Phosphorylation of Atg9 regulates movement to the phagophore assembly site and the rate of autophagosome formation

<p>Macroautophagy is primarily a degradative process that cells use to break down their own components to recycle macromolecules and provide energy under stress conditions, and defects in macroautophagy lead to a wide range of diseases. Atg9, conserved from yeast to mammals, is the only identified transmembrane protein in the yeast core macroautophagy machinery required for formation of the sequestering compartment termed the autophagosome. This protein undergoes dynamic movement between the phagophore assembly site (PAS), where the autophagosome precursor is nucleated, and peripheral sites that may provide donor membrane for expansion of the phagophore. Atg9 is a phosphoprotein that is regulated by the Atg1 kinase. We used stable isotope labeling by amino acids in cell culture (SILAC) to identify phosphorylation sites on this protein and identified an Atg1-independent phosphorylation site at serine 122. A nonphosphorylatable Atg9 mutant showed decreased autophagy activity, whereas the phosphomimetic mutant enhanced activity. Electron microscopy analysis suggests that the different levels of autophagy activity reflect differences in autophagosome formation, correlating with the delivery of Atg9 to the PAS. Finally, this phosphorylation regulates Atg9 interaction with Atg23 and Atg27.</p

Fabrication of nanodiamonds/polyaniline nanocomposite for bilirubin adsorption in hemoperfusion

Carbon-based nanomaterials have been explored as effective adsorbents to remove bilirubin in hemoperfusion therapy. However, developing carbon-based absorbents with both high adsorption capacity and good hemocompatibility remains a challenge in clinical applications. In this study, an efficient adsorbent for bilirubin removal was fabricated by grafting polyaniline (PANI) onto nanodiamonds (NDs). The nanocomposite ND-PANI had negligible effect on the hemolytic activity, confirming its excellent blood compatibility. The adsorption results revealed that the ND-PANI had high adsorption capacities (947 mg/g) and rapid adsorption rate toward bilirubin. Moreover, it exhibited efficient bilirubin adsorption in bovine serum albumin (BSA) solution, indicating its potential for practical application. Additionally, the adsorption kinetics and isotherms were systematically analyzed and modeled, thereby offering insights into the possible adsorption mechanism. Our findings suggest that the ND-PANI could be used as an efficient sorbent for the bilirubin removal, offering a promising avenue for blood purification application.</p

Flow chart of articles identified, included and exclude.

<p>Flow chart of articles identified, included and exclude.</p

Reporting of checklists for ARRIVE Guidelines.

<p>Reporting of checklists for ARRIVE Guidelines.</p

Characteristics of included studies.

<p>Characteristics of included studies.</p