Familial macular degeneration is a clinically and genetically heterogeneous group of disorders characterized by progressive central vision loss. Here we show that an R373C missense mutation in the prominin 1 gene (PROM1) causes 3 forms of autosomal-dominant macular degeneration. In transgenic mice expressing R373C mutant human PROM1, both mutant and endogenous PROM1 were found throughout the layers of the photoreceptors, rather than at the base of the photoreceptor outer segments, where PROM1 is normally localized. Moreover, the outer segment disk membranes were greatly overgrown and misoriented, indicating defective disk morphogenesis. Immunoprecipitation studies showed that PROM1 interacted with protocadherin 21 (PCDH21), a photoreceptor-specific cadherin, and with actin filaments, both of which play critical roles in disk membrane morphogenesis. Collectively, our results identify what we believe to be a novel complex involved in photoreceptor disk morphogenesis and indicate a possible role for PROM1 and PCDH21 in macular degeneration.

Collagen, the major structural component of nearly all mammalian tissues, undergoes extensive proteolytic remodeling during developmental states and a variety of life-threatening diseases such as cancer, myocardial infarction, and fibrosis. While degraded collagen could be an important marker of tissue damage, it is difficult to detect and target using conventional tools. Here, we show that a designed peptide (collagen hybridizing peptide: CHP), which specifically hybridizes to the degraded, unfolded collagen chains, can be used to image degraded collagen and inform tissue remodeling activity in various tissues: labeled with 5-carboxyfluorescein and biotin, CHPs enabled direct localization and quantification of collagen degradation in isolated tissues within pathologic states ranging from osteoarthritis and myocardial infarction to glomerulonephritis and pulmonary fibrosis, as well as in normal tissues during developmental programs associated with embryonic bone formation and skin aging. The results indicate the general correlation between the level of collagen remodeling and the amount of denatured collagen in tissue and show that the CHP probes can be used across species and collagen types, providing a versatile tool for not only pathology and developmental biology research but also histology-based disease diagnosis, staging, and therapeutic screening. This study lays the foundation for further testing CHP as a targeting moiety for theranostic delivery in various animal models.

of data carriers for space-division multiplexing (SDM) beyond traditional wavelength-division multiplexing (WDM) and polarization-division multiplexing (PDM). [3,4] Such high-speed communications, which can reach the speed of Tbit s −1 , are achieved over both free-space and special vortex fiber using OAM beams multiplexing, WDM and PDM together. [5][6][7] High-speed OAM multiplexing communication system, similar to other optical multiplexing communication systems, involves multiplexers and demultiplexers. Traditional OAM multiplexer and demultiplexer consist of OAM generators, such as spatial phase plates (SPPs) or l-forked holograms, and channel combiners, for example, cascaded beam splitters. [3][4][5][6][7][8][9][10][11] The numbers of OAM generators and combiners correspond to the number of channels with independent information uploading by modulators. Therefore, the system becomes complex and less integrated. Several years ago, a method was proposed to solve such complex sequence of holograms and realized multi-OAMs generation and sorting by coordinate transformation. [2] However, this method introduced new challenges. The integration is limited by the distance between two phase plates and the diffraction of light regardless of the thickness of the components used. To make things worse, typical high-speed optical communications, combining not only SDM but also WDM and PDM, require more than one demultiplexer, which further increases the system complexity.In this paper, we report a physical methodology for multiple OAMs multiplexing and demultiplexing by an off-axis designing principle to integrate all the SDM, WDM, and PDM components into one single ultrathin metasurface. With offaxis incidence of beams representing independent information channels, the component can generate independent coaxial vortex beams with different topological charges as a multiplexer. With vortex beams carrying different OAMs, the channels can be separated into fundamental mode beams at the diverse directions as a demultiplexer. Furthermore, the conservations of momentum make this off-axis diffractive component contain dispersion, which demonstrates its great potentials in SDM-WDM system. For the metasurface based on dipole antenna, there are interesting responses to polarization and OAM, which can be used in PDM-WDM system owing to conservations of momentum and angular momentum. Due to these superior properties, designed metasurface demultiplexer has great potential in high integration of SDM, WDM, and Orbital angular momentum (OAM) has recently gained much interest in high-speed optical communication due to its spatial orthogonality. However, complex spatial phase distributions of OAM make the components difficult for nano-photonic integration. In this work, a method to multiplex and demultiplex multiple OAMs, wavelengths, and polarizations channels by a highly integrated off-axis technique on a metasurface is presented. As a multiplexer, beams without OAM can be transferred into coaxial beams carrying different OAM features by d...

Figure 1. Flexible tactile sensors based on the morphology controllable template methods and the morphology uncontrollable template methods and the potential applications in large tactile sensor array, intelligent robot gripper, and artificial tactile sensory memory. Image for "Lithography Template": Reproduced with permission.

Overuse injuries to dense collagenous tissues are common, but their etiology is poorly understood. The predominant hypothesis that micro-damage accumulation exceeds the rate of biological repair is missing a mechanistic explanation. Here, we used collagen hybridizing peptides to measure collagen molecular damage during tendon cyclic fatigue loading and computational simulations to identify potential explanations for our findings. Our results revealed that triple-helical collagen denaturation accumulates with increasing cycles of fatigue loading, and damage is correlated with creep strain independent of the cyclic strain rate. Finite-element simulations demonstrated that biphasic fluid flow is a possible fascicle-level mechanism to explain the rate dependence of the number of cycles and time to failure. Molecular dynamics simulations demonstrated that triple-helical unfolding is rate dependent, revealing rate-dependent mechanisms at multiple length scales in the tissue. The accumulation of collagen molecular denaturation during cyclic loading provides a long-sought “micro-damage” mechanism for the development of overuse injuries.

Peptide-conjugated nanoparticles (NPs) have promising potential for applications in biosensing, diagnosis, and therapeutics because of their appropriate size, unique self-assembly, and specific substrate-binding properties. However, controlled assembly and selective target binding are difficult to achieve with simple peptides on NP surfaces because high surface energy makes NPs prone to self-aggregate and adhere nonspecifically. Here, we report the self-assembly and gelatin binding properties of collagen mimetic peptide (CMP) conjugated gold NPs (CMP-NPs). We show that the orientation of CMPs displayed on the NP surface can control NP assembly either by promoting or hindering triple helical folding between CMPs of neighboring NPs. We also show that CMP-NPs can specifically bind to denatured collagen by forming triple-helical hybrids between denatured collagen strands and CMPs, demonstrating their potential use for detection and selective removal of gelatin from protein mixtures. CMP conjugated NPs offer a simple and effective method for NP assembly and for targeting denatured collagens with high specificity. Therefore, they may lead to new types of functional nanomaterials for detection and study of denatured collagen associated with diseases characterized by high levels of collagen degradation.

Possessing the merits of high efficiency, low consumption, and versatility, emerging photonic memristive and memristive-like devices exhibit an attractive future in constructing novel neuromorphic computing and miniaturized bionic electronic system. Recently, the potential of various emerging materials and structures for photonic memristive and memristive-like devices has attracted tremendous research efforts, generating various novel theories, mechanisms, and applications. Limited by the ambiguity of the mechanism and the reliability of the material, the development and commercialization of such devices are still rare and in their infancy. Therefore, a detailed and systematic review of photonic memristive and memristive-like devices is needed to further promote its development. In this review, the resistive switching mechanisms of photonic memristive and memristive-like devices are first elaborated. Then, a systematic investigation of the active materials, which induce a pivotal influence in the overall performance of photonic memristive and memristive-like devices, is highlighted and evaluated in various indicators. Finally, the recent advanced applications are summarized and discussed. In a word, it is believed that this review provides an extensive impact on many fields of photonic memristive and memristive-like devices, and lay a foundation for academic research and commercial applications.

Although asymmetric supercapacitors (ASCs) can achieve high energy density, the lifespan and power density are severely suppressed due to the low conductivity of using pseudocapacitive or battery‐type electrode materials. Recently, nonporous conductive coordination polymers (c‐CPs) have sparked interests in supercapacitors. However, their performance is expected to be limited by the nonporous features, low specific surface area and absence of ion‐diffusion channels. Here, it is demonstrated that the capacity of nonporous CPs will be significantly enhanced by maximizing the number of faradaic redox sites in their structures through a comparative investigation on three highly conductive nonporous c‐CPs, CuxBHT(x = 3, 4, 5.5). They show excellent capacitance of 312.1 F g‐1 (374.5 C g‐1) (Cu3BHT), 186.7 F g‐1 (224.0 C g‐1) (Cu4BHT) and 89.2 F g‐1 (107.0 C g‐1) (Cu5.5BHT) at 0.5 A g‐1 in a sequence related to the number of electron storage units in structures and outstanding rate performance and cycle stability. Furthermore, the constructed Cu3BHT//MnO2 ASC device exhibits capacity retention of 92% (after 1500 cycles at 3 A g‐1) and delivers a high energy density of 39.1 Wh kg‐1 at power density of 549.6 W kg‐1 within a large working potential window of 0‐2.2 V.