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A cubic Pd and reduced graphene oxide modified glassy carbon electrode (Pd/RGO/GCE) was fabricated to simultaneously detect dopamine (DA) and uric acid (UA) by cyclic voltammetry (CV) and different pulse voltammetry (DPV) methods. Compared with Pd/GCE and RGO/GCE, the Pd/RGO/GCE exhibited excellent electrochemical activity in electrocatalytic behaviors. Performing the Pd/RGO/GCE in CV measurement, the well-defined oxidation peak potentials separation between DA and UA reached to 145mV. By using the differential pulse voltammetry (DPV) technique, the calibration curves for DA and UA were found linear with the concentration range of 0.45-421μM and 6-469.5μM and the detection limit (S/N =3) were calculated to be 0.18μM and 1.6μM, respectively. Furthermore, the Pd/RGO/GCE displayed high selectivity when it was applied into the determination of DA and UA even though in presence of high concentration of interferents. Additionally, the prepared electrochemical sensor of Pd/RGO/GCE demonstrated a practical feasibility in rat urine and serum samples determination.

Microstructural characteristics of Alloy 690TT subjected to fretting corrosion in high temperature water were investigated. The results indicated that there were oxide, tribologically transformed structure (TTS) and deformation layers in worn subsurface. Oxide layer had a multilayered structure: the outer part consisted of Fe-rich spinel oxides and tribolayer which was composed of Fe 3 O 4 and Cr 2 O 3 ; the inner part contained local amorphous Cr-rich oxides. TTS layer consisted of equiaxed nanograins which formed due to dynamic recrystallization of deformed structure. Internal oxidation occurred within TTS layer because the nanograins provided the short-circuits for oxygen diffusion, resulting in the ellipsoid and stripe-like Cr 2 O 3 .

Active vibration isolation technology has been widely used to reduce vibration transmission in many different engineering systems. Magnetic suspension isolator (MSI), as an active isolation actuator, has shown advantages including non-contact, high response frequency, high reliability and long life-span. However, the location and number of active or passive isolators play an important role on reducing the vibration transmission from excitation source to the foundation for the vibration isolation system. The particular set parameters of vibration isolation system with MSIs is conducted to improve the performance of reducing vibration. It proposes the analysis and comparison of different arrangement schemes for MSIs and passive isolators for the single-layer multi-degree freedom vibration isolation system. The resulting arrangement scheme of 4 passive isolators and the location of MSIs are used to get better performance in the power flow of vibration isolation system. This paper presents the hybrid vibration system that integrates active-passive isolation and multi-objective optimization for decision arrangement scheme in reducing the vibration, which has practical application significance in industry.

Highlights • PC10 is the first description of a mAb against PEDV isolated from porcine B cells. • PC10 powerfully neutralizes PEDV and captures infectious PEDV virions in vitro. • PC10 recognizes the conformational epitope of the native spike structure., Porcine epidemic diarrhea (PED), caused by an alpha coronavirus, is a highly contagious disease and causes high morbidity and mortality in suckling piglets. Isolating PEDV neutralizing antibodies from porcine B cells is critical to elucidate the development of PEDV neutralizing antibodies and the protective mechanism of PEDV infection. Here, we described the isolation of a PEDV-neutralizing antibody from the B cell of a vaccinated pig. The antibody, named PC10, was demonstrated to target the conformational epitope of PEDV spike protein, specifically bind to the infected cells of PEDV genogroup 1 and 2 strains, and potently neutralize PEDV infection. PC10 neutralized PEDV infection through interfering with the viral life stages after cellular attachment instead of blocking the attachment of PEDV to cells. These results suggest that PC10 could be a promising candidate for passive protection and inform PEDV vaccine design because of its specificity and substantial neutralization potency.

A bibliometric analysis of the research in the field of Water Footprint (WF) during 2006–2015 was presented with the information related to countries, institutions, journals, categories, top cited publications, keywords, hot issues and research trends. Researches on WF have increased sharply over the past decade. The United States (24.1%), China (19.2%) and Netherlands (16.0%) had high productivity in total publications. Based on co-word and social network analysis (SNA), the USA-China has been most closely correlated in the cooperative web system. University of Twente took the leading position of institutions in total articles and also conducted the most independent, collaborative, first authored, and corresponding authored articles. Journal of Cleaner Production, Environmental Science & Technology and Ecological Indicators are the top three journals with the most publications in this field. A summary of the most frequently used keywords obtained from title, author keywords and keywords plus analysis provided the clues to discover the current research emphases. The mainstream research related to WF was its accounting methodologies and application in water resource management. Water-food-energy nexus, driving mechanism of WF variation, environmental impact of water use and integration of footprint indicators strongly promoted the development of WF research and are getting popular in recent years. Findings provide a better understanding of characteristics of WF research which serves as a useful reference for future studies.

Rutin has a broad range of physiological activities and often used clinically as therapeutic medicine on humans, and it is important to develop sensitive analytical methods for rutin determination. The nanocomposites, consisting of Cu2O, Au nanoparticles and nitrogen-doped graphene (denoted as Cu2O-Au/NG), were successfully fabricated by a facile and green method and used for highly sensitive detection of rutin. The electrochemical methods, such as cyclic voltammetry (CV) and differential pulse voltammetry (DPV) have been used to investigate the electrochemical properties of the fabricated sensors for rutin detection. The results showed that under optimal conditions, Cu2O-Au/NG/GCE exhibited highest sensitivity of 114.94 μA·mM− 1 than the other modified electrodes, and a low detection limit of 30 nM could be achieved with a linear concentration response range from 0.06 to 512.90 μM. The enhanced electrochemical performances could be attributed to the synergistic effect between Cu2O-Au and NG and the outstanding catalytic effect of the Cu2O-Au nanoparticles. Finally, the sensor was successfully used to analyze rutin tablets, showing high potential for practical applications.

The purpose of this study was to develop a recombinant adenovirus with secretory leukoprotease inhibitor (SLPI) promoter-controlled expression for gene therapy of squamous cell carcinoma (SCC). An artificial microRNA targeting epidermal growth factor receptor (EGFR) was designed, and used to construct a replication-defective recombinant adenovirus with SLPI promoter-controlled expression. The silencing efficiency of this vector (Ad-SLPI-EGFRamiR) was detected in Hep-2 cells. Western blotting showed that the expression of 170 kD EGFR was significantly reduced in Hep-2 cells 72 h after infection with Ad-SLPI-EGFRamiR. At a multiplicity of infection (MOI) of 200 pfu/cell, proliferation of Hep-2 cells was highly inhibited by Ad-SLPI-EGFRamiR (inhibition rate: ~70%). The apoptosis rate of Hep-2 cells at 72 h after infection with Ad-SLPI-EGFRamiR at a MOI 35 pfu/cell was 32.8%. The adenovirus constructed was able to specifically inhibit the growth of SCC cells in vitro.

This paper presents a new approach for constructing a mathematical model of the floating raft system directly from input-output measurements in the presence of noise. In contrast to the original OKID/ERA algorithm, which works through the observer Markov parameters, the new approach used observer output residuals to convert the initial stochastic identification to a virtually deterministic identification problem. The extension of deterministic algorithm to stochastic problems by proposed stochastic-to-deterministic conversion can be done with ease. A MIMO (multiple-input multiple-output) system state-space model and an associated Kalman filter gain can be identified. H∞ controller with high robustness to model error is designed to solve multifrequency varying vibration for floating raft system. Both simulated and experimental results confirm the validity and the benefits of the approach.

Objective: Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD. Methods: We investigated the effects of GPER agonist G1 and GPER antagonist G15 on the neurodegeneration of dopaminergic neuron, the activation of microglia, and the production of IL-1β, TNF-α, and IL-6 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of parkinsonism. Furthermore, we confirmed the effects of GPER activation on the production of IL-1β, TNF-α, and IL-6 in an in vitro MPP+ model in BV2 microglial cells. Results: After 12-day treatment with G1, mice showed an increase in the number of tyrosine hydroxylase-immunoreactive cells, reduced activation of microglia, and the abatement of proinflammatory cytokines, and the anti-inflammatory effect of G1 was abolished by G15. Meanwhile, in vitro studies demonstrated that GPER activation also reduced the release of proinflammatory cytokines from BV2 microglial cells after MPP+ stimulation. Conclusion: Our data suggest that GPER mediates the anti-neuroinflammatory effect of estrogen in experimental PD progression.

A bibliometric analysis was conducted to examine the progress and future research trends of non-point source (NPS) pollution during the years 1991-2015 based on the Science Citation Index Expanded (SCI-Expanded) of Web of Science (WoS). The publications referencing NPS pollution were analyzed including the following aspects: document type, publication language, publication output and characteristics, subject category, source journal, distribution of country and institution, author keywords, etc. The results indicate that the study of NPS pollution demonstrated a sharply increasing trend since 1991. Article and English were the most commonly used document type and language. Environmental sciences and ecology, water resources, and engineering were the top three subject categories. Water science and technology ranked first in distribution of journal, followed by Science of the total environment and Environmental Monitoring and Assessment. The USA took a leading position in both quantity and quality, playing an important role in the research field of NPS pollution, followed by the UK and China. The most productive institution was the Chinese Academy of Sciences (Chinese Acad Sci), followed by Beijing Normal University and US Department of Agriculture's Agricultural Research Service (USDA ARS). The analysis of author keywords indicates that the major hotspots of NPS pollution from 1991 to 2015 contained "water," "model," "agriculture," "nitrogen," "phosphorus," etc. The results provide a comprehensive understanding of NPS pollution research and help readers to establish the future research directions.

Astrocytes, as the largest population of glial subtype, play crucial roles in normal brain function and pathological conditions, such as Parkinson’s disease (PD). Restoring the functions of astrocyte is a promising new therapeutic target for PD. Astrocytes can express multiple types of neurotransmitter receptors, including functional α7 nicotinic acetylcholine receptor (α7nAChR). Previously, we found that a non-selective α7nAChR agonist nicotine exerted a protective effect against H2O2-induced astrocyte apoptosis via an α7nAChR-dependent pathway. However, the molecular mechanism of the antiapoptotic response of astroglial α7nAChR has not been studied. In the present study, using pharmacological inhibition and genetic knockout of α7nAChR, we assessed the antiapoptotic effects of an α7nAChR agonist PNU-282987 in primary cultured astrocytes treated with 1-methyl-4-phenylpyridinium (MPP+). PNU-282987 promoted the viability of astrocytes, alleviated MPP+ induced apoptosis, and decreased the number of GFAP+/TUNEL+ cells. Meanwhile, PNU-282987 upregulated the expression of the antiapoptotic protein Bcl-2 and downregulated the expression of the apoptotic protein Bax and cleaved-caspase-3. Moreover, the suppression of the JNK-p53-caspase-3 signaling may underlie the neuroprotective property of PNU-282987. Therefore, PNU-282987 ameliorates astroglial apoptosis induced by MPP+ through α7nAChR-JNK-p53 signaling. Our findings suggest that PNU-282987 may be a potential drug for restoring astroglial functions in the treatment of PD.

Frameshift mutations frequently occur in colorectal cancer (CRC) with microsatellite instability (MSI), but the nature and biological function of many MSI‐associated mutations remain elusive. Here, an MSI frameshift mutation is identified in glioma tumor suppressor candidate region gene 1 (GLTSCR1) that produces two C‐terminal‐truncated proteins. Additionally, GLTSCR1 is verified as a tumor suppressor that inhibits CRC metastasis. Through binding to bromodomains and the phosphorylation‐dependent interaction domain of bromodomain protein 4 (BRD4) via the C‐terminus, GLTSCR1 blocks oncogenic transcriptional elongation. However, truncated GLTSCR1 translocates into the cytoplasm and loses BRD4 binding domain, which induces the phosphorylation of RNA Pol II at Ser2 and dephosphorylation at Ser5, then increases oncogenic transcriptional elongation. Importantly, GLTSCR1 deficiency decreases sensitivity to bromodomain and extra terminal domain inhibitors. This study highlights the molecular mechanism of the GLTSCR1‐BRD4 interaction, which is a potential therapeutic target for CRC., This study reports a microsatellite instability‐selected frameshift mutation in glioma tumor suppressor candidate region gene 1 (GLTSCR1) that converts GLTSCR1 from an antimetastatic gene to a prometastatic gene. A bromodomain protein 4‐GLTSCR1‐DNA model is proposed in which the truncated GLTSCR1 coregulates the oncogenic transcriptional elongation and these findings provide a strong rationale for targeting GLTSCR1 in colorectal cancer.

It was well-known that Berberine, a major bioactive compound extracted from natural plants Coptis chinensis, has anti-diabetic effects for decades in china. Other types of pharmacological activities, such as anti-inflammatory, antimicrobial, hypolipidemic, and anti-cancer effects, have also been examined. At cellular level, these pharmacological activities were mostly an inhibitory effect. However, the cytoprotective effect of berberine was also observed in various types of cells, such as neurons, endothelial cells, fibroblasts, and β-cells. The paradoxical result may be closely associated with characteristics and distribution of berberine within cells, and they can be explained mechanically by mitohormesis, one particular form of hormesis. Here, we reviewed the mitohormetic response and assessed the berberine-induced effects and the possible signaling pathway involved. These findings may contribute to better clinical applications of berberine and indicate that some mitochondria-targeted conventional drugs should be considered carefully in clinical application.

Background Although massive studies have been conducted to investigate the mechanisms of esophageal squamous cell carcinoma (ESCC) carcinogenesis, the understanding of molecular alterations during the malignant transformation of epithelial dysplasia is still lacking, especially regarding epigenetic changes. Results To better characterize the methylation changes during the malignant transformation of epithelial dysplasia, a whole-genome bisulfite sequencing analysis was performed on a series of tumor, dysplastic, and non-neoplastic epithelial tissue samples from esophageal squamous cell carcinoma (ESCC) patients. Promoter hypermethylation in TGF-β receptor type II (TGFBR2), an important mediator of TGF-β signaling, was identified. Further, we evaluated the methylation and expression of TGFBR2 in tumor samples through The Cancer Genome Atlas multiplatform data as well as immunohistochemistry. Moreover, treatment of ESCC cell lines with5-Aza-2′-deoxycytidine, a DNA methyltransferase inhibitor, reactivated the expression of TGFBR2. The lentiviral mediating the overexpression of TGFBR2 inhibited the proliferation of ESCC cell line by inducing cell cycle G2/M arrest. Furthermore, the overexpression of TGFBR2 inhibited the tumor growth obviously in vivo. Conclusions The characterization of methylation silencing of TGFBR2 in ESCC will enable us to further explore whether this epigenetic change could be considered as a predictor of malignant transformation in esophageal epithelial dysplasia and whether use of a TGFBR2 agonist may lead to a new therapeutic strategy in patients with ESCC.

AntiSMASH analysis of genome DNA of

Animal models, notably with non-competitive NMDA receptor antagonist MK801, are commonly used to investigate the mechanisms of schizophrenia and to pursue its mechanism-related drug discoveries.In the current study, we have extensively examined the protective effects of MogrosideV (MogV), a plant-derived three terpene glucoside known to exhibit anti-oxidative and anti-inflammatory activities.Here, we investigated its protective effects against neuronal damages elicited by MK-801 treatment. Our behavioral experimental results showed that MK-801-induced PPI deficits and social withdrawal were prevented by MogV treatment. Moreover, the cellular and neurochemical responses of MK-801 in medial prefrontal cortical cortex (mPFC) were also ameliorated by MogV treatment. Also, profiling metabolites assay through artificial intestinal microbiota was performed to identify bioactive components of MogV. An in vitro study of primary neuronal culture demonstrated that MogV and its metabolite 11-oxo-mogrol treatment prevented the MK-801-induced neuronal damages through the mechanisms of promoting neurite outgrowth, inhibiting cell apoptosis, and [CaThese results suggest therapeutic potential of MogV for schizophrenia.

Isarubrolones are bioactive polycyclic tropoloalkaloids from Streptomyces. Three new isarubrolones (2-4), together with the known isarubrolone C (1) and isatropolones A (5) and C (6, 3( R)-hydroxyisatropolone A), were identified from Streptomyces sp. CPCC 204095. The structures of these compounds were determined using a combination of mass spectrometry, 1D and 2D NMR spectroscopy, and ECD. Compounds 3 and 4 feature a pyridooxazinium unit, which is rarely seen in natural products. Compound 6 could conjugate with amino acids or amines to expand the structural diversity of isarubrolones with a pentacyclic or hexacyclic core. Importantly, 1 and 3-6 were found to induce complete autophagy.

A single-particle enumeration method based on phosphorylation-directed in situ assembly of gold nanoparticles is developed for the ultrasensitive sensing of cellular protein kinase A activity. In comparison to existing strategies, the proposed new method demonstrates five orders of linear range and improves the detection limit up to 10-to-1000 fold without the involvement of target amplification.

The objective of this study was to develop a novel delivery system for recombinant human epidermal growth factor (rhEGF) for chronic wound treatment. Such a delivery system should be of good cargo stability and system mechanical properties in order to guarantee a satisfactory wound-healing effect. rhEGF-containing lyotropic liquid crystalline precursors (rhEGF-LLCPs) with in situ gelation capability were considered as a promising candidate to achieve this aim. Various properties of the optimal formulations (rhEGF-LLCP1 and rhEGF-LLCP2) were characterized, including apparent viscosity, gelation time, in vitro release and phase behavior. The stability of rhEGF and system mechanical properties (i.e. mechanical rigidity and bioadhesive force) were verified. Interestingly, rhEGF-LLCP2 with a larger internal water channel diameter exhibited faster release rate in vitro and then better bioactivity in Balb/c 3T3 and HaCaT cell models. Moreover, rhEGF-LLCP2 showed distinct promotion effects on wound closure, inflammatory recovery and re-epithelization process in Sprague-Dawley rat models. In conclusion, rhEGF-LLCP emerged as a prospective candidate to preserve the stability and enhance the wound-healing effect of rhEGF, which might serve as a new delivery system for chronic wound therapies.

Recent work has made considerable progress in exploring contextual information for human parsing with the Fully Convolutional Network framework. However, there still exist two challenges: (1) inherent relative relationships between parts; (2) scale variation of human parts. To tackle both problems, we propose a Graph-Based Scale-Aware Network for human parsing. First, we embed a Graph-Based Part Reasoning Layer into the backbone network to reason the relative relationship between human parts. Then we construct a Scale-Aware Context Embedding Layer, which consists of two branches to capture scale-specific contextual information, with different receptive fields and scale-specific supervisions. In addition, we adopt an edge supervision to further improve the performance. Extensive experimental evaluations demonstrate that the proposed model performs favorably against the state-of-the-art human parsing methods. More specifically, our algorithm achieves 53.32% (mIoU) on the LIP dataset.

A good prediction of landslide displacement is an essential component for implementing an early warning system. In the Three Gorges Reservoir Area (TGRA), many landslides deform distinctly and in steps from April to September each year under the influence of seasonal rainfall and periodic fluctuation in reservoir water level. The sliding becomes more uniform again from October to April. This landslide deformation pattern leads to accumulated displacement versus time showing a step-wise curve. Most of the existing predictive models express static relationships only. However, the evolution of a landslide is a complex nonlinear dynamic process. This paper proposes a dynamic model to predict landslide displacement, based on time series analysis and long short-term memory (LSTM) neural network. The accumulated displacement was decomposed into a trend term and a periodic term in the time series analysis. A cubic polynomial function was selected to predict the trend displacement. By analyzing the relationships between landslide deformation, rainfall, and reservoir water level, a LSTM model was used to predict the periodic displacement. The LSTM approach was found to properly model the dynamic characteristics of landslides than static models, and make full use of the historical information. The performance of the model was validated with the observations of two step-wise landslides in the TGRA, the Baishuihe landslide and Bazimen landslide. The application of the model to those two landslides demonstrates that the LSTM model provides a good representation of the measured displacements and gives a more reliable prediction of landslide displacement than the static support vector machine (SVM) model. It is concluded that the proposed model can be used to effectively predict the displacement of step-wise landslides in the TGRA.

Figure S1. XRD patterns of PtNi jagged-like nanowires. Figure S2 (a) Pt 4f and (b) Ni 2p deconvoluted XPS spectras of PtNi jagged-like nanowires. Figure S3 The CVs of 0.48 μg PtNi/C modified GCE in 0.1 M BR buffer solution containing 0.5 mM caffeic acid at pH ranging from 1.0 to 7.0 (a) and the plots of the anodic peak potential against pH (b). Figure S4 CVs of the 0.48 μg PtNi/C modified GCE in 0.1 M BR buffer solution (pH = 2.0) containing 0.5 mM caffeic acid at scan rates from 20 to 200 mV s−1 (a) and the plots of anodic and cathodic peak currents to the scan rates (b). Figure S5 The CVs of the 0.48 μg PtNi/C electrode (a) and Pt/C electrode (c) in 0.5 mM CA after various numbers of potential cycles (1–4000 cycles) at a scan rate of 100 mV s−1. The oxidation peak currents of 0.48 μg PtNi/C electrode (b) and Pt/C electrode (d) vs number of cycles. Figure S6 (a) TEM images, (b) HAADF-STEM images and (c) STEM-EDS elemental mapping of Pt-Ni jagged-like nanowires after subjecting the sample to potential cycling for 4000 cycles between 0.1–1.0 V in 0.1 M BR buffer solution electrolyte at 100 mV s−1. Figure S7 Relative analytical response (Ipa/Ip) of PtNi/C electrode in 0.1 M BR buffer solution (pH = 2.0) containing 0.5 mM caffeic acid in presence of different interfering species: 10 mM tannic acid, resveratrol, tartaric acid, gallic acid, citric acid, P-coumaric acid, succinic acid, and malic acid. Table S1 Comparison of the linear range and detection limit between the proposed method and other reported detection methods for caffeic acid. Table S2 Determination of CA in red wine samples (DOCX 2679 kb)

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1&mdash, a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (25 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% &plusmn, 2.2%, and low-density lipoprotein-cholesterol by 31.6% &plusmn, 3.2%, which was more effective than that of the resveratrol (8.4% &plusmn, 2.3%, 6.6% &plusmn, 2.1%) or berberine (10.5% &plusmn, 1.95%, 9.8% &plusmn, 2.58%) monotherapy (p &lt, 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 &micro, mol/L or 20 &micro, mol/L berberine combined with 25 &micro, mol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.

Heteroatom-doping is an effective way to regulate the electronic structure of carbon so as to improve their Na-ion storage capability. In all kinds of heteroatoms, selenium (Se)-doping has rarely been investigated even though Se has unique physicochemical properties. Herein, we report a facile fabrication of Se/N-codoped carbon nanosheets (N/Se-CNs) with 10 at% N and 2 at% Se by an oxidation-selenization process. The synchrotron X-ray photoelectron spectroscopy (XPS) measurements indicate that Se doping can significantly change the electronic structures of carbon nanosheets, because Se can act as stronger electron-withdrawing units for Na storage compared with C and N. Therefore, Se can better play the role of improving the conductivity and wettability of the carbon materials. And Se atoms effectively enlarge the interlayer distance of carbon nanosheets to enhance the Na-ion diffusion kinetics and also generate extra active sites for Na-ion storage. Served as anode materials for SIBs, the N/Se-CNs delivers higher specific capacity and better rate capability compared with only N-doped carbon nanosheets. Therefore, Se-doping is an effective way for improvement of Na-storage capability of carbon materials. Moreover, this work should provide a new pathway for design of carbons doped by heteroatoms with large atomic size towards excellent Na-ion storage.

Transition metallic phosphides (TMPs) have attracted considerable attention for use as efficient and durable electrocatalysts for the hydrogen evolution reaction (HER). However, it is still challenging for TMPs to achieve HER performance similar to that of the state-of-the-art platinum (Pt) catalysts. Herein, we report new amorphous phosphatized ruthenium-iron bimetallic nanoclusters (RuxFeyP-NCs) supported on graphitized carbon nanofibers (CNF), synthesized through a facile two-step method, which combine the merits of several catalyst design strategies. The amorphous structure allows more catalytically active sites to be exposed, and the synergy between Ru and Fe may boost the intrinsic catalytic activity. Moreover, the conductive CNF support facilitates electron transport and firmly immobilizes RuxFeyP-NCs enabling a long-term stability. The resulting RuxFeyP-NCs/CNF with optimal equimolar Ru and Fe (i.e. RuFeP-NCs/CNF) exhibits outstanding Pt-like HER performance, requiring low overpotentials of 65.8 and 16.0 mV to deliver a current density of 10 mA cm−2 in acidic and alkaline solutions, respectively, and showing a long-term stability of 100 h. The density functional theory (DFT) calculations demonstrate that RuFeP-NCs/CNF shows Gibbs free energy of hydrogen adsorption close to that of Pt and much smaller than that of FeP-NCs/CNF and RuxFey-NCs/CNF controls with non-equimolar Ru/Fe, which rationally explains the experimentally observed prominent HER performance of RuFeP-NCs/CNF.

Purpose Triple-negative breast cancer (TNBC) is a subtype of breast cancer. Increasing evidence supports that dysregulation of long noncoding RNAs (lncRNAs) plays a vital role in cancer progression. RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a lncRNA, is characterized as a tumor-propeller in some cancers, but its mechanism in TNBC remains poorly understood. This study aimed to determine whether and how RMRP functions in TNBC. Methods Cell proliferation was determined by cell counting kit-8 (CCK-8) and colony formation assays and cell apoptosis by flow cytometry analysis and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Cell migration and invasion were determined by transwell assays. RNA-binding protein immunoprecipitation (RIP), luciferase reporter, and RNA pulldown assays were implemented to assess the interaction of RMRP with other molecules in TNBC cells. Results RMRP expression was elevated in TNBC cells. RMRP knockdown repressed cell proliferation, migration, and invasion, but induced apoptosis in TNBC. In addition, RMRP was found to target microRNA-766-5p (miR-766-5p) in TNBC cells. Silencing miR-766-5p enhanced cell viability and decreased apoptosis, whereas miR-766-5p overexpression had opposite effects. Furthermore, miR-766-5p was found to bind to yes-associated protein 1 (YAP1). Moreover, miR-766-5p inhibition reversed the repressive effect of RMRP knockdown on the malignant progression of TNBC. Conclusion The present study manifested that RMRP promotes the growth, migration, and invasion of TNBC cells via the miR-766-5p/YAP1 axis. These findings provide novel perspectives for TNBC treatment.

An electrochemiluminescence (ECL) resonance energy transfer system is constructed for 17β-estradiol (E2) detection using α-FeOOH@CdS nanospheres as the ECL-active substrates and Ag NCs as an efficient quencher. CdS QDs loaded onto three-dimensional (3D) urchin-like α-FeOOH nanospheres (α-FeOOH@CdS nanospheres) exhibited excellent ECL responses, which is attributed to dual-amplification of α-FeOOH frameworks. The 3D hierarchical structure of the α-FeOOH nanospheres provided abundant sites for loading ECL-active species, thus significantly improving the ECL performance of substrates; While Fe3+ presented on surface of α-FeOOH nanospheres could be reduced to Fe2+ in negative potentials, after which might activate persulfate in a Fenton-like process, resulting in more sulfate free radicals for more effective ECL responses via electron transfer reactions. Additionally, Ag nanoclusters (Ag NCs) stabilized by single stranded oligonucleotide were introduced as quenching probes for CdS QDs owing to the well-matched donor-acceptor spectrum for efficient energy transfer, which makes them appropriate for detection of E2. The proposed strategy displayed a desirable dynamic range from 0.01 to 10 pg mL−1 with a limit of detection of 0.003 pg mL−1. The proposed strategy based on the ECL-RET strategy offered an ideal way for E2 detection, and also revealed an alternative platform for detection of other small molecules.

A method based on the Stokes vectors was developed for the measurement of electro-optical (EO) coefficients, and the detailed test principle, experimental apparatus and data processing were described. The practicability of this method was illustrated by the determination of the EO coefficient of lanthanum-modified lead zirconate titanate (PLZT) transparent ceramics, and the measurement results indicated that the standard deviation values of the EO coefficients obtained by the Stokes vector method was almost half of that of the values measured using the Senarmont compensator method. The apparatus used for the Stokes vector method consists of only a few optical elements and was easy to adjust and calibrate, thereby enabling scientific, accurate, and efficient EO coefficient measurements for the development of EO materials and devices.

Rejection sensitivity online was prevalent among adolescents that was potential risk factor for affect. The purpose of the study was to examine the relationship between rejection sensitivity on networking sites and sentimental responses through self-assesion and self-esteem respectively and the sequential mediated effect both of them, the research also tested the moderated role of gender. There were 823 adolescents included in this research. They completed a questionnaire packages consisting of 4 scales. The findings indicated that adolescents’ emotional responses to rejection sensitivity on networking sites was significant, the mediating model was remarkable through self-assesion and significant sequential mediated effect both of self-assesion and self-esteem for affect among girls but not boys, however, rejection sensitivity on social networking sites was directly related to negative affect among boys, gender played a moderating role in the relationship between rejection sensitivity on social networking sites and positive affect/negative affect respectively, boys were sensitive to negative affect but girls were sensitive to both of positive and negative affect and boys responsed to stimulus slightly than girls. The findings provided a new insight to the prevention and intervention for the negative affect and improvement for positive affect among adolescents. The implication of the conclusions for understanding and counteracting rejection sensitivity on networking sites were discussed.

In this study, galvanic replacement provides a simple route for the synthesis of PdAg hollow nanoflower structures by using the Ag-seeds as sacrificial templates in the presence of l-ascorbic acid (reductant) and CTAC (capping agent). Transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and EDS mapping were used to characterize the as-prepared PdAg hollow nanoflower catalysts, where they were alloyed nanoflower structures with hollow interiors. By maneuvering the Pd/Ag ratio, we found that the as-prepared Pd1 Ag3 hollow nanoflower catalysts had the optimized performance for catalytic activity toward ethanol oxidation reaction. Moreover, these as-prepared PdAg hollow nanoflower catalysts exhibited noticeably higher electrocatalytic activity as compared to pure Pd and commercial Pd/C catalysts due to the alloyed Ag-Pd composition as well as the hollow nanoflower structures. It is anticipated that this work provides a rational design of other architecturally controlled bimetallic nanocrystals for application in fuel cells.

INTRODUCTION: Several mitochondrial DNA mutations have been reported to be associated with nonsyndromic hearing loss in several families. However, little is known about the prevalence of these mutations in sporadic patients with nonsyndromic sensorineural hearing loss. OBJECTIVE: The purpose of our study was to investigate the incidence of these mitochondrial DNA mutations in such population. METHODS: A total of 178 sporadic patients with nonsyndromic sensorineural hearing loss were enrolled in this study. Genomic DNA was extracted from the peripheral blood sample. We employed the SNaPshot(r) sequencing method to detect five mitochondrial DNA mutations, including A1555G and A827G in 12S rRNA gene and A7445G, 7472insC, and T7511C in tRNASerUCN gene. Meanwhile, we used polymerase chain reaction and sequenced the products to screen GJB2 gene mutations in patients carrying mitochondrial DNA mutations. RESULTS: We failed to detect the presence of A1555G mutation in 12S rRNA gene, and of A7445G, 7472insC, T7511C mutations in tRNASerUCN gene in our population. However, we found that 6 patients (3.37%) were carriers of a homozygous A827G mutation and one of them also carried homozygous GJB2 235delC mutation. CONCLUSION: Our findings in the present study indicate that even in sporadic patients with nonsyndromic sensorineural hearing loss, mitochondrial DNA mutations might also contribute to the clinical phenotype. Resumo Introdução: Diversas mutações do DNA mitocondrial tem sido descritas, em diferentes famílias, associadas à deficiência auditiva não sindrômica. No entanto, pouco se sabe sobrea prevalência dessas mutações em pacientes esporádicos com deficiência auditiva sensorioneural não sindrômica. Objetivo: A finalidade do nosso estudo foi investigar a incidência dessas mutações no DNA mitocondrial nessa população. Método: No total, 178 pacientes esporádicos com deficiência auditiva sensorioneural não sindrômica foram recrutados para participação no estudo. O DNA genômico foi extraído de amostra, de sangue periférico. Utilizamos o método de sequenciamento SNaPshot(r) para detecção de cinco mutações do DNA mitocondrial: A1555G e A827G no gene 12S rRNA e A7445G, 7472insCe T7511C no gene tRNASerUCN. Paralelamente, utilizamos a reação de polimerase em cadeia e sequenciamos os produtos para triagem das mutações no gene GJB2 nos pacientes portadores de mutações no DNA mitocondrial. Resultados: Em nossa população, não conseguimos detectar a presença da mutação A1555G no gene 12S rRNA e nem as mutações A7445G, 7472insC e T7511C no gene tRNASerUCN. Entretanto, constatamos que seis pacientes (3,37%) eram portadores da mutação homozigota A827G; e um deles também portava a mutação homozigota GJB2 235delC. Conclusão: Nossos achados no presente estudo indicam que, mesmo em pacientes esporádicos com deficiência auditiva sensorioneural não sindrômica, as mutações do DNA mitocondrial também podem contribuir para o fenótipo clínico.

Parkinson's disease (PD) is primarily due to the progressive, selective and irreversible loss of dopaminergic (DA) neurons in the substantia nigra (SN). Interestingly, DA neurons in the ventral and lateral SN are much more susceptible than adjacent dopamine neurons in the ventral tegmental area (VTA) not only in human PD but in many PD model systems. However, the molecular causes of regional vulnerability in PD remain unknown. In our previous studies, we established acute PD animal models by administration of MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine), and found that AQP4 knockout mice were significantly more prone to MPTP-induced neurotoxicity. Here, we further observe that AQP4 deficiency resulted in the same susceptible to MPTP between SN DA neuron and VTA neurons both in acute and chronic PD model. Moreover, we show that AQP4 deficiency increased the numbers of reactive astrocytes and microglias not only in the SN and but also in the VTA under basal and MPTP-induced situations. Meanwhile, AQP4 deficiency disrupted the balance of the pro-inflammatory cytokine/neurotrophin in midbrain. Taken together, these results demonstrate that glial AQP4 is involved in the susceptibility differences of DA neurons between SN and VTA, although the precise mechanism of AQP4 remains to be explored. Moreover, these findings also suggest that these susceptibility differences are not only due to intrinsic neuronal factors, but also attribute to differences in astrocytes of these regions.

A hybrid nanostructure of Au–Ag nanorings prepared by decorating the surface of N-doped graphene (NG) was utilized as an electrocatalyst to construct a novel electrochemical sensor. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were used to characterize the as-prepared composites. The Au–Ag nanorings/NG modified electrode exhibited a much better electrochemical response of rutin than that of Au/NG, Ag/NG and NG due to the synergetic catalytic effect between the Au–Ag nanorings and NG. Under optimal conditions, the electrochemical sensor of the Au–Ag nanorings/NG exhibited a wide linear range from 0.05 μM to 241.2 μM (S/N = 3) with a low detection limit of 0.01 μM. In addition, the proposed sensor also displayed good anti-interference ability and long-term stability, which had promising applications in bioassay analysis.

In this article, a nonenzymatic electrochemical sensor based on chemically reduced graphene oxide (RGO) and a Pt nanoparticles (PtNPs) modified glassy carbon electrode has been fabricated and used to determine rutin. The nanocomposites of PtNPs/RGO were characterized by transmission electron microscopy and X-ray diffraction, and the electrochemical behaviors of rutin on PtNPs/RGO were demonstrated by cyclic voltammetry and differential pulse voltammetry. The as-fabricated electrochemical sensor for rutin exhibited a wide linear range from 0.057 to 102.59 μM with a detection limit of 0.02 μM (S/N = 3). Additionally, the as-prepared electrode displayed a good reproducibility, stability and anti-interference ability for the detection of rutin. Finally, the electrode was successfully applied for the determination of rutin in pharmaceutical tablets.

The EGFR-targeting cancer therapies are commonly facing drug resistance, mostly due to mutations. Gene therapy with artificial microRNA targeting EGFR conserved sequence may avoid such problem. In this study, we constructed a recombinant adenovirus expressing EGFR-targeting artificial microRNA and active revCASP3 (Ad-EC), under the control of tumor-specific SLPI promoter, and evaluated its inhibitory effect on HEP-2 cancer cells both in vitro and in vivo. MTT assay showed that cell growth inhibition rate at 72h was 44.0% in Ad-EC group at MOI 50, while the rate was 7.7% in the control virus Ad-GFP group and 3.6% in Cetuximab (500 μg/ml) group respectively. Flow cytometry analysis revealed the late apoptotic cells rate was 36.1% in Ad-EC group, significantly higher than 6.5% of Ad-GFP group (p < 0.001). When Ad-EC (MOI 50) was combined with CDDP (0.25 μg/ml), late apoptotic cells rate increased to 61.2%, significantly higher than each monotherapy group (P < 0.001). The real-time xCELLigence system recorded an effective cell growth inhibition in Ad-EC and CDDP groups, and more enhanced effect in Ad-EC plus CDDP group. Western blot revealed that Ad-EC could inhibit the activation of AKT pathway and ERK1/2 pathway, while Cetuximab had the AKT pathway over-activated. In vivo experiments with HEP-2 xenograft in nude mice confirmed the tumor inhibition in Ad-EC, CDDP and Ad-EC plus CDDP groups compared with PBS group (P < 0.01). Collectively, these data support the effective inhibition of cancer cells by this novel gene therapy strategy.

e12569 Background: Breast cancer (BC) is one of the most common malignant tumors among women in the world. Although under 7% of all BC cases, young BC is more difficult to diagnose and can be aggressive and less likely to respond to treatment. Exploring and identifying potential biomarkers for the diagnosis and prognosis of younger BC patients is necessary. Methods: A total of 1,202 BC patients under 35 years old (YD) were enrolled. Deep sequencing targeting 450 cancer genes was performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) for genomic alteration identification. Statistical analysis was performed by Fisher’s exact test. Results: Of 1,202 young BC patients, 3 were under 20 YD, 85 were 20-25 YD, 371 were 26-30 YD, and 747 were 31-35 YD. Based on pathological, there were 899 infiltrative duct carcinomas, 10 infiltrative lobular carcinomas, and 292 BCs with unclear pathological type. According to molecular features, 587 HR+/HER2- (group I), 118 HR+/HER2+ (group II), 75 HR-/HER2+ (group III) and 193 HR-/HER2- (group IV) were included. Chemotherapy, radiotherapy, endocrine therapy and targeted therapy were received and 1074 patients were followed up. The median overall survival (OS) was 76 (5-156) months. There was no significant difference in OS between different treatments. The median OS was 81 (range 5-156) months, 67 (range 10-153) months, 76 (range 14-146) months, and 78 (range 13-151) months for group I, II, III, and IV, respectively. The significantly lower OS was observed in group II ( P=0.044). Although group II and group III had similar proportion of targeted treatment (43.22% vs 43.24%, respectively), the OS rate was different (67 vs 76 months, P=0.064). Samples from 46 young BC patients were performed on deep sequencing targeting 450 cancer genes. The most common mutations were TP53 (56%), GATA3 (29%), ERBB2 (27%), CDK12 (20%), and FGFR1 (20%). Different from previous studies, only 4.35% (2/46) of BRCA1/2 mutations were detected in this cohort. The mutation frequency of GATA3 in group II was significantly lower than that in group III (0% vs 71.43%, P=0.017). Conclusions: The most common pathological type of young BC was infiltrative duct carcinoma. The OS of HR+/HER2+ patients were significantly lower than that of others. Our results showed that GATA3 could be a potential biomarker for OS prediction for BC with HER2+, which help to further guide targeted therapy in young BC patients.

There is an urgent need to develop efficient, durable, earth-abundant, and low-cost electrocatalysts for the oxygen evolution reaction (OER) that occurs during the electrochemical splitting of water. Herein, we develop a method to synthesize uniform nitrogen-doped bamboo-like carbon nanotubes (NBCNT) encapsulated with NiFeP nanoparticles (NiFeP@NBCNT). When the as-fabricated nanocomposites are used to catalyze the OER, it exhibits exceptionally high activity in alkaline solution (180 mV @10 mA cm−2 and a low Tafel slope of 59 mV dec−1) and outstanding long-term stability. The turnover frequency (TOF) for NiFeP@NBCNT at an overpotential of 350 mV are calculated to 3.38 s−1. The OER reaction mechanism on the NiFeP@NBCNT modified electrode is explored by comparing the XPS spectra before and after electrochemical OER testing. The excellent catalytic properties make NiFeP@NBCNT a promising candidate for electrochemical catalysis in water splitting.

The epithelial cell adhesion molecule (EpCAM) is a known biomarker of circulating tumor cells that plays an important role in tumor metastasis. The detection of EpCAM is vital for personalized diagnosis and therapy but is challenging because of its extremely low concentration in peripheral blood. In our work, an electrochemical aptasensor has been developed to quantitatively detect EpCAM at low concentrations. A gold electrode modified with an aptamer can capture EpCAM, which can then be further recognized by a second aptamer acting as a signal reporter. To amplify the signal, a silica nanoparticle/CdSe complex has been designed to enhance the detection system. First, silica nanoparticles were synthesized to act as carriers for loading many CdSe quantum dots which are capable of binding with the second aptamer by biotin-streptavidin interactions. A molecule of EpCAM can bind with numerous CdSe quantum dots (QDs) to realize significant signal amplification. By stripping square wave voltammetry (SSWV), concentrations down to 10 aM EpCAM can be successfully detected and quantified based on the newly developed aptasensor. The detection linear range is from 10 aM to 100 pM. This principle can also be extended to other biomarkers when a suitable aptamer or antibody is available. This aptasensor is expected to be a potential tool for the diagnosis, therapeutic evaluation and personalized medical care of cancer patients.

To assess the seismic risk probability of frameworks in different seismic fortification intensity zones in China, three fortification intensity framework models-specifically, 6 (0.05 g), 7 (0.1 g), and 8 (0.2 g)-were established as the research objects. The incremental dynamic analysis method was used to conduct a structure seismic fragility assessment, in which the fragility curves as well as the damage probabilities under certain peak ground accelerations were obtained. The risk probabilities of all the seismic damage levels of the frameworks in the next 50 years were calculated using the Monte Carlo method based on a study of the seismic hazard of different fortification intensity zones. The results indicate that, in the next 50 years, the risk probabilities of fortification intensity framework models 6, 7, and 8 exceeding “serious damage” were 1.92, 4.25, and 8.28%, respectively. Additionally, the risk probabilities of the models having a damage degree of “collapse” were 0.14, 0.43, and 1.07%, respectively. Based on the risk probability of the structure, the risk level is classified. This study forms the basis for the comprehensive evaluation of building seismic damage risk and can be used as a reference for the development of building seismic disaster prevention countermeasures.

Microneedle arrays have emerged as an alternative method for transdermal drug delivery. Although micromolding using a centrifugation method is widely used to prepare microneedles in laboratory, few researchers were focused on manufacturing processes capable of facile scale-up. A novel female mold was initially designed in this study, namely double-penetration female mold (DPFM) with the pinpoints covered by waterproof breather membrane which was beneficial to reduce the influence of gas resistance and solution viscosity. In addition, DPFM-based positive-pressure microperfusion technique (PPPT) was proposed for the scale-up fabrication of dissolving microneedle arrays (DMNA). In this method, polymer solution and base solution were poured into the DPFM by pressure difference, followed by drying and demolding. The results of optimal microscopy and SEM revealed that the obtained microneedles were uniformly distributed conical-shaped needles. The skin penetration test showed that DMNA prepared using PPPT were able to penetrate the rat skin with a high penetration rate. To realize the transition of microneedles fabrication from laboratory to industry, an automatic equipment was further designed in this study. Different from micromolding method using centrifugation, the equipment based on PPPT and DPFM has superiorities in the scale-up fabrication of microneedles in a highly effective, controllable, and scalable way.

GATA4, a member of the GATA family, serves a key function in several types of cancer, including hepatoblastoma, gastric cancer and breast cancer. However, the function of GATA4 in nasopharyngeal cancer (NPC) is largely unknown. The present study revealed that GATA4 was upregulated in NPC tissue samples and the NPC cell line, 5–8F. Furthermore, the expression of GATA4 was associated with tumor size, metastasis and poor prognosis. Transwell invasion and wound healing analyses demonstrated that GATA4 promoted cell invasion and migration, respectively. Western blotting and reverse transcription-quantitative polymerase chain reaction revealed that GATA4 overexpression decreased the expression of epithelial markers and increased the expression of mesenchymal markers. By contrast, GATA4 inhibition increased the expression of epithelial markers and decreased the mesenchymal markers. Additionally, chromatin immunoprecipitation and dual-luciferase reporter assays revealed that GATA4 promoted epithelial-mesenchymal transition through transcriptionally activating SLUG. Cell counting kit-8 and colony formation assays were performed to analyze the effect of GATA4 on cell proliferation. The results indicated that GATA4 facilitated cell proliferation in NPC. In conclusion, GATA4 acts as an oncogene and serves crucial roles in NPC and GATA4 may find a potential application as therapeutic option in NPC.

This study uses the Delphi method to conduct questionnaire surveys among 30 professionals in higher education, education theory, and management. The first round of surveys was supported by 19 experts who offered their opinions on the preliminary indicators. Their opinions were classified as agree, disagree, agree after revision, or uncertain. The experts also provided other suggestions and comments. The second round of surveys was an improvement of the first, with 16 experts responding. By calculating the arithmetic mean, full-mark frequency, and coefficient of variation, 17 evaluation indicators for the internationalization of junior faculty were identified, including "results being applied abroad," "applications for foreign funds," "number of records in international search engines," "integrating international issues and multicultural understanding into existing courses," and "extent of international cooperation."

Background The clinical response to anti-programmed cell death 1 (PD-1) antibodies in patients with advanced gastric and gastroesophageal junction (GEJ) cancer in China has not been reported. Methods This study evaluated the efficacy and safety of SHR-1210, an anti-PD-1 antibody, in patients with advanced gastric/GEJ cancer in a phase 1 trial. The associations between candidate biomarkers (programmed death ligand 1 [PD-L1] expression, mismatch repair status, tumor mutation load, and lactate dehydrogenase [LDH] levels) and the efficacy of SHR-1210 were also explored. Results Thirty patients with recurrent or metastatic gastric/GEJ adenocarcinoma who were refractory or intolerant to previous chemotherapy were enrolled between June 2, 2016, and June 8, 2017. Seven patients (23.3%) demonstrated objective responses, including 1 complete response. The objective response rates for patients with PD-L1-positive and PD-L1-negative tumors were 23.1% (3 of 13) and 26.7% (4 of 15), respectively (P = 1.000). Two treatment-related grade 3 or higher adverse events were reported: one was grade 3 pruritus, and the other (3.3%) was grade 5 interstitial lung disease. All 20 patients tested for the mismatch repair status had mismatch repair-proficient tumors, and the response rate was 30.0% (95% confidence interval, 11.9%-54.3%). Patients with a higher mutation load (4 of 10) tended to have better responses than those with fewer mutations (2 of 10), but the difference was not significant (P = .628). Patients with a >10% relative increase from the baseline LDH level were more likely to experience disease progression (90% [9 of 10]) than patients with a ≤10% change (40% [8 of 20]; P = .017). Conclusions Anti-PD-1 antibody SHR-1210 shows encouraging efficacy in patients with advanced gastric/GEJ cancer in China, including mismatch repair-proficient subgroups.

Multiple network anomaly detection methods have been proposed to deal with rapidly increasing attacks and network disruptions. The existing hierarchical heavy hitter (HHH) is well studied, but it is still difficult to identify more specifically targeted anomalies, as they tend to be small in volume, thus, buried in the entire traffic. To resolve this issue, this paper proposes a new two-stage traffic aggregation method: first screening target application traffic and then applying HHH analysis on classified traffic. Characterizing the normal traffic behavior per application through HHH lattice facilitates the detection of anomalies even in the small traffic volume. Our preliminary evaluation reveals that our proposed method has an advantage in effectively detecting anomalies compared to the existing methods. We plan to further elaborate the anomaly detection capability of our proposed method under various traffic data.

Since the impoundment of the Three Gorges Reservoir in mid-2003, slope displacements have occurred and existing landslides have been reactivated. The movement are a threat to the community and the environment. High precipitation in the area increases landslide susceptibility. The relationships among landslide displacement, rainfall and reservoir drawdown were analyzed for the Baijiabao landslide with the Grey relational analysis approach and using eight years of monitored displacement. The results suggest that rainfall triggered the landslide deformation in the earlier years. Then reservoir drawdown and the combined effect of rainfall and drawdown became preponderant. The identification of the triggers is important for selecting mitigation measures and evaluating the risk due to slope movement.