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Mitochondria are highly dynamic organelles whose fragmentation by fission is critical to their functional integrity and cellular homeostasis. Here, we develop a method via optogenetic control of mitochondria-lysosome contacts (MLCs) to induce mitochondrial fission with spatiotemporal accuracy. MLCs can be achieved by blue-light-induced association of mitochondria and lysosomes through various photoactivatable dimerizers. Real-time optogenetic induction of mitochondrial fission is tracked in living cells to measure the fission rate. The optogenetic method partially restores the mitochondrial functions of SLC25A46-/- cells, which display defects in mitochondrial fission and hyperfused mitochondria. The optogenetic MLCs system thus provides a platform for studying mitochondrial fission and treating mitochondrial diseases.

Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) is an immediate early gene that plays a vital role in learning and memory. Arc protein has structural and functional properties similar to viral Group-specific antigen (Gag) protein and mediates the intercellular RNA transfer through virus-like capsids. However, the regulators and secretion pathway through which Arc capsids maneuver cargos are unclear. Here, we identified that phosphatidylinositol-3-phosphate (PI3P) mediates Arc capsid assembly and secretion through the endosomal-multivesicular body (MVB) pathway. Indeed, reconstituted Arc protein preferably binds to PI3P. In HEK293T cells, Arc forms puncta that colocalize with FYVE, an endosomal PI3P marker, as well as Rab5 and CD63, early endosomal and MVB markers, respectively. Superresolution imaging resolves Arc accumulates within the intraluminal vesicles of MVB. CRISPR double knockout of RalA and RalB, crucial GTPases for MVB biogenesis and exocytosis, severely reduces the Arc-mediated RNA transfer efficiency. RalA/B double knockdown in cultured rat cortical neurons increases the percentage of mature dendritic spines. Intake of extracellular vesicles purified from Arc-expressing wild-type, but not RalA/B double knockdown, cells in mouse cortical neurons reduces their surface GlutA1 levels. These results suggest that unlike the HIV Gag, whose membrane targeting requires interaction with plasma-membrane-specific phosphatidyl inositol (4,5) bisphosphate (PI(4,5)P2), the assembly of Arc capsids is mediated by PI3P at endocytic membranes. Understanding Arc's secretion pathway helps gain insights into its role in intercellular cargo transfer and highlights the commonality and distinction of trafficking mechanisms between structurally resembled capsid proteins. [ABSTRACT FROM AUTHOR]

Background: Anastomotic leak after esophagectomy carries important short- and long-term sequelae. The authors conducted a systematic review and meta-analysis to determine its association with surgical volume. Materials and methods: A systematic literature review was performed to identify all studies reporting on anastomotic leak after esophagectomy. Studies with less than 100 cases were excluded. The primary outcome was postesophagectomy anastomotic leak, while secondary outcomes were operative mortality overall and after anastomotic leak. Pooled event rates (PER) were calculated, and the association with annual esophagectomy volume by center was investigated. Results: Of the 3932 retrieved articles, 472 were included (n= 177 566 patients). The PER of anastomotic leak was 8.91% [95% CI =8.32; 9.53%]. The PER of early mortality overall and after an anastomotic leak was 2.49% [95% CI =2.27; 2.74] and 11.39% [95% CI=9.66; 13.39], respectively. Centers with less than 37 annual esophagectomies had a higher leak rate compared to those with greater than or equal to 37 annual esophagectomies (9.58% vs. 8.34%; P= 0.040). On meta-regression, surgical volume was inversely associated with the PER of esophageal leak and of early mortality. Conclusions: The frequency of anastomotic leaks after esophagectomy, perioperative, and leak associated mortality are inversely associated with esophagectomy volume. [ABSTRACT FROM AUTHOR]

Bio-waste is a side product of biomedical research containing carbon, which can be utilized for developing carbon dots (CDs). CDs are known to be useful for a variety of applications because of their unique photoluminescence, low toxicity, and straightforward synthesis. In this paper, we employed a one-step hydrothermal method to prepare CDs from bio-waste as the only reactant. The as-synthesized Cell-CDs were found to be chemically stable and biocompatible. In addition, the spectra of Cell-CDs ' emissions covered the visible light, which is ideal for super-resolution imaging. Particularly, dual-color imaging can be achieved, for example, by staining the plasma membrane with Cell-CDs emitting one color and staining cytosolic organelles with Cell-CDs emitting a different color of fluorescence. Here, we demonstrate such applications by studying the subcellular dynamics of live cells., Competing Interests: The authors declare that there are no competing interests., (© 2024 The Author(s). Smart Medicine published by Wiley‐VCH GmbH on behalf of Wenzhou Institute, University of Chinese Academy of Sciences.)