Throat packing via nasopharyngeal airway for severe trismus cases requiring surgical intervention under general anesthesia: A simplified and innovative approach.

Throat packing is essential in oral and maxillofacial surgeries to prevent blood and tissue debris aspiration, reducing postoperative complications. Traditional oral route methods are often inadequate, especially in severe trismus cases like Oral Submucous Fibrosis (OSMF), TMJ Ankylosis, and post-traumatic conditions due to limited mouth opening. This study introduces a novel technique using a nasopharyngeal airway (NPA) for throat packing. The method involves inserting a hemostatic dressing through an NPA, ensuring minimal invasiveness and effective airway management. Proper positioning is confirmed with a laryngoscope or fiberoptic scope, and the dressing is secured to prevent dislodgement. This technique is easy, reproducible, and less injurious compared to traditional methods. At our center, throat packing via NPA was performed on 35 patients undergoing surgery under general anesthesia, resulting in high satisfaction and no reported complications.

Furanocoumarins promote proteasomal degradation of viral HBx protein and down-regulate cccDNA transcription and replication of hepatitis B virus.

Nucleot(s)ide analogues, the current antiviral treatments against chronic hepatitis B (CHB) infection, are non-curative due to their inability to eliminate covalently closed circular DNA (cccDNA) from the infected hepatocytes. Preclinical studies have shown that coumarin derivatives can effectively reduce the HBV DNA replication. We evaluated the antiviral efficacy of thirty new coumarin derivatives in cell culture models for studying HBV. Furanocoumarins Fc-20 and Fc-31 suppressed the levels of pre-genomic RNA as well as cccDNA, and reduced the secretion of virions, HBsAg and HBeAg. The antiviral efficacies of Fc-20 and Fc31 improved further when used in combination with the hepatitis B antiviral drug Entecavir. There was a marked reduction in the intracellular HBx level in the presence of these furanocoumarins due to proteasomal degradation resulting in the down-regulation of HBx-dependent viral genes. Importantly, both Fc-20 and Fc-31 were non-cytotoxic to cells even at high concentrations. Further, our molecular docking studies confirmed a moderate to high affinity interaction between furanocoumarins and viral HBx via residues Ala3, Arg26 and Lys140. These data suggest that furanocoumarins could be developed as a new therapeutic for CHB infection.

Exploring the Role of Non-synonymous and Deleterious Variants Identified in Colorectal Cancer: A Multi-dimensional Computational Scrutiny of Exomes.

Introduction: Colorectal cancers are the world's third most commonly diagnosed type of cancer. Currently, there are several diagnostic and treatment options to combat it. However, a delay in detection of the disease is life-threatening. Additionally, a thorough analysis of the exomes of cancers reveals potential variation data that can be used for early disease prognosis. Methods: By utilizing a comprehensive computational investigation, the present study aimed to reveal mutations that could potentially predispose to colorectal cancer. Ten colorectal cancer exomes were retrieved. Quality control assessments were performed using FastQC and MultiQC, gapped alignment to the human reference genome (hg19) using Bowtie2 and calling the germline variants using Haplotype caller in the GATK pipeline. The variants were filtered and annotated using SIFT and PolyPhen2 successfully categorized the mutations into synonymous, non-synonymous, start loss and stop gain mutations as well as marked them as possibly damaging, probably damaging and benign. This mutational profile helped in shortlisting frequently occurring mutations and associated genes, for which the downstream multi-dimensional expression analyses were carried out. Results: Our work involved prioritizing the non-synonymous, deleterious SNPs since these polymorphisms bring about a functional alteration to the phenotype. The top variations associated with their genes with the highest frequency of occurrence included LGALS8, CTSB, RAD17, CPNE1, OPRM1, SEMA4D, MUC4, PDE4DIP, ELN and ADRA1A. An in-depth multi-dimensional downstream analysis of all these genes in terms of gene expression profiling and analysis and differential gene expression with regard to various cancer types revealed CTSB and CPNE1 as highly expressed and overregulated genes in colorectal cancer. Conclusion: Our work provides insights into the various alterations that might possibly lead to colorectal cancer and suggests the possibility of utilizing the most important genes identified for wet-lab experimentation.

A screw and wire assisted coronoidectomy procedure: A technical note.

Temporomandibular joint (TMJ) ankylosis and oral submucous fibrosis (OSMF) often exhibit elongated hyperplastic coronoid processes with fibrous attachments to the temporalis muscle. In managing this condition, a vital step involves performing a coronoidotomy or coronoidectomy alongside the primary surgical procedure. While coronoidectomy is preferable due to reattachment issues, its complexity arises from the thickened and elongated coronoid process. Our technical note introduces a screw and wire assisted coronoidectomy method, found to be efficient, replicable, and time-saving.

Targeted HBx gene editing by CRISPR/Cas9 system effectively reduces epithelial to mesenchymal transition and HBV replication in hepatoma cells.

BACKGROUND AND AIMS: Hepatitis B virus X protein (HBx) play a key role in pathogenesis of HBV-induced hepatocellular carcinoma (HCC) by promoting epithelial to mesenchymal transition (EMT). In this study, we hypothesized that inhibition of HBx is an effective strategy to combat HCC. METHODOLOGY AND RESULTS: We designed and synthesized novel HBx gene specific single guide RNA (sgRNA) with CRISPR/Cas9 system and studied its in vitro effects on tumour properties of HepG2-2.15. Full length HBx gene was excised using HBx-CRISPR that resulted in significant knockdown of HBx expression in hepatoma cells. HBx-CRISPR also decreased levels of HBsAg and HBV cccDNA expression. A decreased expression of mesenchymal markers, proliferation and tumorigenic properties was observed in HBx-CRISPR treated cells as compared to controls in both two- and three- dimensional (2D and 3D) tumour models. Transcriptomics data showed that out of 1159 differentially expressed genes in HBx-CRISPR transfected cells as compared to controls, 70 genes were upregulated while 1089 genes associated with cell proliferation and EMT pathways were downregulated. CONCLUSION: Thus, targeting of HBx by CRISPR/Cas9 gene editing system reduces covalently closed circular DNA (cccDNA) levels, HBsAg production and mesenchymal characteristics of HBV-HCC cells. We envision inhibition of HBx by CRISPR as a novel therapeutic approach for HBV-induced HCC.

Variability of groundwater fluoride and its proportionate risk quantification via Monte Carlo simulation in rural and urban areas of Agra district, India.

This study quantifies the groundwater fluoride contamination and assesses associated health risks in fluoride-prone areas of the city of Taj Mahal, Agra, India. The United States Environmental Protection Agency (USEPA) risk model and Monte Carlo Simulations were employed for the assessment. Result revealed that, among various rural and urban areas Pachgain Kheda exhibited the highest average fluoride concentration (5.20 mg/L), while Bagda showed the lowest (0.33 mg/L). Similarly, K.K. Nagar recorded 4.38 mg/L, and Dayalbagh had 1.35 mg/L. Both urban and rural areas exceeded the WHO-recommended limit of 1.5 mg/L, signifying significant public health implications. Health risk assessment indicated a notably elevated probability of non-carcinogenic risk from oral groundwater fluoride exposure in the rural Baroli Ahir block. Risk simulations highlighted that children faced the highest health risks, followed by teenagers and adults. Further, Monte Carlo simulation addressed uncertainties, emphasizing escalated risks for for children and teenagers. The Hazard Quotient (HQ) values for the 5th and 95th percentile in rural areas ranged from was 0.28-5.58 for children, 0.15-2.58 for teenager, and 0.05-0.58 for adults. In urban areas, from the range was 0.53 to 5.26 for children, 0.27 to 2.41 for teenagers, and 0.1 to 0.53 for adults. Physiological and exposure variations rendered children and teenagers more susceptible. According to the mathematical model, calculations for the non-cancerous risk of drinking water (HQ-ing), the most significant parameters in all the targeted groups of rural areas were concentration (CW) and Ingestion rate (IR). These findings hold relevance for policymakers and regulatory boards in understanding the actual impact and setting pre-remediation goals.

A geminivirus crosses the monocot-dicot boundary and acts as a viral vector for gene silencing and genome editing.

INTRODUCTION: Members of the family Geminiviridae have been reported to infect either a monocot plant or a dicot plant, but not both. This study reports a geminivirus, Wheat Dwarf India Virus (WDIV), first identified in wheat, that is capable of infecting both monocot and dicot plants and acting as a viral vector. OBJECTIVES: This study was aimed at developing a broad host range viral vector system for reverse genetics and genome editing. METHODS: Here we used a wheat isolate of WDIV and Ageratum yellow leaf curl betasatellite (AYLCB) for infectivity assays and vector development. We performed Agrobacterium-mediated inoculation of WDIV and AYLCB in wheat, oat, barley, corn, soybean, and tobacco. To examine the potential of WDIV to act as a viral vector, we modified the WDIV genome and cloned DNA fragments of the phytoene desaturase (PDS) genes from wheat and tobacco, separately. For gene editing experiments, tobacco lines expressing Cas9 were infiltrated with a WDIV-based vector carrying gRNA targeting the PDS gene. RESULTS: About 80 to 90% of plants inoculated with infectious clones of WDIV alone or WDIV together with AYLCB showed mild symptoms, whereas some plants showed more prominent symptoms. WDIV and AYLCB were detected in the systemically infected leaves of all the plant species. Furthermore, the inoculation of the WDIV vector carrying PDS fragments induced silencing of the PDS gene in both wheat and tobacco plants. We also observed high-efficiency genome editing in the Cas9-expressing tobacco plants that were inoculated with WDIV vector-carrying gRNA. CONCLUSION: Detection of WDIV in naturally infected wheat, barley, and sugarcane in the field and its ability to systemically infect wheat, oat, barley, corn, soybean, and tobacco under laboratory conditions, provides compelling evidence that WDIV is the first geminivirus identified with the capability of infecting both monocot and dicot plant species. The wide host range of WDIV can be exploited for developing a single vector system for high-throughput genome editing in many plant species.

Genetic analysis of iron, zinc and grain yield in wheat-Aegilops derivatives using multi-locus GWAS.

BACKGROUND: Wheat is a major staple crop and helps to reduce worldwide micronutrient deficiency. Investigating the genetics that control the concentrations of iron (Fe) and zinc (Zn) in wheat is crucial. Hence, we undertook a comprehensive study aimed at elucidating the genomic regions linked to the contents of Fe and Zn in the grain. METHODS AND RESULTS: We performed the multi-locus genome-wide association (ML-GWAS) using a panel of 161 wheat-Aegilops substitution and addition lines to dissect the genomic regions controlling grain iron (GFeC), and grain zinc (GZnC) contents. The wheat panel was genotyped using 10,825 high-quality SNPs and phenotyped in three different environments (E1-E3) during 2017-2019. A total of 111 marker-trait associations (MTAs) (at p-value < 0.001) were detected that belong to all three sub-genomes of wheat. The highest number of MTAs were identified for GFeC (58), followed by GZnC (44) and yield (9). Further, six stable MTAs were identified for these three traits and also two pleiotropic MTAs were identified for GFeC and GZnC. A total of 1291 putative candidate genes (CGs) were also identified for all three traits. These CGs encode a diverse set of proteins, including heavy metal-associated (HMA), bZIP family protein, AP2/ERF, and protein previously associated with GFeC, GZnC, and grain yield. CONCLUSIONS: The significant MTAs and CGs pinpointed in this current study are poised to play a pivotal role in enhancing both the nutritional quality and yield of wheat, utilizing marker-assisted selection (MAS) techniques.

Exploring the Synergistic Mechanism of AP2A2 Transcription Factor Inhibition via Molecular Modeling and Simulations as a Novel Computational Approach for Combating Breast Cancer: In Silico Interpretations.

Studies have shown that transcription factor AP2A2 (activator protein-2 alpha-2) is involved in the expression of DLEC1, a tumor suppressor gene, which, when mutated, will cause breast cancer and is thus an excellent target for breast cancer studies. Therefore, in the present research, a synergistic approach toward combating breast cancer is proposed by blocking AP2A2 factor, and allowing the cancer cells to be sensitive to anti-cancer drugs. The effect of AP2A2 on breast cancer was first understood via gene analysis from cBioPortal. AP2A2 was then modeled using RaptorX and its structure was validated from Ramachandran plots. Using all ligands from MolPort database, molecular docking was performed against AP2A2, from which the top three best docked ligands were studied for toxicity in humans using Protox-II. Once the ligands passed these tests, the best complexes were simulated at 200ns in Desmond Maestro, to comprehend their stabilities, followed by the computations of free energies of binding via Molecular mechanics- Generalized Born Solvent Accessibility method (MM-GBSA). The results showed that molecules MolPort-005-945-556 (sachharolipids), MolPort-001-741-124 (flavonoids), and MolPort-005-944-667 (lignan glycosides) with AP2A2 passed toxicity evaluation and belonged to toxicity classes 6, 5, and 5, respectively, with good docking energies. 200 ns simulations revealed stable complexes with slight conformational changes. Stability of ligands was confirmed via snapshots at every 20 ns of the trajectory. Radial distribution of these molecules against the protein revealed very slight deviation from binding pocket. Additionally, the free binding energies for these complexes were found to be - 54.93 ± 12.982 kcal/mol, - 44.39 ± 14.393 kcal/mol, and - 66.51 ± 13.522 kcal/mol, respectively. A preliminary computational validation of the inability of AP2A2 to bind to DLEC1 in the presence of ligands offers beneficial insights into the potential of these ligands. Therefore, this study sheds light on the potential natural molecules that could stably block AP2A2 with least deviation and act in synergy to aid anti-cancer drugs work on breast cancer cells.

Design of Novel Imidazopyrazine Derivative against Breast Cancer via Targeted NPY1R Antagonist.

INTRODUCTION: Breast cancer is the most frequent malignancy in women with more than one in ten new cancer diagnoses each year. Synthetic products are a key source for the identification of new anticancer medicines and drug leads. OBJECTIVES: Imidazopyrazine is a highly favored skeleton for the design of new anticancer drugs. In silico designed derivatives were screened using computer aided drug design techniques and validated using MTT assay. METHODS: A template-based methodology was used in the current work to create novel Imidazopyrazine derivatives, targeting the NPY1R protein. Molecular docking, Diffusion docking, MD simulation, MM-GBSA and meta-dynamics techniques were followed. MTT assay was performed to validate the activity of principal compound. RESULTS: A docking score of -6.660 and MMGBSA value of -108.008 (+/-) 9.14 kcal/mol was obtained from the investigations conducted. In addition, molecular dynamics simulation was carried out for 500 ns, yielding a stable RMSD and value of 5.6 Å, thus providing insights on the stability of the protein conformation on interaction with the principal compound. Furthermore, the in vivo validation studies conducted via MTT assay showed an IC50 value of 73.45 (+/-) 0.45 µg /mL. CONCLUSION: The research has produced encouraging findings and can be applied as a model for precise enumerations in the future. It also encourages the study of novel synthetic compounds with potential anti-cancer properties.

Effective utilization of discarded reverse osmosis post-carbon for adsorption of dyes from wastewater.

In this study, the deployment of post Reverse Osmosis (RO)-carbon as a adsorbent for dye removal from water has been investigated. The post RO-carbon was thermally activated (RO900), and the material thus obtained exhibited high surface area viz. 753 m2/g. In the batch system, the efficient Methylene Blue (MB) and Methyl Orange (MO) removal was obtained by using 0.08 g and 0.13 g/50 mL adsorbent dosage respectively. Moreover, 420 min was the optimized equilibration time for both the dyes. The maximum adsorption capacities of RO900 for MB and MO dyes were 223.29 and 158.14 mg/g, respectively. The comparatively higher MB adsorption was attributed to the electrostatic attraction between adsorbent and MB. The thermodynamic findings revealed the process as spontaneous, endothermic, and accompanied by entropy increment. Additionally, simulated effluent was treated, and >99% dye removal efficiency was achieved. To mimic an industrial perspective, MB adsorption onto RO900 was also carried out in continuous mode. The initial dye concentration and effluent flow rate were among the process parameters that were optimized using the continuous mode of operation. Further, the experimental data of continuous mode was fitted with Clark, Yan, and Yoon-Nelson models. Py-GC/MS investigation revealed that dye-loaded adsorbents could be pyrolyzed to produce valuable chemicals. The cost and low toxicity associated benefits of discarded RO-carbon over other adsorbents reveal the significance of the present study.

Chronic Hepatitis B Infection: Current and Emerging Therapeutic Strategies.

The chronic infection of the hepatitis B virus (CHB) represents a major public health problem worldwide. Despite the availability of an effective prophylactic vaccine, millions of hepatitis B patients are at increased risk of developing chronic liver disease. The currently available treatments for HBV infection include interferon and nucleos(t)ide analogues that are effective at suppressing viral load and preventing or delaying the progression of liver disease. However, these treatments offer somewhat unsatisfactory clinical cures due to the persistence of the intrahepatic pool of covalently closed circular DNA (cccDNA) that serves as a reservoir for viral progenies and a potential source of recurring infections. Elimination of viral cccDNA remains a challenge for scientists and pharmaceutical industries in order to achieve the eradication and control of HBV infection. This would involve a detailed understanding of the molecular mechanisms of cccDNA formation, its intracellular stability, and regulation during replication and transcription. Recent advances in drug therapy have heralded a new horizon of novel therapeutic approaches for CHB infection, with several promising antiviral and immunomodulatory agents currently in preclinical or clinical testing. However, approval of any new curative therapy would involve rigorous evaluation of the efficacy and safety of each treatment and defining correct endpoints associated with improved clinical outcomes. This article summarizes the current landscape of HBV treatments, and drugs in clinical trials and highlights the most recent anti-HBV small molecules designed to directly target HBV or to improve immune response during chronic infection.

Hepatopulmonary syndrome is associated with low sphingosine-1-phosphate levels and can be ameliorated by the functional agonist fingolimod.

BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS) is characterised by a defect in arterial oxygenation induced by pulmonary vascular dilatation in patients with liver disease. Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, suppresses vasodilation by reducing nitric oxide (NO) production. We investigated the role of S1P in patients with HPS and the role of fingolimod as a therapeutic option in an experimental model of HPS. METHODS: Patients with cirrhosis with HPS (n = 44) and without HPS (n = 89) and 25 healthy controls were studied. Plasma levels of S1P, NO, and markers of systemic inflammation were studied. In a murine model of common bile duct ligation (CBDL), variations in pulmonary vasculature, arterial oxygenation, liver fibrosis, and inflammation were estimated before and after administration of S1P and fingolimod. RESULTS: Log of plasma S1P levels was significantly lower in patients with HPS than in those without HPS (3.1 ± 1.4 vs. 4.6 ± 0.2; p <0.001) and more so in severe intrapulmonary shunting than in mild and moderate intrapulmonary shunting (p <0.001). Plasma tumour necrosis factor-α (76.5 [30.3-91.6] vs. 52.9 [25.2-82.8]; p = 0.02) and NO (152.9 ± 41.2 vs. 79.2 ± 29.2; p = 0.001) levels were higher in patients with HPS than in those without HPS. An increase in Th17 (p <0.001) and T regulatory cells (p <0.001) was observed; the latter inversely correlated with plasma S1P levels. In the CBDL HPS model, fingolimod restored pulmonary vascular injury by increasing the arterial blood gas exchange and reducing systemic and pulmonary inflammation, resulting in improved survival (p = 0.02). Compared with vehicle treatment, fingolimod reduced portal pressure (p <0.05) and hepatic fibrosis and improved hepatocyte proliferation. It also induced apoptotic death in hepatic stellate cells and reduced collagen formation. CONCLUSIONS: Plasma S1P levels are low in patients with HPS and even more so in severe cases. Fingolimod, by improving pulmonary vascular tone and oxygenation, improves survival in a murine CBDL HPS model. IMPACT AND IMPLICATIONS: A low level of plasma sphingosine-1-phosphate (S1P) is associated with severe pulmonary vascular shunting, and hence, it can serve as a marker of disease severity in patients with hepatopulmonary syndrome (HPS). Fingolimod, a functional agonist of S1P, reduces hepatic inflammation, improves vascular tone, and thus retards the progression of fibrosis in a preclinical animal model of HPS. Fingolimod is being proposed as a potential novel therapy for management of patients with HPS.

Eco-Oriented Formulation and Stabilization of Oil-Colloidal Biodelivery Systems Based on GC-MS/MS-Profiled Phytochemicals from Wild Tomato for Long-Term Retention and Penetration on Applied Surfaces for Effective Crop Protection.

Vegetable oils as hydrophobic reserves in oil dispersions (OD) provide a practical approach to halt bioactive degradation for user and environment-efficient pest management. Using biodegradable soybean oil (57%), castor oil ethoxylate (5%), calcium dodecyl benzenesulfonates as nonionic and an-ionic surfactants, bentonite (2%), and fumed silica as rheology modifiers, we created an oil-colloidal biodelivery sytem (30%) of tomato extract with homogenization. The quality-influencing parameters, such as particle size (4.5 µm), dispersibility (97%), viscosity (61 cps), and thermal stability (2 years), have been optimized in accordance with specifications. Vegetable oil was chosen for its improved bioactive stability, high smoke point (257 °C), coformulant compatibility, and as a green build-in-adjuvant by improving spreadability (20-30%), retention and penetration (20-40%). In in vitro testing, it efficiently controlled aphids with 90.5% mortalities and 68.7-71.2% under field-conditions without producing phytotoxicity. Wild tomato-derived phytochemicals can be a safe and efficient alternative to chemical pesticides when combined wisely with vegetable oils.

Discovery of allosteric SHP2 inhibitors through ensemble-based consensus molecular docking, endpoint and absolute binding free energy calculations.

SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase-2) is a cytoplasmic protein -tyrosine phosphatase encoded by the gene PTPN11. It plays a crucial role in regulating cell growth and differentiation. Specifically, SHP2 is an oncoprotein associated with developmental pathologies and several different cancer types, including gastric, leukemia and breast cancer and is of great therapeutic interest. Given these roles, current research efforts have focused on developing SHP2 inhibitors. Allosteric SHP2 inhibitors have been shown to be more selective and pharmacologically appealing compared to competitive catalytic inhibitors targeting SHP2. Nevertheless, there remains a need for novel allosteric inhibitor scaffolds targeting SHP2 to develop compounds with improved selectivity, cell permeability, and bioavailability. Towards this goal, this study applied various computational tools to screen over 6 million compounds against the allosteric site within SHP2. The top-ranked hits from our in-silico screening were validated using protein thermal shift and biolayer interferometry assays, revealing three potent compounds. Kinetic binding assays were employed to measure the binding affinities of the top-ranked compounds and demonstrated that they all bind to SHP2 with a nanomolar affinity. Hence the compounds and the computational workflow described herein provide an effective approach for identifying and designing a generation of improved allosteric inhibitors of SHP2.

Implementation of ensemble machine learning algorithms on exome datasets for predicting early diagnosis of cancers.

Classification of different cancer types is an essential step in designing a decision support model for early cancer predictions. Using various machine learning (ML) techniques with ensemble learning is one such method used for classifications. In the present study, various ML algorithms were explored on twenty exome datasets, belonging to 5 cancer types. Initially, a data clean-up was carried out on 4181 variants of cancer with 88 features, and a derivative dataset was obtained using natural language processing and probabilistic distribution. An exploratory dataset analysis using principal component analysis was then performed in 1 and 2D axes to reduce the high-dimensionality of the data. To significantly reduce the imbalance in the derivative dataset, oversampling was carried out using SMOTE. Further, classification algorithms such as K-nearest neighbour and support vector machine were used initially on the oversampled dataset. A 4-layer artificial neural network model with 1D batch normalization was also designed to improve the model accuracy. Ensemble ML techniques such as bagging along with using KNN, SVM and MLPs as base classifiers to improve the weighted average performance metrics of the model. However, due to small sample size, model improvement was challenging. Therefore, a novel method to augment the sample size using generative adversarial network (GAN) and triplet based variational auto encoder (TVAE) was employed that reconstructed the features and labels generating the data. The results showed that from initial scrutiny, KNN showed a weighted average of 0.74 and SVM 0.76. Oversampling ensured that the accuracy of the derivative dataset improved significantly and the ensemble classifier augmented the accuracy to 82.91%, when the data was divided into 70:15:15 ratio (training, test and holdout datasets). The overall evaluation metric value when GAN and TVAE increased the sample size was found to be 0.92 with an overall comparison model of 0.66. Therefore, the present study designed an effective model for classifying cancers which when implemented to real world samples, will play a major role in early cancer diagnosis.

Whole genome re-sequencing of indian wheat genotypes for identification of genomic variants for grain iron and zinc content.

BACKGROUND: Whole-genome sequencing information which is of abundant significance for genetic evolution, and breeding of crops. Wheat (Triticum spp) is most widely grown and consumed crops globally. Micronutrients are very essential for healthy development of human being and their sufficient consumption in diet is essential for various metabolic functions. Biofortification of wheat grains with iron (Fe) and zinc (Zn) has proved the most reliable and effective way to combat micronutrient associated deficiency. Genetic variability for grain micronutrient could provide insight to dissect the traits. METHODS AND RESULTS: In the current study, 1300 wheat lines were screened for grain Fe and Zn content, out of which only five important Indian wheat genotypes were selected on the basis of Fe and Zn contents. These lines were multiplied during at the National Agri-Food Biotechnology Institute (NABI) and re-sequenced to identify genomic variants in candidate genes for Fe and Zn between the genotypes. Whole genome sequencing generated Ì´ 12 Gb clean data. Comparative genome analysis identified 254 genomic variants in the candidate genes associated with deleterious effect on protein function. CONCLUSIONS: The present study demonstrated the fundamental in understanding the genomic variations for Fe and Zn enrichment to generate healthier wheat grains.

Mitochondria-Targeted, Nanoparticle-Based Drug-Delivery Systems: Therapeutics for Mitochondrial Disorders.

Apart from ATP generation, mitochondria are involved in a wide range of functions, making them one of the most prominent organelles of the human cell. Mitochondrial dysfunction is involved in the pathophysiology of several diseases, such as cancer, neurodegenerative diseases, cardiovascular diseases, and metabolic disorders. This makes it a target for a variety of therapeutics for the diagnosis and treatment of these diseases. The use of nanoparticles to target mitochondria has significant importance in modern times because they provide promising ways to deliver drug payloads to the mitochondria by overcoming challenges, such as low solubility and poor bioavailability, and also resolve the issues of the poor biodistribution of drugs and pharmacokinetics with increased specificity. This review assesses nanoparticle-based drug-delivery systems, such as liposomes, DQAsome, MITO-Porters, micelles, polymeric and metal nanocarriers, as well as quantum dots, as mitochondria-targeted strategies and discusses them as a treatment for mitochondrial disorders.

Managing arsenic (V) toxicity by phosphate supplementation in rice seedlings: modulations in AsA-GSH cycle and other antioxidant enzymes.

The toxic and non-essential metalloid arsenic (As) is ubiquitous in the environment with its absorption from the soil into the plants' roots posing detrimental effects on the crop plants and hence the food availability and food security are also threatened. The present study was intended to reduce the As-induced toxicity in rice seedlings (Oryza sativa L.) by phosphate (PO43-). For this, three concentrations of potassium phosphate (KH2PO4), 50, 100 and 150 µM were supplemented along with 50 µM As exposure to hydroponically grown 7-day-old rice seedlings. Supplementation of PO43- significantly recovered arsenic-induced diminutions in growth parameters and photosynthetic pigment contents which were due to the significant increase in superoxide radical (SOR, O2•¯) and hydrogen peroxide (H2O2). Supplementation of 50 µM PO43- could significantly increase the activity of APX (ascorbate peroxidase) and GR (glutathione reductase) while 100 µM PO43- could increase the activity of DHAR (dehydroascorbate reductase) and monodehydroascorbate reductase (MDHAR). As the amount of PO43- was increased, the ratio of AsA/DHA (reduced to oxidized ascorbate) and GSH/GSSG (reduced to oxidized glutathione) was increased significantly due to increase in the reduced form of the non-enzymes i.e. AsA and GSH. The activity of SOD (superoxide dismutase) and GPX (guaiacol peroxidase) decreased significantly after a substantive increase in their activities due to As stress while the CAT (catalase) activity further enhanced after the supplementation of 50 and 100 µM PO43-. Thus, the As-induced oxidative stress in the rice seedlings was managed by concerted modulations in the activities of SOD, GPX, CAT and AsA-GSH cycle enzymes and metabolites.

Design of Novel Coumarin Derivatives as NUDT5 Antagonists That Act by Restricting ATP Synthesis in Breast Cancer Cells.

Breast cancer, a heterogeneous disease, is among the most frequently diagnosed diseases and is the second leading cause of death due to cancer among women after lung cancer. Phytoactives (plant-based derivatives) and their derivatives are safer than synthetic compounds in combating chemoresistance. In the current work, a template-based design of the coumarin derivative was designed to target the ADP-sugar pyrophosphatase protein. The novel coumarin derivative (2R)-2-((S)-sec-butyl)-5-oxo-4-(2-oxochroman-4-yl)-2,5-dihydro-1H-pyrrol-3-olate was designed. Molecular docking studies provided a docking score of -6.574 kcal/mol and an MM-GBSA value of -29.15 kcal/mol. Molecular dynamics simulation studies were carried out for 500 ns, providing better insights into the interaction. An RMSD change of 2.4 Å proved that there was a stable interaction and that there was no conformational change induced to the receptor. Metadynamics studies were performed to calculate the unbinding energy of the principal compound with NUDT5, which was found to be -75.171 kcal/mol. In vitro validation via a cytotoxicity assay (MTT assay) of the principal compound was carried out with quercetin as a positive control in the MCF7 cell line and with an IC50 value of 55.57 (+/-) 0.7 µg/mL. This work promoted the research of novel natural derivatives to discover their anticancer activity.