Cerium-Doped Nickel Sulfide Nanospheres as Efficient Catalysts for Overall Water Splitting.

The development of non-precious metal electrocatalysts with excellent activity and durability for electrochemical water splitting has always been a goal. Transition metal sulfides are attractive electrocatalysts for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). In this article, we designed and constructed efficient catalysts with multiple synergistic interactions and synthesized Ce-NiS2@NF nanosphere using a solvothermal method. Ce-NiS2@NF exhibits excellent HER performance, OER performance, and overall water splitting capability in alkaline electrolytes, demonstrating good stability. The addition of Ce influences the activity of the catalysts, attributed to the synergistic interactions creating more active sites and higher intrinsic activity through the introduction of Ce heteroatoms. Additionally, the self-supported conductive substrate promotes electron transfer, enhancing the intrinsic activity and active site density of the catalyst. This study provides an in-depth investigation into structural design and performance enhancement, offering ideas for designing efficient catalysts for overall water electrolysis. This work provides an in-depth study in terms of structural design performance enhancement and provides ideas for designing efficient alkaline bifunctional catalysts. Valuable insights have been provided in elucidating the intrinsic mechanism of the catalytic activity of cerium-doped nickel sulfide nanospheres, thus providing new guidance in the field of energy conversion technology.

WNT5B drives osteosarcoma stemness, chemoresistance and metastasis.

BACKGROUND: Treatment for osteosarcoma, a paediatric bone cancer with no therapeutic advances in over three decades, is limited by a lack of targeted therapies. Osteosarcoma frequently metastasises to the lungs, and only 20% of patients survive 5 years after the diagnosis of metastatic disease. We found that WNT5B is the most abundant WNT expressed in osteosarcoma tumours and its expression correlates with metastasis, histologic subtype and reduced survival. METHODS: Using tumor-spheroids to model cancer stem-like cells, we performed qPCR, immunoblotting, and immunofluorescence to monitor changes in gene and protein expression. Additionally, we measured sphere size, migration and forming efficiency to monitor phenotypic changes. Therefore, we characterised WNT5B's relevance to cancer stem-like cells, metastasis, and chemoresistance and evaluated its potential as a therapeutic target. RESULTS: In osteosarcoma cell lines and patient-derived spheres, WNT5B is enriched in stem cells and induces the expression of the stemness gene SOX2. WNT5B promotes sphere size, sphere-forming efficiency, and cell proliferation, migration, and chemoresistance to methotrexate (but not cisplatin or doxorubicin) in spheres formed from conventional cell lines and patient-derived xenografts. In vivo, WNT5B increased osteosarcoma lung and liver metastasis and inhibited the glycosaminoglycan hyaluronic acid via upregulation of hyaluronidase 1 (HYAL1), leading to changes in the tumour microenvironment. Further, we identified that WNT5B mRNA and protein correlate with the receptor ROR1 in primary tumours. Targeting WNT5B through inhibition of WNT/ROR1 signalling with an antibody to ROR1 reduced stemness properties, including chemoresistance, sphere size and SOX2 expression. CONCLUSIONS: Together, these data define WNT5B's role in driving osteosarcoma cancer stem cell expansion and methotrexate resistance and provide evidence that the WNT5B pathway is a promising candidate for treating osteosarcoma patients. KEY POINTS: WNT5B expression is high in osteosarcoma stem cells leading to increased stem cell proliferation and migration through SOX2. WNT5B expression in stem cells increases rates of osteosarcoma metastasis to the lungs and liver in vivo. The hyaluronic acid degradation enzyme HYAL1 is regulated by WNT5B in osteosarcoma contributing to metastasis. Inhibition of WNT5B with a ROR1 antibody decreases osteosarcoma stemness.

Regulation and Function of FOXC1 in Osteoblasts.

Estrogens, which bind to estrogen receptor alpha (ERα), are important for proper bone mineral density. When women go through menopause, estrogen levels decrease, and there is a decrease in bone quality, along with an increased risk for fractures. We previously identified an enhancer near FOXC1 as the most significantly enriched binding site for estrogen receptor alpha (ERα) in osteoblasts. FOXC1 is a transcription factor belonging to a large group of proteins known as forkhead box genes and is an important regulator of bone formation. Here, we demonstrate that 17ß-estradiol (E2) increases the mRNA and protein levels of FOXC1 in primary mouse and human osteoblasts. GATA4 is a pioneer factor for ERα and it is also recruited to enhancers near Foxc1. Knockdown of Gata4 in mouse osteoblasts in vitro decreases Foxc1 expression as does knockout of Gata4 in vivo. Functionally, GATA4 and FOXC1 interact and regulate osteoblast proteins such as RUNX2, as demonstrated by ChIP-reChIP and luciferase assays. The most enriched motif in GATA4 binding sites from ChIP-seq is for FOXC1, supporting the notion that GATA4 and FOXC1 cooperate in regulating osteoblast differentiation. Together, these data demonstrate the interactions of the transcription factors ERα, GATA4, and FOXC1 to regulate each other's expression and other osteoblast differentiation genes.

Promoting Surface Reconstruction of Low-Cost Stainless Steel Catalyst for Efficient Oxygen Evolution Reaction.

The development of cost-effective transition metal catalysts for oxygen evolution reaction (OER) is critical for the production of hydrogen fuel from water splitting. Low-cost and efficient stainless steel-based catalysts are expected to replace the scarce platinum group metals for large-scale energy applications. Here in this work, we report the conversion of commonly available inexpensive and easily accessible 434-L stainless steel (SS) into highly active and stable electrodes by corrosion and sulfuration strategies. The Nix Fe1-x S layer as a pre-catalyst and S-doped Nix Fe oxyhydroxides in situ formed on the catalyst surface are the true active species for OER. The optimized 434-L stainless steel-based electrocatalyst exhibits a low overpotential of 298 mV at 10 mA cm-2 in 1.0 M KOH with a small OER kinetics (the Tafel slope of 54.8 mV dec-1 ) and good stability. This work reveals the 434-L alloy stainless steel with Fe and Cr as the main elements can be used as qualified OER catalysts by surface modification, along with a new mentality to solve the energy and resource waste problems.

Tumor Androgen Receptor Protein Level Is Positively Associated with a Better Overall Survival in Melanoma Patients.

Androgen receptor (AR) is expressed in numerous tissues and serves important biologic functions in skin, prostate, immune, cardiovascular, and neural systems, alongside sexual development. Several studies have associated AR expression and patient survival in various cancers, yet there are limited studies examining the relationship between AR expression and cutaneous melanoma. This study used genomics and proteomics data from The Cancer Proteome Atlas (TCPA) and The Cancer Genome Atlas (TCGA), with 470 cutaneous melanoma patient data points. Cox regression analyses evaluated the association between AR protein level with overall survival and revealed that a higher level of AR protein was positively associated with a better overall survival (OS) (p = 0.003). When stratified by sex, the AR association with OS was only significant for both sexes. The multivariate Cox models with justifications of sex, age of diagnosis, stage of disease, and Breslow depth of the tumor confirmed the AR-OS association in all patients. However, the significance of AR was lost when ulceration was included in the model. When stratified by sex, the multivariate Cox models indicated significant role of AR in OS of female patients but not in males. AR-associated genes were identified and enrichment analysis revealed shared and distinct gene network in male and female patients. Furthermore, AR was found significantly associated with OS in RAS mutant subtypes of melanoma but not in BRAF, NF1, or triple-wild type subtypes of melanoma. Our study may provide insight into the well-known female survival advantage in melanoma patients.

GATA4 and estrogen receptor alpha bind at SNPs rs9921222 and rs10794639 to regulate AXIN1 expression in osteoblasts.

Osteoporosis is a serious public health problem that affects 200 million people worldwide. Genome-wide association studies have revealed the association between several single nucleotide polymorphisms (SNPs) near WNT/ß-catenin signaling genes and bone mineral density (BMD). The activation of ß-catenin by WNT ligands is required for osteoblast differentiation. SNP rs9921222 is an intronic variant of AXIN1 (a scaffold protein in the destruction complex that regulates ß-catenin signaling) that correlates with BMD. However, the biological mechanism of SNP rs9921222 has never been reported. Here, we show that the genotype of SNP rs9921222 correlates with the expression of AXIN1 in human osteoblasts. RNA and genomic DNA were analyzed from primary osteoblasts from 111 different individuals. Homozygous TT at rs9921222 correlates with a higher expression of AXIN1 than homozygous CC. Regional association analysis showed that rs9921222 is in high linkage disequilibrium (LD) with SNP rs10794639. In silico transcription factor analysis predicted that rs9921222 is within a GATA4 motif and rs10794639 is adjacent to an estrogen receptor alpha (ERα) motif. Mechanistically, GATA4 and ERα bind at SNPs rs9921222 and rs10794639 as detected by ChIP-qPCR. Luciferase assays demonstrate that rs9921222 is the causal SNP to alter ERα and GATA4 binding. GATA4 promoted the expression, and in contrast, ERα suppressed the expression of AXIN1 via the histone deacetylase complex member SIN3A. Functionally, the level of AXIN1 negatively correlates with the level of transcriptionally active ß-catenin. In summary, we have discovered a molecular mechanism of the SNP rs9921222 to regulate AXIN1 through GATA4 and ERα binding in human osteoblasts.

Estrogen receptor alpha and NFATc1 bind to a bone mineral density-associated SNP to repress WNT5B in osteoblasts.

Genetic factors and estrogen deficiency contribute to the development of osteoporosis. The single-nucleotide polymorphism (SNP) rs2887571 is predicted from genome-wide association studies (GWASs) to associate with osteoporosis but has had an unknown mechanism. Analysis of osteoblasts from 110 different individuals who underwent joint replacement revealed that the genotype of rs2887571 correlates with WNT5B expression. Analysis of our ChIP-sequencing data revealed that SNP rs2887571 overlaps with an estrogen receptor alpha (ERα) binding site. Here we show that 17ß-estradiol (E2) suppresses WNT5B expression and further demonstrate the mechanism of ERα binding at the enhancer containing rs2887571 to suppress WNT5B expression differentially in each genotype. ERα interacts with NFATc1, which is predicted to bind directly at rs2887571. CRISPR-Cas9 and ChIP-qPCR experiments confirm differential regulation of WNT5B between each allele. Homozygous GG has a higher binding affinity for ERα than homozygous AA and results in greater suppression of WNT5B expression. Functionally, WNT5B represses alkaline phosphatase expression and activity, decreasing osteoblast differentiation and mineralization. Furthermore, WNT5B increases interleukin-6 expression and suppresses E2-induced expression of alkaline phosphatase during osteoblast differentiation. We show that WNT5B suppresses the differentiation of osteoblasts via receptor tyrosine kinase-like orphan receptor 1/2 (ROR1/2), which activates DVL2/3/RAC1/CDC42/JNK/SIN3A signaling and inhibits ß-catenin activity. Together, our data provide mechanistic insight into how ERα and NFATc1 regulate the non-coding SNP rs2887571, as well as the function of WNT5B on osteoblasts, which could provide alternative therapeutic targets for osteoporosis.

Interleukin-1 and Interleukin-6 Polymorphisms Might Influence Predisposition to Hemorrhagic Cerebral Vascular Diseases: A Meta-Analysis.

BACKGROUND: Interleukin-1 (IL-1) and IL-6 polymorphisms might influence predisposition to hemorrhagic cerebral vascular diseases, but the results of already published studies regarding relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases were still controversial and ambiguous. OBJECTIVES: The authors designed this meta-analysis to more precisely estimate the relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases by pooling the results of already published related studies. METHODS: The authors searched PubMed, EMBASE, Web of Science, and CNKI for already published studies. Eighteen already published studies were pooled analyzed in this meta-analysis. RESULTS: The pooled meta-analyses' results showed that distributions of IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms among patients and controls differed significantly. Moreover, distribution of the IL-6 rs1800795 polymorphism among patients and controls from Asians also differed significantly. Further analyses showed similar findings for IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms in aneurysmal subarachnoid hemorrhage (aSAH) subgroup. CONCLUSIONS: This meta-analysis suggested that IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms might influence susceptibility to hemorrhagic cerebral vascular diseases, especially for aSAH. Moreover, IL-6 rs1800795 might influence susceptibility to hemorrhagic cerebral vascular diseases in Asians.

GATA4 regulates mesenchymal stem cells via direct transcriptional regulation of the WNT signalosome.

GATA4 is a transcription factor that regulates osteoblast differentiation. However, GATA4 is expressed at a higher level in mesenchymal stem cells (MSCs) than in osteoblasts. Therefore, the role of GATA4 in limb bud mesenchyme differentiation was investigated in mice by knocking out Gata4 using Cre-recombinase controlled by the Prx1 promoter (herein called Gata4 Prx-cKO mice). µCT analysis of the Gata4 Prx-cKO mice showed a decrease in trabecular bone properties compared with wildtype (Gata4fl/fl) littermates. Gata4 Prx-cKO mice have fewer MSCs as measured by CFU-F assays, mesenchymal progenitor cells (MPC2) (flow cytometry of Sca1+/CD45-/CD34-/CD44hi) and nestin immunofluorescence. Gata4 Prx-cKO bone marrow-derived MSCs have a significant reduction in WNT ligands, including WNT10B, and WNT signalosome components compared to control cells. Chromatin immunoprecipitation demonstrates that GATA4 is recruited to enhancers near Wnt3a, Wnt10b, Fzd6 and Dkk1. GATA4 also directly represses YAP in wildtype cells, and the absence of Gata4 leads to increased YAP expression. Together, we show that the decrease in MSCs is due to loss of Gata4 and a WNT10B-dependent positive autoregulatory loop. This leads to a concurrent increase of YAP and less activated ß-catenin. These results explain the decreased trabecular bone in Gata4 Prx-cKO mice. We suggest that WNT signalosome activity in MSCs requires Gata4 and Wnt10b expression for lineage specification.

Retraction Note: Long noncoding RNA MLK7-AS1 promotes ovarian cancer cells progression by modulating miR-375/YAP1 axis.

An amendment to this paper has been published and can be accessed via the original article.

Iron phosphide anchored nanoporous carbon as an efficient electrode for supercapacitors and the oxygen reduction reaction.

Inspired by their distinctive properties, transition metal phosphides have gained immense attention as promising electrode materials for energy storage and conversion applications. The introduction of a safe and large-scale method of synthesizing a composite of these materials with carbon is of great significance in the fields of electrochemical and materials sciences. In the current effort, we successfully synthesize an iron phosphide/carbon (FeP/C) with a high specific surface area by the pyrolysis of the gel resulting from the hydrothermal treatment of an iron nitrate-phytic acid mixed solution. In comparison with the blank (P/C), the as-synthesized FeP/C appears to be an efficient electrode material for supercapacitor as well as oxygen reduction reaction (ORR) applications in an alkaline medium in a three-electrode system. In the study of supercapacitors, FeP/C shows areal capacitance of 313 mF cm-2 at 1.2 mA cm-2 while retaining 95% of its initial capacitance value after 10 000 cycles, while in the ORR, the synthesized material exhibits high electrocatalytic activity with an onset potential of ca. 0.86 V vs. RHE through the preferred four-electron pathway and less than 6% H2O2 production calculated in the potential range of 0.0-0.7 V vs. RHE. The stability is found to be better than those of the benchmark Pt/C (20 wt%) catalyst.

Long noncoding RNA MLK7-AS1 promotes ovarian cancer cells progression by modulating miR-375/YAP1 axis.

BACKGROUND: Long noncoding RNAs (LncRNAs) have been reported to be abnormally expressed in human ovarian cancer and associated with the proliferation and metastasis of cancer cells. The objective of this study was to investigate the role and the underlying mechanisms of LncRNA MAP3K20 antisense RNA 1 (MLK7-AS1) in ovarian cancer. METHODS: The expression level of MLK7-AS1 was investigated in human ovarian cancer tissues and cell lines. The effects of MLK7-AS1 knockdown on ovarian cancer cell proliferation, migration, invasion and apoptosis were evaluated in vitro using MTT, colony formation assays, wound healing assays, transwell assays and flow cytometry. Furthermore, the in vivo effects were determined using the immunodeficient NSG female mice. Luciferase reporter assays were employed to identify interactions among MLK7-AS1 and its target genes. RESULTS: In the current study, MLK7-AS1 was specifically upregulated in ovarian cancer tissues and cell lines. Knockdown of MLK7-AS1 inhibited the ability of cell migration, invasion, proliferation, colony formation and wound healing, whereas promoted cell apoptosis in vitro. By using online tools and mechanistic analysis, we demonstrated that MLK7-AS1 could directly bind to miR-375 and downregulate its expression. Besides, MLK7-AS1 reversed the inhibitory effect of miR-375 on the growth of ovarian cancer cells, which might be involved in the upregulation of Yes-associated protein 1 (YAP1) expression. Moreover, knockdown MLK7-AS1 expression inhibited primary tumor growth in ovary and metastatic tumors in multiple peritoneal organs including liver and spleen in vivo, which were partly abolished by miR-375 inhibition. Mechanically, we found that MLK7-AS1 modulated the epithelial-mesenchymal transition (EMT) process by interacting with miR-375/YAP1 both in vivo and vitro, which promoted the expression of Slug. CONCLUSIONS: Taken together, our study showed for the first time that MLK7-AS1 interacted with miR-375 to promote proliferation, metastasis, and EMT process in ovarian cancer cells through upregulating YAP1.

Gold nanoparticles supported on mesoporous iron oxide for enhanced CO oxidation reaction.

Herein, we report the synthesis of gold (Au)-loaded mesoporous iron oxide (Fe2O3) as a catalyst for both CO and NH3 oxidation. The mesoporous Fe2O3 is firstly prepared using polymeric micelles made of an asymmetric triblock copolymer poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG). Owing to its unique porous structure and large surface area (87.0 m2 g-1), the as-prepared mesoporous Fe2O3 can be loaded with a considerably higher amount of Au nanoparticles (Au NPs) (7.9 wt%) compared to the commercial Fe2O3 powder (0.8 wt%). Following the Au loading, the mesoporous Fe2O3 structure is still well-retained and Au NPs with varying sizes of 3-10 nm are dispersed throughout the mesoporous support. When evaluated for CO oxidation, the Au-loaded mesoporous Fe2O3 catalyst shows up to 20% higher CO conversion efficiency compared to the commercial Au/Fe2O3 catalyst, especially at lower temperatures (25-150 °C), suggesting the promising potential of this catalyst for low-temperature CO oxidation. Furthermore, the Au-loaded mesoporous Fe2O3 catalyst also displays a higher catalytic activity for NH3 oxidation with a respectable conversion efficiency of 37.4% compared to the commercial Au/Fe2O3 catalyst (15.6%) at 200 °C. The significant enhancement in the catalytic performance of the Au-loaded mesoporous Fe2O3 catalyst for both CO and NH3 oxidation may be attributed to the improved dispersion of the Au NPs and enhanced diffusivity of the reactant molecules due to the presence of mesopores and a higher oxygen activation rate contributed by the increased number of active sites, respectively.

Porous nanozymes: the peroxidase-mimetic activity of mesoporous iron oxide for the colorimetric and electrochemical detection of global DNA methylation.

Nanomaterials (nanozymes) with peroxidase-mimetic activity have been widely used in biosensing platforms as low-cost, relatively stable and prevailing alternatives to natural enzymes. Herein, we report on the synthesis and application of the peroxidase-mimetic activity of mesoporous iron oxide (MIO) for the detection of global DNA methylation in colorectal cancer cell lines. The target DNA was extracted and denatured to get ssDNA followed by direct adsorption onto the surface of a bare screen-printed gold electrode (SPGE). A 5-methylcytosine antibody (5mC) functionalized nanomaterial (MIO-5mC) was then used to recognise the methylcytosine groups present on the SPGE. The MIO-5mC conjugates catalyse the TMB solution in the presence of hydrogen peroxide to give the colorimetric (i.e., naked-eye observation) and electrochemical detection of DNA methylation. The assay could successfully detect as low as 10% difference in the global DNA methylation level in synthetic samples and cell lines with good reproducibility and specificity (%RSD = <5%, for n = 3). This strategy avoids the use of natural enzyme horseradish peroxidase (HRP), traditional PCR based amplification and bisulfite treatment steps that are generally used in many conventional DNA methylation assays. We envisage that our assay could be a low-cost platform with great potential for genome-wide DNA methylation analysis in point-of-care applications.

Shape-controlled synthesis of mesoporous iron phosphate materials with crystallized frameworks.

Herein, we report the preparation of crystalline mesoporous iron phosphate (FePO4, hereafter abbreviated as FeP) materials with 2D-plates and 1D-rods in the presence of an amphiphilic block copolymer (F127), iron nitrate, and phosphoric acid. The dimensionality of mesoporous FeP can be switched by changing the polarity of the synthetic medium.