Cardiorenal syndrome (CRS), a clinical syndrome involving multiple pathological mechanisms, exhibits high morbidity and mortality. According to the primary activity of the disease, CRS can be divided into cardiorenal syndrome (type I and type II), renal heart syndrome (type III and type IV), and secondary heart and kidney disease (type V). The renin-angiotensin-aldosterone system (RAAS) is an important humoral regulatory system of the body that exists widely in various tissues and organs. As a compensatory mechanism, the RAAS is typically activated to participate in the regulation of target organ function. RAAS activation plays a key role in the pathogenesis of CRS. The RAAS induces the onset and development of CRS by mediating oxidative stress, uremic toxin overload, and asymmetric dimethylarginine production. Research on the mechanism of RAAS-induced CRS can provide multiple intervention methods that are of great significance for reducing end-stage organ damage and further improving the quality of life of patients with CRS.
Chronic kidney disease (CKD) is a major public health issue that is highly prevalent worldwide. Pyroptosis is an important pathological mechanism underlying kidney cell damage in CKD and is associated with the classic caspase-1-mediated pathway and nonclassic caspase-4/5/11-mediated pathway. The NLRP3-caspase-1-GSDMD signaling pathway is the key mechanism of kidney cell pyroptosis in CKD, and noncoding RNAs such as lncRNAs and miRNAs are important regulators of kidney cell pyroptosis in CKD. In addition, the NLRP1/AIM2-caspase-1-GSDMD and caspase-3-GSDME signaling pathways have also been shown to mediate kidney cell pyroptosis. Traditional Chinese medicine (TCM) and extracts can interfere with the occurrence and development of kidney cell pyroptosis in CKD by inhibiting the NLRP3 signaling pathway and oxidative stress, activating Nrf-2 signaling, protecting mitochondrial integrity, regulating AMPK signaling, and regulating TXNIP/NLRP3 axis, which have become increasingly prominent. It is critical to explore the effects of TCM on kidney cell pyroptosis in CKD and its mechanisms to identify targets and develop new and effective drugs.
The ''missing wedge'' of a single tilt in electron tomography introduces severe artifacts into the reconstructed results. To reduce the ''missing wedge'' effect, a widely used method is ''multiple-tilt reconstruction,'' which collects projections using multiple axes. However, as the number of tilt series increases, the computing and memory costs also rise. The degree of parallelism is limited by the sample thickness, and a large memory requirement cannot be met by most multicore computers. In our study, we present a new fully distributed multipletilt simultaneous iterative reconstruction technique (DM-SIRT). To improve the parallelism of the reconstruction process and reduce the memory requirements of each process, we formulate the multiple-tilt reconstruction as a consensus optimization problem and design a DM-SIRT algorithm. Experiments show that in addition to slightly better resolution, DM-SIRT can obtain a 13.9 3 accelerated ratio compared with the full multiple-tilt reconstruction version. It also has a 97% decrease in memory overhead and is 16 times more scalable than the full reconstruction version.
BackgroundThe main purpose is to establish an ideal arrhythmia model with isoproterenol and explore its mechanism.MethodsFifty healthy male SD rats were randomly divided into the control (CON) group, subcutaneous injection (SC) group(ISO 5 mg/kg for 2 consecutive days), intraperitoneal injection (IP) group (ISO 5 mg/kg for 2 consecutive days), 2+1 group (ISO 5mg/kg by SC for 2 consecutive days, then ISO 3mg /kg by IP for 1 day), 6+1 group ( ISO 5mg/kg by SC for 6 consecutive days, then ISO 3mg /kg by IP for 1 day).The ECG were recorded by BL-420F system. The pathological changes in myocardial tissue were observed by HE and Masson staining. The serum cTnI, TNF-α, IL-6, and IL-1β levels were detected by ELISA. Serum CK, LDH and oxidative stress-related indicators were detected by an automatic biochemical analyser. ResultsThe cardiomyocytes in the CON group rats were normal, while those in the other groups showed signs of disorder, unclear borders, and lysis and necrosis, especially in the 6+1 group. The incidence of arrhythmia, arrhythmia score, and the levels of serum myocardial enzymes, troponin, and some inflammatory factors in the 2+1 group and 6+1 group were higher than those in the single injection way (P<0.01 or P<0.05). The indicators in the 6+1 group were mostly higher than those in the 2+1 group (P<0.01), and the SOD level in the 6+1 group was lower than that in the CON group; the MDA and NO higher(P<0.01 or P<0.05). ConclusionThe combined mode of ISO injection (SC with IP) is more likely to induce arrhythmia than single ISO injection. The "6+1" method of ISO injection can establish a more stable arrhythmia model. Cardiomyocyte damage induced by oxidative stress and inflammation is an important mechanism.
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