The impact of tumor size on the prognosis and chemotherapy efficacy in stage I/II colon cancer patients.

Background: The impact of tumor size on the survival and chemotherapy reponse of early-stage colon cancer remains unclear. Our study explored the effect of tumor size on overall survival (OS) and postoperative chemotherapy efficacy in patients with stage I/II colon cancer. Methods: Stage I/II colon cancer patients from the Surveillance, Epidemiology and End Results (SEER) database and a China center were extracted as two cohorts respectively. X-tile program was adopted to acquire optimal cutoff points of tumor size (16mm and 49mm). Harrell's concordance index (c-index) and time-dependent receiver operating characteristic curve (ROC) were used to indicate discrimination ability of prognostic factors. Results: Overall, 104,908 and 168 stage I/II postoperative colon cancer patients from SEER database and a China center were eligible, respectively. Kaplan-Meier analysis showed that large tumor size was associated with poor OS in two cohorts. The effect of tumor size on OS gradually decreased as the T stage increased both before PSM (c-index 0.535 for T1N0M0 and 0.506 for T4N0M0, p<0.05) and after PSM (c-index 0.543 for T1N0M0, p<0.05; c-index 0.543 for T4N0M0, p>0.05). Stratified analyses showed that chemotherapy improved the OS rate by 9.5% (chemotherapy vs. non-chemotherapy: 83.5% vs. 73.0%) or 12.8% (chemotherapy vs. non-chemotherapy: 85.7% vs. 72.9%) before and after PSM in T2N0M0 patients with tumor size >49 mm, but not in T1N0M0. The survival benefit provided by chemotherapy for T2N0M0 patients with large tumor was also validated in the Chinese cohort. Conclusions: Large tumor size was a risk factor for stage I/II colon cancer, especially for T1N0M0. Tumor size could serve as a complementary factor guiding postoperative chemotherapy for T2N0M0 patients.

Tailoring the Hydrogen Spillover Effect in Ni-Based Heterostructure Catalysts for Boosting the Alkaline Hydrogen Oxidation Reaction.

Improving the catalytic efficiency of platinum group metal-free (PGM-free) catalysts for the sluggish alkaline hydrogen oxidation reaction (HOR) is crucial to the anion exchange membrane fuel cell. Recently, numerous Ni-based heterostructures have been designed based on bifunctional theory to enhance HOR activity by optimizing the binding energy of both H* and OH*; however, their activities are still far inferior to those of PGM catalysts. Indeed, the long transfer pathway for intermediates between different active sites in such heterostructures has rarely been investigated, which could be the reason for the bottleneck. Here, we design a Ni/MoOxHy heterostructure catalyst to promote H* migration from the Ni side to the interface for alkaline HOR via the hydrogen spillover effect. In situ X-ray absorption fine structure, Raman characterizations, H/D kinetic isotope effects, and theoretical calculations have proven facile H* migration from the Ni side to the interface, which further reacts with OH* on the MoOxHy surface. Besides, the hydrogen spillover effect is also beneficial for the preservation of the metallic phase of Ni during the reaction. The catalyst exhibits a high activity with Jk,m of 58.5 mA mgNi-1 and j0,s of 42 µA cmNi-2, which is among the best PGM-free catalysts and is even comparable to some PGM catalysts. It also shows the highest power density (511 mW cm-2) as a PGM-free anode when assembled into fuel cells under moderate back pressure. These findings prove that in addition to optimizing electrophilicity and oxophilicity for active sites, we could also improve the HOR activity from the transfer pathway for intermediates, which provides insight into the design of other efficient HOR catalysts.

Hydrogen sulfide inhibits skeletal muscle ageing by up-regulating autophagy through promoting deubiquitination of adenosine 5'-monophosphate (AMP)-activated protein kinase α1 via ubiquitin specific peptidase 5.

BACKGROUND: Hydrogen sulfide (H2S), the third gasotransmitter discovered, regulates a variety of physiological functions. Whether H2S alleviates skeletal muscle ageing by regulating autophagy has not been reported. METHODS: Mice were administered 150 mg/kg/day of D-galactose ( D-gal), and C2C12 myotubes were cultured in 20 g/L D-gal to induce ageing. Sodium hydrosulfide (NaHS) was employed as an exogenous donor in the treatment group. The intracellular concentration of H2S was quantified by the 7-azido-4-methylcoumarin fluorescence probe. The proteins involved in the ubiquitin-mediated degradation of AMPKα1 were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation (Co-IP). S-sulfhydration of USP5 was tested by a biotin-switch assay. Associated proteins were analysed by western blot. RESULTS: NaHS was found to effectively restore the H2S content in both ageing gastrocnemius (+91.89%, P < 0.001) and C2C12 myotubes (+27.55%, P < 0.001). In comparison to the D-gal group, NaHS was observed to increase the mean cross-sectional area of muscle fibres (+44.91%, P < 0.001), to decrease the collagen volume fraction of gastrocnemius (-81.32%, P = 0.001) and to reduce the ß-galactosidase-positive area of C2C12 myotubes (-28.74%, P < 0.001). NaHS was also found to reverse the expression of muscle atrophy F box protein (MAFbx), muscle-specific RING finger protein 1 (MuRF1), Cyclin D1 and p21 in the ageing gastrocnemius tissue (MAFbx: -31.73%, P = 0.008; MuRF1: -32.37%, P = 0.003; Cyclin D1: +45.34%, P = 0.010; p21: -25.53%, P = 0.022) and C2C12 myotubes (MAFbx: -16.38%, P < 0.001; MuRF1: -16.45%, P = 0.003; Cyclin D1: +40.23%, P < 0.001; p21: -35.85%, P = 0.026). The AMPKα1-ULK1 pathway was activated and autophagy was up-regulated in NaHS-treated gastrocnemius tissue (p-AMPKα1: +61.61%, P = 0.018; AMPKα1: +30.64%, P = 0.010; p-ULK1/ULK1: +85.87%, P = 0.005; p62: -29.07%, P < 0.001; Beclin1: +24.75%, P = 0.007; light chain 3 II/I [LC3 II/I]: +55.78%, P = 0.004) and C2C12 myotubes (p-AMPKα1: +77.49%, P = 0.018; AMPKα1: +26.18%, P = 0.022; p-ULK1/ULK1: +38.34%, P = 0.012; p62: -9.02%, P = 0.014; Beclin1: +13.36%, P < 0.001; LC3 II/I: +79.38%, P = 0.017; autophagy flux: +24.88%, P = 0.034) compared with the D-gal group. The effects of NaHS on autophagy were comparable to those of acadesine and LYN-1604, and chloroquine could reverse its effects on ageing. LC-MS/MS and Co-IP experiments demonstrated that USP5 is a deubiquitinating enzyme of AMPKα1. Following the knockdown of USP5, the activation of AMPKα1 was decreased (p-AMPKα1: -42.10%, P < 0.001; AMPKα1: -43.93%, P < 0.001), autophagy was inhibited (p-ULK1/ULK1: -27.51, P = 0.001; p62: +36.00, P < 0.001; Beclin1: -22.15%, P < 0.001) and NaHS lost its ability to up-regulate autophagy. NaHS was observed to restore the expression (gastrocnemius: +62.17%, P < 0.001; C2C12 myotubes: +37.51%, P = 0.003) and S-sulfhydration (+53.07%, P = 0.009) of USP5 and reduce the ubiquitination of AMPKα1. CONCLUSIONS: H2S promotes the deubiquitination of AMPKα1 by increasing the expression and S-sulfhydration of USP5, thereby up-regulating autophagy and alleviating skeletal muscle ageing.

Tertiary lymphoid structures: new immunotherapy biomarker.

Immunotherapy shows substantial advancement in cancer and is becoming widely used in clinical practice. A variety of biomarkers have been proposed to predict the efficacy of immunotherapy, but most of them have low predictive ability. Tertiary lymphoid structures (TLSs), the aggregation of multiple lymphocytes, have been found to exist in various tumor tissues. TLSs have been shown to correlate with patient prognosis and immunotherapy response. This review summarizes the characteristics of TLSs and the inducing factors of TLS formation, presents available evidence on the role of TLSs in predicting immunotherapy response in different cancers, and lastly emphasizes their predictive potential for neoadjuvant immunotherapy efficacy.

Local Charge Transfer Unveils Antideactivation of Ru at High Potentials for the Alkaline Hydrogen Oxidation Reaction.

The activity of Ru-based alkaline hydrogen oxidation reaction (HOR) electrocatalysts usually decreases rapidly at potentials higher than 0.1 V (vs a reversible hydrogen electrode (RHE)), which significantly limits the lifetime of fuel cells. It is found that this phenomenon is caused by the overadsorption of the O species due to the overcharging of Ru nanoparticles at high potentials. Here, Mn1Ox(OH)y clusters-modified Ru nanoparticles (Mn1Ox(OH)y@Ru/C) were prepared to promote charge transfer from overcharged Ru nanoparticles to Mn1Ox(OH)y clusters. Mn1Ox(OH)y@Ru/C exhibits high HOR activity and stability over a wide potential range of 0-1.0 V. Moreover, a hydroxide exchange membrane fuel cell with a Mn1Ox(OH)y@Ru/C anode delivers a high peak power density of 1.731 W cm-2, much superior to that of a Pt/C anode. In situ X-ray absorption fine structure (XAFS) analysis and density functional theory (DFT) calculations reveal that Mn in Mn1Ox(OH)y clusters could receive more electrons from overcharged Ru at higher potentials and significantly decrease the overadsorption of the O species on Ru, thus permitting the HOR on Ru to proceed at high potentials. This study provides guidance for the design of alkaline HOR catalysts without activity decay at high potentials.

Association between FOXP3 polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population.

Background: Forkhead box P3 (FOXP3) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between FOXP3 polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population. Materials and methods: We genotyped single nucleotide polymorphisms at loci of the FOXP3 gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of FOXP3 in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups. Results: The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, p = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, p = 0.038). The proportions of the three genotypes of rs2232365 (p = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of FOXP3 was markedly greater in the NMOSD group than in the control group (p = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (p = 0.004 and 0.007, respectively). Conclusion: FOXP3 polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of FOXP3 rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. FOXP3 mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decreased in acute non-treatment patients compared with healthy controls.

Ultralow-Loading Ruthenium-Iridium Fuel Cell Catalysts Dispersed on Zn-N Species-Doped Carbon.

Developing low-loading platinum-group-metal (PGM) catalysts is one of the key challenges in commercializing anion-exchange-membrane-fuel-cells (AEMFCs), especially for hydrogen oxidation reaction (HOR). Here, ruthenium-iridium nanoparticles being deposited on a Zn-N species-doped carbon carrier (Ru6Ir/Zn-N-C) are synthesized and used as an anodic catalyst for AEMFCs. Ru6Ir/Zn-N-C shows extremely high mass activity (5.87 A mgPGM -1) and exchange current density (0.92 mA cm-2), which is 15.1 and 3.9 times that of commercial Pt/C, respectively. Based on the Ru6Ir/Zn-N-C AEMFCs achieve a peak power density of 1.50 W cm-2, surpassing the state-of-the-art commercial PtRu catalysts and the power ratio of the normalized loading is 14.01 W mgPGM anode -1 or 5.89 W mgPGM -1 after decreasing the anode loading (87.49 µg cm-2) or the total PGM loading (0.111 mg cm-2), satisfying the US Department of Energy's PGM loading target. Moreover, the solvent and solute isotope separation method is used for the first time to reveal the kinetic process of HOR, which shows the reaction is influenced by the adsorption of H2O and OH-. The improvement of the hydrogen bond network connectivity of the electric double layer by adjusting the interfacial H2O structure together with the optimized HBE and OHBE is proposed to be responsible for the high HOR activity of Ru6Ir/Zn-N-C.

Optimizing Hydrogen and Hydroxyl Adsorption over Ru/WO2.9 Metal/Metalloid Heterostructure Electrocatalysts for Highly Efficient and Stable Hydrogen Oxidation Reactions in Alkaline Media.

The development of high-performance, stable and platinum-free electrocatalysts for the hydrogen oxidation reaction (HOR) in alkaline media is crucial for the commercial application of anion exchange membrane fuel cells (AEMFCs). Ruthenium, as an emerging HOR electrocatalyst with a price advantage over platinum, still needs to solve the problems of low intrinsic activity and easy oxidation. Herein, Ru nanoparticles are anchored on the oxygen-vacancy-rich metalloid WO2.9 by interfacial engineering to create abundant and efficient Ru and WO2.9 interfacial active sites for accelerated HOR in alkaline media. Ru/WO2.9/C displays excellent catalytic activity with mass activity (8.29 A mgNM -1) and specific activity (1.32 mA cmNM -2), which are 2.5/3.3 and 21.8/8.3 times that of PtRu/C and Pt/C, respectively. Moreover, Ru/WO2.9/C exhibits excellent CO tolerance and operational stability. Experimental and theoretical studies reveal that the improved charge transfer from Ru to WO2.9 in the metal/metalloid heterostructure significantly tune the electronic structure of Ru sites and optimize the hydrogen binding energy (HBE) of Ru. While, WO2.9 provides abundant hydroxyl adsorption sites. Therefore, the equilibrium adsorption of hydrogen and hydroxyl at the interface of Ru/WO2.9 will be realized, and the oxidation of metal Ru would be avoided, thereby achieving excellent HOR activity and durability.

V-O Species-Doped Carbon Frameworks Loaded with Ru Nanoparticles as Highly Efficient and CO-Tolerant Catalysts for Alkaline Hydrogen Oxidation.

Efficient and CO-tolerant catalysts for alkaline hydrogen oxidation (HOR) are vital to the commercial application of anion exchange membrane fuel cells (AEMFCs). Herein, a robust Ru-based catalyst (Ru/VOC) with ultrasmall Ru nanoparticles supported on carbon frameworks with atomically dispersed V-O species is prepared elaborately. The catalyst exhibits a remarkable mass activity of 3.44 mA µgPGM, which is 31.3 times that of Ru/C and even 4.7 times higher than that of Pt/C. Moreover, the Ru/VOC anode can achieve a peak power density (PPD) of 1.194 W cm-2, much superior to that of Ru/C anode and even better than that of Pt/C anode. In addition, the catalyst also exhibits superior stability and exceptional CO tolerance. Experimental results and density functional theory (DFT) calculations demonstrate that V-O species are ideal OH- adsorption sites, which allow Ru to release more sites for hydrogen adsorption. Furthermore, the electron transfer from Ru nanoparticles to the carbon substrate regulates the electronic structure of Ru, reducing the hydrogen binding energy (HBE) and the CO adsorption energy on Ru, thus boosting the alkaline HOR performance and CO tolerance of the catalyst. This is the first report that oxophilic single atoms distributed on carbon frameworks serve as OH- adsorption sites for efficient hydrogen oxidation, opening up new guidance for the elaborate design of high-activity catalysts for the alkaline HOR.

Exogenous H2S alleviates senescence of glomerular mesangial cells through up-regulating mitophagy by activation of AMPK-ULK1-PINK1-parkin pathway in mice.

Hydrogen sulfide (H2S) is the third gas signaling molecule that has been shown to be involved in the regulating vital activities in the body, including inhibition of aging. However, it is unknown whether H2S alleviates aging in the kidney and glomerular mesangial cells (GMCs) by modulating their mitophagy. Here, results of experiments in vivo and in vitro showed that compared with control group, the renal function of mice and GMCs viability were decreased in D-gal (D-galactose) group, while the activity of SA-ß-gal and p21 expression were increased, Cyclin D1 and Klotho expressions were decreased; H2S content and CSE expression were lower; ROS and MDA contents and mitochondrial permeability transition pore (mPTP) opening were risedose; ATP production and mitochondrial membrane potential (Δψm) were reduced; Apoptotic rate, the expression of Cleaved caspase-9 and -3, Cyt c, p62 and Drp1 were enhanced and the expression of Bcl-2, Mfn2, Beclin-1, LC3 II/I, PINK1 and parkin were decreased. In addition, phospho-AMPK/AMPK and phospho-ULK1/ULK1 were also decreased significantly. Compared with the D-gal group, the changes of above indexes were reversed in the D-gal + NaHS (Sodium hydrosulfide, an exogenous H2S donor) group. The reverse effects of NaHS were similar to that of AICAR (an AMPK agonist) and kinetin (a PINK1 agonist), respectively. Taken together, these results suggest that exogenous H2S increases mitophagy and inhibits apoptosis as well as oxidative stress through up-regulation of AMPK-ULK1-PINK1-parkin pathway, which delays kidney senescence in mice.

Unilateral Orbitopathy Caused by Skull Base Chordoid Meningioma.

Chordoid meningioma (CM) makes up only 1% of all meningiomas. Most cases of this variant are locally aggressive, have high growth potential, and are likely to recur. Although CMs are known to be invasive, they rarely extend into the retro-orbital space. Herein, we report a case of a central skull base CM in a 78-year-old woman whose only manifestation was unilateral proptosis with impaired vision resulting from the tumor extending into the retro-orbital space through the superior orbital fissure. The diagnosis was confirmed by analysis of specimens collected during endoscopic orbital surgery, which simultaneously relieved the protruding eye and restored the patient's visual acuity by decompressing the oppressed orbit. This rare presentation of CM reminds physicians there may be lesions outside the orbit that can cause unilateral orbitopathy and that endoscopic orbital surgery can be used to confirm its diagnosis as well as treat it.

Dengue virus co-opts innate type 2 pathways to escape early control of viral replication.

Mast cell products and high levels of type 2 cytokines are associated with severe dengue disease. Group 2 innate lymphoid cells (ILC2) are type-2 cytokine-producing cells that are activated by epithelial cytokines and mast cell-derived lipid mediators. Through ex vivo RNAseq analysis, we observed that ILC2 are activated during acute dengue viral infection, and show an impaired type I-IFN signature in severe disease. We observed that circulating ILC2 are permissive for dengue virus infection in vivo and in vitro, particularly when activated through prostaglandin D2 (PGD2). ILC2 underwent productive dengue virus infection, which was inhibited through CRTH2 antagonism. Furthermore, exogenous IFN-ß induced expression of type I-IFN responsive anti-viral genes by ILC2. PGD2 downregulated type I-IFN responsive gene and protein expression; and urinary prostaglandin D2 metabolite levels were elevated in severe dengue. Moreover, supernatants from activated ILC2 enhanced monocyte infection in a GM-CSF and mannan-dependent manner. Our results indicate that dengue virus co-opts an innate type 2 environment to escape early type I-IFN control and facilitate viral dissemination. PGD2 downregulates type I-IFN induced anti-viral responses in ILC2. CRTH2 antagonism may be a therapeutic strategy for dengue-associated disease.

PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2.

Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS and established PHF5A as potential therapeutic target.

Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes.

Background: Exosomes, as natural intercellular information carriers, have great potential in the field of drug delivery. Many studies have focused on modifying exosome surface proteins to allow drugs to specifically target cancer cells. Methods: In this study, human cord blood mesenchymal stromal cell-derived exosomes were used in the delivery of anti-miRNA oligonucleotides so as to be specifically ingested by tumor cells to perform anti-tumor functions. Mesenchymal stem cells modified by the fusion gene iRGD-Lamp2b were constructed to separate and purify exosomes, and the anti-miRNA-221 oligonucleotide (AMO) was loaded into the exosomes by electroporation. Results: The AMO-loaded exosomes (AMO-Exos) effectively inhibited the proliferation and clonal formation of colon cancer cells in vitro, and it was further found that AMO-Exos was taken up by tumor cells through interaction with the NRP-1 protein. The results of a xenograft tumor model also showed that iRGD-modified exosomes were obviously enriched in tumor sites, exerting excellent anti-tumor efficacy. In vivo imaging showed that exosomes were mainly distributed in liver, spleen, and lung tissues. Conclusion: Our results suggest that genetically modified exosomes could be an ideal natural nanostructure for anti-miRNA oligonucleotide delivery.

TMEM106C contributes to the malignant characteristics and poor prognosis of hepatocellular carcinoma.

Transmembrane protein (TMEM) is a kind of integral membrane protein that spans biological membranes. The functions of most members of the TMEM family are unknown. Here, we conducted bioinformatic analysis and biological validation to investigate the role of TMEM106C in HCC. First, GEPIA and OncomineTM were used to analyze TMEM106C expression, which was verified by real-time PCR and western blot analyses. Then, the biological functions of TMEM106C were explored by CCK8 and transwell assays. The prognostic value of TMEM106C was analyzed by UALCAN. LinkedOmics was used to analyze TMEM106C pathways generated by Gene Ontology. A protein-protein interaction network (PPI) was constructed by GeneMANIA. We demonstrated that TMEM106C was overexpressed in HCC and that inhibition of TMEM106C significantly suppressed the proliferation and metastasis of HCC through targeting CENPM and DLC-1. Upregulation of TMEM106C was closely correlated with sex, tumor stage, tumor grade and prognosis. Overexpression of TMEM106C was linked to functional networks involving organelle fission and cell cycle signaling pathways through the regulation of CDK kinases, E2F1 transcription factors and miRNAs. Our data demonstrated that TMEM106C contributes to malignant characteristics and poor prognosis in HCC, which may serve as a prognostic biomarker and potential therapeutic target.

Fabrication of a Micro-Electromechanical System-Based Acetone Gas Sensor Using CeO2 Nanodot-Decorated WO3 Nanowires.

Preparation of reliable, stable, and highly responsive gas-sensing devices for the detection of acetone has been considered to be a key issue for the development of accurate disease diagnosis systems via exhaled breath. In this paper, novel CeO2 nanodot-decorated WO3 nanowires are successfully synthesized through a sequential hydrothermal and thermolysis process. Such CeO2 nanodot-decorated WO3 nanowires exhibited a remarkable enhancement in acetone-sensing performance based on a miniaturized micro-electromechanical system device, which affords high response (S = 1.30-500 ppb, 1.62-2.5 ppm), low detection limit (500 ppb), and superior selectivity toward acetone. The improved performance of the acetone sensor is likely to be originated from the fast carrier transportation of WO3 nanowires, the formation of WO3-CeO2 heterojunctions, and the existence of large amounts of oxygen vacancies in CeO2. The improved reaction thermodynamics and sensing mechanisms have also been revealed by the specific band alignment and X-ray photoelectron spectroscopy analysis.

Precise preparation of WO3@SnO2 core shell nanosheets for efficient NH3 gas sensing.

Development of high-performance ammonia (NH3) sensor is imperative for monitoring NH3 in the living environment. In this work, to obtain a high performance NH3 gas sensor, structurally well-defined WO3@SnO2 core shell nanosheets with a controllable thickness of SnO2 shell layer have been employed as sensing materials. The prepared core shell nanosheets were used to obtain a miniaturized gas sensor based on micro-electro-mechanical system (MEMS). By tuning the thickness of SnO2 layer via atomic layer deposition, a series of WO3@SnO2 core-shell nanosheets with tunable sensing properties were realized. Particularly, the sensor base on the fabricated WO3@SnO2 nanosheets with 20-nm SnO2 shell layer demonstrated superior gas sensing performance with the highest response (1.55) and selectivity toward 15 ppm NH3 at 200 °C. This remarkable enhancement of NH3 sensing ability could be ascribed to the formation of unique WO3-SnO2 core-shell heterojunction structure. The detailed mechanism was elucidated by the heterojunction-depletion model with the help of specific band alignment.

Hierarchical highly ordered SnO2 nanobowl branched ZnO nanowires for ultrasensitive and selective hydrogen sulfide gas sensing.

Highly sensitive and selective hydrogen sulfide (H2S) sensors based on hierarchical highly ordered SnO2 nanobowl branched ZnO nanowires (NWs) were synthesized via a sequential process combining hard template processing, atomic-layer deposition, and hydrothermal processing. The hierarchical sensing materials were prepared in situ on microelectromechanical systems, which are expected to achieve high-performance gas sensors with superior sensitivity, long-term stability and repeatability, as well as low power consumption. Specifically, the hierarchical nanobowl SnO2@ZnO NW sensor displayed a high sensitivity of 6.24, a fast response and recovery speed (i.e., 14 s and 39 s, respectively), and an excellent selectivity when detecting 1 ppm H2S at 250 °C, whose rate of resistance change (i.e., 5.24) is 2.6 times higher than that of the pristine SnO2 nanobowl sensor. The improved sensing performance could be attributed to the increased specific surface area, the formation of heterojunctions and homojunctions, as well as the additional reaction between ZnO and H2S, which were confirmed by electrochemical characterization and band alignment analysis. Moreover, the well-structured hierarchical sensors maintained stable performance after a month, suggesting excellent stability and repeatability. In summary, such well-designed hierarchical highly ordered nanobowl SnO2@ZnO NW gas sensors demonstrate favorable potential for enhanced sensitive and selective H2S detection with long-term stability and repeatability.

High-throughput screening identified miR-7-2-3p and miR-29c-3p as metastasis suppressors in gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) is one of the most aggressive and lethal tumors, with extremely high metastatic activity and poor prognosis. Previously we have studied miRNAs that promote metastasis and progression of GBC, the aim of present study was to systematically elucidate the metastasis suppressor miRNAs in GBC. METHODS: A novel designed high-throughput screening method that combined high content screening (HCS) and miRNA microarray analysis was conducted to filter out anti-metastatic miRNAs of GBC. Frozen samples were analyzed for the expression of goal miRNAs by real-time PCR. The biological functions of miRNAs were studied by transwell, immunoblot. Liver metastasis model via spleen injection was further examined in nude mice. Kaplan-Meier and Cox regression analyses were used to analyze the effect of goal miRNAs on overall survival. The target genes and interaction network of goal miRNAs were determined by whole transcriptome genome sequencing. RESULTS: Out of the miRNAs library, a series of prominent metastatic suppressor miRNA candidates were filtered out. Among them, miR-7-2-3p and miR-29c-3p were discovered downregulated in GBC, and upregulation of them could reverse epithelial-mesenchymal transition and decrease the metastasis ability of GBC cells in vitro and in vivo, which was dominated by the miRNA-mRNA-lncRNA co-expression network. And DCLK1 and SLC36A1 are the direct target genes of miR-7-2-3p and miR-29c-3p. Moreover, the deficiency of miR-7-2-3p and miR-29c-3p was closely associated with poor prognosis of GBC patients. CONCLUSIONS: Our findings indicate that miR-7-2-3p and miR-29c-3p play crucial roles in the pathogenesis and worse prognosis of GBCs, which may serve as prognosis biomarkers and promise potential therapeutic targets in the future.