ObjectiveDysregulation of transfer RNA (tRNA)-derived small noncoding RNA (tsRNA) signatures in human serum has been found in various diseases. Here, we determine whether the signatures of tsRNAs in serum can serve as biomarkers for diagnosis or prognosis of systemic lupus erythematosus (SLE).MethodsInitially, small RNA sequencing was employed for the screening serum tsRNAs obtained from SLE patients, followed by validation with TaqMan probe-based quantitative reverse transcription-PCR (RT-PCR) assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy. The biological functions of tsRNAs were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) assay.ResultsWe first analyzed tsRNA signatures in SLE serum and identified that tRF-His-GTG-1 was significantly upregulated in SLE serum. The combination of tRF-His-GTG-1 and anti-dsDNA could serve as biomarkers for diagnosing SLE with a high area under the curve (AUC) of 0.95 (95% CI = 0.92–0.99), sensitivity (83.72%), and specificity (94.19%). Importantly, the noninvasive serum tRF-His-GTG-1 could also be used to distinguish SLE with LN or SLE without LN with AUC of 0.81 (95% CI, 0.73–0.88) and performance (sensitivity 66.27%, specificity 96.15%). Moreover, the serum tsRNA is mainly secreted via exosome and can directly target signaling molecules that play crucial roles in regulating the immune system.ConclusionIn this study, it has been demonstrated for the first time that serum tsRNAs can be employed as noninvasive biomarkers for the efficient diagnosis and prediction of nephritis in SLE.

miRNA-20b has been shown to be aberrantly expressed in several tumor types. However, the clinical significance of miRNA-20b in the prognosis of patients with hepatocellular carcinoma (HCC) is poorly understood, and the exact role of miRNA-20b in HCC remains unclear. The aim of the present study was to investigate the association of the expression of miR-20b with clinicopathological characteristics and overall survival of HCC patients analyzed by Kaplan-Meier analysis and Cox proportional hazards regression models. Meanwhile, the HIF-1α and VEGF targets of miR-20b have been confirmed. We found not only miR-20b regulation of HIF-1α and VEGF in normal but also regulation of miR-20b in hypoxia. This mechanism would help the tumor cells adapt to the different environments thus promoting the tumor invasion and development. The whole study suggests that miR-20b, HIF-1α, and VEGF serve as a potential therapeutic agent for hepatocellular carcinoma.

Interferon-α (IFNα) has multiple antitumor effects including direct antitumor toxicity and the ability to potently stimulate both innate and adaptive immunity. However, its clinical applications in the treatment of malignancies have been limited because of short half-life and serious adverse reactions when attempting to deliver therapeutically effective doses. To address these issues, we fused IFNα2a to the anti-vascular endothelial growth factor and receptor 2 (VEGFR2) antibody JZA00 with the goal of targeting it to the tumor microenvironment where it can stimulate the antitumor immune response. The fusion protein, JZA01, is effective against colorectal cancer by inhibiting angiogenesis, exhibiting direct cytotoxicity, and activating the antitumor immune response. Although JZA01 exhibited reduced IFNα2 activity compared with native IFNα2, VEGFR2 targeting permitted efficient antiproliferative, proapoptotic, antiangiogenesis, and immune-stimulating effects against the colorectal tumors HCT-116 and SW620. JZA01 showed efficacy in NOD-SCID mice-bearing established HCT-116 tumors. In conclusion, this study describes an antitumor immunotherapy that is highly promising for the treatment of colorectal cancer.

An optimal experiment design assumes the existence of an initial or nominal process model. The efficiency of this procedure depends on how the initial model is chosen. This creates a practical dilemma as estimating the model is precisely what the experiment tries to achieve. A novel approach to experiment design for identification of nonlinear systems is developed, with the purpose of reducing the influence of poor initial values. The experiment design and the parameter estimation are conducted iteratively under a receding-horizon framework. By taking steady-state prior knowledge into account, constraints on the parameters can be derived. Such constraints help reduce influence of poor initial models. The proposed algorithm is illustrated through examples to demonstrate its efficiency. V V C 2010 American Institute of Chemical Engineers AIChE J, 57: [2808][2809][2810][2811][2812][2813][2814][2815][2816][2817][2818][2819][2820] 2011 Keywords: receding-horizon design, optimal experiment design, constrained EKF IntroductionOptimal experiment design aims at determining optimal experiment conditions to achieve a specific set of objectives. Experiment design is a broad subject that includes aspects such as input design, operating point design, and sampling time design. Although a significant amount of literature on optimal experiment design for linear systems has been published since the 1970s, 1,2 the optimal experiment design concerning nonlinear systems has remained largely unexplored.One significant challenge for nonlinear experiment design as well as parameters identification is that the sensitivity functions used to search for optimal conditions depend on the unknown model parameters. Three existing methods have been proposed to address this challenge: minimax experiment design, ED (expectation of determinant)/EID (expectation of the inverse of determinant)-optimal design, and adaptive experiment design.Minimax experiment design attempts to achieve robust experiment by minimizing the largest possible modeling error. This approach needs no prior information about parameter distributions. There are two recent representative publications on this topic. Rojas et al.3 developed a method of optimizing the worst case of modeling error over the parameter set, while a convex optimization algorithm is implemented on a linear system. In conjunction, Welsh and Rojas 4 proposed an algorithm to solve a robust optimal experiment design problem by scenario approach. To construct convex or semidefinite convex problems, both techniques formulate the identification problem in frequency domain, but neither of the methods can be used for identification in nonlinear system. Moreover, the optimality objective function for nonlinear identification is generally difficult to be formulated as a convex or semidefinite convex problem.Another group of methods (especially popular in bioscience fields) are experiment designs by optimizing over the expected determinant of a Fisher information matrix Correspondence concerning this article ...

Although interferon α (IFN α ) and anti-angiogenesis antibodies have shown appropriate clinical benefit in the treatment of malignant cancer, they are deficient in clinical applications. Previously, we described an anti-vascular endothelial growth factor receptor 2 (VEGFR2)-IFN α fusion protein named JZA01, which showed increased in vivo half-life and reduced side effects compared with IFN α , and it was more effective than the anti-VEGFR2 antibody against tumors. However, the affinity of the IFN α component of the fusion protein for its receptor-IFNAR1 was decreased. To address this problem, an IFN α -mutant fused with anti-VEGFR2 was designed to produce anti-VEGFR2-IFN α mut, which was used to target VEGFR2 with enhanced anti-tumor and anti-metastasis efficacy. Anti-VEGFR2-IFN α mut specifically inhibited proliferation of tumor cells and promoted apoptosis. In addition, anti-VEGFR2-IFN α mut inhibited migration of colorectal cancer cells and invasion by regulating the PI3K–AKT–GSK3 β –snail signal pathway. Anti-VEGFR2-IFN α mut showed superior anti-tumor efficacy with improved tumor microenvironment (TME) by enhancing dendritic cell maturation, dendritic cell activity, and increasing tumor-infiltrating CD8 + T cells. Thus, this study provides a novel approach for the treatment of metastatic colorectal cancer, and this design may become a new approach to cancer immunotherapy.