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Colorectal cancers (CRCs) are characterized by diffuse infiltration of tumor cells into the regional lymph nodes and metastasis to distant organs, and its highly invasive nature contributes to disease recurrence and poor outcomes. The molecular mechanisms underlying CRC cell invasion remain incompletely understood. Here, we identified the upregulation of DNA damage repair-related protein RAD23B in CRC cells and tissues and showed that it associates with coronin 1C or coronin 3 (CORO1C) to facilitate invasion. We found that knockdown of RAD23B expression significantly inhibited the proliferation, invasion, and migration abilities of CRC cells both in vitro and in vivo, and suppressed the talin1/2/integrin/FAK/RhoA/Rac1/CORO1C signaling pathways. Interestingly, RAD23B interacted and co-localized with CORO1C, and CORO1C aggregated toward the margin of cancer cells in both CRC cells and tissues when RAD23B overexpressed. Mechanistically, overexpression of RAD23B and/or CORO1C further increased invadopodia formation and matrix degradation in SW480 and HCT8 CRC cells. Conversely, silencing of RAD23B expression suppressed tumorigenesis and liver metastasis in xenotransplant murine models. Furthermore, we found that RAD23B was significantly overexpressed in paired tumor tissues (n = 720) compared to adjacent non-tumor tissues (n = 694) of patients with CRC. Finally, we identified a strong correlation between higher levels of cytoplasmic expression of RAD23B, and poor prognosis and liver metastasis in CRC patients. Taken together, our data highlight a novel RAD23B-CORO1C signaling axis in CRC cell invasion and metastasis that may be of clinical significance.

Background Multicenter experiments have frequently been performed in clinical biomarker studies. However, center effects should not be ignored. In this study, for the first time,we estimated the multicenter variations of the urinary metabolome in China. Methods In this study, midstream urine samples from a total of 83 healthy individuals were collected in four centers in Beijing and Changchun. Liquid chromatography-high resolution mass spectrometry -based metabolomics was used to analyze the differences among the four centers. Results Within the same city, there were significant variations in the urinary metabolome among the three centers. Different centers had unique differential metabolites. Amino acids, N-acetylglucosamine, glutathione, and NAD metabolism contributed to the multicenter variation. The metabolomics variation between Beijing and Changchun was obviously higher than that within the same city (Beijing). The variations between Beijing and Changchun were associated with tetrapyrrole metabolism, hememetabolism, and eicosanoid signaling. Conclusions This study provides insights into the center and regional effect of the urinary metabolome in China. Our results might benefit the experimental design of multicenter urinary metabolome research in the clinic.

Amniotic fluid contains large amounts of proteins produced by amnion epithelial cells, fetal tissues, fetal excretions and placental tissues; thus, it is an important potential source of biomarkers for identifying fetal pathologies. In this study, a pooled AF sample from 7 healthy volunteers was used to provide a comprehensive profile of normal human AF proteome using immunoaffinity depletion of 14 high-abundance proteins. Each individual AF sample was used to analyze inter-individual variations with iTRAQ method. As a result, a total of 2881 non-redundant proteins were identified, and 1624 proteins were quantified based on the peak intensity-based semi-quantification (iBAQ) method. Gene Ontology (GO) analysis showed that the AF proteome was enriched in extracellular region and extracellular matrix. Further function annotation showed that the top canonical pathway was axonal guidance signaling. The inter-individual variation analysis of 7 individual AF samples showed that the median inter-individual CV (Coefficient of variation) was 0.22. iBAQ quantification analysis revealed that the inter-individual variations were not correlated with protein abundance. GO analysis indicated that intracellular proteins tended to have higher CVs, and extracellular proteins tended to have lower CVs. These data will contribute to a better understanding of amniotic fluid proteomic analysis and biomarker discovery. SIGNIFICANCE: Amniotic fluid is an important potential source of biomarkers for identifying fetal pathologies. This study provided a large database for the normal human amniotic fluid proteome and analysis of inter-individual variations in amniotic fluid proteomes, which will offer a baseline reference for further AF proteomic analysis and pregnancy-related disease biomarker discovery.

Mass spectrometry (MS)-based urinary proteomics is increasingly used for clinical research. A critical step in urinary proteomic analysis comprises the implementation of a reliable sample preparation method with high yields of peptides and proteins. In this study, we developed a urinary sample preparation method, DRA-Urine (Direct reduction/alkylation in urine), which urinary proteins were directly reduced/alkylated in urine, and then precipitated by acetone, washed and digestion on an ultrafilter unit. The qualitative and quantitative comparison of different urinary sample preparation methods (in-solution methods and ultrafilter-assisted methods) showed that DRA-Urine could achieve better results. Adapting DRA-Urine protocol to a 96-well format, namely 96DRA-Urine, shortened the time for buffer change and improved sample preparation throughput. The results showed that 96DRA-Urine displayed similar proteomic performance to DRA-Urine. Finally, the 96DRA-Urine method was used in a label-free, small pilot biomarker discovery analysis for differential urinary proteome analysisof bladder cancer urine. The results showed that urinary proteins could differentiate bladder cancer (BCa) patients from healthy controls and distinguish high-grade BCa from low-grade BCa with area under the curve (AUC) values of 0.972 and 0.847, respectively. Consequently, the 96DRA-Urine method might be a high-throughput method for preparing body fluid samples used in clinical research but needs to be further verified.

We prove, among others, the following regularity criterion for the solutions to the Navier–Stokes equations: If u is a global weak solution satisfying the energy inequality and ω = ∇ × u , then u is regular on ( 0 , T ) , T > 0 , if two components of ω belong to the space L q ( 0 , T ; B ˙ ∞ , ∞ − 3 / p ) for p ∈ ( 3 , ∞ ) and 2 / q + 3 / p = 2 . This result is an improvement of the results presented by Chae and Choe (1999) [7] or Zhang and Chen (2005) [38] . Our method of the proof uses a suitable application of the Bony decomposition and can also be used for the proofs of some other kin criteria. One such example is presented in Appendix.

In this paper we establish a new regularity criterion for the 3D incompressible MHD equations via ∂ 3 u 3 and the magnetic field b . By considering different weights in spatial variables, we show in anisotropic Lebesgue spaces if ∂ 3 u 3 and b satisfy certain space–time integrable conditions, which are almost optimal from the scaling invariant point of view, then a weak solution ( u , b ) is actually regular. This result gives new insights into the understanding of regularity theory of weak solutions.

Hippocampus and temporal cortex are important brain regions, which play distinct, but complimentary roles in mediating learning and memory. Herein, we utilized label-free differential proteome strategy to explore function of normal human hippocampus and temporal cortex in learning and memory. As a result, a total of 5529 and 5702 proteins were identified in hippocampus and temporal cortex, respectively, 516 of which were significantly differential expressed, with abundance span 5 orders of magnitudes. Pathways analysis showed that temporal cortex was involved in growth of axons growth and synapse density regulation, through which could regulate long-term potentiation and long-term retention of trace memory. Hippocampus was involved in regulation of cell survival and cell viability, and regulates neurons proliferation by actin dynamics changes, through which involved in both short-term memory and long-term memory. Four selected differential proteins were further validated by Western blot and immunohistochemistry. For the first time, we identified proteins and associated pathways of hippocampus and temporal cortex in human cognition process using proteomic strategy, which would provide references for generating corresponding insights in hippocampus and temporal cortex-related cognitive function. The original data files can be downloaded at http://211.102.209.254/page/PSV023.html;?url = 1489542083729AFHp (password: kYxh). Significance This study explored the potential molecular mechanism of hippocampus and temporal cortex in human cognition function using proteomics strategy, which will offer a baseline reference for further cognitive disorders study and reveal insights into physiology of temporal cortex and hippocampus.

We discuss an integrable Camassa–Holm type equation with cubic nonlinearity. Asymptotic profile has been shown in the sense that strong solutions arising from algebraic decaying initial data will keep this property at infinity in the spatial variable in its lifespan. Moreover, for a global solution, measure of potential support is presented.

Glaucoma is the leading cause of irreversible blindness worldwide. The proteome characterization of glaucoma is not clearly understood. A total of 175 subjects, including 57 primary acute angle-closure glaucoma (PAACG), 50 Primary chronic angle-closure glaucoma (PCACG), 35 neovascular glaucoma (NVG) and 33 cataract patients, were enrolled and comparison proteomic analysis was provided. Above samples were randomly divided into discovery group or validation group, whose AH proteome were analyzed by data-independent acquisition method or by parallel reaction monitor method. The common proteome features of three types of glaucoma were immune response, lipid metabolism and cell death. Three proteins, VTN, SERPIND1 and CD14, showed significantly up-regulated in glaucoma, and could discriminate glaucoma from cataract. Mutual differential proteomic analysis of PAACG, PCACG and NVG showed different proteome characterization of the three types of glaucoma. NVG was characterized with activated angiogenesis. PAACG was characterized with activation of inflammation response. SERPIND1 was discovered to play vital role in glaucoma occurrences, which is associated with eye transparency decrease and glucose metabolism. This study would provide insights in understanding proteome characterization of glaucoma and benefit the clinical application of AH proteome. Funding Statement: This work was supported by the National Key Research and Development Program of China (No. 2016 YFC 1306300, 2018YFC0910202), National Natural Science Foundation of China (No. 30970650, 31200614, 31400669, 81371515, 81170665, 81560121, 81572082), Beijing Natural Science Foundation (No. 7173264, 7172076), Peking Union Medical College Hospital (No.2016-2.27), and Biologic Medicine Information Center of China, National Scientific Data Sharing Platform for Population and Health. Declaration of Interests: All authors have no conflict of interest. Ethics Approval Statement: The study was approved by the Institutional Review Board of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. Informed consent was obtained from each participant before enrolment.

Glaucoma is the leading cause of irreversible blindness worldwide. The proteome characterization of glaucoma is not clearly understood. A total of 175 subjects, including 57 primary acute angle-closure glaucoma (PAACG), 50 primary chronic angle-closure glaucoma (PCACG), 35 neovascular glaucoma (NVG), and 33 cataract patients, were enrolled and comparison proteomic analysis was provided. The samples were randomly divided into discovery group or validation group, whose aqueous humor proteome was analyzed by data-independent acquisition or by parallel reaction monitoring. The common proteome features of three types of glaucoma were immune response, lipid metabolism, and cell death. Three proteins, VTN, SERPIND1, and CD14, showed significant upregulation in glaucoma and could discriminate glaucoma from cataract. Mutual differential proteomic analysis of PAACG, PCACG, and NVG showed different proteome characterization of the three types of glaucoma. NVG was characterized with activated angiogenesis. PAACG was characterized with activation of inflammation response. SERPIND1 was discovered to play vital role in glaucoma occurrences, which is associated with eye transparency decrease and glucose metabolism. This study would provide insights in understanding proteome characterization of glaucoma and benefit the clinical application of AH proteome., Graphical Abstract, Highlights • Aqueous humor proteome of different glaucoma (PACG, NVG) was profiled. • Potential protein biomarkers for glaucoma were proposed. • Potential mechanism of glaucoma was described. • SERPIND1 was discovered to have potential value for glaucoma diagnosis., In Brief Liu et al. characterized the proteome of aqueous humor from three types of glaucoma. Fifty-seven primary acute angle-closure glaucoma (PAACG), 50 primary chronic angle-closure glaucoma (PCACG), 35 neovascular glaucoma (NVG), and 33 cataract patient samples were analyzed using data-independent analysis and parallel reaction monitoring. Lipid metabolism, immune response, and cell death pathways showed different degrees of activation among the three types of glaucoma but were all higher relative to cataract. SERPIND1 was discovered as a vital protein in glaucoma.

Objective To identify candidate urinary protein biomarkers to distinguish medulloblastoma (MB) patients from healthy patients or benign brain disease control patients. Methods The tandem mass tag (TMT)-labeled quantitative proteomics approach was used to identify differential proteins in the urinary proteome of 9 pre- and postsurgery MB patients and 9 healthy control patients, respectively. Ingenuity pathway analysis was used for functional annotation of differential proteins. The biomarker candidates were validated by the parallel reaction monitoring (PRM) method in 112 samples (29 pre- and postsurgery MB patients, 26 healthy control patients, and 28 benign brain disease control patients). Receiver operating characteristic (ROC) curves were developed to evaluate candidate biomarkers. Results A total of 114 differential proteins were found. Bioinformatic analysis revealed that the urinary proteome could reflect changes in MB. Seventeen candidate biomarkers were validated by PRM. The combination of CADH1, FGFR4 and FIBB could be used to discriminate MB patients from healthy control patients with an area under the curve (AUC) of 0.973, and the combination of CADH1 and FIBB showed good discriminative power for differentiating MB from benign brain disease with an AUC of 0.884. Conclusion This report describes the first application of a TMT-PRM workflow to identify and validate MB–specific biomarkers in urine. These findings might contribute to the application of urinary proteomics for detecting and monitoring MB. Biological significance Medulloblastoma (MB) is among the most common pediatric brain malignancies. This tumor has a highly aggressive clinical course with a high tendency for relapses. Magnetic resonance imaging (MRI) is the major means of diagnosis and for radiographic surveillance after surgery. In MRI, sedation is often required in young children, which could expose them to a series of risks, including airway obstruction and even death. Aside from MRI, there is no reliable biomarker for clinical screening or monitoring of the disease. These facts introduce the clinical need of noninvasive biomarkers for early screening or monitoring of MB. This study is focused on the investigation of a marker panel based on urinary proteome, as a tool for the detection of MB in selected patients at risk. Upon evaluation of the marker model in an independent blinded set of 112 samples, the panel (CADH1, FGFR4 and FIBB) could be used to discriminate MB patients from healthy control patients with an area under the curve (AUC) of 0.973, and the combination of CADH1 and FIBB showed good discriminative power for differentiating MB from benign brain disease with an AUC of 0.884.

Plasma metabolomics and lipidomics have been commonly used for biomarker discovery for the rich metabolic information they provide. Studies in white and Japanese populations suggested that gender and age can affect circulating plasma metabolite profiles; however, the Chinese population has not been surveyed. In our study, we profiled Chinese plasma metabolome and lipidome in a cohort of 534 healthy adults and reported an overview of metabolic characteristics in the Chinese population. Inter-individual analysis showed that inter-individual variations of the plasma metabolome and lipidome were 0.645 and 0.568, respectively. Further differential analysis indicated that gender and age would affect the metabolic status. Metabolic pathways such as fatty-acid metabolism, nicotinate and nicotinamide metabolism, steroidogenesis process and tryptophan metabolism were found to vary with gender and age. Comparison of metabolism characteristics between Chinese and other western population suggested that plasma metabolomics could reflect regional and ethnic differences, to some extent. Further, using the above strategy, renal cell carcinoma (RCC) biomarkers were explored based on age- and gender-matched healthy subjects, 34 patients with benign kidney lesions and 143 patients with RCC. Metabolic and lipid profiling of the plasma could significantly differentiate cancer cases from healthy controls and benign controls, with an area under the curve (AUC) of 0.971 and 0.839, respectively. Our study provides an overview of plasma metabolic characteristics in a Chinese population and suggests that plasma metabolomics and lipidomics are useful strategies for biomarker discovery. Funding Statement: This work was supported by National Basic Research Program of China (Nos. 2013CB530805 and 2014CBA02005), Major collaborative innovation projects (No. 2017-I2M-1-009), Key Basic Research Program of the Ministry of Science and Technology of China (No. 2013FY114100), the National Natural Science Foundation of China (No. 30970650, 31200614, 31400669, 81371515 and 81670611), Beijing Natural Science Foundation (No. 5132028), Basic scientific research (2017PT310004) and Biologic Medicine Information Center, National Scientific Data Sharing Platform for Population and Health. Declaration of Interests: The authors declare no conflict of interests. Ethics Approval Statement: This study was approved by the Institutional Review Board of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences.

In this work, we will establish a sufficient condition for the regularity criterion to the 3D MHD equations in terms of one directional derivative of the pressure. More precisely, we prove that if ? π ? x 3 ( x , t ) ? L 2 1 - r ( 0 , T ; M ? 2 , 3 r ( R 3 ) ) ???for? 0 < r < 1 , then the solution ( u , b ) is regular. We obtain some improvement of the related results in Berselli and Galdi (2002), Cao and Wu (2010), Jia and Zhou (2012), Lin and Du (2013) and Yamazaki (2013).

Endometriosis is a common gynecologic disorder and due to a lack of non-invasive detection methods, it can take up to 12 years before an affected woman obtains a diagnosis and receives appropriate treatment. Therefore, the identification of a specific biomarker that can be detected quickly and non-invasively is urgently needed. In this study, the urine proteome, a potentially rich source of biomarkers, is examined in patients with or without endometriosis in an attempt to identify novel protein biomarkers that can be used to diagnose endometriosis. This study is the first to combine tandem mass tags and parallel reaction monitoring approaches to aid in identifying and validating urine biomarkers for endometriosis. The findings presented herein support previous conclusions that endometriosis is a chronic inflammatory disease. Additionally, Histone 4 was identified as a potential biomarker and/or therapeutic target for endometriosis. At a cutoff of 14.2, the area under the curve for H4 was 0.848, with a sensitivity of 70% and specificity of 80%. Moreover, to our knowledge, this is the first study to observe an elevated histone level in body fluids obtained from endometriosis patients. While this study provides a good foundation, further studies are required to further validate the results presented. Significance Endometriosis is a common gynecologic disorder and due to a lack of non-invasive detection methods, it can take up to 12 years before an affected woman obtains a diagnosis and receives appropriate treatment. Therefore, the identification of a specific biomarker that can be detected quickly and non-invasively is urgently needed. We believe our results have an important impact on detection and treatment of endometriosis. Firstly, this study is the first to combine tandem mass tags and parallel reaction monitoring approaches to aid in identifying and validating urine biomarkers for endometriosis, which has established the methodology required for subsequent studies. Secondly, this is also the first study to observe an elevated histone level in body fluids obtained from endometriosis patients. Compared with other urine biomarkers reported in literature, histone 4 has a potential to serve as a biomarker of endometriosis and a therapeutic target. Thirdly, our study supports previous conclusions that endometriosis is a chronic inflammatory disease. These findings can warrant further investigation of the pathophysiology of endometriosis.

We consider the asymptotic behavior of solutions for a modified two-component Camassa–Holm (MCH2) system which arises in shallow water theory. It is proved that the corresponding solution to initial data with algebraic decay at infinity will retain this property in its lifespan.

In this paper, we establish sufficient conditions on the initial data to guarantee blow-up phenomenon for the modified two-component Camassa–Holm (MCH2) system.

We discuss the two-component Camassa–Holm system which arises in shallow water theory. This paper is concerned with the asymptotic description of solutions in the following sense: the corresponding solution to initial data with algebraic decay at infinity will retain this property at infinity in its lifespan.

In this paper, we consider a modified two-component Camassa–Holm (MCH2) system which arises in shallow water theory. We analyze the wave breaking mechanism by establishing some new blow-up criteria for this system formulated either on the line or with space-periodic initial condition.

In this paper, we consider the periodic weakly dissipative Dullin–Gottwald–Holm equation. The present work is mainly concerned with blow-up phenomena for the Cauchy problem for this new kind of equation. We apply the optimal constant to give sufficient conditions via an appropriate integral form of the initial data, which guarantee the finite-time singularity formation for the corresponding solution.

We consider a two-component Degasperis–Procesi system which arises in shallow water theory. We analyze some aspects of blow up mechanism, traveling wave solutions and the persistence properties. Firstly, we discuss the local well-posedness and blow up criterion; a new blow up criterion for this system with the initial odd condition will be established. Finally, the persistence properties of strong solutions will also be investigated.

Background As urine is less complex than plasma and accumulates substantial physiological and pathophysiological changes from both plasma and the urinary system, it is regarded as an ideal source of sample for biomarker studies. Methods To gain a better understanding of the biological functions of urinary proteins and their association with human diseases, we did an in-depth urinary proteome analysis, using urine samples from 24 healthy individuals, that was based on multiple separation strategies, including direct one-dimensional liquid chromatography–tandem mass spectrometry (1DLC/MS/MS), two-dimensional LC/MS/MS, and gel-eluted liquid fraction entrapment electrophoresis (GELFrEE) and liquid-phase isoelectric focusing (LP-IEF) followed by 2DLC/MS/MS. Findings We identified 6412 proteins, of which 2213 had not been reported in previous studies and 2571 were relatively and absolutely quantitated (spanning a magnitude of 10 6 ) with an intensity-based absolute quantification algorithm. Tissue-based analysis revealed that 514 tissue-enriched proteins from 27 tissues and 917 tissue-enhanced proteins from 32 tissues could be detected in urine, suggesting that the urinary proteome might have an important role in studying the physiological and pathological changes of the related organs, such as the brain and kidney. We selected potential urinary biomarkers that were previously identified for glioma and IgA nephropathy by filtering biomarkers from the publicly accessible Human Urine Proteome Database and verified them by Western blotting. We also observed that deeper separation allowed identification of more tissue-related and disease-specific proteins. All the detailed information—such as protein name, accession number, peptide sequence, sequence coverage, and biomarker application—could be obtained from the Human Urine Proteome Database, which provides information for prediction of urinary candidate biomarkers and modification of targeted proteomics workflow. Interpretation Urine might indicate the physiological and pathological changes of several organs and could therefore be used as a promising source of sample for biomarker discovery, especially for brain and kidney diseases. Funding This work was supported by the National Basic Research Program of China (2013CB530805 and 2014CBA02005), the Key Basic Research Program of the Ministry of Science and Technology of China (2013FY114100), the National Natural Science Foundation of China (31200614 and 31400669), and the Beijing Natural Science Foundation (5132028).

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.