DOCK4 is a novel prognostic biomarker and correlated with immune infiltrates in colon adenocarcinoma.

BACKGROUND: Dedicator for cytokinesis 4 (DOCK4) is a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. However, the functions of DOCK4 concerning the tumor microenvironment (TME) in colon adenocarcinoma (COAD) remain uncertain. METHODS: The TIMER and GEPIA databases were used to analyze the DOCK4 expression between COAD tissues and adjunct normal tissues. The PrognoScan database was used to assess the prognosis of DOCK4 expression in COAD. The co-expression networks of DOCK4 in COAD were constructed by the LinkedOmics website. Furthermore, the correlation between DOCK4 expression and TME of COAD was explored using TIMER and TISIDB databases. Finally, the clone formation assay was used to further verify the function of DOCK4 in COAD. The Western blotting assay was used to confirm the mechanism related to DOCK4 in COAD. RESULTS: The DOCK4 expression was different significantly in COAD tissues and paracancerous tissues. The DOCK4 was found to play a poor role in the prognosis of patients with COAD. The DOCK4 was found to participate in the TME by promoting immune evasion of COAD. The reduction of DOCK4 expression inhibited the clone formation and Ras-associated protein 1A (Rap1A) expression of HCT116 cells. CONCLUSIONS: DOCK4 potentially plays an important role in the regulation of TME in COAD. DOCK4 facilitates the development through the Rap1A pathway, thus becoming a novel prognostic biomarker in COAD.

A customized strategy to design intercalation-type Li-free cathodes for all-solid-state batteries.

Pairing Li-free transition-metal-based cathodes (MX) with Li-metal anodes is an emerging trend to overcome the energy-density limitation of current rechargeable Li-ion technology. However, the development of practical Li-free MX cathodes is plagued by the existing notion of low voltage due to the long-term overlooked voltage-tuning/phase-stability competition. Here, we propose a p-type alloying strategy involving three voltage/phase-evolution stages, of which each of the varying trends are quantitated by two improved ligand-field descriptors to balance the above contradiction. Following this, an intercalation-type 2H-V1.75Cr0.25S4 cathode tuned from layered MX2 family is successfully designed, which possesses an energy density of 554.3 Wh kg-1 at the electrode level accompanied by interfacial compatibility with sulfide solid-state electrolyte. The proposal of this class of materials is expected to break free from scarce or high-cost transition-metal (e.g. Co and Ni) reliance in current commercial cathodes. Our experiments further confirm the voltage and energy-density gains of 2H-V1.75Cr0.25S4. This strategy is not limited to specific Li-free cathodes and offers a solution to achieve high voltage and phase stability simultaneously.

Application Value of Nutrition Support Team in Chemotherapy Period of Colon Cancer Based on Internet Multidisciplinary Treatment Mode.

Objective: To explore the application value of the nutrition support team in chemotherapy period of colon cancer based on the internet multidisciplinary treatment mode. Methods: For the method of retrospective study, 90 patients with colon cancer admitted to our hospital from August 2018 to August 2020 were selected as the study subjects. They were equally divided into the experimental group (n = 45) and the control group (n = 45) according to the order of initials and the method of parity group. The control group was given conventional nutrition support, and the experimental group was given the nutrition support under the internet multidisciplinary treatment mode. The serum tumor marker levels (CEA and CA19-9), immune function indexes, nutrition indicators, and the incidence of adverse reactions were compared between the two groups before and after intervention. Results: The serum tumor marker levels in the experimental group after intervention were significantly lower than those in the control group (P < 0.001). The immune function indexes in the experimental group after intervention were significantly better than those in the control group (P < 0.001). The nutrition indicators in the experimental group after intervention were significantly better than those in the control group (P < 0.001). The incidence of gastrointestinal adverse reactions above grade 2 in the experimental group was significantly lower than that in the control group (P < 0.05). There were 20 patients with myelosuppression, 2 patients with neurotoxicity, and 1 patient with hand and foot syndrome in the experimental group, while 22 patients with myelosuppression, 4 patients with neurotoxicity, and 2 patients with hand and foot syndrome in the control group, with no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion: The nutrition support team under the internet multidisciplinary treatment mode can improve the immune function of chemotherapy patients with colon cancer and enhance their nutritional level, thereby reducing the incidence of adverse reactions and improving the chemotherapy effects.

Analysis of the Antenna Array Orientation Performance of the Interferometric Microwave Radiometer (IMR) Onboard the Chinese Ocean Salinity Satellite.

The Chinese Ocean Salinity Satellite is designed to monitor global sea-surface salinity (SSS). One of the main payloads onboard the Chinese Ocean Salinity Satellite, named the Interferometric Microwave Radiometer (IMR), is a two-dimensional interferometric radiometer system with an L-band, Y-shaped antenna array. The comparison of two different array orientations is analyzed by an end-to-end simulation based on the configuration of the IMR. Simulation results of the different array orientations are presented and analyzed, including the brightness temperature (TB) images, the distribution of the incidence angles in the field of view, the TB radiometric resolutions, the spatial resolutions, the number of measurements in the Earth grid and the expected SSS accuracy. From the simulations we conclude that one of the array orientations has better performance for SSS inversion than the other one. The advantages mainly result in wider swath and better SSS accuracy at the edge of the swath, which then improve the accuracy of the monthly SSS after averaging. The differences of the Sun's effects for two different array orientations are also presented. The analysis in this paper provides the guidance and reference for the in-orbit design of the array orientation for the IMR.

Inter-Sensor Calibration between HY-2B and AMSR2 Passive Microwave Data in Land Surface and First Result for Snow Water Equivalent Retrieval.

The self-designed HaiYang-2B (HY-2B) satellite was launched on 24 October 2018 in China at 22:57 UT in a 99.34° inclination sun-synchronous orbit. The Scanning Microwave Radiometer (SMR) on the core observatory has the capability to provide near-real-time multi-channel brightness temperature (Tb) observations, which are designed mainly for improving the level of marine forecasting and monitoring, serving the development and utilization of marine resources. After internal calibration and ocean calibration, the first effort to retrieve land surface snow parameters was performed in this study, which obtained extremely low accuracy both in snow extent and snow mass. Accordingly, land inter-sensor calibration was carried out between SMR and the Advanced Microwave Scanning Radiometer 2 (AMSR2) in order to broaden the research and application of SMR data on the Earth's land surface. Finally, we evaluated the consistency of the snow extent and snow mass derived from the initial and land-calibrated SMR data. The results indicated that a systematic SMR cold deviation whose magnitude depends on the channel is present for all the compared channels. After intercalibration, the conformity of the snow extent and snow mass were substantially improved compared to before; the relative bias of the snow extent and snow mass decreased from -49.97% to 2.97% and from -51.71% to 3.01%, respectively.

Emodin enhances cisplatin-induced cytotoxicity in human bladder cancer cells through ROS elevation and MRP1 downregulation.

BACKGROUND: Chemoresistance is one of the most leading causes for tumor progression and recurrence of bladder cancer. Reactive oxygen species (ROS) plays a key role in the chemosensitivity of cancer cells. In the present study, emodin (1,3,8-trihydroxy-6-methylanthraquinone) was applied as a ROS generator in combination with cisplatin in T24 and J82 human bladder cancer cells. METHODS: Cell viability and apoptosis rate of different treatment groups were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM). The expression of transporters was measured at both the transcription and translation levels using PCR and western blotting. In vitro findings were confirmed by in vivo experiments using tumor-bearing mice. The expression of multidrug resistance-associated protein 1 (MRP1) in tumour tissue was measured using immunohistochemistry and side effects of the emodin/cisplatin co-treatment were investigated by histological examination. RESULTS: Emodin increased the cellular ROS level and effectively enhanced the cisplatin-induced cytotoxicity of T24 and J82 human bladder cancer cells through decreasing glutathione-cisplatin (GSH-cisplatin) conjugates. It blocked the chemoresistance of T24 and J82 cells to cisplatin through suppressing the expression of MRP1. This effect was specific in T24 and J82 cells but not in HCV-29 normal bladder epithelial cells. Consistent with in vitro experiments, emodin/cisplatin co-treatment increased the cell apoptosis and repressed the MRP1 expression in xenograft tumors, and without obvious systemic toxicity. CONCLUSIONS: This study revealed that emodin could increase the cisplatin-induced cytotoxicity against T24 and J82 cells via elevating the cellular ROS level and downregulating MRP1 expression. We suggest that emodin could serve as an effective adjuvant agent for the cisplatin-based chemotherapy of bladder cancer.

The effects of buthionine sulfoximine on the proliferation and apoptosis of biliary tract cancer cells induced by cisplatin and gemcitabine.

Patients with biliary tract cancer (BTC) have a poor prognosis. Advanced BTC patients have been treated with cisplatin in combination with gemcitabine, however, the treatment has had little impact on survival rates, and more effective treatments are urgently required for this disease. Previous studies discovered that buthionine sulfoximine (BSO), a potent inhibitor of glutathione (GSH) synthesis, was able to enhance the cytotoxic effect of various drugs in cancer cells. Phase I studies demonstrated that continuous-infusion of BSO was relatively non-toxic and resulted in the depletion of tumor GSH. However, the synergistic effect of BSO and cisplatin in BTC cells remains unknown, and no reports are available regarding sensitization to gemcitabine by BSO. In the present study, the effect of BSO in combination with cisplatin or gemcitabine in the treatment of BTC cells was examined in vitro. Cytotoxic effects were measured using an MTT assay, Annexin V assay and fluorescence-activated cell sorting analysis. Antiapoptotic protein expression levels were examined using western blot analysis. The results revealed that a sub-toxic concentration of BSO was capable of significantly enhancing cisplatin-induced apoptosis in BTC cells. The mechanisms of BSO's effect on BTC cells may be attributable to the reduction of GSH levels and downregulation of the expression of antiapoptotic proteins (Bcl-2, Bcl-xL and Mcl-1). Furthermore, BSO enhanced the antiproliferative effect of gemcitabine. In conclusion, the present data are the first results to indicate that BSO may sensitize BTC cells to standard first-line chemotherapeutic agents (cisplatin and gemcitabine). Combining BSO with cisplatin and gemcitabine is a promising therapeutic strategy for the treatment of BTC.

Expressions of farnesoid X receptor and myeloid cell leukemia sequence 1 protein are associated with poor prognosis in patients with gallbladder cancer.

BACKGROUND: Farnesoid X receptor (FXR) regulates tumorigenesis, but its clinical significance in gallbladder cancer (GBC) remains unclear. This study investigated its clinical and prognostic significance in GBC patients, as well as its association with the anti-apoptotic protein, myeloid cell leukemia sequence 1 (MCL1) protein. METHODS: FXR and MCL1 expression in 42 primary GBC and 15 normal gallbladder tissues were analyzed by immunohistochemistry. The patients and samples were collected from Ren Ji Hospital from January 2005 to December 2010. Their association with clinicopathologic factors and prognosis, as well as the correlation between FXR and MCL1 protein expression were analyzed by statistical analyses. RESULTS: Compared with normal gallbladder tissues, FXR expression was decreased and MCL1 expression was increased in GBC, during progression of tumor node metastasis (TNM) stage. The Kaplan-Meier survival analysis showed that FXR low-expression and MCL1 over-expression were significantly associated with overall poor survival. Furthermore, multivariate analysis showed that FXR and MCL1 are both prognostic factors for GBC patients. FXR low-expression was significantly correlated with MCL1 over-expression. CONCLUSION: FXR might be a new molecular marker to predict the prognosis of patients with GBC and a novel therapeutic target.

Characterization of cancer stem-like cells derived from a side population of a human gallbladder carcinoma cell line, SGC-996.

The cancer stem cell (CSC) hypothesis proposes that CSCs, which can renew themselves proliferate infinitely, and escape chemotherapy, become the root of recurrence and metastasis. Previous studies have verified that side population (SP) cells, characterized by their ability to efflux lipophilic substrate Hoechst 33342, to share many characteristics of CSCs in multiplying solid tumors. The purpose of this study was to sort SP cells from a human gallbladder carcinoma cell line, SGC-996 and to preliminarily identify the biological characteristics of SP cells from the cell line. Using flow cytometry we effectively sorted SP cells from the cell line SGC-996. SP cells not only displayed higher proliferative, stronger clonal-generating, more migratory and more invasive capacities, but showed stronger resistance. Furthermore, our experiments demonstrated that SP cells were more tumorigenic than non-SP counterparts in vivo. Real-time PCR analysis and immunocytochemistry showed that the expression of ATP-binding cassette subfamily G member 2 (ABCG2) was significantly higher in SP cells. Hence, these results collectively suggest that SP cells are progenitor/stem-like cells and ABCG2 might be a candidate marker for SP cells in human gallbladder cancer.