Several nickel complexes bearing sterically bulky phosphino-phenolate ([P,O]) ligands were synthesized and explored as catalysts for olefin (co)polymerization. In the absence of an activator, the complexes showed very high catalytic activities (up to 10 7 g mol Ni −1 h −1 ) for ethylene polymerization even at 90 °C or with the addition of a large amount of a polar additive (such as ethyl alcohol, diethyl ether, acetone, or even water), affording linear polymers with high molecular weights (up to 6.53 × 10 5 ). In contrast, most of the previously reported nickel catalysts suffer from severe activity suppression at elevated temperature. It is rare that a catalyst has so many good performances simultaneously, including high catalytic activity, good tolerance for polar groups, strong thermal stability, and yielding high molecular weight linear polyethylene. Most importantly, these bulky nickel complexes used in this study also effectively copolymerized ethylene with challenging polar vinyl monomers, including commercially available acrylates and an acrylamide. As we expected, introducing a bulky substituent group on the phosphorus atom of the complex was vital for enhanced catalytic activity and the formation of high molecular weight linear copolymers. Microstructure analyses revealed that the polar functional units were mainly incorporated into the polymer main chain and also located at the chain end with insertion percentages of up to 7.4 mol %. The bulky [P,O] neutral nickel complexes reported herein are promising alternatives to the well-established palladium catalysts for direct copolymerization of olefins with commercially available polar vinyl comonomers.
To reveal effect of electronic or steric modification of phosphino-phenolate nickel complex for preparing optimized catalysts, we take elaborated studies on structure-performance relationship by finely modifying substituents on ortho-phenoxy position or phosphorus moiety of this catalyst. It reveals that these newly synthesized complexes are thermally robust, and exhibits very high activity (up to 10 7 g mol Ni À 1 h À 1 ) in ethylene polymerization even at 120°C. Associated with stoichiometric experiments, experimental results prove that nickel complexes bearing electron-withdrawing substituents on ortho-phenoxy position or electron-donating substituents on phosphorus atom show higher activity than contrastive catalysts toward ethylene polymerization and ethylene-methyl acrylate (MA) copolymerization. Among these catalysts, 3 g bearing a strong electronwithdrawing substituent on ortho-phenoxy position exhibits the highest activity, and produces copolymers with the highest molecular weight and analogous MA incorporation. Various challenging polar vinyl monomers, like polyethylene glycol monomethyl ether acrylate, can be efficiently copolymerized with ethylene.
A series of methyl nickel complexes with phosphino-naphtholate chelate ligands have been strategically designed, synthesized, and fully characterized. These catalysts showed extremely high activity toward ethylene polymerization and ethylene/unsaturated acid ester copolymerization without any activator under mild conditions. The catalytic activity for ethylene polymerization was up to 3.0 × 10 7 g PE mol Ni −1 h −1 , which was the topmost among the neutral nickel catalysts previously reported. Besides, the catalytic activity for ethylene/methyl acrylate (MA) copolymerization was also outstanding (up to 3.7 × 10 5 g mol Ni −1 h −1 ) among the representative Ni and Pd catalytic systems, which could mediate E/MA copolymerization. More remarkably, a very challenging 1,1-disubstituted difunctional ethylene comonomer, dimethyl itaconate, was copolymerized with ethylene by these catalysts to give end-difunctional polyethylene with double ester groups and molecular weight up to 10 700 directly.
Cancer poses a significant threat to human health worldwide, and many therapies have been used for its palliative and curative treatments. Vincristine has been extensively used in chemotherapy. However, there are two major challenges concerning its applications in various tumors: (1) Vincristine's antitumor mechanism is cell-cycle-specific, and the duration of its exposure to tumor cells can significantly affect its antitumor activity and (2) Vincristine is widely bio-distributed and can be rapidly eliminated. One solution to these challenges is the encapsulation of vincristine into liposomes. Vincristine can be loaded into conventional liposomes, but it quickly leak out owing to its high membrane permeability. Numerous approaches have been attempted to overcome this problem. Vincristine has been loaded into PEGylated liposomes to prolong circulation time and improve tumor accumulation. These liposomes indeed prolong circulation time, but the payout characteristic of vincristine is severer, resulting in a compromised outcome rather than a better efficacy compared to conventional sphingomyelin (SM)/cholesterol (Chol) liposomes. In 2012, the USA Food and Drug Administration (FDA) approved SM/Chol liposomal vincristine (Marqibo Õ ) for commercial use. In this review, we mainly focus on the drug's rapid leakage problem and the potentially relevant solutions that can be applied during the development of liposomal vincristine and the reason for conventional liposomal vincristine rather than PEGylated liposomes has access to the market.
Background
Epithelial‐to‐mesenchymal transition (EMT) has been gradually considered as one of the major pathways that causes the production of interstitial myofibroblasts in diseased kidneys.
Materials and Methods
The study was done to investigate the effect of a bone marrow stromal cell (BMSCs) transplant on rat podocytes and diabetic nephropathy (DN) rats in high‐glucose concentration, and to explore the effect of miR‐124a on BMSC therapy. High glucose–injured podocytes and streptozotocin‐induced DN rats have been respectively used as injury models in in vitro and in vivo studies. Podocyte viability was measured using the Cell Counting Kit‐8 assay. Renal pathological examination was observed by HE staining and Masson staining. The messenger RNA and protein levels were determined via real‐time polymerase chain reaction and Western blotting, respectively.
Results
By mediating the activation of caveolin‐1 (cav‐1) and β‐catenin and affecting the expression levels of EMT biomarkers including p‐cadherin, synaptopodin, fibroblast‐specific protein‐1, α‐smooth muscle actin and snail, our in vitro study confirmed that miR‐124a played a significant role in the treatment of high glucose–induced podocyte injury by BMSCs. The therapeutic effects of the BMSC transplant on DN rats were also proved to be further enhanced by miR‐124a overexpression in BMSCs, and such a phenomenon was accompanied by the improvement of renal fibrosis and mitigation of DN‐related kidney impairment. Regulation of fibronectin, collagen1, and EMT‐related proteins was closely implicated with the mechanism, and the activation of cav‐1 and β‐catenin was also possibly involved.
Conclusion
The study demonstrated the pivotal effect of miR‐124a on BMSC therapy for DN rats via mitigating EMT and fibrosis. Our results provide a novel insight into how therapeutic effects of BMSCs can be improved at the posttranscriptional level.
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