[2-DG improves lung ischemia/reperfusion injury by inhibiting NLRP3-mediated pyroptosis in rats].

The aim of this study was to investigate whether the protective effect of 2-deoxyglucose (2-DG) on lung ischemia/reperfusion (I/R) injury is mediated by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis in rats. Male Sprague-Dawley rats were randomly divided into control group, 2-DG group, lung I/R injury group (I/R group) and 2-DG+I/R group. 2-DG (0.7 g/kg) was intraperitoneally injected 1 h prior to lung ischemia. The tissue structure was measured under light microscope. Lung injury parameters were detected. The contents of malondialdehyde (MDA), myeloperoxidase (MPO) and lactate were determined by commercially available kits. ELISA was used to detect the levels of IL-1ß and IL-18. Western blot, qRT-PCR and immunofluorescence staining were used to measure the expression changes of glycolysis and pyroptosis related indicators. The results showed that there was no significant difference in the parameters between the control group and the 2-DG group. However, the lung injury parameters, oxidative stress response, lactic acid content, IL-1ß, and IL-18 levels were significantly increased in the I/R group. The protein expression levels of glycolysis and pyroptosis related indicators including hexokinase 2 (HK2), pyruvate kinase 2 (PKM2), NLRP3, Gasdermin superfamily member GSDMD-N, cleaved-Caspase1, cleaved-IL-1ß and cleaved-IL-18, and the gene expression levels of HK2, PKM2 and NLRP3 were markedly up-regulated in the I/R group compared with those in the control group. The expression of HK2 and NLRP3 was also increased detected by immunofluorescence staining. Compared with the I/R group, the 2-DG+I/R group exhibited significantly improved alveolar structure and inflammatory infiltration, reduced lung injury parameters, and decreased expression of glycolysis and pyroptosis related indicators. These results suggest that 2-DG protects against lung I/R injury possibly by inhibiting NLRP3-mediated pyroptosis in rats.

Study on the Alkali-Free Three-Component Flooding System in the Daqing Oilfield.

ASP flooding is an important method to further improve oil recovery by a large margin. At present, it has entered the stage of industrial application, but there are still problems of scaling in the injection production system and high production maintenance costs. Based on the industrialized mature technology of weak alkali ASP flooding, sodium chloride is used to replace sodium carbonate, and the alkali-free three-component flooding (TC) system in the Daqing Oilfield is developed by mixing with petroleum sulfonate and partially hydrolyzed polyacrylamide. Based on the experiments of viscosity increasing, interface performance, stability, adsorption, and oil displacement effect, the differences between the alkali-free TC system and the weak alkali ASP system are compared and analyzed. The laboratory research results show that both systems are basically the same in terms of viscosity, viscoelasticity, shear resistance, interfacial activity, stability, and flowability. Due to the lack of alkaline water, the adsorption, emulsification, and oil displacement performance of the alkali-free TC system is slightly lower than that of the weak alkali ASP system. The recovery factor of core flooding can be increased by 27.31% over water flooding, which is 2.56 percentage points lower than that of the weak alkali ASP system. On the premise of the same 1% EOR effect, the agent cost of the alkali-free system is 17.02% lower than that of the alkali ASP system. This article innovatively verifies the feasibility of using NaCl instead of Na2CO3 and explains the mechanism of significantly improving oil recovery in composite systems under alkali-free conditions from the ion level. However, the emulsification effect of the alkali-free TC system is relatively weak. The next step of research would be to consider adding an E-surfactant to enhance the emulsification performance of the composite system. By improving the system composition, technical references are provided for the efficient development of other terrestrial sandstone oilfields.

Investigation of the Degradation of LiPF6- in Polar Solvents through Deep Potential Molecular Dynamics.

The nonaqueous electrolyte based on lithium hexafluorophosphate (LiPF6) is the dominant liquid electrolyte in lithium-ion batteries (LIBs). However, trace protic impurities, including H3O+, alcohols, and hydrofluoric acid (HF), can trigger a series of side reactions that lead to rapid capacity fading in high energy density LIBs. It is worth noting that this degradation process is highly dependent on the polarity of the solvents. In this work, a deep potential (DP) model is trained with a certain commercial electrolyte formula through a machine learning method. H3O+ is anchored with polar solvents, making it difficult to approach the PF6-, and suppressing the degradation process quickly at room temperature. Control experiments and simulations at different temperatures or concentrations are also performed to verify it. This work proposes a precise model to describe the solvation structure quantitatively and offers a new perspective on the degradation mechanism of PF6- in polar solvents.

Subtle adjustment of the cyclic potential on electro-activated glassy carbon electrodes for sensitive sensing of methyl parathion.

Facile electro-activated glassy carbon electrodes (e-GCEs), which are prepared in electrolyte solution with a certain potential for a few seconds, have been verified to improve analytical performance toward not a few electro-active molecules recently. Nevertheless, how and why the potential plays an important role is not clear, and has even not received enough consideration. In this paper, we found that the mode and the range of applied potential significantly impacted the sensitivity of methyl parathion (MP), which is a typical pesticide with the electro-active group of -NO2. Compared with constant potential, the e-GCE with cyclic potential provided a much more stable baseline during MP detection. Additionally, the electro-oxidation peak current of MP at around -0.1 V on it was higher than another changeable potential (constant current). What's more interesting, with cyclic potential for 50 segments from -2 to 1.5 V, the peak current value increased by 30 times in comparison with a bare GCE, but only 2 times from -2 to 1 V. Then after systematic investigation including structures of the electrode surface and functional groups, we speculated that the produced group of O-CO in the process of activation and remaining groups of C-O and CO on the bare GCE surface are beneficial for adsorbing MP molecules leading to enhanced peak current. Employing the proposed e-GCE, the limit of detection of MP reached 0.015 µM and the reproducibility was perfect. This work elucidates the potent impact of electro-activation potential parameters on electroanalysis behaviors.

EFL teachers' engagement: The impact of well-being and emotion regulation.

As foreign language education is a challenging and complex activity, investigating the factors that influence English as foreign language (EFL) teachers' engagement may be an interesting area of research. In this field, teachers' engagement is considered an important factor related to people's perception of work. With the emergence of Positive Psychology (PP), and with regard to the role of constructive emotion variables in teachers' engagement, more attention was paid to the practical aspects of life, and it views well-being as a crucial concern for individuals' success. Emotion regulation (ER), as another emotional trait, is noteworthy as it aids in managing the favorable and unfavorable emotions educators commonly encounter in educational settings. Therefore, the constructs of well-being and emotion regulation and their role in the EFL setting have been highlighted. Therefore, the current study sought to assess the effects of well-being and emotion regulation in EFL teachers' engagement. To this end, 410 Chinese EFL teachers were chosen to complete three scales, namely engagement, well-being and ER. Structural Equation Modeling (SEM) was run to inspect the responses of the teachers. The results specified that both ER and well-being had significant impacts on the engagement of Chinese EFL teachers. Indeed, 65 percent of changes in the EFL educators' engagement can be predicted by their well-being, and about 73 percent can be predicted by their emotional regulation. The consequences for EFL instructors, teacher trainers, and other academic stakeholders are also presented in detail.

Numerical Simulation of Component Transfer and Oil Drive of Nonalkali Ternary Emulsion Systems.

So far, alkali/surfactant/polymer flooding is widely used in oilfields to improve recovery. However, the introduction of alkali to the ternary composite leads to substantial damage formation, accelerates the scaling and corrosion loss in all aspects of surface injection and recovery, and consequently increases the cost of oil recovery in the ternary composite drive field. Therefore, environmentally friendly means are in urgent demand. Alternatively, a new non-alkali ternary drive system with salt instead of alkali has been developed based on the basis of ternary composite drive in the Daqing oilfield. In this experiment, a mathematical model of oil repelling by a salt-substituted alkali-free ternary emulsion system is formed, followed by the verification of the wet-lab experiments. The results show that the alkali-free ternary emulsion system can have a synergistic effect of complex salt and petroleum sulfonate surfactant and represents a wide range of ultralow interfacial tensions and good oil-repelling performances. The chromatographic separation occurs in the transmission process due to the adsorption of porous media, and the lower the permeability and the lower the injection rate, the higher the chromatographic separation degree. The use of multistage plug injection can narrow the difference of flow rate between high and low permeability layers and improve the recovery rate to 61.59%. Herein, the results provide theoretical guidance for the application of an alkali-free ternary emulsification system.

Radiomics based on machine learning algorithms could predict prognosis and postoperative chemotherapy benefits of patients with gastric cancer: a retrospective cohort study.

Background: Traditional clinical characteristics have certain limitations in evaluating cancer prognosis. The radiomics features provide information on tumor morphology, tissue texture, and hemodynamics, which can accurately reflect personalized predictions. This study investigated the clinical value of radiomics features on contrast-enhanced computed tomography (CT) images in predicting prognosis and postoperative chemotherapy benefits for patients with gastric cancer (GC). Methods: For this study, 171 GC patients who underwent radical gastrectomy and pathology confirmation of the malignancy at the First Affiliated Hospital of Wenzhou Medical University were retrospectively enrolled. The general information, pathological characteristics, and postoperative chemotherapy information were collected. Patients were also monitored through telephone interviews or outpatient treatment. GC patients were randomly divided into the developing cohort (n=120) and validation cohort (n=51). The intra-tumor areas of interest inside the tumors were delineated, and 1,218 radiomics features were extracted. The optimal radiomics risk score (RRS) was constructed using 8 machine learning algorithms and 29 algorithm combinations. Furthermore, a radiomics nomogram that included clinicopathological characteristics was constructed and validated through univariate and multivariate Cox analyses. Results: Eleven prognosis-related features were selected, and an RRS was constructed. Kaplan-Meier curve analysis showed that the RRS had a high prognostic ability in the developing and validation cohorts (log-rank P<0.01). The RRS was higher in patients with a larger tumor size (≥3 cm), higher Charlson score (≥2), and higher clinical stage (Stages III and IV) (all P<0.001). Furthermore, GC patients with a higher RRS significantly benefited from postoperative chemotherapy. The results of univariate and multivariate Cox regression analyses demonstrated that the RRS was an independent risk factor for overall survival (OS) and disease-free survival (DFS) (P<0.001). A visual nomogram was established based on the significant factors in multivariate Cox analysis (P<0.05). The C-index was 0.835 (0.793-0.877) for OS and 0.733 (0.677-0.789) for DFS in the developing cohort. The calibration curve also showed that the nomogram had good agreement. Conclusions: A nomogram that combines the RRS and clinicopathological characteristics could serve as a novel noninvasive preoperative prediction model with the potential to accurately predict the prognosis and chemotherapy benefits of GC patients.

Durable underwater super-oleophobic/super-hydrophilic conductive polymer membrane for oil-water separation.

Oily sewage has made serious impact on environment and people's life, and its treatment has become a global problem to be urgently solved. Oil-water separation has been considered to be an effective method to treat oily sewage at present. In this work, an underwater super-oleophobic/super-hydrophilic membrane with oil-water separation and self-cleaning properties was fabricated by electrochemical oxidation of sodium lignosulfonate doped polypyrrole. The membrane showed super-hydrophilicity for water-removal in air and super-hydrophilicity for oil-removal underwater in both oxidation and reduction states. The oil-water separation efficiency of the membranes for different organics exceeded 98.44%, no matter in oxidation or reduction state. Moreover, the membrane still exhibited excellent performance in terms of the oil-water separation efficiency and flux after 70 cycles, which were greater than 97.18% and 70.14 L·m-2·h-1, respectively. Simultaneously, through exploration of the mechanism, it was found that the larger anion kept intact in the membrane during the redox process, which made the stability of composition and performance. Thus, the membrane with advantageous properties, including underwater super-oleophobic/super-hydrophilicity, high oil-water separation efficiency, high circulating rate and stability, has significant potential in separation and collection of oily sewage.

Design for bird strike crashworthiness using a building block approach applied to the Flying-V aircraft.

The Flying-V aircraft concept promises better fuel-burn performance over conventional tube-and-wing configurations, integrating the passenger cabin and cargo volume into the lifting surface. However, the wing-fuselage and cockpit windows of the Flying-V are exposed to the flight direction, posing a new challenge to the design and certification of structures in terms of bird strikes. This study is a first step towards understanding the dynamic load path and contribution of each structural element on the bird strike resistance of the Flying-V leading-edge structures. The objective is to propose a building block approach to design the Flying-V's leading edge bird strike crashworthiness that complies with the EASA's certification CS25.631 using a 4lb bird impacted at a sea level cruising speed of 70 m/s. An additional requirement by the authors is to keep the structure within the elastic deformation during the impact of a 4lb bird to avoid the need for repairs in the Flying-V fuselage. Plasticity generated in the structure is regarded as damage and is used as a comparative parameter. At the highest building block level, a sensitivity analysis is performed to identify the effect of the thickness of each structural element on the plasticity and weight of the leading-edge structures. The trends are used to modify the baseline design and achieve a reduction of 80% of the plastic energy. The critical case of a 133 m/s impact of a 4lb bird at the cruise altitude of 37000 ft is also evaluated, and the results show penetration.

ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer.

Abnormal expression and remodeling of cytoskeletal regulatory proteins are important mechanisms for tumor development and chemotherapy resistance. This study systematically analyzed the relationship between differential expression of cytoskeleton genes and prognosis in gastric cancer (GC). We found the Arf GTP-activating protein ASAP1 plays a key role in cytoskeletal remodeling and prognosis in GC patients. Here we analyzed the expression level of ASAP1 in tissue microarrays carrying 564 GC tissues by immunohistochemistry. The results showed that ASAP1 expression was upregulated in GC cells and can be served as a predictor of poor prognosis. Moreover, ASAP1 promoted the proliferation, migration, and invasion of GC cells both in vitro and in vivo. We also demonstrated that ASAP1 inhibited the ubiquitin-mediated degradation of IQGAP1 and thus enhanced the activity of CDC42. The activated CDC42 upregulated the EGFR-MAPK pathway, thereby promoting the resistance to chemotherapy in GC. Taken together, our results revealed a novel mechanism by which ASAP1 acts in the progression and chemotherapy resistance in GC. This may provide an additional treatment option for patients with GC.

NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation.

The 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in the regulation of cell proliferation and metastasis formation and is upregulated in multiple cancers. However, the biological significance of NSUN2 in gastric cancer (GC) and the modification of NSUN2 itself have not been fully investigated. Here, we analyzed the expression level of NSUN2 in tissue microarrays containing 403 GC tissues by immunohistochemistry. NSUN2 was upregulated in GC, and that it was a predictor of poor prognosis. NSUN2 promotes the proliferation, migration, and invasion of GC cells in vitro. We also demonstrated that small ubiquitin-like modifier (SUMO)-2/3 interacts directly with NSUN2 by stabilizing it and mediating its nuclear transport. This facilitates the carcinogenic activity of NSUN2. Furthermore, m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells showed that m5C-methylated genes are involved in multiple cancer-related signaling pathways. PIK3R1 and PCYT1A may be the target genes that participate in GC progression. Our findings revealed a novel mechanism by which NSUN2 functions in GC progression. This may provide new treatment options for GC patients.

The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer.

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.

Commensal flora triggered target anti-inflammation of alginate-curcumin micelle for ulcerative colitis treatment.

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease characterized by dysregulation of colon immune response. Curcumin (Cur) has strong anti-inflammatory activities, but the application is severely hindered by the extremely hydrophobicity and pitiful bioavailability. Alginate (Alg), a natural polysaccharide with ideal solubility and biosafety, was introduced to prepare the esterified alginate-curcumin conjugate (Alg-Cur) and constructed stable Alg-Cur micelle in physiological solutions. Compared with crystalline Cur, the target anti-inflammatory activities of Alg-Cur were systematically investigated. The results showed that Alg-Cur exerted effective anti-inflammatory effects in Raw 264.7 cells. After oral administration, 92.32 % of Alg-Cur reached colon, and the ester bonds were quickly sheared by abundant esterase produced by commensal anaerobic flora. The released Cur was quickly absorbed in-situ in monomolecular state, and effectively ameliorated the colonic inflammation and tissue damage by inhibiting the TLR4 expression in colonic epithelial cell, reducing the transcription and expression of the pro-inflammation cytokines downstream, as well as the infiltration of lymphocytes, macrophages and neutrophils. The Alg-Cur micelle effectively enhanced the hydrophilicity and bioavailability of Cur, and the commensal flora triggered Cur release showed great potential for UC treatment.

The diverse roles of circular RNAs in pancreatic cancer.

Pancreatic cancer is one of the malignant tumors with poor prognosis. The molecular mechanisms of pancreatic oncogenesis and malignant progression are not fully elucidated. Several key signaling pathways, such as Notch, Wnt and hedgehog pathways, are important to drive pancreatic carcinogenesis. Recently, noncoding RNAs, especially circular RNAs (circRNAs), have been characterized to participate into pancreatic cancer development. Therefore, in this review article, we describe the association between circRNAs and pancreatic cancer prognosis. Moreover, we discuss how circRNAs are involved in regulation of cellular processes in pancreatic cancer, including proliferation, apoptosis, cell cycle, migration, invasion, EMT, metastasis, angiogenesis, drug resistance and immune escape. Furthermore, we mention that several compounds could regulate the expression of circRNAs, indicating that targeting circRNAs by compounds might be helpful for treating pancreatic cancer patients.

Patients with Helicobacter pylori-positive gastric cancer with human cytomegalovirus infection have a low tendency of advanced lymphatic metastasis in a Chinese population.

Recognized as a group I carcinogen for gastric cancer (GC) and a factor involved in the development of GC, Helicobacter pylori serves a major part in GC research. However, most studies have focused on H. pylori itself, ignoring the complicated pathogenic microbiological environment of GC and neglecting the synergistic or antagonistic effects of H. pylori with other pathogenic microorganisms. Increasing evidence has revealed that the human cytomegalovirus (HCMV) is present in several types of tumors and serves an important role in the neoplastic process of certain human malignant tumors, including GC. The aim of the present study was to explore the role of HCMV and H. pylori co-infection in GC. HCMV and H. pylori infection was analyzed in paired gastric tumor and peri-tumoral tissues from 134 (98 male and 36 female) patients using PCR. The results revealed that a total of 74 (55.2%) patients had H. pylori infection, 58 patients (43.3%) had HCMV infection, and 34 (25.4%) patients had both HCMV and H. pylori infection. Univariate and multivariate analyses demonstrated that H. pylori infection was independently associated with advanced lymphatic metastasis [P=0.007; odds ratio (OR)=3.51]. Furthermore, compared with HCMV-/H. pylori -, neither HCMV+/H. pylori - nor HCMV+/H. pylori + were associated with metastasis, but HCMV-/H. pylori + co-infection status was an independent risk factor for advanced lymphatic metastasis (P=0.005; OR=6.00). In conclusion, GC co-infected with HCMV and H. pylori exhibited a low tendency of lymph node metastasis. HCMV may interact with H. pylori to inhibit the process of lymphatic metastasis, and the mechanism requires further investigation.

Efficacy of the Preoperative Albumin-Bilirubin Grade for Predicting Survival and Outcomes of Postoperative Chemotherapy for Advanced Gastric Cancer.

PURPOSE: The liver function index can predict the prognosis of hepatocellular carcinoma and many other non-neoplastic diseases. We aimed to determine whether the preoperative albumin-bilirubin (ALBI) grade could predict the prognosis of patients with gastric cancer (GC). PATIENTS AND METHODS: Data of 243 patients with GC who underwent radical resection were collected retrospectively. Patients were divided into the high ALBI (>-2.34) and low ALBI (≤-2.34) grade groups. Overall survival was analyzed between the two groups using the Kaplan-Meier curves. Univariate and multivariate analyses identified the independent factors associated with postoperative complications and overall survival. RESULTS: The postoperative complication rates were higher in the high ALBI grade group than in the low ALBI grade group (P=0.005). The high ALBI grade group also had worse overall survival (P<0.001), especially TNM stage II-III patients (stage II, P=0.043; stage III, P<0.001). In the high ALBI grade group, patients with TNM stage III not undergoing chemotherapy had significantly worse survival times (P=0.001). High ALBI grade (P=0.032), Charlson score of 1-2 (P=0.007), and laparotomy surgery (P=0.045) were independent risk factors for postoperative complications. High ALBI grade (P=0.005), age ≥70 years (P=0.002), nutritional risk screening score 2002 score of 5-6 (P=0.019), tumor located in the cardia (P=0.020), diffuse tumor (P<0.001), and TNM stage III (P<0.001) were independent risk factors for overall survival. CONCLUSION: Preoperative ALBI grade could predict postoperative complications and overall survival of patients with GC, especially those with TNM stages II-III. This grading method has the advantages of preoperative availability, simplicity, and objectivity and aids in improving preoperative prognosis prediction and in achieving better outcomes of postoperative chemotherapy.

Long noncoding RNAs: functions and mechanisms in colon cancer.

Evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in the carcinogenesis and progression of a wide variety of human malignancies including colon cancer. In this review, we describe the functions and mechanisms of lncRNAs involved in colon oncogenesis, such as HOTAIR, PVT1, H19, MALAT1, SNHG1, SNHG7, SNHG15, TUG1, XIST, ROR and ZEB1-AS1. We summarize the roles of lncRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in colon cancer. In addition, we briefly highlight the functions of circRNAs in colon tumorigenesis and progression, including circPPP1R12A, circPIP5K1A, circCTIC1, circ_0001313, circRNA_104916 and circRNA-ACAP2. This review provides the rationale for anticancer therapy via modulation of lncRNAs and circular RNAs (circRNAs) in colon carcinoma.

Celastrol induces ROS-mediated apoptosis via directly targeting peroxiredoxin-2 in gastric cancer cells.

Background: Oxidative stress from elevated reactive oxygen species (ROS) has been reported to induce cell apoptosis and may provide a means to target cancer cells. Celastrol is a natural bioactive compound that was recently shown to increase ROS levels and cause apoptosis in cancer cells. However, the underlying mechanism for this cytotoxic action remains unclear and direct molecular targets of Celastrol have not been identified. Methods: Proteome microarray, surface plasmon resonance, isothermal titration calorimetry and molecular simulation were used to identify the molecular target of Celastrol. Binding and activity assays were used to validate the interaction of Celastrol with target protein in cell-free and gastric cancer cell lysates. We then assessed target transcript levels in in biopsy specimens obtained from patients with gastric cancer. Gastric cancer growth-limiting and cytotoxic activity of Celastrol was evaluated in BALB/c nu/nu mice. Results: Our data show that Celastrol directly binds to an antioxidant enzyme, peroxiredoxin-2 (Prdx2), which then inhibits its enzyme activity at both molecular and cellular level. Inhibition of Prdx2 by Celastrol increased cellular ROS levels and led to ROS-dependent endoplasmic reticulum stress, mitochondrial dysfunction, and apoptosis in gastric cancer cells. Functional tests demonstrated that Celastrol limits gastric cancer cells, at least in part, through targeting Prdx2. Celastrol treatment of mice implanted with gastric cancer cells also inhibited tumor growth, associated with Prdx2 inhibition and increased ROS. Analysis of human gastric cancer also showed increased Prdx2 levels and correlation with survival. Conclusion: Our studies have uncovered a potential Celastrol-interacting protein Prdx2 and a ROS-dependent mechanism of its action. The findings also highlight Prdx2 as a potential target for the treatment of gastric cancer.

Opposing biological functions of the cytoplasm and nucleus DAXX modified by SUMO-2/3 in gastric cancer.

Death domain-associated protein (DAXX) is a complex biological multifunctional protein and is involved in the tumorigenesis and progression of multiple cancers. The accumulation of DAXX in the nucleus is a common phenomenon in tumor cells. However, altering the subcellular localizations of DAXX results in different biological functions, and we also found that its nuclear/cytoplasmic ratio (NCR) was associated with poor prognosis in gastric cancer (GC). In this study, we investigated the effect of cytoplasmic and nuclear DAXX (cDAXX and nDAXX) in GC and the underlying mechanisms. Immunohistochemical detection performed in 323 GC tissues reveled that cDAXX was associated with a better survival, while high nDAXX expression suggested a poorer prognosis outcome. Upregulation of DAXX in the cytoplasm inhibited cell proliferation and promoted apoptosis, whereas downregulation of DAXX in the nucleus displayed opposite effects. Moreover, Transwell assays revealed that DAXX enhanced GC cell migration and invasion. Analysis from the Gene Expression Profile Interactive Analysis (GEPIA) database showed that the expression of DAXX was significantly associated with SUMO-2/3 in GC tissues. Co-immunoprecipitation combined with immunofluorescence analysis indicated that DAXX interacted directly with SUMO-2/3. Subsequently, down-regulating the expression of SUMO-2/3 resulted in altered subcellular localization of DAXX. Bioinformatics analysis showed that RanBP2 may act as SUMO E3 ligase to promote nuclear-plasma transport via combining with RanGAP1. Taken together, our results indicated that DAXX plays opposing roles in GC and suggest a new model whereby cDAXX, nDAXX, and SUMO-2/3 form a molecular network that regulates the subcellular localization of DAXX and thereby modulates its opposing biological effects. Thus, our findings provide a foundation for future studies of DAXX as a novel therapeutic target for patients with GC.