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Background: Dysfunction of vascular endothelial cells (ECs) plays a central role in the pathogenesis of cardiovascular complications in diabetes. SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) is a key regulator of chromatin structure and DNA repair, but its role in ECs remains surprisingly unexplored. The current study was designed to elucidate the regulated expression and function of SMARCA5 in diabetic ECs.Methods: SMARCA5 expression was evaluated in ECs from diabetic mouse and human circulating CD34+ cells using quantitative reverse transcription polymerase chain reaction and Western blot. Effects of SMARCA5 manipulation on ECs function were evaluated using cell migration, in vitro tube formation and in vivo wound healing assays. Interaction among oxidative stress, SMARCA5 and transcriptional reprogramming was elucidated using luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation.Results: Endothelial SMARCA5 expression was significantly decreased in diabetic rodents and humans. Hyperglycemia-suppressed SMARCA5 impaired EC migration and tube formation in vitro, and blunted vasculogenesis in vivo. Contrarily, overexpression of SMARCA5 in situ by a SMARCA5 adenovirus-incorporated hydrogel effectively promoted the rate of wound healing in a dorsal skin punch injury model of diabetic mice. Mechanistically, hyperglycemia-elicited oxidative stress suppressed SMARCA5 transactivation in a signal transducer and activator of transcription 3 (STAT3)-dependent manner. Moreover, SMARCA5 maintained transcriptional homeostasis of several pro-angiogenic factors through both direct and indirect chromatin-remodeling mechanisms. In contrast, depletion of SMARCA5 disrupted transcriptional homeostasis to render ECs unresponsive to established angiogenic factors, which ultimately resulted in endothelial dysfunction in diabetes.Conclusion: Suppression of endothelial SMARCA5 contributes to, at least in part, multiple aspects of endothelial dysfunction, which may thereby exacerbate cardiovascular complications in diabetes.

Due to their large bandwidth and impressive data speed, millimeter-wave (mmWave) radios are expected to play a key role in the 5G and beyond (e.g., 6G) communication networks. Yet, to release mmWave’s true power, the highly directional mmWave beams need to be aligned perfectly. Most existing beam alignment methods adopt an exhaustive or semi-exhaustive space scanning, which introduces up to seconds of delays. To eliminate the need for complex space scanning, this article presents an Ultra-wideband (UWB)-assisted mmWave communication framework, which leverages the co-located UWB antennas to estimate the best angles for mmWave beam alignment. One major challenge of applying this idea in the real world is the barrier of limited antenna numbers. Commercial-Off-The-Shelf (COTS) devices are usually equipped with only a small number of UWB antennas, which are not enough for the existing algorithms to provide an accurate angle estimation. To solve this challenge, we design a novel Multi-Frequency MUltiple SIgnal Classification (MF-MUSIC) algorithm, which extends the classic MUltiple SIgnal Classification (MUSIC) algorithm to the frequency domain and overcomes the antenna limitation barrier in the spatial domain. Extensive real-world experiments and numerical simulations illustrate the advantage of the proposed MF-MUSIC algorithm. MF-MUSIC uses only three antennas to achieve an accurate angle estimation, which is a mere 0.15° (or a relative difference of 3.6%) different from the state-of-the-art 16-antenna-based angle estimation method.

Abstract: Malignant tumor is one of the diseases threatening human life and health. Traditional antitumor therapy has some limitations in clinical application, so the development of targeted antitumor drugs has become one of the important research directions of cancer medicine. Since the first tyrosine kinase inhibitor was approved in 2001, this research field has attracted global attention. In this survey, the Web of Science database was adopted to make a bibliometric analysis of the global scientific production of receptor tyrosine kinases in recent 20 years. A total of 14378 documents related to the subject were retrieved and analyzed according to six main aspects: area, journal, country, institution, authors, and keywords. The results show that the United States is currently in a leading position in this field and has established the largest cooperation network with other countries. Harvard University has made the greatest contribution to the field of receptor tyrosine kinases, including the number of publications, the average number of citations per paper, and the h-index. Besides, PLOS One ranked first among the top 15 academic journals in the number of publications related to receptor tyrosine kinases during the survey period. Our research comprehensively evaluates the research status and cooperation network of receptor tyrosine kinases, hoping help researchers to guide their projects or find potential collaborators.

Talent revitalization is the key link of rural revitalization. The central government allocates special funds for the training of rural revitalization talents every year, among which rural tourism talents provide human resources guarantee for the development of rural tourism, and the performance evaluation of this fund is very important. Taking comprehensive quality, investment, development level and satisfaction as indicators, this paper evaluates the effect of revitalizing rural tourism talents in A district, and puts forward targeted suggestions.

Background: Dementia, mainly Alzheimer’s disease (AD) and vascular dementia (VaD), remains a global health challenge. Previous studies have demonstrated the benefits of acupuncture therapy (AT) in improving dementia. Nevertheless, the therapeutic targets and integrated biological mechanisms involved remain ambiguous. Objective: To identify therapeutic targets and biological mechanisms of AT in treating dementia by integrated analysis strategy. Methods: By the identification of differentially expressed genes (DEGs) of AD, VaD, and molecular targets of AT active components, the acupuncture therapeutic targets associated with the biological response to AD and VaD were extracted. Therapeutic targets-based functional enrichment analysis was conducted, and multiple networks were constructed. AT-therapeutic crucial targets were captured by weighted gene co-expression network analysis (WGCNA). The interactions between crucial targets with AT active components were verified by molecular docking. Results: Our results demonstrated that 132 and 76 acupuncture therapeutic targets were associated with AD and VaD. AT-therapeutic crucial targets including 58 for AD and 24 for VaD were captured by WGCNA, with 11 in shared, including NMU, GRP, TAC1, ADRA1D, and SST. In addition, 35 and 14 signaling pathways were significantly enriched by functional enrichment analysis, with 6 mutual pathways including neuroactive ligand-receptor interaction, GABAergic synapse, calcium signaling pathway, cAMP signaling pathway, chemokine signaling pathway, and inflammatory mediator regulation of TRP channels. Conclusion: The improvement of AD and VaD by AT was associated with modulation of synaptic function, immunity, inflammation, and apoptosis. Our study clarified the therapeutic targets of AT on dementia, providing valuable clues for complementing and combining pharmacotherapy.

The function of mitochondrial fusion and fission is one of the important factors causing ischemia-reperfusion (I/R) injury in diabetic myocardium. Aldehyde dehydrogenase 2 (ALDH2) is abundantly expressed in heart, which involved in the regulation of cellular energy metabolism and stress response. However, the mechanism of ALDH2 regulating mitochondrial fusion and fission in diabetic myocardial I/R injury has not been elucidated. In the present study, we found that the expression of ALDH2 was downregulated in rat diabetic myocardial I/R model. Functionally, the activation of ALDH2 resulted in the improvement of cardiac hemodynamic parameters and myocardial injury, which were abolished by the treatment of Daidzin, a specific inhibitor of ALDH2. In H9C2 cardiomyocyte hypoxia-reoxygenation model, ALDH2 regulated the dynamic balance of mitochondrial fusion and fission and maintained mitochondrial morphology stability. Meanwhile, ALDH2 reduced mitochondrial ROS levels, and apoptotic protein expression in cardiomyocytes, which was associated with the upregulation of phosphorylation (p-PI3K

Mo doping and Se vacancy engineering synergistically boost electrocatalytic water oxidation.

A novel CDK20 small molecule inhibitor discovered by artificial intelligence based on an AlphaFold-predicted structure demonstrates the first application of AlphaFold in hit identification for efficient drug discovery.

In order to effectively control and predict the settlement deformation of the surrounding ground surface caused by deep foundation excavation, the deep foundation pit project of Baoding City Automobile Technology Industrial Park is explored as an example. The initial population approach of the whale algorithm (WOA) is optimized using Cubic mapping, while the weights of the shrinkage envelope mechanism are adjusted to avoid the algorithm falling into local minima, the improved whale algorithm (IWOA) is proposed. Meanwhile, 10 benchmark test functions are selected to simulate the performance of IWOA, and the advantages of IWOA in learning efficiency and convergence speed are verified. The IWOA-LSTM deep foundation excavation deformation prediction model is established by optimizing the input weights and hidden layer thresholds in the deep long short-term memory (LSTM) neural network using the improved whale algorithm. The IWOA-LSTM prediction model is compared with LSTM, WOA-optimized LSTM (WOA-LSTM) and traditional machine learning, the results show that the final prediction score of the IWOA-LSTM prediction model is higher than the score of other models, and the prediction accuracy is better than that of traditional machine learning.