Ion adsorption promotes Frank-van der Merwe growth of 2D transition metal tellurides.

Reliable synthesis methods for high-quality, large-sized, and uniform two-dimensional (2D) transition-metal dichalcogenides (TMDs) are crucial for their device applications. However, versatile approaches to growing high-quality, large-sized, and uniform 2D transition-metal tellurides are rare. Here, we demonstrate an ion adsorption strategy that facilitates the Frank-van der Merwe growth of 2D transition-metal tellurides. By employing this method, we grow MoTe2 and WTe2 with enhanced lateral size, reduced thickness, and improved uniformity. Comprehensive characterizations confirm the high quality of as-grown MoTe2. Moreover, various characterizations verify the adsorption of K+ and Cl- ions on the top surface of MoTe2. X-ray photoelectron spectroscopy (XPS) analysis reveals that the MoTe2 is stoichiometric without K+ and Cl- ions and exhibits no discernable oxidation after washing. This top surface control strategy provides a new controlling knob to optimize the growth of 2D transition-metal tellurides and holds the potential for generalized to other 2D materials.

Scalable Synthesis of High-Quality Ultrathin Ferroelectric Magnesium Molybdenum Oxide.

The development of ultrathin, stable ferroelectric materials is crucial for advancing high-density, low-power electronic devices. Nonetheless, ultrathin ferroelectric materials are rare due to the critical size effect. Here, a novel ferroelectric material, magnesium molybdenum oxide (Mg2 Mo3 O8 ) is presented. High-quality ultrathin Mg2 Mo3 O8 crystals are synthesized using chemical vapor deposition (CVD). Ultrathin Mg2 Mo3 O8 has a wide bandgap (≈4.4 eV) and nonlinear optical response. Mg2 Mo3 O8 crystals of varying thicknesses exhibit out-of-plane ferroelectric properties at room temperature, with ferroelectricity retained even at a 2 nm thickness. The Mg2 Mo3 O8 exhibits a relatively large remanent polarization ranging from 33 to 52 µC cm- 2 , which is tunable by changing its thickness. Notably, Mg2 Mo3 O8 possesses a high Curie temperature (>980 °C) across various thicknesses. Moreover, the as-grown Mg2 Mo3 O8 crystals display remarkable stability under harsh environments. This work introduces nolanites-type crystal into ultrathin ferroelectrics. The scalable synthesis of stable ultrathin ferroelectric Mg2 Mo3 O8 expands the scope of ferroelectric materials and may prosper applications of ferroelectrics.

Identification of cuproptosis-based molecular subtypes, construction of prognostic signature and characterization of immune landscape in colon cancer.

Background: Cuproptosis is a newly discovered form of cell death induced by targeting lipoacylated proteins involved in the tricarboxylic acid cycle. However, the roles of cuproptosis-related genes (CRGs) in the clinical outcomes and immune landscape of colon cancer remain unknown. Methods: We performed bioinformatics analysis of the expression data of 13 CRGs identified from a previous study and clinical information of patients with colon cancer obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. Colon cancer cases were divided into two CRG clusters and prognosis-related differentially expressed genes. Patient data were separated into three corresponding distinct gene clusters, and the relationships between the risk score, patient prognosis, and immune landscape were analyzed. The identified molecular subtypes correlated with patient survival, immune cells, and immune functions. A prognostic signature based on five genes was identified, and the patients were divided into high- and low-risk groups based on the calculated risk score. A nomogram model for predicting patient survival was developed based on the risk score and other clinical features. Results: The high-risk group showed a worse prognosis, and the risk score was related to immune cell abundance, microsatellite instability, cancer stem cell index, checkpoint expression, immune escape, and response to chemotherapeutic drugs and immunotherapy. Findings related to the risk score were validated in the imvigor210 cohort of patients with metastatic urothelial cancer treated with anti-programmed cell death ligand 1. Conclusion: We demonstrated the potential of cuproptosis-based molecular subtypes and prognostic signatures for predicting patient survival and the tumor microenvironment in colon cancer. Our findings may improve the understanding of the role of cuproptosis in colon cancer and lead to the development of more effective treatment strategies.

A novel oxidative stress- and ferroptosis-related gene prognostic signature for distinguishing cold and hot tumors in colorectal cancer.

Oxidative stress and ferroptosis exhibit crosstalk in many types of human diseases, including malignant tumors. We aimed to develop an oxidative stress- and ferroptosis-related gene (OFRG) prognostic signature to predict the prognosis and therapeutic response in patients with colorectal cancer (CRC). Thirty-four insertion genes between oxidative stress-related genes and ferroptosis-related genes were identified as OFRGs. We then performed bioinformatics analysis of the expression profiles of 34 OFRGs and clinical information of patients obtained from multiple datasets. Patients with CRC were divided into three OFRG clusters, and differentially expressed genes (DEGs) between clusters were identified. OFRG clusters correlated with patient survival and immune cell infiltration. Prognosis-related DEGs in three clusters were used to calculate the risk score, and a prognostic signature was constructed according to the risk score. In this study, patients in the low-risk group had better prognosis, higher immune cell infiltration levels, and better responses to fluorouracil-based chemotherapy and immune checkpoint blockade therapy than high-risk patients; these results were successfully validated with multiple independent datasets. Thus, low-risk CRC could be defined as hot tumors and high-risk CRC could be defined as cold tumors. To further identify potential biomarkers for CRC, the expression levels of five signature genes in CRC and adjacent normal tissues were further verified via an in vitro experiment. In conclusion, we identified 34 OFRGs and constructed an OFRG-related prognostic signature, which showed excellent performance in predicting survival and therapeutic responses for patients with CRC. This could help to distinguish cold and hot tumors in CRC, and the results might be helpful for precise treatment protocols in clinical practice.

PANoptosis-based molecular clustering and prognostic signature predicts patient survival and immune landscape in colon cancer.

PANoptosis is a newly-discovered cell death pathway that involves crosstalk and co-ordination between pyroptosis, apoptosis, and necroptosis processes. However, the roles of PANoptosis-related genes (PRGs) in prognosis and immune landscape of colon cancer remain widely unknown. Here, we performed a bioinformatics analysis of expression data of nineteen PRGs identified from previous studies and clinical data of colon cancer patients obtained from TCGA and GEO databases. Colon cancer cases were divided into two PRG clusters, and prognosis-related differentially expressed genes (PRDEGs) were identified. The patient data were then separated into two corresponding distinct gene clusters, and the relationship between the risk score, patient prognosis, and immune landscape was analyzed. The identified PRGs and gene clusters correlated with patient survival and immune system and cancer-related biological processes and pathways. A prognosis signature based on seven genes was identified, and patients were divided into high-risk and low-risk groups based on the calculated risk score. A nomogram model for prediction of patient survival was also developed based on the risk score and other clinical features. Accordingly, the high-risk group showed worse prognosis, and the risk score was related to immune cell abundance, cancer stem cell (CSC) index, checkpoint expression, and response to immunotherapy and chemotherapeutic drugs. Results of quantitative real-time polymerase chain reaction (qRT-PCR) showed that LGR5 and VSIG4 were differentially expressed between normal and colon cancer samples. In conclusion, we demonstrated the potential of PANoptosis-based molecular clustering and prognostic signatures for prediction of patient survival and tumor microenvironment (TME) in colon cancer. Our findings may improve our understanding of the role of PANoptosis in colon cancer, and enable the development of more effective treatment strategies.

TRPP2 ion channels: The roles in various subcellular locations.

TRPP2 (PC2, PKD2 or Polycytin-2), encoded by PKD2 gene, belongs to the nonselective cation channel TRP family. Recently, the three-dimensional structure of TRPP2 was constructed. TRPP2 mainly functions in three subcellular compartments: endoplasmic reticulum, plasma membrane and primary cilia. TRPP2 can act as a calcium-activated intracellular calcium release channel on the endoplasmic reticulum. TRPP2 also interacts with other Ca2+ release channels to regulate calcium release, like IP3R and RyR2. TRPP2 acts as an ion channel regulated by epidermal growth factor through activation of downstream factors in the plasma membrane. TRPP2 binding to TRPC1 in the plasma membrane or endoplasmic reticulum is associated with mechanosensitivity. In cilium, TRPP2 was found to combine with PKD1 and TRPV4 to form a complex related to mechanosensitivity. Because TRPP2 is involved in regulating intracellular ion concentration, TRPP2 mutations often lead to autosomal dominant polycystic kidney disease, which may also be associated with cardiovascular disease. In this paper, we review the molecular structure of TRPP2, the subcellular localization of TRPP2, the related functions and mechanisms of TRPP2 at different sites, and the diseases related to TRPP2.

Controlled Synthesis of a Two-Dimensional Non-van der Waals Ferromagnet toward a Magnetic Moiré Superlattice.

Two-dimensional (2D) magnetic materials provide an ideal platform for spintronics, magnetoelectrics, and numerous intriguing physical phenomena in 2D limits. Moiré superlattices based on 2D magnets offer an avenue for controlling the spin degree of freedom and engineering magnetic properties. However, the synthesis of high-quality, large-grain, and stable 2D magnets, much less obtaining a magnetic moiré superlattice, is still challenging. We synthesize 2D ferromagnets (trigonal Cr5Te8) with controlled thickness and robust stability through chemical vapor deposition. Single-unit-cell-thick flakes with lateral sizes of tens of micrometers are obtained. We observe the layer-by-layer growth mode for the crystal formation in non-van der Waals Cr5Te8. The robust anomalous Hall signal confirms that Cr5Te8 of varying thickness have a long-range ferromagnetic order with an out-of-plane easy axis. There is no obvious change of the Curie temperature when the thickness of Cr5Te8 decreases from 52.1 to 7.2 nm. Here, we construct diverse 2D non-van der Waals/van der Waals vertical heterostructures (Cr5Te8/graphene, Cr5Te8/h-BN, Cr5Te8/MoS2). A uniform moiré superlattice is formed in the heterostructure through a lattice mismatch. The successful growth of 2D Cr5Te8 and a related moiré superlattice introduces 2D non-van der Waals ferromagnets into moiré superlattice research, thus highlighting prospects for property investigation of a non-van der Waals magnetic moiré superlattice and massive applications which require a scalable approach to magnetic moiré superlattices.

Exocyst controls exosome biogenesis via Rab11a.

Tumor cells actively release large quantities of exosomes, which pivotally participate in the regulation of cancer biology, including head and neck cancer (HNC). Exosome biogenesis and release are complex and elaborate processes that are considered to be similar to the process of exocyst-mediated vesicle delivery. By analyzing the expression of exocyst subunits and their role in patients with HNC, we aimed to identify exocyst and its functions in exosome biogenesis and investigate the molecular mechanisms underlying the regulation of exosome transport in HNC cells. We observed that exocysts were highly expressed in HNC cells and could promote exosome secretion in these cells. In addition, downregulation of exocyst expression inhibited HN4 cell proliferation by reducing exosome secretion. Interestingly, immunofluorescence and electron microscopy revealed the accumulation of multivesicular bodies (MVBs) after the knockdown of exocyst. Autophagy, the major pathway of exosome degradation, is not activated by this intracellular accumulation of MVBs, but these MVBs are consumed when autophagy is activated under the condition of cell starvation. Rab11a, a small GTPase that is involved in MVB fusion, also interacted with the exocyst. These findings suggest that the exocyst can regulate exosome biogenesis and participate in the malignant behavior of tumor cells.

Molecular classification reveals the diverse genetic and prognostic features of gastric cancer: A multi-omics consensus ensemble clustering.

BACKGROUND: Globally, gastric cancer (GC) is the fifth most common tumor. It is necessary to identify novel molecular subtypes to guide patient selection for specific target therapeutic benefits. METHODS: Multi-omics data, including transcriptomics RNA-sequencing (mRNA, LncRNA, miRNA), DNA methylation, and gene mutations in the TCGA-STAD cohort were used for the clustering. Ten classical clustering algorithms were executed to recognize patients with different molecular features using the "MOVICS" package in R. The activated signaling pathways were evaluated using the single-sample gene set enrichment analysis. The differential distribution of gene mutations, copy number alterations, and tumor mutation burden was compared, and potential responses to immunotherapy and chemotherapy were also assessed. RESULTS: Two molecular subtypes (CS1 and CS2) were recognized by ten clustering algorithms with consensus ensembles. Patients in the CS1 group had a shorter average overall survival time (28.5 vs. 68.9 months, P = 0.016), and progression-free survival (19.0 vs. 63.9 months, P = 0.008) as compared to those in the CS2 group. Extracellular associated biological process activation was higher in the CS1 group, while the CS2 group displayed the enhanced activation of cell cycle-associated pathways. Significantly higher total mutation numbers and neoantigens were observed in the CS2 group, along with specific mutations in TTN, MUC16, and ARID1A. Higher infiltration of immunocytes was also observed in the CS2 group, reflective of the potential immunotherapeutic benefits. Moreover, the CS2 group could also respond to 5-fluorouracil, cisplatin, and paclitaxel. The similar diversity in clinical outcomes between CS1 and CS2 groups was successfully validated in the external cohorts, GSE62254, GSE26253, GSE15459, and GSE84437. CONCLUSION: The findings provided novel insights into the GC subtypes through integrative analysis of five -omics data by ten clustering algorithms. These could provide potential clinical therapeutic targets based on the specific molecular features.

Extracellular Matrix-Associated Pathways Promote the Progression of Gastric Cancer by Impacting the Dendritic Cell Axis.

BACKGROUND: Gastric cancer (GC) is the third most frequent malignant tumour in the Chinese population, let alone the whole world. Recently, most prognostic models have only focused on the levels of several genes, miRNAs, lncRNAs, gene mutations, or DNA methylation; however, the activation status of biological pathways is more stable and can reflect the comprehensive inner conditions of tumours. METHODS: We collected samples from the Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort and GSE62254 cohort, with a total of 594 patients. We employed GSEA to first compare the diverse activated signalling pathways between dead GC patients and living patients. The least absolute shrinkage and selection operator (LASSO) regression analysis was subsequently performed by the "glmnet" package to generate a prognostic signature. RESULTS: We extracted a total of 218 genes from the KEGG Focal Adhesion and KEGG ECM Receptor Interaction pathways, which showed significant activation in dead GC patients in two enrolled cohorts, for subsequent LASSO analysis. In the TCGA-STAD cohort, patients in the high-risk group faced a significantly poorer prognosis than those in the low-risk group (P < 0.001, HR: 4.62, 95% CI: 3.447-6.183), with an AUC of 0.694. In the GSE62254 cohort, the HR value was 4.94 (95% CI: 3.413-7.165), and the AUC value was as high as 0.834. A high-risk score and poor prognosis correlated with infiltrated dendritic cells, and the receptor of IFN-α was also positively linked with the risk score, as well as poor prognosis. GC patients with high-risk scores were more likely to respond to CTLA4 treatment but not PD1 treatment. CONCLUSION: Taken together, we established and verified an extracellular matrix prognostic model of gastric cancer patients. The model can be used to evaluate the risk of death of GC patients, as well as the response to anti-CTLA4 immunotherapy.

Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer.

Gastric cancer (GC) is a heavy health burden around the world, which is the fifth most frequent tumor and leads to the third most common cancer-related deaths. It is urgent to identify prognostic markers as the guideline for personalized treatment and follow-up. We accessed the prognostic value of Early B-cell factors (EBFs) in GC. A total of 415 GC tissues and 34 normal tissues from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, 616 external patients from GSE15459, GSE22377, GSE51105, GSE62245 were enrolled for analysis. Univariate and multivariate Cox regression analyses were employed to evaluate the sole and integrative prognostic value of EBFs, respectively. Genetic alterations, DNA methylation of EBFs were also evaluated, as well as the involved signaling pathways. We revealed that increased EBFs associated with the poor prognosis of GC patients, the prognostic model was established in TCGA-STAD cohort, and validated in Gene Expression Omnibus (GEO) cohorts, with effectiveness in both HER2 positive and negative patients. DNA methylation was involved in the impact on prognosis. Cell cycle, immune-associated, and MAPK pathways were influenced by EBFs. Anti-CTLA4 immunotherapy is more suitable for EBFs determining high-risk groups, but not anti-PD-1/PD-L1 therapy. 5-Fluorouracil, methotrexate, vorinostat are suitable to inhibit the function of EBFs. Our new findings provide novel insight into the prediction of prognosis and clinical treatment of GC patients based on EBFs.

Testicular orphan receptor 4 (TR4) promotes papillary thyroid cancer invasion via activating circ-FNLA/miR-149-5p/MMP9 signaling.

The incidence and mortality of papillary thyroid cancer (PTC) have steadily increased. Although conventional therapies are very effective toward differentiated PTC patients, very limited therapeutic options are applicable to those patients with distant metastases. Therefore, better understanding of the molecular biology of metastatic PTC helps identify novel targets and facilitates the development of new therapies. In this study, we first found that testicular orphan receptor 4 (TR4) was significantly increased in PTC tumors spreading to lymph nodes compared to the paired primary tumors. Experimental evidence suggested that TR4 drove PTC progression via promoting its cell invasion and cell migration. Mechanistically, TR4 transcriptionally regulated the expression level of circ-filamin A (FLNA), which competed with matrix metalloproteinase 9 (MMP9) for microRNA (miR)-149-5p binding and led to an increased protein level of MMP9. Interruption assays with various gene manipulations verified that the TR4/circ-FLNA/miR-149-5p/MMP9 signaling axis played a central role in cell invasion and cell migration of PTC cells. Moreover, a xenografted mouse model also confirmed that the TR4/circ-FLNA signal promoted PTC tumor growth. Overall, our study pinpoints the oncogenic role of TR4 in PTC development, and the targeting of TR4/circ-FLNA/miR-149-5p/MMP9 signaling may be an alternative option for metastatic PTC patients.

Impact of Prepackaged Low-Residue Diet on Bowel Preparation for Colonoscopy: A Meta-analysis.

This meta-analysis aimed to evaluate the impact of prepackaged low-residue diet (PLRD) on bowel preparation for colonoscopy. We searched PubMed, Web of Science, EMBASE, and Cochrane Library databases from inception to August 2020. Randomized controlled trials (RCTs) comparing PLRD with clear liquid diet (CLD) or self-prepared LRD were considered for inclusion. The analysis calculated the odds ratio (OR) for the rate of adequate bowel preparation, patient tolerance, willingness to repeat bowel preparation, tolerability of bowel preparation, and overall adverse effects. Five RCTs published between 2006 and 2019 (N = 561) were included in our meta-analysis. Compared with the traditional CLD or self-prepared LRD, PLRD showed significantly higher rates of adequate bowel preparation (OR, 2.16; 95% confidence interval [CI], 1.18-3.98; p = .01), patient tolerance (OR, 1.99; 95% CI, 1.30-3.07; p = .002), and willingness to repeat the bowel preparation (OR, 1.68; 95% CI, 1.05-2.70; p = .03), with no differences in adverse events (OR, 0.93; 95% CI, 0.59-1.46; p = .75). Prepackaged low-residue diet improved bowel preparation quality, patient tolerance, and willingness to repeat bowel preparations. Importantly, PLRD does not increase the incidence of adverse events. This suggests that it is effective and safe to use PLRD for bowel preparation before colonoscopy.

Integrate analysis of the promote function of Cell division cycle-associated protein family to pancreatic adenocarcinoma.

Background: The cell division cycle-associated (CDCA) protein family plays a pivotal role in the regulation of the cell cycle during tumorigenesis and predicts the prognosis of tumors, but an analysis of these proteins in pancreatic adenocarcinoma (PAAD) is still lacking. Methods: Oncomine and GEPIA were used to observe the expression and prognostic value of eight CDCAs in pan-cancer. Univariate Cox analysis of single CDCAs and multivariate Cox analysis of all eight CDCAs were performed to evaluate the integrated prognostic value of CDCAs, and the results are displayed as hazard ratios (HRs) and 95% confidence intervals (95% CIs). K-M plots and receiver operating characteristics curves were used to display the predicted function and accuracy of CDCAs to determine the risk score. Annotation of CDCA-related genes, gene sets enrichment analysis (GSEA) and gene sets variation analysis (GSVA) were performed to reveal the CDCAs that impact biological processes. Results: CDCAs expression in most tumors is higher than that in normal tissues and is associated with a poor prognosis. Regarding PAAD, increased CDCA expression along with advanced PAAD tumor stage, NUF2, CDCA2, CDCA3, CDCA4 and CDCA5 expression are risk factors for poor prognosis, while CBX2 expression is a protective factor (P < 0.05). The integrated prognostic value of CDCAs in PAAD patients was validated by SurvExpress in the TCGA-PAAD cohort (P < 0.001, HR = 2.16, 95% CI = 1.41-3.3) and the ICGC-PACA cohort (P < 0.001, HR = 2.56, 95% CI = 1.73-3.79). Genetic alteration and DNA methylation of CDCAs might not affect the prognosis of PAAD patients. After comparing high- and low-risk groups separated by CDCA risk scores, the activated pathways were revealed and included the cell cycle, DNA repair, P53, MYC-targets, E2F-targets and PI3K pathways. Conclusion: CDCAs can predict the OS prognosis of PAAD patients. The cell cycle, DNA repair, E2F, P53 and PI3K signaling pathways, in which CDCAs are involved, impact the tumorigenesis of PAAD.

MiR-200c-3p increased HDMEC proliferation through the notch signaling pathway.

Excessive proliferation of vascular endothelial cells can cause hemangioma. Although typically benign, hemangiomas can become life-threatening. The microRNA miR-200c-3p is abnormally expressed in some types of tumors, but its expression, biological role, and mechanism of action in infantile hemangioma remain to be fully elucidated. The expression levels of miR-200c-3p in hemangioma tissue were compared with those in adjacent healthy tissue by using bioinformatics analyses and TargetScan. Western blot, enzyme-linked immunosorbent assay, and Cell Counting Kit 8 analyses were used to determine the biological function and site of action of miR-200c-3p in human dermal microvascular endothelial cells (HDMECs). MiR-200c-3p was one of the top 10 differentially expressed genes between healthy tissue, and hemangiomas tissues, having markedly decreased expression in hemangioma tissue. Reduction of miR-200c-3p expression in HDMECs through the transfection of a miR-200c-3p inhibitor significantly increased HDMEC proliferation. The addition of the Notch signaling pathway inhibitor DAPT to HDMECs transfected with the miR-200c-3p inhibitor eliminated the inhibitor-induced enhancement of proliferation in HDMECs. These findings indicate that miR-200c-3p targets the Notch signaling pathway to promote the proliferation of vascular endothelial cells, suggesting that miR-200c-3p plays an important role in the pathogenesis of hemangioma.

The role of miRNAs in colorectal cancer progression and chemoradiotherapy.

Colorectal cancer (CRC) is known as the third most common cancer as well as the fourth most deadly cancer worldwide. CRC accounts for approximately 10 % of all new cancer cases globally, remaining the second most frequent cause of cancer-related deaths. MicroRNAs (miRNAs) are a class of small noncoding RNAs that can affect a variety of cellular and molecular targets. Depending on the cell environment in which the information is expressed, miRNAs can serve as a CRC suppressor or promoter and play essential roles in several biological processes. In this review, we summarized the relationship between miRNAs and proliferation, metastasis, angiogenesis, autophagy, apoptosis, and the chemoradiotherapy of CRC, revealing that relevant miRNAs could serve as potential targets for CRC therapy.

Orai-IGFBP3 signaling complex regulates high-glucose exposure-induced increased proliferation, permeability, and migration of human coronary artery endothelial cells.

INTRODUCTION: Diabetes-associated endothelium dysfunction might be linked to disturbances in Ca2+ homeostasis. Our main objective is to reveal the potential mechanisms by which high-glucose (HG) exposure promotes increased proliferation of human coronary artery endothelial cells (HCAECs) in culture, and that store-operated Ca2+ entry (SOCE) and insulin-like growth factor binding protein 3 (IGFBP3) contribute to this proliferation. RESEARCH DESIGN AND METHODS: We detected the expression levels of Ca2+ release-activated calcium channel proteins (Orais), IGFBP3 and proliferating cell nuclear antigen of HCAECs cultured in HG medium for 1, 3, 7, and 14 days and in streptozotocin-induced diabetic mouse coronary endothelial cells. Coimmunoprecipitation and immunofluorescence technologies were used to detect the interactions between Orais and IGFBP3 of HCAECs exposed to HG environment, and to detect IGFBP3 expression and proliferation after treatment of HCAECs cultured in HG medium with an agonist or inhibitor of SOCE. Similarly, after transfection of specific small interfering RNA to knock down IGFBP3 protein expression, SOCE activity and Orais expression were tested. Some processes related to endothelial dysfunction, such as migration, barrier function and adhesion marker expression, are also measured. RESULTS: HG exposure promoted increased proliferation of HCAECs in culture and that SOCE and IGFBP3 contributed to this proliferation. In addition, we also found that Orais and IGFBP3 were physically associated and regulated each other's expression levels. Besides, their expression levels and interactions were enhanced in HCAECs after exposure to HG. HG exposure promotes cell migration, but reduces barrier function and adherens junction protein expression levels in HCAECs. CONCLUSION: Orais and IGFBP3 formed a signaling complex that mediated HCAEC proliferation during HG exposure in culture. Meanwhile, we also found that SOCE stimulates proliferation of HCAECs by regulating IGFBP3, thereby promoting the occurrence and progression of coronary atherosclerosis in diabetes. It is worth noting that our findings may shed new light on the mechanisms of increased proliferation in HCAECs in diabetes and suggest the potential value of SOCE and IGFBP3 as therapeutic targets for coronary atherosclerosis in individuals with diabetes.

Development and Validation of the B Cell-Associated Fc Receptor-like Molecule-Based Prognostic Signature in Skin Cutaneous Melanoma.

METHODS: 461 patients with CM from The Cancer Genome Atlast- (TCGA-) CM cohort and 290 pateints from the GSE65904 cohort were enrolled. Student's t-test was used to compare the differences, and Pearson's correlation coefficient was employed to evaluate associations. The Kaplan-Meier (K-M) survival analysis was used to evaluate overall survival (OS). The multivariate Cox regression was conducted to generate the FCRL prognostic signature. GSEA analysis and TIMER were employed to study the potential mechanisms. RESULT: Patients with Breslow's depth high or equal to 3 cm had the lower expression of FCRL1-6 (all, P < 0.05), which indicates poor OS, as well as age, stage, and Breslow's depth subgroups (all, P < 0.001). The overall FCRL1-6 prognostic signature was generated in the TCGA cohort (K-M, P < 0.001; area under the curve (AUC), 0.649 for 3-year OS) and validated in the GSE65904 cohort (K-M, P < 0.001; AUC, 0.659 for 3-year OS). The GSEA results revealed that high expression of FCRLs indicated activated immune-associated pathways, and FCRLs are positively associated with the infiltration of B cells. CONCLUSION: Highly expressed FCRLs were observed associated with a favourable OS of CM. FCRL1-6-based prediction signature could act as a biomarker to predict the prognosis of patients with CM.

What is the impact of BIRC5 gene polymorphisms on urinary cancer susceptibility? Evidence from 9348 subjects.

As a member of apoptosis inhibition gene family, baculoviral IAP repeat containing 5 (BIRC5) protein acts as a survival factor in oncology through multiple ways. There are huge inconsistent results between urinary cancer risk and BIRC5 polymorphisms, so we searched and documented all eligible articles to clear up the mystery with the help of meta-analysis. According to the inclusion and exclusion criteria, we performed an overall search in Web of Science, PubMed, Google Scholar, Medline, CNKI and Wanfang database with pre-set search strategy up to November 2019. Z-test was performed to determine the statistical difference by Odds ratios (ORs) and 95% confidence intervals (CIs). The stability of the pooled ORs was conducted by one-way sensitivity analyses, Begg's funnel plots and Egger's test were employed to access the potential publication bias. The relationship of polymorphisms and BIRC5 expression was exposed by in-silico analysis, as well as the effects to tumorigenesis and prognosis. Finally, we enrolled 19 case-control studies to conducted this meta-analysis. An upgrade risk in rs9904341 of BIRC5 were revealed to be associated with urinary cancer in allele contrast model (OR = 1.222, P = 0.012), homozygote contrast model (OR = 1.579, P = 0.0001) and recessive contrast model (OR = 1.433, P < 0.001), as well as rs2071214 polymorphism in the subgroup analysis of BCa in allele contrast model (OR = 1.362, P = 0.011) and recessive contrast model (OR = 1.417, P = 0.015). On the other hand, rs17878467 variant plays an important role in prevent the tumorigenicity of urinary cancer in allele contrast model (OR = 0.672, P = 0.009), heterozygote contrast model (OR = 0.585, P = 0.006) and dominant contrast model (OR = 0.595, P = 0.004). In conclusion, we found that BIRC5 rs9904341, rs2071214 polymorphisms might cause the increased risk of urinary cancer, while rs17878467 reduces risk.

Hierarchically Porous Co/Cox My (M = P, N) as an Efficient Mott-Schottky Electrocatalyst for Oxygen Evolution in Rechargeable Zn-Air Batteries.

Tailoring composition and morphology of electrocatalysts is of great importance in improving their catalytic performance. Herein, a salt-templated strategy is proposed to construct novel multicomponent Co/Cox My (M = P, N) hybrids with outstanding electrocatalytic performance for the oxygen evolution reaction (OER). The obtained Co/Cox My hybrids present porous sheet-like architecture consisting of many hierarchical secondary building-units. The synthetic strategy depends on a facile and effective dissolution-recrystallization-pyrolysis process under NH3 atmosphere of the precursors, which does not involve any surfactant or long-time hydrothermal pretreatment. That is different from the conventional methods for the synthesis of hierarchical nitrides/phosphides. Benefitting from unique composition/structure-dependent merits, the Co/Cox My hybrids as a typical Mott-Schottky electrocatalyst exhibit good OER performance in an alkaline medium compared with their counterparts, as evidenced by a low overpotential of 334 mV at 10 mA cm-2 and a small Tafel slope of 79.2 mV dec-1 , as well as superior long-term stability. More importantly, the Co/Cox My +Pt/C achieves higher voltaic efficiency and several times longer cycle life than conventional RuO2 +Pt/C catalysts in rechargeable Zn-air batteries. It is envisioned that the present work can provide a new avenue for the development of Mott-Schottky electrocatalysts for sustainable energy storage.