Unlocking the influence of PNPLA3 mutations on lipolysis: Insights into lipid droplet formation and metabolic dynamics in metabolic dysfunction-associated steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) covers a range of liver conditions marked by the buildup of fat, spanning from simple fatty liver to more advanced stages like metabolic dysfunction-associated steatohepatitis and cirrhosis.

Methods: Our in-depth analysis of PNPLA3_WT and mutants (I148M (MT1) and C15S (MT2)) provides insights into their structure-function dynamics in lipid metabolism, especially lipid droplet hydrolysis and ABHD5 binding. Employing molecular docking, binding affinity, MD analysis, dissociation constant, and MM/GBSA analysis, we delineated distinct binding characteristics between wild-type and mutants.

Amend the Mental Health Care Act 2017: A Survey of Indian psychiatrists (Part 2).

Background: Information about the experience of practicing psychiatrists with the use of the Mental Health Care Act (MHCA), 2017, India, after 5 years of its promulgation has not been available.

Aim: The present study was carried out to understand the experience of the practicing psychiatrists in using and complying with the MHCA 2017 and to bring out the problems and suggested reforms, if any, in various provisions of the MHCA 2017.

Methods: An online survey by practicing psychiatrists of Indian Psychiatric Society on the various sections and provisions of the MHCA 17 was carried out through structured and open-ended responses.

Optimum diagnostic pathway and pathologic confirmation rate of early stage lung cancer: Results from the VIOLET randomised controlled trial.

Background: Pathologic confirmation of lung cancer influences treatment selection for suspected early-stage lung cancer. High pre-treatment tissue confirmation rates are recommended. We sought to define management and outcomes of patients undergoing surgery for primary lung cancer in a UK multi-centre clinical trial.

Integrating structure-guided and fragment-based inhibitor design to combat bedaquiline resistant : a molecular dynamics study.

The first FDA approved, MDR-TB inhibitory drug bedaquiline (BDQ), entraps the c-ring of the proton-translocating F region of enzyme ATP synthase of , thus obstructing successive ATP production. Present-day BDQ-resistance has been associated with cardiotoxicity and mutation(s) in the atpE gene encoding the c subunit of ATP synthase (ATPc) generating five distinct ATPc mutants: Ala63→Pro, Ile66→Met, Asp28→Gly, Asp28→Val and Glu61→Asp. We created three discrete libraries, first by repurposing bedaquiline via scaffold hopping approach, second one having natural plant compounds and the third being experimentally derived analogues of BDQ to identify one drug candidate that can inhibit ATPc activity more efficiently with less toxic properties.