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Background: Colorectal cancer (CRC) comprises a large proportion of malignant tumors, and early detection of CRC is critical for effective treatment and optimal prognosis. We aimed to discover and validate serum autoantibodies for early detection of CRC. Methods: Combined with CRC-associated autoantibodies discovered by serological proteome and multiplex analyses, 26 predefined autoantibodies were evaluated in 315 samples (130 CRCs, 75 advanced adenomas, and 110 healthy controls) by protein microarray analysis. Autoantibodies with potential detection value were verified by enzyme-linked immunosorbent assays (ELISAs). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the accuracy of the biomarkers. Results: Four serum autoantibodies (ALDH1B1, UQCRC1, CTAG1, and CENPF) showed statistically different levels between patients with advanced neoplasm (CRC or advanced adenoma) and controls in microarray analysis, which were validated by ELISAs. Among the four biomarkers, the ALDH1B1 autoantibody showed the highest detection value with area under the curve (AUC) values of 0.70 and 0.74 to detect CRC and advanced adenoma with sensitivities of 75.68 and 62.31% and specificities of 63.06 and 73.87%, respectively. By combining the four biomarkers, the performance was improved with an AUC of 0.79 to detect CRC and advanced adenomas. Conclusion: The ALDH1B1 autoantibody has a good potential for early detection of CRC and advanced adenoma, and measuring serum autoantibodies against tumor-associated antigens may improve detection of early CRC.

Background: In our previous study, we demonstrated that 14-kDa phosphohistidine phosphatase (PHP14) was upregulated in fibrotic liver tissue and involved in cell migration. In this study, we evaluated PHP14 as a therapeutic target for liver fibrosis and investigated the mechanism by which it mediated liver fibrosis in vivo. Methods: Liver fibrosis was induced in mice by carbon tetrachloride (CCl 4 ) administration. The preventive and therapeutic effect of PHP14 inhibition on liver fibrosis was evaluated by injection of the adeno-associated viral containing short hairpin RNA (shRNA) against Phpt1 (AAV- Phpt1) via tail vein into mice before or after 1 week of CCl4 treatment. The effect of AAV- Phpt1 on fibrosis was evaluated by real-time PCR, Western blotting, Immunohistochemistry and RNA sequencing (RNA-Seq). Flow cytometric, Transwell and adoptive transfer assays were used to assess the cell migration and infiltration. Finding: Liver fibrosis was significantly improved after AAV-Phpt1 administration in the CCl4 model. Notably, cell infiltration was significantly suppressed after PHP14 knockdown. Besides HSCs, we found the migration of macrophage was significantly inhibited by PHP14 knockdown, resulting in decreased accumulation of macrophages in the liver injury areas. RNA-seq results revealed that PHP14 knockdown in vivo influenced the environment of fibrogenesis and relevant signaling pathways, subsequently affecting myofibroblast activation. Interpretation: PHP14 inhibition can attenuate liver fibrosis and can be considered a potential therapeutic target for liver fibrosis. Funding Statement: Beijing Natural Science Foundation ( 7202034 to A. Xu), National Natural Science Foundation of China (81670539 and 81970524 to H. You, 81773800 to X. Zhang) Declaration of Interests: The authors disclose no conflicts. Ethics Approval Statement: All animal work was performed under the ethical guidelines of the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (Beijing, China).

Hepatocellular carcinoma (HCC) is more frequently observed and aggressive in men compared with women. Increasing evidence demonstrates that the sex disparity appears to be mediated by the stimulatory effects of androgens and the protective effects of estrogen in the development and progression of HCC. In the past few decades, studies on the sex difference of HCC mainly focused on the effect of sex hormones on the transactivation of hepatitis B virus X protein and the release of inflammatory cytokines, and these studies have further intensified in recent years. Sex hormones are also involved in genetic alterations and DNA damage repair in hepatocytes through binding to their specific cellular receptors and affecting the corresponding signaling pathways. Furthermore, the theory of sex chromosomes participating in HCC has been considered. The present review discussed the recent advances in the molecular mechanisms of sex disparity in HCC, with the aim of improving the understanding of the underlying critical factors and exploring more effective methods for the prevention and treatment of HCC.

Hydrogel photonic crystal-based optical sensors usually can only be used as free-standing films. Here, a doped microgel colloidal crystal film was developed as glucose sensor, which exploits structural order–disorder transition, instead of change in lattice constant, to report an analyte. Changing glucose concentration induces a change in structural order degree in the crystal and hence a change in the intensity of the stop band, and thus reports glucose concentration in the media. The response is fast and reversible. As the overall swelling degree of the gel does not change, it can be used as substrate-attached film.

Recently there has been a significant interest to perform real-time analytical queries in systems that can handle both “big data” and “fast data”. In this paper, we propose an approximate answering approach, called ROSE, which can manage the big and fast data streams and support complex analytical queries against the data streams. To achieve this goal, we start with an analysis of existing query processing techniques in big data systems to understand the requirements of building a distributed analytic sketch. We then propose a sampling-based sketch that can extract multi-faced samples from asynchronous data streams, and augment its usability with accuracy-lossless distributed sketch construction operations, such as splitting, merging and union. The experimental results with real-world data sets indicate that compared with state-of-the-art approximate answering engine BlinkDB, our techniques can obtain more accurate estimates and improve 2 times of system throughput. When compared with distributed memory-computing system Spark, our system can achieve 2 orders of magnitude improvement on query response time.

Plentiful emerging applications need strict requirement on query response time for different operators over distributed streaming data. As a result, approximate answering approach with accurate sketch has become an important solution to process the fast arrival streams. In this paper, we propose a dynamic sketching framework, which can sample elements from streams with out-of-order data arrival and provide an error-guaranteed estimation schema for many different operators. Within the sketch, we first extract characteristics of uniform sampling and exponential sampling from one-pass streaming data and organize them to support (ξ, δ)-approximation for different operators, such as aggregation operators (e.g., sum, count) and quantile operators (e.g., quantiles, median). Moreover, we construct the sketch in an accuracy lossless and dynamic manner by such operations as sketch splitting and sketch merging without any pori knowledge. The experimental results indicate that when compared to big data analytic systems (Spark, BlinkDB), our approach can achieve 3 times of throughput improvement and 2 orders of magnitude improvement in query response time.

The controlled introduction of artificial extrinsic defects is critical to achieve the functions of photonic crystals. Smart defects capable of responding to external stimuli lead to more advanced applications. Here we report a microgel colloidal crystal with a defect state which could be induced and erased reversibly by external stimuli. The crystal was assembled from PNIPAM microgel and P(NIPAM-AAc) microgel of the same size. The resulting doped crystal does not exhibit a defect state in its stop band because of the similar optical properties of the dopant and the host. By increasing the pH value, however, the dopant P(NIPAM-AAc) spheres swell to a larger size and turn into real defects in the crystal, resulting in the appearance of defect state. Adjusting the pH value back restores the size of the dopant spheres, and thus erases the defect state. Temperature, a second external stimulus, could also be used to induce and erase defect states of the crystal.