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Angiotensin receptor blockers have been reported to be beneficial to liver fibrosis, but the relevant molecular and cellular mechanisms remain unclear. We herein investigated whether low-dose angiotensin receptor blocker alleviated liver fibrosis through mechanotransduction regulation. Hydrostatic pressure-induced liver fibrosis model was established in mice by ligating partially the inferior vena cava, and then randomly received a very low dose of losartan (0.5 mg/kg) or placebo treatment for 8 weeks. We found that losartan administration interfered the expression of several mechanotransductive molecules, and effectively alleviated liver fibrosis. Using a commercial device, we further confirmed that ex vivo loading of hepatic stellate cells to 50 mmHg hydrostatic pressure for 24 h significantly upregulated RhoA, ROCK, AT1R, and p-MLC2, which was effectively attenuated by adding 10 nM losartan in medium. Our in vivo and ex vivo experimental data suggest that low-dose angiotensin receptor blockers may alleviate hydrostatic pressure-induced liver fibrosis by altering the mechanotransduction properties of hepatic stellate cells. NEW & NOTEWORTHY Our ex vivo and in vivo experiments clearly indicated that low-dose losartan alleviated liver fibrosis, likely by modulating the mechanotransduction properties of HSCs. Uncovering the biomechanical signaling pathway of ARB treatment on liver fibrosis will be helpful to develop novel molecular targeting therapy for liver diseases., American journal of physiology-Gastrointestinal and liver physiology, 322(4), pp. G446-G456; 2022

The abundant defects in bismuth boosted the formate selectivity of electrocatalytic CO2 reduction.

Aims: This study aimed to investigate the indocyanine green (ICG) dose in real‐time fluorescent cholangiography during laparoscopic cholecystectomy (LC) with a 4K fluorescent system. Methods: A randomized controlled clinical trial was conducted in patients who underwent LC for treatment of cholelithiasis. Using the OptoMedic 4K fluorescent endoscopic system, we compared four different doses of ICG (1, 10, 25, and 100 µg) administered intravenously within 30 min preoperatively and evaluated the fluorescence intensity (FI) of the common bile duct and liver background and the bile-to-liver ratio (BLR) of the FI at three timepoints: before surgical dissection of the cystohepatic triangle, before clipping the cystic duct, and before closure. Results: Forty patients were randomized into four groups, and 33 patients were fully analyzed, with 10 patients in Group A (1 µg), 7 patients in Group B (10 µg), 9 patients in Group C (25 µg), and 7 patients in Group D (100 µg). The preoperative baseline characteristics were compared among groups (p > 0.05). Group A showed no or minimal FI in the bile duct and liver background, while Group D showed extremely high FIs in the bile duct and in the liver background at the three timepoints. Groups B and C presented with visible FI in the bile duct and low FI in the liver background. With increasing ICG doses, the FIs in the liver background and bile duct gradually increased at the three timepoints. The BLR, however, showed no increasing trend with an increasing ICG dose. A relatively high BLR on average was found in Group B, without a significant difference compared to the other groups (p > 0.05). Conclusion: An ICG dose ranging from 10 µg to 25 µg by intravenous administration within 30 min preoperatively was appropriate for real‐time fluorescent cholangiography in LC with a 4K fluorescent system. Registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR No: ChiCTR2200064726)

Background In today's dynamic market economy, applying irrational design thinking to garment fabric design is an innovative design method for garment brands to establish personalized and independent design style. From the perspective of vocational skill education and educational psychology, how to cultivate applied talents to adapt to the development of enterprises has become a problem we should pay attention to. In particular, it can quickly capture the emotional and behavioral changes in irrational factor design. Research Objects and Methods Guided by the actual working process of fashion designers, this paper simulates the work project tasks in teaching, and analyzes the project teaching objectives, project teaching tasks, project teaching background, basic theory of project teaching, project teaching implementation process, project teaching implementation process, project teaching objectives, project teaching objectives, project teaching objectives, project teaching objectives, project teaching objectives, project teaching contents, project teaching contents Project teaching content, project teaching goal, project teaching goal, project teaching goal, project teaching goal, project teaching goal, project teaching implementation process, project teaching goal, project teaching content, project teaching content, project teaching content, project teaching content and project, and discusses the application of project case analysis in clothing fabric irrational design from six aspects of project teaching. Results A two-tier structural equation model of service encounter, relationship interest and customer voluntary performance was constructed; The service encounter dimension includes the ease of use of technical services, the economy of technical services, the economy of interpersonal services and the initiative of interpersonal services; The dimension of relationship interests includes six sub dimensions: trust interests, social interests, special treatment interests, honor interests, knowledge interests and identity interests; Customer voluntary performance means loyalty, cooperation and participation. In the verification of the relationship part, the hypothesis is valid, the relationship interest plays an intermediary role in service encounter and customer voluntary performance, and the multi cluster model is also homogeneous and stable. At the same time, in this process, taking the two dimensions of emotional regulation as the mediating variable, psychological quality as the independent variable and various indicators of mental health as the dependent variable, the mediating model a (cognitive reappraisal) and model B (expression inhibition) were established. Each variable is packaged for convenient analysis, the packaging strategy is factor analysis, and the three special factors of psychological quality are three packages of psychological quality. Trait anxiety, depression, loneliness, cognitive reappraisal and expression inhibition were snake shaped according to the load of factor analysis, forming three packages respectively. The fitting index standard of mediation model is: cfitli is greater than 0.90, RM sea is less than 0.08 and SRMR is less than 0.05. The fitting results of model a and model B are as follows: model a: x2 = 175.21, DF = 23, CFI = 0.97, TLI = 0.96, RMSEA = 0.07; Model B: x2 = 507.46, DF = 79, CFI = 0.97, TLI = 0.96, RMSEA = 0.06. The fitting indexes in model a and model B meet the standard. The mediating effect of cognitive reappraisal and expression inhibition between psychological quality and various negative indicators of mental health is significant. The bootstrap test shows (see Table 3): in model a, only cognitive reappraisal has a significant mediating effect between psychological quality and loneliness, while in model B, expression inhibition has a significant mediating effect between psychological quality and trait anxiety, depression and loneliness. In model a, the indirect effect of cognitive reappraisal on psychological quality and loneliness accounted for 6.5% of the total effect. In model B, the indirect effects accounted for 2.3%, 5.1% and 7.8% of the total effects respectively. Irrational design thinking refers to the way of thinking of art design, which deliberately breaks the rationality of thinking and makes the design interesting. The applied teaching mode of applying artistic thinking to the actual market work should be based on the actual working process of the enterprise. The project work simulation teaching combines the requirements of educational psychology for students' progressive knowledge with the open knowledge points of art to cultivate technical application-oriented talents with innovative design thinking. Conclusion As a form of thinking, irrational design thinking is closely related to fashion design. People can inspire and promote each other with different ways of thinking, which is the necessary thinking quality of innovative talents. We can fully understand the role of irrational thinking in garment fabric design and consciously strengthen the cultivation of irrational thinking ability, which can not only further improve the knowledge structure and broaden thinking, but also fully release the spirit of innovation and improve learning ability. In short, we should give full play to the important role of irrational factors in design elements, actively pay attention to the changes of students' psychological emotion and behavior, the changes of students' ability, the impact of students' psychological emotion and behavior on classroom learning effect and healthy behavior, and be good builders, managers, coordinators and collaborators of design methods. According to the psychological characteristics of these groups, we should actively and flexibly organize rich activities, strive to create a relaxed and harmonious living atmosphere, create a friendly and mutually beneficial teaching relationship, encourage and guide these groups, adjust their psychology and adapt to the new environment. Acknowledgement Research on the Development and Application of Recycled Textile Products Based on Public Commercial Space (Supported by the Project of Excellent Young Innovative Talents Training Program of Guangdong General Universities, Project No. 2018GWQNCX069, Li Wenjuan).

Mechanical forces can modulate the immune response, mostly described as promoting the activation of immune cells, but the role and mechanism of pathological levels of mechanical stress in lymphocyte activation have not been focused on before. By an ex vivo experimental approach, we observed that mechanical stressing of murine spleen lymphocytes with 50 mmHg for 3 h induced the nuclear localization of NFAT1, increased C-Jun, and increased the expression of early activation marker CD69 in resting CD8+ cells. Interestingly, 50 mmHg mechanical stressing induced the nuclear localization of NFAT1; but conversely decreased C-Jun and inhibited the expression of CD69 in lymphocytes under lipopolysaccharide or phorbol 12-myristate 13-acetate/ionomycin stimulation. Additionally, we observed similar changes trends when comparing RNA-seq data of hypertensive and normotensive COVID-19 patients. Our results indicate a biphasic effect of mechanical stress on lymphocyte activation, which provides insight into the variety of immune responses in pathologies involving elevated mechanical stress.

Background New therapeutic drug for breast cancer (BRCA), especially triple negative BRCA (TNBC), is urgently needed. Even though 2-(4-morpholinoanilino)-6-cyclohexylaminopurine (reversine) is an aurora kinase inhibitor, it also inhibits some cancer cells and human BRCA cells. However, the potential roles of reversine as a novel therapeutic agent for the treatment of BRCA remains unknown and must be further investigation. Thus, the relationship of reversine to aurora kinase in BCRA has not been reported. The relationship between AURKB and survival rate in BRCA has never been reported. Herein, we tested the roles of reversine on different BRCA cell line subtypes. We also investigated the relationship between AURKB and survival rate in BRCA as well as reversine to Aurora kinase expression in BCRA cell lines, including TNBC subtype, 4T1, MDA-MB-231, and luminal subtype MCF-7. Methods Cell viability and apoptosis were detected using Cell Counting Kit-8 and flow cytometry analysis, respectively. Apoptotic and tumor-related proteins were tested using Western blot analysis. Important microRNAs that regulate BRCA were analyzed using RT-PCR. UALCAN public databases were used to analyze the targeted gene profiles, and the PROGgeneV2 database was used to study the prognostic implications of genes. Results Reversine inhibits cell proliferation and induces cell apoptosis by modulating caspase-3 and bax/bcl-2 among the three cell lines. Data from the UALCAN public database show that BRCA tissues expressed high gene levels of AURKB, TIMP1, MMP9, and TGFB1 compared with the normal tissue. Among the over-expressed genes in BRCA, AURKB ranks 9th in TNBC, 49th in luminal subtype, and 48th in HER2 subtype. High AURKB level in BRCA is highly related to the low survival rate in patients displayed in 18 databases searched via PROGgeneV2. The protein levels of aurora B kinase (Aurora B), which is encoded by AURKB gene, are highly suppressed by reversine in the three cell lines. The tumor-related proteins TGF-β1, TIMP1, and MMP9 are partially suppressed by reversine but with different sensitivity in the three cell lines. The reversine-affected microRNAs, such as miR129-5p, miR-199a-3p, and miR-3960, in MDA-MB-231 cell line might be the research targets in TNBC regulation. Conclusions In BRCA, the level of AURKB are over-expressed and is related to low survival rate. Reversine contributes to anti-growth effect in BRCA cell lines, especially for TNBC, by modulating the aurora B. However, the invasiveness, metastasis, and anti-tumor effects of reversine in vivo and in vitro must be further investigated. Electronic supplementary material The online version of this article (10.1186/s12935-019-0885-z) contains supplementary material, which is available to authorized users.

Additional file 1. The information of the antibodies used in present work.

In this paper we introduce the so-called Beliefs-Obligations-Intentions-Desires or BOID architecture. It contains feedback loops to consider all effects of actions before committing to them, and mechanisms to resolve conflicts between the outputs of its four components. Agent types such as realistic or social agents correspond to specific types of conflict resolution embedded in the BOID archecture.