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While embedding in the global value chain (GVC), avoiding becoming a “pollution shelter” is an urgent issue that needs to be solved for the low-carbon economic development of countries along the Belt and Road. This study empirically analyzes the impact of manufacturing GVC embedding on carbon emissions and its mechanism from the perspectives of the embedding position and degree of the GVC. It then carries out group regressions by different industries, value chain embedding modes, and so on. Finally, this study constructs static and dynamic panel models to verify the nonlinear relationship between manufacturing GVC embedding and carbon emissions. The results show that the improvement of the embedding position of GVC in the manufacturing industry promotes an increase in carbon emissions; the deeper the embedding degree of GVC, the more conducive it is to carbon emissions reduction. Compared with the service industry, the impact of manufacturing GVC embedding on carbon emissions is more significant; regardless of the value chain embedding model, the deeper the embedding degree, the more conducive it is to carbon emissions reduction. Technological progress can weaken the impact of GVC embedding on carbon emissions. There is a U-shaped relationship between the GVC embedding position and carbon emissions in the manufacturing industry and an inverted U-shaped relationship between the GVC embedding degree and carbon emissions. This study provides beneficial insights for countries along the Belt and Road to embed into the GVC to avoid falling into the dilemma of “pollution growth”.

Brain barrier is both a protective permeability hurdle and a limitation site where therapeutic agents are excluded to enter the target region. Designing drug vehicle to overcome this notorious barrier bottle is challenging. Herein, we construct a stimuli-responsive self-assembled nanovesicle that delivers water-soluble drugs to prevent the efflux transport of brain barriers by responding to the endogenously occurring signals in Alzheimer's disease (AD) brain microenvironment. Once stimuli-responsive vesicles are accumulated in intracerebrally, the intrinsically occurring legumain endopeptidase cleaves the Ac-Ala-Ala-Asn-Cys-Asp (AK) short peptide on the drug vesicles to expose the 1,2 thiol amino group to cyclize with the cyano groups on 2-cyano-6-aminobenzothiazole (CABT) of the chaperone vesicles, thus triggering the formation of cross-linked micrometre-scale vesicles. Such a structural alteration completely prevents further brain barriers efflux. The superior neuroprotective capacity of cross-linked vesicles is validated in senescence accelerated mouse prone 8 (SAMP8). This smart multi-drug delivery vesicle is promising to serve as a powerful system for AD treatment and can be adapted for the therapy of other central nervous system (CNS) disorders., Graphical abstract a) Responsive cross-linked of large compound vesicles formed in intracerebrally. b) Inhibition of brain barrier efflux and synergistic treatment of AD.Image 1, Highlights • Drug efflux is a bottleneck for treating many disorders, such as Alzheimer's diseases (AD). • The key to success in drug brain parenchyma anchoring is specific targeting delivery. • Functionalized vesicles provided the possibility of inhibiting the efflux transport and increasing drug brain enrichment. • Legumain-induced aggregated multi-drug delivery vesicle is promising to serve as a powerful system for AD treatment.

Advanced drug vehicle exploitation and the sophisticated synergy mechanism revelation are two great difficulties in combination therapy. Compared with most readily available polymer micelles, some undiscovered complex chemical design principles limit the expanding research of polymer vesicles. Here, polycaprolactone (PCL)-g-Dextran vesicle that dextran brush steric hindrance guide PCL lamellae-aligned growth was synthesized. The effect of the glycometabolism multi-drug vesicle combination treatment and synergism mechanism were investigated on senescence-accelerated mouse prone 8 (SAMP8) mice. The main insulin sensitizer drug could improve the memory ability of mice to a small extent, and the main insulin secretion promoter drug had little beneficial effect. Moreover, the triple anti-insulin resistant drugs of insulin (INS), repaglinide (REP) and metformin hydrochloride (MET) activated the glycometabolism-related bio-signals, and the energy cycle was normalized successfully. The insulin intracellular uptake and utilization efficiency could be the reason for the gap. The upregulation of the brain-derived neurotrophic factor (BDNF) protein confirmed that the crosstalk between the mitochondria and synapse contributes to the nerve repair. This study provided an excellent drug combination vesicle to treat Alzheimer's disease (AD). The discovery of the combination mechanism leads to an improvement in the AD clinical treatment.

Current forms of medication for Alzheimer's disease (AD) provide a symptomatic benefit limited to those with early onset, but there is no single drug available for later stage patients. Given the recent failures of AD drugs in clinical trials, an intensive treatment strategy based on drug combination that is approved is attractive. At present, the greatest difficulty lies in the low accumulation of drugs in the brain. All hydrophilic drugs are limited by the physical and biochemical barriers within the blood–brain barrier and lipophilic drugs are often transported back into the blood by efflux pumps located in the blood–brain barrier. Here, we select elevated asparagine endopeptidase (AEP) as a target to trigger in situ cross-linking of small sized particles to form large sized drug clusters to block the efflux of the brain. Subsequently, responsive cross-linking micelles (RCMs) loaded with the acetylcholinesterase inhibitor, donepezil (DON), the microtubule therapeutic agent, Paclitaxel (PTX), and the glucose metabolism disorder regulator, insulin (INS) are investigated, with a focus on high levels of drug accumulation in the brain in AD. These smart multi-drug delivery RCMs provide a powerful system for AD treatment and can be adapted for other central nervous system (CNS) disorders.