Lysosomal Signaling Promotes Longevity by Adjusting Mitochondrial Activity

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Proteomic Analysis of Extracellular Vesicles for Cancer Diagnostics

Extracellular vesicles (EVs) including exosomes and microvesicles are lipid bilayer‐encapsulated nanoparticles released by cells, ranging from 40 nm to several microns in diameter. Biological cargoes including proteins, RNAs, and DNAs can be ferried by EVs to neighboring and distant cells via biofluids, serving as a means of cell‐to‐cell communication under normal and pathological conditions, especially cancers. On the other hand, EVs have been investigated as a novel “information capsule” for early disease detection and monitoring via liquid biopsy. This review summarizes current advancements in EV subtype characterization, cancer EV capture, proteomic analysis technologies, as well as possible EV‐based multiomics for cancer diagnostics.     

Thick Electrode Batteries: Principles,Opportunities, and Challenges

The ever‐growing portable electronics and electric vehicle markets heavily influence the technological revolution of lithium batteries (LBs) toward higher energy densities for longer standby times or driving range. Thick electrode designs can substantially improve the electrode active material loading by minimizing the inactive component ratio at the device level, providing a great platform for enhancing the overall energy density of LBs. However, extensive efforts are still needed to address the challenges that accompany the increase in electrode thickness, not limited to sluggish charge kinetics and electrode mechanical instability. In this review, the principles and the recent developments in the fabrication of thick electrodes that focus on low‐tortuosity structural designs for rapid charge transport and integrated cell configuration for improved energy density, cell stability, and durability are summarized. Advanced thick electrode designs for application in emerging battery chemistries such as lithium metal electrodes, solid state electrolytes, and lithium–air batteries are also discussed with a perspective on their future opportunities and challenges. Finally, suggestions on the future directions of thick electrode battery development and research are suggested.     

Slide‐free imaging of hematoxylin‐eosin stained whole‐mount tissues using combined third‐harmonic generation and three‐photon fluorescence microscopy

Intraoperative margin assessment of surgical tissues during cancer surgery is clinically important, especially in the case of tissue conserving surgery like Mohs micrographic surgery in which minimization of the surgical area is considered crucial. Frozen pathology is the gold standard of assessing excised tissues for signs of remaining cancerous lesions. The current protocol, however, is time‐consuming and labor‐intensive. Instead of the complex frozen sectioning, staining, and traditional white light microscopy imaging protocol, optically sectioned histopathological imaging of hematoxylin‐eosin stained whole‐mount skin tissues with a subfemtoliter resolution is demonstrated by using nonlinear microscopy in this study. With our proposed method, the reagents of staining and the contrast of imaging are fully consistent with the current clinical standard of frozen pathology, thus facilitating rapid intraoperative assessment of surgical tissues for future applications. Image: Slide‐free nonlinear microscopy imaging of H&E stained whole‐mount skin tissue showing the morphology of sweat glands.      

甘蔗脱毒健康种苗中单糖转运蛋白基因差异表达分析

旨在探讨脱毒处理对单糖转运蛋白表达量的影响,分析了3种甘蔗单糖转运蛋白基因SGT1、SGT2和PST2a在健康种苗和常规种苗不同生长时期的表达量差异。结果显示,在苗期和分蘖期甘蔗脱毒健康种苗叶片中SGT1、SGT2和PST2a表达量高于未脱毒种苗;在拔节期和成熟期甘蔗脱毒健康种苗未成熟茎节中SGT1、SGT2和PST2a表达量也高于未脱毒种苗;而在成熟茎节中表达量没有差异。苗期和分蘖期甘蔗叶片以及未成熟茎节中细胞生长分裂旺盛,需要利用大量单糖以提供能源和生物合成的前体物质。结果表明,该3种单糖转运蛋白基因表达量上升可能提供更多单糖用于细胞代谢,促进脱毒健康种苗的快速生长及最终生物量的积累。     

A Zebrafish Model of Myelodysplastic Syndrome Produced through tet2 Genomic Editing

The ten-eleven translocation 2 gene (TET2) encodes a member of the TET family of DNA methylcytosine oxidases that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to initiate the demethylation of DNA within genomic CpG islands. Somatic loss-of-function mutations of TET2 are frequently observed in human myelodysplastic syndrome (MDS), which is a clonal malignancy characterized by dysplastic changes of developing blood cell progenitors, leading to ineffective hematopoiesis. We used genome-editing technology to disrupt the zebrafish Tet2 catalytic domain. tet2^m/m (homozygous for the mutation) zebrafish exhibited normal embryonic and larval hematopoiesis but developed progressive clonal myelodysplasia as they aged, culminating in myelodysplastic syndromes (MDS) at 24 months of age, with dysplasia of myeloid progenitor cells and anemia with abnormal circulating erythrocytes. The resultant tet2^m/m mutant zebrafish lines show decreased levels of 5hmC in hematopoietic cells of the kidney marrow but not in other cell types, most likely reflecting the ability of other Tet family members to provide this enzymatic activity in nonhematopoietic tissues but not in hematopoietic cells. tet2^m/m zebrafish are viable and fertile, providing an ideal model to dissect altered pathways in hematopoietic cells and, for small-molecule screens in embryos, to identify compounds with specific activity against tet2 mutant cells.     

Enhancing antisense efficacy with multimers and multi-targeting oligonucleotides (MTOs) using cleavable linkers

The in vivo potency of antisense oligonucleotides (ASO) has been significantly increased by reducing their length to 8–15 nucleotides and by the incorporation of high affinity RNA binders such as 2′, 4′-bridged nucleic acids (also known as locked nucleic acid or LNA, and 2′,4′-constrained ethyl [cET]). We now report the development of a novel ASO design in which such short ASO monomers to one or more targets are co-synthesized as homo- or heterodimers or multimers via phosphodiester linkers that are stable in plasma, but cleaved inside cells, releasing the active ASO monomers. Compared to current ASOs, these multimers and multi-targeting oligonucleotides (MTOs) provide increased plasma protein binding and biodistribution to liver, and increased in vivo efficacy against single or multiple targets with a single construct. In vivo, MTOs synthesized in both RNase H-activating and steric-blocking oligonucleotide designs provide ≈4–5-fold increased potency and ≈2-fold increased efficacy, suggesting broad therapeutic applications.     

Object-Oriented Classification of Sugarcane Using Time-Series Middle-Resolution Remote Sensing Data Based on AdaBoost

Most areas planted with sugarcane are located in southern China. However, remote sensing of sugarcane has been limited because useable remote sensing data are limited due to the cloudy climate of this region during the growing season and severe spectral mixing with other crops. In this study, we developed a methodology for automatically mapping sugarcane over large areas using time-series middle-resolution remote sensing data. For this purpose, two major techniques were used, the object-oriented method (OOM) and data mining (DM). In addition, time-series Chinese HJ-1 CCD images were obtained during the sugarcane growing period. Image objects were generated using a multi-resolution segmentation algorithm, and DM was implemented using the AdaBoost algorithm, which generated the prediction model. The prediction model was applied to the HJ-1 CCD time-series image objects, and then a map of the sugarcane planting area was produced. The classification accuracy was evaluated using independent field survey sampling points. The confusion matrix analysis showed that the overall classification accuracy reached 93.6% and that the Kappa coefficient was 0.85. Thus, the results showed that this method is feasible, efficient, and applicable for extrapolating the classification of other crops in large areas where the application of high-resolution remote sensing data is impractical due to financial considerations or because qualified images are limited.