Shwetakshi Sharma

Climate change is intensifying the complexity and severity of pest–pathogen interactions in agriculture, threatening global food security. Rising temperatures, elevated CO ₂ levels, shifting precipitation patterns, and extreme weather events are reshaping vector ecology, accelerating insect development, altering pathogen virulence, and disrupting plant defense systems. These changes enhance the frequency of co‐infections, increase herbivore pressures, and promote the emergence and spread of invasive pests and diseases, such as maize lethal necrosis and citrus greening. At the plant level, hormonal crosstalk between salicylic acid (SA) and jasmonic acid (JA) pathways is disrupted, undermining resistance mechanisms, particularly under high temperatures and altered carbon‐to‐nitrogen ratios. Resistance genes and quantitative resistance are increasingly compromised, while existing integrated pest management (IPM) strategies face reduced efficacy due to climate‐sensitive biocontrol agents and pesticides. Effective mitigation demands a paradigm shift toward climate‐resilient crop protection strategies. This includes forecasting models, adaptive surveillance systems, microbiome engineering, and agroecological diversification. Regional vulnerabilities further necessitate context‐specific adaptation and crop breeding approaches. Bridging current knowledge gaps requires long‐term, multifactorial field studies and interdisciplinary research that integrates plant physiology, entomology, pathology, and climatology to develop holistic and future‐ready solutions.

Nitrogen-bearing heterocycles continue to shape modern medicinal chemistry owing to their structural adaptability and capacity to participate in diverse biochemical interactions. Within this class, pyrimidine frameworks have emerged as especially influential, providing a chemically economical core from which varied pharmacological profiles can be engineered. Their modular architecture supports precise functionalization, enabling the design of molecules with activities spanning antiviral, anticancer, anti-inflammatory, antibacterial, antitubercular, antimalarial and neuroactive domains. Recent studies demonstrate that integrating pyrimidine cores with complementary heterocycles particularly thiazole units can substantially enhance target engagement, strengthen metabolic stability and yield more favourable pharmacodynamic profiles. This review summarizes the current progress in the development of pyrimidine-based scaffolds, emphasizing the relationship between structural modification and biological response. The collective findings underscore the continued relevance of pyrimidine chemistry as a driver in the discovery of next-generation therapeutic agents.

Breast cancer (BC) is the most prevalent form of cancer among women worldwide, accounting for approximately 36% of cancer cases. Due to its inimitable path

The present study describes the development and validation of a simple and rapid HPLC method for the simultaneous quantification of exemestane and thymoquinone. The separation of both compounds was performed on a 5 μ C-18 column utilizing phase A as water/methanol (45:5 v/v) and phase B as acetonitrile (50 v/v) (total ratio of A/B = 40:60 v/v) in isocratic elution mode as the mobile phase at a flow rate of 0.8 mL/min. Further, the Box–Behnken design was used for optimizing the analytical method. The proposed method was validated for various parameters, and all parameters were found to be within an acceptable range. The simultaneous detection of both drugs was monitored at 243 nm with a retention time of 5.73 and 6.93 min, respectively. Moreover, the forced degradation studies were conducted under various stress conditions, and the relevance of the validated RP-HPLC method was further explored for the estimation of drugs from lipid-based nanoformulation. Taken together, the study construed the development of an efficient and robust method that could be used for the quantification of these agents in various in vitro as well as in vivo models.

For achieving high effectiveness in the management of breast cancer, coadministration of drugs has attracted a lot of interest as a mode of therapy when compared to a single chemotherapeutic agent that often results in reduced therapeutic end results. Owing to their proven effectiveness, good patient compliance, and lower costs, oral anticancer drugs have received much attention. In the present work, we formulated the chitosan-coated nanoliposomes loaded with two lipophilic agents, namely, exemestane (EXE) and genistein (GEN). The formulation was prepared using the ethanol injection method, which is considered a simple method for getting the nanoliposomes. The formulation was optimized using Box-Behnken design (BBD) and was extensively characterized for particle size, ζ-potential, Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. The sizes of conventional and coated liposomes were found to be 104.6 ± 3.8 and 120.3 ± 6.4 nm with a low polydispersity index of 0.399 and 0.381, respectively. The ζ-potential of the liposomes was observed to be -16.56 mV, which changed to a positive value of +22.4 mV, clearly indicating the complete coating of the nanoliposomes by the chitosan. The average encapsulation efficiency was found to be between 70 and 80% for all prepared formulations. The compatibility of the drug with excipients and complete dispersion of the drug inside the system were verified by FTIR, XRD, and DSC studies. Furthermore, the in vitro release studies concluded the sustained release pattern following the Korsmeyer-Peppas model as the best-fitting model with Fickian diffusion. Ex vivo studies showed better permeation of the chitosan-coated liposomes, which was further confirmed by confocal studies. The prepared chitosan-coated liposomes showed superior antioxidant activity (94.56%) and enhanced % cytotoxicity (IC50 7.253 ± 0.34 μM) compared to the uncoated liposomes. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay displayed better cytotoxicity of the chitosan-coated nanoliposomes compared to the plain drug, showing the better penetration and enhanced bioavailability of drugs inside the cells. The formulation was found to be safe for administration, which was confirmed using the toxicity studies performed on an animal model. The above data suggested that poorly soluble lipophilic drugs could be successfully delivered via chitosan-coated liposomes for their effective delivery in breast cancer.

Exemestane (EXE), an irreversible aromatase inhibitor, is employed as a therapy for hormone-dependent breast cancer. Several studies have also established the budding effects of genistein (GEN) in various types of cancer such as breast, prostate, as well as skin due to its feeble estrogenic and anti-estrogenic properties. Considering the promising benefits of GEN, it was combined with EXE to accomplish superior therapeutic efficiency with fewer side effects. The quantification of the exact concentration of EXE and GEN when delivered as a combination would be required for which HPLC method was developed and validated. For this purpose, the C18 ODS column having dimensions of 150 × 4.6 mm, 5 μm, using mobile phase A as methanol:water (35:15, v/v), with formic acid (0.01%), and B as acetonitrile (in the ratio of A:B--30:70 v/v) at a flow rate of 1 mL/min was commonly used. The Box-Behnken design was chosen as our experimental model, and the interactions among the independent and dependent variables were analyzed. Parameters like linearity, system suitability, specificity, precision (intra- and interday), robustness, ruggedness, LOD (limit of detection), and LOQ (limit of quantification) were selected for the validation of our proposed method. EXE and GEN were eluted individually at 245 and 270.5 nm, respectively, while both of the agents were determined simultaneously at 256 nm, showing retention time as 2.10 and 1.67 min, respectively, and the calibration plot was observed to be linear in the range of 5-110 μg/mL. Hence, the method that we developed and validated was found to be suitable for the identification of both the drugs simultaneously in combination and in our in-house-developed nanoformulation.