Discovery of AZD8421: A Potent CDK2 Inhibitor with Selectivity Against Other CDK Family Members and the Human Kinome.

Targeting CDK2 with first generation CDK2 inhibitors suffered from a reduced therapeutic index likely due to toxicity stemming from lack of selectivity against the CDK family and other kinases. Recently, CDK2 has been identified as a mediator of resistance to CDK4/6 inhibitors in the context of high levels of cyclin E expression. Discovery of highly selective CDK2 inhibitors may minimize off-target effects, reduce toxicity observed with first generation CDK2 inhibitors, and allow precise targeting of aberrant cell cycle progression and resistance mechanisms mediated by high cyclin E/CDK2 activity.

Identification of superior rice donors with enhanced nitrogen use efficiency using a comprehensive multivariate genotype selection strategy.

Improving nitrogen use efficiency (NUE) of rice plants utilizing a few end-of-season traits poses a severe phenotyping bottleneck in exploring the genetic diversity of a large population and genotype selection accuracy. Therefore, a comprehensive multivariate genotype selection strategy was developed to explore maximum genetic variation of 300 diverse rice genotypes and accurately select promising rice donors with enhanced NUE traits on a multi-year (2019, 2021, and 2022) -trait (126 traits) -environment (2) -temporal (5) -location (3) scale. The multi-trait genotype ideotype distance index (MGIDI) ranked Cauvery, Suweon, RPW9-4 (SSI) and BAM3690 (IC463705) as superior NUE genotypes; Moroberekan, PUSA1121 and BAM8315 (Basmati 370) as low NUE genotypes.

Subtractive Proteomic Approaches to Identify Drug Targets: An Analysis on Hypothetical Proteins of Multidrug-Resistant .

is a Gram-negative pathogen responsible for nosocomial infections. The exploration of novel therapeutic targets within its proteome is essential for developing successful therapies for combating infections caused by this organism. Employing in silico approaches, this study aims to identify drug targets from hypothetical proteins of .

Assessing thermal environmental changes of a semi-arid city using multi-temporal LCZ approach: a case study of Pune, India.

The unprecedented growth of urbanization demands making cities and human settlements inclusive, safe, resilient, and sustainable. The present study is the first multi-temporal local climate zones (LCZ) mapped in India. It is used to assess the spatio-temporal growth of the city over the past two decades and its impact on its thermal environment.

Evidence-based approach for intraabdominal drainage in pancreatic surgery: A systematic review and meta-analysis.

Background: Historically intraoperative drains were employed after pancreatic surgery but over the last decade, there has been debate over the routine usage of drains.

Aim: To assess the necessity of intra-abdominal drain placement, identify the most effective drain type, and determine the optimal timing for drain removal.

Methods: A systematic review of electronic databases, including PubMed, MEDLINE, PubMed Central, and Google Scholar, was conducted using Medical Subject Headings and keywords until December 2023.