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A layer-by-layer (LbL) assembly strategy was developed to prepare multilayered double hydroxide/polyoxometalate shell-coated magnetic nanoparticles. The introduction of functional shells not only offered abundant affinity sites of metal oxide and metal ions but also increased the surface area for the contact with targets. By combining the enrichment strategies of immobilized metal ion affinity chromatography and metal oxide affinity chromatography, the nanomaterial can capture phosphopeptides via a synergistic effect. The method presented a low detection limit of 0.1 fmol in combination with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis. The nanomaterial showed satisfactory selectivity (1:1:5000 M ratio of α-/ß-casein/bovine serum albumin), good recovery (92.07%), high adsorption capacity (117.6 mg g-1), and ten times reusability for capturing phosphopeptides.
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Nanopartículas de Magnetita , Fosfopéptidos , Aniones , Caseínas , Cromatografía de Afinidad/métodos , Hidróxidos , Nanopartículas de Magnetita/química , Óxidos , Fosfopéptidos/análisis , PolielectrolitosRESUMEN
OBJECTIVE: Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men which is associated with profound metabolic changes. Systematic analysis of the metabolic alterations and identification of new biomarkers may benefit PCa diagnosis and a deep understanding of the pathological mechanism. The purpose of this study was to determine the metabolic features of PCa. METHODS: Plasma and urine metabolites from 89 prostate cancer (PCa) patients, 84 benign prostatic hyperplasia (BPH) patients, and 70 healthy males were analyzed using LC-MS/MS and GC-MS. The Orthogonalised Partial Least Squares Discriminant Analysis (OPLS-DA) was used to find the significantly changed metabolites. The clinical value of the candidate markers was examined by receiver operating characteristic curve analysis and compared with prostate-specific antigen (PSA). RESULTS: Multivariate statistical analyses found a series of altered metabolites, which related to the urea cycle, tricarboxylic acid cycle (TCA), fatty acid metabolism, and the glycine cleavage system. Plasma Glu/Gln showed the highest predictive value (AUC = 0.984) when differentiating PCa patients from healthy controls, with a higher sensitivity than PSA (96.6% vs. 94.4%). Both Glu/Gln and PSA displayed a low specificity when differentiating PCa patients from BPH patients (<53.2%), while the combination of Glu/Gln and PSA can further increase the diagnostic specificity to 66.9%. CONCLUSIONS: The present study showed the metabolic features of PCa, provided strong evidence that the amide nitrogen and the energy metabolic pathways could be a valuable source of markers for PCa. Several candidate markers identified in this study were clinically valuable for further assessment.
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Cromatografía Liquida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Nitrógeno/metabolismo , Próstata , Hiperplasia Prostática , Neoplasias de la Próstata , Anciano , Metabolismo Energético , Humanos , Masculino , Redes y Vías Metabólicas , Metabolómica/métodos , Tamaño de los Órganos , Próstata/diagnóstico por imagen , Próstata/metabolismo , Próstata/patología , Antígeno Prostático Específico/análisis , Hiperplasia Prostática/sangre , Hiperplasia Prostática/patología , Hiperplasia Prostática/orina , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/orina , Reproducibilidad de los ResultadosRESUMEN
Lithium/sulfur (Li/S) batteries have emerged as one of the most promising next-generation energy storage systems with advantages of high theoretical energy density, low cost and environmental friendliness. However, problems regarding to severe shuttle effect of soluble polysulfide, poor electronic/ionic conductor of solid charged/discharged products (S8 and Li2S), and fatal swell of volume along with the growth of Li dendrites greatly deteriorate the sulfur utilization and capacity retention during extended charge-discharge cycles. With advantages of high nitrogen content, lithiophilic modulation and tunable charge density and charge transfer, carbon nitride (g-C3N4) has played a positive role in restricting the shuttle effects and dendrite formation. This minireview mainly discusses these research achievements of g-C3N4 in Li/S batteries, aiming to provide a basic understanding and direct guidance for further research and development of functionalized g-C3N4 materials in electrical energy storage. The two-dimensional (2D) structure of g-C3N4 with abundant hierarchical pores improves its accommodation capacity for sulfur by effectively confining the lithium polysulfides (LiPSs) into the pores, and provides favorable channels for ion diffusion. The rich nitrogen and carbon defects further offer more active sites for strongly adsorbing LiPSs and bridge electron transfer pathway at atomic scale for catalytic reactions to accelerate redox kinetics of Li/S conversion chemistry. Moreover, the features of lithiophilic wettability, high adsorption energy and densely distributed lithiophilic N of g-C3N4 provide a large number of adhesive sites for lithium cation (Li+) and disperse the nucleation sites to enable uniform nucleation and deposition of Li on the anode surface and to suppress formation and growth of Li dendrites. Finally, the g-C3N4 also effectively regulates the wettability between Li anode and solid inorganic electrolyte, and reduces the crystallinity of solid polymer electrolyte to enhance the Li+ migration ability and ionic conductivity.
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The selective decomposition of formic acid (FA) traditionally needs to be carried out under high temperature with the noble metal-based catalysts. Meanwhile, it also encounters a separation of H2and CO2for pure H2production. The photocatalytic FA dehydrogenation under mild conditions can meet a growing demand for sustainable H2generation. Here, we reported a photocatalytic selective H2release from FA decomposition at low temperature for pure H2production by Pt/g-C3N4. Low-cost and easy-to-obtained urea was utilized to produce carbon nitride as the metal-free semiconductor photocatalyst, along with a photodeposition to obtain Pt/g-C3N4. The electrochemical evidences clearly demonstrate the photocatalytic activity of Pt/g-C3N4to produce H2and CO2in one-step FA decomposition. And, the impedance is the lowest under simulated solar light of 70 mW cm-2with a faster electron transfer kinetic. Under simulated solar light, H2production rate is up to 1.59 mmol · h-1· g-1for FA with concentration at 2.65 mol l-1, 1700 000 times larger than that under visible light and 1928 times under ultraviolet (UV) light. DFT calculations further elucidate that nitrogen (N) active site at the g-C3N4has an excellent adsorption towards CO2molecule capture. Then, H2molecules are selectively released to simultaneously separate H2and CO2in solution. Platinum (Pt) at Pt/g-C3N4as the catalytic site contributes into the acceleration of H2production.
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Chemical fabrication of a nanocomposite structure for electrode materials to regulate the ion diffusion channels and charge transfer resistances and Faradaic active sites is a versatile strategy towards building a high-performance supercapacitor. Here, a new ternary flower-sphere-like nanocomposite MnO2-graphite (MG)/reduced graphene oxide (RGO) was designed using the RGO as a coating for the MG. MnO2-graphite (MnO2-4) was obtained by KMnO4 oxidizing the pretreated graphite in an acidic medium (pH = 4). The GO coating was finally reduced by the NaBH4 to prepare the ternary nanocomposite MG. The microstructures and pore sizes were investigated by x-ray diffraction, scanning electron microscopy, thermogravimetric analysis, and nitrogen adsorption/desorption. The electrochemical properties of MG were systematically investigated by the cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy in Na2SO4 solution. The MG as an electrode material for supercapacitor exhibits a specific capacitance of 478.2 and 454.6 F g-1 at a current density of 1.0 and 10.0 A g-1, respectively. In addition, the capacitance retention was 90% after 8,000 cycles. The ternary nanocomposite enhanced electrochemical performance originates from the specific flower-sphere-like morphology and coating architecture bringing higher specific surface area and lower charge transfer resistance (Rct).
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Exfoliated magadiite nanosheets embedded with Fe3O4 were constructed. Advantage was taken of the strong coordination between the silanol groups in magadiite nanosheets and the Gd3+ ion to prepare the final adsorbent, Gd3+-immobilized magnetic magadiite nanosheets. The adsorbent with two-dimensional (2D) morphology offered high surface area and abundant Gd3+ contents for phosphopeptides enrichment, on which Fe3O4 with positive electricity incorporated the magnetic properties. Combining with matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI TOF-MS), the method showed low detection limit (0.05 fmol). The feasibility of using the 2D nanocomposite for phosphopeptides enrichment was demonstrated using mixtures of ß-casein and bovine serum albumin (1:5000). The standard deviation of captured phosphopeptides in three repeated experiments were in the range 0.15-0.42 (< 0.5% RSD). Further evaluation revealed that the nanocomposite was capable of enriching phosphopeptides from non-fat milk, human saliva, and serum. A novel Gd3+-immobilized two-dimensional magnetic magadiite nanosheets-based enrichment platform was designed. The developed material was employed as the adsorbent for the selective enrichment of phosphopeptides by coupling with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The material was successfully applied to enrich phosphopetides from standard peptide mixtures, nonfat milk, human saliva, and serum.
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Gadolinio/química , Extracción Líquido-Líquido/métodos , Nanoestructuras/química , Fosfopéptidos/aislamiento & purificación , Silicatos/química , Adsorción , Animales , Caseínas/química , Caseínas/aislamiento & purificación , Bovinos , Óxido Ferrosoférrico/química , Humanos , Límite de Detección , Fenómenos Magnéticos , Leche/química , Fosfopéptidos/química , Saliva/química , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/aislamiento & purificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Conducting polymers tethered with molecular recognition elements are good candidates for biosensing applications such as detecting a target molecule with selectivity. We develop a new monomer, namely, 3,4-ethylenedioxythiophene bearing a pyridylboronic acid moiety (EDOT-PyBA), for label-free detection of sialic acid as a cancer biomarker. PyBA, which is known to show specific binding to sialic acid in acid conditions is used as a synthetic ligand instead of lectins. PyBA confirms the enhanced binding affinity for sialic acid at pH 5.0-6.0 compared with traditional phenylboronic acid. Poly(EDOT-PyBA) is electrodeposited on a planar glassy carbon electrode and the obtained film is successfully characterized by X-ray photoelectron spectroscopy, scanning electron microscopy, atomic force microscopy, water contact angle measurements, and electrochemical impedance spectroscopy. The specific interaction of PyBA with sialic acid at the solution/electrode interface is detected by differential pulse voltammetry in a dynamic range 0.1-3.0 mM with a detection limit of 0.1 mM for a detection time of 3 min. The sensitivity covers the total level of free sialic acid in human serum and the assay time is the shorter than that of other methods. The poly(EDOT-PyBA) electrode successfully detects spiked sialic acid in human serum samples. Owing to its processability, mass productivity, and robustness, polythiophene conjugated with "boronolectin" is a candidate material for developing point-of-care and wearable biosensors.
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Precise catalytic regulation of carbon radical generation by a highly active oxygen radical to abstract the H atom in a C-H bond is an effective method for the selective activation of C-H synthetic chemistry. Herein, we report a facile catalyst system with commercially available copper(II)/{PMo12} to form a tert-butanol radical intermediate for the selective oxidation of benzylic C-H bonds. The reaction shows a broad range of substrates (benzyl methylene, benzyl alcohols) with good functional group tolerance and chemical selectivity. The corresponding carbonyl compounds were synthesized with good yields under mild conditions. DFT calculations and experimental analysis further demonstrated a reasonable carbon radical mechanism for this type of organic transformation reaction.
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An efficient and refined method for the separation of six aconitine-type alkaloids from the alkaline prepared "Kusnezoff monkshood root" was established. It is the first study that two new lipo-alkaloids were successfully isolated from refined sample by pH-zone-refining counter-current chromatography rather than synthetic method. It was of interest that a great deal of lipo-alkaloids was produced in crude extract from the alkalization of "Kusnezoff monkshood root." A refined sample method was proposed to enrich two types of alkaloids by liquid-liquid extraction, i.e. lipo-alkaloids and monoester-diterpenoid alkaloids. The pH-zone-refining counter-current chromatography was performed with an optimized two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3:5:4:5, v/v), where upper organic phase was added to 3 mmol/L triethylamine as a retainer and lower aqueous mobile phase was added to 3 mmol/L hydrochloric acid as an eluter. As a result, six aconitum alkaloids, including two lipo-alkaloids (8-lino-14-benzoylaconine, 8-pal-14-benzoylaconine), three monoester-diterpenoid alkaloids (14-benzoylmesaconine, 14-benzoylaconine, beyzoyldeoxyaconine), and one aconine alkaloid (neoline) were acquired from the plant at the same time. The anti-inflammatory activities of the two new lipo-alkaloids were compared to the six alkaloids in vitro, in cyclo-oxygen-ase-2 inhibition assays. The separation mechanism of six alkaloids by pH-zone-refining counter-current chromatography was illustrated.
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Aconitum/química , Alcaloides/aislamiento & purificación , Antiinflamatorios/aislamiento & purificación , Inhibidores de la Ciclooxigenasa 2/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Alcaloides/química , Alcaloides/farmacología , Amoníaco/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Bicarbonatos/química , Distribución en Contracorriente , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/farmacología , Concentración de Iones de Hidrógeno , Extracción Líquido-Líquido , Conformación Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Most prostate cancers (Pcas) develop into castration-resistant prostate cancer (CRPC) after receiving androgen deprivation therapy (ADT). The expression levels of PLCε and wnt3a are increased in Pca and regulate androgen receptor (AR) activity. However, the biological function and mechanisms of PLCε and wnt3a in CRPC remain unknown. In this study, we found that the expression levels of PLCε, wnt3a, and AR were significantly increased in CRPC tissues as well as bicalutamide-resistant-LNCaP and enzalutamide-resistant-LNCaP cells. In addition, PLCε knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and enzalutamide by inhibiting the activity of the wnt3a/ß-catenin/AR signaling axis. Interestingly, the resistance of LNCaP cells docetaxel is related to PLCε but not the wnt3a/ß-catenin pathway. We also found that the combination of PLCε knockdown and enzalutamide treatment synergistically suppressed cell proliferation, tumor growth, and bone metastasis using in vitro and in vivo experiments. Our study revealed that PLCε is involved in the progression of drug-resistance in CRPC and could be a new target for the treatment of CRPC.
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Surface defects in relation to surface compositions, morphology, and active sites play crucial roles in photocatalytic activity of graphitic carbon nitride (g-C3N4) material for highly reactive oxygen radicals production. Here, we report a high-efficiency carbon nitride supramolecular hybrid material prepared by patching the surface defects with inorganic clusters. Fe (III) {PO4[WO(O2)2]4} clusters have been noncovalently integrated on surface of g-C3N4, where the surface defects provide accommodation sites for these clusters and driving forces for self-assembly. During photocatalytic process, the activity of supramolecular hybrid is 1.53 times than pure g-C3N4 for the degradation of Rhodamine B (RhB) and 2.26 times for Methyl Orange (MO) under the simulated solar light. Under the mediation of H2O2 (50 mmol L-1), the activity increases to 6.52 times for RhB and 28.3 times for MO. The solid cluster active sites with high specific surface area (SSA) defect surface promoting the kinetics of hydroxide radicals production give rise to the extremely high photocatalytic activity. It exhibits recyclable capability and works in large-scale demonstration under the natural sunlight as well and interestingly the environmental temperature has little effects on the photocatalytic activity.
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Novel sulfur (S) anchoring materials and the corresponding mechanisms for suppressing capacity fading are urgently needed to advance the performance of Li/S batteries. Here, we designed and synthesized a graphene-like oxygenated carbon nitride (OCN) host material that contains tens of micrometer scaled two-dimensional (2D) rippled sheets, micromesopores, and oxygen heteroatoms. N content can reach as high as 20.49 wt %. A sustainable approach of one-step self-supporting solid-state pyrolysis (OSSP) was developed for the low-cost and large-scale production of OCN. The urea in solid sources not only provides self-supporting atmospheres but also produces graphitic carbon nitride (g-C3N4) working as 2D layered templates. The S/OCN cathode can deliver a high specific capacity of 1407.6 mA h g(-1) at C/20 rate with 84% S utilization and retain improved reversible capacity during long-term cycles at high current density. The increasing micropores, graphitic N, ether, and carboxylic O at the large sized OCN sheet favor S utilization and trapping for polysulfides.
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In this paper, the CdS samples were prepared using thiourea or sodium sulfide as sulfur source by hydrothermal or solvothermal synthesis method, the results of XRD, TEM and SEM showed all the samples belong to hexagonal CdS nano-material with different morphologies. Using the degradation of methyl orange solution as a model reaction, the photocatalytic performance of different CdS samples was measured, and the samples prepared using thiourea as sulfur source exhibited better photocatalytic activity than those using sodium sulfide as sulfur source. The factors on degradation effect were discussed including the pH value of degradation system and the type of light source. The degradation effect of CdS samples increased with the pH value decreased, and the degradation effect was better when the methyl orange solution was irradiated under sunlight than under 250 W mercury lamp.
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Here, two-dimensional magnetic graphite nitride nanosheets were synthesized, over which molybdenum trioxide was distributed evenly. The magnetic nanocomposite served as an enrichment platform for phosphopeptides based on metal oxide affinity chromatography and anion-exchange chromatography. Owing to the abundant affinity sites, positive electricity, and large surface area, the nanocomposite had high selectivity (α-casein/ß-casein/bovine serum albumin, 1:1:5000), sensitivity (0.1 fmol), quantitative recovery (91.3%), and good recyclability (10 cycles). The nanocomposite also showed good enrichment performance for phosphopeptides from non-fat milk, human serum, saliva, and A549 cell lysate. The results demonstrated the value of this material in phosphorylated proteomics.
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Grafito , Nanocompuestos , Caseínas/química , Cromatografía de Afinidad/métodos , Grafito/química , Humanos , Fenómenos Magnéticos , Molibdeno , Nanocompuestos/química , Óxidos , Fosfopéptidos/química , Titanio/químicaRESUMEN
Two Sulfonate substituted rhodamine hydrophilic fluorescent probes RbS1 and RbS2 were designed and synthesized for specific detection of Fe3+. It was found that the probe RbS2 was stronger than RbS1 in the water solubility test. Both of them displayed responses to Fe3+ with a apparent fluorescence enhancement at 585 nm, accompanied with a distinct fluorescence change to pink. Upon addition of Fe3+ ions (0-16 µM), the emission intensity of RbS1 and RbS2 increased to 40 and 70 fold, which exhibited a good linear relationship with the concentration of Fe3+. The detection limits of RbS1 and RbS2 for sensing Fe3+ were 0.64 µM and 0.56 µM, respectively. The binding ratios of the RbS1 and RbS2 to Fe3+ were 1:1 and the recycling ability for Fe3+ was reasonable. RbS1 and RbS2 have been successfully applied to the determination of Fe3+ in real water samples with satisfactory recovery and accuracy. In further living fish imaging test, the probe RbS2 was distributed into abdomen, which exhibited better fluorescence imaging ability than that of RbS1.
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Colorantes Fluorescentes , Hierro , Animales , Imagen Óptica , Rodaminas , Espectrometría de FluorescenciaRESUMEN
Efficient enrichment and identification of phosphopeptides are of great significance in biological applications. Glycocyamine functionalized magnetic layered double hydroxides (Fe3O4@LDH@NH2-GAA) was fabricated through an easy process. The magnetic composite possessed high surface area, good biocompatibility, and fast magnetic response. Fe3O4@LDH@NH2-GAA, combining not only metal ions (Cu2+ and Ga3+) in LDH but also functional guanidyl groups in glycocyamine, offered multiple affinity sites for phosphopeptides enrichment. With these favorable characters, it exhibited high selectivity (ß-casein: bovine serum albumin = 1:5000), low detection limit (0.1 fmol), satisfactory enrichment recovery (94.5%), high adsorption capacity (82.4 mg g-1), and good repetitiveness. Moreover, the efficient enrichment of phosphopeptides by Fe3O4@LDH@NH2-GAA from nonfat milk, human saliva, serum, and A549 cell lysates further confirmed its great potential for trace biological detection and proteomic analysis.
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Fosfopéptidos , Proteómica , Caseínas , Glicina/análogos & derivados , Humanos , Hidróxidos , Fenómenos MagnéticosRESUMEN
An efficient Rh(iii)-catalyzed synthesis of 2-arylindole derivatives via intermolecular C-H annulation of arylhydrazines with sulfoxonium ylides was accomplished. A variety of 2-acetyl-1-arylhydrazines with sulfoxonium ylides were converted into 2-arylindoles in satisfactory yields. Excellent selectivity and good functional group tolerance of this transformation were also observed.
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BACKGROUND: Circular RNAs (circRNAs) play a crucial role in gene expression regulation. CircHIPK3 is a circRNA derived from Exon 2 of HIPK3 gene and its role in prostate cancer (PCa) is still unclear. METHODS: CCK8 assays, flow cytometry and colony formation assays were performed to assess the effects of circHIPK3 in PCa cells. Bioinformatics analysis, RNA pull-down assay, RNA immunoprecipitation assay (RIP), and luciferase activity assay were performed to dissect the mechanism underlying circHIPK3-mediated G2/M transition in PCa cells. RESULTS: CircHIPK3 expression was upregulated in PCa cells and prostate cancer tissues. Overexpression of circHIPK3 or circHIPK3 silencing altered PCa viability, proliferation and apoptosis in vitro. CircHIPK3 could sponge miR-338-3p and inhibit its activity, resulting in increased expression of Cdc25B and Cdc2 in vitro. CONCLUSION: CircHIPK3 promotes G2/M transition and induces PCa cell proliferation by sponging miR-338-3p and increasing the expression of Cdc25B and Cdc2. CircHIPK3 may play an oncogenic role in PCa.
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Constructing noble metal-free electrocatalytically active sites for the simultaneous hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline solution is key to realizing electricity-driven water splitting in practical applications. Here, we rationally designed Co(OH)2@CoSe nanorods (NRs) as an excellent bifunctional electrocatalyst by an in situ electrochemical transformation strategy, where the Co-based nanorod template was converted into Co(OH)2@CoSe at the cathode. The obtained electrode exhibits superior electrocatalytic activity for both the HER (overpotential of 208 mV at 20 mA cm-2) and the OER (268 mV at 20 mA cm-2) at high current density in a 1 M KOH solution. The theoretical calculations and experimental evidence indicate that the chemical coupling Co-OH active site between Co(OH)2 and CoSe regulates the hydrogen adsorption and desorption energy and fast electron transfer capability, which is responsible for the improved HER. Moreover, the Co(OH)2@CoSe NRs can be further converted into CoOOH nanosheets which serve as OER active sites. Toward practical electrolytic cell applications, the Co(OH)2@CoSe nanorods as both the cathode and anode achieved a current density of 100 mA cm-2 at 1.94 V for overall water splitting, better than that of noble metal-based electrocatalysts.
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Castration-resistant prostate cancer (CRPC) is a progressed stage of prostate cancer, which requires better understanding of the mechanisms and remains an unmet clinical need. As a common oncogene, K-Ras is associated with malignant behavior in different types of tumors but its role in CRPC is unknown. The present study aims to find the mechanism of K-Ras in CRPC and whether it can be used as a crucial molecule for the treatment of CRPC. For this purpose, tissue samples from primary prostate cancer (PPC) and CRPC patients were analyzed by immunohistochemistry and the data showed that K-Ras was elevated in CRPC. More importantly, higher K-Ras expression was related to a shorter recurrence-free survival time in patients with CRPC. In addition, K-Ras promoted the invasion, migration, and drug resistance of CRPC cells by activation of PLCε/PKCε signaling pathway. Meanwhile, the inhibitor of K-RasG12C mutants was able to inhibit malignant behavior of CRPC cells in vitro and in vivo. Inhibitors of K-RasG12C mutants have entered clinical trials. Taken together, the study shows that K-Ras may activate PKCε through PLCε, resulting in the alterations of malignant behavior of CRPC. Inhibitor 9, an inhibitor of the K-RasG12C mutant, has a strong anti-tumor effect in CRPC, which potentially suggests that inhibitors of this nature may serve as a promising treatment for CRPC.