•A logistics network model under the environment of low-carbon is proposed.•Solution processes with PSO and GA are constructed.•The validity and reliability of the model are verified by a calculating ...case study.•Provides a reference for the design of forward and reverse logistics network.
In view of the rapid development of low-carbon economy, the increasing distribution demand and returned demand which caused by the short shelf life and spoilage of fresh food, network and route planning model of a two-stage forward/reverse logistics is firstly proposed for fresh food e-commerce enterprises under the environment of low-carbon emissions (The objective in the first stage is to minimize the overall cost of the system, and the minimum overall cost of the circulation-type distribution vehicles routing is considered in the second stage). And the validity of the model is verified by adopting genetic algorithm (GA) and particle swarm optimization (PSO) algorithm with the study of the fresh food e-commerce enterprises of Shanghai. Furthermore, a good reference can be provided to build the forward and reverse logistics network and optimal route planning model of fresh food e-commerce enterprises and reduce the carbon emissions during its operation process.
Autophagy is an evolutionarily conserved process responsible for the degradation and recycling of cytoplasmic components through autolysosomes. Targeting AR axis is a standard strategy for prostate ...cancer treatment; however, the role of AR in autophagic processes is still not fully understood. In the present study, we found that AR played a negative role in AR degrader celastrol-induced autophagy. Knockdown of AR in AR-positive prostate cancer cells resulted in enhanced autophagy. Ectopic expression of AR in AR-negative prostate cancer cells, or gain of function of the AR signaling in AR-positive cells, led to suppression of autophagy. Since miR-101 is an inhibitor of autophagy and its expression was decreased along with AR in the process of celastrol-induced autophagy, we hypothesize that AR inhibits autophagy through transactivation of miR-101. AR binding site was defined in the upstream of miR-101 gene by luciferase reporter and ChIP assays. MiR-101 expression correlated with AR status in prostate cancer cell lines. The inhibition of celastrol-induced autophagy by AR was compromised by blocking miR-101; while transfection of miR-101 led to inhibition of celastrol-induced autophagy in spite of AR depletion. Furthermore, mutagenesis of the AR binding site in miR-101 gene led to decreased suppression of autophagy by AR. Finally, autophagy inhibition by miR-101 mimic was found to enhance the cytotoxic effect of celastrol in prostate cancer cells. Our results demonstrate that AR inhibits autophagy via transactivation of miR-101, thus combination of miR-101 mimics with celastrol may represent a promising therapeutic approach for treating prostate cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Celastrol has potential application for the treatment of prostate cancer. However it causes autophagy as a protective response in prostate and other types of cancers, thus unveiling the underlying ...mechanisms may benefit its future application. In the present study, we demonstrate that the miR-17-92a cluster plays a negative role in celastrol induced-autophagy. Dissection of miR-17-92a cluster revealed the role of miR-17 seed family (miR-20a and miR-17) in autophagy inhibition in the context of prostate cancer cells. Autophagy-related gene ATG7 was validated as a target of miR-17 seed family by dual-luciferase assay and qPCR. Celastrol induced autophagy was inhibited by miR-20a or miR-17, while the inhibitory effects were rescued in the presence of pcDNA-ATG7 lacking 3′ UTR, demonstrating that these two members target ATG7 to inhibit celastrol-induced autophagy. As celastrol degrades androgen receptor (AR), a key transcription factor in prostate cancer cells, we further investigated whether AR affected miR-17-92a expression in prostate cancer cells. AR binding sites were found in the promoter and two introns of miR-17-92a. In addition, higher expression levels of miR-17-92a were observed in AR positive cells compared with AR negative cells. Ectopic expression of AR could enhance the expression of miR-17-92a cluster in AR-negative prostate cancer cells while knockdown of AR decreased miR-17-92a expression in AR-positive cells, demonstrating the regulation of AR on miR-17-92a transcription. In summary, our results demonstrate that celastrol downregulates AR and its target miR-17-92a, leading to autophagy induction in prostate cancer cells.
•MiR-17-92a cluster plays a negative role in autophagy regulation.•MiR-17-92a targets ATG7 for autophagy inhibition.•AR transactivates miR-17-92a cluster.
Pulmonary fibrosis is an end-stage respiratory disease characterized by fibroblast proliferation and accumulation of extracellular matrix and collagen, which is accompanied by inflammatory damage. ...The disease is mainly based on pulmonary dysfunction and respiratory failure, the incidence of it is increasing year by year, and the current treatment methods for it are limited. In recent years, it has been found that gut microbes play a crucial role in the pathogenesis and development of pulmonary fibrosis. The microecological disturbance caused by changes in the composition of the intestinal flora can affect the course of pulmonary fibrosis. The regulatory network or information exchange system for gut-lung crosstalk is called the “gut-lung axis”. This review focuses on the frontier research on entero-pulmonary regulation in pulmonary fibrosis and on intervention strategies for changing the gut microbiota to improve pulmonary fibrosis, including fecal microbiota transplantation, traditional Chinese medicine interventions, and supplementation with probiotics. In addition, the present problems in this field are also raised in order to provide strong theoretical and strategic support for the future exploration of regulatory mechanisms and therapeutic drug development. This paper reviews the interaction of the intestinal flora with pulmonary fibrosis, introduces the research progress for improving pulmonary fibrosis through interventions targeted at the intestinal flora, and provides new ideas for the treatment of pulmonary fibrosis.
With the rapid development of our economy, the demand for reverse logistics is becoming increasingly urgent. This paper proposes a multi-period and dynamic joint construction model to build the ...reverse logistics network and verifies the feasibility of the rendered model by adopting particle swarm optimization (PSO) algorithm and genetic algorithm (GA) with a case study of the apparel E-commerce enterprises of Shanghai. The calculation indicates that, compared with traditional single-period reverse logistics system, dynamic joint construction model is more accordant with the practical situation, the capacity of multi-period model node is easier to optimize and the total operation cost of multi-period model reduces a lot. Furthermore, this research provides reference for reducing the operation costs as well as the building of regional reverse logistics network.
Under the uncertain market demand and quality level, a total profit model of green closed-loop supply chain system (GCL-SCS) considering corporate environmental responsibility (CER) and government ...differential weight subsidy (GDWS) is constructed. Based on incentive-compatibility theory, the optimal subsidy allocation policy and green investment level were explored. Fuzzy chance-constrained programming (FCCP) is used to clarify the uncertainty factors of this model; while genetic algorithm (GA) and CPLEX are used to find and compare a calculating example's approximate optimal solution about this model. The main calculating results indicate that: (1) Enterprises can make optimal recycling, production and sales strategies according to different potential demand; (2) Without government subsidy, enterprises' higher green investment level will reduce their average gross profit, increase the quality level of recycled products and decrease the recycling rate, hence reduce their environmental protection willingness; (3) Based on incentive-compatibility theory, when government subsidy weight is set as 0.34~0.41 for consumers, enterprises' higher green investment level will enhance their average gross profit, reduce the quality level of recycled products and increase the recycling rate, which will improve their environmental protection willingness; (4) Under uncertain environment, the combination of reasonable government subsidy policy and enterprises green investment can make up for the defect of enterprises green investment alone, maximize utilities of government and enterprises, and optimize the green closed loop supply chain.
The methane in the coal seams of abandoned mines is a valuable natural gas resource. However, the ultra-low permeability of coal seams restricts the extraction of coalbed methane. The liquid nitrogen ...fracturing technology is a novel approach suitable for enhancing the permeability of coal seams in abandoned mines. The ultra-low temperature could potentially facilitate the growth and propagation of pores and fractures in coal seams. In this study, we observed inconsistent alterations in coal properties measured by multiple instruments at different scales, whether in dry or wet coal specimens. This suggests that the mechanisms influencing the pore structure due to LN
2
treatment differ across various scales in dry and wet coal specimens. For dry specimens, heterogeneous thermal deformation and freezing shrinkage exhibited opposing effects during LN
2
treatment. Thermal stress-induced micro-fractures might counteract the freezing contraction of micropores in coal matrices, preventing a significant decrease in coal macropores and fractures. In wet specimens, the effects of LN
2
treatment on wet coal specimens were predominantly controlled by frost heaving. However, due to low water saturation, LN
2
treatment had negligible effects on coal micropores, even in the presence of local frost heaving. In field applications, water migration from smaller to larger pores could further diminish the impact of LN
2
treatment on micropores.
Article highlights
LN
2
treatment has different effects on the change in pore structure of coal at multi-scale.
The thermal stress-induced fractures and micropores contraction occur in coal matrices.
Water migration may further reduce the effects of LN
2
treatment on the micropores of coal.
Terpenoids are a large variety of natural products with remarkable diverse biological functions, and have a wide range of applications in flavors, pharmaceuticals, biofuels, pigments, and so on. ...However, limited production of terpenoids from natural resources constrains their use of bulk commodity products.
In vivo
synthetic biosystem, harnessing living organisms to produce terpenoids, has been broadly used and in-depth reviewed for terpenoids production, which has inherent weaknesses, such as slow reaction rate, low product yield, toxic intermediates, and high separation cost. In
vitro
synthetic biosystem, harboring numerous enzymes and/or coenzymes assembled into an
in vitro
enzymatic bioreactions, can obviate part of problems associated with
in vivo
style. In this review, the general design of
in vitro
synthetic biosystem is presented with seven supporting examples: mevalonate, isoprene, limonene, pinene, farnesene, amorpha-4,11-diene and taxadiene. The efforts for the large-scale implementation of in
vitro
synthetic biosystem have been addressed to enzymes engineering, computational modeling and cofactors recycle. The review also discusses the challenges and solutions for the large-scale implementation of
in vitro
synthetic biosystem around enzymes stability and cofactors recycle. This review may suggest
in vitro
synthetic biosystems become a realistic option for the production of diverse valuable terpenoids, even expand to other commodity chemicals.
As the increasing trend of global consumption of waste electrical and electronic equipment (WEEE), the recycling of WEEE has been thought highly of. In order to solve the problems of high economic ...cost, environmental detrimental caused by improper recycling, ignorance of social benefits of recycling, uncertain recycling amount and single recycling channel in recycling process of WEEE, this paper proposes a sustainable multi-objective WEEE double recycling channel fuzzy programming model based on triple bottom line (TBL) theory. First of all, TBL is used to develop sustainable multi-objective recycling models concerning economy, environment and society. Secondly, the model is fuzzed. This process includes two steps: the first step is to take WEEE recycling quantity as a triangular fuzzy parameter, and use fuzzy chance constraint method to transform fuzzy constraint into an equivalent clear condition; the second step is to fuzzify suboptimal objective in the model by defining objective membership degree, and transform multi-objective optimization problem into a single-objective optimization problem based on the maximum satisfaction. Finally, taking a recycling enterprise in Shantou, China, as an example, genetic algorithm (GA) and particle swarm optimization (PSO) are comparatively used to solve a calculation case related to the model and the contribution of the model is verified by comparing economic cost, environmental impact and social benefits of the dual recycling channels.
An integrated multi-objective multi-period multi-stage government-enterprise joint model is constructed to recycle used lead battery effectively. The feasibility of the model is validated with a ...numerical example by adopting a two-phase heuristic algorithm nesting GA/PSO. The results show that the negative effect to the surroundings of the operation in the system is minimized, and the facility resources are fully utilized because of the multi-period arrangement of recycling activities in the system. In addition, the arrangement of the locations and quantities of its nodes in different stages not only reduces the uncertain risk of the system, but optimizes the input of money, manpower and material during the whole operation process. The study provides a reference for the design of joint construction of government-enterprise reverse logistics network and its optimal operation, especially for the recovery of this kind of used products with high negative externality.
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