The development of two-dimensional metasurfaces has shown great potential in quantum-optical technologies because of the excellent flexibility in light-field manipulation. By integrating a metalens array with a nonlinear crystal, we demonstrate a 100-path spontaneous parametric down-conversion photon-pair source in a 10 × 10 array, which shows promise for high-dimensional entanglement and multiphoton-state generation. We demonstrate two-, three- and four-dimensional two-photon path entanglement with different phases encoded by metalenses with fidelities of 98.4, 96.6, and 95.0%, respectively. Furthermore, four-photon and six-photon generation is observed with high indistinguishability of photons generated from different metalenses. Our metalens-array–based quantum photon source is compact, stable, and controllable, indicating a new platform for integrated quantum devices.

Abstract-Matrix metalloproteinases (MMPs) have been implicated in the process of neovascularization. However, the exact roles of individual MMPs in vessel formation are poorly understood. To study the putative role of MMP-2 in ischemia-induced neovascularization, a hindlimb ischemia model was applied to MMP-2 ϩ/ϩ and MMP-2 Ϫ/Ϫ mice. Serial laser Doppler blood-flow analysis revealed that the recovery of the ischemic/normal blood-flow ratio in MMP-2 Ϫ/Ϫ young and old mice remained impaired throughout the follow-up period. At day 35, microangiography and anti-L-lectin immunohistochemical staining revealed lesser developed collateral vessels and capillary formation in both old and young MMP-2 Ϫ/Ϫ mice compared with the age-matched MMP-2 ϩ/ϩ mice. An aortic-ring culture assay showed a markedly impaired angiogenic response in MMP-2 Ϫ/Ϫ mice, which was partially recovered by supplementation of the culture medium with recombinant MMP-2. Aorta-derived endothelial cells or bone marrow-derived endothelial progenitor cell (EPC)-like c-Kit ϩ cells from MMP-2 Ϫ/Ϫ showed marked impairment of invasive or/and proliferative abilities. At day 7, plasma and ischemic tissues of vascular endothelial growth factor protein were reduced in MMP-2 Ϫ/Ϫ . Flow cytometry showed that the numbers of EPC-like CD31 ϩ c-Kit ϩ cells in peripheral blood markedly decreased in MMP-2-deficient mice. Transplantation of bone marrow-derived mononuclear cells from MMP-2 ϩ/ϩ mice restored neovascularization in MMP-2 Ϫ/Ϫ young mice. These data suggest that MMP-2 deficiency impairs ischemia-induced neovascularization through a reduction of endothelial cell and EPC invasive and/or proliferative activities and EPC mobilization. (Circ Res. 2007;100:904-913.) Key Words: ischemia Ⅲ angiogenesis Ⅲ matrix metalloproteinase Ⅲ endothelium Ⅲ mobilization Ⅲ migration I t is well known that the process of new blood vessel formation is associated with extracellular matrix (ECM) remodeling involving various proteolytic systems. Among such systems, matrix metalloproteinases (MMPs) are a family of zincdependent endopeptidases comprising at least 20 members that are collectively capable of degrading all known ECM components. 1,2 A number of studies have shown that various kinds of MMPs were upregulated in ischemia-induced angiogenesis. 3 Although MMP activity is commonly thought to be involved in the process of angiogenesis, this notion has been challenged by recent studies using genetic or biological target methods. It has been reported that MMP-9 deficiency reduced neovascularization and tumor growth. 4 Study of membrane-type1 (MT1)-MMP knockout mice revealed that the deficiency impaired neovascularization in a mouse corneal micropocket model. 5 Whereas MMP-1 and MMP-10 appear to control the process of vascular regression rather than morphogenesis. 6 On the other hand, certain MMPs, including MMP-12 and MMP-7, are capable of converting plasminogen into angiostatin to inhibit endothelial cell (EC) tubulogenesis in vitro. 7 Interestingly, it has been reported that tiss...

Smooth muscle cell (SMC) migration from the tunica media to the intima, a key event in neointimal formation, requires proteolytic degradation of elastin-rich extracellular matrix barriers. Although cathepsin S (Cat S) is overexpressed in atherosclerotic and neointimal lesions, its exact role in SMC behavior remains primarily unresolved. We examined the involvement of Cat S on SMC migration through an extracellular matrix barrier and its localization in SMCs. A selective Cat S inhibitor and the endogenous inhibitor cystatin C significantly attenuated SMC invasion across elastin gel. Western blotting and cell surface biotinylation analysis demonstrated localization of the 28-kd active form of Cat S on the SMC surface, consistent with its role in the proteolysis of subcellular matrices. Treatment with interferon-gamma or interleukin-beta1 significantly augmented the ability of SMC membranes to degrade elastin along with a significant increase in the level of active Cat S compared with controls. Immunofluorescence and confocal microscopy showed a punctuated pattern of Cat S clusters at the periphery of SMCs; further studies demonstrated partial co-localization of Cat S and integrin alphanubeta3 at the cell surfaces. These findings demonstrate that active Cat S co-localizes with integrin alphanubeta3 as a receptor on the SMC surface, playing an important role in the invasive behavior of SMCs.

No abstract