Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 in head and neck cancer.

Dynamic interactions within the tumor micro-environment drive patient response to immune checkpoint inhibitors. Existing preclinical models lack true representation of this complexity. Using a Head and Neck cancer patient derived TruTumor histoculture platform, the response spectrum of 70 patients to anti-PD1 treatment is investigated in this study. With a subset of 55 patient samples, multiple assays to characterize T-cell reinvigoration and tumor cytotoxicity are performed. Based on levels of these two response parameters, patients are stratified into five sub-cohorts, with the best responder and non-responder sub-cohorts falling at extreme ends of the spectrum. The responder sub-cohort exhibits high T-cell reinvigoration, high tumor cytotoxicity with T-cells homing into the tumor upon treatment whereas immune suppression and tumor progression pathways are pre-dominant in the non-responders. Some moderate responders benefit from combination of anti-CTLA4 with anti-PD1, which is evident from better cytotoxic T-cell: T-regulatory cell ratio and enhancement of tumor cytotoxicity. Baseline and on-treatment gene expression signatures from this study stratify responders and non-responders in unrelated clinical datasets.

1,3,4-Oxadiazoles as Anticancer Agents: A Review.

Among the deadliest diseases, cancer is characterized by tumors or an increased number of a specific type of cell because of uncontrolled divisions during mitosis. Researchers in the current era concentrated on the development of highly selective anticancer medications due to the substantial toxicities of conventional cytotoxic drugs. Several marketed drug molecules have provided resistance against cancer through interaction with certain targets/growth factors/enzymes, such as Telomerase, Histone Deacetylase (HDAC), Methionine Aminopeptidase (MetAP II), Thymidylate Synthase (TS), Glycogen Synthase Kinase-3 (GSK), Epidermal Growth Factor (EGF), Vascular Endothelial Growth Factor (VEGF), Focal Adhesion Kinase (FAK), STAT3, Thymidine phosphorylase, and Alkaline phosphatase. The molecular structure of these drug molecules contains various heterocyclic moieties that act as pharmacophores. Recently, 1,3,4- oxadiazole (five-membered heterocyclic moiety) and its derivatives attracted researchers as these have been reported with a wide range of pharmacological activities, including anti-cancer. 1,3,4- oxadiazoles have exhibited anti-cancer potential via acting on any of the above targets. The presented study highlights the synthesis of anti-cancer 1,3,4-oxadiazoles, their mechanism of interactions with targets, along with structure-activity relationship concerning anti-cancer potential.

Synthetic approaches and applications of an underprivileged 1,2,5-oxadiazole moiety: A review.

1,2,5-oxadiazole belongs to five-membered heterocyclic compounds with two nitrogen and one oxygen atom. In comparison with other heterocyclic moieties, 1,2,5-oxadiazoles moiety is considered as underprivileged as it attracted little attention of the researchers although lot of scopes and possible applications in medicinal, material and agriculture science. 1,2,5-oxadiazole and its derivatives have been reported as good pharmacophores as carbonic anhydrase inhibitors, antibacterial, vasodilating agents, antimalarial, anticancer, etc. In the presented manuscript, we reviewed granted patents and different synthetic strategies which have been reported for the synthesis of 1,2,5-oxadiazoles such as cycloaddition, dimerization, cyclodehydration, condensation, thermolysis, nitration, oxidation and ring-conversion. These synthetic methods have also been analysed for their merits and demerits. The manuscript also highlighted various applications of 1,2,5-oxadiazole and its derivatives. We hope that researchers across the scientific streams will be benefitted from the presented review articles for designing their work related to 1,2,5-oxadiazoles.

Nanotechnology-enabled biofortification strategies for micronutrients enrichment of food crops: Current understanding and future scope.

Nutrient deficiency in food crops severely compromises human health, particularly in under privileged communities. Globally, billions of people, particularly in developing nations, have limited access to nutritional supplements and fortified foods, subsequently suffering from micronutrient deficiency leading to a range of health issues. The green revolution enhanced crop production and provided food to billions of people but often falls short with respect to the nutritional quality of that food. Plants may assimilate nutrients from synthetic chemical fertilizers, but this approach generally has low nutrient delivery and use efficiency. Further, the overexposure of chemical fertilizers may increase the risk of neoplastic diseases, render food crops unfit for consumption and cause environmental degradation. Therefore, to address these challenges, more research is needed for sustainable crop yield and quality enhancement with minimum use of chemical fertilizers. Complex nutritional disorders and 'hidden hunger' can be addressed through biofortification of food crops. Nanotechnology may help to improve food quality via biofortification as plants may readily acquire nanoparticle-based nutrients. Nanofertilizers are target specific, possess controlled release, and can be retained for relatively long time periods, thus prevent leaching or run-off from soil. This review evaluates the recent literature on the development and use of nanofertilizers, their effects on the environment, and benefits to food quality. Further, the review highlights the potential of nanomaterials on plant genetics in biofortification, as well as issues of affordability, sustainability, and toxicity.

Effects of water deficit stress on agronomic and physiological responses of rice and greenhouse gas emission from rice soil under elevated atmospheric CO2.

Rice is the foremost staple food in the world, safeguarding the global food and nutritional security. Rise in atmospheric carbon dioxide (CO2) and water deficits are threatening global rice productivity and sustainability. Under real field conditions these climatic factors often interact with each other resulting in impacts that are remarkably different compared to individual factor exposure. Rice soils exposed to drought and elevated CO2 (eCO2) alters the biomass, diversity and activity of soil microorganisms affecting greenhouse gas (GHG) emission dynamics. In this review we have discussed the impacts of eCO2 and water deficit on agronomic, biochemical and physiological responses of rice and GHGs emissions from rice soils. Drought usually results in oxidative stress due to stomatal closure, dry weight reduction, formation of reactive oxygen species, decrease in relative water content and increase in electrolyte leakage at almost all growth and developmental phases of rice. Elevated atmospheric CO2 concentration reduces the negative effects of drought by improving plant water relations, reducing stomatal opening, decreasing transpiration, increasing canopy photosynthesis, shortening crop growth period and increasing the antioxidant metabolite activities in rice. Increased scientific understanding of the effects of drought and eCO2 on rice agronomy, physiology and GHG emission dynamics of rice soil is essential for devising adaptation options. Integration of novel agronomic practices viz., crop establishment methods and alternate cropping systems with improved water and nutrient management are important steps to help rice farmers cope with drought and eCO2. The review summarizes future research needs for ensuring sustained global food security under future warmer, drier and high CO2 conditions.

Identification, expression analysis, and molecular modeling of Iron-deficiency-specific clone 3 (Ids3)-like gene in hexaploid wheat.

Graminaceous plants secrete hydroxylated phytosiderophores encoded by the genes iron-deficiency-specific clone 2 (Ids2) and iron-deficiency-specific clone 3 (Ids3). An effort was made to identify a putative ortholog of Hodeum vulgare Ids3 gene in hexaploid wheat. The protein structure of TaIDS3 was modeled using homology modeling and structural behavior of modeled structure was analyzed at 20 ns. The simulation trajectory using molecular dynamics simulation suggested the model to be stable with no large fluctuations in residues and local domain level RMSF values (< 2.4 Å). In addition, the ProFunc results also predict the functional similarity between the proteins of HvIDS3 and its wheat ortholog (TaIDS3). The TaIds3 gene was assigned to the telomeric region of chromosome arm 7AS which supports the results obtained through bioinformatics analysis. The relative expression analysis of TaIds3 indicated that the detectable expression of TaIds3 is induced after 5th day of Fe starvation and increases gradually up to 15th day, and thereafter, it decreases until 35th day of Fe-starvation. This reflects that Fe deficiency directly regulates the induction of TaIds3 in the roots of hexaploid wheat. The identification of HvIds3-like gene in wheat has opened up new opportunities to enhance the nutrient quality in wheat through biofortification program.

Sorption of cadmium from aqueous solution using pretreated rice husk.

The sorption of Cd(II) from aqueous solution by rice husk, a surplus agricultural byproduct was investigated. Some simple and low-cost chemical modifications resulted in increasing the sorption capacity of raw rice husk (RRH) from 8.58 mg/g to 11.12, 20.24, 16.18 mg/g and reducing the equilibrium time from 10 h of RRH to 2, 4 and 1 h for epichlorohydrin treated rice husk (ERH), NaOH treated rice husk (NRH), sodium bicarbonate treated rice husk (NCRH), respectively. The effect of pH, sorption kinetics and isotherms were studied in batch experiments. Good correlation coefficient was obtained for pseudo second-order kinetic model, which agreed with chemisorption as the rate-limiting mechanism. Sorption isotherm test showed that equilibrium sorption data were better represented by Langmuir model than the Freundlich model. The highly efficient low cost and the rapid uptake of Cd(II) by NCRH indicated that it could be an excellent alternative for the removal of heavy metal by sorption process.