Simultaneous Inhibition of Vanadium Dissolution and Zinc Dendrites by Mineral-Derived Solid-State Electrolyte for High-Performance Zinc Metal Batteries.

Designing solid electrolyte is deemed as an effective approach to suppress the side reaction of zinc anode and active material dissolution of cathodes in liquid electrolytes for zinc metal batteries (ZMBs). Herein, kaolin is comprehensively investigated as raw material to prepare solid electrolyte (KL-Zn) for ZMBs. As demonstrated, KL-Zn electrolyte is an excellent electronic insulator and zinc ionic conductor, which presents wide voltage window of 2.73 V, high ionic conductivity of 5.08 mS cm-1, and high Zn2+ transference number of 0.79. For the Zn//Zn cells, superior cyclic stability lasting for 2200 h can be achieved at 0.2 mA cm-2. For the Zn//NH4V4O10 batteries, stable capacity of 245.8 mAh g-1 can be maintained at 0.2 A g-1 after 200 cycles along with high retention ratio of 81%, manifesting KL-Zn electrolyte contributes to stabilize the crystal structure of NH4V4O10 cathode. These satisfying performances can be attributed to the enlarged interlayer spacing, zinc (de)solvation-free mechanism and fast diffusion kinetics of KL-Zn electrolyte, availably guaranteeing uniform zinc deposition for zinc anode and reversible zinc (de)intercalation for NH4V4O10 cathode. Additionally, this work also verifies the application possibility of KL-Zn electrolyte for Zn//MnO2 batteries and Zn//I2 batteries, suggesting the universality of mineral-based solid electrolyte.

Retraction Note: Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/ß-catenin signaling pathway.

The authors have retracted this article [1] because there are errors in Figures 4a and 4b.

Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/ß-catenin signaling pathway.

BACKGROUND: Long non-coding RNA (lncRNA) actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is oriented in an antisense direction to the protein-coding gene AFAP1 in the opposite strand. Previous studies showed that lncRNA AFAP1-AS1 was upregulated and acted as an oncogene in a variety of tumors. However, the expression and biological functions of lncRNA AFAP1-AS1 in tongue squamous cell carcinoma (TSCC) are still unknown. METHODS: The expression level of AFAP1-AS1 was measured in 103 pairs of human TSCC tissues and corresponding adjacent normal tongue mucous tissues. The correlation between AFAP1-AS1 and the clinicopathological features was evaluated using the chi-square test. The effects of AFAP1-AS1 on TSCC cells were determined via a CCK-8 assay, clone formation assay, flow cytometry, wound healing assay and transwell assay. Furthermore, the effect of AFAP1-AS1 knockdown on the activation of the Wnt/ß-catenin signaling pathway was investigated. Finally, CAL-27 cells with AFAP1-AS1 knockdown were subcutaneously injected into nude mice to evaluate the effect of AFAP1-AS1 on tumor growth in vivo. RESULTS: In this study, we found that lncRNA AFAP1-AS1 was increased in TSCC tissues and that patients with high AFAP1-AS1 expression had a shorter overall survival. Short hairpin RNA (shRNA)-mediated AFAP1-AS1 knockdown significantly decreased the proliferation of TSCC cells. Furthermore, AFAP1-AS1 silencing partly inhibited cell migration and invasion. Inhibition of AFAP1-AS1 decreased the activity of the Wnt/ß-catenin pathway and suppressed the expression of EMT-related genes (SLUG, SNAIL1, VIM, CADN, ZEB1, ZEB2, SMAD2 and TWIST1) in TSCC cells. In addition, CAL-27 cells with AFAP1-AS1 knockdown were injected into nude mice to investigate the effect of AFAP1-AS1 on tumorigenesis in vivo. Downregulation of AFAP1-AS1 suppressed tumor growth and inhibited the expression of EMT-related genes (SLUG, SNIAL1, VIM, ZEB1, NANOG, SMAD2, NESTIN and SOX2) in vivo. CONCLUSIONS: Taken together, our findings present a road map for targeting the newly identified lncRNA AFAP1-AS1 to suppress TSCC progression, and these results elucidate a novel potential therapeutic strategy for TSCC.

Cellular prion protein is involved in decidualization of mouse uterus.

Prion protein (PrP) is encoded by a single copy gene Prnp in many cell and tissue types. PrP is very famous for its infectious conformers (PrPSC) resulting in transmissible spongiform encephalopathies. At present, physiological functions of its cellular isoform (PrPC) remain ambiguous. Although PrPC expression has been found in uterus, whether it functions in maternal-fetal dialogue during early pregnant is unknown. In this study, we examined PrPC mRNA and protein in the uterus of peri-implantation mice, and found that they were expressed with a spatiotemporal dynamic pattern. Interestingly, PrPC was significantly increased in the decidual zones around the implanting embryos at the implantation window stage. To further demonstrate that PrPC is involved in the decidualization of mouse uterus during embryo implantation, we constructed the artificial decidualization models and the delayed implantation models. Once the pseudopregnant mice were artificially induced to decidualization, the PrPC expression then increased significantly in the decidua zone. And also, if the delayed implantation embryos were allowed to implant, PrPC protein was also simultaneously improved in stromal cells surrounding the implanting embryos. Moreover, PrPC expression can be inhibited by progesterone but upregulated by estrogen in mouse uterus. These results suggest that PrPC may play an important role in embryo implantation and decidualization.

NGL-2 Is a New Partner of PAR Complex in Axon Differentiation.

Neuronal polarization is pivotal for neural network formation during brain development. Axon differentiation is a hallmark of initial neuronal polarization. Here, we report that the leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2) as a polarity regulator that localizes asymmetrically in rat hippocampal neurons and is required for differentiation of the future axon. NGL-2 was associated with PAR complex, and this interaction resulted in local stabilization of axonal microtubules. Further study showed that the C terminal of NGL-2 binds to the PDZ domain of PAR6, and NGL-2 interacts with PAR3 and atypical PKCζ (aPKCζ), with PAR6 acting as a bridge or modifier. Then, NGL-2 regulates the local stabilization of microtubules and promotes axon differentiation by the aPKCζ/microtubule affinity-regulating kinase 2 pathway. These findings reveal the critical role of NGL-2 in regulating axon differentiation in rat hippocampal neurons and reveal a novel partner of the PAR complex.

Up-Regulation of microRNA-183 Promotes Cell Proliferation and Invasion in Glioma By Directly Targeting NEFL.

Glioblastoma multiforme (GBM) is the most common and lethal type of primary malignant brain tumor. In recent years, increasing reports suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for human cancers, including GBM. The expression and roles of microRNA-183 (miR-183) has been explored in several types of human cancers, including in GBM, and plays important roles in tumor initiation and progression. However, its biological functions in GBM remain largely unknown. In this study, we demonstrated that miR-183 was significantly up-regulated in astrocytoma tissues and glioblastoma cell lines. Introduction of miR-183 mimics into U251 cells could promoted, while its antisense oligos inhibited cell proliferation and invasion. Moreover, we identified neurofilament light polypeptide (NEFL) as a novel target gene of miR-183. The expression levels of NEFL are inversely correlated with that of miR-183 in human astrocytoma clinical specimens. In addition, NEFL-siRNA could significantly attenuate the inhibitory effects of knockdown miR-183 on the proliferation and invasion of U251 cells via mTOR signaling pathway. Overall, This study revealed that miR-183 promotes glioma cell proliferation by targeting NEFL, and also demonstrated that miR-183 could be a potential target for GBM treatment.

Positive association between serum apolipoprotein M levels and hepatitis B virus DNA load in HBeAg-negative chronic hepatitis B.

BACKGROUND: Hepatitis virus B (HBV) has infected millions of people worldwide. Notably, such infections can be associated with hepatic complications. Levels of apolipoprotein M (apoM), a component of high-density lipoprotein (HDL), are known to be significantly elevated in patients with chronic hepatitis B (CHB). The aim of this study was to investigate the relationship between HBV DNA load in serum and serum apoM levels in patients with CHB. METHODS: A total of 73 HBeAg-negative CHB patients, 50 HBeAg-positive CHB patients, and 79 non-CHB controls were included in the study cohort. The age and body mass index (BMI) of the study participants were matched. Serum levels of apoM and the HBV antigens HBsAg and HBeAg were measured by enzyme-linked immunosorbent assay (ELISA) analysis. Serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), cholesterol, and triglycerides (TG) were assessed using an automatic biochemical analyzer. Serum HBV DNA levels were quantified by real-time PCR analysis. Data were analyzed by Spearman's rank correlation coefficient, Pearson correlation coefficient, and multivariate linear regression model (continuous variables), or Student's t-test (mean differences). RESULTS: Both the HBeAg-negative CHB and HBeAg-positive CHB patient groups exhibited elevated serum levels of apoM. Moreover, serum apoM levels were positively correlated with serum HBV DNA levels in HBeAg-negative CHB patients (r = 0.394, p < 0.001). Conversely, there was no significant relationship between apoM and HBV DNA levels in the HBeAg-positive CHB group (r = 0.197, p = 0.170). The median log copies/mL value for HBV DNA (4.00) was considered the cutoff point for the HBeAg-negative CHB group. Notably, a significant number of patients with HBV DNA levels above the cutoff point also had higher serum apoM levels (63.38 ± 29.84 vs. 41.41 ± 21.84; p = 0.001). CONCLUSIONS: Our findings reveal that the correlation between serum apoM levels and viral loads may depend on HBeAg status, as serum apoM levels were positively correlated with HBV DNA levels in HBeAg-negative CHB patients. These results suggest that HBeAg may play a role in apoM-related lipid metabolism and anti-inflammatory functions in hepatitis B patients. Thus, our findings may facilitate the clinical management of HBV infection.

NGX6a is degraded through a proteasome-dependent pathway without ubiquitination mediated by ezrin, a cytoskeleton-membrane linker.

Our previous study demonstrated that the NGX6b gene acts as a suppressor in the invasion and migration of nasopharyngeal carcinoma (NPC). Recently, we identified the novel isoform NGX6a, which is longer than NGX6b. In this study, we first found that NGX6a was degraded in NPC cells and that this degradation was mediated by ezrin, a linker between membrane proteins and the cytoskeleton. Specific siRNAs against ezrin increase the protein level of NGX6a in these cells. During degradation, NGX6a is not ubiquitinated but is degraded through a proteasome-dependent pathway. The distribution pattern of ezrin was negatively associated with NGX6a in an immunochemistry analysis of a nasopharyngeal carcinoma tissue microarray and fetus multiple organ tissues and Western blot analysis in nasopharyngeal and NPC cell lines, suggesting that ezrin and NGX6a are associated and are involved in the progression and invasion of NPC. By mapping the interacting binding sites, the seven-transmembrane domain of NGX6a was found to be the critical region for the degradation of NGX6a, and the amino terminus of ezrin is required for the induction of NGX6a degradation. The knockdown of ezrin or transfection of the NGX6a mutant CO, which has an EGF-like domain and a transmembrane 1 domain, resulted in no degradation, significantly reducing the ability of invasion and migration of NPC cells. This study provides a novel molecular mechanism for the low expression of NGX6a in NPC cells and an important molecular event in the process of invasion and metastasis of nasopharyngeal carcinoma cells.

MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ.

Glioblastoma (GBM) is the most lethal brain tumor due to the resistance to conventional therapies, such as radiotherapy and chemotherapy. TAZ, an important mediator of the Hippo pathway, was found to be up-regulated in diverse cancers, including in GBM, and plays important roles in tumor initiation and progression. However, little is known about the regulation of TAZ expression in tumors. In this study, we found that miR-125a-5p is an important regulator of TAZ in glioma cells by directly targeting the TAZ 3' UTR. MiR-125a-5p levels are inversely correlated with that of TAZ in normal astrocytes and a panel of glioma cell lines. MiR-125a-5p represses the expression of TAZ target genes, including CTGF and survivin, and inhibits cell proliferation and induces the differentiation of GBM cells; whereas over-expression of TAZ rescues the effects of miR-125a-5p. This study revealed a mechanism for TAZ deregulation in glioma cells, and also demonstrated a tumor suppressor role of miR-125a-5p in glioblastoma cells.

MicroRNA-421 is a new potential diagnosis biomarker with higher sensitivity and specificity than carcinoembryonic antigen and cancer antigen 125 in gastric cancer.

CONTEXT: The sensitivity and specificity of blood microRNA-421 (miR-421) as a gastric cancer (GC) biomarker has not been determined. OBJECTIVE: To investigate the diagnostic value of blood miR-421 as GC biomarker. MATERIALS AND METHODS: miR-421 in serum and peripheral blood mononuclear cells (PBMCs) of 90 GC patients and 90 controls was detected by quantitative real-time PCR. The correlation of miR-421 to GC clinicopathological features as well as the diagnostic value of miR-421 comparing to carcinoembryonic antigen (CEA) and cancer antigen 125 (CA-125) were analyzed. RESULTS: miR-421 increased significantly in GC patients than in controls. miR-421 in either serum or PBMCs had higher sensitivity and specificity than CEA and CA-125 in GC diagnosis. The GC positive prediction rates of miR-421 were also significantly higher than those of CEA and CA-125. DISCUSSION AND CONCLUSIONS: miR-421 in serum or PBMCs may be a new potential diagnostic biomarker for GC.

MiR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma.

The 5-year survival rate for colorectal cancer is approximately 55 % because of its invasion and metastasis. The epithelial-mesenchymal transition (EMT) is one of the well-defined processes during the invasion and distant metastasis of primary epithelial tumors. miR-429, a member of the miR-200 family of microRNAs, was previously shown to inhibit the expression of transcriptional repressors ZEB1/delta EF1 and SIP1/ZEB2, and regulate EMT. In this study, we showed that miR-429 was significantly downregulated in colorectal carcinoma (CRC) tissues and cell lines. We found that miR-429 inhibited the proliferation and growth of CRC cells in vitro and in vivo, suggesting that miR-429 could play a role in CRC tumorigenesis. We also showed that downregulation of miR-429 may contribute to carcinogenesis and the initiation of EMT of CRC by targeting Onecut2. Further researches indicated that miR-429 inhibited the cells migration and invasion and reversed TGF-ß-induced EMT changes in SW620 and SW480 cells. miR-429 could reverse the change of EMT-related markers genes induced by TGF-ß1, such as E-cadherin, CTNNA1, CTNNB1, TFN, CD44, MMP2, Vimentin, Slug, Snail, and ZEB2 by targeting Onecut2. Taken together, our data showed that transcript factor Onecut2 is involved in the EMT, migration and invasion of CRC cells; miR-429 inhibits the initiation of EMT and regulated expression of EMT-related markers by targeting Onecut2; and miR-429 or Onecut2 is the important therapy target for CRC.

Reliability of Droplet Digital PCR Alone and in Combination with Interleukin-6 and Procalcitonin for Prognosis of Bloodstream Infection.

Purpose: Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy. Patients and Methods: This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR. Results: The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P=0.0182), PCT (P=0.0029), and CRP (P=0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P=0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA<7 was lower than that of the SOFA≥7 (P=0.0334). ddPCR (OR: 1.789, P=0.035) monitoring combined with PCT (OR: 1.787, P=0.035) holded predictive value for SOFA progression (AUC=0.7913, P=0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P=0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P=0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P=0.0003). Conclusion: In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions.

F10 gene hypomethylation, a putative biomarker for glioma prognosis.

Tumors are usually characterized by an imbalance in cytosine methylation, including hypomethylation of CpG islands. In this study, bisulfite sequencing PCR was used to assess the promoter methylation status of coagulation factor X (F10) gene in tumors of 96 glioma patients and in glioma cells U251, SF767, and SF126, and the effect of promoter hypomethylation on protein expression was evaluated immunohistochemically. The study showed that the demethylation ratio of F10 in SF126, SF767, and U251 cells was 38.6, 26.4, and 24.3% respectively. Hypomethylation of F10 was detected in 82.3% of glioma specimens and in no normal brain tissues, with significant correlation with its protein expression. However there was no remarkable relationship between F10 hypomethylation and sex, age, and advanced tumor grade. The correlation between F10 hypomethylation, protein expression, and overall survival (OS) was statistically significant. Hypomethylation of F10 promoter in gliomas accounted for F10 encoding protein FX overexpression and aggressive biological behavior in a subset of patients. Furthermore, in the F10 hypomethylation group, OS was shorter for patients with F10 overexpression than for those without. Detection of these epigenetic changes in tumors may provide important information regarding prognosis.

LRRC4 inhibits the proliferation of human glioma cells by modulating the expression of STMN1 and microtubule polymerization.

LRRC4 is a tumor suppressor of glioma, and it is epigenetically inactivated commonly in glioma. Our previous study has shown that induction of LRRC4 expression inhibits the proliferation of glioma cells. However, little is known about the mechanisms underlying the action of LRRC4 in glioma cells. We employed two-dimensional fluorescence differential gel electrophoresis (2-D DIGE) and MALDI -TOF/TOF-MS/MS to identify 11 differentially expressed proteins, including the significantly down-regulated STMN1 expression in the LRRC4-expressing U251 glioma cells. The levels of STMN1 expression appeared to be positively associated with the pathogenic degrees of human glioma. Furthermore, induction of LRRC4 over-expression inhibited the STMN1 expression and U251 cell proliferation in vitro, and the glioma growth in vivo. In addition, induction of LRRC4 or knockdown of STMN1 expression induced cell cycle arrest in U251 cells, which was associated with modulating the p21, cyclin D1, and cyclin B expression, and the ERK phosphorylation, and inhibiting the CDK5 and cdc2 kinase activities, but increasing the microtubulin polymerization in U251 cells. LRRC4, at least partially by down-regulating the STMN1expression, acts as a major glioma suppressor, induces cell cycle arrest and modulates the dynamic process of microtubulin, leading to the inhibition of glioma cell proliferation and growth. Potentially, modulation of LRRC4 or STMN1 expression may be useful for design of new therapies for the intervention of glioma.

MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma.

BACKGROUND: Perturbation of DNA methylation is frequent in cancers and has emerged as an important mechanism involved in tumorigenesis. To determine how DNA methylation is modified in the genome of primary glioma, we used Methyl-DNA immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays to identify differentially DNA methylation sequences between primary glioma and normal brain tissue samples. METHODS: MeDIP-chip technology was used to investigate the whole-genome differential methylation patterns in glioma and normal brain tissues. Subsequently, the promoter methylation status of eight candidate genes was validated in 40 glioma samples and 4 cell lines by Sequenom's MassARRAY system. Then, the epigenetically regulated expression of these genes and the potential mechanisms were examined by chromatin immunoprecipitation and quantitative real-time PCR. RESULTS: A total of 524 hypermethylated and 104 hypomethylated regions were identified in glioma. Among them, 216 hypermethylated and 60 hypomethylated regions were mapped to the promoters of known genes related to a variety of important cellular processes. Eight promoter-hypermethylated genes (ANKDD1A, GAD1, HIST1H3E, PCDHA8, PCDHA13, PHOX2B, SIX3, and SST) were confirmed in primary glioma and cell lines. Aberrant promoter methylation and changed histone modifications were associated with their reduced expression in glioma. In addition, we found loss of heterozygosity (LOH) at the miR-185 locus located in the 22q11.2 in glioma and induction of miR-185 over-expression reduced global DNA methylation and induced the expression of the promoter-hypermethylated genes in glioma cells by directly targeting the DNA methyltransferases 1. CONCLUSION: These comprehensive data may provide new insights into the epigenetic pathogenesis of human gliomas.

Palladium/Copper Cocatalyzed C-H Activation and C-C Bond Regioselective Cleavage Reaction for the Synthesis of Fused Chromeno Quinolines.

A method for the synthesis of fused chromeno quinolines by the palladium/copper cocatalyzed C-H bond activation and C-C bond cleavage reaction has been developed. A variety of fused chromeno quinoline derivatives could be synthesized by coumarin derivatives and anilines through the C-C bond cleavage/C-H functionalization/C-C bond formation process. The MTT assay was used to evaluate the chromeno quinolines against the human cervix tumor cells (HeLa), 3c and 9c without coordination metals showed good inhibition effect.

Correction: MiR-101 reverses the hypomethylation of the LMO3 promoter in glioma cells.

[This corrects the article DOI: 10.18632/oncotarget.3181.].

Bonded- and discreted-Lindqvist hexatungstate-based copper hybrids as heterogeneous catalysts for the one-pot synthesis of 2-phenylquinoxalines via 2-haloanilines with vinyl azides or 3-phenyl-2H-azirines.

One bonded- and one discreted-Lindqvist hexatungstate-based copper hybrids (Cu-POMs) ([Cu2(O)OH(phen)2]2[W6O19]·6H2O (1) and [Cu2(phen)4Cl] [HW6O19]·2H2O (2) (phen = 1,10-phenanthroline)) were controllably synthesized and routinely characterized. Cu-POMs 1-2 consisted of identical [W6O19] unit and similar copper-phen complexes, the two units are bonded via four Cu-O chemical bonds in compound 1; however, compound 2 is discreted and stabilized by intermolecular electrostatic interactions. Importantly, these Cu-POMs catalysts were first applied in the novel reaction for the preparation of 2-phenylquinoxalines via the one-pot coupling and oxidation reactions of 2-haloanilines with vinyl azides or 3-phenyl-2H-azirines under mild conditions, and Cu-POMs 1 showed higher catalytic performance in good yields (79-84%). The reactions exhibit some functional group tolerance and allow for the preparation of a number of 2-phenylquinoxalines.