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Chemotherapy is widely used in a variety of solid tumors, such as lung cancer, gastric cancer and breast cancer. The genotoxic drugs, such as cisplatin, suppress cancer progression either by inhibition cell proliferation or facilitating apoptosis. However, the chemotherapy resistance remains an urgent challenge in cancer therapy, especially in advanced stages. Several studies showed that the activation of pro-survival pathways, such as PI3K-AKT, participated in mediating chemotherapy resistance. The insights into the molecular mechanisms for underlying chemotherapy resistance are of great importance to improve cancer patient survival in advanced stages. The HOIP protein belongs to the RING family E3 ubiquitin ligases and modulates several atypical ubiquitination processes in cellular signaling. Previous studies showed that HOIP might be an important effector in modulating cancer cell death under genotoxic drugs. Here, we report that HOIP associates with PTEN and facilitates PTEN degradation in cancer cells. Depletion of HOIP causes cell cycle arrest and apoptosis, which effects could be rescued by PTEN silencing. Besides, the survival data from public available database show that HOIP expression correlates with poor survival in several types of chemotherapy-treated cancer patients. In conclusion, our study establishes a novel mechanism by which HOIP modulates PTEN stability and facilitates chemotherapy resistance in malignancies.

Background Breast cancer is the most common cancer in women worldwide. More than 70% of breast cancers are estrogen receptor (ER) alpha positive. Compared with ER alpha-negative breast cancer, which is more aggressive and has a shorter survival time, ER alpha-positive breast cancer could benefit from endocrine therapy. Selective estrogen receptor modulators, such as tamoxifen, are widely used in endocrine therapy. Approximately half of ER alpha-positive breast cancer patients will eventually develop endocrine resistance, making it a major clinical challenge in therapy. Thus, decoding the throughput of estrogen signaling, including the control of ER alpha expression and stability, is critical for the improvement of breast cancer therapeutics. Methods TRIM3 and ER alpha protein expression levels were measured by western blotting, while the mRNA levels of ER alpha target genes were measured by RT–PCR. A CCK-8 assay was used to measure cell viability. RNA sequencing data were analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling activity was accomplished with luciferase assays, RT–PCR and western blotting. Protein stability assays and ubiquitin assays were used to detect ER alpha protein degradation. Ubiquitin-based immunoprecipitation assays were used to detect the specific ubiquitination modification on the ER alpha protein. Results In our current study, we found that TRIM3, an E3 ligase, can promote ER alpha signaling activity and breast cancer progression. TRIM3 depletion inhibits breast cancer cell proliferation and migration, while unbiased RNA sequencing data indicated that TRIM3 is required for the activity of estrogen signaling on the -genome-wide scale. The immunoprecipitation assays indicated that TRIM3 associates with ER alpha and promotes its stability, possibly by inducing K63-linked polyubiquitination of ER alpha. In conclusion, our data implicate a nongenomic mechanism by which TRIM3 stabilizes the ER alpha protein to control ER alpha target gene expression linked to breast cancer progression. Conclusion Our study provides a novel posttranslational mechanism in estrogen signaling. Modulation of TRIM3 expression or function could be an interesting approach for breast cancer treatment. Graphical abstract

Breast cancer is one of the most common malignancies worldwide, while the luminal types (ERα positive) accounts for two third of all breast cancer cases. Although ERα positive breast cancer could be effective controlled by endocrine therapy, most of the patients will develop endocrine resistance, which becomes a headache clinical issue for breast cancer field. Endocrine resistance could be caused by multiple pathway disorders, the dys-regulation of ERα signaling might be a critical factor, which makes it urgent and important to reveal the potential molecular mechanism of ERα signaling. In our current study, we identified a new deubiquitination enzyme USP1 through screening the whole DUB (Deubiquitinases) siRNA library. The expression of USP1 is elevated in human breast cancer compared with normal mammary tissues. Importantly, USP1 expression levels are specially correlated with poor survival in ERα positive patients. USP1 depletion inhibited breast cancer cell progression and ERα signaling activity. Immuno-precipitation assays indicate that USP1 associates with ERα and promotes its stability possibly via inhibiting ERα K48-linked poly-ubiquitination. In conclusion, our data implicate a non-genomic mechanism by USP1 via stabilizing ERα protein controls ERα target gene expression linked to breast cancer progression.

Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL‐33 on allograft survival, and additional ILC2 depletion in Treg‐depleted DEREG mice completely abolished the protective effects of IL‐33, indicating that ILC2s play critical roles in IL‐33‐mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL‐33‐treated mice: IL‐10 producing ILC2s (ILC210) and non‐IL‐10 producing ILC2s (non‐ILC 10). Intravenous transfer of ILC210 cells, but not non‐ILC 10, prolonged islet allograft survival in an IL‐10‐dependent manner. Locally transferred ILC210 cells led to long‐term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy., This study reveals a major protective role of the IL‐33/ILC2 axis in islet transplantation that could be potentiated as a therapeutic strategy. Adoptive transfer of ex vivo expanded IL‐10‐producing ILC2s (ILC210) significantly prolonged allograft survival.

The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33–treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo–expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo–expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33–ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy.

The traditional pixel domain tracking algorithms are often applied to rigid objects which move slowly in simple background. But it performs very poor for non-rigid object tracking. In order to solve this problem, this paper proposes a tracking method of rapid detection in compressed domain. Convex hull formed by Self-adaptive boundary searching method and rule-based clustering are adopted for the detector in order to reduce the complexity of the algorithm. At the tracking stage, Kalman filtering is used to forecast the location of the objective. Meanwhile, as the whole process is completed in the compressed domain, it can meet the real-time requirement compared with other algorithms. And it tracks the target more precisely. The experimental results show that the proposed method has the following properties: (1) more advantages in tracking small-sized objects; (2) a better effect when track a fast moving objects; (3) faster tracking speed.

To reasonably evaluate the seismic safety of concrete dams,by introducing the ageing degradation function into dynamic damage constitutive model, a method which is used to evaluate the seismic safety of long-term operating concrete dams is proposed,the method can consider the effect of ageing of concrete on the safety assessment of the dam under earthquake load.The ageing damage model also is adopted to evaluate the 1ife of concrete dam.In order to illustrate the application of the model, examplification is given according to the model at the end of the paper.The results show that the effects of ageing damage on the dynamic response of the dam are significant under earthquake load. The nvestigations, in this paper, are not only important improvement for seismic safety evaluation method of oncrete dam, but also the solid foundations for further study on the seismic safety of inservice concrete dams.

This paper presents a new method of facial expression recognition using the multi-feature fusion weighted principal component analysis (WPCA) and the improved support vector machines(SVMs). It employed the WPCA with multi-features to extract the facial expression feature and the SVMs to classify human facial expression. A simple way based on the distribution of action units in the different facial area is introduced to determine the weights. The detailed procedures for facial expression training and recognition algorithms are given. Facial expression recognition experimental results on the CKACFEID facial expression database indicate that Radial Basis Function (RBF) SVM performs better than Linear and Polynomial SVMs. We also provide experimental evidence that the proposed method using the WPCA which is convenient to get the training templates, easy to match and recognize has a higher recognition rate for all the basic expressions than other methods using the pure PCA (PPCA). The final recognition rates of the WPCA can achieve 88.25% whereas the PPCA gives 84.75% in our experiments.

In order to determine the reasonable design proposal of the powerhouse at the dam toe, combination with the practice of a hydropower station, the three-dimensional finite element method is used to study the rules of deformation and stress of the powerhouse under all kinds of working condition. It is shown that the sliding stability of the dam can be improved by counting in the interaction between dam and plant. The joining hydropower with dam can also reduce the deformation of the hydro turbine caused by high downstream water level. These investigations provide reliable basis for structural optimization design of the powerhouse.

Due to the steel radial gates’ characteristics of structural and acting forces, the investigation on parametric resonance of radial gates’ arms has always been the hot topic in the research field of radial gate’s dynamic stability. In this paper, the simplified space frame is taken as the analytical model, and according to the elastomer perturbation equation and beam element model of thin-walled structure, the dynamic instability region of radial gates can be obtained by the finite element method, then the computational method is applied to calculate the main regions of dynamic instability for a working radial gate. Furthermore, combing with the physical and numerical models, a new method recognizing the parameter resonance of steel radial gates is proposed. The investigations, in this paper, are not only important improvement for the radial gates’ parametric vibration computational method, but also a solid foundation for further study on the dynamic stability of radial gate structure.