Liposomes have made remarkable achievements as drug delivery vehicles in the clinic.Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs,but seem...Liposomes have made remarkable achievements as drug delivery vehicles in the clinic.Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs,but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents,thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy.In this study,a series of weak acid drug derivatives were designed by a simplistic one step synthesis,which could be remotely loaded into liposomes by p H gradient method.Cabazitaxel(CTX)weak acid derivatives were selected to evaluate regarding its safety profiles,pharmacodynamics,and pharmacokinetics.CTX weak acid derivative liposomes were superior to Jevtanaa in terms of safety profiles,including systemic toxicity,hematological toxicity,and potential central nerve toxicity.Specifically,it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons.Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.展开更多
It is known from classical differential geometry that one can reconstruct a curve with (n - 1) prescribed curvature functions, if these functions can be differentiated a certain number of times in the usual sense and ...It is known from classical differential geometry that one can reconstruct a curve with (n - 1) prescribed curvature functions, if these functions can be differentiated a certain number of times in the usual sense and if the first (n - 2) functions are strictly positive. It is established here that this result still holds under the assumption that the curvature functions belong to some Sobolev spaces, by using the notion of derivative in the distributional sense. It is also shown that the mapping which associates with such prescribed curvature functions the reconstructed curve is of class C∞.展开更多
We clarify the relation between the subcategory D_(hf)~b(A) of homological finite objects in D^b(A)and the subcategory K^b(P) of perfect complexes in D^b(A), by giving two classes of abelian categories A with enough p...We clarify the relation between the subcategory D_(hf)~b(A) of homological finite objects in D^b(A)and the subcategory K^b(P) of perfect complexes in D^b(A), by giving two classes of abelian categories A with enough projective objects such that D_(hf)~b(A) = K^b(P), and finding an example such that D_(hf)~b(A)≠K^b(P). We realize the bounded derived category D^b(A) as a Verdier quotient of the relative derived category D_C^b(A), where C is an arbitrary resolving contravariantly finite subcategory of A. Using this relative derived categories, we get categorical resolutions of a class of bounded derived categories of module categories of infinite global dimension.We prove that if an Artin algebra A of infinite global dimension has a module T with inj.dimT <∞ such that ~⊥T is finite, then D^b(modA) admits a categorical resolution; and that for a CM(Cohen-Macaulay)-finite Gorenstein algebra, such a categorical resolution is weakly crepant.展开更多
基金financially supported by the National Nature Science Foundation of China(U1608283)the Career Development Program for Young and Middle-aged Teachers in Shenyang Pharmaceutical University
文摘Liposomes have made remarkable achievements as drug delivery vehicles in the clinic.Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs,but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents,thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy.In this study,a series of weak acid drug derivatives were designed by a simplistic one step synthesis,which could be remotely loaded into liposomes by p H gradient method.Cabazitaxel(CTX)weak acid derivatives were selected to evaluate regarding its safety profiles,pharmacodynamics,and pharmacokinetics.CTX weak acid derivative liposomes were superior to Jevtanaa in terms of safety profiles,including systemic toxicity,hematological toxicity,and potential central nerve toxicity.Specifically,it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons.Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.
文摘It is known from classical differential geometry that one can reconstruct a curve with (n - 1) prescribed curvature functions, if these functions can be differentiated a certain number of times in the usual sense and if the first (n - 2) functions are strictly positive. It is established here that this result still holds under the assumption that the curvature functions belong to some Sobolev spaces, by using the notion of derivative in the distributional sense. It is also shown that the mapping which associates with such prescribed curvature functions the reconstructed curve is of class C∞.
基金supported by National Natural Science Foundation of China(Grant Nos.11271251 and 11431010)
文摘We clarify the relation between the subcategory D_(hf)~b(A) of homological finite objects in D^b(A)and the subcategory K^b(P) of perfect complexes in D^b(A), by giving two classes of abelian categories A with enough projective objects such that D_(hf)~b(A) = K^b(P), and finding an example such that D_(hf)~b(A)≠K^b(P). We realize the bounded derived category D^b(A) as a Verdier quotient of the relative derived category D_C^b(A), where C is an arbitrary resolving contravariantly finite subcategory of A. Using this relative derived categories, we get categorical resolutions of a class of bounded derived categories of module categories of infinite global dimension.We prove that if an Artin algebra A of infinite global dimension has a module T with inj.dimT <∞ such that ~⊥T is finite, then D^b(modA) admits a categorical resolution; and that for a CM(Cohen-Macaulay)-finite Gorenstein algebra, such a categorical resolution is weakly crepant.
