Navigating interdisciplinary research:Historical progression and contemporary challenges

Interdisciplinary research plays a crucial role in addressing complex problems by integrating knowledge from multiple disciplines.This integration fosters innovative solutions and enhances understanding across various fields.This study explores the historical and sociological development of interdisciplinary research and maps its evolution through three distinct phases:pre-disciplinary,disciplinary,and post-disciplinary.It identifies key internal dynamics,such as disciplinary diversification,reorganization,and innovation,as primary drivers of this evolution.Additionally,this study highlights how external factors,particularly the urgency of World War II and the subsequent political and economic changes,have accelerated its advancement.The rise of interdisciplinary research has significantly reshaped traditional educational paradigms,promoting its integration across different educational levels.However,the inherent contradictions within interdisciplinary research present cognitive,emotional,and institutional challenges for researchers.Meanwhile,finding a balance between the breadth and depth of knowledge remains a critical challenge in interdisciplinary education.

Deacetylation of TFEB promotes fibrillar Aβ degradation by upregulating lysosomal biogenesis in microglia

Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid pla- que pathogenesis in Alzheimer＇s disease （AD）. Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB （TFEB）, an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ （fAβ） degra- dation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APPIPS1 transgenic mice. Our findings reveal that deacetylaUon of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.