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MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells. MiR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of doxorubicin (DOX) by targeting HMGB1. The miR-142-3p/HMGB1 axis might be an important pathway regulating the sensitivity of breast cancer cells. Image 1 [ABSTRACT FROM AUTHOR]

• The failure risk of carbon reduction technology and a new kind of risk hedging tool, carbon insurance is studied. • Carbon insurance can lower the entry threshold of green investment for the manufacturer. • Carbon insurance can increase manufacturer's production quantity and expected profit. • Different compensation modes and strategic roles of the insurer lead to different environmental impacts. • Carbon insurance plays a better role in reducing carbon emissions without government enforcement. Carbon insurance is an emerging green financial instrument, which makes significant differences in spreading the failure risk of innovative but immature carbon reduction technology, thereby ensuring enterprises for low-carbon transition. We consider a carbon insurance supply chain including a manufacturer and an insurer. The manufacturer produces and sells a product to customers. To reduce carbon emission and thus save cost under cap-and-trade mechanism, the manufacturer invests in a new but immature carbon reduction technology, and he purchases a carbon insurance from the insurer to hedge the failure risk. We first reveal that carbon insurance can lower the manufacturer's entry barrier of green investment, attracting more firms, especially small and medium-sized enterprises, to adopt carbon reduction technology. Besides, the manufacturer buying carbon insurance produces more products and earns more profit than not buying. For the environmental impacts, the compensation mode of carbon insurance takes an important role. The carbon insurance can further reduce carbon emissions under a certain condition if the insurer compensates the manufacturer with carbon. However, it always leads to higher carbon emission if the insurer compensates the manufacturer with funds. The impacts of carbon insurance also are influenced by the strategic choice of the insurer. The manufacturer earns the most profit and emits the most carbon if the insurer is non-strategic. In contrast, the manufacturer earns less but emits less carbon if the insurer is strategic. Meanwhile, carbon insurance can play a better role in reducing carbon emissions when the manufacturers volunteer to reduce carbon emissions but are not government-mandated. Finally, we provide corresponding management implications for different situations. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to develop a stable and biodegradable tacrolimus loaded nanocarrier that enhanced tacrolimus corneal penetration and delivered in a sustained manner, thus to create a promising treatment to prevent immune rejection after corneal allografts. Spherical tacrolimus loaded methoxy poly (ethylene glycol)- block -poly (D,L)-lactic- co -glycolic acid (mPEG- b -PLGA) micelles with a mean diameter of 81.3 ± 1.3 nm were prepared by the solvent-evaporation-induced self-assembly. The physicochemical properties of tacrolimus loaded mPEG- b -PLGA micelles were evaluated, and the in vitro release behavior, degradation, cytotoxicity and bio-safety were all assessed. The ex vivo permeation of tacrolimus using rabbit corneas was also performed, and the cumulative permeation amount of tacrolimus from mPEG- b -PLGA micelles was significantly higher than 0.05% tacrolimus eye drops (p < 0.05). These results indicated that the formulations were feasible for intraocular drug delivery. Compared with 0.05% tacrolimus eye drops, the in vivo immunofluorescence analysis indicated the tacrolimus loaded mPEG- b -PLGA micelles remarkably inhibit the immune rejection after corneal allograft, with the lower expression levels of nuclear factor of activated T cells (NFAT), cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8). In conclusion, we provided evidences that tacrolimus loaded mPEG- b -PLGA micelles would be a promising treatment for immune rejection after corneal transplantation. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

FK506 (tacrolimus) is an effective immunosuppressant, but its poor water solubility and low bioavailability impose barriers to ocular drug delivery. The nanomicelles (NMs) formulations comprised of amino-terminated poly(ethylene glycol- block -poly(D,L)-lactic acid) (NH 2 -PEG- b -PLA) and hydroxypropyl methylcellulose (HPMC) were developed to increase the penetration of hydrophobic drugs in the eye and enhance the drug bioavailability for ocular disorder therapy. Spherical FK506/NH 2 -PEG- b -PLA/HPMC NMs with mean diameter of 101.4 ± 1.3 nm were prepared by solvent-evaporation-induced self-assembly in aqueous solution. The NMs that sufficiently solubilized FK506 were evaluated in terms of stability, drug loading, encapsulation efficiency, surface tension, cellular cytotoxicity and in vitro release, and the results revealed the NMs were suitable for intraocular drug delivery. Compared with the 0.05% FK506 suspension drops, the in vitro permeation amount of FK506 from NMs exhibited significant increase. Besides, the higher concentration and longer retention of FK506 in ocular tissue were also confirmed in vivo. Furthermore, the FK506/NH 2 -PEG- b -PLA/HPMC NMs obviously inhibited the allograft rejection after corneal transplantation in rats. In conclusion, FK506/NH 2 -PEG- b -PLA/HPMC NMs formulations as a promising ocular drug delivery system would be able to improve the bioavailability and efficacy of FK506 in anti-allograft rejection. [ABSTRACT FROM AUTHOR]

The increased awareness of the need for protecting the environment and policies relating to carbon emissions has resulted in manufacturers viewing carbon emissions as one of the most critical elements affecting production decisions. As a gradually maturing production form, remanufacturing plays an increasingly pivotal role in economy, environment and society. This paper extends the classical EOQ model, considers carbon emissions in (re)manufacturing activities and product transportation and builds an inventory cost model with carbon constraints. The optimal batch and quantity of manufacturing/remanufacturing and the frequency of cyclic remanufacturing are derived with and without carbon constraints through analysis of the model. At the same time, this paper investigates the impact of carbon emissions quota and its trade prices, remanufacturing ratio and different means of transportation on manufacturers’ decisions. The examples show that the batch size of manufacturing and remanufacturing is identical within the period with carbon constraints; the batch size of manufacturing without carbon constraints is less than remanufacturing with carbon constraints; the results are just the opposite in terms of the batch of remanufacturing and the number of remanufactured products. In other words, the (re)manufacturers’ total cost and carbon emissions with carbon constraints are lower than those without carbon constraints. Starting from the real-life circumstances, this article considers manufacturers’ total cost with imperfect remanufacturing, varied means of transportation, carbon quota and its trade, which have not been taken into account previously, the manufacturer’s optimal decisions are derived. Meanwhile, the analysis of carbon quota can provide some insights for governments and enterprises in terms of carbon emissions rights allocation. [ABSTRACT FROM AUTHOR]