal route. The ZnO/CdS heterostructures were synthesized using a two-step ultrasonicated hydrothermal route and characterized by morphological, structural, and optical studies. The samples were then applied for photocatalytic degradation of Methyl Red dye with pH variation studies. The X-ray diffractogram peaks show mixed hexagonal structures with decreased particle size with increasing CdS content. It was found that the samples exhibited mixed hexagonal structures with reduced particle size and increased CdS content. The average size of ZnO and ZnO/CdS doped nanocomposites was about 30, 29, 19, and 17 nm, respectively. FESEM and TEM micrographs of ZnO/CdS heterostructures exhibit hexagonal arrangements with increased CdS content. Photoluminescence spectra show excellent luminescence in the visible region. Using the visible light spectrum, excellent photocatalytic behavior is reported to degrade Methyl Red dye at different photoluminescence pH values. The photoluminescence studies of pigments after degradation shows that the OH* radical formation is more at pH9 than pH4. As a result, 95% degradation of dyes was observed in the primary region, at pH 9, with ZnO/CdS catalyst under the visible light source. This research indicates that ZnO/CdS heterostructures can be a promising photocatalyst for degrading organic pollutants in wastewater treatment.

Guar (Cyamopsis tetragonoloba(L.) Taub.) is an economically important, drought‐tolerant legume crop affected by moderate to high salinity. Guar has various industrial applications, including gum extracted from seeds that is widely used in the oil and natural gas industries. In this investigation, we evaluated the salinity tolerance of different guar genotypes and their relation to genetic mechanisms regulating guar responses to salinity stress. We screened 24 guar genotypes in a greenhouse lysimeter system under control (electrical conductivity (EC) = 1.46 dS m−1) and high salinity (EC = 13.65 dS m−1) treatments. Both length and biomass of shoots were significantly affected by salinity compared to roots, indicating higher shoot than root sensitivity to salinity. Twenty‐four genotypes were classified based on salt tolerance index for each trait. Tissue ion analysis revealed that roots accumulated over 10‐fold higher Na than leaves, demonstrating that guar effectively regulated the root‐to‐shoot movement of Na+. However, higher Cl concentrations in leaves than roots indicated less regulatory control of Cl−movement. Based on the morphological traits and tissue ion analysis, six genotypes (PI 164486, PI 253186, PI 26152, PI 158125, PI 179926, and PI 263698) with different responses to salinity were selected for gene expression analysis. Expression patterns of different genes showed that a complex network of component traits, including Na+exclusion, Cl−exclusion, and tissue tolerance, regulate salinity tolerance in guar. Hence, the genetic information about different component traits will benefit guar breeders in developing new varieties that are more tolerant to salinity than current ones. Guar shoots are more sensitive to salinity than roots.Guar plants regulate the root‐to‐shoot movement of sodium efficiently, but not of chloride.Sodium exclusion, chloride exclusion, and tissue tolerance were important traits under salinity stress in guar.Guar genotypes varied for the component traits related to salinity tolerance mechanisms.

Mesenchymal stromal cells (MSCs) have evolved as an invaluable therapeutic cell type due to their broad therapeutic properties. Bone marrow-derived MSCs are currently being applied in numerous clinical trials, and the initial results have been encouraging. However, heterogeneous responsiveness amongst patients is also being experienced; therefore, the efficacy of MSCs in vivois still debatable. Host microenvironment plays an essential role in determining the fate of MSCs in vivo. Recent studies have indicated the role of toll-like receptors (TLR) in modulating the biological properties of MSCs. TLRs are expressed by MSCs, and activation of TLR3 and TLR4 can alter the functionality of MSCs. While MSCs can suppress the effector and memory T cell function by promoting regulatory T cells, the effect of TLR activation on MSC-mediated immune cell induction is still not well understood. This study was performed to understand the TLR licensing of MSCs and its impact on MSC-mediated immunomodulation. We found that TLR3 mediated activation of MSCs (TLR3-MSCs) increased the expression of G-CSF & IL-10 while TLR4-mediated activation of MSCs led to an increase in CXCL-1, CXCL-10, and CXCL-12. To study the immunological aspect, an in vitroco-culture model was established-to imitate the brief in vivointeraction of MSCs and immune cells. We found that TLR3-MSCs led to increase in CD4 and CD8 naive T (TNAI) cells and vice versa for effector (TEFF) and memory T (TMEM) cells, while TLR4-MSCs did not show any effect.

Nowadays, voluminous unstructured data is steaming on the Web/social media. It is not easy for individuals to find relevant information quickly from such a vast unstructured corpus. Text summarizing is the process of retrieving relevant information in brief without changing the fundamental meaning of information. Manual text summarization takes much time, cost and effort to summarise. Researchers worked on different machine learning approaches to summarise the text in the past but still lagging for better-summarised results. In this paper, initially, we used reinforced learning (with attention layer) as the base model. We analysed its performance analysis, and later we proposed a deep learning-based model and evaluated using Bilingual Evaluation Understudy (BLEU) value of 0.4 and Recall-Oriented Understudy for Gisting Evaluation (ROUGE) with a value of 0.6 on a large corpus at sentence level on a standard dataset. The proposed model shows promising results of accuracy and correctness as compared to the state-of-the-art.

This paper presents the bearing capacity determination of strip footing placed on sand underlain by clay and subjected to inclined loading. The bearing capacity equation is derived within the framework of limit equilibrium by following the projected area approach. The inclinations of load spread were selected by performing an additional finite element analysis. A parametric study was conducted to highlight the effect of various input parameters such as i) the thickness of the top sand layer, ii) embedment depth of footing, iii) the friction angle of sand and cohesion of clay, and iv) inclination of the applied load. The obtained results for a vertically loaded footing are slightly underestimated with that available in the literature. The computed bearing capacity values for a foundation with inclined loading compare favorably for lower inclination angle but slightly overestimates for higher load inclination angle, concerning that obtained using the available formula in the literature.

Glioblastoma (GBM) is a complex brain cancer with frequent relapses and high mortality and still awaits effective treatment. Mitochondria dysfunction is a pathogenic condition in GBM and could be a prime therapeutic target for ceasing GBM progression. Strategies to overcome brain solid tumor barriers and selectively target mitochondria within specific cell types may improve GBM treatment. Here, we present hypericin-conjugated gold nanoparticles (PEG-AuNPs@Hyp) where hypericin is a mitochondrion-targeting agent exhibiting multimodal therapy by critically impacting the IDH2 gene (Isocitrate dehydrogenase) and its interaction with polycomb methyltransferase EZH1/2 for GBM therapy. It significantly localizes in mitochondria by enhanced cellular uptake in the human GBM cell lines/three-dimensional (3D) culture model under red-light exposure. It triggers oxidative stress and changes the mitochondrial potential, with increased Bax/Bcl2 ratio enhancing GBM cell death. The suppressed expression of mutated IDH2 and polycomb group of proteins upon PEG-AuNPs@Hyp/light exposure regulates mitochondria-targeting-mediated GBM metabolism with epigenetic repression of complex machinery function. Polyubiquitination and proteasomal degradation of EZH1 indicate the implication of these polycomb proteins in GBM progression. Chromatin immunoprecipitation reveals the IDH2 and EZH1/EZH2 direct interaction, confirming the role played by IDH2 in modulating the expression of EZH1 and EZH2. In vivostudies further displayed better tumor ablation in a GBM tumor-bearing nude mouse model. The present multimodal nanoformulation compromised the functional dependency of polycomb on mitochondrial IDH2 and established the mechanism of GBM inhibition.

Pulp washing is a prime activity in the process industry that involves diffusion–dispersion phenomena. A huge amount of cost, time, and ecological issues are entailed in waste-water management. To reduce this environmental load and to achieve higher efficiency, the mathematical models are developed and solved with different techniques by the various researchers. In the present study, quintic Hermite interpolating polynomials are used to approximate the trial function for solving the mathematical model of diffusion–dispersion phenomena. The purpose behind this study is to derive an accurate result with less CPU time and effect for some important parameters such as Peclet number, cake thickness, and interstitial velocity of the pulp washing process. Two problems, first with the constant coefficient and second with the variable coefficient are worked out by the proposed scheme. After getting the desired results for the linear model, the method is applied to the nonlinear model. The results indicate that the Peclet number plays a leading role in the pulp washing process whereas, the cake thickness and interstitial velocity both are having a lesser effect. The efficiency, accuracy, and applicability of the method is derived using L2norm, L∞norms, and rate of convergence. The suitability of the proposed technique is well weighed up when compared with the earlier published results and displays a wider scope of industrial applicability.

Changes in phenology, growth, biomass production and photosynthetic parameters in Trifolium repensL. were studied under Free Air CO2Enrichment (FACE; 550 ± 50 µmol mol−1[CO2]) and Free Air Temperature Increment FATI for 2 years during 2010–11 and 2011–12 in temperate Himalaya. Plant height, root volume, leaf area and dry biomass of T. repensincreased from 8.8 to 33.5% under elevated [CO2] but decreased from 4.6 to 58.1% under elevated temperature compared to ambient environment. Leaf area increased by 24.1 and 29.5% under elevated [CO2], however, elevated temperature reduced leaf area by 78.1 and 38.6% compared to ambient conditions during 2010–11 and 2011–12, respectively. Leaf net photosynthetic rates (PN) and stomatal conductance (gS) measured at 390 ± 10 µmol m−2s−1CO2, declined under FACE and FATI environment as compared to control conditions, with greater reduction during year 2011–12 than 2010–11. The values of PNin year 2011–2012 during spring and autumn were lower by 13% and 7% under FACE and 24% and 18% under FATI, respectively, compared to ambient (control) conditions, when measured at 400 µmol m−2s−1. For year 2012, gSshowed a decrease by 26% and 39% under FACE and by 21% under FATI during spring and autumn months, respectively, compared to ambient conditions. All phenological stages were significantly advanced under elevated temperature but showed a delayed response under elevated [CO2] as compared to ambient conditions.

Acute myeloid leukemia (AML) is a malignant disorder of hematopoietic progenitor cells with a poor prognosis of 26% of patients surviving 5 years after diagnosis. Poor bioavailability and solubility are significant factors limiting the efficacy of chemopreventive agents. In AML, the epigenetic regulator polycomb group of protein member EZH2 is highly expressed and is essential for the survival of leukemic cells. An EZH2-specific inhibitor, EPZ011989, encapsulated in human serum albumin nanoparticles (HSANPs) was synthesized for the first time via the desolvation method. The noncovalent interactions between EPZ011989 and HSANPs in nanocomposites facilitating the efficient loading and sustainable release of the drug showed enhanced cellular uptake and nuclear localization of EPZ011989-loaded HSANPs in human AML cell lines. The reduction of cell viability, colony formation inhibition, cell cycle arrest at the G2/M phase, and cell proliferation assay promoting apoptosis through the loss of mitochondrial homeostasis exerting antileukemic activity were evident. The real-time polymerase chain reaction (PCR) and western blot-based studies showed that the present nanoformulation reduces the level of PcG proteins, including EZH2, BMI-1, etc. This downregulation is associated with reduced H3K27me3 and H2AK119ub modifications conferring chromatin compaction. The immunoprecipitation study showed the physical interaction of EZH2 and c-Myb can be linked to the regulation of leukemogenesis. Further investigation revealed the mechanism of EZH2 and c-Myb downregulation via ubiquitination and proteasomal degradation pathway, confirmed by using proteasome inhibitor, suggesting the key role of proteasomal degradation machinery. Moreover, c-Myb interacted with the EZH2 promoter, which is evident by the chromatin immunoprecipitation assay and siRNA silencing. Furthermore, the formulation of EPZ011989 in HSANPs improved its biodistribution in vivo and showed excellent aqueous dispersibility and biocompatibility. In vivo studies further showed that EPZ011989-loaded HSANPs reduce the expression of CD11b+and CD45+markers in immunophenotyping from peripheral blood and bone marrow in engrafted nude mice. Targeted depletion of EZH2 alleviated the disease progression in nude mice and prolonged their survival. The findings provide valuable experimental evidence for the targeted epigenetic therapy of AML. The present results demonstrate an epigenetic regulation-based superior antileukemic therapy.

ABSTRACTBackground: The poor biopharmaceutical properties of thymoquinone (TQ) obstruct its development as a hepatoprotective agent. To surmount the delivery challenges of TQ, phospholipid nanoconstructs (PNCs) were constructed.Method: PNCs were constructed employing microemulsification technique and systematic optimization by three-factor three level Box-Behnken design.Result: Optimized PNC composition exhibited nano size (<100 nm), spherical morphology, within acceptable range of polydispersity index (0.55), high drug entrapment efficiency (>90%), controlled drug release pattern, and neutral surface charge (zeta potential of −0.65 mV). After oral administration of a single dose of PNC, it showed a relative bioavailability of 386.03% vis-à-visplain TQ suspension. Further, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-à-vispure TQ suspension and silymarin, as evidenced by reduction in the ALP, ALT, AST, bilirubin, and albumin level and ratified by histopathological analysis.Conclusion: TQ-loaded PNCs can be efficient nano-platforms for the management of hepatic disorders and promising drug delivery systems to enhance oral bioavailability of this hydrophobic molecule.

Aims: The study was aimed to develop mucoadhesive buccal tablets using Aster ericoides leaves mucilage. Background: Mucilages are naturally occurring high-molecular-weight polyuronides, which have been extensively studied for their application in different pharmaceutical dosage forms. Objective: The objective of the present research was to establish the mucilage isolated from the leaves of Aster ericoides as an excipient for the formulation of the mucoadhesive buccal tablet. Methods: The mucilage was isolated from the leaves of Aster ericoides by maceration, precipitated with acetone and characterized. Tablets were prepared using wet granulation technique and evaluated for various official tests. Results: The mucilage was found to be non-toxic on A-431 and Vero cell lines. It was insoluble but swellable in cold and hot water. The results indicate that mucilage can form a three-dimensional network. The pH of the mucilage (6.82 ± 0.13) indicated that it might be non-irritant to the buccal cavity. The mucilage was found to be free from microbes. The release of drug was by Fickian diffusion. The in vivo buccal tablet acceptance was 80%. No significant difference between the diastolic blood pressure of standard and Aster tablets treated volunteer group was recorded. Conclusion: It might be concluded that the isolated mucilage from the leaves of Aster ericoides may be used as an excipient for the development of mucoadhesive buccal tablets. Other: However, to prove the potency of the polymer, in vivo bioavailability studies in human volunteers are needed along with chronic toxicity studies in suitable animal models.

Understanding the intricacies of herbs and foods against bacterial infections is paramount for informed therapeutic choices. Delving into this domain, current study was focused to assess antimicrobial properties of Viola canescensorgan specific extracts against prevalent respiratory tract pathogens (Klebsiella pneumoniae, Staphylococcus aureus,and Streptococcus pneumonia). Our methodology entailed proximate composition, TPC, TFC, Total condensed tannins and comprehensive chemical profiling by GC-MS, UPLC-PDA, and UPLC-MS/MS. Further, in-vitro,antioxidant potential through ABTS ֹ+and DPPH ֹ radical scavenging assays was assessed. The root showed higher amount of proximate composition than its counterparts. Further, ethanol extract showed highest TPC (32.15±0.92mg GAE/g), TFC (125.61±2.28mg RE/g), and comparable TCT with methanol extract (34±0.19mg CE/g). UPLC analysis showed that p-coumaric acid was most predominant followed by rutin and luteolin among the V. canescensparts. In GC/MS analysis, methyl linoleate emerged as a major component as 10.70%, 17.62%, and 35.90% in flowers, leaves, and roots, respectively. Further, UHPLC- MS/MS data-based METLIN search revealed the presence of flavonoids, coumarins, terpenoids, and fatty acid derivatives etc. Chemo-metric analysis also showed variations of metabolites in different parts. All samples showed significant antioxidant activity with highest in methanol and ethanol flower extracts (0.037±0.001, 0.071±0.001 DPPHֹ and ABTS ֹ +IC50mg/mL). The study suggested aerial parts can be a promising source of antioxidant and antimicrobial agents that may protect against respiratory tract pathogens similar to azithromycin. This substantiates the potential of V. canescensas a foundational ingredient for novel therapeutics.

•MicroRNA has emerged as one of the master regulators of plant developmental processes.•miRNA has emerged as new candidate for modulating responses to abiotic stress.•miRNA targets transcription factors and/or the gene responsible for enhancing adaptive potential of plants.•This review presents salient findings on miRNA-mediated alleviation of deleterious effects of drought stress in rice.•We also discuss the miRNA-based strategies for stress tolerance, limitations in using them and the future perspectives.

Multiple cancers exhibit aberrant protein arginine methylation by both type I arginine methyltransferases, predominately protein arginine methyltransferase 1 (PRMT1) and to a lesser extent PRMT4, and by type II PRMTs, predominately PRMT5. Here, we perform targeted proteomics following inhibition of PRMT1, PRMT4, and PRMT5 across 12 cancer cell lines. We find that inhibition of type I and II PRMTs suppresses phosphorylated and total ATR in cancer cells. Loss of ATR from PRMT inhibition results in defective DNA replication stress response activation, including from PARP inhibitors. Inhibition of type I and II PRMTs is synergistic with PARP inhibition regardless of homologous recombination function, but type I PRMT inhibition is more toxic to non-malignant cells. Finally, we demonstrate that the combination of PARP and PRMT5 inhibition improves survival in both BRCA-mutant and wild-type patient-derived xenografts without toxicity. Taken together, these results demonstrate that PRMT5 inhibition may be a well-tolerated approach to sensitize tumors to PARP inhibition.

Kufri Bahar, a leading potato variety is facing a problem of deshaped elongated tubers. Deshaping of tubers in form of elongation with jelly end formation leads to spoilage during transportation and storage. This elongation may be due to the stress conditions and/or enhanced gibberellic acid (GA) formation during micropropagation. Photoperiod and EDTA salts are reported to influence the GA concentration. Therefore, the effect of photoperiod and EDTA salts was investigated on the endogenous GA concentration of tissue culture microplants of potato vars Kufri Bahar and Kufri Lauvkar. The GA concentration in microplants grown in tissue culture media with Na-EDTA, Fe-EDTA and without EDTA ranged from 0.84 to 1.95 nmol/ml FW (fresh weight). In the present study, no correlation was observed between EDTA and GA concentration. Shoot length, internodal distance and number of nodes were more in microplants grown under a long photoperiod (16 h). Root length, number of roots and the number of leaves were high in short photoperiod (12 h) grown microplants. Gibberellic acid content showed similar trend as that of shoot length and ranged from 0.65 to 1.49 nmol/ml. Concentration of GA was more in var. Kufri Bahar compared to var. Kufri Lauvkar under the long photoperiod, which showed that Kufri Bahar is more responsive to photoperiod. High GA content in var. Kufri Bahar microplants grown under the long photoperiod could be the possible reason for tuber elongation. Therefore, to avoid the deshaping of tubers, the photoperiod during in vitro propagation may be shortened, particularly for var. Kufri Bahar.

Pyrabactin resistance 1 (PYR1) and related abscisic acid (ABA) receptors are new targets for manipulating plant drought tolerance. Here, we identify and use PYR1 hypersensitive mutants to define ligand binding hotspots and show that these can guide improvements in agonist potency. One hotspot residue defined, A160, is part of a pocket that is occupied by ABA’s C6 methyl or by the toluyl methyl of the synthetic agonist quinabactin (QB). A series of QB analogues substituted at the toluyl position were synthesized and provide up to 10-fold gain in activity in vitro. Furthermore, we demonstrate that hypersensitive receptors can be used to improve the sensitivity of a previously described mammalian cell ABA-regulated transcriptional circuit by three orders of magnitude. Collectively, our data show that the systematic mapping of hypersensitivity sites in a ligand-binding pocket can help guide ligand optimization and tune the sensitivity of engineered receptors.

Vegetative propagation of potatoes makes it possible for potato viruses to be transmitted through tubers. Potato virus A (PVA) is one of these viruses, which belongs to the Potyvirusgenus in the Potyviridaefamily. Potato tuber yield can be reduced by 30–40% by PVA alone. Losses can be further exacerbated by potato virus X and/or potato virus Y infection. PVA is transmitted primarily by several species of aphids in non-persistent manner. With the aim of resolving this problem, we developed one-step reverse transcription-recombinase polymerase amplification (RT-RPA), a highly sensitive and cost-effective method for detecting PVA in both potato tubers and leaves. Detection and amplification are performed using isothermal conditions in this method. There was good amplification of the coat protein gene in PVA with all three primers tested. To conduct this study, a primer set that can amplify specific 185 base pair (bp) product was selected. PVA detection was optimized by 30-min amplification reactions, which showed no cross-reactivity with other potato viruses. A simple heating block or water bath was used to amplify PVA product using RT-RPA at a temperature range of 38–42 °C. In comparison to conventional reverse transcription-polymerase chain reaction (RT-PCR), the newly developed RT-RPA protocol exhibited high sensitivity for both potato leaves and tuber tissues. Using cellular paper-based simple RNA extraction procedure, the virus was detected in leaf samples as efficiently as purified total RNA. We also found that combining LiCl-based RNA precipitation with cellular paper discs allowed us to successfully optimize RNA extraction for one-step RT-RPA for detecting PVA in tubers. Tests using this simplified one-step RT-RPA method were successfully applied to 300 samples of both leaves and tubers from various potato cultivars. In our knowledge, this is the first report of an RT-RPA assay utilizing simple RNA obtained from either cellular disc paper or LiCl coupled with cellular disc paper to detect PVA. As a result, this method was equally sensitive and specific for detecting PVA in potatoes. The developed RT-RPA assay is more versatile, durable, and do not require highly purified RNA templates, thus providing an effective alternative to RT-PCR assays for screening of germplasm, certifying planting materials, breeding for virus resistance, and real-time monitoring of PVA.

ABSTRACTRNA binding proteins have emerged as critical oncogenic factors and potential targets in cancer therapy. In this study, we evaluated Musashi1 (Msi1) targeting as a strategy to treat glioblastoma (GBM); the most aggressive brain tumor type. Msi1 expression levels are often high in GBMs and other tumor types and correlate with poor clinical outcome. Moreover, Msi1 has been implicated in chemo- and radio-resistance. Msi1 modulates a range of cancer relevant processes and pathways and regulates the expression of stem cell markers and oncogenic factors via mRNA translation/stability. To identify Msi1 inhibitors capable of blocking its RNA binding function, we performed a ~ 25,000 compound fluorescence polarization screen. NMR and LSPR were used to confirm direct interaction between Msi1 and luteolin, the leading compound. Luteolin displayed strong interaction with Msi1 RNA binding domain 1 (RBD1). As a likely consequence of this interaction, we observed via western and luciferase assays that luteolin treatment diminished Msi1 positive impact on the expression of pro-oncogenic target genes. We tested the effect of luteolin treatment on GBM cells and showed that it reduced proliferation, cell viability, colony formation, migration and invasion of U251 and U343 GBM cells. Luteolin also decreased the proliferation of patient-derived glioma initiating cells (GICs) and tumor-organoids but did not affect normal astrocytes. Finally, we demonstrated the value of combined treatments with luteolin and olaparib (PARP inhibitor) or ionizing radiation (IR). Our results show that luteolin functions as an inhibitor of Msi1 and demonstrates its potential use in GBM therapy.

In the present work, short glass fiber-reinforced polyester-based hybrid composites are fabricated by the incorporation of Al2O3particulates with three different weight percentages (0 wt.%, 10 wt.% and 20 wt.%) to evaluate their physical, mechanical, and thermo-mechanical behavior. A theoretical model has been developed for erosive wear conditions and results are compared with the experimental outcomes in order to validate the model. The mechanical properties are simulated using an explicit FE code software ANSYS. In this work, erosion test is conducted by using popular evolutionary Taguchi’s (L27) orthogonal array design to optimize the experimental results. It is observed from the analysis that the peak erosion rate occurs at 75° impingement angle for Al2O3-filled composites, whereas for unfilled composites, it occurs at 60° impingement angle. The thermo-mechanical characteristics such as storage modulus (E′), loss modulus (E″), and damping properties (Tan δ) are investigated in the temperature range of 25–200 ℃. It is observed that the slope corresponding to the temperature-dependent decay of the storage modulus for 10 wt.% and 20 wt.%, Al2O3-filled composite is much higher as compared to 0 wt.% Al2O3-filled composite in the temperature range of 25–75 ℃. However, the storage modulus for 10 wt.% and 20 wt.% Al2O3-filled composites remain almost same in the range of 25–60 ℃. Finally, the surface morphology of the eroded composites is examined by using scanning electron microscope and the possible wear mechanisms are discussed.

Abstract:Valeriana jatamansiis an important Himalayan medicinal and aromatic herb. An experiment was conducted to study the effect of environmental conditions and vermicompost at free air CO2enrichment (FACE) and free air temperature increase (FATI) facilities of CSIR-Institute of Himalayan Bioresource Technology, Palampur, India during 2013-2015. Experiment comprised of six treatments with two factors, viz., three levels of environmental conditions viz., ambient conditions (390 μmol mol-1), elevated CO2 (550±50 μmol mol-1) and elevated temperature (2.5±0.5°C above ambient) and two levels of vermicompost (control and with vermicompost). Experiments were laid out in completely randomized design (CRD) with five replications. Essential oil was obtained from rhizomes and roots of V. jatamansiafter 12 months of exposure to elevated CO2 and temperature by hydrodistillation in a Clevenger type apparatus for 6 h. Elevated CO2 enhanced the essential oil content by 17.7 % and elevated temperature decreased by 4.3 % as compared to ambient conditions. Essential oil composition was significantly affected by different treatments. Patchouli alcohol, bornyl acetate, β-patchoulene, germacrene D, monoterpene hydrocarbons and oxygenated sesquiterpenes were significantly higher in FACE and FATI as compared to ambient. Vermicompost application increased trans-β-guaiene, globulol, β-patchoulene, camphene, germacrene D and bornyl acetate content. These results indicate that elevated CO2 jatamansi. and temperature alters essential oil content and composition of V.

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Background: The purpose of the study was to explore the therapeutic potential of Betulinic acid (BA) in streptozotocin (STZ) induced memory damage in experimental rats. Methods: STZ (3 mg/kg bilaterally) as intracerebroventrical (icv) route was administered on day 1 and 3 in rats. Donepezil (5 mg/kg/day po), used as standard, and BA (5, 10 and 15 mg/kg/day po) were administered after 1 h of 1st STZ infusion up to 21 days. Object recognition task (ORT) for non-spatial, Morris water maze (MWM) for spatial and locomotor activity were performed to evaluate behavioral changes in rats. On 22nd day, animals were decapitated and hippocampus was separated to perform biochemical (AChE, LPO, GSH, nitrite), neuroinflammatory (TNF-a, IL-1ß, and IL-6), neurotransmitters (NTs) (dopamine, norepinephrine and serotonin) analysis. Results: STZ infusion significantly impaired memory as observed in MWM and ORT, increased oxidative stress, pro-inflammatory cytokine’s level and altered NTs level. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA dose dependently (5, 10 and 15 mg/kg) significantly restore STZ induced memory changes and pathological abnormalities in rat brain. Conclusions: The findings of the current study suggests that BA protect rat brain from STZ induced neuronal damage viaacting through multiple mechanisms and would be used to curb cognitive decline associated with neurodegenerative disorders especially AD.

With the eradication of poliovirus, the focus has now shifted to environmental surveillance of poliovirus to determine the circulating polioviruses in an area. L20B and RD cell lines are used for isolation of polioviruses. It is imperative to study the efficacy of these cell line in isolating polioviruses from environmental samples. The present study was carried out to determine the sensitivity and specificity of L20B cell line for isolation of polioviruses from environmental samples. L20B and RD cell lines are used for isolation of polioviruses. Molecular characterization was done by using real time RT-PCR. A total of 432 sewage samples from Delhi and Punjab were processed for the isolation of polioviruses during Jan–Dec 2015. 96.76% of the samples were positive in either of the cell lines. Non-polio enteroviruses were obtained in 50 samples on primary isolation. On RT-PCR, 347 (94.29%) samples yielded polioviruses and the rest (21) non-polio enteroviruses or non-enteroviruses. A total of 703 isolates were obtained. 635 isolates were found polioviruses by PCR (90.33%), 20 isolates were found to be NPEV (2.84%) and 48 (6.83%) were found to be NEV. Out of the 20 NPEV isolates, 14 were from RLR (RD-L20B-RD) route and six isolates were from LR (L20B-RD) route. All 48 NEV isolates were from LR route. Thus L20B cell line is more sensitive as compared to RD cell line for isolation of polioviruses however it is not absolutely specific for polioviruses.

Atopic Dermatitis (AD) is a diverse skin condition with a range of shapes, localization, and progression of the disease. Even though its pathophysiology is multifaceted and not entirely comprehended, it appears to be the consequence of a mix of environmental and genetic variables that cause skin barrier disruption, dermal and systemic immunological imbalance, a significant hereditary influence, and skin microbiome dysbiosis. AD is now a major global health concern owing to its rising incidence over the past few decades. For topical distribution of numerous medications, nano-based formulations have been widely investigated during the past decade. Nanoparticles have been used for transdermal applications but their distribution over stratum corneum(SC), the primary skin barrier, is still difficult. Recent advancements in microneedle array (MN) technology, particularly the use of nanoparticles (NPs) that transport both lipophilic and hydrophilic medicinal drugs, have shown promise in the administration of a variety of formulations. Microneedles (MNs) are the devices that physically penetrate the stratum corneum to effectively traverse the epidermal barrier producing minor invasion and improving patient medication adherence. These are the microscale methods to significantly widen range of medications available for transdermal administration. The current work focuses on the developments associated with the use of microneedles and nanoparticles for efficient penetration of numerous drugs. The review also focuses on the significance of microneedles in treating atopic dermatitis, and various microneedles under preclinical and clinical studies have been summarised along with regulatory challenges and toxicity issues.

Increasing drought and diminishing freshwater supplies have stimulated interest in developing small molecules that can be used to control transpiration. Receptors for the plant hormone abscisic acid (ABA) have emerged as key targets for this application, because ABA controls the apertures of stomata, which in turn regulate transpiration. Here, we describe the rational design of cyanabactin, an ABA receptor agonist that preferentially activates Pyrabactin Resistance 1(PYR1) with low nanomolar potency. A 1.63 Å X-ray crystallographic structure of cyanabactin in complex with PYR1 illustrates that cyanabactin’s arylnitrile mimics ABA’s cyclohexenone oxygen and engages the tryptophan lock, a key component required to stabilize activated receptors. Further, its sulfonamide and 4-methylbenzyl substructures mimic ABA’s carboxylate and C6 methyl groups, respectively. Isothermal titration calorimetry measurements show that cyanabactin’s compact structure provides ready access to high ligand efficiency on a relatively simple scaffold. Cyanabactin treatments reduce Arabidopsiswhole-plant stomatal conductance and activate multiple ABA responses, demonstrating that its in vitropotency translates to ABA-like activity in vivo. Genetic analyses show that the effects of cyanabactin, and the previously identified agonist quinabactin, can be abolished by the genetic removal of PYR1 and PYL1, which form subclade A within the dimeric subfamily III receptors. Thus, cyanabactin is a potent and selective agonist with a wide spectrum of ABA-like activities that defines subfamily IIIA receptors as key target sites for manipulating transpiration.

Environmental surveillance of polioviruses has been used as an important tool in monitoring circulation of wild polioviruses and/or Vaccine derived polioviruses in sewage samples. It is important to distinguish Sabin like isolates from non-Sabin like; ELISA & dual stage real time RT-PCR have been used for the same. Current study was carried out on sewage isolates to compare ELISA & RT-PCR with sequencing to distinguish Sabin like from non-Sabin like. Out of 468 sewage specimens, 91 (19.44%) were non-polio enteroviruses positive and 377 (80.56%) were polio positive by virus isolation method. A total of 488 polio virus isolates were detected by L20B and RD route which were further subjected to ELISA and RT-PCR. The results were compared with sequencing. On comparison, the specificity of ELISA was only 66.67% in spite of very low sensitivity (3.43%). The sensitivity of RT-PCR was 97.71% which makes it a good primary screening test for detection of non-Sabin like viruses. However, the specificity was only 33.33%. RT-PCR appears to be a sensitive tool for detecting non-Sabin like viruses however; the isolates which are non-Sabin like by RT-PCR may not necessarily be mutated viruses. ELISA cannot be used for differentiation of Sabin likes from non-Sabin likes due to low sensitivity.

Objective: In the current research study, a colon targeted pulsatile drug delivery system (PDDS) of venlafaxine hydrochloride (VH) was designed for chronotherapy of depression. Method: A capsular device was designed having body insoluble throughout gastrointestinal tract (GIT) fluid and cap soluble in small intestine fluid. The granules of VH was filled in the body and separated from the cap with the help of a hydrophilic polymer plug. Plugs were made up of blend of HPMC K100M and xanthan gum (1:1). Finally, an enteric coating was applied on entire capsule using 5 %w/v ethylcellulose (EC) solution. Results: In in vitro release studies, the enteric coat of the EC was insoluble for 2 h in pH 1.2 (stomach), but get solubilized in pH 7.4 phosphate buffer (small intestine). The cap of the capsule solubilizes in pH 7.4, which exposed the hydrophilic plug to absorb the nearby fluid and swell. After maximum swelling, the plugs got ejected out from the capsule body causing the release of VH granules into colon (pH 6.8 phosphate buffer). Conclusion: Formulations containing high amount of polymer in plug showed 5 h lag time, which was considered optimum for a delivery system to reach colon and release the drug.

Background: Potato flour, being nutritious and a high source of carbohydrates, has been explored for the manufacturing of biscuits. Methods: Replacement of refined wheat flour with potato flour at various levels (5 to 30%) was done for the preparation of biscuit. The physicochemical and functional properties of wheat flour, potato flour prepared from Kufri Chipsona-1 and flour blends were also studied. Results: The nutritional composition of potato flour indicated a higher fibre (3.50%) and carbohydrate (82.79%) content than wheat flour. Wheat flour showed higher water holding capacity (7.4 ml g-1), oil holding capacity (2.8 ml g-1), water retention capacity (50.4%) and alkaline water retention capacity (55.8%) than potato flour. The crude fibre and carbohydrate content of biscuits increased significantly (p<0.05) from 2.34 to 3.52% and 68.88 to 69.72%, respectively, after incorporation of potato flour. The spread ratio of biscuits decreased with incorporation of potato flour. The L* value decreased significantly (p<0.05) from 30.44 to 25.47 whereas the hardness of biscuits increased significantly (p<0.05) from 9.8 N to 20.8 N on increasing the level of potato flour incorporation. Conclusion: The sensory characteristics of biscuits prepared by replacing wheat flour by 25% potato flour were similar to control sample. The functional properties also showed an increasing trend with increase in the incorporation of potato flour.

•The present study focused on blanching methods influence upon starch fractions of potatoes processing varieties.•Kufri Frysona had the highest starch content of 69.27g ̸ 100 g, resistant starch (61.91g/100g) and RDS content (4.96 g/100 g) were also higher. In addition, the raw Kufri Frysona samples had an SDS content of 2.4 g/100g, which increased by microwave blanching to 27.7 g/100g.•The starch fractions analysis has proved to be sensitive to changes in treatment conditions with varietal difference, likely to affect glycemic response.

AbstractWide applications and low oil content of damask rose have made it mandatory to design agro practices which can increase the oil yield and quality. Therefore, experiments were conducted to study the variation in essential oil content and composition of damask rose (Rosa damascenaMill.) by potassium nitrate (KNO3) foliar spray and use of sodium chloride salt (NaCl) during distillation of flowers under western Himalayas during 2012 at CSIR-Institute of Himalayan Bioresource Technology, Palampur, India. The quantity was measured as the ratio of oil to rose flower (v/w, %) and the quality was evaluated using the oil composition. The essential oil content and composition were affected by foliar spray of KNO3on rose plants and addition of NaCl in water during distillation. Significantly higher number of flowers and flower yield were recorded by the application of 900 ppm KNO3. The percentage of citronellol+nerol, increased with application of KNO3up to 900 ppm and declined thereafter. Geraniol content increased with application of KNO3up to 1200 ppm. Flowers treated with 75 g NaCl/kg of rose flowers showed an increase of 42% oil yield over control. Beside this a decrease of 44% and an increase of 26% were observed in the percentage of hydrocarbons and monoterpene alcohols, respectively, in this treatment compared to control.

Plant growth promoting rhizobacteria are beneficial bacteria are one of the major groups of microbes that can be found in the rhizosphere, in association with roots which can enhance the growth of plant directly or indirectly. The present study aimed to isolate plant growth promoting and disease suppressing bacterial isolates native to rhizosphere soil and/or endophytic tissues of ginger plants from two different major growing location of each of Solan and Sirmour districts of H.P. (India). Nutrient agar, Jensen’s medium, Pikovskaya’s medium and soil extract medium are used for screening of microbial population associated with ginger and ginger roots, while for the population assessment, Pikovskaya’s medium was used. The highest microbial count on ginger was at Sirmour (Narag), while the PSB +ve colonies (87.72) and % P solublizers to PVK count (79.00) associated with ginger root was highest at Solan (Kandaghat), Himachal Pradesh.

AbstractDNA cryptography is a novel field being taken up by the researcher community for research now days in order to have secure communication on a network. This technique is inspired from biological science, in which DNA is used as an information carrier from one generation to another. DNA cryptography is proposed for a secure end to end communication due to the vast parallelism and extra ordinary information density that are inherent in any DNA molecule. In this paper previous algorithm based on DNA cryptography is enhanced in terms of its security parameter by incurring feistel inspired structure in it. This adds some sort of confusion and diffusion, which makes it complex enough that it restricts the adversary to perform any kind of brute force attack. Encryption and decryption time is also compared on the basis of variable plaintext size.

Analyzing the patterns of earthquakes and creating a system to detect them, can help to minimize loss of lives. Existing sensor based detection works failed to distinguish between earthquakes and other external vibrational noises that may be caused due to construction or other external sources. In the proposed work, to overcome this drawback, first in-depth structural analysis of shear walls is done to find a structurally suitable location to install the sensor in a building. Further, MPU6050 sensor is used to reduce the complexity and make the circuit less bulky. This sensor consists of an accelerometer which measures the change in acceleration and a gyroscope which records the shaking pattern of the ground. Since this shaking pattern is exhibited exclusively by an earthquake occurrence, the proposed model distinguishes between earthquake and other non-hazardous vibrations efficiently. With the considered model for machine learning algorithms, we were able to achieve 99.82% of accuracy, which is an important factor for earthquake detection.