The Effect of Fairness Concern on Carbon Emission Reduction and Revenue Distribution in Construction Supply Chain: Power Structure Perspective

This paper invested a two-echelon construction supply chain that consists of a general contractor and a subcontractor. This paper constructs the centralized model and the decentralized models, respectively, and studies the emission reduction and revenue distribution strategies of construction supply chain considering fairness concern and cap-and-trade. Numerical analysis is carried out to analyze the influence of cap-and-trade and fairness concern on the optimal decision and the maximum profit of construction supply chain. This paper shows that, under cap-and-trade policy, the centralized model has the best emission reduction effect and the highest supply chain profit without fairness concern, while the general contractor’s Stackelberg model has the best emission reduction effect and the highest supply chain profit with fairness concern. In the two scenarios, the Vertical Nash model is the most unfavorable to emission reduction, and it will also seriously damage the interests of enterprises. In practice, supply chain should choose the general contractor’s Stackelberg model and avoid the Vertical Nash model. Because fairness concern of the subcontractor will damage the supply chain profits and emission reduction performance, the general contractor shall try to select the subcontractor with lower fairness concern to avoid the loss of profit. Besides, enterprises should actively take measures to reduce fairness concern, such as enterprises signing the contract price confidentiality clause, which aims to reduce fairness concern of the subcontractor. The results of this paper can not only enrich the research content of construction supply chain management, but also provide references for the government to formulate emission reduction policies.

Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers

Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is the most common liver disorder in developed countries. Although many new therapeutics for NASH are present in the drug development pipeline, there are still no approved drugs. One of the reasons that makes NASH drug development challenging is the lack of appropriate animal NASH models that resolve issues arising from inter-species differences between humans and rodents. In the present study, we developed a choline-deficient, L-amino-acid-defined, high-fat-diet (CDAHFD)-induced human NASH model using human liver chimeric mice. We demonstrated human hepatocyte injury by an elevation of plasma human alanine aminotransferase 1 in mice fed CDAHFD. Histological analysis showed that CDAHFD feeding induced similar histological changes to human NASH patients, including ballooning, inflammation, apoptosis, regeneration of human hepatocytes, and pericellular and perisinusoidal fibrosis. The chimeric mice fed CDAHFD were treated with a peroxisome-proliferator-activated receptor α/δ agonist, Elafibranor. Elafibranor ameliorated steatosis, ballooning of hepatocytes, and preserved fibrosis progression. We developed a novel humanized NASH model that can elucidate pathophysiological mechanisms and predict therapeutic efficacy in human NASH. This model will be useful in exploring new drugs and biomarkers in the early stages of human NASH.

Addressing Spatial Heterogeneity in the Discrete Generalized Nash Model for Flood Routing

River flood routing is one of the key components of hydrologic modeling and the topographic heterogeneity of rivers has great effects on it. It is beneficial to take into consideration such spatial heterogeneity, especially for hydrologic routing models. The discrete generalized Nash model (DGNM) based on the Nash cascade model has the potential to address spatial heterogeneity by replacing the equal linear reservoirs into unequal ones. However, it seems impossible to obtain the solution of this complex high order differential equation directly. Alternatively, the strict mathematical derivation is combined with the deeper conceptual interpretation of the DGNM to obtain the heterogeneous DGNM (HDGNM). In this work, the HDGNM is explicitly expressed as a linear combination of the inflows and outflows, whose weight coefficients are calculated by the heterogeneous S curve. Parameters in HDGNM can be obtained in two different ways: optimization by intelligent algorithm or estimation based on physical characteristics, thus available to perform well in both gauged and ungauged basins. The HDGNM expands the application scope, and becomes more applicable, especially in river reaches where the river slopes and cross-sections change greatly. Moreover, most traditional routing models are lumped, whereas the HDGNM can be developed to be semidistributed. The middle Hanjiang River in China is selected as a case study to test the model performance. The results show that the HDGNM outperforms the DGNM in terms of model efficiency and smaller relative errors and can be used also for ungauged basins.

Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.

Anti-Autophagy Mechanism of Zhi Gan Prescription Based on Network Pharmacology in Nonalcoholic Steatohepatitis Rats

Background and Aims: Zhi Gan prescription (ZGP) has been clinically proven to exert a favorable therapeutic effect on nonalcoholic steatohepatitis (NASH). This study purpose to reveal the underlying molecular mechanisms of ZGP action in NASH.Methods: Systematic network pharmacology was used to identify bioactive components, potential targets, and the underlying mechanism of ZGP action in NASH. High fat (HF)-induced NASH model rats were used to assess the effect of ZGP against NASH, and to verify the possible molecular mechanisms as predicted by network pharmacology.Results: A total of 138 active components and 366 potential targets were acquired in ZGP. In addition, 823 targets of NASH were also screened. In vivo experiments showed that ZGP significantly improved the symptoms in HF-induced NASH rats. qRT-PCR and western blot analyses showed that ZGP could regulate the hub genes, PTEN, IL-6 and TNF in NASH model rats. In addition, ZGP suppressed mitochondrial autophagy through mitochondrial fusion and fission via the PINK/Parkin pathway.Conclusion: ZGP exerts its effects on NASH through mitochondrial autophagy. These findings provide novel insights into the mechanisms of ZGP in NASH.

Synergic effect of atorvastatin and ambrisentan on sinusoidal and hemodynamic alterations in a rat model of nash

Background & Aims: In non-alcoholic steatohepatitis (NASH) decreased nitric oxide and increased endothelin-1 (ET-1) released by sinusoidal endothelial cells (LSEC), induce hepatic stellate cells (HSC) contraction and contribute to portal hypertension (PH). Statins improve LSEC function, while ambrisentan is a selective endothelin-receptor-A antagonist. We aimed to analyse the combined effects of atorvastatin and ambrisentan on liver histopathology and hemodynamics, together with assessing the underlying mechanism in a rat NASH model. Methods: Diet-induced NASH rats were treated with atorvastatin (10 mg/kg/day), ambrisentan (30 mg/kg/day or 2 mg/kg/day) or the combination for 2 weeks. Hemodynamic parameters were registered and liver histology and serum biochemical determinations analysed. Expression of proteins were studied by immunoblots. Conditioned media experiments were performed in LSEC. HSC were characterized by RT-PCR and a collagen lattice contraction assay was performed. Results: Atorvastatin and ambrisentan act synergistically in combination to completely normalize liver hemodynamic and reverse histological NASH by 75%. Atorvastatin reversed the sinusoidal contractile phenotype improving endothelial function, while ambrisentan prevented the contractile response in HSC by blocking ET-1 response. Additionally, ambrisentan also increased eNOS phosphorylation levels in LSEC, via facilitating the stimulation of endothelin-receptor-B in these cells. Furthermore, the combined treated group reduced to normal serum ALT levels and showed restoration of the HSC quiescent phenotype. Conclusions: Combination of atorvastatin and ambrisentan remarkably improves liver histology and PH in a diet-induced NASH model. By recovering LSEC function, together with inhibiting the activation and contraction of HSC, this combined treatment may be an effective treatment for patients with NASH.

The Mechanism of Increased Intestinal Palmitic Acids Absorption and The Impact On Hepatic Stellate Cell Activation in Non-Alcoholic Steatohepatitis

Dietary palmitic acids (PAs) promote liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). This study aimed to clarify the intestinal absorption kinetics of dietary PAs and the effect of trans-portal PAs on the activation of hepatic stellate cells (HSCs) involved in liver fibrosis in patients with NASH. First, we found that the concentration of blood PAs after meals was significantly increased in NASH patients compared to control patients (P < 0.01). Second, gene expressions associated with fat absorption and chylomicron formation, such as CD36 and MTP, were significantly increased in the intestine of the NASH model rats fed a high-fat-cholesterol diet compared to control rats. Furthermore, portal PA levels after meals in the NASH model rats were significantly higher compared to control and non-alcoholic fatty liver (NAFL) rats (P<0.01). Third, PA injection via the portal vein to the liver in control rats increased the mRNA levels associated with the activation of HSCs and the expression of α-SMA in liver tissues. Our study showed an increased intestinal absorption of dietary-derived PA in NASH. The rapid increase in PAs via the portal vein to the liver may activate HSCs and affect the development of liver fibrosis in NASH.