RESUMO
Endothelial barrier disruption plays a key role in the pathophysiology of heat stroke (HS). Knockout of DNAJA1 (DNAJA1KO) is thought to be protective against HS based on a genomewide CRISPRCas9 screen experiment. The present study aimed to illustrate the function of DNAJA1KO against HS in human umbilical vein endothelial cells. DNAJA1KO cells were infected using a lentivirus to investigate the role of DNAJA1KO in HSinduced endothelial barrier disruption. It was shown that DNAJA1KO could ameliorate decreased cell viability and increased cell injury, according to the results of Cell Counting Kit8 and lactate dehydrogenase assays. Moreover, HSinduced endothelial cell apoptosis was inhibited by DNAJA1KO, as indicated by Annexin VFITC/PI staining and cleavedcaspase3 expression using flow cytometry and western blotting, respectively. Furthermore, the endothelial barrier function, as measured by transepithelial electrical resistance and FITCDextran, was sustained during HS. DNAJA1KO was not found to have a significant effect on the expression and distribution of cell junction proteins under normal conditions without HS. However, DNAJA1KO could effectively protect the HSinduced decrease in the expression and distribution of cell junction proteins, including zonula occludens1, claudin5, junctional adhesion molecule A and occludin. A total of 4,394 proteins were identified using proteomic analysis, of which 102 differentially expressed proteins (DEPs) were activated in HSinduced wildtype cells and inhibited by DNAJA1KO. DEPs were investigated by enrichment analysis, which demonstrated significant enrichment in the 'calcium signaling pathway' and associations with vascularbarrier regulation. Furthermore, the 'myosin lightchain kinase (MLCK)MLC signaling pathway' was proven to be activated by HS and inhibited by DNAJA1KO, as expected. Moreover, DNAJA1KO mice and a HS mouse model were established to demonstrate the protective effects on endothelial barrier in vivo. In conclusion, the results of the present study suggested that DNAJA1KO alleviates HSinduced endothelial barrier disruption by improving thermal tolerance and suppressing the MLCKMLC signaling pathway.
Assuntos
Proteínas de Choque Térmico HSP40 , Golpe de Calor , Animais , Humanos , Camundongos , Golpe de Calor/genética , Golpe de Calor/metabolismo , Proteínas de Choque Térmico HSP40/genética , Células Endoteliais da Veia Umbilical Humana , Camundongos Knockout , Proteômica , Transdução de SinaisRESUMO
Gesture recognition through surface electromyography (sEMG) provides a new method for the control algorithm of bionic limbs, which is a promising technology in the field of human-computer interaction. However, subject specificity of sEMG along with the offset of the electrode makes it challenging to develop a model that can quickly adapt to new subjects. In view of this, we introduce a new deep neural network called CSAC-Net. Firstly, we extract the time-frequency feature from the raw signal, which contains rich information. Secondly, we design a convolutional neural network supplemented by an attention mechanism for further feature extraction. Additionally, we propose to utilize model-agnostic meta-learning to adapt to new subjects and this learning strategy achieves better results than the state-of-the-art methods. By the basic experiment on CapgMyo and three ablation studies, we demonstrate the advancement of CSAC-Net.
Assuntos
Gestos , Redes Neurais de Computação , Algoritmos , Eletromiografia , Humanos , AprendizagemRESUMO
The B3PW91/6-31G** theoretical method was carried out to optimize the structure of 12 polynitro imidazo [4,5-e] oxadiazolo [3,4-b] pyrazine compounds (two structural type). The influence of nitro groups on the structure, oxygen balance, density, heat of formation, detonation performances, and charge were investigated. The results showed that the oxygen balance, density, heat of formation, detonation velocity, detonation pressure, and detonation heat increased with different relationships when the number of nitro groups increased. The contribution of the dinitroethylene group to energy was greater than that of the nitroimino group. On the whole, the sensitivity of all compounds increased with the number of -NO2 groups, and the second type of compound is more sensitive because of more nitro groups. The alkaline of the amine will decrease with the increasing number of -NO2 groups, and nitrification action will become more difficult. Graphical abstract Polynitro imidazo [4, 5-e] oxadiazolo [3, 4-b] pyrazine compoundsá .