The Optimization Study of Rheological Characteristics of Wind Power Grease Based on Gel-State.

The gel-state grease plays a vital and indispensable role in the long-term operation of wind turbines. To reduce carbon emissions and increase the reliability of wind turbines, this paper takes the gel-state Mobil SHC 461WT grease as the study object. Firstly, the rheological properties of the gel-state Mobil SHC 461WT grease were investigated using the Anton Paar MCR302 rotational rheometer. Secondly, the rheological characteristics of three different gel states of the Mobil SHC 461WT grease (additive content of 0.1% of RFM3000, SK3115, and PV611, respectively, in the gel-state Mobil SHC 461WT grease) were optimized under the same conditions. Finally, according to the experimental results and the Herschel-Bulkley (H-B) model, the RFM3000 additive has the best effect on improving the rheological characteristics of the gel-state Mobil SHC 461WT grease. This research provides a new idea and direction for the technological advancement of the gel-state grease industry.

Phase separation of RNF214 promotes the progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

USP15 in Cancer and Other Diseases: From Diverse Functionsto Therapeutic Targets.

The process of protein ubiquitination and deubiquitination plays an important role in maintaining protein stability and regulating signal pathways, and protein homeostasis perturbations may induce a variety of diseases. The deubiquitination process removes ubiquitin molecules from the protein, which requires the participation of deubiquitinating enzymes (DUBs). Ubiquitin-specific protease 15 (USP15) is a DUB that participates in many biological cell processes and regulates tumorigenesis. A dislocation catalytic triplet was observed in the USP15 structure, a conformation not observed in other USPs, except USP7, which makes USP15 appear to be unique. USP15 has been reported to be involved in the regulation of various cancers and diseases, and the reported substrate functions of USP15 are conflicting, suggesting that USP15 may act as both an oncogene and a tumor suppressor in different contexts. The importance and complexity of USP15 in the pathological processes remains unclear. Therefore, we reviewed the diverse biological functions of USP15 in cancers and other diseases, suggesting the potential of USP15 as an attractive therapeutic target.

Inhibiting the Activity of ABCG2 by KU55933 in Colorectal Cancer.

BACKGROUND: Therapeutic resistance is a frequent problem of cancer treatment and a leading cause of mortality in patients with metastatic colorectal cancer (CRC). Recent insight into the mechanisms that confer multidrug resistance has elucidated that the ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) assists cancer cells in escaping therapeutic stress caused by toxic chemotherapy. Therefore, it is necessary to develop ABCG2 inhibitors. OBJECTIVES: In the present study, we investigated the inhibitory effect of KU55933 on ABCG2 in CRC. METHODS: The cytotoxicity assay and drug accumulation assay were used to examine the inhibitory effect of KU55933 on ABCG2. The protein expressions were detected by Western blot assay. The docking assay was performed to predict the binding site and intermolecular interactions between KU55933 and ABCG2. RESULTS: KU55933 was more potent than the known ABCG2 inhibitor fumitremorgin C to enhance the sensitivity of mitoxantrone and doxorubicin and the intracellular accumulation of mitoxantrone, doxorubicin and rhodamine 123 inside CRC cells with ABCG2 overexpression. Moreover, KU55933 did not affect the protein level of ABCG2. Furthermore, the docking data showed that KU55933 was tightly located in the drug-binding pocket of ABCG2. CONCLUSION: In summary, our data presented that KU55933 could effectively inhibit the drug pump activity of ABCG2 in colorectal cancer, which is further supported by the predicted model that showed the hydrophobic interactions of KU55933 within the drug-binding pocket of ABCG2. KU55933 can potently inhibit the activity of ABCG2 in CRC.

AZ32 Reverses ABCG2-Mediated Multidrug Resistance in Colorectal Cancer.

Colorectal cancer is a common malignancy with the third highest incidence and second highest mortality rate among all cancers in the world. Chemotherapy resistance in colorectal cancer is an essential factor leading to the high mortality rate. The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) confers multidrug resistance (MDR) to a range of chemotherapeutic agents by decreasing their intracellular content. The development of novel ABCG2 inhibitors has emerged as a tractable strategy to circumvent drug resistance. In this study, an ABCG2-knockout colorectal cancer cell line was established to assist inhibitor screening. Additionally, we found that ataxia-telangiectasia mutated (ATM) kinase inhibitor AZ32 could sensitize ABCG2-overexpressing colorectal cancer cells to ABCG2 substrate chemotherapeutic drugs mitoxantrone and doxorubicin by retaining them inside cells. Western blot assay showed that AZ32 did not alter the expression of ABCG2. Moreover, molecule docking analysis predicted that AZ32 stably located in the transmembrane domain of ABCG2. In conclusion, our result demonstrated that AZ32 could potently reverse ABCG2-mediated MDR in colorectal cancer.

A Non-canonical BRCT-Phosphopeptide Recognition Mechanism Underlies RhoA Activation in Cytokinesis.

Cytokinesis partitions the cell contents to complete mitosis. During cytokinesis, polo-like kinase 1 (PLK1) activates the small GTPase RhoA to assemble a contractile actomyosin ring. PLK1 is proposed to pattern RhoA activation by creating a docking site on the central spindle that concentrates the RhoA guanine nucleotide exchange factor ECT2. However, ECT2 targeting to the central spindle is dispensable for cytokinesis, indicating that how PLK1 controls RhoA activation remains unresolved. To address this question, we employed an unbiased approach targeting ∼100 predicted PLK1 sites in two RhoA regulators: ECT2 and the centralspindlin complex, composed of CYK4 and kinesin-6. This comprehensive approach suggested that the only functionally critical PLK1 target sites are in a single cluster in the CYK4 N terminus. Phosphorylation of this cluster promoted direct interaction of CYK4 with the BRCT repeat module of ECT2. However, mutational analysis in vitro and in vivo led to the surprising finding that the interaction was independent of the conserved "canonical" residues in ECT2's BRCT repeat module that, based on structurally characterized BRCT-phosphopeptide interactions, were presumed critical for binding. Instead, we show that the ECT2 BRCT module binds phosphorylated CYK4 via a distinct conserved basic surface. Basic surface mutations mimic the effects on cytokinesis of loss of CYK4 cluster phosphorylation or inhibition of PLK1 activity. Together with evidence for ECT2 autoinhibition limiting interaction with CYK4 in the cytoplasm, these results suggest that a spatial gradient of phosphorylated CYK4 around the central spindle patterns RhoA activation by interacting with ECT2 on the adjacent plasma membrane.

Hospital-based integrated diabetes care management: an overview.

To provide continuous, accessible, and quality care, a diabetes share-care program has been in place in Taiwan for several years. Lukang Christian Hospital, a member of the diabetes share-care network, endeavors to provide "patient-centered" care aimed at increasing care quality and reducing diabetic complications. Information technology has been employed by the hospital for monitoring care quality and analyzing cost-effectiveness. Structured health-care programs have also been developed to ensure the completeness of diabetes care and to encourage self-management of individuals at high risk for diabetes. The implementation of these strategies has led to progressive improvement in quality measures and spawned novel and creative ways to deliver care services.