Deciphering Physio-Biochemical Basis of Tolerance Mechanism for Sesame (Sesamum indicum L.) Genotypes under Waterlogging Stress at Early Vegetative Stage.

Waterlogging represents a substantial agricultural concern, inducing harmful impacts on crop development and productivity. In the present study, 142 diverse sesame genotypes were examined during the early vegetative phase to assess their response under waterlogging conditions. Based on the severity of symptoms observed, 2 genotypes were classified as highly tolerant, 66 as moderately tolerant, 69 as susceptible, and 5 as highly susceptible. Subsequent investigation focused on four genotypes, i.e., two highly tolerant (JLT-8 and GP-70) and two highly susceptible (R-III-F6 and EC-335003). These genotypes were subjected to incremental stress periods (0 h, 24 h, 48 h, 72 h, and 96 h) to elucidate the biochemical basis of tolerance mechanisms. Each experiment was conducted as a randomized split-plot design with three replications, and the statistical significance of the treatment differences was determined using the one-way analysis of variance (ANOVA) followed by the Fisher least significant difference (LSD) test at p ≤ 0.05. The influence of waterlogging stress on morphological growth was detrimental for both tolerant and susceptible genotypes, with more severe consequences observed in the latter. Although adventitious roots were observed in both sets of genotypes above flooding levels, the tolerant genotypes exhibited a more rapid and vigorous development of these roots after 48 h of stress exposure. Tolerant genotypes displayed higher tolerance coefficients compared to susceptible genotypes. Furthermore, tolerant genotypes maintained elevated antioxidant potential, thereby minimizing oxidative stress. Conversely, susceptible genotypes exhibited higher accumulation of hydrogen peroxide (H2O2) and malondialdehyde content. Photosynthetic efficiency was reduced in all genotypes after 24 h of stress treatment, with a particularly drastic reduction in susceptible genotypes compared to their tolerant counterparts. Tolerant genotypes exhibited significantly higher activities of anaerobic metabolism enzymes, enabling prolonged survival under waterlogging conditions. Increase in proline content was observed in all the genotypes indicating the cellular osmotic balance adjustments in response to stress exposure. Consequently, the robust antioxidant potential and efficient anaerobic metabolism observed in the tolerant genotypes served as key mechanisms enabling their resilience to short-term waterlogging exposure. These findings underscore the promising potential of specific sesame genotypes in enhancing crop resilience against waterlogging stress, offering valuable insights for agricultural practices and breeding programs.

Directional molecular transport in iron redox flow batteries by interfacial electrostatic forces.

The mounting global energy demand urges surplus electricity generation. Due to dwindling fossil resources and environmental concerns, shifting from carbon-based fuels to renewables is vital. Though renewables are affordable, their intermittent nature poses supply challenges. In these contexts, aqueous flow batteries (AFBs), are a viable energy storage solution. This study tackles AFBs' energy density and efficiency challenges. Conventional strategies focus on altering molecule's solubility but overlook interface's transport kinetics. We show that triggering electrostatic forces at the interface can significantly enhance the mass transport kinetics of redox active molecules by introducing a powerful electrostatic flux over the diffusional flux, thereby exerting a precise directionality on the molecular transport. This approach of controlling the directionality of molecular flux in an all iron redox flow battery amplifies the current and power rating with approximately 140 % enhancement in the energy density.

Virtual screening of acetylcholinesterase inhibitors through pharmacophore-based 3D-QSAR modeling, ADMET, molecular docking, and MD simulation studies.

Alzheimer's disease (AD) is a leading cause of dementia in elderly patients. The pathophysiology of AD includes various pathways, such as the degradation of acetylcholine, amyloid-beta deposition, neurofibrillary tangle formation, and neuroinflammation. Many studies showed that targeting acetylcholinesterase enzyme (AChE) to improve acetylcholine can be an effective option to treat AD. In the current work, we employed a 3D QSAR-based approach to generate a pharmacophore to screen a chemical library of compounds that may inhibit AChE. Data from experimental studies were collected and used for the generation of pharmacophores. More than 1 million compounds were screened, and further drug-like properties were determined via in-silico ADMET studies. Techniques like molecular docking and molecular dynamics simulation were performed to analyze the binding of novel AChE inhibitors. A novel AChE inhibitor ligand-1 was identified as best with a docking score of -13.560 kcal/mol with RMSD of 1.71 Å during a 100 ns MD run. Further biological studies can give an insight into the potential of ligand-1 as a therapeutic agent for AD. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00189-1.

Analysis of Auxin-Encoding Gene Family in Vigna radiata and It's Cross-Species Expression Modulating Waterlogging Tolerance in Wild Vigna umbellata.

Mungbean is known to be susceptible to waterlogging (WL) stress. Some of the wild species have the potential to tolerate this through various physiological and molecular mechanisms. Auxin Response Factor (ARF) and Auxin/Indole Acetic Acid (AUX/IAA), an early responsive gene family, has multiple functions in growth, development, and stress tolerance. Here, we report the first comprehensive analysis of the ARF and AUX/IAA gene family in mungbean. A total of 26 ARF and 19 AUX/IAA genes were identified from the mungbean genome. The ARF and AUX/IAA candidates were clearly grouped into two major clades. Further, the subgrouping within the major clades indicated the presence of significant diversity. The gene structure, motif analysis, and protein characterization provided the clue for further fundamental research. Out of the10 selected candidate genes, VrARF-5, VrARF-11, VrARF-25, and VrAUX/IAA-9 were found to significantly multiple-fold gene expression in the hypocotyl region of WL-tolerant wild relatives (PRR 2008-2) provides new insight into a role in the induction of lateral root formation under WL stress. The analysis provides an insight into the structural diversity of ARF and AUX/IAA genes in mungbean. These results increase our understanding of ARF and AUX/IAA genes and therefore offer robust information for functional investigations, which can be taken up in the future and will form a foundation for improving tolerance against waterlogging stress.

Fisetin-Loaded Nanostructured Lipid Carriers: Formulation and Evaluations against Advanced and Metastatic Melanoma.

Fisetin (Fis), a natural flavonoid with anticancer effects, suffers from delivery constraints. Fisetin-nanostructured lipid carriers (NLCs) were developed for better efficacy against metastatic melanoma, employing the design of experiment (DoE) approach. The optimized NLCs depict a particle diameter of 135.0 ± 5.5 nm, a polydispersity index (PDI) of 0.176 ± 0.035, and an entrapment efficiency of 78.16 ± 1.58%. The formulation was stable over a period of 60 days and demonstrated sustained release of the drug (74.79 ± 3.75%) over 96 h. Fis-NLCs depicted at least ∼3.2 times lower IC50 value and ∼1.8 times higher drug uptake at 48 h in A-375 and B16F10 cells compared to that of Fis. It also inhibited the mobility of melanoma cells and induced cell cycle arrest at the G1/S phase. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot results show enhanced expression of Nrf2/NQO1 genes and an apoptotic effect by the upregulation of BAX mRNA expression. The protein levels of BAX and p53 were ∼2-fold higher compared with that of pure Fis. In-vivo studies demonstrated 5.9- and 10.7-fold higher inhibition in melanoma-associated metastasis in the lungs and liver, respectively. The outcomes from this study demonstrated Fis-NLCs as an effective tool against melanoma.

The multifaceted role of extracellular vesicles in prostate cancer-a review.

Prostate cancer is the second most prominent form of cancer in men and confers the highest mortality after lung cancer. The term "extracellular vesicles" refers to minute endosomal-derived membrane microvesicles and it was demonstrated that extracellular vesicles affect the environment in which tumors originate. Extracellular vesicles' involvement is also established in the development of drug resistance, angiogenesis, stemness, and radioresistance in various cancers including prostate cancer. Extracellular vesicles influence the general environment, processes, and growth of prostate cancer and can be a potential area that offers a significant lead in prostate cancer therapy. In this review, we have elaborated on the multifaceted role of extracellular vesicles in various processes involved in the development of prostate cancer, and their multitude of applications in the diagnosis and treatment of prostate cancer through the encapsulation of various bioactives.

Investigating the impact of terminal heat stress on contrasting wheat cultivars: a comprehensive analysis of phenological, physiological, and biochemical traits.

Terminal heat stress has become one of the major threats due to global climate change which is significantly affecting the production and productivity of wheat crop. Therefore, it is necessary to identify key traits and genotypes to breed heat-tolerant wheat. The present study was undertaken with the objective of comparing the effects of heat stress (HSE) and extended heat stress (EHSE) on phenological-physio-biochemical traits of contrasting heat-tolerant and heat-susceptible genotypes during the reproductive phase. Phenological traits exhibited significant reduction under EHSE compared to HSE. Heat-tolerant genotypes maintained balanced phenological-physio-biochemical traits, while heat-sensitive genotypes showed significant reductions under both stress regimes. Among phenological traits, DM (R2 = 0.52) and BY (R2 = 0.44) have shown a positive effect on seed yield, indicating that biomass and crop duration contributed to the yield advantage under stress. During the grain filling stage, both the normalized difference vegetation index (NDVI) and chlorophyll (Chl) exhibited consistently positive impacts on grain yield under both HSE and EHSE conditions. This could be attributed to the enhanced photosynthesis resulting from delayed senescence and improved assimilate remobilization under terminal heat stress. The biochemical activity of superoxide dismutase (SOD), peroxidase (POX), and ascorbate peroxidase (APX) was induced in tolerant genotypes under HSE. The correlation of canopy temperature with phenological-physio-biochemical traits remained static under HSE and EHSE, suggesting CT as the best selection parameter for heat tolerance. The traits showing a positive association with yield and that are less affected under stress could be used for selecting tolerant genotypes under stress environments. These tolerant genotypes can be used to develop mapping populations to decipher the genes conferring tolerance as well as to study the molecular basis of tolerance.

A Concise Review on Natural Products and Their Derivatives for Breast Cancer Treatment.

Cancer is a leading cause of death worldwide. Among other cancers, breast cancer has been found to produce maximum number of cases in 2020. Different factors including geographical, genetic, hormonal, oral contraceptives and modern lifestyle could be responsible for the development of breast cancer and different pathways can be targeted for breast cancer treatment. The various conventional approaches used for the treatment of breast cancer including radiotherapy, chemotherapy, hormone and immunotherapy. But due to the side effects associated with these conventional treatments such as non-selectivity, multidrug resistance and bioavailability, there is a need for the development of better therapeutic agents for breast cancer treatment. Several natural products have been explored for breast cancer treatment. However, many of these natural products suffered from the limitations of poor water solubility and possess toxic side effects. To overcome these limitations, several structural analogs of natural products have been synthesized and possess potent anti-breast cancer effects with less side effects over their precursor molecules. In the present manuscript, we describe the pathogenesis of breast cancer, some potent natural products used in the treatment of breast cancer and their selected structural analogs possessing potent anti-breast cancer effects. Database such as Science direct, Pubmed and Google scholar were searched using keywords 'risk factors', 'screening methods','receptors', and 'natural products and derivatives', Registered clinical trials on selected natural products were also analyzed. Present study concludes that eight selected natural products and their derivatives possess wide potential to exhibit anti-breast cancer effects and could be explored further to develop better chemotherapeutic agents against breast cancer.

F3 peptide functionalized liquid crystalline nanoparticles for delivering Salinomycin against breast cancer.

Salinomycin (Sal) is a potent veterinary antibiotic known to offer significant toxicity to the variety of neoplastic cells. Its therapeutic utility is limited due to its higher lipophilicity (logP 7.5) and poor hydrophilicity. Liquid crystalline nanoparticles (LCNPs) known to offer a suitable delivery platform for these kinds of drugs. The overexpressed nucleolin receptor on the cell surface and cytoplasm, could be selected as a target in cancer therapy. The present study involves the development and characterization of the F3 peptide functionalized LCNPs for delivering Sal (F3-Sal-NPs) for selectively targeting to the nucleolin receptor. The optimized LCNPs were characterized for particle size, zeta potential, surface morphology, drug release kinetics and stability. The LCNPs have a structure similar to nematic phases. In vitro drug release studies revealed sustained drug release characteristics (89.5 ± 1.5% at 120 h) with F3-Sal-NPs. The cytotoxicity results demonstrated that F3-Sal-NPs were 4.8, 2.6 and 5.5 folds more effective than naïve drug in MDA-MB-468, MDA-MB-231 and MCF-7 cells, respectively and the cell cycle was arrested in the S and G2/M phases. The expression of the gene responsible for the stemness (CD44 gene), apoptosis (BAX/Bcl-2 ration) and angiogenesis (LCN-2) was reduced by F3-Sal-NPs treatment. Ex vivo hemolytic toxicity was reduced (6.5 ± 1.5%) and the pharmacokinetics and bioavailability of Sal was improved with F3-Sal-NPs. The in vivo antitumor efficacy was tested in EAC bearing mice, where F3-Sal-NPs significantly reduced the tumor growth by 2.8-fold compared to pure Sal and induced necrosis of tumor cells. The results clearly demonstrate the outstanding performance of F3 peptide functionalized LCNPs for delivering Sal against breast cancer.

Fisetin in Cancer: Attributes, Developmental Aspects, and Nanotherapeutics.

Cancer is one of the major causes of mortality, globally. Cancerous cells invade normal cells and metastasize to distant sites with the help of the lymphatic system. There are several mechanisms involved in the development and progression of cancer. Several treatment strategies including the use of phytoconstituents have evolved and been practiced for better therapeutic outcomes against cancer. Fisetin is one such naturally derived flavone that offers numerous pharmacological benefits, i.e., antioxidant, anti-inflammatory, antiangiogenic, and anticancer properties. It inhibits the rapid growth, invasiveness, and metastasis of tumors by hindering the multiplication of cancer cells, and prompts apoptosis by avoiding cell division related to actuation of caspase-9 and caspase-8. However, its poor bioavailability associated with its extreme hydrophobicity hampers its clinical utility. The issues related to fisetin delivery can be addressed by adapting to the developmental aspects of nanomedicines, such as formulating it into lipid or polymer-based systems, including nanocochleates and liposomes. This review aims to provide in-depth information regarding fisetin as a potential candidate for anticancer therapy, its properties and various formulation strategies.

Angiopep-2 Grafted PAMAM Dendrimers for the Targeted Delivery of Temozolomide: In Vitro and In Vivo Effects of PEGylation in the Management of Glioblastoma Multiforme.

The present study was aimed to synthesize, characterize, and evaluate the angiopep-2 grafted PAMAM dendrimers (Den, G 3.0 NH2) with and without PEGylation for the targeted and better delivery approach of temozolomide (TMZ) for the management of glioblastoma multiforme (GBM). Den-ANG and Den-PEG2-ANG conjugates were synthesized and characterized by 1H NMR spectroscopy. The PEGylated (TMZ@Den-PEG2-ANG) and non-PEGylated (TMZ@Den-ANG) drug loaded formulations were prepared and characterized for particle size, zeta potential, entrapment efficiency, and drug loading. An in vitro release study at physiological (pH 7.4) and acidic pH (pH 5.0) was performed. Preliminary toxicity studies were performed through hemolytic assay in human RBCs. MTT assay, cell uptake, and cell cycle analysis were performed to evaluate the in vitro efficacy against GBM cell lines (U87MG). Finally, the formulations were evaluated in vivo in a Sprague-Dawley rat model for pharmacokinetics and organ distribution analysis. The 1H NMR spectra confirmed the conjugation of angiopep-2 to both PAMAM and PEGylated PAMAM dendrimers, as the characteristic chemical shifts were observed in the range of 2.1 to 3.9 ppm. AFM results revealed that the surface of Den-ANG and Den-PEG2-ANG conjugates were rough. The particle size and zeta potential of TMZ@Den-ANG were observed to be 229.0 ± 17.8 nm and 9.06 ± 0.4 mV, respectively, whereas the same for TMZ@Den-PEG2-ANG were found to be 249.6 ± 12.9 nm and 10.9 ± 0.6 mV, respectively. The entrapment efficiency of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were calculated to be 63.27 ± 5.1% and 71.48 ± 4.3%, respectively. Moreover, TMZ@Den-PEG2-ANG showed a better drug release profile with a controlled and sustained pattern at PBS pH 5.0 than at pH 7.4. The ex vivo hemolytic study revealed that TMZ@Den-PEG2-ANG was biocompatible in nature as it showed 2.78 ± 0.1% hemolysis compared to 4.12 ± 0.2% hemolysis displayed by TMZ@Den-ANG. The outcomes of the MTT assay inferred that TMZ@Den-PEG2-ANG possessed maximum cytotoxic effects against U87MG cells with IC50 values of 106.62 ± 11.43 µM (24 h) and 85.90 ± 9.12 µM (48 h). In the case of TMZ@Den-PEG2-ANG, the IC50 values were reduced by 2.23-fold (24 h) and 1.36-fold (48 h) in comparison to pure TMZ. The cytotoxicity findings were further confirmed by significantly higher cellular uptake of TMZ@Den-PEG2-ANG. Cell cycle analysis of the formulations suggested that the PEGylated formulation halts the cell cycle at G2/M phase with S-phase inhibition. In the in vivo studies, the half-life (t1/2) values of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were enhanced by 2.22 and 2.76 times, respectively, than the pure TMZ. After 4 h of administration, the brain uptake values of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were found to be 2.55 and 3.35 times, respectively, higher than that of pure TMZ. The outcomes of various in vitro and ex vivo experiments promoted the use of PEGylated nanocarriers for the management of GBM. Angiopep-2 grafted PEGylated PAMAM dendrimers can be potential and promising drug carriers for the targeted delivery of antiglioma drugs directly to the brain.

Capturing agro-morphological variability for tolerance to terminal heat and combined heat-drought stress in landraces and elite cultivar collection of wheat.

Climate change has resulted in extreme temperature and drought around the globe, which poses serious threat to food security. Both heat and drought stress affects the production and productivity of wheat crop. The present study was undertaken to evaluate 34 landraces and elite cultivars of Triticum spp. for phenological and yield-related traits under optimum, heat, and combined heat-drought stress environments during 2020-2021 and 2021-2022. The pooled analysis of variance showed significant genotype × environment interaction, suggesting an influence of stress on trait expression. The trait performance of genotypes exhibited significant reduction under combined heat-drought stress as compared to optimum and heat stress environments. The maximum seed yield penalty was observed under combined heat-drought stress environment as compared to heat stress alone. Regression analysis indicated significant contribution of number of grains per spike towards stress tolerance. Based on Stress Tolerance Index (STI), genotypes Local-17, PDW 274, HI-8802, and HI-8713 were identified to be tolerant to both heat and combined heat and drought stress at Banda, whereas genotypes DBW 187, HI-8777, Raj 4120, and PDW 274 were tolerant at Jhansi location. The genotype PDW 274 showed stress tolerance under all treatments at both the locations. The genotypes PDW 233 and PDW 291 showed highest stress susceptibility index (SSI) across the environments. The number of grains per spike and test kernel weight were positively associated with seed yield across the environments and locations. The selected genotypes Local-17, HI 8802, and PDW 274 were identified to be the potential sources of heat and combined heat-drought tolerance, which may be utilized in hybridization to develop tolerant wheat genotypes and also for mapping of underlying genes/quantitative trait loci (QTLs).

Nanoconstructs for theranostic application in cancer: Challenges and strategies to enhance the delivery.

Nanoconstructs are made up of nanoparticles and ligands, which can deliver the loaded cargo at the desired site of action. Various nanoparticulate platforms have been utilized for the preparation of nanoconstructs, which may serve both diagnostic as well as therapeutic purposes. Nanoconstructs are mostly used to overcome the limitations of cancer therapies, such as toxicity, nonspecific distribution of the drug, and uncontrolled release rate. The strategies employed during the design of nanoconstructs help improve the efficiency and specificity of loaded theranostic agents and make them a successful approach for cancer therapy. Nanoconstructs are designed with a sole purpose of targeting the requisite site, overcoming the barriers which hinders its right placement for desired benefit. Therefore, instead of classifying modes for delivery of nanoconstructs as actively or passively targeted systems, they are suitably classified as autonomous and nonautonomous types. At large, nanoconstructs offer numerous benefits, however they suffer from multiple challenges, too. Hence, to overcome such challenges computational modelling methods and artificial intelligence/machine learning processes are being explored. The current review provides an overview on attributes and applications offered by nanoconstructs as theranostic agent in cancer.

A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive phenotype of breast cancer with associated chemoresistance. The development of chemo- or radioresistance could be attributed to diverse tumor microenvironments, overexpression of membrane proteins (transporters), epigenetic changes, and alteration of the cell signaling pathways/genes associated with the development of cancer stem cells (CSCs). AIM OF REVIEW: Due to the diverse and heterogeneous nature of TNBC, therapeutic response to the existing modalities offers limited scope and thus results in reccurance after therapy. To establish landmark therapeutic efficacy, a number of novel therapeutic modalities have been proposed. In addition, reversal of the resistance that developed during treatment may be altered by employing appropriate therapeutic modalities. This review aims to discuss the plethora of investigations carried out, which will help readers understand and make an appropriate choice of therapy directed toward complete elimination of TNBC. KEY SCIENTIFIC CONCEPTS OF REVIEW: This manuscript addresses the major contributory factors from the tumor microenvironment that are responsible for the development of chemoresistance and poor prognosis. The associated cellular events and molecular mechanism-based therapeutic interventions have been explained in detail. Inhibition of ABC transporters, cell signaling pathways associated with CSCs, and epigenetic modification offers promising results in this regard. TNBC progression, invasion, metastasis and recurrence can also be inhibited by blocking multiple cell signaling pathways, targeting specific receptors/epigenetic targets, disrupting bioenergetics and generating reactive oxygen species (ROS).

Dual role of Nrf2 in cancer: molecular mechanisms, cellular functions and therapeutic interventions.

BACKGROUND: Nrf2 regulates oxidative stress, which is essential for cellular function. Fundamental initiation of Nrf2 in many malignancies increases prosurvival genes & endorses tumour cell propagation via metabolic reprogramming, suppression of tumour programmed cell death, & increased cancer stem cell self-renewal potential. More specifically, Nrf2 has been associated with cancer cell chemoresistance, radioresistance & inflammation-induced carcinogenesis.  METHODS AND RESULTS: Many Nrf2 inhibitors have been revealed for tumour treatment and targeting Nrf2 could be an effective cancer therapeutic method. Before spreading, cancer cells adapt to their surroundings. Cancer cells usually have mutations in tumor suppressor genes. In a variety of malignancies, somatic mutations & other anomalies in the Nrf2 genes, as well as renowned cancer suppressor genes including TP53, CDKN2A, PTEN & PIK3CA, have been found. In tumour cells, somatic mutations in the Nrf2 genes, as well as additional mechanisms that affect Nrf2 binding, and produce aberrant Nrf2 activation. Uncontrolled Nrf2 causes tumour cells to become resistant to antineoplastic drugs & reactive oxygen species (ROS), as well as guiding them toward metabolic reprogramming.  CONCLUSIONS: As a result, Nrf2 has been studied as potential malignancy treatment target. We covered the pathways, mechanisms, and dual characteristics of Nrf2 in malignancy in this article. We also discussed how Nrf2 inhibitors are targeted against cancer in this review.

Techniques to Treat Slow-Flow/No-Reflow During Primary Percutaneous Coronary Intervention.

OBJECTIVE: The aim of this study was to compare TIMI flow after administering intracoronary (IC) medications through various routes for the treatment of slow flow/no-reflow during primary PCI. METHODS: Two independent parallel cohorts of the patients who underwent primary PCI for STEMI and developed slow/no-reflow were recruited. Selection of cohort was based on the route of administration of IC medications as proximal or distal. Post administration TIMI follow was compared between the two cohorts. RESULTS: A total of 100 patients were included in both, proximal and distal, cohort. Distribution of angiographic, clinical and demographic characteristics was not significant between the two cohorts except prevalence of hypertension, and diabetes mellitus. Frequency of hypertension, and diabetes mellitus were 45 % vs.70 %; p < 0.001 and 28 % vs. 44 %; p = 0.018 among patients in distal and proximal cohort respectively. Final TIMI III flow was achieved in significantly higher number of patients in distal cohort with the frequency of 88 % vs. 76 %; p = 0.027 as compared to proximal cohort. CONCLUSION: Administration of IC medication via distal route is observed to be more effective for the treatment of slow flow/no-reflow during primary PCI. Distal route via export catheter or perforated balloon technique should be preferred wherever feasible.

5d CIDR-Heatsynch improves the circulatory estradiol levels, estrus expression and conception rate in anestrus buffalo (Bubalus bubalis).

The present study aimed to investigate whether increasing estradiol (E2) during preovulatory period would increase estrous expression, luteal profiles and conception rate in 5d CIDR based timed AI protocol. A total 156 anestrus buffalo allocated (78 per group) to either 5d CIDR-Cosynch (d-5: CIDR + GnRH; d0: PGF2α+CIDR removal; 72 h post-CIDR removal: GnRH) or 5d CIDR-Heatsynch (d-5: CIDR + GnRH; d0: PGF2α+CIDR removal; 24 h post-CIDR removal: estradiol benzoate) group. All the buffaloes inseminated at 72 and 84 h post-CIDR removal. A subset of buffalo (n = 58) were subjected to examination of the follicle diameter and luteal profile during protocol, post-AI on days 5 and 12. The buffalo in 5d CIDR-Heatsynch had greater (p < .05) E2 concentrations, estrus induction and increasing trend (p < .08) for conception rate (57.7% vs. 43.6%) than 5d CIDR-Cosynch. The percentage of pregnant buffalo that exhibited estrus signs was greater (p < .01) in 5d CIDR-Heatsynch than 5d CIDR-Cosynch. Positive correlation (p < .01) was observed between POF and E2 concentrations; POF and CL diameter, CL diameter and P4 concentrations. Estrus response and P4 concentrations were indicators of probability of pregnancy. In conclusion, 5d CIDR-Heatsynch tended to improve conception rate. The estrus expression and P4 concentrations (d5 and 12 post-first-AI) is the indicator of probability of pregnancy in buffalo.

Multi-location evaluation of mungbean (Vigna radiata L.) in Indian climates: Ecophenological dynamics, yield relation, and characterization of locations.

Crop yield varies considerably within agroecology depending on the genetic potential of crop cultivars and various edaphic and climatic variables. Understanding site-specific changes in crop yield and genotype × environment interaction are crucial and needs exceptional consideration in strategic breeding programs. Further, genotypic response to diverse agro-ecologies offers identification of strategic locations for evaluating traits of interest to strengthen and accelerate the national variety release program. In this study, multi-location field trial data have been used to investigate the impact of environmental conditions on crop phenological dynamics and their influence on the yield of mungbean in different agroecological regions of the Indian subcontinent. The present attempt is also intended to identify the strategic location(s) favoring higher yield and distinctiveness within mungbean genotypes. In the field trial, a total of 34 different mungbean genotypes were grown in 39 locations covering the north hill zone (n = 4), northeastern plain zone (n = 6), northwestern plain zone (n = 7), central zone (n = 11) and south zone (n = 11). The results revealed that the effect of the environment was prominent on both the phenological dynamics and productivity of the mungbean. Noticeable variations (expressed as coefficient of variation) were observed for the parameters of days to 50% flowering (13%), days to maturity (12%), reproductive period (21%), grain yield (33%), and 1000-grain weight (14%) across the environments. The genotype, environment, and genotype × environment accounted for 3.0, 54.2, and 29.7% of the total variation in mungbean yield, respectively (p < 0.001), suggesting an oversized significance of site-specific responses of the genotypes. Results demonstrated that a lower ambient temperature extended both flowering time and the crop period. Linear mixed model results revealed that the changes in phenological events (days to 50 % flowering, days to maturity, and reproductive period) with response to contrasting environments had no direct influence on crop yields (p > 0.05) for all the genotypes except PM 14-11. Results revealed that the south zone environment initiated early flowering and an extended reproductive period, thus sustaining yield with good seed size. While in low rainfall areas viz., Sriganganagar, New Delhi, Durgapura, and Sagar, the yield was comparatively low irrespective of genotypes. Correlation results and PCA indicated that rainfall during the crop season and relative humidity significantly and positively influenced grain yield. Hence, the present study suggests that the yield potential of mungbean is independent of crop phenological dynamics; rather, climatic variables like rainfall and relative humidity have considerable influence on yield. Further, HA-GGE biplot analysis identified Sagar, New Delhi, Sriganganagar, Durgapura, Warangal, Srinagar, Kanpur, and Mohanpur as the ideal testing environments, which demonstrated high efficiency in the selection of new genotypes with wider adaptability.

Role of STAT3 in the initiation, progression, proliferation and metastasis of breast cancer and strategies to deliver JAK and STAT3 inhibitors.

INTRODUCTION: Breast cancer (BC) accounts for the majority of cancers among the female population. Anomalous activation of various signaling pathways has become an issue of concern. The JAK-STAT signaling pathway is activated in numerous cancers, including BC. STAT3 is widely involved in BCs, as 40 % of BCs display phosphorylated STAT3. JAK-STAT signaling is crucial for proliferation, survival, metastasis and other cellular events associated with the tumor microenvironment. Hence, targeting this pathway has become an area of interest among researchers. KEY FINDINGS: This review article focuses on the role of STAT3 in the initiation, proliferation, progression and metastasis of BC. The roles of various phytochemicals, synthetic molecules and biologicals against JAK-STAT and STAT3 in various cancers have been discussed, with special emphasis on BC. SIGNIFICANCE: JAK and STAT3 are involved in various phases from initiation to metastasis, and targeting this pathway is a promising approach to inhibit the various stages of BC development and to prevent metastasis. A number of phytochemicals and synthetic and biological molecules have demonstrated potential inhibitory effects on JAK and STAT3, thereby paving the way for the development of better therapeutics against BC.

Immunomodulatory potential of Nyctanthes abrortristis stem bark.

BACKGROUND: Phytotherapeutic modulation of the immune system to mitigate infectious ailments has been in vogue all over the world. OBJECTIVE: The present work has been designed to scientifically explore the immunomodulatory potential of Nyctanthes arbortristis stem bark using mice models. MATERIALS & METHOD: Methanolic (MNA) and aqueous (ANA) extracts of N. arbortristis stem bark were evaluated for possible modulation in humoral immunity through serum immunoglobulin estimation. The variation in cellular immunity was assessed using neutrophil adhesion test, carbon clearance assay, and cyclophosphamide-induced neutropenia. RESULTS AND DISCUSSION: Administration of MNA and ANA (both at 200 mg/kg, p.o.) significantly augmented the levels of serum immunoglobulins (humoral antibody), neutrophil adhesion, and phagocytic index (a measure of carbon clearance). Extracts also guarded the animals against cyclophosphamide-induced leukopenia, especially neutropenia. CONCLUSION: Results indicate that cellular and humoral immune responses were aroused by pretreatment of the animal with methanol and aqueous extract of N. arbortristis. Thus, the methanol and aqueous extract of N. arbortristis stem bark possesses a significant immunostimulant activity and can be used to uplift the immune system in the infectious condition.