Biomarkers are measurable changes associated with the disease. Urine can reflect the changes of the body while blood is under control of the homeostatic mechanisms; thus, urine is considered an important source for early and sensitive disease biomarker discovery. A comprehensive profile of the urinary proteome will provide a basic understanding of urinary proteins. In this paper, we present an in-depth analysis of the urinary proteome based on different separation strategies, including direct one dimensional liquid chromatography–tandem mass spectrometry (LC/MS/MS), two dimensional LC/MS/MS, and gel-eluted liquid fraction entrapment electrophoresis/liquid-phase isoelectric focusing followed by two dimensional LC/MS/MS. A total of 6085 proteins were identified in healthy urine, of which 2001 were not reported in previous studies and the concentrations of 2571 proteins were estimated (spanning a magnitude of 106) with an intensity-based absolute quantification algorithm. The urinary proteins were annotated by their tissue distribution. Detailed information can be accessed at the “Human Urine Proteome Database” (www.urimarker.com/urine).

Urine is an important source of biomarkers. A single proteomics assay can identify hundreds of differentially expressed proteins between disease and control samples; however, the ability to select biomarker candidates with the most promise for further validation study remains difficult. A bioinformatics tool that allows accurate and convenient comparison of all of the existing related studies can markedly aid the development of this area. In this study, we constructed the Urinary Protein Biomarker (UPB) database to collect existing studies of urinary protein biomarkers from published literature. To ensure the quality of data collection, all literature was manually curated. The website (http://122.70.220.102/biomarker) allows users to browse the database by disease categories and search by protein IDs in bulk. Researchers can easily determine whether a biomarker candidate has already been identified by another group for the same disease or for other diseases, which allows for the confidence and disease specificity of their biomarker candidate to be evaluated. Additionally, the pathophysiological processes of the diseases can be studied using our database with the hypothesis that diseases that share biomarkers may have the same pathophysiological processes. Because of the natural relationship between urinary proteins and the urinary system, this database may be especially suitable for studying the pathogenesis of urological diseases. Currently, the database contains 553 and 275 records compiled from 174 and 31 publications of human and animal studies, respectively. We found that biomarkers identified by different proteomic methods had a poor overlap with each other. The differences between sample preparation and separation methods, mass spectrometers, and data analysis algorithms may be influencing factors. Biomarkers identified from animal models also overlapped poorly with those from human samples, but the overlap rate was not lower than that of human proteomics studies. Therefore, it is not clear how well the animal models mimic human diseases. Molecular & Cellular

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in 2D system. To date, HOTIs have been theoretically predicted and experimentally realized in elastics, [34,35] microwaves, [36] electric circuits, [37] photonics, [38][39][40] and acoustic systems. [41][42][43][44][45][46] In order to make HOTIs more attractive for real-world applications as in sound wave control, several hurdles must be overcome. For example, most of the reported results focus solely on a single frequency band, whose limitations ought to be overcome in order to provide a broadband response for topologically robust acoustics. Also, the above reported acoustic implementations have, for the most part, been implemented inside waveguides or were designed in an acoustically rigid enclosure, which hinders their capabilities from external insonification. Lastly, in terms of compactness, it is desired to utilize building blocks of the HOTI on a subwavelength scale in order to confine sound in tight areas beyond the diffraction limit.In this work, we design topologically protected acoustic corner states at deep subwavelength scales by constructing a perforated crystal, also known as holey metamaterials. The advantage in using holey metamaterials resides in their high levels of integration and miniaturization at scales much smaller than the sound wavelength. Without being pierced by holes, those metamaterials would not be able to sustain surface-confined wave propagation. With perforations on the other hand, externally incident radiation is able to bind to the structure in the form of "spoof" surface acoustic waves (SAWs), thus enabling sound energy confinement way beyond the classical diffraction limit. [47,48] In addition to breaking the diffraction limit for spoof SAWs, we demonstrate that a topological phase transition, which is derived from an extended 2D Zak phase, can be tuned by simply shrinking or expanding the distance among a group of holes within the unit cell. Beyond measuring corner states within multiple nontrivial bandgaps, the first-order resonance in particular displays the strongest topological sound energy confinement down to a feature size of λ/50. Lastly, we experimentally verify their resilience against defects and design a HOTI device for topological subwavelength imaging, which may be relevant for sound energy focusing and detection. Figure 1a illustrates the schematic of deep-subwavelength acoustic SOTI under consideration, which is realized by a perforated rigid material whose holes are arranged in a square lattice. The perforation depth and the radii of holes are H = 12 cm and r = 0.5 cm, respectively. The lattice constant is a = 4.8 cm.The center-to-center distance between the adjacent holes in the unit cell is defined as R, which is chosen to be R/a = 0.5 for the Higher-order topological insulators (HOTIs) belong to a new class of materials with unusual topological phases. They have garnered considerable attention due to their capabilities in confining energy at the hinges and corners, which is entirely protected by the topology, and have thus become attractive structures for...