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Abstract Mismatch Repair (MMR) mechanisms play a pivotal role in rectifying DNA replication errors and maintaining the stability of DNA microsatellite structure. Colorectal cancer (CRC) can be characterized into microsatellite stability (MSS) and microsatellite instability (MSI) subtypes based on the functionality of MMR. MSI CRC notably exhibits enhanced chemotherapy resistance, attributable to diminished MMR-related protein expression. Cold atmospheric plasma (CAP) has emerged as a promising treatment modality, demonstrating efficacy in inducing apoptosis in various cancer cells. However, the therapeutic impact of CAP on MSI colorectal cancer, and the underlying mechanisms remain elusive. In this study, we investigated the effects of CAP on MSI (MC38, HCT116, and LOVO) and MSS (CT26 and HT29) CRC cell lines. We are probing into the products of CAP treatment. Our findings indicate that CAP treatment induces comparable effects on apoptosis, reactive oxygen species (ROS), and reactive nitrogen species (RNS), as well as the expression of apoptosis-related proteins in both MSI and MSS cells. Mechanistically, CAP treatment led to an elevation in the expression of mismatch repair proteins (MLH1 and MSH2), particularly in MSI cells, which notably have been proven to facilitate the activation of apoptosis-related proteins. Collectively, our study reveals that CAP enhances apoptotic signaling and induces apoptosis in MSI colorectal cancer cells by upregulating the expression of MMR-related proteins, thereby reinforcing MMR stabilization.

In the realm of Australian agriculture, the invasive presence of two round snail species, Cernuella virgata and Theba pisana, and two conical snail species, Cochlicella acuta and Cochlicella barbara, has inflicted substantial economic losses. Effective integrated snail management hinges on precise monitoring of snail populations, yet current manual sampling techniques are prohibitively labour-intensive and susceptible to errors. This study underscores the imperative for a machine vision system capable of accurately and efficiently observing snail populations in the diverse landscapes of Australian broadacre no-till cropping fields. The inherent challenges of varied plant residues, gravels, and soil types in crop fields demands a sophisticated optical system to detect small, clustered, and camouflaged snails. Through a meticulous exploration of spectral features and detectability, employing different combinations of wavelengths and machine learning algorithms, this study yielded the promising findings that live round snails, dead round snails, live conical snails, dead conical snails, and complex field materials, were classified with F1 scores ranging from 0.7 to 0.9. This study not only highlights the potential of such a machine vision system, but also delineates ongoing challenges that warrant further investigation. The insights derived serve as a guide for the development of a robust machine vision system aimed at mitigating the impact of pest snails in agricultural fields.

The tea tussock moth is a pest that damages tea leaves, affecting the quality and yield of tea and causing huge economic losses. The efficient asymmetric total synthesis of the sex pheromone of the tea tussock moth was achieved using commercially available starting materials with a 25% overall yield in 11 steps. Moreover, the chiral moiety was introduced by Evans’ template and the key C-C bond construction was accomplished through Julia–Kocienski olefination coupling. The synthetic sex pheromone of the tea tussock moth will facilitate the subsequent assessment and implementation of pheromones as environmentally friendly tools for pest management.

Seven new lanthanide coordination polymers, namely [Ln(cpt)3H2O)]n(Ln = La (1), Pr (2), Sm (3), Eu (4), Gd (5), Dy (6), and Er (7)), which were synthesized under hydrothermal conditions using 4′-(4-(4-carboxyphenyloxy)phenyl)-4,2′:6′,4′-tripyridine (Hcpt) as the ligand. The crystal structures of these seven complexes were determined using single-crystal X-ray diffraction, and they were found to be isostructural, crystallizing in the triclinic P1- space group. The Ln(III) ions were nine-coordinated with tricapped trigonal prism coordination geometry. The Ln(III) cations were coordinated by carboxylic and pyridine groups from (cpt)− ligands, forming one-dimensional ring-chain structures. Furthermore, the luminescent properties of complexes 1–7 were investigated using fluorescent spectra in the solid state. The fluorescence sensing experiments demonstrated that complex 4 exhibits high selectivity and sensitivity for detecting Co2+, Cu2+ ions, and nitrobenzene. Moreover, complex 3 shows good capability for detecting Cu2+ ions and nitrobenzene. Additionally, the sensing mechanism was also thoroughly examined through theoretical calculations.

Abstract In this study, by injecting cold plasma into the silk fibroin (SF) solution, and adding poly (3,4‐ethylenedioxythiophene): polystyrene sulfonic acid (PEDOT:PSS) into the SF solution, the conductive SF‐PEDOT:PSS hydrogel modified by plasma was successfully prepared. The changes of the electrochemical parameters and structure of SF‐PEDOT:PSS hydrogels after plasma modification were observed with plasma discharge time (60, 120, 180 s) and the type of working gas (Ar, air, He) as variables. The results of electrochemical impedance spectroscopy show that both argon plasma and helium plasma can reduce the impedance of SF‐PEDOT:PSS hydrogel in the extremely low‐frequency range (10−2–10° Hz), and a longer discharge time shrinks the impedance, while the impact of air plasma on the impedance of hydrogel is not obvious. The capacitance results show that both argon and helium plasma can make the capacitance of hydrogel larger, and the longer discharge time leads to the larger capacitance. While air plasma can reduce the capacitance of hydrogel. The results of Fourier infrared absorption spectroscopy and X‐ray diffraction spectrum show that the secondary structure of SF is mainly β‐fold. The results of Raman show that PEDOT:PSS is successfully incorporated into hydrogel, and there exists random coil conformation of SF in hydrogel. The results of X‐ray photoelectron spectroscopy show that the SF‐PEDOT:PSS hydrogel mainly contains C, O, and N elements.

Three new metal coordination polymers with different spatial structure, namely {[Co2(H2O)6(4-PDCA)2]2·3H2O}n (SNUT-12), {[Cd(H2O)2(4-PDCA)]·2H2O}n (SNUT-13) and [Zn2(4-PDCA)2]n (SNUT-14), where H2(4-PDCA) = 1-(4-carboxyphenyl)-5-methyl-4-oxo-1,4-dihydropyridazine-3-carboxylic acid, were synthesized by changing the central ion with the same ligand under solvothermal and hydrothermal conditions, which were further characterized by single crystal X-ray diffraction, powder XRD, FT-IR and TGA. Single crystal X-ray analysis revealed that SNUT-12 exhibits a 1D infinite zigzag chains which were constructed by Cobalt(II) ion and 4-PDCA2− ligand, SNUT-13 features a 2D ladder-like structure. Meanwhile, SNUT-14 displays 2-fold 3D → 3D parallel interpenetrating frameworks. In addition, SNUT-12 exhibited high electrocatalytic oxygen evolution reaction, and SNUT-13, SNUT-14 showed strong fluorescence at room temperature.

Cyclodepsipeptides are a large family of peptide-related natural products consisting of hydroxy and amino acids linked by amide and ester bonds. A number of cyclodepsipeptides have been isolated and characterized from fungi and bacteria. Most of them showed antitumor, antifungal, antiviral, antimalarial, and antitrypanosomal properties. Herein, this review summarizes the recent literatures (2010–2022) on the progress of cyclodepsipeptides from fungi and bacteria except for those of marine origin, in order to enrich our knowledge about their structural features and biological sources.

Fatty acid and central carbon metabolism are crucial energy metabolism reactions. However, to date, few studies have examined their distribution characteristics within the alfalfa–rhizobia symbiotic system. To clarify the distributional differences and accumulation rates of fatty acids and central carbon with this system, we measured the plant phenotype, nodule formation, nitrogen fixation capacity, and key nitrogen metabolism enzyme activities of Medicago sativa ‘Gannong No. 9’ 35 days post-inoculation (dpi) with Sinorhizobia meliloti LL11. Additionally, we employed targeted metabolomics to analyze central carbon and fatty acid metabolites in various tissue samples of symbiotic and control (C.K.) plants, as well as in S. meliloti LL11. We found that plant height; root length; aboveground fresh and dry weights; underground fresh and dry weights; and nitrate reductase, nitrogen reductase, glutamine synthetase, and glutamate synthase activities were significantly higher in the leaves and roots of symbiotic plants than in those of C.K. plants. Compared to symbiotic plants, C.K. plants exhibited higher total central carbon and fatty acid metabolite content, accounting for 38.61% and 48.17% of C.K. plants, respectively. We detected 32 central carbon and 40 fatty acid metabolites in S. meliloti LL11, with succinate (343,180.8603 ng·mL−1) and hexadecanoic acid (4889.7783 ng·mL−1) being the most. In both symbiotic and C.K. plants, central carbon metabolite was considerably higher than the fatty acid metabolite central. Moreover, the carbon metabolites found in symbiotic plants were primarily distributed in pink nodule roots (PNRs), with malate exhibiting the highest content (4,800,612.3450 ng·g−1), accounting for 53.09% of total central carbon metabolite content. Fatty acid metabolites were mainly found in pink root nodules (P.N.s), which are sites of nitrogen fixation. Trans-10-nonadecenoic acid and hexadecanoic acid exhibited the highest contents, comprising >15% of the total fatty acid metabolite content. We found that petroselaidic acid is only present in P.N., which seems to be closely related to the nitrogen fixation reaction in P.N. In general, symbiotic plants transfer central carbon metabolites to nodules via PNRs to drive nitrogen fixation. However, in P.N.s, these metabolites are limited, leading to accumulation in PNRs. Fatty acid metabolites, crucial for nitrogen fixation, are prevalent in P.N.s. Conversely, C.K. plants without nitrogen fixation distribute these metabolites primarily to the stems, emphasizing growth. This study provides new insights into the energy metabolism of symbiotic nitrogen fixation.

Tracking the evolution of air pollutants has a critical impact on our ability to further improve air quality, which have been extensively studied in the North China Plain (NCP), the Yangtze River Delta (YRD) and the Pearl River Delta (PRD) regions, but remain poorly characterized in Guizhou located in the east of Yunnan-Guizhou Plateau. Here, we analyzed spatiotemporal variations and trends of six criteria air pollutants, i.e., inhalable particles (PM10), fine particle (PM2.5), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2) and ozone (O3), from 2016 to 2020 in the focus major cities in Guizhou, taking advantage of the extensive network data available since 2016. The annual mean concentrations of the six criteria air pollutants were substantially lower than China’s national ambient air quality standard (NAAQS-II), confirmed a significant improvement of air quality in Guizhou. The annual mean concentrations of PM10, PM2.5, SO2, CO and NO2 all decreased year by year during 2016–2020 in the focus major cities, and the highest decrease occurred in fall or winter. By contrast, O3 increased with a rate ranged from 0.85 μg·m−3 yr−1 (95% CI: 0∼1.78) to 3.71 μg·m−3 yr−1 (95% CI: 2.54∼5.13), and the highest increase occurred in spring or summer, revealing a strong impetus for reducing O3 pollution. Correlations among the six criteria air pollutants unveiled that the correlation coefficients between PM2.5 and NO2 were higher than those of between PM2.5 and SO2 in most focus major cities, mirroring a priority to control NOx to further reduce PM2.5 pollution in Guizhou. The focus of curbing O3 pollution in Guizhou should be redesigned to mitigate multiple precursors from multiple sectors, and efficient control strategies to mitigate warm seasons O3 pollution should also be implemented in cold seasons. Our results will benefit for our knowledge about current air pollution situation and police makers for future air pollution control in Guizhou.

The proliferation of pharmaceuticals in the aqueous environment has adversely impact on human health and ecosystem balance. Pharmaceutical contaminations are difficult to remove effectively by conventional treatment technologies. In order to degrade carbamazepine (CBZ) efficiently, a common antiepileptic drug, three plasma discharge modes were studied, including liquid-phase discharge, air gas-liquid jet and dielectric barrier discharge. It is noteworthy that the degradation efficiency and energy yield reached to highest levels (0.11 g/kWh) when operating at 225 W input power under liquid phase discharge, compared with the other discharge modes. The parameters of concentration, electrode distance, volume, input power and frequency of the discharge were also evaluated and optimized. Plasma emission spectroscopy revealed the degradation process is mainly attributed to reactive oxygen species (ROS), while the role of reactive nitrogen species was not significant. The contributions of diverse ROS were assessed by radical quenching experiments, including p-benzoquinone, p-phthalic acid and tert-butanol. The possible degradation intermediates and pathways of CBZ were tested and analyzed by liquid chromatography-mass spectrometry (LC-MS). Comprehensively consideration of cleanliness, degradation efficiency and application difficulty, liquid-phase discharge treatment is a promising technology for water treatment.

This paper concerns enhancing a lead detection sensor using a combination of polypyrrole (PPy), Nafion (N), and ionic liquid (IL) with thick-film or screen-printing technology on sensitive material-based carbon electrodes. Electrode characterization using a scanning electron microscope (SEM) was conducted to see the morphology of sensitive materials, showing that the spherical particles were distributed evenly on the electrode surface. Analysis using energy dispersive spectroscopy (EDS) shows that the element's atomic composition is 84.92 %, 8.81 %, 6.26 %, and 0.01 % for carbon, nitrogen, oxygen, and bismuth, respectively. Potentiostat measurement with the ambient temperature of 25 °C on a standard lead solution with concentration ranging from 0.05 to 0.5 mg/l yields an average output voltage ranging from 2.16 to 2.27 V. It can be concluded that the sensor is able to detect lead with a sensitivity of 0.21 V in each addition of solution concentration (mg/l) and give an 84 % concentration contribution to the voltage.

AimsThis study aimed to investigate the efficacy and safety of CSP in patients with a high percentage of ventricular pacing and heart failure with HFmrEF.MethodsPatients who underwent CSP for HFmrEF and ventricular pacing >40% were consecutively enrolled from January 2018 to May 2021. All participants were followed up at least 12 months. Clinical data including cardiac performance and lead outcomes were compared before and after the procedure. Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. HFmrEF was defined as heart failure with the LVEF ranging from 41%–49%.ResultsCSP was successfully performed in 64 cases (96.97%), which included 16 cases of left bundle branch pacing (LBBP) and 48 cases of His bundle pacing (HBP). After a mean of 23.12 ± 8.17 months follow-up, NYHA classification (P

Monitoring dynamic balance during gait is critical for fall prevention in the elderly. The current study aimed to develop recurrent neural network models for extracting balance variables from a single inertial measurement unit (IMU) placed on the sacrum during walking. Thirteen healthy young and thirteen healthy older adults wore the IMU during walking and the ground truth of the inclination angles (IA) of the center of pressure to the center of mass vector and their rates of changes (RCIA) were measured simultaneously. The IA, RCIA, and IMU data were used to train four models (uni-LSTM, bi-LSTM, uni-GRU, and bi-GRU), with 10% of the data reserved to evaluate the model errors in terms of the root-mean-squared errors (RMSEs) and percentage relative RMSEs (rRMSEs). Independent t-tests were used for between-group comparisons. The sensitivity, specificity, and Pearson’s r for the effect sizes between the model-predicted data and experimental ground truth were also obtained. The bi-GRU with the weighted MSE model was found to have the highest prediction accuracy, computational efficiency, and the best ability in identifying statistical between-group differences when compared with the ground truth, which would be the best choice for the prolonged real-life monitoring of gait balance for fall risk management in the elderly.

6G technology is now attracting many scientific researchers due to its prominent features including high mobility, high data rate, high operating frequency, and ultra-low end-to-end delay. Compared to the 5G, 6G has certain advantages that can transform smart healthcare to a new advanced intelligent healthcare system, where multiple issues and concerns of the services (e.g., slow ambulance response) are effectively resolved. In such a communication system, patients and service providers communicate with each other via an open internet channel. Since the healthcare data is important and very sensitive, security and privacy in the healthcare network become prominent. In this paper, we introduce a 6G-aided intelligent healthcare environment. Our work also proposes a solution called Centerless User-Controlled Single Sign-On (CL-UCSSO) for achieving a convenient and cost-saving communication in a multi-server system constructed. A three-factor mechanism (combining smart card, password and biometrics) and time bound property are integrated to design the protocol with fast authentication that allows patients and providers to efficiently establish secure communications. Security proof of the proposed protocol is provided using well-known verification tools including RoR model, AVISPA simulation and BAN logic. Results of performance comparisons on various aspects show that our work provides more functionalities and incurs less cost compared with the related works.

Histone lysine crotonylation (KCR), a novel epigenetic modification, is important in regulating a broad spectrum of biological processes and various diseases. However, whether KCR is involved in neuropathic pain remains to be elucidated. We found KCR occurs in macrophages, sensory neurons, and satellite glial cells of trigeminal ganglia (TG), neurons, astrocytes, and microglia of the medulla oblongata. KCR in TG was detected mainly in small and medium sensory neurons, to a lesser extent in large neurons. Peripheral nerve injury elevated KCR levels in macrophages in the trigeminal and dorsal root ganglia and microglia in the medulla oblongata but reduced KCR levels in sensory neurons. Inhibition of histone crotonyltransferases (p300) by intra-TG or intrathecal administration of C646 significantly alleviated partial infraorbital nerve transection (pIONT)- or spinal nerve ligation (SNL)-induced mechanical allodynia and thermal hyperalgesia. Intra-TG or intrathecal administration of Crotonyl coenzyme A trilithium salt to upregulate KCR dose-dependently induced mechanical allodynia and thermal hyperalgesia in mice. Mechanismly, inhibition of p300 alleviated pIONT-induced macrophage activation and reduced the expression of pain-related inflammatory cytokines Tnfα, Il1β and chemokines Ccl2 and Cxcl10. Correspondingly, exogenous crotonyl-CoA induced macrophage activation and the expression of Tnfα, Il1β, Il6, Ccl2 and Ccl7 in TG, which C646 can repress. These findings suggest that histone crotonylation might be functionally involved in neuropathic pain and neuroinflammation regulation.

Phosphorylation of the serine 139 of the histone variant H2AX (γH2AX) is a DNA damage marker that regulates DNA damage response and various diseases. However, whether γH2AX is involved in neuropathic pain is still unclear. We found the expression of γH2AX and H2AX decreased in mice dorsal root ganglion (DRG) after spared nerve injury (SNI). Ataxia telangiectasia mutated (ATM), which promotes γH2AX, was also down-regulated in DRG after peripheral nerve injury. ATM inhibitor KU55933 decreased the level of γH2AX in ND7/23 cells. The intrathecal injection of KU55933 down-regulated DRG γH2AX expression and significantly induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. The inhibition of ATM by siRNA could also decrease the pain threshold. The inhibition of dephosphorylation of γH2AX by protein phosphatase 2A (PP2A) siRNA partially suppressed the down-regulation of γH2AX after SNI and relieved pain behavior. Further exploration of the mechanism revealed that inhibiting ATM by KU55933 up-regulated extracellular-signal regulated kinase (ERK) phosphorylation and down-regulated potassium ion channel genes, such as potassium voltage-gated channel subfamily Q member 2 (Kcnq2) and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in vivo, and KU559333 enhanced sensory neuron excitability in vitro. These preliminary findings imply that the down-regulation of γH2AX may contribute to neuropathic pain.

ObjectiveThis study aimed to explore the outcomes of His-Purkinje conduction system pacing (HPCSP) and to screen the predictors of left ventricular (LV) complete reverse remodeling in patients with true left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF).MethodsPatients who underwent HPCSP for true LBBB and HFrEF from April 2018 to August 2020 were consecutively enrolled. All participants were followed up for at least 1 year. Thrombosis, infection, lead dislodgement, perforation, and other complications were observed after HPCSP. Clinical data, including echocardiographic parameters, electrocardiogram measurements, and cardiac function, were assessed before and after the procedure.ResultsA total of 46 patients were enrolled. HPCSP was successfully deployed in 42 cases (91.30%), which included 37 cases with His bundle pacing (HBP) and 5 cases with left bundle branch pacing (LBBP). The QRS duration decreased significantly (169.88 ± 19.17 ms vs. 113.67 ± 20.68 ms, P < 0.001). Left ventricular end-systolic volume (LVESV) (167.67 ± 73.20 ml vs. 85.97 ± 62.24 ml, P < 0.001), left ventricular end-diastolic diameter (LVEDD) (63.57 ± 8.19 mm vs. 55.46 ± 9.63 mm, P = 0.003) and left ventricular ejection fraction (LVEF) (26.52 ± 5.60% vs. 41.86 ± 11.56%, P < 0.001) improved dramatically. Complete reverse remodeling of the LV with normalized LVEF and LVEDD was found in nearly half of the patients (45.24%). A short QRS duration after HPCSP was a strong predictor of normalized LVEF and LVEDD (P < 0.001). The thresholds increased markedly in two patients approximately 6 months after HBP. No patients died during the total follow-up period of 20.07 ± 6.45 months.ConclusionComplete reverse remodeling of the LV could be found in nearly half of the patients with HFrEF and true LBBB after HPCSP, and the short QRS duration after HPCSP was a strong predictor.

In this work, the surface of carbon cloth is treated by plasma jet to improve its hydrophilicity. The symmetrical carbon cloth-based supercapacitor is assembled with the carbon cloth treated by plasma as the active electrodes and sodium chloride solution as the electrolyte. With the discharge time (1 min, 2 min, 3 min) and working gas types (argon, air, helium) of plasma as variables, the effects of different plasma on the hydrophilicity of carbon cloth are observed, and the changes of the electrochemical properties of the supercapacitors with single or double carbon cloth electrodes treated by different plasma are studied. The contact angle test results show that the plasma of different working gases can weaken the hydrophobicity of carbon cloth, and the helium plasma can make the carbon cloth change from hydrophobicity to hydrophilicity. The electric capacity calculated by cyclic voltammetry shows that plasma can increase the electric capacity of carbon cloth-based supercapacitors. The electric capacity of carbon cloth-based supercapacitors with two carbon cloth electrodes treated by plasma is larger than that of single carbon cloth electrode treated by plasma. The argon and helium plasma with longer discharge time can significantly improve the electric capacity of carbon cloth-based supercapacitors. The galvanostatic charge-discharge curve shows that different working gases of plasma can make carbon cloth-based supercapacitors obtain pseudocapacitance, increase the charge-discharge time and electric capacity. From the AC impedance spectrum, it can be concluded that the plasma of any kind of working gas can reduce the impedance and charge transfer resistance of the carbon cloth-based supercapacitor. The longer plasma discharge time lead to the smaller impedance, and the impedance of the supercapacitor with both carbon cloth electrodes treated by plasma is smaller.

The aim of this study was to investigate the association between nadir platelet count and acute kidney injury (AKI) or 28-day all-cause mortality induced by hemorrhagic shock (HS), and to determine the cutoff value of nadir platelet count in HS clinical practice. This retrospective study included hospitalized patients enrolled in a tertiary-care teaching hospital from January 1, 2010 to December 31, 2015. Clinical data from HS admitted to the intensive care unit (ICU) were evaluated. Nadir platelet count was defined as the lowest values in the first 48 h. Multivariate logistic regression and Cox proportional hazards regression were used to assess the correlation between nadir platelet count and AKI or 28-day all-cause mortality induced by HS, respectively; the area under receiver operating characteristic (AU-ROC) and Youde’s index were used to determine the optimal cutoff value of nadir platelet count. Kaplan-Meier’s method and log-rank test were assessed for the 28-day all-cause mortality in AKI and non-AKI groups. Of 1589 patients screened, 84 patients (mean age,37.1 years; 58 males) were included in the primary analysis in which 30 patients with AKI. Multiple logistic results indicated that nadir platelet count was a risk factor of AKI (OR = 0.71,95% confidence interval [CI] 0.54–0.93, P < 0.05). Cox regression analysis revealed that nadir platelet count was independent risk factors for 28-day all-cause mortality (Hazard ratios [HR]0.89,95%CI 0.76–0.99, P < 0.05). Kaplan-Meier curve showed that 28-day all-cause mortality was significantly higher in patients with AKI than non-AKI (P < 0.001).These results suggest that nadir platelet count in the first 48 h is a new biomarker for AKI and 28-day all-cause mortality induced by HS. Moreover, the risk for AKI and 28-day all-cause mortality in HS patients decreased by 29% and 11%, respectively, for every 10 × 109/L increase in platelet count. Additional studies are needed to investigate whether elevation of nadir platelet count reduces the risk in different genders.

Structural optimisation of robotic manipulators is critical for any manipulator used in confined semi-structured environments, such as in agriculture. Many robotic manipulators utilised in semi-structured environments retain the same characteristics and dimensions as those used in fully-structured industrial environments, which have been proven to experience low dexterity and singularity issues in challenging environments due to their structural limitations. When implemented in environments other than fully-structured industrial environments, conventional manipulators are liable to singularity, joint limits and workspace obstacles. This makes them inapplicable in confined semi-structured environments, as they lack the flexibility to operate dexterously in such challenging environments. In this paper, structural optimisation of a hyper-redundant cable-driven manipulator is proposed to improve its performance in semi-structured and challenging confined spaces, such as in agricultural settings. The optimisation of the manipulator design is performed in terms of its manipulability and kinematics. The lengths of the links and the joint angles are optimised to minimise any error between the actual and desired position/orientation of the end-effector in a confined semi-structured task space, as well as to provide optimal flexibility for the manipulators to generate different joint configurations for obstacle avoidance in confined environments. The results of the optimisation suggest that the use of a redundant manipulator with rigid short links can result in performance with higher dexterity in confined, semi-structured environments, such as agricultural greenhouses.

The secondary metabolites of Fusarium sporotrichioides, an endophytic fungus with anti-tumor activity isolated from Rauvolfia yunnanensis Tsiang, were investigated. Five trichothecenes, including one previously undescribed metabolite, were isolated and identified. Their structures were elucidated by means of extensive spectroscopic methods; the absolute configuration of compound 1 was determined by the ECD method. Surprisingly, 8-n-butyrylneosolaniol (3) exhibited stronger anti-tumor activity than T-2 toxin against Huh-7 cell line, with an IC50 value of 265.9 nM. 8-n-butyrylneosolaniol (3) promoted apoptosis induction in Huh-7 cells. Moreover, cell cycle analysis showed that cell cycle arrest caused by 8-n-butyrylneosolaniol (3) at the G2/M phase resulted in cell proliferation inhibition and pro-apoptotic activity. Further studies showed a significant decrease in mitochondrial membrane permeabilization and a significant increase in ROS generation, which led to the activation of caspase cascades and subsequent cleavage of PARP fragments. In conclusion, 8-n-butyrylneosolaniol (3) induced cell apoptosis in Huh-7 cells via the mitochondria-mediated apoptotic signaling pathway, which could be a leading compound for anti-tumor agents.

Oleanolic acid (OA), a natural triterpenoid, which has the development prospects in anti-tumor therapy is a widely used hepatoprotective drug in China. It has been reported that OA can cause liver toxicity after higher doses or longer-term use. Therefore, the study aims to explore the possible hepatotoxicity mechanism based on liver metabolic profiles. Liver metabolic profiles were obtained from untargeted ultrahigh performance liquid chromatography (UHPLC)-Q Exactive Orbitrap mass spectrometry (MS) technique. It was found that altered bile acid, amino acid, and energy metabolism might be at least partly responsible for OA-induced hepatotoxicity. Bile acid metabolism, as the most important pathway, was verified by using UHPLC-TSQ-MS, indicating that conjugated bile acids were the main contributors to OA-induced liver toxicity. Our findings confirmed that increased bile acids were the key element of OA hepatotoxicity, which may open new insights for OA hepatotoxicity in-depth investigations, as well as provide a reference basis for more hepatotoxic drug mechanism research.

Background/Aims: Glial cell line-derived neurotrophic factor (GDNF) is an important factor promoting invasive glioma growth. This study was performed to reveal a unique mechanism of glioma cell proliferation and migration. Methods: Human U251 glioma cells were used to screen the optimal GDNF concentration and treatment time to stimulate proliferation and migration. MicroRNA (MiRNA) expression profiles were detected by microarray and confirmed by real-time polymerase chain reaction (PCR). The target genes of differentially expressed miRNAs were predicted by miRWalk, and those targeted by multiple miRNAs were screened with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A regulatory miRNA network was constructed using ingenuity pathway analysis (IPA). Target gene expression of differentially expressed miRNAs was examined by real-time PCR or mRNA microarray. Results: The results show that 50 ng/mL GDNF for 24 h significantly promotes U251 glioma cell proliferation and migration (P < 0.05). Seven miRNAs (hsa-miR-194-5p, hsa-miR-152-3p, hsa-miR-205-5p, hsa-miR-629-5p, hsa-miR-3609, hsa-miR-183-5p, and hsa-miR-487b-3p) were significantly up-regulated after GDNF treatment (P < 0.05). These miRNAs are primarily involved in signal transduction, cell adhesion and cell cycle through mitogen-activated protein kinase (MAPK) signaling, focal adhesion and glioma signal pathways. Five of these miRNAs (hsa-miR-194-5p, hsa-miR-152-3p, hsa-miR-205-5p, hsa-miR-183-5p, and hsa-miR-487b-3p) co-regulate TP53 and Akt. mRNA expression levels of four genes co-targeted by two or more up-regulated miRNAs were significantly decreased after GDNF treatment (P < 0.05). Conclusion: GDNF treatment of U251 glioma cells significantly increased the expression of seven miRNAs involved in cell adhesion and the cell cycle.

Healthcare is now an important part of daily life because of rising consciousness of health management. Medical professionals can know users’ health condition if they are able to access information immediately. Telemedicine systems, which provides long distance medical communication and services, is a multi-functional remote medical service that can help patients in bed in long-distance communication environments. As telemedicine systems work in public networks, privacy preservation issue of sensitive and private transmitted information is important. One of the means of proving a user’s identity are user-controlled single sign-on (UCSSO) authentication scheme, which can establish a secure communication channel using authenticated session keys between the users and servers of telemedicine systems, without threats of eavesdropping, impersonation, etc., and allow patients access to multiple telemedicine services with a pair of identity and password. In this paper, we proposed a smartcard-based user-controlled single sign-on (SC-UCSSO) for telemedicine systems that not only remains above merits but achieves privacy preservation and enhances security and performance compared to previous schemes that were proved with BAN logic and automated validation of internet security protocols and applications (AVISPA).

In this study, acoustic streaming flows inside micro-channels induced by three different types of obstruction—gaseous bubble, liquid droplet and solid bulge—are compared and investigated experimentally by particle tracking velocimetry (PTV) and numerically using the finite element method (FEM). The micro-channels are made by poly(dimethylsiloxane) (PDMS) using soft lithography with low-cost micro-machined mold. The characteristic dimensions of the media are 0.2 mm in diameter, and the oscillation generated by piezoelectric actuators has frequency of 12 kHz and input voltages of 40 V. The experimental results show that in all three obstruction types, a pair of counter-rotating vortical patterns were observed around the semi-circular obstructions. The gaseous bubble creates the strongest vortical streaming flow, which can reach a maximum of 21 mm/s, and the largest u component happens at Y/D = 0. The solid case is the weakest of the three, which can only reach 2 mm/s. The liquid droplet has the largest v components and speed at Y/D = 0.5 and Y/D = 0.6. Because of the higher density and incompressibility of liquid droplet compared to the gaseous bubble, the liquid droplet obstruction transfers the oscillation of the piezo plate most efficiently, and the induced streaming flow region and average speed are both the largest of the three. An investigation using numerical simulation shows that the differing interfacial conditions between the varying types of obstruction boundaries to the fluid may be the key factor to these differences. These results suggest that it might be more energy-efficient to design an acoustofluidic device using a liquid droplet obstruction to induce the stronger streaming flow.

BACKGROUND:Frozen-thawed embryo transfer (FET) has become a routine procedure in assisted reproductive technology (ART). In FET, although blastocysts cultured from thawed cleavage-stage embryos are associated with better perinatal outcomes. it may increase cycle cancellation due to no suitable embryo to transfer. The overall clinical outcomes following transfer of thawed cleavage-stage FET and blastocysts cultured from thawed cleavage-stage embryos in young and advanced age patients remains unclear. Therefore, we aimed to identify the optimal FET strategy in young and advanced age women who undergo FET. METHODS:This retrospective study included 16,387 thaw cycles. We retrospectively analyzed data of couples who had completed the first FET cycle. Two FET strategies were studied: transfer of thawed cleavage-stage embryos (strategy A) or blastocysts cultured from thawed cleavage-stage embryos (strategy B). The clinical and neonatal outcomes of two FET strategies were compared in young (

AIM: To discuss the application of anterior segment optic coherence tomography(AS-OCT)in the diagnosis of corneal ulcer.METHODS: The cross linear scan was used in 88 patients(88 eyes)with corneal lesion by AS-OCT to gather the image data, observe the pathological changed tissue by measuring all layers for patients with initial inspection, providing important visual images and data for treatments. All the patients were followed up for 2mo. RESULTS: Clear images with structure of all layers were obtained. It can provide the intuitive image data and scan the same position and show the changes during the treatment. CONCLUSION: AS-OCT can discover the important condition immediately. It also can monitor course of disease dynamically, provide the intuitive image data for clinical treatment.

Aim Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice. Methods Adult male mice were given atorvastatin (10, 30, and 100 mg/kg, po) daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined. Results Repeated administration of atorvastatin did not affect animal body weight gain or liver weights. Serum enzyme activities were in the normal range. Histologically, the high dose of atorvastatin produced scattered swollen hepatocytes, foci of feathery-like degeneration, together with increased expression of Egr-1 and metallothionein-1. Atorvastatin increased the expression of Cyp7a1 in the liver, along with FXR and SHP. In contract, atorvastatin decreased the expression of bile acid transporters Ntcp, Bsep, Ostα, and Ostβ. The most dramatic change was the 30-fold induction of Cyp7a1. Because Cyp7a1 is a circadian clock-controlled gene, we further examined the effect of atorvastatin on clock gene expression. Atorvastatin increased the expression of clock core master genes Bmal1 and Npas2, decreased the expression of clock feedback genes Per2, Per3, and the clock targeted genes Dbp and Tef, whereas it had no effect on Cry1 and Nr1d1 expression. Conclusion Repeated administration of atorvastatin affects bile acid metabolism and markedly increases the expression of the bile acid synthesis rate-limiting enzyme gene Cyp7a1, together with alterations in the expression of circadian clock genes.

Introduction: Little is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype. Methods: This study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of interest analysis was performed on fractional anisotropy maps, in addition to mean, radial, and axial diffusivity maps, aligned to a common template space using a diffeomorphic, tensor-based registration method. The analysis focused on brain regions known to be affected in AD including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses assessed the impact of APOE4, parental family history of AD, age, and sex on white matter microstructure in late middle-aged participants (aged 47–76 years). Results: Both APOE4 and parental family history were associated with microstructural white matter differences. Participants with parental family history of AD had higher FA in the genu of the corpus callosum and the superior longitudinal fasciculus. We observed an interaction between family history and APOE4, where participants who were family history positive but APOE4 negative had lower axial diffusivity in the uncinate fasciculus, and participants who were both family history positive and APOE4 positive had higher axial diffusivity in this region. We also observed an interaction between APOE4 and age, whereby older participants (≥65 years of age) who were APOE4 carriers, had higher MD in the superior longitudinal fasciculus and in the portion of the cingulum bundle running adjacent to the cingulate cortex, compared to non-carriers. Older participants who were APOE4 carriers also showed higher radial diffusivity in the genu compared to non-carriers. Across all participants, age had an effect on FA, MD, and axial and radial diffusivities. Sex differences were observed in FA and radial diffusivity. Conclusion: APOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics—both expected and unexpected—may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD.

The geometric error motions of rotary stages greatly affect the accuracy of constructed machines such as machine tools, measuring instruments, and robots. In this paper, an embedded sensor system for real-time measurement of two radial and three angular error motions of a rotary stage is proposed, which makes use of a rotary encoder with multiple scanning heads to measure the rotational angle and two radial error motions and a miniature autocollimator to measure two tilt angular errors of the axis of rotation. The assembly errors of the grid disc of the encoder and the mirror for autocollimator are also evaluated and compensated. The developed measuring device can be fixed inside the rotary stage. In the experiments, radial error motions of two points on the axis (h = 5 mm and 60 mm) were measured and calibrated with LVDTs, and the data showed that the radial error motions of the axis were less than 20 μm, and the calibration residual errors were less than 2 μm. When intermittent external forces were applied to the stage, the change of the stage’s error motion could also be monitored accurately.

Nine new 3′-N-phenylsulfonyl docetaxel analogs were synthesized in good yields from the key intermediate N-phenylsulfonyl oxazolidine via a six-step route. These analogs were tested for anti-hepatitis B virus (HBV) activity in vitro. Compounds 3e, 3g and 3j showed more potent inhibitory activity against HBeAg secretion than the positive control lamivudine. Further extensive SAR and mechanistic studies will be reported in due course.

Oleanolic acid (OA) is a triterpenoid and a fantastic molecule with many beneficial effects. However, high-doses and long-term use can produce adverse effects. This study aimed to characterize the hepatotoxic potential of OA. Mice were given OA at doses of 100–3,000 µmol/kg (45–1,350 mg/kg), po for 10 days, and the hepatotoxicity was determined by serum biochemistry, histopathology, and toxicity-related gene expression via real-time RT-PCR. Animal body weight loss was evident at OA doses of 1,000 µmol/kg and above. Serum alanine aminotransferase activities were increased in a dose-dependent manner, indicative of hepatotoxicity. Serum total bilirubin concentrations were increased, indicative of cholestasis. OA administration produced dose-dependent pathological lesions to the liver, including inflammation, hepatocellular apoptosis, necrosis, and feathery degeneration indicative of cholestasis. These lesions were evident at OA doses of 500 µmol/kg and above. Real-time RT-PCR revealed that OA produced dose-dependent increases in acute phase proteins (MT-1, Ho-1, Nrf2 and Nqo1), decreases in bile acid synthesis genes (Cyp7a1 and Cyp8b1), and decreases in liver bile acid transporters (Ntcp, Bsep, Oatp1a1, Oatp1b2, and Ostβ). Thus, the clinical use of OA and OA-type triterpenoids should balance the beneficial effects and toxicity potentials.

Complete neighbourhood preserving embedding (CNPE) is a recently proposed approach to overcome the drawbacks of neighbourhood preserving embedding (NPE) which is difficult to directly apply to face recognition because of computational complexity. However, there are still disadvantages for CNPE: (i) CNPE is time‐consuming when N is large, here N is the sample size; (ii) the solutions of CNPE may suffer from the degenerate eigenvalue problem, that is, several eigenvectors with the same maximal eigenvalue, which make them not optimal in terms of the discriminant ability. In this study, the authors proposed a new approach, namely improved complete neighbourhood preserving (ICNPE), to address the drawbacks of CNPE. ICNPE is more efficient than CNPE and can overcome the degenerate eigenvalue problem of CNPE. Experiments on the Olivetti & Oracle Research Laboratory (ORL), Yale, PIE (pose, illumination and expression) and Alex Martinez and Robert Benavente (AR) face databases show the effectiveness of the proposed ICNPE.

AIM: To evaluate the efficacy of sliding transplantation of auto-corneal limbus stem cell combined with mitomycin C(MMC)on pterygium treatment. METHODS: Totally, 79 patients(89 eyes)who received treatment at our hospital were selected. Eighty-nine eyes of 79 patients with pterygium were randomly divided into two groups: 40 patients(45 eyes)in group A underwent sliding limbal autograft transplantation with MMC and 39 patients(44 eyes)in group B underwent simple limbal autograft transplantation. Recurrence rate and complications were observed during the 12-month follow-up.RESULTS: One of 45 eyes(2%)of group A and six of 44 eyes(14%)in group B were recurrent with significant difference(PP>0.05).CONCLUSION: Sliding transplantation of auto-corneal limbus stem cell combined with MMC for pterygium had advantages of lower recurrence rate, rapid recovery and less complications.

Gauge repeatability and reproducibility studies are significant to quality improvement and quality control. The approaches are always applied to determine the capability of the measurement system. Much of the literature in this field mainly focuses on univariate and multivariate measurement systems. However, the state-of-the-art methods are not appropriate when the quality of a product is characterized by a profile. Therefore, this paper proposes a method for the measured values which can be characterized by a simple linear profile. In addition, the slopes and intercepts of these profiles often vary due to measurement error. Thus, the simple linear profile gauge studies can be considered as a two-response (slope and intercept) problem. X-values transformation is used to make the slope and intercept of each profile independent. ANOVA is utilized to estimate the variance component of measurement error and other sources of variation. Then, the criteria precision to tolerance ratio and percent R&R are introduced to assess the simple linear profile measurement system capability. Finally, the proposed approach is applied to the spring length and elasticity measurement which demonstrates how to implement the method.

With the rapid growth of data communications in size and complexity, the threat of malicious activities and computer crimes has increased accordingly as well. Thus, investigating efficient data processing techniques for network operation and management over large-scale network traffic is highly required. Some mathematical approaches on flow-level traffic data have been proposed due to the importance of analyzing the structure and situation of the network. Different from the state-of-the-art studies, we first propose a new decomposition model based on accelerated proximal gradient method for packet-level traffic data. In addition, we present the iterative scheme of the algorithm for network anomaly detection problem, which is termed as NAD-APG. Based on the approach, we carry out the intrusion detection for packet-level network traffic data no matter whether it is polluted by noise or not. Finally, we design a prototype system for network anomalies detection such as Probe and R2L attacks. The experiments have shown that our approach is effective in revealing the patterns of network traffic data and detecting attacks from large-scale network traffic. Moreover, the experiments have demonstrated the robustness of the algorithm as well even when the network traffic is polluted by the large volume anomalies and noise.

Oxidative stress and glutathione (GSH) depletion are implicated in mycocystin hepatotoxicity. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in microcystin-induced liver injury, Nrf2-null, wild-type, and Keap1-hepatocyte knockout (Keap1-HKO) mice were treated with microcystin (50 μg/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Microcystin increased serum alanine aminotransferase and aspartate aminotransferase activities, and caused extensive inflammation and necrosis in Nrf2-null and wild-type mice, but not in Keap1-HKO mice. Oxidative stress and inflammation are implicated in microcystin-induced hepatotoxicity, as evidenced by increased lipid peroxidation and increased expression of pro-inflammatory genes, such as neutrophil-specific chemokines mKC and MIP-2, and pro-inflammatory cytokines IL-1β and IL-6. The increased expression of these pro-inflammatory genes was attenuated in Keap1-HKO mice. Nrf2 and Nqo1 mRNA and protein were higher in Keap1-HKO mice at constitutive levels and after microcystin. To further investigate the mechanism of the protection, hepatic GSH and the mRNA of GSH-related enzymes were determined. Microcystin markedly depleted liver GSH by 60-70% in Nrf2 and WT mice but only 35% in Keap1-HKO mice. The mRNAs of GSH conjugation and peroxide reduction enzymes, such as Gstα1, Gstα4, Gstμ, and Gpx2 were higher in livers of Keap1-HKO mice, together with higher expression of the rate-limiting enzyme for GSH synthesis (Gclc). Organic anion transport polypeptides were increased by microcystin with the most increase in Keap1-HKO mice. In conclusion, this study demonstrates that higher basal levels of Nrf2 and GSH-related genes in Keap1-HKO mice prevented microcystin-induced oxidative stress and liver injury.

AIM: To explore the clinical significances and changes of related parameters of corneal endothelial cell in keratouveitis patients before and after treatment.METHODS:Fifty-two keratouveitis patients(52 eyes)diagnosed and treated in our hospital from October 2012 to December 2013 were collected. Before and after treatment, the related parameters of corneal endothelial cell in all patients were measured with non-contact corneal specular microscope and these parameters were statistically analyzed. RESULTS: Compared with the normal group, obvious endothelial cell edema and great variation was observed in diseased group. The shorter duration of treatment, the better the recovery of endothelial cells and the fewer cells lose. Conversely, the longer the healing of normal hexagonal cell ratio was smaller, the larger the coefficient of variation. Before and after treatment, the differences of each parameter were statistical significance(PCONCLUSION: The functional recovery of corneal endothelial cell has directly relation with disease times.

The scanning laser Doppler vibrometry (SLDV) technique provides velocities of a structure at 2-dimensional (2-D) angularly evenly spaced (in the laser scanning sense) data points. This causes an unevenly spaced data point distribution on the surface of the test structure. In many cases evenly spaced data point distribution with square or rectangular grids is highly desirable. In this study the SLDV velocity data of a partial surface area of an aircraft fuselage were mapped to truly spatial evenly spaced coordinates by using the spatial DFT-IDFT technique with minimum distortion. This 2-D data mapping technique certainly is not limited to the fuselage, hut can he very useful for many other 3-D structures.

BACKGROUND: Previous studies have demonstrated that QX-314, an intracellular sodium channel blocker, can enter into nociceptors through capsaicin-activated TRPV1 or permeation of the membrane by chemical enhancers to produce a sensory-selective blockade. However, the obvious side effects of these combinations limit the application of QX-314. A new strategy for targeting delivery of QX-314 into nociceptors needs further investigation. The aim of this study is to test whether acidic QX-314, when dissolves in acidic solution directly, can enter into nociceptors through acid-activated TRPV1 and block sodium channels from the intracellular side to produce a sensory-specific analgesic effect. METHODOLOGY/PRINCIPAL FINDINGS: Acidic solution or noradrenaline was injected intraplantarly to induce acute pain behavior in mice. A chronic constrictive injury model was performed to induce chronic neuropathic pain. A sciatic nerve blockade model was used to evaluate the sensory-specific analgesic effects of acidic QX-314. Thermal and mechanical hyperalgesia were measured by using radiant heat and electronic von Frey filaments test. Spinal Fos protein expression was determined by immunohistochemistry. The expression of p-ERK was detected by western blot assay. Whole cell clamp recording was performed to measure action potentials and total sodium current in rats DRG neurons. We found that pH 5.0 PBS solution induced behavioral hyperalgesia accompanied with the increased expression of spinal Fos protein and p-ERK. Pretreatment with pH 5.0 QX-314, and not pH 7.4 QX-314, alleviated pain behavior, inhibited the increased spinal Fos protein and p-ERK expression induced by pH 5.0 PBS or norepinephrine, blocked sodium currents and abolished the production of action potentials evoked by current injection. The above effects were prevented by TRPV1 channel inhibitor SB366791, but not by ASIC channel inhibitor amiloride. Furthermore, acidic QX-314 employed adjacent to the sciatic nerve selectively blocked the sensory but not the motor functions in naïve and CCI mice. CONCLUSIONS/SIGNIFICANCE: Acid solution is a suitable medium for introducing QX-314 into nociceptors through TRPV1 channels to produce a sensory-specific analgesic effect.

This paper presents a new automated change detection method for detecting breaches in the integrity of and attached objects in front of fence wires in multiple outdoor images of the same scene containing fence wires acquired by a mobile camera from slightly different viewing positions, angles and at different times. To detect significant changes, edges of fence wires firstly have to be extracted from multiple outdoor images using a combination of the Sobel detector and an adaptive thresholding technique. Secondly, morphological operations such as dilation and erosion are applied into binary images produced by the previous process in enhancing the binary images. Next, an area-based algorithm is applied to enhanced binary images in separating small and big objects based on their average areas determined once in the calibration process. Finally, objects that survive are then fed into a fuzzy inference system in calculating their possibility values. Based on these possibility values, the survived objects can be classified as significant or unimportant changes. Experimental results demonstrate that the method has a high success rate (94.12%) in detecting true positives in these kinds of multiple outdoor images.

A data-assimilated Taiwan Ocean Prediction (ATOP) system is being developed at the National Central University, Taiwan. The model simulates sea-surface height, three-dimensional currents, temperature and salinity and turbulent mixing. The model has options for tracer and particle-tracking algorithms, as well as for wave-induced Stokes drift and wave-enhanced mixing and bottom drag. Two different forecast domains have been tested: a large-grid domain that encompasses the entire North Pacific Ocean at 0.1° × 0.1° horizontal resolution and 41 vertical sigma levels, and a smaller western North Pacific domain which at present also has the same horizontal resolution. In both domains, 25-year spin-up runs from 1988 - 2011 were first conducted, forced by six-hourly Cross-Calibrated Multi-Platform (CCMP) and NCEP reanalysis Global Forecast System (GSF) winds. The results are then used as initial conditions to conduct ocean analyses from January 2012 through February 2012, when updated hindcasts and real-time forecasts begin using the GFS winds. This paper describes the ATOP system and compares the forecast results against satellite altimetry data for assessing model skills. The model results are also shown to compare well with observations of (i) the Kuroshio intrusion in the northern South China Sea, and (ii) subtropical counter current. Review and comparison with other models in the literature of ¡§(i)¡¨ are also given.

BackgroundWith the rise of mobile technology, an increasing number of people use mobile-based social media to access health information. Many scholars have explored the nature of health information on social media; however, the impact of such information on people was understudied. ObjectiveThis study aimed to examine the nature and impact of health information on mobile-based social media. Specifically, we investigated how the levels of threat and efficacy of breast cancer prevention information affect individuals’ engagement with the information, such as readings and likes. MethodsBreast cancer prevention articles posted on a Chinese mobile-based social media platform (ie, WeChat Subscription Account [WeChat SA]) from January 1 to December 31, 2017, were extracted using the Python Web Crawler. We used content analysis and analysis of covariance to analyze our data. ResultsThe results revealed that the vast majority of titles and main bodies of the articles involved one of the extended parallel process model components: threat or efficacy. ConclusionsBreast cancer prevention information on WeChat SA was well designed. Both threat and efficacy significantly affected the number of readings, whereas only efficacy had a significant effect on the number of likes. Moreover, breast cancer prevention information that contained both high levels of threat and efficacy gained the largest number of readings and likes.

Assessing climate change impacts on crop phenology is essential for developing adaptation options. To better understand crop response and adaptation to climate change, there is an urgent need to investigate whether the impacts weakens and how crops responds to recent climate warming, as well as the roles of different drivers in crop phenology change. Here, we analyzed the spatiotemporal changes in maize phenology and the underlying mechanisms over 1981–2018 using up-to-date 6106 phenological observations at 327 agro-meteorological stations in China. We found that during 1981–2018 maize sowing and maturity dates were generally delayed by 0.6 and 1.2 d per decade, respectively, whereas heading date was advanced by 0.9 d per decade. Maize phenology was most negatively correlated with rising minimum temperature (night-time warming), followed by maximum (daytime) temperature, and least by mean temperature. The trends in maize phenology and the correlation between growth periods and temperature generally declined from 1981 to 1999 to 2000–2018 for both spring and summer maize, although climate warming during growth period did not slow down. The phenological response to temperature weakened mainly owing to agricultural managements, especially cultivar shifts. Climate change shortened growth period by 3.4 and 1.7 d per decade but cultivar shifts prolonged it by 4.5 and 2.1 d per decade for spring and summer maize, respectively. Our study highlights that maize phenology is more sensitive to night-time warming than daytime warming, and cultivar shifts far outweigh climate change. These findings foster the understanding of spatiotemporal dynamics of maize phenology and its drivers, which can benefit to develop effective climate change adaptation options for different regions.

Peroxisome proliferator-activated receptors γ (PPARγ) is a master regulator that controls energy metabolism and cell fate. PPARγ2, a PPARγ isoform, is highly expressed in the normal prostate but expressed at lower levels in prostate cancer tissues. In the present study, PC3 and LNCaP cells were used to examine the benefits of restoring PPARγ2 activity. PPARγ2 was overexpressed in PC3 and LNCaP cells, and cell proliferation and migration were detected. Hematoxylin and eosin (H&E) staining was used to detect pathological changes. The genes regulated by PPARγ2 overexpression were detected by microarray analysis. The restoration of PPARγ2 in PC3 and LNCaP cells inhibited cell proliferation and migration. PC3-PPARγ2 tissue recombinants showed necrosis in cancerous regions and leukocyte infiltration in the surrounding stroma by H&E staining. We found higher mixed lineage kinase domain-like (MLKL) and lower microtubule-associated protein 1 light chain 3 (LC3) expression in cancer tissues compared to controls by immunohistochemistry (IHC) staining. Microarray analysis showed that PPARγ2 gain of function in PC3 cells resulted in the reprogramming of lipid- and energy metabolism-associated signaling pathways. These data indicate that PPARγ2 exerts a crucial tumor-suppressive effect by triggering necrosis and an inflammatory reaction in human prostate cancer.

In the test of the electromagnetic radiation blocking effect of the navigation receiver, it is found that the sensitivity of the navigation receiver to single frequency continuous waves and sinusoidal amplitude modulation waves will change with the change in the satellite useful signal strength. This phenomenon reflects that the sensitivity of frequency equipment to multi-frequency electromagnetic radiation is not fixed to a certain extent. In order to make up for the deficiency that the existing multi-frequency electromagnetic radiation evaluation methods can only deal with a single situation, this paper uses the time delay characteristics of the circuit response, introduces the concepts of normalized interference levels and signal duty cycles, establishes the evaluation model of the multi-frequency non-intermodulation electromagnetic radiation blocking effect of frequency equipment, and puts forward the prediction method of the multi-frequency electromagnetic radiation blocking effect of frequency equipment. Taking a certain type of BeiDou navigation receiver as the test object, the single-frequency continuous wave and double-frequency continuous wave electromagnetic radiation blocking effect tests are carried out by using the full-level irradiation method. The test data are substituted into the model established in this paper for verification. The results show that the maximum evaluation error of the model is 2.23 dB. The model and the effect prediction method established in this paper are of great significance for the survival ability evaluation of frequency equipment in complex electromagnetic environments.

The accurate representation of surface characteristic is an important process to simulate surface energy and water flux in land-atmosphere boundary layer. Coupling crop growth model in land surface model is an important method to accurately express the surface characteristics and biophysical processes in farmland. However, the previous work mainly focused on crops in single cropping system, less work was done in multiple cropping systems. This article described how to modify the sub-model in the SiBcrop to realize the accuracy simulation of leaf area index (LAI), latent heat flux (LHF) and sensible heat flux (SHF) of winter wheat growing in double cropping system in the North China Plain (NCP). The seeding date of winter wheat was firstly reset according to the actual growing environment in the NCP. The phenophases, LAI and heat fluxes in 2004–2006 at Yucheng Station, Shandong Province, China were used to calibrate the model. The validations of LHF and SHF were based on the measurements at Yucheng Station in 2007–2010 and at Guantao Station, Hebei Province, China in 2009–2010. The results showed the significant accuracy of the calibrated model in simulating these variables, with which the R2, root mean square error (RMSE) and index of agreement (IOA) between simulated and observed variables were obviously improved than the original code. The sensitivities of the above variables to seeding date were also displayed to further explain the simulation error of the SiBcrop Model. Overall, the research results indicated the modified SiBcrop Model can be applied to simulate the growth and flux process of winter wheat growing in double cropping system in the NCP.

Edge computing has played an important role in enabling 5G technology which supports a great number of connected narrow-band IoT devices. In an edge computing architecture enabled with global mobile network, edge or IoT devices are wirelessly connected to the edge of the network. Data acquisition and processing will be handled at or close to the edge of the network in a distributed way. Since edge computing is a heterogeneous distributed interactive system with multiple domains and entities, it might suffer from potential attacks and threats. To provide a trusted edge computing, there must have a robust scheme that allows all participants to mutually authenticate in a secure and privacy-preserved way. With the rapid development of IoT technologies, mobile networks and edge computing architecture, single server has been unable to meet the needs of users. In this paper, we propose a privacy-preserved end-to-end password-based authenticated key exchange protocol for multi-server architecture in edge computing networks. Our protocol allows an end user to use an easy-to-remember password to login to the server, then through foreign agent compute a shared key with another end user for specific use of services. The proposed protocol provides strong user anonymity during communication process. Besides, the proposed protocol is proved to be secure using BAN logic and AVISPA tool. Furthermore, performance analysis shows that the proposed protocol gains stronger security and better computational efficiency. Providing lightweight computation with short key size of ECC, our work is a solution to lower latency and improve efficiency in edge computing networks.

Electronic healthcare (e-health) has gained more and more research attention in recent years, due to its flexibility and convenience. E-health is efficiently enabled by telecare medicine information system (TMIS). TMIS provides seamless transfer and timely sharing of medical information for specific healthcare services. Since communications in TMIS are carried out through unreliable channels, data security and user privacy concerns become prominent. With traditional single-server architecture, users must store massive credentials, which causes inefficient communication and significant overhead. Moreover, user credentials in previously proposed schemes are stored at server side, suffering potential risks. Our work proposes a three-factor user-controlled single sign-on (UCSSO) with fast authentication and privacy protection for TMIS. The contributions of this paper are as follows. Our work integrates three factors including password, smart card and biometrics in authentication procedure, for providing a high-security and privacy-preserved communication. We introduce single sign-on solution that allows users to log in to multiple servers using a single password. User-controlled mechanism is proposed to address insider attacks and the risk that registration center may be compromised. The proposed scheme is designed with fast authentication mechanism that helps to efficiently establishes new session key. Our work is proved secure using BAN logic, ROR model, and AVISPA toolset. The results of performance comparison show that our scheme provides more security properties and bears the least overhead, compared with competitive schemes.

Cinnabar has been used for treatment of various disorders for thousands of years. The medical use of cinnabar, however, has been controversial because of its heavy metal mercury content. A large quantity of studies indicate that the toxicity of cinnabar is far below other inorganic or organic mercury-containing compounds. Yet, the underlying molecular basis has remained unresolved. Here, we investigated the beneficial effects of cinnabar on serum-nutrient starvation-elicited cell injury. Our findings showed that treatment of human renal proximal tubular cells (HK-2) with 4 nM cinnabar effectively inhibited nutrient deprivation induced apoptosis, reduced intracellular reactive oxygen species generation and increased GSH content, which was contrary to the exacerbated apoptotic cell death and oxidative stress in cells treated with HgCl2 at equal mercury concentration. In addition, cinnabar exerted robust antioxidative and antiapoptotic effects in cells under dual challenges of nutrient deprivation and treatment of H2O2. The protein expression levels of both CHOP and PERK were remarkably down-regulated in the cells treated with cinnabar compared to the control cells or cells treated with HgCl2. Overall, our data indicates that cinnabar at low concentration exerts anti-oxidative stress and anti-apoptosis effects by inhibiting the expression of the endoplasmic reticulum stress pathway proteins CHOP and PERK.