Engineering Metallic Alloy Electrode for Robust and Active Water Electrocatalysis with Large Current Density Exceeding 2000 mA cm-2.

The amelioration of brilliantly effective electrocatalysts working at high current density for the oxygen evolution reaction (OER) is imperative for cost-efficient electrochemical hydrogen production. Yet, the kinetically sluggish and unstable catalysts remain elusive to large-scale hydrogen (H2) generation for industrial applications. Herein, a new strategy is demonstrated to significantly enhance the intrinsic activity of Ni1-xFex nanochain arrays through a trace proportion of heteroatom phosphorus doping that permits robust water splitting at an extremely large current density of 1000 and 2000 mA cm-2 for 760 h. The in situ formation of Ni2P and Ni5P4 on Ni1-xFex nanochain arrays surface and hierarchical geometry of the electrode significantly promote the reaction kinetics and OER activity. The OER electrode provides exceptionally low overpotentials of 222 and 327 mV at current densities of 10 and 2000 mA cm-2 in alkaline media, dramatically lower than benchmark IrO2 and is among the most active catalysts yet reported. Remarkably, the alkaline electrolyzer renders a low voltage of 1.75 V at a large current density of 1000 mA cm-2, indicating outperformed overall water splitting. The electrochemical fingerprints demonstrate vital progress toward large-scale H2 production for industrial water electrolysis.

Unlocking the Potential of High Entropy Alloys in Electrochemical Water Splitting: A Review.

The global pursuit of sustainable energy is focused on producing hydrogen through electrocatalysis driven by renewable energy. Recently, High entropy alloys (HEAs) have taken the spotlight in electrolysis due to their intriguing cocktail effect, broad design space, customizable electronic structure, and entropy stabilization effect. The tunability and complexity of HEAs allow a diverse range of active sites, optimizing adsorption strength and activity for electrochemical water splitting. This review comprehensively covers contemporary advancements in synthesis technique, design framework, and physio-chemical evaluation approaches for HEA-based electrocatalysts. Additionally, it explores design principles and strategies aimed at optimizing the catalytic activity, stability, and effectiveness of HEAs in hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and overall water splitting. Through an in-depth investigation of these aspects, the complexity inherent in constituent element interactions, reaction processes, and active sites associated with HEAs is aimed to unravel. Eventually, an outlook regarding challenges and impending difficulties and an outline of the future direction of HEA in electrocatalysis is provided. The thorough knowledge offered in this review will assist in formulating and designing catalysts based on HEAs for the next generation of electrochemistry-related applications.

Potential role of minichromosome maintenance protein 2 as a screening biomarker in esophageal cancer high-risk population in China.

Minichromosome maintenance proteins are novel proliferative markers that have been proposed as diagnostic markers in many cancers. We evaluated the potential role of minichromosome maintenance protein 2 as a screening biomarker and compared it with proliferating cell nuclear antigen and Ki67 in a population survey of esophageal squamous cell carcinoma. A total of 299 esophageal samples from a high-risk region in China, including 171 from an endoscopy population survey, 30 from brushing cytology, and 98 from surgery and autopsy, underwent immunostaining with minichromosome maintenance protein 2, proliferating cell nuclear antigen, and Ki67 antibodies. Minichromosome maintenance protein 2 expression was confined to the proliferative compartment of normal and abnormal esophageal epithelium and particularly manifested in the surface layer of dysplasia and carcinoma in situ. The expression of proliferating cell nuclear antigen and Ki67 was positively correlated with that of minichromosome maintenance protein 2 (r(s) >0.39, P < .01); but their positive nuclei seldom reached the surface layer, and the labeling indices were significantly lower than those for minichromosome maintenance protein 2 in dysplasia (P < .05) and carcinoma in situ (P < .001). The sensitivity and specificity of minichromosome maintenance protein 2 in diagnosing dysplasia were 91.3% and 61.8%, respectively, higher than those for proliferating cell nuclear antigen (88.4% and 47.1%) and Ki67 (78.3% and 57.8%). Nine of 10 cancer and paracancerous surface-brushing samples expressed minichromosome maintenance protein 2, and the detection was higher than that for proliferating cell nuclear antigen (8/10 and 7/10) and Ki67 (7/10 and 7/10). However, none of 10 normal surface-brushing samples expressed the 3 markers. Minichromosome maintenance protein 2 is more sensitive and specific than proliferating cell nuclear antigen and Ki67 in indicating esophageal dysplasia. Minichromosome maintenance protein 2 immunostaining combined with surface brushing could be valuable in screening patients at high risk of cancer in mass surveys.

Analysis of basement membrane structure and inflammation during the development of esophageal squamous cell carcinoma in the Chinese Chaoshan high risk region.

BACKGROUND & AIMS: To investigate relationships between basement membrane structure, inflammation, beta1 integrin expression, activation of ERK/MAPK signaling pathways, and cell proliferation in esophageal mucosa at various stages during the evolution of esophageal squamous cell carcinoma. METHODS: Three tissue arrays were made of 228 tissue cores from 428 surgically-resected specimens. The arrays included 26 samples of normal epithelium, 28 with hyperplasia, 18 with dysplasia, 27 with carcinoma in situ and 129 with invasive carcinoma. In addition, 21 cases of hyperplasia, 13 cases of dysplasia and 13 case of carcinoma in situ were obtained by manual microdissection of unfixed frozen tissue. Hematoxylin and eosin stained sections were used to evaluate the epithelium and inflammation. The periodic acid-Schiff stain and an immunohistochemical stain for laminin were used to examine the structure of basement membranes. The expression of beta1 integrin, p-ERK, and Ki67 were evaluated by quantitative immunohistochemistry. RT-PCR and Western blots were also used to detect expression of beta1 integrin. RESULTS: Quantitative scales were developed to classify basement membrane structure and inflammation. Basement membrane alterations correlated with the degree of epithelial change (chi2 = 501.9, p < 0.01) and with the degree of lymphocytic infiltration in the lamina propria and epithelium (chi2 = 273.4, p < 0.01). There was a significant relationship between the extent of basement membrane alteration and the expression of beta1 integrin, p-ERK, and Ki67. CONCLUSIONS: The correlations suggest that there is a direct relationship between basement membrane structure and the development of esophageal squamous cell carcinoma.

Altered expression of ezrin in esophageal squamous cell carcinoma.

Ezrin is a membrane-cytoskeletal linker belonging to the ezrin-radixin-moesin (ERM) family and has been suggested to be involved in tumorigenesis. In this study we investigated ezrin expression pattern in normal esophageal mucosa and esophageal squamous cell carcinoma (ESCC) and the correlation with clinical characteristics. Immunohistochemical staining showed a tendency for ezrin to translocate from membrane to cytoplasm in the progression from normal epithelium to invasive carcinoma of the esophagus. By Western blot, we found that ezrin expression was downregulated in 13 ESCC specimens and upregulated in 36 others. Moreover, quantitative real-time RT-PCR demonstrated that ezrin mRNA level in normal esophageal mucosa was 3.60 +/- 3.60 times that in ESCC (p<0.001). Proliferating cell nuclear antigen (PCNA) expression level was higher in ezrin downregulated group compared with that in ezrin upregulated group (p<0.05). However, there was no significant association between ezrin expression and clinical characteristics. The results suggested that the localization of ezrin by immunohistochemistry may be useful in the diagnosis of ESCC, and ezrin may play a suppressive role in the tumorgenesis of ESCC.

Prognostic and clinicopathological features of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D1 expression in human esophageal squamous cell carcinoma.

AIM: To investigate the expression of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D(1) in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. METHODS: Expression of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D(1) was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. RESULTS: The reduced expression rate of E-cadherin, alpha-catenin, beta-catenin and gamma-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression rate was 56.5%. Expression of gamma-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (chi(2) = 4.183 and chi(2) = 5.035, respectively, P<0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (chi(2) = 5.769, P<0.05). Reduced expression of E-cadherin and gamma-catenin was associated with poor differentiation of tumor, reduced expression of gamma-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and gamma-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and in reduced expression one and were 78% and 48% in gamma-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of alpha-catenin correlated with that of E-cadherin and beta-catenin (P<0.05). CONCLUSION: The reduced expression of E-cadherin and gamma-catenin, but not alpha-catenin, beta-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.

Effects of selenium and iodine on the expression of c-fos and c-jun mRNA and their proteins in cultured rat hippocampus neurons.

OBJECTIVE: To study the effect of selenium (Se) and iodine (I) and the compound of both on the proto-oncogenes c-fos and c-jun mRNA and their protein expression in the cultured rat hippocampus neurons. METHODS: Using the technique of serum free hippocampus neuron culture, different doses of Se and I and Se + I compound were added into the medium. The expression of the mRNA of c-fos, c-jun in hippocampus neurons cultured for 1, 3, 5, 7 and 10 d were studied using both in situ hybridization and SABC immunohistochemical technique. RESULTS: Both Se and I could enhance the expression of c-fos, c-jun mRNA and their proteins, especially the combination of I and Se able to give a remarkable effect on c-jun mRNA expression. CONCLUSIONS: Se and I may effect the expression of both c-fos and c-jun mRNA, especially the c-jun mRNA and its protein of hippocampus neurons, and thus may effect the differentiation and development of neurons.

[The promoter effects of sodium butyrate on the malignant transformation of the immortalized esophageal epithelium induced by human papillomavirus].

OBJECTIVE: Study on the promoter effects of sodium butyrate in high or low dosages on carcinogenesis process, based on the immortalization of human fetal esophageal epithelium induced by human papillomavirus (HPV) 18E(6)E(7) genes. METHODS: The immortalized esophageal epithelium SHEE was treated with high concentration of the sodium butyrate (80 mmol/L) and then with low concentration (5 mmol/L) for 8 weeks respectively. The cells were cultured continuously without sodium butyrate for 14 weeks. The morphology, proliferation and apoptosis of the cells were studied by phase contrast microscopy, immunohistochemistry and flow cytometry. The dead and the viable cells were assayed by fluorescent microscopy with Hoechst 33342 and Propidium iodide staining. Tumorigenesis of the cells was assessed by soft agar colony formation and by transplantation of cells into nude mice and SCID mice. RESULTS: When cells were exposed to high concentration of sodium butyrate, cell death was increased leaving few live cells. When cells were cultured in the medium with low concentration of sodium butyrate, the first proliferative stage appeared. Removal of the butyrate caused the cell to enter a crisis stage with a long doubling time resembling senescent cells. After the crisis stage, the cells progressed to the second proliferation stage with continuous replication and atypical hyperplasia. At the end of the second proliferative stage, carcinogenesis of the cells appeared with large colonies in soft-agar and tumor formation in transplanted SCID mice and nude mice. CONCLUSIONS: The malignant change of the immortalized epithelium by the effects of sodium butyrate is the consequence of a two-stage mortality mechanism: cells death by butyrate cytotoxicity and cell crisis by abrogation of sodium butyrate. These data reveal that in high dosage, sodium butyrate induces cell death and in low dosage, it induces cell proliferation, which emphasizes the importance of butyrate as a promotor of carcinogenesis.

Immortal phenotype of the esophageal epithelial cells in the process of immortalization.

To search for potential biomarkers used to monitor the process of immortalization, we investigated the relative level of telomerase activity and other immortal phenotypes in the SHEE esophageal epithelial cell line. This human fetal esophageal epithelial cell line, induced by human papilloma virus (HPV) 18 E6E7, was continually propagated over 100 passages. Fourteenth passage cells (SHEE14) were cultured in a flask with a serum-free medium and continually cultured to the 30th passage (SHEE30). Cells of SHEE14, SHEE20 and SHEE30 were examined according to cell morphology, cell cycle, apoptosis, contact-inhibition growth, anchorage- dependency, dose-dependency to epithelial growth factors (EGF), telomerase activity and tumorigenicity. The SHEE14 cells exhibited good differentiation with contact-inhibition and anchorage-dependent growth. The SHEE20 cells exhibited increase of senescent and apoptotic cells, and difficulty in propagation. The SHEE30 cells exhibited a higher proliferative index and some undifferentiated cells, with weakened contact-inhibition and anchorage-dependent growth. The telomerase was activated in cells of SHEE30, but not in SHEE14 and SHEE20 cells. The different response to dose-dependency to EGF was not statistically different in SHEE14 and SHEE30. Three groups of cells displayed lack of tumor formation in nude mice. Compared with SHEE14 and SHEE20, SHEE30 cells were of immortalized status with immortal phenotype, which consisted of telomerase activity, increase of cell proliferation, weakened contact-inhibition and anchorage-dependent growth, dose dependency to EGF and lack of tumor formation. From passage 14 to 30th passage, SHEE cells went through cellular senescence, apoptosis and immortalization. With a view toward diagnostic and biological aspects, telomerase activity is a crucial step and a cardinal requirement for immortalization. The telomerase activity and other immortal phenotypes are potential markers for monitoring the process of immortalization.