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Optimization of an intra-city express delivery network from three to two levels is of great interest to suppliers and customers for reducing costs and improving service efficiency. One feasible solution is to identify critical nodes in the three-level network and upgrade them as transshipment facilities in the two-level one. However, traditional optimization models seldom combine empirical business data, composite metrics, and objective evaluation rules. We proposed an approach integrating empirical data, multi-criteria decision-making methods based on the real-world application of the SF Express Chengdu branch. We also developed a mathematical optimization model using statistical and operations management techniques combined with logistics expertise for a location decision. First, the appropriateness of each service point as a candidate transshipment facility is evaluated from internal and external perspectives by applying multiple centrality assessment from complex network theory and fuzzy Technique for Order Preference by Similarity to an Ideal Solution, respectively. Second, 16 candidate transshipment facilities are selected by combining these two ways. Then, a multi-objective integer programming model is built to obtain the optimal number, locations of transshipment facilities, and the corresponding service points covered by each transshipment facility. Using this multi-methodologic approach, we show that the optimized two-level network is economically feasible and simply applicable, with the total cost and average delivery time reduced by 18.41% and 6 h, respectively. This article is of practical significance and provides an important reference for optimizing ground express service networks for other large cities. [ABSTRACT FROM AUTHOR]

Recently, the trend of obesity is becoming increasingly prevalent, and the underlying pathogenesis of obesity is complex and needs to be researched further. In this study, we report a decreased expression of let-7a-5p in the white adipose tissue (WAT) of animals with obesity. Using the RNA oligo, let-7a-5p over-expression or suppression–expression is achieved, impacting the proliferation and differentiation of preadipocytes in vitro. Srebf2 mechanistically interacts with the metabolic effect of let-7a-5p and participates in lipid accumulation by regulating Srebf2 downstream signaling. Moreover, let-7a-5p binds to Thbs1 to interact with the PI3K-AKT-mTOR pathway, down-regulating the phosphorylation levels of AKT, mTOR, and S6K1 to decrease lipid accumulation. In conclusion, our study highlights the physiological significance of let-7a-5p in lipid accumulation and suggests that the let-7a-5p/Srebf2 and let-7a-5p/Thbs1/PI3K-AKT-mTOR axes may represent potential mechanisms for controlling lipid accumulation in obesity. [ABSTRACT FROM AUTHOR]

Obesity, a major global health issue, is increasingly associated with the integral role of long non-coding RNA (lncRNA) in adipogenesis. Recently, we found that lncRNA-MSTRG4710 was highly expressed in the liver of rabbits fed a high-fat diet, but whether it is involved in lipid metabolism remains unclear. A series of experiments involving CCK-8, EDU, qPCR, and Oil Red O staining demonstrated that the overexpression of MSTRG4710 stimulated the proliferation and differentiation of preadipocytes while its knockdown inhibited these processes. Bioinformatics analysis showed that miR-29b-3p was a potential target gene of MSTRG4710, and IGF1 was a downstream target gene of miR-29b-3p. Luciferase reporter gene analysis and qPCR analysis confirmed that miR-29b-3p was a potential target gene of MSTRG4710, and miR-29b-3p directly targeted the 3′UTR of IGF1. The overexpression of miR-29b-3p was observed to regulate IGF1 protein and mRNA levels negatively. Additionally, a total of 414 known differentially expressed genes between the miR-29b-3p mimic, miR-29b-3p negative control (NC), siMSTRG4710, and siMSTRG4710-NC group were screened via transcriptome sequencing technology. The GO- and KEGG-enriched pathways were found to be related to lipid metabolism. The study also established that miR-29b-3p targets IGF1 to inhibit preadipocyte proliferation and differentiation. Notably, IGF1 knockdown significantly reduced preadipocyte proliferation and differentiation. Furthermore, co-transfection of pcDNA3.1(+)-MSTRG4710 and mimics into rabbit preadipocytes revealed that the mimics reversed the promotional effect of pcDNA3.1(+)-MSTRG4710. In conclusion, these results uncover that MSTRG4710 positively regulated cell proliferation and adipogenesis by the miR-29b-3p/IGF1 axis. Our findings might provide a new target for studying adipogenesis in rabbit preadipocytes and obesity. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether high‐fat diet (HFD) could cause growth, behavioural, biochemical and morphological changes in young female rabbits. Thirty‐six female rabbits were randomly divided into two groups fed with either a high‐fat diet (HFD) or a standard normal diet (SND) for 5 weeks. Growth and behavioural changes were recorded during the 5‐week feeding period. Tissue samples, including blood and adipose tissue, were obtained after slaughter. HFD rabbits weighed more by the end of the feeding period, had a higher percent body weight and adipose tissue weight change and had longer body and bust lengths than SND rabbits. HFD rabbits significantly reduced their feed intake and feeding frequency during the fourth and fifth weeks. HFD rabbits also showed lower frequency of drinking and resting and increased stereotypical behaviour. Besides, HFD rabbits showed significant physiological abnormalities. HFD rabbits had higher serum cholesterol (TC) and triglycerides (TG) levels than SND rabbits at the end of the feeding period, and higher free fatty acid (FFA) levels than rabbits in the SND group after the third week of feeding. Serum thyroxine (T4) increased significantly in week 2 and week 5 and triiodothyronine (T3) increased significantly in week four. However, there was no significant change in serum glucose (GLU) and insulin (INS) levels. Additionally, HFD reduced the area and diameter of perirenal and subcutaneous fat cells and increased their density. Our findings suggest that HFD rabbits had higher weight gains, accumulation of fat, and more behavioural changes than SND rabbits. Although high levels of fat in the diet had a low impact on hyperglycaemia, it could lead to hyperlipidemia and hyperthyroidism. Our results also suggest that sustained HFD may cause the proliferation of adipocytes in young female rabbits. [ABSTRACT FROM AUTHOR]