A novel fusion protein consisting of anti-ANGPTL3 antibody and interleukin-22 ameliorates diabetic nephropathy in mice

IntroductionThe pathogenic mechanisms of diabetic nephropathy (DN) include podocyte injury, inflammatory responses and metabolic disorders. Although the antagonism of Angiopoietin-like protein 3 (ANGPTL3) can alleviate proteinuria symptoms by inhibiting the activation of integrin αvβ3 on the surface of podocytes, it can not impede other pathological processes, such as inflammatory responses and metabolic dysfunction of glucolipid. Interleukin-22 (IL-22) is considered to be a pivotal molecule involved in suppressing inflammatory responses, initiating regenerative repair, and regulating glucolipid metabolism.MethodsGenes encoding the mIL22IgG2aFc and two chains of anti-ANGPTL3 antibody and bifunctional protein were synthesized. Then, the DN mice were treated with intraperitoneal injection of normal saline, anti-ANGPTL3 (20 mg/kg), mIL22Fc (12 mg/kg) or anti-ANGPTL3 /IL22 (25.3 mg/kg) and irrigation of positive drug losartan (20mg/kg/d) twice a week for 8 weeks.ResultsIn this research, a novel bifunctional fusion protein (anti-ANGPTL3/IL22) formed by the fusion of IL-22 with the C-terminus of anti-ANGPTL3 antibody exhibited favorable stability and maintained the biological activity of anti-ANGPTL3 and IL-22, respectively. The fusion protein showed a more pronounced attenuation of proteinuria and improved dysfunction of glucolipid metabolism compared with mIL22Fc or anti-ANGPTL3. Our results also indicated that anti-ANGPTL3/IL22 intervention significantly alleviated renal fibrosis via inhibiting the expression of the inflammatory response-related protein nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) p65 and NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Moreover, transcriptome analysis revealed the downregulation of signaling pathways associated with injury and dysfunction of the renal parenchymal cell indicating the possible protective mechanisms of anti-ANGPTL3/IL22 in DN.ConclusionCollectively, anti-ANGPTL3/IL22 bifunctional fusion protein can be a promising novel therapeutic strategy for DN by reducing podocyte injury, ameliorating inflammatory response, and enhancing renal tissue recovery

Prefabricated housing subsidy analysis in China based on an evolutionary game model

Prefabricated housing and cast-in-site housing are two alternatives for selection by developers and customers. The government, as the policy maker, creates incentive policies to encourage developers and customers to choose prefabricated housing. This paper aims to analyze the subsidy mechanism to theoretically confirm the subsidies’ scopes, amounts and end times through an evolutionary game model and simulation. In the game model, government subsidies affect the interactions between developers and customers in the decision-making process. The findings are as follows: 1) The developer housing subsidy can lower the housing price, while the customer housing subsidy can increase the price; 2) The government should first offer the developers a larger subsidy amount during the early development stage and then offer the customers a smaller subsidy amount later; 3) The government should determine the end time based on the proportion of developers and customers who choose prefabricated housing; 4) A higher prefabrication ratio may not always improve the development of prefabricated housing, and there is an optimal production scale that creates the best development situation. The empirical analysis shows that this model can help the government develop reasonable and optimal subsidy policies within the limit of budget to stimulate developers and customers

Research on the rework risk core tasks in prefabricated construction in China

PurposeThe purpose of this paper is to assess the process of prefabricated construction (PC) and analyze the impacts of rework risk to identify the core tasks for which the rework risk has severe impacts.Design/methodology/approachThe methods consist of a literature review, expert interviews, a questionnaire survey and a rework risk function. The expert interviews and questionnaire survey were administered to experts in the entire process of PC from the dimensions of rework frequency, rework cost and rework time. Descriptive and inferential statistics were employed to analyze the data. The rework risk function was based on the loss expectancy method.FindingsThere are 13 core tasks that have higher impacts than the average level. The core tasks in the design stage account for 100% of the tasks in the stage, those in the manufacturing stage account for 20% and those in the construction stage account for 23.1%. Compared with the other stages, the design stage is characterized by significantly more frequent rework, higher rework costs and longer rework time. The manufacturing stage is characterized by significantly higher rework costs than the construction stage. The manufacturing stage and construction stage are co-reliant, and both are impacted by the design stage.Practical implicationsThe findings provide stakeholders with a clear understanding of the core tasks of the PC process and represent a method for identifying core tasks. Stakeholders can learn from this to focus on the core tasks to reduce rework risk and manage the process with the priority of PC rework management based on the following order: design &gt; manufacturing &gt; construction. The approach is suitable for core task identification in other areas.Originality/valueThis research provides insight into rework risk management and provides a novel analysis method for rework risk and PC management from the perspective of the construction process. The findings are valuable for supporting stakeholders in making effective construction plans to reduce the impacts of rework risk in PC and provide a reference for future research on process optimization.</jats:sec

Double-sided friction stir welding of 2195 aluminum-lithium alloy

Based on the response surface design， the optimal process parameters for single-side friction stir welding（FSW） of 2195 Al-Li alloy sheets are studied. It is found that the higher the rotation speed and the lower the welding speed， the higher the tensile strength of the welded joint. The results show that in the single-side FSW， when the pin length is 2/3 length of the thickness of the plate， the root of the weld appears unwelded defects， the fracture form of the welded joint is between brittle and plastic fracture， and the tensile strength of the joint is poor. Based on the optimum process parameters of single-sided welding， double-sided FSW can overcome the unwelded defects at the root of single-sided welding. Under different tool pressures， when the stirring head speed is 1600 r/min， the feed speed is 150 mm/min， and the pressure is 0.1 mm， the double-sided welding can improve the tensile strength of the welded joint by about 10% and the elongation of the welded joint by 10%. In two-sided FSW， the material flow on the forward side is obvious， and the fracture mode of the welded joint is a plastic fracture. In double-sided welding， the plate is subjected to secondary stirring and heating， resulting in increased softening of the material in the welding area.The microhardness of the double-sided welded joint is further reduced than that of the single-sided welding

PREFABRICATED HOUSING SUBSIDY ANALYSIS IN CHINA BASED ON AN EVOLUTIONARY GAME MODEL

Prefabricated housing and cast-in-site housing are two alternatives for selection by developers and customers. The government, as the policy maker, creates incentive policies to encourage developers and customers to choose prefabricated housing. This paper aims to analyze the subsidy mechanism to theoretically confirm the subsidies’ scopes, amounts and end times through an evolutionary game model and simulation. In the game model, government subsidies affect the interactions between developers and customers in the decision-making process. The findings are as follows: 1) The developer housing subsidy can lower the housing price, while the customer housing subsidy can increase the price; 2) The government should first offer the developers a larger subsidy amount during the early development stage and then offer the customers a smaller subsidy amount later; 3) The government should determine the end time based on the proportion of developers and customers who choose prefabricated housing; 4) A higher prefabrication ratio may not always improve the development of prefabricated housing, and there is an optimal production scale that creates the best development situation. The empirical analysis shows that this model can help the government develop reasonable and optimal subsidy policies within the limit of budget to stimulate developers and customers.</jats:p