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Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed and treated in advanced tumor stages with poor prognosis. More effective screening programs and novel therapeutic means are urgently needed. Recent studies have regarded tight junction protein claudin 18.2 (CLDN18.2) as a candidate target for cancer treatment, and zolbetuximab (formerly known as IMAB362) has been developed against CLDN18.2. However, there are few data reported thus far related to the clinicopathological characteristics of CLDN18.2 expression for PDAC.To investigate the expression of CLDN18.2 in PDAC patients and subsequently propose a new target for the treatment of PDAC.The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, and European Genome-phenome Archive databases were first employed to analyze theThe gene expression ofCLDN18.2 expression is frequently increased in PDAC patients. Thus, it may act as a potential therapeutic target for zolbetuximab in PDAC.

Table S1: The primers of target genes detected by qRT-PCR

Figure S1 JASPAR bioinformatics software was used to analyse the human VEGF and Cyclin D1 promoter region. Figure S2. The COX-2/PGE2 axis regulates HIF-2α levels through a p-VHLmediated degradation pathway under hypoxic conditions. Figure S3 COX-2-specific inhibitors synergistically enhance the anti-tumour activity of sorafenib treatment Figure S4. The COX-2/PGE2 axis regulates HIF-2α activity to promote hepatocellular carcinoma development and reduce the sensitivity of sorafenib treatment.

Purpose: Hypoxia-inducible factor-2α (HIF2α) is regarded as a preferential target for individualized hepatocellular carcinoma (HCC) treatment and sorafenib resistance. Our study aimed to identify the regulatory mechanisms of HIF2α activity under hypoxic conditions. We sought to determine whether the COX-2/PGE2 axis is involved in the regulatory mechanisms of HIF2α activity and of sorafenib resistance in hypoxic HCC cells.Experimental Design: The cell viability, migration, and invasion abilities were measured to analyze the effects of HIF2α on hypoxic HCC cells. Both in vitro and in vivo HCC models were used to determine whether the COX-2/PGE2 axis is a driver of HIF2α level and activity, which then reduces the sensitivity of sorafenib treatment in hypoxic HCC cells.Results: Under hypoxic conditions, the COX-2/PGE2 axis effectively stabilized HIF2α and increased its level and activity via decreasing von Hippel-Lindau protein (p-VHL) level, and also enhanced HIF2α activity by promoting HIF2α nuclear translocation via MAPK pathway. The activation of HIF2α then led to the enhanced activation of VEGF, cyclin D1, and TGFα/EGFR pathway to mediate HCC development and reduce the sensitivity of sorafenib. More importantly, COX-2–specific inhibitors synergistically enhanced the antitumor activity of sorafenib treatment.Conclusions: Our data obtained demonstrate that the COX/PGE2 axis acts as a regulator of HIF2α expression and activity to promote HCC development and reduce sorafenib sensitivity by constitutively activating the TGFα/EGFR pathway. This study highlights the potential of COX-2–specific inhibitors for HCC treatment and particularly for enhancing the response to sorafenib treatment. Clin Cancer Res; 24(13); 3204–16. ©2018 AACR.

Virtual synchronous generators (VSGs) with inertia characteristics are generally adopted for the control of distributed generators (DGs) in order to mimic a synchronous generator. However, since the amount of virtual inertia in VSG control is usually constant and given by trial and error, the real power and frequency oscillations of a battery energy storage system (BESS) occurring under load variation result in the degradation of the control performance of the DG. Thus, in this study, a novel virtual inertia estimation methodology is proposed to estimate suitable values of virtual inertia for VSGs and to suppress the real power output and frequency oscillations of the DG under load variation. In addition, to improve the function of the proposed virtual inertia estimator and the transient responses of the real power output and frequency of the DG, an online-trained Petri probabilistic wavelet fuzzy neural network (PPWFNN) controller is proposed to replace the proportional integral (PI) controller. The network structure and the online learning algorithm using backpropagation (BP) of the proposed PPWFNN are represented in detail. Finally, on the basis of the experimental results, it can be concluded that superior performance in terms of real power output and frequency response under load variation can be achieved by using the proposed virtual inertia estimator and the intelligent PPWFNN controller.

Oxygen is essential for most life forms. Insufficient oxygen supply can disrupt homeostasis and compromise survival, and hypoxia-induced cardiovascular failure is fatal in many animals, including humans. However, certain species have adapted and evolved to cope with hypoxic environments and are therefore good models for studying the regulatory mechanisms underlying responses to hypoxia. Here, we explored the physiological and molecular responses of the cardiovascular system in two closely related hypoxia-adapted species with different life histories, namely, Qinghai voles (氧气对于大多数生物来说都是必不可少的。氧气供应不足会破坏机体平衡甚至危及生命，缺氧引起的心血管衰竭对包括人类在内的许多动物来说都是致命的。值得注意的是，自然界中的一些生物已经适应了低氧环境，这使它们成为研究低氧环境下心血管系统调控机制的良好模型。青海田鼠（

Low cost electrodes with high activity and stability are the key to water splitting for green hydrogen production. Herein, an efficient integrated Ni/CoFe LDH array electrocatalyst is synthesized by a one-step electrodeposition strategy. The Ni/CoFe LDH shows splendid electrocatalytic performance for water oxidation, with a low overpotential (324 mV at a 50 mA cm−2 current output), a small Tafel slope (32 mV dec−1), and excellent durability. The improved activity can be attributed to the synergy of the electronic structure fine-tuning and the hydrophilic nanostructured surface.

Identifying informal e-waste recycling activity is crucial for preventing health hazards caused by e-waste pollution. This study attempted to build a prediction model for e-waste recycling activity based on the differential exposure biomarkers of the populations between the e-waste recycling area (ER) and non-ER. This study recruited children in ER and non-ER and conducted a quasi-experiment among the adult investigators to screen differential exposure or effect biomarkers by measuring urinary 25 volatile organic compound (VOC) metabolites, 18 metals/metalloids, and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Compared with children of the non-ER, the ER children had higher metal/metalloid (e.g., manganese [Mn], lead [Pb], antimony [Sb], tin [Sn], and copper [Cu]) and VOC exposure (e.g., carbon-disulfide, acrolein, and 1-bromopropane) levels, oxidative DNA damage, and non-carcinogenic risks. Individually added 8-OHdG, VOC metabolites, and metals/metalloids to the support vector machine (SVM) classifier could obtain similar classification effects, with the area under curve (AUC) ranging from 0.741 to 0.819. The combined inclusion of 8-OHdG and differential VOC metabolites, metals/metalloids, and mixed indexes (e.g., product items or ratios of different metals/metalloids) in the SVM classifier showed the highest performance in predicting e-waste recycling activity, with an AUC of 0.914 and prediction accuracy of 83.3 %. "Sb × Mn", followed by "Sn × Pb/Cu", "Sb × Mn/Cu", and "Sn × Pb", were the top four important features in the models. Compared with non-ER children, the levels of urinary Mn, Pb, Sb, Sn, and Cu in ER children were 1.2 to 2.4 times higher, while the levels of "Sb × Mn", "Sn × Pb/Cu", "Sb × Mn/Cu", and "Sn × Pb" were 3.5 to 4.7 times higher, suggesting that these mixed indexes could amplify the differences between e-waste exposed and non-e-waste exposed populations. With the continued inclusion of new biomarkers of e-waste pollution in the future, our prediction model is promising for screening informal e-waste recycling sites.

To maximize the utilization and response to the high oxidative stress environment of tumor sites while avoiding the dilemma of enhancing reactive oxygen species (ROS) response in a single way, mitochondrial targeting combined with fluorescent self-reporting polymeric nanocarriers (1K-TPP and 2K-TPP) with grafted structures were synthesized via a chemoenzymatic method in a high yield to simultaneously enhance the drug delivery of endogenous ROS responses. 1K-TPP and 2K-TPP loaded doxorubicin (DOX) at a high content over 12% and formed homogeneous spherical micelles. In vitro, both of them showed promising high sensitivity (detection limit below 200 nM H2O2), fast response, and ratiometric fluorescent self-reporting properties (fluorescent enhancement more than 200 times) to ROS and excellent stability under physiological conditions, while achieving a rapid release of the DOX in response to 1 mM H2O2. Cell co-localization experiments exhibited that they had favorable mitochondrial targeting, and mitochondrial isolation experiments also confirmed that the TPP-modified 1K-TPP selectively accumulated nearly three times in mitochondria than that in total cells. The internalization of 1K-TPP and 2K-TPP into cancer cells was greatly improved by nearly 200% compared to that of unmodified control (1K-OH and 2K-OH) and also explored a unique energy-dependent endocytosis. Furthermore, stimulation of endogenous ROS enhanced the green fluorescence intensity (up to 51.4%) of the linked probe so as to destroy the internal structure of the nanocarriers, achieving self-reporting of the drug's intracellular release and tracking of the intracellular location of nanocarriers. The cytotoxicity of DOX-loaded 1K-TPP and 2K-TPP in tumor cells with a higher ROS content showed statistical superiority to that of 1K-OH and 2K-OH, benefiting from the extremely good endogenous ROS response sensitivity leading to the differential selective release of drugs. These results demonstrate the potential of 1K-TPP and 2K-TPP, especially for 1K-TPP, as mitochondria-targeted, fluorescent self-reporting nanocarriers for combined enhancement of endogenous ROS responsiveness.

We report FeOOH supported on Ni foam which enables highly efficient UOR electrocatalysis and can be readily produced through a hydrolysis reaction. Our developed UOR catalyst as the anode can provide a current density of 200 mA cm−2 at 1.427 V vs. RHE, as well as remarkable operational stability, representing the best yet reported noble metal-free urea electrolyser.

Chaotic systems have been intensively studied for their roles in many applications, such as cryptography, secure communications, nonlinear controls, etc. However, the limited complexity of existing chaotic systems weakens chaos-based practical applications. Designing chaotic maps with high complexity is attractive. This paper proposes the exponential sine chaotification model (ESCM), a method of using the exponential sine function as a nonlinear transform model, to enhance the complexity of chaotic maps. To verify the performance of the ESCM, we firstly demonstrated it through theoretical analysis. Then, to exhibit the high efficiency and usability of ESCM, we applied ESCM to one-dimensional (1D) and multi-dimensional (MD) chaotic systems. The effects were examined by the Lyapunov exponent and it was found that enhanced chaotic maps have much more complicated dynamic behaviors compared to their originals. To validate the simplicity of ESCM in hardware implementation, we simulated three enhanced chaotic maps using a digital signal processor (DSP). To explore the ESCM in practical application, we applied ESCM to image encryption. The results verified that the ESCM can make previous chaos maps competitive for usage in image encryption.

Pyridine-Si-xanthene, a novel near-infrared fluorescent dye, dispalys better photophysical properties compared with Si-rhodamines including improved modifiability and red-shifted emission wavelength. The application is exemplified through the development of a lysosomes-targeting probe capable of imaging cysteine in cells and in vivo.

As important members of the reactive sulfur species (RSS), biological thiols including cysteine, homocysteine and glutathione play crucial roles in many physiological and pathological processes. Development of highly sensitive and selective methods for biothiol detection is of great significance. In this work, we developed a hemicyanine based probe (HXPIS) for near-infrared fluorescence detection of biological thiols in living cells and tissues. The probe HXPIS is capable of detecting biothiols with high selectivity as well as low detection limit (less than 11 nM). In addition, confocal laser scanning microscopy experiments of HeLa cells and Escherichia coli showed that HXPIS could be used to monitor intracellular and bacterial levels of biothiols. Furthermore, HXPIS was applied to distinguish live and dead Escherichia coli. Finally, the imaging of rat liver tissue slices demonstrated the outstanding staining and penetrating ability of the near infrared fluorescent probe.

In comparison with the prevalent 2D material-supported single atom catalysts (SACs), the design and fabrication of SACs with single molecule substrates are still challenging. Here we introduce a new type of SAC in which a recently identified all-boron fullerene B40 is employed as the support and its catalytic performance toward the nitrogen reduction reaction (NRR) process is explored in theory. Taking advantage of the novel heptagonal ring substructure on the sphere and the electron-deficient nature of boron, the atomic metals are facile to reside on B40 to form atomically dispersed η7-B40M exohedral complexes. Among a series of candidates, originating from the proper metal-adsorbate interactions, the atomic tungsten-decorated B40W is screened out as the most feasible catalyst for the NRR with a low over-potential and high selectivity to passivate the competitive hydrogen evolution process.

The efficient and rapid formation of natural gas hydrate is of great significance for its large-scale industrial application, which is inseparable from the intensive study of hydrate formation mechanism. Most of the previous studies focused on the growth of hydrate crystals and the effects of different factors on the morphology. However, the research specifically on the nucleation and theoretical analysis of tetra-n-butylammonium bromide (TBAB) hydrate has not been reported. In this work, the nucleation of TBAB hydrate in 2 μL droplets was studied using high-speed photography. Combined with the classical nucleation theory, a model for calculating the Gibbs free energy required for TBAB hydrate nucleation by fugacity is proposed. Through this model and combined with macro experimental phenomena, it is calculated for the first time that the maximum critical nucleation size of A-type TBAB hydrate is about 29(±6) A and that of B-type TBAB hydrate is about 15.6(±6) A. This work has great significance for further study of hydrate formation kinetics.

A mitochondria targeting and immobilized fluorescent probe (Rd1) using triphenylphosphonium as the targeting group and methoxymaleimide as the fixed site is designed for the detection of ClO-. The methoxymaleimide fixed group can react with nucleophiles, such as the reactive thiol groups present in mitochondrial polypeptides and proteins, and form covalent bonds to immobilize the probe within mitochondria. The immobilization of Rd1 enhances its ability to withstand the risk of leakage from mitochondria. Methoxymaleimide shows better reactivity toward Cys than glutathione (GSH), which decreases the ineffective labeling of GSH when it covalently bonds with the reactive thiol residues of mitochondrial proteins; furthermore, it can resist hydrolysis during a long-term storage in water, compared with the classic benzyl chloride fixed unit. The imaging results indicate that Rd1 displays enhanced retention within the mitochondria of cells and tissues upon the decrease of mitochondrial membrane potential (MMP) caused by different stimulations. Furthermore, it possesses the ability to visualize exogenous and endogenous ClO- in living cells, tissues, and zebrafishes.

The viscosity of lysosome is reported to be a key indicator of lysosomal functionality. However, the existing mechanical methods of viscosity measurement can hardly be applied at the cellular or subcellular level. Herein, a BODIPY-based two-photon fluorescent probe was presented for monitoring lysosomal viscosity with high spatial and temporal resolution. By installing two morpholine moieties to the fluorophore as target and rotational groups, the TICT effect between the two morpholine rings and the main fluorophore scaffold endowed the probe with excellent viscosity sensitivity. Moreover, Lyso-B succeeded in showing the impact of dexamethasone on lysosomal viscosity in real time.

The substituent cross-interaction effect in the substituted benzylidene anilines ( p -X C 6 H 4 CH N C 6 H 4 Y- p ) has been observed and widely investigated. In order to investigate whether the substituent cross-interaction effect exist in all the conjugated systems containing C N polar bond, this paper employed 2-X-5-Y pyrimidines as the model compounds for study. The influences of substituents X and Y on the 1 H NMR and 13 C NMR chemical shifts of 2, 5-disubsitituted pyrimidines have been systematically investigated. Quantitative structure-chemical shifts relationship models have been built for δ (H 4,6 ), δ (C 2 ), δ (C 4,6 ) and δ (C 5 ) with four to six molecular descriptors. These models were confirmed of good stability and predictive performances by leave-one-out cross validation. This study indicates that the substituent effects of 2,5-disubstituted pyrimidines are much more complex than that of the substituted benzylidene anilines. More structural factors besides of Hammett parameter should be taken into consideration. Different from the substituted benzylidene anilines, the cross-interaction effect (Δ σ 2 ) of substituents X and Y has little contribution to δ (H 4,6 ), δ (C 2 ), δ (C 5 ) and δ (C 4,6 ) of 2,5-disubstituted pyrimidines.

A novel reaction-based fluorescent probe (ATC-Hg) was designed and synthesized via the "covalent assembly" principle, which exhibited excellent selectivity and high sensitivity for Hg2+ and CH3Hg+. Moreover, it is the first Hg(ii) sensitive fluorescent probe that has been successfully applied in imaging in both cells and Escherichia coli.

As fluorescent probes, the small Stokes shift and ACQ effect limit the application of BINOL derivatives. Herein, a new series of BINOL derivatives were synthesized which could be turned from ACQ to AIE fluorophores by changing the electron withdrawing group. Among these compounds, BIN-COP exhibits an obvious AIE property with low cytotoxicity. The bioimaging performance indicated that the designed fluorophores could be successfully used for bioimaging.

Measuring the pionic structure function is of high interests as it provides a new area for understanding the strong interaction among quarks and testing the QCD predictions. To this purpose, we investigate the feasibility and the expected impacts of a possible experiment on EicC. We show the simulation results on the statistical precision of an EicC measurement, based on the model of leading neutron tagged DIS process and the parton distribution functions of the pion from JAM18 global analysis. The simulation shows that at EicC, the kinematics cover $x_��$ range from 0.01 to 1, and $Q^2$ range from 1 GeV$^2$ to 50 GeV$^2$, within the acceptable statistical uncertainty. Assuming an integrated luminosity of 50 fb$^{-1}$, in the low-$Q^{2}$ region ($, 9 pages, 12 figures

As a well-known regression clustering algorithm, fuzzy c-regressions (FCR) has been widely studied and applied in various areas. However, FCR appears to be rather sensitive to the undesirable initialization and the presence of noise or outliers in data sets. As a modified alternative, possibilistic c-regressions (PCR) can ameliorate the problem of noise and outliers, but it depends more heavily on initial values. Besides, the number of models should be determined a priori in both algorithms. To overcome these issues, this paper proposes a generalized alternative, called fuzzy weighted c-harmonic regressions (FWCHR), in which, a dynamic-like weight term based on the distinguished feature of the harmonic average is first introduced to enhance robustness. Furthermore, FWCHR can encompass FCR and PCR if some conditions are satisfied. And then a generalized mountain method (GMM) is proposed to automatically determine the number of models and estimate the initial values, which makes the proposed FWCHR algorithm totally unsupervised. Some numerical simulations and real applications are conducted to validate the performance of our algorithms.

A dual-site fluorescent probe with double bond and aldehyde as reactive sites, was designed for the selective detection of sulfite and biothiols. Sulfite reacts with conjugate bond selectively, while Cys responses with aldehyde and GSH occurs substitution reaction. Different interactions cause different absorption and fluorescence responses. Moreover, it could be further applied in imaging in living cells.

Mixed-metal uranium-based endohedral clusterfullerenes, Sc

This paper presents the high resolution dynamic on-resistance measurement for GaN device at the system level. The proposed method improves the measurement output linearity and vertical accuracy. It is achieved by omitting the high voltage blocking diode in the main measurement signal path and using the negligible active clamp resistance compared to the instrument resistance. This method also reduces the measurement transient time that provides a fast measurement performance which is important for high speed testing. In this paper the theoretical analysis, method, and hardware designed are explained in detail. In the end, a system verification was built to verify the proposed method.

Dissociative electron attachments to OCS with the attachment energies of 4.3, 4.7, 5.0, 6.2, 6.5, 6.8, and 7.0 eV are investigated by measuring the S − momentum distributions with time-sliced anion velocity image mapping technique. In this energy range, the ground-state fragmentation, e − + OCS → CO( X ˜ 1 Σ+) + S − (2Pu), is only one dissociation pathway allowed in energy. All velocity images show the predominant feature of the low-speed S − ions, but the middle- and high-speed S − ions appear at the higher attachment energies (6.2–7.0 eV). The trimodel speed distribution of S − ion should be attributed to the different populations of the rovibrational states of CO fragment, however, the dynamic details of above dissociations are still unclear and demand theoretical calculations.

BACKGROUND Plenty of evidence has suggested that long non-coding RNAs (lncRNAs) have played a vital part may act as prognostic biomarkers in a variety of cancers. The aim of this study was to screen survival-related lncRNAs and to construct a lncRNA-based prognostic model in patients with cutaneous melanoma (CM). METHODS We obtained lncRNAs expression profiles and clinicopathological data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A lncRNA-based prognostic model was established in training set. The established prognostic model was evaluated, and validated in the validation set. Then, a prognostic nomogram combining the lncRNA-based risk score and clinicopathological characteristics was developed in training set, and assessed in the validation set. The accuracy of the model was evaluated by the discrimination and calibration plots. RESULTS A total of 212 lncRNAs were identified to be differentially expressed in CM. After univariate analysis, LASSO penalized regression analysis, and multivariate analysis, 3 lncRNAs were used to construct risk score model. The proposed risk score model could divide patients into high-risk and low-risk groups with significantly different survival in both training set and validation set. The ROC curve showed good performance in survival prediction in both sets. Furthermore, the nomogram for predicting 3-, 5-, and 10-year OS was established based on lncRNA-based risk score and clinicopathologic factors. The prognostic accuracy of the risk model was confirmed by the discrimination and calibration plots in both training set and validation set. CONCLUSIONS We established a novel three lncRNA-based risk score model and nomogram to predict overall survival of CM. The proposed nomogram may provide information for individualized treatment in CM patients.

A new series of purine-based derivatives with easy availability and colour tunability were synthesized and could be used for lipid droplet imaging., Recently, tetraphenylethene, triphenylamine and other man-made core AIE luminescent materials (AIEgens) have attracted significant scientific interest. However, the design and synthesis of natural product based, facile and color tunable AIEgens remains challenging. Herein, a novel series of AIEgens based on purine-core molecular rotors is reported, which can be facilely synthesized and shows color tunable emission. Moreover, these purine-based AIEgens exhibit lipid droplet specific properties in live cellular imaging with low background, high selectivity and excellent biocompatibility.

This paper proposes a new individual load forecasting method based on data mining technologies. First, the hierarchical cluster analysis is performed to analyze the historical daily load. Next, the results of hierarchical clustering, the week type and weather factors are used to establish a decision tree. Then, the SVM model is established on history days which are similar with the forecast date. Finally, the forecasted load is obtained through the SVM forecasting model. Case studies using real load data show that the proposed new method can improve the accuracy of individual load forecasting.