Defect Engineering in Bi-Based Photo/Electrocatalysts for Nitrogen Reduction to Ammonia.

Main group Bi-based materials have gained popularity as N2 reduction reaction (NRR) photo/electrocatalysts due to their ability to inhibit competitive H2 evolution reactions (HER) and the unique N2 adsorption activities. The introduction of defects in Bi-based catalysts represents a highly effective strategy for enhancing light absorption, promoting efficient separation of photogenerated carriers, optimizing the activity of free radicals, regulating electronic structure, and improving catalytic performance. In this review, we outline the various applications of state of the defect engineering in Bi-based catalysts and elucidate the impact of vacancies on NRR performance. In particular, the types of defects, methods of defects tailoring, advanced characterization techniques, as well as the Bi-based catalysts with abundant defects and their corresponding catalytic behavior in NRR were elucidated in detail. Finally, the main challenges and opportunities for future development of defective Bi-based NRR catalysts are discussed, which provides a comprehensive theoretical guidance for this field.

In silico analysis of the association between long non-coding RNA family with sequence similarity 99 member A (FAM99A) and hepatic cancer.

The link between family with sequence similarity 99 member A (FAM99A), a type of long non-coding RNA, and tumourigenesis remains ambiguous. Therefore, in this study, the authors conducted an expression profile analysis of FAM99A based on 33 types of cancer within The Cancer Genome Atlas project. The expression profile data revealed low expression levels of FAM99A in hepatocellular carcinoma, cholangiocarcinoma, and testicular germ cell tumour tissues than in the normal control tissues. Survival analysis indicated a correlation between low FAM99A expression and worse survival outcome in patients with hepatic cancer. Further investigation revealed the possible implication of DNA methylation, but not copy number variation, in FAM99A-associated hepatic tumourigenesis. The authors also identified a set of differentially expressed genes between patients with hepatic cancer and negative controls, which were found to be related to biochemical metabolism or the cell cycle. Additionally, FAM99A expression may be associated with the infiltration status of several immune cells, such as dendritic cells, natural killer cells, and neutrophils. Overall, FAM99A may function as a prognostic marker that is potentially associated with DNA methylation, immune cell infiltration, and biochemical metabolism in hepatic cancer.

Construction of S-Scheme heterojunction Ni11(HPO3)8(OH)6/CdS photocatalysts with open framework surface for enhanced H2 evolution activity.

The emerging S-scheme heterojunction shows a particular superiority in enhancing the efficiency of charge separation in photocatalyst. Herein, a Ni11(HPO3)8(OH)6/CdS heterojunctions (NiPO/CdS) are constructed for the first time by loading open framework structure NiPO on the surface of CdS nanoparticles (CdS NPs). The built-in electric field generated at the interface promotes the directional migration of photogenerated electrons from NiPO to CdS. This S-scheme pathway achieves a strong redox capacity and efficient carrier separation. More importantly, the unique triangular and hexagonal channels of NiPO facilitate the exposure of CdS active sites for proton adsorption, H2 production and escape. The hydrogen evolution rate of NiPO/CdS is 39 mmol g-1 h-1 under visible light irradiation, which is 6.5 times higher than that of pure CdS. The NiPO/CdS heterojunction also exhibits remarkable long-term stability. This study provides a new strategy for the ingenious design of S-scheme photocatalysts with excellent photocatalytic performance.

Graphene oxide coupled high-index facets CdZnS with rich sulfur vacancies for synergistic boosting visible-light-catalytic hydrogen evolution in natural seawater: Experimental and DFT study.

Constructing photocatalysts with high activity and anti-photocorrosion is a key to harvesting hydrogen energy from seawater efficiently. Herein, graphene oxide closely coupled high-index facets CdZnS with rich sulfur vacancies (Vs-CZS@GO) has been successfully synthesized via one-pot sulfidation accompanied pyrolysis. DFT calculation confirmed the delicate surface/interface/defect engineering endowed high-index facets Vs-CZS@GO with a lower ΔGH* value and significant charge transfer behavior for efficient H2-generation. The synergistic effect of sulfur vacancy, high-index facets, and tightly coupling interface not only enhanced intrinsic active sites and carrier separation efficiencies, but also greatly promoted H2 evolution rate and stability. Consequently, Vs-CZS@GO displayed a significantly high H2-generation rate of 23.2 mmol∙g-1∙h-1 in natural seawater under visible-light irradiation, which is up to 82% of that in pure water. This work provides deeply insight into the synergistic regulation of electronic structure for exposed high-index facets photocatalysts via defect engineering and interface engineering for synergistic boosting visible-light-to-H2 evolution.

Expression Patterns of Ezrin and AJAP1 and Clinical Significance in Breast Cancer.

Ezrin and adherens junction-associated protein 1 (AJAP1) are structural proteins which are involved in numerous human malignancies. However, little is known about the relationship between them in breast cancer. This study was set out to investigate the relationship between them and to further explore the mechanism of AJAP1-mediating cytoskeleton in breast cancer progression. Ezrin and AJAP1 expressions were detected in 377 samples of breast cancer by immunohistochemistry, and different expression patterns between AJAP1 and Ezrin with clinicopathological parameters were analyzed. Besides, univariate and multivariate Cox models were used to evaluate their prognostic potential. Enzyme-linked immunosorbent assay, Western blot, qRT-PCR, and phalloidin staining of F-actin were used to explore the relationship and the mechanism between AJAP1 and Ezrin in cytoskeleton arrangement. 377 cases of breast cancer results showed that AJAP1 expression was negatively related with histological grade and lymph node involvement and could be an independent prognosis marker of breast cancer. AJAP1 expression tended to be higher in the Ezrin-negative expression case. Patients with AJAP1negative and Ezrinpositive expression had a worse prognosis (p < 0.0001) and shorter DFS (p = 0.015). More importantly, AJAP1 depletion increased the cell ability of F-actin formation through promoting Ezrin expression. AJAP1 depletion might mediate breast cancer malignancy potential through promoting Ezrin expression and cytoskeleton formation.

Photogenerated Oxygen Vacancies in Hierarchical Ag/TiO2 Nanoflowers for Enhanced Photocatalytic Reactions.

Oxygen vacancy (Vo) creation and morphology controlling make significant contributions to the electronic and structural regulation of metal oxide semiconductors, yet an investigation about convenient approaches for fabricating hierarchical catalyst with abundant oxygen vacancies still has significant challenges. Here, we report a unique method to create abundant oxygen vacancies in hierarchical Ag/TiO2 nanoflowers during photocatalytic reaction, which is accompanied by light absorption variation and surface plasmon resonance (SPR) enhancement. Its high efficiency of photocatalytic H2 evolution (the highest apparent quantum yield reaches 3.2% at 365 nm) and rhodamine B degradation can be considered as benefits from the synergistic effects of the well-arranged hierarchical structure, the photogenerated oxygen vacancies, and the SPR of cocatalyst Ag. This work proposes an effective strategy to optimize the synthesis of regular hierarchical structures and enriches the research on the vital function of oxygen vacancies in photocatalytic reactions.

ß-Catenin nuclear localization positively feeds back on EGF/EGFR-attenuated AJAP1 expression in breast cancer.

BACKGROUND: Adherent junction associated protein 1 (AJAP1), a typical molecule of adherent junctions, has been found to be a tumor suppressor in many cancer types. Aberrant activation of ß-catenin has been demonstrated to be associated with malignant biological properties of tumors including breast cancer. This study aimed to investigate the function and mechanism of AJAP1-mediated ß-catenin activity of breast cancer lines in vitro and in breast cancer patients. METHODS: AJAP1 and ß-catenin expressions in breast cancer tissues and cell lines were detected by immunohistochemistry, western blotting and qRT-PCR. The EGF/EGFR axis-mediated AJAP1 attenuated ß-catenin nuclear location was measured by western blotting, immunofluorescence assay, co-immunoprecipitation, luciferase assay and ubiquitination assays. Furthermore, the function of AJAP1 and ß-catenin regulated breast cancer progression was explored both in vivo and in vitro. RESULTS: It was found that AJAP1 had a high negative correlation with ß-catenin nuclear expression and was a novel tumor suppressor in breast cancer. AJAP1 loss can mediate ß-catenin accumulated in cytoplasm and then transferred it to the nucleus, activating ß-catenin transcriptional activity and downstream genes. Additionally, ß-catenin can reverse the invasion, proliferation ability and tumorigenicity of the depletion of AJAP1 caused both in vivo and in vitro. Besides, EGF/EGFR also involved in the process of AJAP1-depiction induced ß-catenin transactivation to the nucleus. More importantly, EGFR depletion/AJAP1 knocked down promoted the progression of breast cancer by regulating the activity of ß-catenin nuclear transactivation. CONCLUSION: This study demonstrated that AJAP1 acted as a putative tumor suppressor while ß-catenin nuclear localization positively fed back on EGF/EGFR-attenuated AJAP1 expression in breast cancer, which might be beneficial to develop new therapeutic targets for decreasing nuclear ß-catenin-mediated malignancy in breast cancer.

Clinical significance of PDEF factor expression and its relation to androgen receptor in ER- breast cancer.

AIMS: The mechanism of androgen receptor (AR) promoting tumour growth in oestrogen receptor-negative (ER- ) breast cancer (BC) is undetermined. Prostate-derived ETS factor (PDEF) is highly restricted to the hormone-regulated tissues of epithelial cells, such as those in the prostate, breast and other tissues. It has been demonstrated that PDEF expression is associated with AR in prostate cancer. In this research, we aimed to investigate the relationship between PDEF and AR in ER- BC. METHODS AND RESULTS: We immunohistochemically evaluated the correlation between PDEF and AR expression in 246 cases of ER- invasive BC, and investigated their relationship in ER- BC cell lines. The expression of PDEF was associated with the positive expression of AR (P < 0.001) and a worse survival rate (P = 0.006). PDEF+ tumours were significantly more often AR+ (P < 0.001). AR and PDEF were more often co-expressed and the series of AR+ PDEF+ (126 of 246, 51.2%) had a poor survival rate (P = 0.046). In Cox models, PDEF expression (P = 0.028) was an independent predictor for overall survival (OS). At the cellular protein and mRNA levels, our experiments also showed a statistically significant positive correlation between PDEF and AR, and that PDEF may be regulated by AR. CONCLUSIONS: PDEF is associated with markers of bad prognosis, supporting its role as a growth promoter in ER- BC. Our findings also provide evidence that PDEF is strongly correlated with AR expression in ER- breast cancer; it may be a downstream target gene of AR and a potential prognostic factor in ER- BC.

Expression of EMT markers and mode of surgery are prognostic in phyllodes tumors of the breast.

Phyllodes tumors of the breast are rare neoplasms that account for <1% of all mammary tumors and 2-3% of fibro-epithelial neoplasms of the breast. We evaluated the clinicopathological characteristics of a cohort of 246 Chinese patients in relation to the expression of epithelial-to-mesenchymal (EMT) markers in benign, borderline and malignant tumors and the prognostic value of different surgical regimens. We observed that survival outcomes correlated with the mode of surgical management in the three patient groups. Expression of E-cadherin, Snail, Slug and Twist were higher in epithelial cells from borderline and malignant tumors than those in benign tumors, whereas the expression of N-cadherin was opposite. Levels of the EMT markers Snail and Slug in the stromal compartment increased with the advancing tumor grade. Expression of mesenchymal stem cell markers contributed to the inherent heterogeneity in the malignant tumors. Based on Cox models, surgical management emerged as an independent predictor for disease-free survival, whereas a history of recent growth and tumor grade were independent predictors for overall survival. These findings show that expression of EMT markers, the mode of surgical management, and a history of recent tumor growth had prognostic potential for patients with phyllodes tumors of the breast.

Postmastectomy radiotherapy benefit in Chinese breast cancer patients with T1-T2 tumor and 1-3 positive axillary lymph nodes by molecular subtypes: an analysis of 1369 cases.

The aim of this study was to examine the association between molecular subtype (MST) and prognosis and research the postmastectomy radiotherapy (PMRT) effect in T1-T2 tumors with 1-3 positive axillary lymph nodes (ALNs). This retrospective study studied breast cancer patients with T1-T2 tumors and 1-3 positive ALNs according to MST: Luminal A, Luminal B, human epidermal growth factor receptor-2 (Her-2) positive, and Triple negative. The impact of adjuvant PMRT in T1-T2 tumors with 1-3 positive ALNs was also assessed. This study included 1369 patients: 33.0 % Luminal A, 42.9 % Luminal B, 11.9 % Her-2 positive, and 12.2 % Triple negative. On univariate and multivariate analyses, MST was associated with locoregional relapse (LRR). Kaplan-Meier analysis showed that PMRT significantly decreased LRR risk (p = 0.017) and distant metastasis (DM) risk (p < 0.0001). In subgroup analysis, PMRT showed significant benefits of improvement in LRR in patients with younger age, positive lymphovascular invasion (LVI), and ratio of positive lymph nodes (LNs) >25 %. Moreover, the nomogram could more accurately predict LRR (c-index 0.75) in T1-2N1 breast cancer patients. MST associated with patient outcomes in breast cancer patients with T1-T2 tumors and 1-3 positive ALN. It makes sense to offer PMRT for patients aged<40 years old, LVI, 2 and 3 positive lymph nodes, and ratio of positive LNs >25 %.

C-kit overexpression correlates with KIT gene copy numbers increases in phyllodes tumors of the breast.

We determined c-kit expression in the stroma and epithelia of benign, borderline, and malignant phyllodes tumors (PTs), respectively, as well as the relationship between c-kit expression in stromal elements and KIT gene copy number variations (CNVs). To assess c-kit expression and KIT CNVs, 348 PT cases were studied: 120 (34.4 %) benign cases, 115 (33.1 %) borderline cases, and 113 (32.5 %) malignant cases. All of these cases were evaluated for c-kit (CD117) expression using immunohistochemistry. Forty-two cases (29 c-kit-positive in the stromal cells cases and 13 negative cases) were investigated for KIT gene CNVs via genomic polymerase chain reaction (PCR). The overall rate of c-kit positivity in the stroma was 46.8 %, as well as 24.2, 53.1, and 64.6 %, respectively, in PTs of three different grades. However, in the majority of cases, the epithelia were c-kit positive (98.2 %), and the positivity was 100, 99.1, and 95 % in PTs of three different grades, respectively. There was a significant change in the expression of c-kit in the stroma and epithelia according to grade (P < 0.001, P = 0.014). From the genomic PCR results, we can confirm that c-kit positivity in the stroma is directly correlated with KIT gene copy numbers increases (P = 0.003, P = 0.041). We demonstrated that c-kit expression in the stroma of PTs is positively associated with malignancy. c-Kit epithelial positivity was inversely correlated with PTs malignancy. c-Kit overexpression in the stroma was related to KIT gene copy numbers increases.

Abnormal expression of Nek2 and ß-catenin in breast carcinoma: clinicopathological correlations.

AIMS: NIMA-related kinase 2 (Nek2) and ß-catenin are important centrosome regulatory factors. The aim of this study was to detect the possible disparity in their expression among normal breast tissue, invasive ductal carcinoma (IDC), concomitant ductal carcinoma in situ (DCIS), and pure DCIS, and to explore its correlation with clinicopathological factors. METHODS AND RESULTS: We used immunohistochemistry to detect protein expression of Nek2 and ß-catenin in breast cancer tissues from 60 cases of pure DCIS, 348 cases of IDC and 137 cases of concomitant DCIS with that in normal breast tissues from the same 137 concomitant DCIS patients as controls. As compared with normal tissue, expression of Nek2 and ß-catenin in the cytoplasm was significantly increased in IDC and DCIS (P < 0.05), and variation in expression was also observed in different grades of IDC (P < 0.01). Also, cytoplasmic expression of Nek2 and and of ß-catenin were correlated with each other in IDC and DCIS (P < 0.01). In addition, they were both related to Ki67 immunoreactivity (P < 0.05). Furthermore, our study also revealed a correlation between their expression and some clinicopathological factors. We found that Nek2 cytoplasmic expression was associated with grade and tumour size (P < 0.01) in IDC, whereas ß-catenin cytomembrane expression showed significant variation with grades, TNM stages, lymphoid node status, oestrogen receptor status, and molecular subtype (P < 0.05); a difference in expression was also observed between IDC and DCIS (P < 0.05). Also, ß-catenin cytoplasmic expression was associated with TNM stage (P < 0.05). Expression of Nek2 at the mRNA level was detected in 50 pairs of breast cancer specimens and matched normal tissues by reverse transcriptase polymerase chain reaction, and the result showed increased expression in IDC. CONCLUSIONS: This study suggests that abnormal expression of Nek2 and ß-catenin might be one of the mechanisms of tumorigenesis, especially of abnormal tumour proliferation. They may represent new potential targets for therapeutic intervention.

A retrospective study of breast cancer subtypes: the risk of relapse and the relations with treatments.

Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate relapse for patients with the major subtypes of breast cancer as classified using immunohistochemical assay and to investigate the patterns of benefit from the therapies over the past years. The study population included primary, operable 2,118 breast cancer patients, all non-specific infiltrative ductal carcinoma, with the median age of 53.2 years. All patients underwent local and/or systemic treatments. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. The expression of estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 were analyzed by immunohistochemistry. All patients were classified into the following categories: luminal A, luminal B, HER2 overexpressing, basal-like, and unclassified subtypes. Ki-67 was detected in luminal A subtype. The median follow-up time was 67.9 months. Luminal A tumors had the lowest rate of relapse (12.7%, P < 0.001), while luminal B, HER2 overexpression, and basal-like subtypes were associated with an increased risk of relapse (15.7, 19.1, 20.9%). Molecular subtypes retained independent prognostic significance (P < 0.001). In luminal A subtype, adjunctive radiotherapy could decrease the risk of relapse (P = 0.005), Ki67 positive was a high-risk factor for relapse (P < 0.001), and adjuvant chemotherapies could reduce the relapse for the patients with risk factors (P < 0.001). Adjuvant hormone therapy was an effective treatment for ER-positive tumors (P < 0.001). Molecular subtypes of breast cancer could robustly identify the risk of recurrence and were significant in therapeutic decision making. The model combined subtype and clinical pathology was a significant improvement. Luminal A tumors might represent two distinct subsets which demonstrated distinct prognosis and therapy response.

Chromosome aberrations associated with centrosome defects: a study of comparative genomic hybridization in breast cancer.

Centrosome abnormalities occur frequently in various tumors and can cause chromosomal instability and eventually promote cancer development. We investigated the chromosome aberrations associated with centrosome abnormalities in 30 cases of breast cancer, combining immunohistochemical staining and comparative genomic hybridization. Except for some common chromosome alterations (including gains of 1q, 8q, 17q, 20q, and Xq and losses of 8p, 11q, 13q, 14q, 16q, 17p, 22q, and Xp) that have also been seen more frequently in other studies, we discovered some new changes that have rarely been reported, including gains at 2p, 5p, 10p, 15q, 16p, 18q, 21q, and 22q and losses at 6p, 8p23, 11p13-pter, 13q34, and 14q32-qter. We also identified some changes (such as gains of 17q, 20q, and Xq and losses of 17p, 13q, and 14q) harboring candidate genes. We also explored the expression of centrosome protein in different molecular subtypes of breast cancer. Our findings provide a new way to explore the molecular mechanisms of breast tumorigenesis and accordingly potential new targets for therapy for this disease.

Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study.

Phyllodes tumors are not quite rare fibroepithelial neoplasms of the breast that show a broad spectrum of clinical behaviour. The molecular genetic features of the heterogenous groups of neoplasms have not been studied in detail yet. We have used comparative genomic hybridization to analyze chromosomal copy number changes in 36 cases of phyllodes tumors (including benign, borderline and malignant phyllodes tumors, 12 cases each). The average number of chromosome copy changes (range) in benign, borderline and malignant phyllodes tumors were 5.58 (0-20), 14.08 (3-23), and 12.42 (0-29) respectively. In benign phyllodes tumors the number of gains and losses was in balance (2.50 vs 3.08), while in borderline and malignant phyllodes tumors gains occurred more often than losses (9.25 vs 4.83, 9.5 vs 2.92). The result suggests the molecular cytogenetics of borderline and malignant phyllodes tumors is similar, and the most striking difference with benign phyllodes tumors is an increased number of chromosomal gains in a nonrandom distribution. Gains of 4q12 seem especially to be involved in the progression of benign to borderline and malignant phyllodes tumors, possibly because of overexpression of oncogenes at these loci.