Regulating valence states of CuFe-PBA for the simultaneous electrochemical detection of Cd2+, Pb2+ and Hg2+ in food application.

Prussian blue analogues, as prospective electrode materials, play a crucial role in detecting heavy metal ions (HMIs), a process closely related to their electron transfer capacities and active surfaces. Here, etched copper-iron Prussian blue analogues (CuFe-PBA) are synthesized through a combination of flash nanoprecipitation (FNP) and an alkali etching process. Furthermore, this study investigates the impact of ammonia on the electronic structure of CuFe-PBA and its electrochemical detection capabilities for HMIs. The etched CuFe-PBA (e-CuFe-PBA) exhibits excellent detection performance for Cd2+, Pb2+ and Hg2+ with 17.6 µA µM-1, 24.2 µA µM-1 and 26.2 µA µM-1, respectively, due to the fact that the ammonia etching not only modulates the electronic properties of the surface of CuFe-PBA but also reduces the degree of agglomeration and enhances the accessible surface area. Additionally, it demonstrates excellent stability and resistance to interference, having been successfully applied to detect HMIs in food samples such as preserved eggs and apple juice. These results provide a new strategy for the use of Prussian blue analogues as electrochemical sensors for food safety applications.

Ce-doped multi-phase NiMo-based phosphorus/sulfide heterostructure for efficient photo-enhanced overall water splitting at high current densities.

NiMo-based electrocatalysts are widely regarded as promising electrocatalysts for overall water splitting (OWS). However, to solve the problem of slow reaction kinetics and serious deactivation at high current density, the reasonable design of NiMo-based electrocatalysts is still a great challenge. In this work, NiMo-based phosphorus/sulfide heterostructure electrocatalysts with different Ce doping ratios (5%/10%/15%Ce-NiMo-PS@NF) have been designed using the combination of cation doping and heterostructure engineering. The doping of Ce not only changes the electronic environment of the heterostructure, accelerates the electron transport at the heterostructure interface, but also enhances the light absorption capacity of the heterostructure. The experimental results show that 10%Ce-NiMo-PS@NF has the best photo-enhanced electrocatalytic activity (hydrogen evolution reaction (HER): η1000 = 250 mV, oxygen evolution reaction (OER): η1000 = 242 mV, and OWS: E1000 = 1.864 V). In addition, its solar-to-hydrogen (STH) efficiency in a photoelectric coupled water splitting system is as high as 18.68%. This study not only provides a new method for the synthesis of new heterostructure electrocatalysts, but also provides a reference for the rational use of light energy to enhance electrocatalytic activity.

Defective ferrocene-based metal-organic frameworks for efficient solar-powered water oxidation via the ligand competition and etching effect.

Two-dimensional metal-organic frameworks are considered to be promising electrocatalytic materials due to their ultrathin lamellar structure, ultrahigh porosity and large surface area, but there are still many challenges such as the embedding of organic ligands leading to low density of active sites and poor conductivity. Herein, we synthesize two-dimensional ferrocene-based metal-organic frameworks nanosheet electrocatalysts via the one-step hydrothermal hydrogen peroxide etching method. The prepared FcNi-BDC-H2O2/NF exhibits excellent oxygen evolution reaction performance with a current density of 100 mA·cm-2 at only 258 mV and a small driving potential of 1.542 V (10 mA·cm-2) is required to achieve overall water splitting. Significantly, an overall water-cracked cell using a solar cell assembly achieves the solar hydrogen conversion efficiency of 19.5%. The introduction of high electronegativity ferrocene and the etching of H2O2 increase the Ni3+ content of FcNi-BDC-H2O2, and expose more unsaturated active sites, which improve the intrinsic activity of the catalysts and the mass transfer rate during the catalytic process. Moreover, the FcNi-BDC-H2O2/NF demonstrates significant urea oxidation reaction performance, achieving a potential of 1.35 V and producing 10 mA·cm-2. This study presents a viable approach to investigating highly efficient electrocatalysts for oxygen evolution reaction and urea oxidation reaction using MOF-based bifunctional catalysts.

Sea urchin-like amorphous MgNiCo mixed metal hydroxide nanoarrays for efficient overall water splitting under industrial electrolytic conditions.

Exploring amorphous mixed transition metal hydroxide electrocatalysts with high performance and stability for overall water splitting is a difficult challenge under industrial electrolytic conditions. Herein, a sea urchin-like amorphous MgNiCo hydroxide (MgxNi1-xCo-OH, 0 < x < 1), self-assembled from nanowire arrays, is synthesized by the hydrothermal process. The synergistic effect between Mg and Ni/Co adjusts their crystal structure and morphology, which can improve the inherent activity and provide more active sites. Benefiting from the favorable structural features, Mg0.5Ni0.5Co-OH exhibits superior electrocatalytic oxygen and hydrogen evolution reaction (OER and HER) activity with a low overpotential of 277 and 110 mV (10 mA cm-2) in 1 M KOH at 25 °C. Furthermore, overpotentials of 239 and 197 mV are required to achieve a current density of 50 mA cm-2 for the OER and HER under simulated industrial electrolysis conditions (5 M KOH at 65 °C). Notably, Mg0.5Ni0.5Co-OH remarkably accelerates water splitting with a low voltage of 1.938 and 1.699 V for 50 mA cm-2 in 1 M KOH at 25 °C and 5 M KOH at 65 °C, respectively. This work presents a novel amorphous strategy to design and construct sea urchin-like mixed metal hydroxide bifunctional efficient electrocatalysts for industrial applications.

Fusobacterium nucleatum Infection Induces Malignant Proliferation of Esophageal Squamous Cell Carcinoma Cell by Putrescine Production.

Esophageal squamous cell carcinoma (ESCC) is a malignant upper digestive tract cancer, and its pathogenesis and etiology are poorly understood. Because gut microbes commonly impact progression, metastasis, and immunotherapy responses in colorectal cancer (CRC), the roles of the esophageal microbiota in ESCC have gradually drawn attention. As reported previously, Fusobacterium nucleatum (Fn), the notable "culprit" of CRC, can also influence the prognosis of ESCC in clinical studies. However, thus far, the underlying mechanism is unclear. In this study, 73 Chinese ESCC samples were collected. In those clinical samples, the abundance of Fn was found to be higher in tumors than in adjacent normal tissues, and a high abundance of Fn was correlated with shorter survival. Furthermore, using in vitro experiments, we demonstrated that Fn can invade ESCC cells, enhancing their proliferation capacity. The mechanism study revealed that Fn can produce high levels of putrescine after invasion, which disturbs polyamine metabolism and promotes the malignant proliferation of ESCC cells. In conclusion, Fn infection was found in Chinese ESCC tumor tissue samples and may promote ESCC progression by disturbing the polyamine metabolism pathway. IMPORTANCE Nowadays, the complex and varied interactions between microbes and human body are known to be crucial for maintaining the health of the human body. However, knowledge concerning the influence of esophageal microbes on the progression of esophageal squamous cell carcinoma is limited. Here, in our study, we confirmed that F. nucleatum can invade ESCC cells and consequently promote their proliferation, suggesting that esophageal microbes likely influence the progression of ESCC in clinical settings. Because the esophagus connects the oral cavity and stomach, acting as a canal for transporting foods, its special physical location makes it easily exposed to microorganisms. Thus, it is necessary to explore the interaction between esophageal microbes and ESCC.

Author Correction: Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Elevated DHODH expression promotes cell proliferation via stabilizing ß-catenin in esophageal squamous cell carcinoma.

As a key enzyme in de novo pyrimidine biosynthesis, the expression level of dihydroorotate dehydrogenase (DHODH) has been reported to be elevated in various types of malignant tumors and its tumor-promoting effect was considered to relate to its pyrimidine synthesis function. Here, we revealed one intriguing potential mechanism that DHODH modulated ß-catenin signaling in esophageal squamous cell carcinoma (ESCC). We demonstrated that DHODH directly bound to the NH2 terminal of ß-catenin, thereby, interrupting the interaction of GSK3ß with ß-catenin and leading to the abrogation of ß-catenin degradation and accumulation of ß-catenin in the nucleus, which in turn, resulted in the activation of ß-catenin downstream genes, including CCND1, E2F3, Nanog, and OCT4. We further demonstrated that the regulation of ß-catenin by DHODH was independent of DHODH catalyzing activity. Univariate and multivariate analyses suggested that DHODH expression might be an independent prognostic factor for ESCC patients. Collectively, our study highlights the pivotal role of DHODH mediated ß-catenin signaling and indicates that DHODH may act as a multi-functional switcher from catalyzing pyrimidine metabolism to regulating tumor-related signaling pathways in ESCC.

Cadmium inhibits apoptosis of human esophageal epithelial cells by upregulating CDK6.

Cadmium (Cd) exposure in environment is associated with development of esophageal cancer. However, the mechanisms of Cd-induced carcinogenesis are still not been fully cleared, and the present study aimed to explore the possible etiological mechanism of Cd-induced esophageal cancer. Human esophageal epithelial cell lines (HET-1A and KYSE450) were treated with CdCl2 at 0.05 mg/l for 12, 24 h, and the then the apoptosis were detected using flow cytometry with annexin-V-FITC/PI staining. Results showed that apoptosis of treatment groups was significantly inhibited, and decreased reactive oxygen species (ROS) production played a key role in the inhibitory effects by upregulating Bcl-2 and downregulating Caspase-3/9. The relief of oxidative stress during Cd exposure was actively promoted by the increased nicotinamide adenine dinucleotide phosphoric acid and glutathione levels. To investigate the causes of enhanced intracellular antioxidant capacity, the activity of pyruvate kinase (PK), a key enzyme of glycolysis, was detected. Our results showed that PK activity was inhibited, suggesting that glycolysis process was blocked which promoted more intermediate metabolites of glycolysis to be used for reduced nicotinamide adenine dinucleotide phosphoric acid (NADPH) or other antioxidants synthesis. PK activity was closely correlated with phosphorylation of pyruvate kinase M2 (PKM2), and a highly negative correlation (correlation coefficients: -0.835, p < 0.05) between them was found. Western blotting showed the overphosphorylation of PKM2 in Cd-exposed cells, resulting from increased expression of cyclin-dependent kinases 6 (CDK6). These results suggested a possible mechanism of carcinogenic: Cd-induced upregulation of CDK6 in esophageal cell lines caused PKM2 overphosphorylation inhibiting PK activity, thereby shunting glucose-derived carbon into the pentose phosphate pathway and promoting the production of NADPH and reduced glutathione (GSH) to neutralize ROS, which finally results in the inhibited apoptosis.

Decreased ZNF750 promotes angiogenesis in a paracrine manner via activating DANCR/miR-4707-3p/FOXC2 axis in esophageal squamous cell carcinoma.

ZNF750 is one novel significantly mutated gene identified in esophageal squamous cell carcinoma (ESCC) using next-generation sequencing. However, its clinically relevant and potential mechanisms have remained elusive. Using genomic sequencing of 612 ESCC patients, we analyzed the associations of ZNF750 mutations with clinicopathologic features and its prognostic value. We further investigated the function and underlying mechanism of ZNF750 in angiogenesis. The results showed ZNF750 mutations/deletions are significantly associated with malignant progression and poor prognosis of ESCC patients. Decreased ZNF750 in ESCC cells induces enhanced angiogenesis of human umbilical vein endothelial cells (HUVECs) and human arterial endothelial cells (HAECs), and the effect may be indirectly mediated by FOXC2. RNA-seq and ChIP shows lncRNA DANCR is a direct downstream target of ZNF750. Furtherly, knockdown ZNF750 evokes DANCR expression, which prevents miR-4707-3p to interact with FOXC2 as a microRNA sponge in a ceRNA manner, leading to enhanced FOXC2 signaling and angiogenesis. In contrast, ZNF750 expression reverses the effect. Our study reveals a novel mechanism of ZNF750, highlights a significance of ZNF750 as a metastatic and prognostic biomarker, and offers potential therapeutic targets for ESCC patients harboring ZNF750 mutations.

Novel ESCC-related gene ZNF750 as potential Prognostic biomarker and inhibits Epithelial-Mesenchymal Transition through directly depressing SNAI1 promoter in ESCC.

Background: Cancer genomic studies have identified Zinc Finger Protein 750 (ZNF750) was a novel significantly mutated gene in esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of ZNF750 in the development of ESCC. Methods: Genomic data from 4 reported ESCC cohorts were used to analyze the mutation profile of ZNF750. Tissue microarrays were used to detect its expression in 308 ESCC samples. Furtherly, the effects of ZNF750 on proliferation, colony formation, migration and invasion were tested in ESCC cells. PCR-array, chromatin immunoprecipitation (ChIP), luciferase reporter assays, and rescue assay were used to explore the mechanism of ZNF750. Correlation of ZNF750 with its target genes was analyzed in TCGA data from various SCC types. Results: ZNF750 was frequently mutated in ESCC and the most common type was nonsense mutation. Its nucleus/cytoplasm ratio in ESCC was significantly lower than that in paired non-tumor tissues; it was an independent and potential predictor for survival in ESCC patients. Furtherly, ZNF750 knockdown significantly promoted proliferation, colony formation, migration and invasion in ESCC cells. PCR-array showed epithelial-to-mesenchymal transition (EMT) was the main biologic process affected by ZNF750. Moreover, ZNF750 directly bound to the promoter region of SNAI1 and depressed its activity. Decreased ZNF750 up-regulated SNAI1 expression and promoted EMT phenotype. SNAI1 knockdown partially reversed the malignant phenotype induced by ZNF750 knockdown. Further TCGA data analyses showed ZNF750 expression was positively correlated with E-cadherin and negatively correlated with SNAI1, N-cadherin and Vimentin in ESCC and other SCC samples. Conclusion: Our results suggest that ZNF750 may act as a tumor suppressor by directly repressing SNAI1 and inhibiting EMT process in ESCC and other types of SCC.

Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) ranks fourth among cancer-related deaths in China due to the lack of actionable molecules. We performed whole-exome and T-cell receptor (TCR) repertoire sequencing on multi-regional tumors, normal tissues and blood samples from 39 ESCC patients. The data revealed 12.8% of ERBB4 mutations at patient level and functional study supported its oncogenic role. 18% of patients with early BRCA1/2 variants were associated with high-level contribution of signature 3, which was validated in an independent large cohort (n = 508). Furthermore, knockdown of BRCA1/2 dramatically increased sensitivity to cisplatin in ESCC cells. 5% of patients harbored focal high-level amplification of CD274 that led to massive expression of PD-L1, and might be more sensitive to immune checkpoint blockade. Finally, we found a tight correlation between genomic and TCR repertoire intra-tumor heterogeneity (ITH). Collectively, we reveal high-level ITH in ESCC, identify several potential actionable targets and may provide novel insight into ESCC treatment.

Life-Style Habits in a High-Risk Area for Upper Gastrointestinal Cancers: a Population-Based Study from Shanxi, China.

BACKGROUND: Cancer is a burden on humanity and ranks as a leading cause of morbidity and mortality in China. Shanxi province has its unique cancer patterns and the burden is increasing. In this study, we aimed to assess the pattern of dietary habits and life-style in Shanxi, a high-risk area for upper gastrointestinal cancers in China and further evaluate the trends in cancer incidence and mortality based on registered data. MATERIALS AND METHODS: Data on lifestyle, diet, physical activity were obtained from the household health survey at Zhongyang from 2013 to 2015. Cancer diagnoses were reported to Shanxi Center for Disease Control and Prevention (SCDCP). Population-based cancer incidence data and mortality data of 2012 were collected from the SCDCP. All incidence and death rates were expressed per 100,000 populations. Univariate analysis was performed using the Chi-squared test or Fisherandapos;s exact test. RESULTS: Overall, deficiencies in fresh fruits and vegetable food, and intake of hot food, salted food, or pickled food are serious problems in Shanxi, especially in rural areas. Upper gastrointestinal cancers were the most commonly diagnosed cancers, and the incidence in rural areas is higher than those in urban areas. Cervical cancer is the most common cancer for females. Moreover, the agespecific incidence exhibited an increased trend before 40 years old. Consistent with the previous literature, our epidemiological investigation results suggest that lifestyle, nutrition deficient, and infections were major risk factors for upper gastrointestinal cancers or cervical cancer in Shanxi. Facing a serious situation, we further explored defensible recommendations for the general public in order to promote changes in environments that support healthful eating and physical activity habits, to reduce cancer risk. CONCLUSIONS: Our results present the current cancer trends in Shanxi and its related etiologic risk factors and provide a theoretical basis to guide public health efforts to prevent and control cancers in the province.

RAD51B as a potential biomarker for early detection and poor prognostic evaluation contributes to tumorigenesis of gastric cancer.

Gastric cancer (GC) is a common and deadly disease worldwide. Outcomes of patients are poor largely due to chemoresistance or recurrence. Thus, identifying novel biomarkers to predict response to therapy and/or prognosis are urgently needed. RAD51B, a key player in DNA repair/recombination, has the potential to be a candidate oncogene and biomarker for cancer diagnosis and prognosis. However, its relationship with GC remains unclear. To evaluate clinicopathological and prognostic significance of RAD51B in GC, we examined messenger RNA (mRNA) and protein expression via quantitative real-time polymerase chain reaction (qRT-PCR) from 69 and tissue microarray from 144 GC patients, respectively. Our results showed that RAD51B mRNA expression was significantly up-regulated in tumors compared to that of matched noncancerous tissues (P < 0.001). In parallel, RAD51B protein showed a mainly nucleus-staining pattern, and the positive rate in tumors and stomach atypical hyperplasia was significantly higher than that in matched noncancerous tissues (P = 0.015). Moreover, high level of RAD51B protein was correlated with advanced stage (P = 0.009), aggressive differentiation (P = 0.022), and lymph node metastasis (P = 0.001). Further, Kaplan-Meier analysis indicated that patients with high level of RAD51B expression exhibited worse overall survival compared to patients with low level (P = 0.040). A multivariate Cox regression analysis suggested that RAD51B may be an independent prognostic factor for GC patients in Chinese population (P = 0.004). Additionally, functional studies indicated that over-expression of RAD51B promoted cell proliferation, aneuploidy, and drug resistance, while RAD51B knockdown led to G1 arrest and sensitized cells to 5-fluorouracil (5-FU). In conclusion, RAD51B may act as an oncogene during GC progression, and its hyper-expression may be a potential biomarker for early detection and poor prognosis of GC.