Targeting Src SH3 domain-mediated glycolysis of HSC suppresses transcriptome, myofibroblastic activation, and colorectal liver metastasis.

BACKGROUND AND AIMS: Transforming growth factor-beta 1 (TGFß1) induces HSC activation into metastasis-promoting cancer-associated fibroblasts (CAFs), but how the process is fueled remains incompletely understood. We studied metabolic reprogramming induced by TGFß1 in HSCs. APPROACHES AND RESULTS: Activation of cultured primary human HSCs was assessed by the expression of myofibroblast markers. Glucose transporter 1 (Glut1) of murine HSC was disrupted by Cre recombinase/LoxP sequence derived from bacteriophage P1 recombination (Cre/LoxP). Plasma membrane (PM) Glut1 and glycolysis were studied by biotinylation assay and the Angilent Seahorse XFe96 Analyzer. S.c. HSC/tumor co-implantation and portal vein injection of MC38 colorectal cancer cells into HSC-specific Glut1 knockout mice were performed to determine in vivo relevance. Transcriptome was obtained by RNA sequencing of HSCs and spatialomics with MC38 liver metastases. TGFß1-induced CAF activation of HSCs was accompanied by elevation of PM Glut1, glucose uptake, and glycolysis. Targeting Glut1 or Src by short hairpin RNA, pharmacologic inhibition, or a Src SH3 domain deletion mutant abrogated TGFß1-stimulated PM accumulation of Glut1, glycolysis, and CAF activation. Mechanistically, binding of the Src SH3 domain to SH3 domain-binding protein 5 led to a Src/SH3 domain-binding protein 5/Rab11/Glut1 complex that activated Rab11-dependent Glut1 PM transport under TGFß1 stimulation. Deleting the Src SH3 domain or targeting Glut1 of HSCs by short hairpin RNA or Cre recombinase/LoxP sequence derived from bacteriophage P1 recombination suppressed CAF activation in mice and MC38 colorectal liver metastasis. Multi-omics revealed that Glut1 deficiency in HSCs/CAFs suppressed HSC expression of tumor-promoting factors and altered MC38 transcriptome, contributing to reduced MC38 liver metastases. CONCLUSION: The Src SH3 domain-facilitated metabolic reprogramming induced by TGFß1 represents a target to inhibit CAF activation and the pro-metastatic liver microenvironment.

Metabolic reprogramming and its clinical implication for liver cancer.

Cancer cells often encounter hypoxic and hypo-nutrient conditions, which force them to make adaptive changes to meet their high demands for energy and various biomaterials for biomass synthesis. As a result, enhanced catabolism (breakdown of macromolecules for energy production) and anabolism (macromolecule synthesis from bio-precursors) are induced in cancer. This phenomenon is called "metabolic reprogramming," a cancer hallmark contributing to cancer development, metastasis, and drug resistance. HCC and cholangiocarcinoma (CCA) are 2 different liver cancers with high intertumoral heterogeneity in terms of etiologies, mutational landscapes, transcriptomes, and histological representations. In agreement, metabolism in HCC or CCA is remarkably heterogeneous, although changes in the glycolytic pathways and an increase in the generation of lactate (the Warburg effect) have been frequently detected in those tumors. For example, HCC tumors with activated ß-catenin are addicted to fatty acid catabolism, whereas HCC tumors derived from fatty liver avoid using fatty acids. In this review, we describe common metabolic alterations in HCC and CCA as well as metabolic features unique for their subsets. We discuss metabolism of NAFLD as well, because NAFLD will likely become a leading etiology of liver cancer in the coming years due to the obesity epidemic in the Western world. Furthermore, we outline the clinical implication of liver cancer metabolism and highlight the computation and systems biology approaches, such as genome-wide metabolic models, as a valuable tool allowing us to identify therapeutic targets and develop personalized treatments for liver cancer patients.

Protein diaphanous homolog 1 (Diaph1) promotes myofibroblastic activation of hepatic stellate cells by regulating Rab5a activity and TGFß receptor endocytosis.

TGFß induces the differentiation of hepatic stellate cells (HSCs) into tumor-promoting myofibroblasts but underlying mechanisms remain incompletely understood. Because endocytosis of TGFß receptor II (TßRII), in response to TGFß stimulation, is a prerequisite for TGF signaling, we investigated the role of protein diaphanous homolog 1 (known as Diaph1 or mDia1) for the myofibroblastic activation of HSCs. Using shRNA to knockdown Diaph1 or SMIFH2 to target Diaph1 activity of HSCs, we found that the inactivation of Diaph1 blocked internalization and intracellular trafficking of TßRII and reduced SMAD3 phosphorylation induced by TGFß1. Mechanistic studies revealed that the N-terminal portion of Diaph1 interacted with both TßRII and Rab5a directly and that Rab5a activity of HSCs was increased by Diaph1 overexpression and decreased by Diaph1 knockdown. Additionally, expression of Rab5aQ79L (active Rab5a mutant) increased whereas the expression of Rab5aS34N (inactive mutant) reduced the endosomal localization of TßRII in HSCs compared to the expression of wild-type Rab5a. Functionally, TGFß stimulation promoted HSCs to express tumor-promoting factors, and α-smooth muscle actin, fibronection, and CTGF, markers of myofibroblastic activation of HSCs. Targeting Diaph1 or Rab5a suppressed HSC activation and limited tumor growth in a tumor implantation mouse model. Thus, Dipah1 and Rab5a represent targets for inhibiting HSC activation and the hepatic tumor microenvironment.

lncRNA UCA1 inhibits esophageal squamous-cell carcinoma growth by regulating the Wnt signaling pathway.

Esophageal squamous-cell carcinoma (ESCC) is one of the most common tumors worldwide. Recent studies suggested that long noncoding RNAs (lncRNAs) might play a key role in regulating cellular processes and cancer progression. One of the lncRNAs, urothelial carcinoma associated 1 (UCA1), is known to be dysregulated in several cancers, including bladder carcinoma, colorectal, melanoma, breast, gastric, and ESCC. However, contributions of UCA1 to ESCC remain largely undiscovered. In order to understand the role and mechanisms underlying UCA1 in ESCC, the association of UCA1 expression with risk of esophageal cancer development was determined in 106 esophageal cancer tissues of ESCC patients and adjacent normal tissues using real-time reverse-transcription polymerase chain reaction (PCR). The relative expression of UCA1 was significantly reduced in cancer versus adjacent normal tissues suggesting an enhanced risk of esophageal cancer. To investigate the biological functions of UCA1 in ESCC, it was of interest to examine whether overexpression of UCA1 might influence cell proliferation, apoptosis, cell cycle distribution, migration, and invasion in vitro using EC109 cells. Our results demonstrated that UCA1 decreased cell proliferation, migration, invasion, and cell cycle progression of EC109 cells. Further, mRNA microarray analysis of overexpressed UCA1 in EC109 cells revealed that abnormal expression of UCA1 also inhibited the Wnt signaling pathway. Gene levels of DKK1 were elevated while C-myc fell significantly in overexpressed UCA1 EC109 cells. Interestingly, Western blot demonstrated no significant differences in relative expression of CTNNB1 (ß-catenin) but marked reduction in ß-catenin (active form) levels in both total and nuclear proteins. These results suggest that UCA1 may inhibit ESCC growth by regulating the Wnt signaling pathway. In conclusion, UCA1 may be a novel biomarker involved in ESCC development that may provide a potential therapeutic target for ESCC.

Protective effect of taurine on down-regulated expression of thyroid hormone receptor genes in brains of mice exposed to arsenic.

This study aimed at evaluating protective effect of taurine on the down-regulated expressions of thyroid hormone receptor (TR) genes in brains of mice exposed to arsenic (As). The SPF mice were randomly divided into As exposure group, protective group, and control group. The As exposure group was administered with 4 ppm As(2)O(3) through drinking water for 60 days. The protective group was treated with both 4 ppm As(2)O(3) and 150 mg/kg taurine. The control group was given with drinking water alone. The gene expressions of TR in the mouse brains of the three groups were analyzed by real-time PCR. Their protein expressions were examined by Western blot and immunohistochemistry. Our results showed that the gene expression of TRß, a very important regulator of Camk4 transcription, was down-regulated in cerebral and cerebellar tissues of mice exposed to As. The expression of TRß1 protein in the cerebral or cerebellar tissue significantly decreased in the group exposed to As compared to the control group. However, the expressions of TRß gene and TRß1 protein were significantly rescued in the group coadministered with taurine as antioxidant. These results indicated that taurine may have the protective effect on the down-regulated expressions of TR in brains of mice exposed to As.

N-nitrosamines-mediated downregulation of LncRNA-UCA1 induces carcinogenesis of esophageal squamous by regulating the alternative splicing of FGFR2.

Concerns are raised over the risk to digestive system's tumors from the N-nitrosamines (NAs) exposure in drinking water. Albeit considerable studies are conducted to explore the underlying mechanism responsible for NAs-induced esophageal squamous cell carcinoma (ESCC), the exact molecular mechanisms remain largely unknown, especially at the epigenetic regulation level. In this study, it is revealed that the urinary concentration of N-Nitrosodiethylamine is higher in high incidence area of ESCC, and the lncRNA-UCA1(UCA1) is significantly decreased in ESCC tissues. In vitro and in vivo experiments further show that UCA1 is involved in the malignant transformation of Het-1A cells and precancerous lesions of the rat esophagus induced by N-nitrosomethylbenzylamine (NMBzA). Functional gain and loss experiments verify UCA1 can affect the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Mechanically, through binding to heterogeneous nuclear ribonucleoprotein F (hnRNP F) protein, UCA1 regulates alternative splicing of fibroblast growth factor receptor 2 (FGFR2), which promotes the FGFR2IIIb isoform switching to FGFR2 IIIc isoform, and the latter activates epithelial-mesenchymal transition via PI3K-AKT signaling pathways impacting tumorigenesis. Therefore, NAs-mediated downregulation of UCA1 promotes ESCC progression through targeting hnRNP F/FGFR2/PI3k-AKT axis, which provides a new chemical carcinogenic target and establishes a previously unknown mechanism for NAs-induced ESCC.

Janus Z-scheme heterostructure of ZnIn2S4/MoSe2/In2Se3 for efficient photocatalytic hydrogen evolution.

Artificial manipulation of charge separation and transfer are central issues dominating hydrogen evolution reaction triggered via photocatalysis. Herein, through elaborate designing on the architecture, band alignment, and interface bonding mode, a sulfur vacancy-rich ZnIn2S4-based (Vs-ZIS) multivariate heterostructure ZnIn2S4/MoSe2/In2Se3 (Vs-ZIS/MoSe2/In2Se3) with specific Janus Z-scheme charge transfer mechanism is constructed through a two-step hydrothermal process. Steering by the Janus Z-scheme charge transfer mechanism, photogenerated electrons in the conduction band of MoSe2 transfer synchronously to the valence band of Vs-ZIS and In2Se3, resulting in abundant highly-active photogenerated electrons reserved in the conduction band of Vs-ZIS and In2Se3, therefore significantly enhancing the photocatalytic activity of hydrogen evolution. Under visible light irradiation, the optimized Vs-ZIS/MoSe2/In2Se3 with the mass ratio of MoSe2 and In2Se3 to ZnIn2S4 at 3 % and 30 %, respectively, performs a high hydrogen evolution rate of 124.42 mmol·g-1·h-1, about 43.5-folds of the original ZIS photocatalyst. Besides, an apparent quantum efficiency (AQE) of 22.5 % at 420 nm and favorable durability are also achieved over Vs-ZIS/MoSe2/In2Se3 photocatalyst. This work represents an important development in efficient photocatalysts and donates a sound foundation for the design of regulating charge transfer pathways.

Higher-Order Multiphoton Absorption Upconversion Lasing Based on ZnO/ZnMgO Multiple Quantum Wells.

In the progress of nonlinear optics, multiphoton absorption (MPA) upconversion lasing enables many vital applications in bioimaging, three-dimensional optical data storage, and photodynamic therapy. Here, efficient four-photon absorption upconversion lasing from the ZnO/ZnMgO multiple quantum wells (MQWs) at room temperature is realized. Moreover, the MPA upconversion lasing and third-harmonic generation peak generated in the MQWs under the excitation of a femtosecond (fs) laser pulse were observed concurrently, and the essential differences between each other were studied comprehensively. Compared with the ZnO film, the upconversion lasing peak of the ZnO/ZnMgO MQWs exhibits a clear blue shift. In addition, the four-photon absorption upconversion photoluminescence (PL) intensity was enhanced in the MQWs/Au nanoparticles (NPs) by the metal-localized surface plasmons (LSPs). The work paves the way for short-wavelength lasers by taking advantage of the high stability and large exciton binding energy of the MQWs' structures.

PD-L1 promotes myofibroblastic activation of hepatic stellate cells by distinct mechanisms selective for TGF-ß receptor I versus II.

Intrahepatic cholangiocarcinoma (ICC) contains abundant myofibroblasts derived from hepatic stellate cells (HSCs) through an activation process mediated by TGF-ß. To determine the role of programmed death-ligand 1 (PD-L1) in myofibroblastic activation of HSCs, we disrupted PD-L1 of HSCs by shRNA or anti-PD-L1 antibody. We find that PD-L1, produced by HSCs, is required for HSC activation by stabilizing TGF-ß receptors I (TßRI) and II (TßRII). While the extracellular domain of PD-L1 (amino acids 19-238) targets TßRII protein to the plasma membrane and protects it from lysosomal degradation, a C-terminal 260-RLRKGR-265 motif on PD-L1 protects TßRI mRNA from degradation by the RNA exosome complex. PD-L1 is required for HSC expression of tumor-promoting factors, and targeting HSC PD-L1 by shRNA or Cre/loxP recombination suppresses HSC activation and ICC growth in mice. Thus, myofibroblast PD-L1 can modulate the tumor microenvironment and tumor growth by a mechanism independent of immune suppression.

[The differential expression of Stathmin in the spinal cord tissue of hens exposed to tri-o-cresyl phosphate].

OBJECTIVE: To screen the differently expressed proteins related to regulating the depolymerization of microtubules in the spinal cord of hens exposed to tri-o-cresyl phosphate (TOCP) and to provide target protein evidence for exploring the mechanisms of the delayed neurotoxicology (OPIDN) induced by organophosphorus compounds (OPs). METHODS: Forty two Roman hens were randomly divided into three groups, i.e. TOCP group treated with 1000 mg/kg TOCP; intervention group treated with 40 mg/kg phenylmethanesulfonyl fluoride (PMSF) before 1000 mg/kg TOCP treatment and control group treated with tap water. Four hens in each group were sacrificed on the 5th and 20th days after exposure, respectively. Spinal cords were separated and homogenates at low temperature, and the total proteins were extracted. The OPIDN symptoms observed and recorded in the remaining 6 hens in each group. The differently expressed proteins related to regulating the depolymerization of microtubules were screen by two-dimensional electrophoresis and mass spectroscopy (MS). RESULTS: The OPIDN symptoms appeared on the 5th day after exposure in TOCP group, which were gradually serious with time. The results by two-dimensional electrophoresis and MS showed that the Stathmin expression was downregulated 3.4 times and 2.8 times in TOCP group, respectively, as compared with the control and PMSF intervention groups. However, there was no significant difference of the Stathmin expression between control group and PMSF intervention group. CONCLUSION: The Stathmin expression in the spinal cord tissues of hens exposed to TOCP significantly downregulated. Moreover, the downregulated Stathmin expression may be related to excess polymerization of microtubules and the mechanism of OPIDN.

Interfacial chemical bond and internal electric field modulated Z-scheme Sv-ZnIn2S4/MoSe2 photocatalyst for efficient hydrogen evolution.

Construction of Z-scheme heterostructure is of great significance for realizing efficient photocatalytic water splitting. However, the conscious modulation of Z-scheme charge transfer is still a great challenge. Herein, interfacial Mo-S bond and internal electric field modulated Z-scheme heterostructure composed by sulfur vacancies-rich ZnIn2S4 and MoSe2 was rationally fabricated for efficient photocatalytic hydrogen evolution. Systematic investigations reveal that Mo-S bond and internal electric field induce the Z-scheme charge transfer mechanism as confirmed by the surface photovoltage spectra, DMPO spin-trapping electron paramagnetic resonance spectra and density functional theory calculations. Under the intense synergy among the Mo-S bond, internal electric field and S-vacancies, the optimized photocatalyst exhibits high hydrogen evolution rate of 63.21 mmol∙g-1·h-1 with an apparent quantum yield of 76.48% at 420 nm monochromatic light, which is about 18.8-fold of the pristine ZIS. This work affords a useful inspiration on consciously modulating Z-scheme charge transfer by atomic-level interface control and internal electric field to signally promote the photocatalytic performance.

Molybdenum sulfide-modified metal-free graphitic carbon nitride/black phosphorus photocatalyst synthesized via high-energy ball-milling for efficient hydrogen evolution and hexavalent chromium reduction.

Improving the photocatalytic property of metal-free photocatalyst is still a challenging work. Herein, a novel high-efficiency molybdenum sulfide (MoS2)-modified metal-free graphitic carbon nitride (g-C3N4)/black phosphorus (BP) photocatalyst (MCN/BP/MS) was synthesized on a large scale via high-energy ball milling process. The optimized MCN/BP/MS exhibits the excellent hydrogen evolution rate of 2146.8 µmol·g-1·h-1, and hexavalent chromium (Cr(Ⅵ)) reduction activity with an apparent rate constant of 0.1464 min-1 and a degradation rate of 100% in 25 min. Detailed characterizations and mechanism research verified that the significantly improved photocatalytic activity of MCN/BP/MS mainly profited from the matched band structure, enhanced light absorption, intense interface contact, as well as the type-Ⅰ/Z hybrid charge transfer mechanism, which gave rise to a consecutive multistep charge migration, thus the photocarriers transfer and separation can be greatly promoted, and the photogenerated electrons with high reducing capacity can be preserved. This work not only provides a high-efficiency g-C3N4-based noble-metal-free photocatalyst, but also affords a beneficial inspiration for improving the photocatalytic property of the metal free photocatalyst.

Focal Adhesion Kinase Promotes Hepatic Stellate Cell Activation by Regulating Plasma Membrane Localization of TGFß Receptor 2.

Transforming growth factor ß (TGFß) induces hepatic stellate cell (HSC) differentiation into tumor-promoting myofibroblast, although underlying mechanism remains incompletely understood. Focal adhesion kinase (FAK) is activated in response to TGFß stimulation, so it transmits TGFß stimulus to extracellular signal-regulated kinase and P38 mitogen-activated protein kinase signaling. However, it is unknown whether FAK can, in return, modulate TGFß receptors. In this study, we tested whether FAK phosphorylated TGFß receptor 2 (TGFßR2) and regulated TGFßR2 intracellular trafficking in HSCs. The FAKY397F mutant and PF-573,228 were used to inhibit the kinase activity of FAK, the TGFßR2 protein level was quantitated by immunoblotting, and HSC differentiation into myofibroblast was assessed by expression of HSC activation markers, alpha-smooth muscle actin, fibronectin, or connective tissue growth factor. We found that targeting FAK kinase activity suppressed the TGFßR2 protein level, TGFß1-induced mothers against decapentaplegic homolog phosphorylation, and myofibroblastic activation of HSCs. At the molecular and cellular level, active FAK (phosphorylated FAK at tyrosine 397) bound to TGFßR2 and kept TGFßR2 at the peripheral plasma membrane of HSCs, and it induced TGFßR2 phosphorylation at tyrosine 336. In contrast, targeting FAK or mutating Y336 to F on TGFßR2 led to lysosomal sorting and degradation of TGFßR2. Using RNA sequencing, we identified that the transcripts of 764 TGFß target genes were influenced by FAK inhibition, and that through FAK, TGFß1 stimulated HSCs to produce a panel of tumor-promoting factors, including extracellular matrix remodeling proteins, growth factors and cytokines, and immune checkpoint molecule PD-L1. Functionally, targeting FAK inhibited tumor-promoting effects of HSCs in vitro and in a tumor implantation mouse model. Conclusion: FAK targets TGFßR2 to the plasma membrane and protects TGFßR2 from lysosome-mediated degradation, thereby promoting TGFß-mediated HSC activation. FAK is a target for suppressing HSC activation and the hepatic tumor microenvironment.

Novel-miR-4885 Promotes Migration and Invasion of Esophageal Cancer Cells Through Targeting CTNNA2.

Esophageal cancer is one of the most common cancers worldwide. It is critical to find early diagnostic biomarkers for esophageal cancer. MicroRNAs (miRNAs) play important regulatory roles in occurrence and development of esophageal cancer, which has the diagnostic and prognostic values. The aim of the study was to evaluate the potential diagnostic value of the novel miRNA. The novel miRNA was predicted using miRDeep2 software and validated by quantitative reverse transcription PCR (qRT-PCR) and the TA-cloning sequencing of the PCR products. The expression of the novel miRNA in esophageal cancer tissues and adjacent tissues was also analyzed by qRT-PCR. The EdU staining and transwell method were used to detect the capacity of cell proliferation, migration, and invasion. Besides, the target gene CTNNA2 of novel-miR-4885 was verified via qRT-PCR, western blot, luciferase reporter assay, and RNA immunoprecipitation. We identified the novel-miR-4885, the expression level was confirmed by qRT-PCR in the esophageal cancer cells. The result of TA-cloning sequencing was consistent with the prediction and the pre-miRNA had a standard hairpin stem-loop structure. In addition, the expression of novel-miR-4885 was upregulated in esophageal cancer tissue compared with that in adjacent tissue (p < 0.05). Further, the assays showed that overexpression novel-miR-4885 could improve the cell proliferation, migration, and invasion with an average fold change of 1.19, 1.59, and 2.34, respectively. Novel-miR-4885 can bind to 3' untranslated region of CTNNA2 to reduce cell adhesion and promote epithelial-mesenchymal transition in esophageal cancer cell. The expression of N-cadherin, ß-catenin, Vimentin, and α-smooth muscle actin was upregulated, while that of E-cadherin and ZO-1 proteins was downregulated through western blot. Novel miRNA present in esophageal cancer cells was validated, supplementing the miRNA database. Meantime, the possible functional mechanisms were explored, and the results showed that the novel miRNA may serve as potential biomarker for the diagnosis of esophageal cancer.

LincRNA-ROR promotes metastasis and invasion of esophageal squamous cell carcinoma by regulating miR-145/FSCN1.

BACKGROUND AND OBJECTIVE: In an attempt to discover a new biomarker for early diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC), the regulation mechanism of large intergenic non-coding RNA-regulator of reprogramming (lincRNA-ROR) as a microRNA (miRNA) sponge was studied. PATIENTS AND METHODS: ROR expression in 91 pairs of ESCC tissue samples and matched adjacent tissues was quantified with real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The ROR-miRNA-mRNA regulatory network was built with 161 esophageal cancer (EC) tissues and 11 adjacent tumor tissues from The Cancer Genome Atlas (TCGA) database. A total of 96 cases of ESCC from TCGA database were collected for analysis on survival rates. The regulatory relationship between ROR, miR-145 and FSCN1 was verified in ESCC cells via qRT-PCR, dual luciferase reporter (DLR) assay, RNA immunoprecipitation (RIP) and Western blotting. The transwell method was used to detect cell migration and invasion. RESULTS: ROR expression in ESCC tumor tissues was significantly higher than in the adjacent tissues, p<0.001. The survival rate of ESCC patients with high ROR expression levels was lower than that of patients with low ROR expression levels (p<0.001). ROR overexpression could downregulate miR-145 by up to 50% was proven by RIP, DLR assay, and qRT-PCR. Two effective binding sites of ROR to miR-145 were verified by DLR assay. One of the sites has never been cited in the literature. The Western blotting results showed that FSCN1 was a downstream target of ROR/miR-145 (p<0.05). Transwell assays were used to show that overexpression of ROR enhanced migration and invasion behavior of ESCC and miR-145 hindered these effects. CONCLUSION: ROR acted as a competitive endogenous RNA (ceRNA) of miR-145 in ESCC. A novel, effective miR-145 binding site of ROR was discovered. The ROR/miR-145/FSCN1 pathway was shown to take part in the metastasis of ESCC. ROR is likely an oncogene biomarker for ESCC early diagnosis and prognosis.

Identification of extracellular matrix protein 1 as a potential plasma biomarker of ESCC by proteomic analysis using iTRAQ and 2D-LC-MS/MS.

PURPOSE: This study was aimed to conduct a proteomics profiling analysis on plasma obtained from ESCC patients with the goal of identifying appropriate plasma protein biomarkers in the progression of ESCC. EXPERIMENTAL DESIGN: Plasma from 28 ESCC patients and 28 healthy controls (HC) were analyzed by iTRAQ combined with 2D-LC-MS/MS. ProteinPilot software was used to identify the differentially expressed plasma proteins in ESCC compared to HC. Western blot was performed to verify the expression of selected proteins in 37 independent ESCC patients and 37 HC. Transwell and MTT assays were used to detect the biological function of ECM1 protein in vitro. RESULTS: Nineteen (four upregulated and fifteen downregulated) proteins were identified as differentially expressed between ESCC and HC (p <0.05). Biological functions of these proteins are involved in cell adhesion, cell apoptosis and metabolic processes, visual perception and immune response. Of these, extracellular matrix 1 (ECM1) and lumican (LUM) were selected further confirmation by Western blot (p <0.05), which were consistent with the iTRAQ results. Furthermore, the migration ability of EC9706 cell line after overexpressing ECM1 was increased significantly (p <0.05). The proliferation ability of HUVEC cell was enhanced when treated with the culture supernatants of EC9706 overexpressed ECM1(p <0.05). CONCLUSION AND CLINICAL RELEVANCE: This proteome analysis indicate that ECM1 is a potential novel plasma protein biomarker for the detection of primary ESCC and evaluation of neoplasms progression.

Subchronic exposure to arsenic inhibits spermatogenesis and downregulates the expression of ddx3y in testis and epididymis of mice.

Arsenic (As) is a ubiquitous environmental contaminant. Excess As exposure is considered one of the top health threats worldwide. As-induced Male reproductive toxicity is causing wide concern. The goal of this study is to determine whether subchronic As exposure inhibits Ddx3y expression, an Y-linked gene important in spermatogenesis and sperm maturation, and whether the inhibited expression of Ddx3y is closely associated with As-induced male reproductive toxicity Adult mice were given drinking water alone or water containing 1, 2, and 4mg/l arsenic trioxide (As(2)O(3)) for 60 days. After the treatment, the weights of testis and epididymis were analyzed. The sperm quality, spermatogenesis, and histological alteration of the testis and epididymis were observed by microscope. Furthermore, the expressions of Ddx3y gene and its protein in the testis and epididymis were examined by real-time reverse transcription PCR, Western blotting, and immunohistochemistry. Compared with untreated mice, the weights of testis and epididymis were reduced, sperm motility and the number of stage VII cells in the seminiferous epithelium section were decreased, sperm malformation ratio was increased, and histopathological alterations were observed in As-treated mice. The gene and protein expression of Ddx3y in testis and epididymis were significantly downregulated in As-exposed mice. Subchronic As exposure has detrimental effects on spermatogenesis and sperm development. It also downregulates Ddx3y expressions in testis and epididymis. Our results indicated that Ddx3y may be an important target gene of As and the downregulated expression of Ddx3y may be closely related to male reproductive toxicity induced by As.

Nanostructured Al-ZnO/CdSe/Cu2O ETA solar cells on Al-ZnO film/quartz glass templates.

The quartz/Al-ZnO film/nanostructured Al-ZnO/CdSe/Cu2O extremely thin absorber solar cell has been successfully realized. The Al-doped ZnO one-dimensional nanostructures on quartz templates covered by a sputtering Al-doped ZnO film was used as the n-type electrode. A 19- to 35-nm-thin layer of CdSe absorber was deposited by radio frequency magnetron sputtering, coating the ZnO nanostructures. The voids between the Al-ZnO/CdSe nanostructures were filled with p-type Cu2O, and therefore, the entire assembly formed a p-i-n junction. The cell shows the energy conversion efficiency as high as 3.16%, which is an interesting option for developing new solar cell devices.PACS: 88.40.jp; 73.40.Lq; 73.50.Pz.

Fabrication and ultraviolet photoresponse characteristics of ordered SnOx (x ≈ 0.87, 1.45, 2) nanopore films.

Based on the porous anodic aluminum oxide templates, ordered SnOx nanopore films (approximately 150 nm thickness) with different x (x ≈ 0.87, 1.45, 2) have been successfully fabricated by direct current magnetron sputtering and oxidizing annealing. Due to the high specific surface area, this ordered nanopore films exhibit a great improvement in recovery time compared to thin films for ultraviolet (UV) detection. Especially, the ordered SnOx nanopore films with lower x reveal higher UV light sensitivity and shorter current recovery time, which was explained by the higher concentration of the oxygen vacancies in this SnOx films. This work presents a potential candidate material for UV light detector.PACS: 81.15.Cd, 81.40.Ef, 81.70.Jb, 85.60.Gz.