Administration of protopine prevents mitophagy and acute lung injury in sepsis

Introduction: Sepsis is a severe life-threatening infection that induces a series of dysregulated physiologic responses and results in organ dysfunction. Acute lung injury (ALI), the primary cause of respiratory failure brought on by sepsis, does not have a specific therapy. Protopine (PTP) is an alkaloid with antiinflammatory and antioxidant properties. However, the function of PTP in septic ALI has not yet been documented. This work sought to investigate how PTP affected septic ALI and the mechanisms involved in septic lung damage, including inflammation, oxidative stress, apoptosis, and mitophagy.Methods: Here, we established a mouse model induced by cecal ligation and puncture (CLP) and a BEAS-2B cell model exposed to lipopolysaccharide (LPS).Results: PTP treatment significantly reduced mortality in CLP mice. PTP mitigated lung damage and reduced apoptosis. Western blot analysis showed that PTP dramatically reduced the expression of the apoptosis-associated protein (Cleaved Caspase-3, Cyto C) and increased Bcl-2/Bax. In addition, PTP decreased the production of inflammatory cytokines (IL-6, IL-1β, TNF-α), increased glutathione (GSH) levels and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) levels. Meanwhile, PTP significantly reduced the expression of mitophagy-related proteins (PINK1, Parkin, LC-II), and downregulated mitophagy by transmission electron microscopy. Additionally, the cells were consistent with animal experiments.Discussion: PTP intervention reduced inflammatory responses, oxidative stress, and apoptosis, restored mitochondrial membrane potential, and downregulated mitophagy. The research shows that PTP prevents excessivemitophagy and ALI in sepsis, suggesting that PTP has a potential role in the therapy of sepsis

Improved Double-Layer Soil Consolidation Theory and Its Application in Marine Soft Soil Engineering

Marine soft soil foundation is a double-layer foundation structure with a crust layer and soft substratum. Moreover, it is common that there are various forms of drainage. Accordingly, based on Terzaghi’s consolidation theory and the continuous drainage boundary conditions theory of controllable drainage conditions, an improved double-layer soil consolidation theory considering continuous drainage boundary conditions was proposed. To improve the computational efficiency and accuracy, the Laplace transform and the Stehfest algorithm was used to deduce the numerical solution of the improved double-layer soil consolidation theory considering continuous drainage boundary conditions and to compile a computer program. Subsequently, the theory was validated and analyzed by the degenerated model of the perfectly permeable boundary conditions and the semi-permeable boundary conditions, respectively, which showed that this theory has higher accuracy. Simultaneously, the analysis of double-layer consolidation settlement under continuous drainage boundary conditions for marine soft soil foundation of Guangxi Binhai Highway was carried on. The result showed that the consolidation settlement calculated by the improved double-layer consolidation theory presented is basically consistent with the field measurement results, and that the correlation coefficient between them is higher. Accordingly, the research results can provide useful basic information for marine soft foundation engineering

Cable-driven MIS robot with intuitive manipulability and direct force feedback

The master-slave control mode of minimally invasive surgery (MIS) robot systems improves intuitive manipulability of MIS, but it cuts off direct force feedback between the master and slave manipulator. In order to design a MIS robot with both intuitive manipulability and direct force feedback, the following studies were conducted. Firstly, based on a new task division of the console surgeon and operating-table surgeon, a new model of an MIS robots system was proposed, in which the operating-table surgeon worked as main surgeon and the console surgeon worked as assistant surgeon. Secondly, according to the workspace requirement of MIS, a symmetrical cable-driven MIS robot was designed including structure, layout of driving cable and motion characteristics. Thirdly, the prototype was manufactured and related experiments were carried out, such as flexibility experiment, position control accuracy experiment and motion performance experiment. The study is important for both improving intuitive manipulability and realizing force feedback of MIS robot

A new criteria for acute on preexisting kidney dysfunction in critically ill patients

AbstractCritically ill patients with preexisting kidney dysfunction (PKD) are at high risk for acute kidney injury (AKI). Nevertheless, there is no criteria for screening and classifying AKI in patients with PKD. In this study, after assessing relationship between the change in SCr from baseline and in-hospital mortality, a new criteria, named APKD, for identifying AKI in PKD was proposed. APKD defined AKI in critically ill patients with PKD as an absolute increase of ≥ 0.2 mg/dL in SCr within 48 h or an increase in SCr ≥ 1.1 times over baseline within 7 d. APKD detected more AKI among PKD patients compared with the other criteria. Additionally, the AKI patients identified by APKD but missed by the other criteria had higher mortality than those without AKI. APKD shows higher sensitivities than KDIGO criteria in predicating in-hospital mortality. APKD, but not the KDIGO, is effective for staging the severity of AKI in patients with PKD. In conclusion, APKD is more effective in screening and classifying AKI in critically ill patients with PKD compared with the earlier criteria, and it may helpful in guiding clinical treatment and predicting prognosis

Th17/Treg balance: the bloom and wane in the pathophysiology of sepsis

Sepsis is a multi-organ dysfunction characterized by an unregulated host response to infection. It is associated with high morbidity, rapid disease progression, and high mortality. Current therapies mainly focus on symptomatic treatment, such as blood volume supplementation and antibiotic use, but their effectiveness is limited. Th17/Treg balance, based on its inflammatory property, plays a crucial role in determining the direction of the inflammatory response and the regression of organ damage in sepsis patients. This review provides a summary of the changes in T-helper (Th) 17 cell and regulatory T (Treg) cell differentiation and function during sepsis, the heterogeneity of Th17/Treg balance in the inflammatory response, and the relationship between Th17/Treg balance and organ damage. Th17/Treg balance exerts significant control over the bloom and wanes in host inflammatory response throughout sepsis

Additional file 3 of Comprehensive analysis of alternative polyadenylation regulators concerning CD276 and immune infiltration in bladder cancer

Additional file 3: Supplementary Table 2. Correlation statistics between CPSF3 and immune checkpoint-related genes

Additional file 5 of Comprehensive analysis of alternative polyadenylation regulators concerning CD276 and immune infiltration in bladder cancer

Additional file 5: Supplementary Table 4. The patients’ clinical information (n = 16) in this study

Additional file 2 of Comprehensive analysis of alternative polyadenylation regulators concerning CD276 and immune infiltration in bladder cancer

Additional file 2: Supplementary Table 1. The results of the GSEA

Additional file 1 of Comprehensive analysis of alternative polyadenylation regulators concerning CD276 and immune infiltration in bladder cancer

Additional file 1: Supplementary Figure 1. Consensus clustering for APA regulators in bladder cancer (BC). (A–D) Four heat maps exhibit the clustering matrix for APA regulators in BC patients for k = 3, 4, 5, and 6. The tighter and clearer the clusters are, the more optimal the cluster. (E) Delta area curve of consensus clustering for k = 2–6. (F) Principal component analysis of BC patients' APA regulator expression profiles demonstrates two patient clusters