Sandeep Rana

Cyclin-dependent kinase 9 (CDK9), a member of the cyclin-dependent protein kinase (CDK) family, is involved in transcriptional elongation of several target genes. CDK9 is ubiquitously expressed and has been shown to contribute to a variety of malignancies such as pancreatic, prostate and breast cancers. Here we report the development of a heterobifunctional small molecule proteolysis targeting chimera (PROTAC) capable of cereblon (CRBN) mediated proteasomal degradation of CDK9. In HCT116 cells, it selectively degrades CDK9 while sparing other CDK family members. This is the first example of a PROTAC that selectively degrades CDK9.

Cyclin dependent kinase (CDK) inhibitors have been the topic of intense research for nearly 2 decades due to their widely varied and critical functions within the cell. Recently CDK9 has emerged as a druggable target for the development of cancer therapeutics. CDK9 plays a crucial role in transcription regulation; specifically, CDK9 mediated transcriptional regulation of short-lived antiapoptotic proteins is critical for the survival of transformed cells. Focused chemical libraries based on a plethora of scaffolds have resulted in mixed success with regard to the development of selective CDK9 inhibitors. Here we review the regulation of CDK9, its cellular functions, and common core structures used to target CDK9, along with their selectivity profile and efficacy in vitro and in vivo.

There is a significant advancement in the modification of extruders for the commercial application in food processing sector, especially during the last three decades. Extrusion is one among the most commercially successful technology, escalating its demand in the diverse field of the food industry, including food processing, digital food marketing (3-D printed food) and food packaging. The paper aims to review the developments in the last 5 years. The novel innovations include hot-melt extrusion, supercritical fluid assisted extrusion and extrusion-based 3-D printing. Hot-melt extrusion finds application in developing food with taste-masking properties of functional components and with high repeatability andy targeted delivery with widespread application in meat replacements, cheese, cocoa etc. The supercritical fluids assisted extrusion is used to develop products rich in nutrients that are heat sensitive. Extrusion based 3-D printing is the latest trend focusing on digitalizing commercial food market with nutritionally personalized and geometrically complex food products. The review also gives lights to the application of extrusion in the food packaging sector as biodegradable polymers replacing synthetic petroleum products. It can be inferred that novel technologies in the extrusion have a promising future for the commercialization of both product and technology.

≤ 0.05). Medicine and surgery residency programs should be cognizant of and closely monitor the effects of COVID-19 crisis-related factors on residents' stress and anxiety levels. Transparent communication, telemedicine, online lectures/meetings, procedure simulations, advocacy groups, and wellness resources may help to mitigate some of the challenges posed by the pandemic.