We herein propose a bioengineering approach where bacterial outer membrane vesicles (OMVs) were coated on drug-loaded polymeric micelles to generate an innovative nanomedicine for effective cancer immunotherapy and metastasis prevention. Whereas OMVs could activate the host immune response for cancer immunotherapy, the loaded drug within polymeric micelles would exert both chemotherapeutic and immunomodulatory roles to sensitize cancer cells to cytotoxic T lymphocytes (CTLs) and to kill cancer cells directly. We demonstrated that the systemic injection of such a bioinspired immunotherapeutic agent would not only provide effective protective immunity against melanoma occurrence but also significantly inhibited tumor growth in vivo and extended the survival rate of melanoma mice. Importantly, the nanomedicine could also effectively inhibit tumor metastasis to the lung. The bioinspired immunomodulatory nanomedicine we have developed repurposes the bacterial-based formulation for cancer immunotherapy, which also defines a useful bioengineering strategy to the improve current cancer immunotherapeutic agents and delivery systems.
The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201908185.Cell-membrane-derived biomimetic nanoplatforms have revolutionized the design of cancer vaccine by providing targeted delivery, specific recognition, antigen presentation, and immune stimulation [1] and diverse eukaryotic membrane vesicles have been developed for vaccine design, including blood cells, [2] Adv.
1121Lagrangian spheres, symplectic surfaces and the symplectic mapping class group TIAN-JUN LI WEIWEI WU Given a Lagrangian sphere in a symplectic 4-manifold .M; !/ with b C D 1, we find embedded symplectic surfaces intersecting it minimally. When the Kodaira dimension Ä of .M; !/ is 1, this minimal intersection property turns out to be very powerful for both the uniqueness and existence problems of Lagrangian spheres. On the uniqueness side, for a symplectic rational manifold and any class which is not characteristic, we show that homologous Lagrangian spheres are smoothly isotopic, and when the Euler number is less than 8, we generalize Hind and Evans' Hamiltonian uniqueness in the monotone case. On the existence side, when Ä D 1, we give a characterization of classes represented by Lagrangian spheres, which enables us to describe the non-Torelli part of the symplectic mapping class group. 53D05, 53D12, 53D42 IntroductionFor a symplectic 4-manifold .M; !/, symplectic surfaces and Lagrangian surfaces are of complementary dimensions. Thus we can ask what can be said about their intersection pattern. Welschinger investigated this problem for a Lagrangian torus L in [54], where he proves that the class OEL pairs trivially with any effective class, and a symplectic sphere with positive Chern number can be isotoped symplectically away from L.In the case when L is a Lagrangian sphere in S 2 S 2 with a product symplectic form, Hind [22] constructed two transverse foliations of symplectic spheres where each sphere intersects L in a single point. This is used to show that every such L is Hamiltonian isotopic to the antidiagonal. For a Lagrangian sphere L in a symplectic Del Pezzo surface with Euler number at most 7, Evans showed in [13] that it can be displaced from certain symplectic spheres with positive Chern number up to Hamiltonian isotopy, and applied this displacement result to prove the uniqueness of Hamiltonian isotopy class of Lagrangian spheres. In Section 3, we generalize Evans' displacement result in two ways, the first being:Theorem 1.1 Let L be a Lagrangian sphere in a symplectic 4-manifold .M; !/, and A 2 H 2 .M I Z/ with A 2 1. Suppose A is represented by a symplectic sphere C . Then C can be isotoped symplectically to another representative of A which intersects L minimally.In this paper all surfaces are smooth, embedded, connected and oriented. We say that two closed surfaces intersect minimally if they intersect transversely at jkj points, where k is the homological intersection number.The second generalization is for symplectic surfaces of arbitrary genus in manifolds with b C D 1. To state it let E ! be the set of ! -exceptional classesTheorem 1.2 Suppose .M; !/ is a symplectic 4-manifold with b C D 1 and L is a Lagrangian sphere. Assume A 2 H 2 .M; Z/ satisfies !.A/ > 0; A 2 > 0 and A E 0 for all E 2 E ! . Then there exists a symplectic surface in the class nA intersecting L minimally for large n 2 N .These theorems on minimal intersection are this paper's main innovation. Theorem 1.2 is proved by...
Enantioselective synthesis of fully substituted allenes has been a challenge due to the non-rigid nature of the axial chirality, which spreads over three carbon atoms. Here we show the commercially available simple Rh complex may catalyse the CMD (concerted metalation/deprotonation)-based reaction of the readily available arenes with sterically congested tertiary propargylic carbonates at ambient temperature affording fully substituted allenes. It is confirmed that the excellent designed regioselectivity for the C–C triple bond insertion is induced by the coordination of the carbonyl group in the directing carbonate group as well as the steric effect of the tertiary O-linked carbon atom. When an optically active carbonate was used, surprisingly high efficiency of chirality transfer was realized, affording fully substituted allenes in excellent enantiomeric excess (ee).
We find a non-displaceable Lagrangian torus fiber in a semi-toric system which is superheavy with respect to a certain symplectic quasi-state. The proof employs both 4-dimensional techniques and those from symplectic field theory. In particular, our result implies Lagrangian $\mathbb{R}P^{2}$ is not a stem in $\mathbb{C}P^{2}$, answering a question of Entov and Polterovich.
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