Alzheimer's disease (AD) pathogenesis feature progressive neurodegeneration, amyloid-β plaque formation, and neurofibrillary tangles. Ample evidence has indicated the involvement of epigenetic pathways in AD pathogenesis. Here, we show that the expression of microRNA 650 (miR-650) is altered in brains from AD patients. Furthermore, we found that the processing of primary miR-650 to mature miR-650 is misregulated. Bioinformatic analysis predicted that miR-650 targets the expression of three AD-associated components: Apolipoprotein E (APOE), Presenilin 1 (PSEN1), and Cyclin-Dependent Kinase 5 (CDK5), and we have experimentally confirmed that miR-650 is able to significantly reduce the expression of APOE, PSEN1, and CDK5 in vitro. Importantly, the overexpression of miR-650 was further shown to significantly alter the CDK5 level and ameliorate AD pathologies in APP-PSEN1 transgenic mice. Overall, our results indicate that miR-650 influences AD pathogenesis through regulation of CDK5.
Methionine metabolism is critical for the maintenance of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) pluripotency. However, little is known about the regulation of the methionine cycle to sustain ESC pluripotency. Here, we show that adenosylhomocysteinase (AHCY), an important enzyme in the methionine cycle, is critical for the maintenance and differentiation of mouse embryonic stem cells (mESCs). We show that mESCs exhibit high levels of methionine metabolism, whereas decreasing methionine metabolism via depletion of AHCY promotes mESCs to differentiate into the three germ layers. AHCY is posttranslationally modified with an O-linked β-N-acetylglucosamine sugar (O-GlcNAcylation), which is rapidly removed upon differentiation. O-GlcNAcylation of threonine 136 on AHCY increases its activity and is important for the maintenance of trimethylation of histone H3 lysine 4 (H3K4me3) to sustain mESC pluripotency. Blocking glycosylation of AHCY decreases the ratio of S-adenosylmethionine versus S-adenosylhomocysteine (SAM/SAH), reduces the level of H3K4me3, and poises mESC for differentiation. In addition, blocking glycosylation of AHCY reduces somatic cell reprogramming. Thus, our findings reveal a critical role of AHCY and a mechanistic understanding of O-glycosylation in regulating ESC pluripotency and differentiation.
Nanoscale Solvent Exchange In article number 2305779, Hongyu Chen and co-workers achieve real-time monitoring of nanoscale solvent exchange within silica micropores with millisecond resolution. This accomplishment involves embedding a rotor-based fluorophore into colloidal silica nanoparticles, which enables precise fluorescence detection of diffusion-related microenvironment changes and quantitative analysis of solvent-molecule transport diffusion rates.
Pressure ulcers (PU) refer to local tissue ulceration and necrosis caused by long-term compression and friction brought on by tissue ischemia and hypoxia. Diabetic wounds do not easily heal, and once a pressure ulceration occurs, it is difficult to deal with. The purpose of this study was to analyze the current research status of PUs in diabetic patients.The Science Citation Index Expanded (SCI-E) database was searched with terms of "Pressure Ulcer" and "Diabetes". Citespace software was used to analyze the annual distribution of the number of target documents and the distribution of countries, institutions, journals, authors, and keywords used in these works.In all, 1271 documents were retrieved, with a total citation frequency of 47,081, and an h-index of 101. The top 5 countries in terms of the number of publications were the United States, the United Kingdom, China, Australia, and the Netherlands; the top 5 countries in centrality were the Netherlands, the United States, Canada, Japan, and France. The institutions with the greatest number of publications were the University of Amsterdam, Cardiff University, The University of Washington, and the University of Manchester. The institutions with the highest centrality were the University of Amsterdam, the University of Groningen, the University of Washington, the University of Adelaide, Baylor College of Medicine, and Queensland University of Technology. The authors with a highest number of publications were Bus SA, Apelqvist J, and the International Working Group on the Diabetic Foot, and Hinchliffe RJ. Only 2 authors had a centrality score above 0.01. Journals such as Diabetes Metabolism Research and Reviews, Diabetes Care, and Journal of Wound Care showed considerable influence in this field. Keyword analysis indicated that the use of keywords in this field is not uniform, and the focus of research on PUs in diabetic patients lies the risk and management of foot ulcers.There are few studies concerning PUs in patients with diabetes and little collaboration between authors. The current focus in this field is on the risk and management of foot ulcers.
We show that it is possible to spontaneously form all-enclosed compartments with microporous shells and enriched biopolymers via simple coprecipitation of silica and biopolymers. The reaction involves mild conditions and tolerates the random mixing of multiple reagents. Such a synthetic advance points to a new direction for resolving the chicken-egg dilemma of how the early life forms were hosted: without a physical barrier it would be difficult to maintain organized reactions, but without organized reactions, it would be difficult to create a cell membrane. In our synthesis, the divalent cation Ca2+ plays a critical role in the co-precipitation and in creating hollow compartments after simple dilution with water. The precursor of silica, poly(silicic acid), is a negatively charged, cross-linked polymer. It could be co-precipitated with negatively charged biopolymers such as DNA and proteins, whereas the remaining silica precursor forms a conformal and microporous shell on the surface of the initial precipitate. After etching, the biopolymers are retained inside the hollow compartments. The fact that multiple favorable conditions are easily brought together in enclosed compartments opens new possibilities in theorizing the host of early life forms.
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