Nitrogen and Sulfur Co-Doped Carbon-Coated Ni3 S2 /MoO2 Nanowires as Bifunctional Catalysts for Alkaline Seawater Electrolysis.

Bifunctional catalysts have inherent advantages in simplifying electrolysis devices and reducing electrolysis costs. Developing efficient and stable bifunctional catalysts is of great significance for industrial hydrogen production. Herein, a bifunctional catalyst, composed of nitrogen and sulfur co-doped carbon-coated trinickel disulfide (Ni3 S2 )/molybdenum dioxide (MoO2 ) nanowires (NiMoS@NSC NWs), is developed for seawater electrolysis. The designed NiMoS@NSC exhibited high activity in alkaline electrolyte with only 52 and 191 mV overpotential to attain 10 mA cm-2 for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively. Significantly, the electrolyzer (NiMoS@NSC||NiMoS@NSC) based on this bifunctional catalyst drove 100 mA cm-2 at only 1.71 V along with a robust stability over 100 h in alkaline seawater, which is superior to a platinum/nickel-iron layered double hydroxide couple (Pt||NiFe LDH). Theoretical calculations indicated that interfacial interactions between Ni3 S2 and MoO2 rearranged the charge at interfaces and endowed Mo sites at the interfaces with Pt-like HER activity, while Ni sites on Ni3 S2 surfaces at non-interfaces are the active centers for OER. Meanwhile, theoretical calculations and experimental results also demonstrated that interfacial interactions improved the electrical conductivity, boosting reaction kinetics for both HER and OER. This study presented a novel insight into the design of high-performance bifunctional electrocatalysts for seawater splitting.

Label-free and highly sensitive detection of microRNA from cancer cells via target-induced cascade amplification generation of lighting-up RNA aptamers.

The abnormal expression levels of miRNAs have been proven to be highly related to the generation of various diseases and are also closely associated with the stages and types of disease development. The novel RNA aptamers-based homogenous fluorescent methods were simple, with low background signal and high signal-to-noise ratio, but lacked effective signal amplification technology to achieve sensitive detection of trace miRNA markers. There is an urgent need for combining effective nucleic acid amplification technology with RNA aptamer to achieve highly sensitive and accurate detection of miRNA. For this purpose, a new DNA multi-arm nanostructure-based dual rolling circle transcription machinery for the generation of lighting-up MG RNA aptamers is constructed for label-free and highly sensitive sensing of miRNA-21. In this system, the target miRNA-21 induces a structural transformation of the DNA multi-arm nanostructure probe to recycle miRNA-21 and trigger two independent rolling circle transcription reactions to generate two long RNAs, which can partially hybridize with each other to generate large amounts of complete MG RNA aptamers. These RNA aptamers can associate with organic MG dye to produce significantly enhanced fluorescence signals to accomplish ultrasensitive miRNA-21 detection down to 0.9 fM. In addition, this method exhibits high selectivity to distinguish miRNA-21 even with single nucleotide mismatch, and also has potential application capability to monitor different expression levels of miRNA-21 from different cancer cells. The effective collaboration between MG RNA aptamer and rolling circle transcription reaction makes this fluorescent method show the significant advantages of low background signal, high signal-to-noise ratio and high detection sensitivity. It has great potential to be a promising means to achieve label-free and highly sensitive monitoring of other trace biological markers via a simple change of target sequence.

In-situ reconstruction of rock-like 3D hierarchical MIL-53(Fe) self-supporting electrode with oxygen vacancy induced ultra-long stable and efficient water oxidation.

The exploitation of efficient, stable and cheap electrocatalyst for oxygen evolution reaction (OER) is very significant to the development of energy technology. In this study, Fe-based metal-organic frameworks (MIL-53(Fe)) self-supporting electrode with a 3D hierarchical open structure was developed through a semi-sacrificial strategy. The self-supporting electrode exhibits an excellent OER performance with an overpotential of 328 mV at 100 mA cm-2 in 1 M KOH, which is superior than that of IrO2 catalyst. Importantly, the optimized self-supporting electrode could operate at 100 mA cm-2 for 520 h without visible decrease in activity. It was also found that the structure of MIL-53(Fe) was in-situ self-reconstructed into oxyhydroxides during OER process. However, the 3D hierarchical open structure assembled with nano-microstructures kept well, which ensured the long-term stability of our self-supporting electrode for OER. Furthermore, density functional theory (DFT) calculations reveal that the FeOOH with rich oxygen vacancy transformed from MIL-53(Fe) plays a key role for the OER catalytic activity. And, the uninterrupted formation of oxygen vacancy during OER process ensures the continuous OER catalytic activity, which is the original source for the ultra-long stability of the self-supporting electrode toward OER. This work explores the way for the construction of efficient self-supporting oxygen electrodes based on MOFs.

Regulation of the electronic structure of a RuNi/MoC electrocatalyst for high-efficiency hydrogen evolution in alkaline seawater.

Alkaline seawater electrolysis offers a way to generate hydrogen without carbon emissions. However, developing highly efficient catalysts that can sustain high performance and stability for the hydrogen evolution reaction (HER) in alkaline seawater is a formidable challenge. Here, a nanowire (NW) of a RuNi/MoC heterojunction embedded in N-doped carbon (RuNi/MoC@NC) was developed as a potent HER catalyst. The catalyst required only 21 mV at 10 mA cm-2 for HER in alkaline seawater, which surpasses 20% Pt/C. Moreover, using nickel foam (NF) as a catalyst carrier, an electrolyzer composed of RuNi/MoC@NC and nickel-iron layered double hydroxide (NiFe LDH) needed only 1.81 V at 500 mA cm-2 for full water splitting and showed long-term stability (over 500 h). Theoretical calculation revealed that the Ru and Ni sites in the catalyst had the optimal adsorption energy for hydrogen and water, respectively, which synergistically lowered the energy barrier for HER. This work offered an efficient method to design a highly effective HER catalyst for alkaline seawater splitting.

Interfacial Electron Regulation and Composition Evolution of NiFe/MoC Heteronanowire Arrays for Highly Stable Alkaline Seawater Oxidation.

In alkaline seawater electrolysis, the oxygen evolution reaction (OER) is greatly suppressed by the occurrence of electrode corrosion due to the formation of hypochlorite. Herein, a catalyst consisting of MoC nanowires modified with NiFe alloy nanoparticles (NiFe/MoC) on nickel foam (NF) is prepared. The optimized catalyst can deliver a large current density of 500 mA cm-2 at a very low overpotential of 366 mV in alkaline seawater, respectively, outperforming commercial IrO2 . Remarkably, an electrolyzer assembled with NiFe/MoC/NF as the anode and NiMoN/NF as the cathode only requires 1.77 V to drive a current density of 500 mA cm-2 for alkaline seawater electrolysis, as well as excellent stability. Theory calculation indicates that the initial activity of NiFe/MoC is attributed to increased electrical conductivity and decreased energy barrier for OER due to the introduction of Fe. We find that the change of the catalyst in the composition occurred after the stability test; however, the reconstructed catalyst has an energy barrier close to that of the pristine one, which is responsible for its excellent long-term stability. Our findings provide an efficient way to construct high-performance OER catalysts for alkaline seawater splitting.

Programmable bidirectional dynamic DNA nano-device for accurate and ultrasensitive fluorescent detection of trace MUC1 biomarker in serums.

Accurate and ultrasensitive detection of biomarkers is significance for the diagnosis of diseases at early stage. For this purpose, we herein develop a bidirectional dynamic DNA nano-device for amplified fluorescent detection of tumor marker of mucin 1 (MUC1). The nano-device is constructed by immobilizing two sets of DNA cascade catalytic probes on two opposite directions of a single-stranded DNA tracker to limit probe reactants to a compact space. Once target MUC1 binds to the aptamer sequence, the initiator DNA locked in the duplex DNA substrate can be released to induce DNA-initiated cascade hybridization reactions (DCHRs) simultaneously in two opposite directions along the tracker DNA, accompanying the displacement of two quencher labeled-DNA intermediate initiators to facilitate successively execution of DCHRs on the DNA nano-devices, which results in the separation of fluorophore (FAM) and quencher (Dabycl) to produce substantially recovered fluorescent signals for rapid and sensitive detection of MUC1 with a detection limit down to 0.18 pM. In addition, this strategy also exhibits high selectivity against other interfering proteins and potential application capacity in real serum samples, indicating its promising application prospects in disease diagnosis and treatment.

miR-3196 acts as a Tumor Suppressor and Predicts Survival Outcomes in Patients With Gastric Cancer.

BACKGROUND: Gastric cancer is one of the most common malignancies worldwide with high mortality. Therefore, identifying cancer-related biomarkers for predicting prognosis and progression of gastric cancer is essential. This study aimed to investigate the clinical value and functional role of microRNA-3196 in gastric cancer. METHODS: The relative expression levels of microRNA-3196 in gastric cancer tissues and adjacent normal tissues were detected by quantitative reverse transcription-polymerase chain reaction. In this study, quantitative reverse transcription-polymerase chain reaction, cell proliferation assay, and Transwell migration and invasion assays were performed to explore microRNA-3196 expression level and its effects on cell proliferation, migration, and invasion in gastric cancer cells. The Kaplan-Meier method and multivariate Cox regression analyses were used to explore the prognostic significance of microRNA-3196 in gastric cancer. Dual-luciferase report assay was performed to validate the potential target gene regulated by microRNA-3196 in gastric cancer. RESULTS: The expression of microRNA-3196 was downregulated in gastric cancer tissues and cell lines. Downregulation of microRNA-3196 was associated with lymph node metastasis and Tumor Node Metastasis (TNM) stage. The Kaplan-Meier curve analysis indicated that patients with low expression of microRNA-3196 had a poor prognosis, and the Cox regression analysis results showed microRNA-3196 expression was an independent prognostic factor of gastric cancer. Moreover, overexpression of microRNA-3196 inhibited cell proliferation, migration, and invasion, while knockdown of microRNA-3196 promoted these cellular behaviors in AGS and MKN45 cells. OTX1 may be a potential target gene regulated by microRNA-3196 in gastric cancer. CONCLUSIONS: These results suggested that microRNA-3196 might not only a tumor suppressor in gastric cancer cells by modulating OTX1 but also might be an independent prognostic biomarker and therapeutic target of gastric cancer.

Downregulation of miR-484 is associated with poor prognosis and tumor progression of gastric cancer.

BACKGROUND: Gastric cancer is one of the most common cancers leading to high cancer mortality. MicroRNA-484 (miR-484) has been evaluated as a biomarker for various types of cancers. The subject of this study is to investigate the functional role of miR-484 in gastric cancer. METHODS: The expression of miR-484 in gastric cancer was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Kaplan-Meier survival and Cox regression analyses were employed to explore the prognostic significance of miR-484 in gastric cancer. The functional role of miR-484 in gastric cancer was determined by CCK-8 and Transwell assays. RESULTS: The results showed that miR-484 was significantly downregulated in gastric cancer tissues and cell lines. The downregulation of miR-484 was closely related to differentiation, lymph node metastasis, TNM stage, and poor prognosis. Cox regression analyses demonstrated that miR-484 was an independent prognosis indicator for gastric cancer patients. Additionally, the downregulation of miR-484 enhanced cell proliferation, migration, and invasion in gastric cancer cells. CONCLUSION: These data demonstrated that miR-484 can serve as a potential prognostic biomarker and therapeutic target for gastric cancer and it may be involved in the progression of gastric cancer.

Synthesis of Gelatin-Based Dual-Targeted Nanoparticles of Betulinic Acid for Antitumor Therapy.

Betulinic acid (BA) is a natural antitumor agent and has biological activity against multiple human tumor cell lines with low cytotoxicity to normal cells, while the high hydrophobicity and the short half-life of this compound limit its clinical application. Here, gelatin-based dual-targeted nanoparticles of BA are promising to solve this problem. Hydrophobic BA is loaded in cyclodextrin to increase its solubility and prolong the circulation time in vivo. The nanoscale drug delivery systems can further enhance the bioavailability and the antitumor effect of BA and are passively targeted to the tumor tissue sites by enhanced permeability and retention effect. The RGD sequence of gelatin specifically recognizes tumor cells and brings agents into tumor cells. The nanoparticles were characterized by transmission electron microscopy, Fourier transform infrared, nuclear magnetic resonance, etc. In addition, we observed antitumor activity of the nanoparticles using both cell-based assays and mouse xenograft tumors, which proved that betulinic acid/gelatin-γ-cyclodextrin nanoparticles had a better tumor inhibition effect than betulinic acid/γ-cyclodextrin inclusion compound.

Influence of verapamil on the pharmacokinetics of oridonin in rats.

Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear.Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism.Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes.Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 µL/min/mg protein).Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug-drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic.

Tumor-Targeting Peptide for Redox-Responsive Pt Prodrug and Gene Codelivery and Synergistic Cancer Chemotherapy.

A new codelivery system combining prodrug strategy, siRNA/BAplatin @CRGDK NPs, to overcome cisplatin (CDDP) resistance in human breast cancer was designed and researched. Negatively charged siRNA was deposited onto the surface of tumor-targeting peptide-functionalized BAplatin@CRGDK NPs. SiRNA/BAplatin@CRGDK NPs could facilitate cellular uptake of BAplatin and increase the cell proliferation suppression effect of Pt against MDA-MB-231/DDP cells. The tumor-to-kidney uptake ratio of the siRNA/BAplatin@CRGDK NPs in MB-231/DDP tumors is 2.4-fold higher than that of cisplatin in MB-231/DDP tumors, thus giving rise to more significant antitumor efficacy. It demonstrated that the siRNA/BAplatin@CRGDK NPs is a potential, safe, and efficient therapeutic agent for cancer therapy.

NMDA receptor subunit and CaMKII changes in rat hippocampus by congenital HCMV infection: a mechanism for learning and memory impairment.

The aim of this study was to investigate the effects of congenital human cytomegalovirus infection on the expression levels of N-methyl-D-aspartate receptors (NRs) and Ca/calmodulin-dependent protein kinase II (CaMKII) in the hippocampal neurons of neonatal Sprague-Dawley (SD) rats. Pregnant SD rats were divided into an experimental group and a control group (n=10 in each group). Spatial learning and memory of the offspring of SD rats were evaluated using the Morris water-maze test. Pathological studies of hippocampus sections were carried out. The concentration of [Ca] was measured using a dual-wavelength spectrophotometer method. The expression levels of NRs were detected by an immunohistochemical study. Western blot was performed to detect the expression level of CaMKII. In the Morris water-maze test, the rats in the experimental group showed significantly increased escape latency and distance traveled than the control group. Damaged and structural disorders of the dentate granule in the hippocampus were found in the experimental rats. Immunohistochemistry results showed that the expression levels of NR subunits in the hippocampus of the experimental group were significantly decreased. The concentration of [Ca] in the experimental group was significantly increased. In contrast, the level of CaMKII in the experimental group was significantly decreased. The expressions of the NR subunit and CaMKII were decreased in rat hippocampus by human cytomegalovirus congenital infection, which may be associated with the mechanism underlying the impairment of learning and memory function.