Search

Background and Purpose: The aim of this study was to investigate the association between daytime napping frequency and the incidence of essential hypertension or stroke as well as to validate causality in this relationship via Mendelian randomization (MR). Methods: We conducted Cox regression analysis on 358 451 participants free of hypertension or stroke from UK Biobank. To validate the results of the observational analysis, we conducted a 2-sample MR for daytime napping frequency (123 single-nucleotide polymorphisms) with essential hypertension in FinnGen Biobank, stroke, and ischemic stroke in MEGASTROKE consortium and performed a corresponding 1-sample MR on the UK Biobank data. Results: Compared with never napping, usually napping was associated with a higher risk of essential hypertension (hazard ratio, 1.12 [95% CI, 1.08–1.17]), stroke (hazard ratio, 1.24 [95% CI, 1.10–1.39], and ischemic stroke (hazard ratio, 1.20 [95% CI, 1.05–1.36]) in our prospective observational analysis. Both the 1-sample and 2-sample MR results indicated that increased daytime napping frequency was likely to be a potential causal risk factor for essential hypertension in FinnGEN (odds ratio, 1.43 [95% CI, 1.06–1.92]) and UK Biobank (odds ratio, 1.40 [95% CI, 1.28–1.58]). The 2-sample MR results supported the potential causal effect of nap frequency on ischemic stroke in MEGASTROKE (odds ratio, 1.29 [95% CI, 1.04–1.62]). Conclusions: Prospective observational and MR analyses provided evidence that increased daytime nap frequency may represent a potential causal risk factor for essential hypertension. The potential causal association of increased nap frequency with ischemic stroke was supported by 2-sample MR and prospective observational results.

Soil salinization is one of key drivers for the degradation of soil quality and yield in arable land. To accurately and quickly evaluate soil salt content in Yinchuan Plain, field and indoor hyperspectral data were processed with first order differential (FDR) transformation, then the feature bands were identified by stepwise regression (SR). Partial least squares regression (PLSR) and support vector machines (SVM) were used to build models, which were verified to figure out the optimal hyperspectral type for the study area. Moreover, segmented and global corrections were performed to process poor hyperspectral, aiming to improve the accuracy of soil salt content inversion. The results showed that the accuracy of soil salt content inversion model based on field hyperspectral data was 58.9% higher than that of the indoor hyperspectral data. The accuracy of the inversion was improved through the segmented and global correction of the indoor hyperspectral. We found that the segmented correction is more accurate for the PLSR model (土壤盐渍化是导致土壤质量下降、耕地减产的重要因素之一。为准确快速评价银川平原土壤含盐量,本研究对野外高光谱数据和室内高光谱数据进行一阶微分(FDR)变换,逐步回归(SR)筛选特征波段,利用偏最小二乘回归(PLSR)与支持向量机(SVM)进行建模,明确适用于本地区土壤含盐量准确反演的光谱类型,并对较差光谱类型进行分段校正与全局校正,尝试提高土壤含盐量反演精度。结果表明: 基于野外光谱的土壤含盐量反演模型精度比室内光谱平均高58.9%;对室内光谱进行分段校正、全局校正后反演精度均有提高,其中,PLSR以分段校正精度更高,建模决定系数(

The problem of maximizing a normalized monotone non-submodular set function subject to a cardinality constraint arises in the context of extracting information from massive streaming data. In this paper, we present four streaming algorithms for this problem by utilizing the concept of diminishing-return ratio. We analyze these algorithms to obtain the corresponding approximation ratios, which generalize the previous results for the submodular case. The numerical experiments show that our algorithms have better solution quality and competitive running time when compared to an existing algorithm.

In this paper, we investigate the problem of minimizing the ratio of normalized non-negative monotone non-submodular set function f and normalized non-negative monotone set function g. We take advantage of the greedy technique and get a performance guarantee depending on the generalized curvature and inverse generalized curvature of f, as well as the submodularity ratio of g. Our results generalize the works of Bai et al. (Algorithms for optimizing the ratio of submodular functions. In: Proceedings of the 33rd International Conference on Machine Learning, 2016) and Qian et al. (Optimizing ratio of monotone set functions. In: Proceedings of the 26th International Joint Conference on Artificial Intelligence, 2017).

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrated that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses revealed key residues that the interactions between govern the PTP-MEG2 and NSF-pY83 site, specify PTP-MEG2 substrate selectivity and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface revealed that PTP-MEG2 controls the fusion pore opening through non-NSF dependent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we discovered that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 site. Further structural and biochemical analysis confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies extended mechanistic insights in complex exocytosis processes.HIGHLIGHTSPTP-MEG2 regulates multiple steps of exocytosis.A crystal structure of the PTP-MEG2/phosphor-NSF-pY83 segment was obtained.Functional delineation of the PTP-MEG2/NSF interface led to the discovery of new PTP-MEG2 substrates.PTP-MEG2 regulates fusion pore opening and extension through the DYNAMIN2-pY125 site and MUNC18-1 pY145 site.The distinct structural basis of the recognition of substrates by PTP-MEG2 allows selective inhibitor design.

Abdominal aortic aneurysm (AAA) is a chronic dilated disease of the aorta that is characterized by chronic inflammation. Curcumin (Cur) is previously showed to attenuate AAA by inhibiting inflammatory response in ApoE −/− mice. Since Cur has the limitations of aqueous solubility and instability. Here, we focus on the role of curcumin nicotinate (CurTn), a Cur derivative is derived from Cur and nicotinate. An in vitro model of AAA was established by treating vascular smooth muscle cells (VSMCs) with II (Ang-II). Gene and protein expressions were examined by quantitative real-time PCR (qPCR) or western blotting. Cell migration and pyroptosis were determined by transwell assay and flow cytometry. The interaction between plasmacytoma variant translocation 1 (PVT1), miR-26a and krüppel-like factor 4 (KLF4) was predicted by online prediction tool and confirmed by luciferase reporter assay. CurTn reduced Ang-II-induced AAA-associated proteins, inflammatory cytokine expressions, and attenuated pyroptosis in VSMCs. PVT1 overexpression suppressed the inhibitory effect of CurTn on AngII-induced pyroptosis and inflammatory in VSMCs by sponging miR-26a. miR-26a directly targeted KLF4 and suppressed its expression, which eventually led to the deactivation of the PI3K/AKT signaling pathway. Besides, the regulatory effect of CurTn on pyroptosis of VSMCs induced by Ang-II was reversed through the PVT1/miR-26a/KLF4 pathway. In short, CurTn suppressed VSMCs pyroptosis and inflammation though mediation PVT1/miR-26a/KLF4 axis by regulating the PI3K/AKT signaling pathway, CurTn might consider as a potential therapeutic target in the treatment of AAA.

An investigation on the interface reactions and boron isotope fractionation in a steady-state carbonate-seawater system was performed to better understand boron incorporation into CaCO3 in a natural environment. In seawater, inorganic carbonate crystals did not precipitate even when the solution reached saturation and the presence of carbonic anhydrase enzyme promotes the process, indicating the precipitation kinetics of inorganic carbonates from natural seawater is fairly slow. Both theoretical and experimental evidence proved that boron incorporation into calcite might be defined as an adsorption-precipitation process rather than a substitution of CO32− by HBO32− in the crystal lattice, where the charged B(OH)4- ions adsorb preferentially over H3BO3 onto positively charged calcite crystal surfaces and finally co-precipitate into occlusions or inclusions after new layers of calcites formed. The Langmuir isotherm well describes the adsorption process, yielding a maximum adsorption capacity [B]solid-max of 0.33 ± 0.04 mg⋅g−1 and an equilibrium constant K of 0.0053 ± 0.0003. Langmuir kinetics also describes previous studies with [B]solid-max of 71.4–418 μg⋅g−1 for calcite and aragonite, covering the variation of boron contents in a variety of biogenic carbonates. The boron isotope fractionations in ulexite-seawater and calcite-seawater systems are distinct. In the former one the fractionation factor (αulexite-seawater = 0.995 ± 0.001) suggests that both trigonal and tetrahedral species of boron enter into ulexite crystals via rapid precipitation, and in the latter one (α4-3 = 0.9736 ± 0.004) confirms that only the charged B(OH)4- species interacts with the crystal surface in calcite.

Except for extensive studies in core formation and volatile-element depletion processes using radiogenic Ag isotopes (i.e. the Pd-Ag chronometer), recent research has revealed that the mass fractionation of silver isotopes is in principle controlled by physico-chemical processes (e.g. evaporation, diffusion, chemical exchange etc.) during magmatic emplacement and hydrothermal alteration. As these geologic processes only produce very minor variations of δ109Ag from -0.5 ‰ to +1.1‰, more accurate and precise measurements are required. In this work, a robust linear relationship between instrumental mass discrimination of Ag and Pd isotopes was obtained at the Ag/Pd molar ratio of 1:20. In Au-Ag ore-deposits, silver minerals have complex paragenetic relationships with other minerals (e.g. chalcopyrite, sphalerite, galena, and pyrite etc.). It is difficult to remove such abundant impurities completely because the other metals are tens to thousands of times richer than silver. Both quantitative evaluation of ma...

Cycling of CO2 between the oceans and the atmosphere has significant impacts on the global climate change. The accurate reconstructions of paleo-pH and atmospheric-oceanic carbon cycling using geochemical tracers (e.g., δ11B, B/Ca) in marine carbonates are reviewed in this work, including the fundamental mechanisms and the remaining challenges in these proxies and the progresses in understanding of evolution of paleo-climate and seawater pH from the late Permian to postindustrial periods. The proxies provide new insight into the evolution of atmospheric CO2 concentrations at time scales from tens of millions to thousands of years, and the direct evidence to the significant ocean acidification during the mass extinction events, and the CO2 cycling in ocean-atmosphere system during the Last Deglaciation and post-industrial periods. On the basis of extensive investigation, it could be concluded that: (i) the carbon dioxide levels and their impacts on Earth surface temperature during the Cenozoic cooling, the Pliocene warmth, and the mid-Pleistocene transition have been evaluated by the combination of multiple proxies; (ii) the benthic/planktonic foraminiferal B/Ca and δ11B data provided consistent implications for global climate variations during the Late Pleistocene, the Late Glacial, Last Glacial Maximum, and the Younger Dryas event; (iii) perturbations of surface ocean pH at the Permo-Triassic (P-T) boundary, the Pliensbachian-Toarcian (Pl-To) boundary, the Cretaceous-Paleogene (K/Pg) boundary and the Palaeocene-Eocene Thermal Maximum (PETM) global warming event were triggered by the large injection of carbon, the short episodic pulses of volcanogenic CO2, the Chicxulub impact, and the volcanism activities of the North Atlantic Igneous Province, respectively; (iv) the ocean acidification in the equatorial and polar Pacific during the Last Deglaciation implied an expanded zone of equatorial upwelling and resultant CO2 emission from higher subsurface dissolved inorganic carbon concentration. The acceleration of modern acidification in post-industrial time was not only driven by anthropogenic CO2 but also varied synchronously with inter-decadal changes in Asian Winter Monsoon Intensity.

Evaporites of Middle Miocene Badenian stage occur widely in basins from the Carpathian Mountain region (Poland, Slovakia and Ukraine), but their source and formation process are still debatable. A detailed boron isotope study in combination with previous chlorine isotope and chemistry data of the salt samples from three localities (Wieliczka mine, Trans-Carpathian Basin, East Slovakian Basin) reveal ranges of δ11B (−4.5 to +35.7‰) and δ37Cl (−0.2 to +0.8‰). Modelling calculation indicates that both Rayleigh fractionation and incorporation of fluid inclusion solutes cannot cause such a large shift on δ11B values in halite. Instead, the B and Cl isotope data imply multiple brine sources, including evaporite brine, dissolved diapiric halite and basin brine in addition to the predominant seawater source during the formation of these evaporites. At Wieliczka salt mine, a positive δ11B excursion (from −5‰ to + 30‰) matches the negative δ37Cl variation (from +0.5 ± 0.1‰ to -0.2‰) stratigraphically upwards, which indicate both terrestrial boron and non-marine chloride made significant contributions to the composition of the basin brine during the early development of the basin. In the upper column, the δ11B values are within the marine range, but show influence by the sorption of boron onto clay, whereas the δ37Cl values at +0.5‰ still indicate the presence of non-marine chloride, possibly from recrystallized, diapiric halite. In the Trans-Carpathian Basin, constant δ37Cl (+0.3‰) and δ11B (+15‰) in the middle of the profile are consistent with a dominant marine source, whereas the lower δ11B (+2.2‰) and higher δ37Cl (+0.8‰) in the lower column suggest terrestrial fresh water flowed into the basin during the formation of basal halite. Halites in the upper part of the profile show near 0‰ of δ37Cl, suggesting incorporation of Cl from a mixture of expelled basin brines. In the Slovakian Basin, the δ11B values (+18.1 to +19.1‰) at the base of the profile lie within the marine range, but high δ37Cl values (+0.7 to +0.8‰) require a non-marine chloride source. In the upper part of the profile, boron isotope data indicate a change from marine (+12.2 to +23.4‰) to non-marine (+5.4 to +6.1‰) derivation of B, but the sources of Cl remain marine (+0.0 to +0.5‰). Overall, both B and Cl isotopes show coupled variation in the Middle Miocene Badenian evaporites and suggest multiple sources of B and Cl.

Mesenchymal stem cell (MSC)-based regeneration, specifically cell aggregate or cell sheet engineering, is a promising approach for tissue reconstruction. Considering the advantages of ease of harvest and lack of immune rejection, the application of autologous MSCs (i.e., patients’ own MSCs) in regenerative medicine has developed considerable interest. However, the impaired cell viability and regenerative potential following MSCs impacted by disease remain a major challenge. Resveratrol (RSV) exhibits reliable and extensive rejuvenative activities that have received increasing clinical attention. Here, we uncovered that resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates. Periodontal ligament MSCs (PDLSCs) from normal control subjects (N-PDLSCs) and periodontitis patients (P-PDLSCs) were investigated. Compared to N-PDLSCs, P-PDLSCs were less capable of forming cell aggregates, and P-PDLSC aggregates showed impaired osteogenesis and regeneration. These functional declines could be mimicked in N-PDLSCs by tumor necrosis factor alpha (TNF-α) treatment. Notably, a TNF-α-induced functional decline in N-PDLSC aggregates was rescued by RSV application. More importantly, in both N-PDLSCs and P-PDLSCs, RSV promoted cell aggregate formation and improved their osteogenic potential. Furthermore, as proven ectopically in vivo, the tissue regenerative capability of P-PDLSC aggregates was also enhanced after RSV treatment during aggregate formation in vitro. Finally, in a rat in situ regeneration model, we successfully applied both N-PDLSC aggregates and P-PDLSC aggregates to repair periodontal defects upon long-term functional improvements by RSV preconditioning. Together, our data unravel a novel methodology for using pharmacology (i.e., RSV)-based cell aggregate engineering to improve the functionality and facilitate the regeneration of MSCs from both healthy and inflammatory microenvironments, shedding light on improving the application of autologous MSC-mediated regenerative medicine., Regenerative medicine: Red wine compound helps rejuvenate stem cells A molecule found in the skin of red grapes enhances the regenerative capacity of adult stem cells. Researchers in China led by Yan Jin from Fourth Military Medical University, Xi’an, and Ya-Ping Pan from China Medical University, Shenyang, isolated stem cells capable of making the different specialized cells found in the skeletal tissues from the connective tissue located at the root of tooth-bearing bones. They showed that stem cells taken from people with serious gum disease could not mature and develop into tissue-forming aggregates as well as stem cells taken from healthy individuals. Treatment of healthy stem cells with a pro-inflammatory signaling molecule impaired development, but subsequent exposure to resveratrol, the compound in grape skin, restored cellular health. Resveratrol also promoted regeneration in the diseased stem cells and in rodent models of gum disease.

Luminal fluid reabsorption plays a fundamental role in male fertility. We demonstrated that the ubiquitous GPCR signaling proteins Gq and β-arrestin-1 are essential for fluid reabsorption because they mediate coupling between an orphan receptor ADGRG2 (GPR64) and the ion channel CFTR. A reduction in protein level or deficiency of ADGRG2, Gq or β-arrestin-1 in a mouse model led to an imbalance in pH homeostasis in the efferent ductules due to decreased constitutive CFTR currents. Efferent ductule dysfunction was rescued by the specific activation of another GPCR, AGTR2. Further mechanistic analysis revealed that β-arrestin-1 acts as a scaffold for ADGRG2/CFTR complex formation in apical membranes, whereas specific residues of ADGRG2 confer coupling specificity for different G protein subtypes, this specificity is critical for male fertility. Therefore, manipulation of the signaling components of the ADGRG2-Gq/β-arrestin-1/CFTR complex by small molecules may be an effective therapeutic strategy for male infertility.

Somatostatin secreted by pancreatic δ cells mediates important paracrine interactions in Langerhans islets, including maintenance of glucose metabolism through the control of reciprocal insulin and glucagon secretion. Disruption of this circuit contributes to the development of diabetes. However, the precise mechanisms that control somatostatin secretion from islets remain elusive. Here, we found that a super-complex comprising the cullin 4B-RING E3 ligase (CRL4B) and polycomb repressive complex 2 (PRC2) epigenetically regulates somatostatin secretion in islets. Constitutive ablation of CUL4B, the core component of the CRL4B-PRC2 complex, in δ cells impaired glucose tolerance and decreased insulin secretion through enhanced somatostatin release. Moreover, mechanistic studies showed that the CRL4B-PRC2 complex, under the control of the δ cell-specific transcription factor hematopoietically expressed homeobox (HHEX), determines the levels of intracellular calcium and cAMP through histone posttranslational modifications, thereby altering expression of the Cav1.2 calcium channel and adenylyl cyclase 6 (AC6) and modulating somatostatin secretion. In response to high glucose levels or urocortin 3 (UCN3) stimulation, increased expression of cullin 4B (CUL4B) and the PRC2 subunit histone-lysine N-methyltransferase EZH2 and reciprocal decreases in Cav1.2 and AC6 expression were found to regulate somatostatin secretion. Our results reveal an epigenetic regulatory mechanism of δ cell paracrine interactions in which CRL4B-PRC2 complexes, Cav1.2, and AC6 expression fine-tune somatostatin secretion and facilitate glucose homeostasis in pancreatic islets.

This paper applies natural experiment to research on 120 college students, recording their performances of creativity under different time and anticipatory stress conditions. By using SPSS software to deal with the results of experiments, effects of different stress conditions on one’s creativity performance have been studied. The conclusions indicate that, under higher-time stress, the creativity performance is much more considerable with higher anticipations; under lower-time stress, the performance of creativity stays stable no matter how the level of anticipation is; under lower-time stress, the performance of creativity is much higher than that in higher-time stress, in spite of level of anticipations; under lower-time and higher-anticipatory stress, the level of creativity is the highest; under lower-time and higher-anticipatory stress, the flexibility of creativity is the most considerable; under lower time stress, the fluency and peculiarity is remarkable than that in higher-time-stress condition. Therefore, when facing plenty of tasks during work, employees and managers should judge the emergency and importance of theses work as well as control and arrange the finishing time and speed reasonably, which is helpful to deal with these problems.

As enterprise organizations expand and intensive competition increases continuously, the practice of performance management has undergone dramatic development. Performance management is seen as core value to survive and gain competitive advantages in markets. KPI and balanced-score card model, therefore, have been widely used in the performance appraisal of enterprises. Yet they are not effectively utilized. Furthermore, there is still blank in research based on KPI model and balanced-score card model in security industry. This paper discusses the theory basis of performance management. Then it studies KPI model and balanced-score card model and puts forward a model combined with KPI model and balanced-score card model. This paper is an empirical research on S Security Company. Questionnaire survey and interview of the manager Mr. Li in charge of HRM in the company were conducted. Then problems and causes in project performance appraisal system are analyzed. The paper finally uses analysis of variance (ANOVA) and Analytic Hierarchy Process (AHP) to determine the final weights of indicators in its project performance appraisal system. Results shall be used as guideline for performance management in similar practice in security industry.

Targeting the problem of high real-time requirements in astronomical data processing, this paper proposes a real-time early warning model for light curves based on a Gated Recurrent Unit (GRU) network. Using the memory function of the GRU network, a prediction model of the light curve is established, and the model is trained using the collected light curve data, so that the model can predict a star magnitude value for the next moment based on historical star magnitude data. In this paper,we calculate the difference between the model prediction value and the actual observation value and set a threshold. If the difference exceeds the set threshold, the observation value at the next moment is considered to be an abnormal value, and a warning is given. Astronomers can carry out further certification based on the early warning and in combinationwith other means of observation. Themethod proposed in this paper can be applied to real-time observations in time domain astronomy.

Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-β-arrestin-1 signalling complex. Replacing the C-terminal region of β-arrestin-1 with its counterpart on β-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between β-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes., Angiotensin II type 1 receptor (AT1R)-mediated acute catecholamine release is modulated by β-arrestin. Here the authors show that β-arrestin-1 recruits the Ca2+ channel TRPC3 and the PLCγ to the AT1R-β-arrestin complex, triggering G protein-independent calcium influx and catecholamine secretion.

Background Stress is a conserved physiological response in mammals. Whereas moderate stress strengthens memory to improve reactions to previously experienced difficult situations, too much stress is harmful. Methods We used specific β-adrenergic agonists, as well as β 2 -adrenergic receptor (β2AR) and arrestin knockout models, to study the effects of adaptive β2AR activation on cognitive function using Morris water maze and object recognition experiments. We used molecular and cell biological approaches to elucidate the signaling subnetworks. Results We observed that the duration of the adaptive β2AR activation determines its consequences on learning and memory. Short-term formoterol treatment, for 3 to 5 days, improved cognitive function; however, prolonged β2AR activation, for more than 6 days, produced harmful effects. We identified the activation of several signaling networks downstream of β2AR, as well as an essential role for arrestin and lactate metabolism in promoting cognitive ability. Whereas Gs–protein kinase A–cyclic adenosine monophosphate response element binding protein signaling modulated monocarboxylate transporter 1 expression, β-arrestin-1 controlled expression levels of monocarboxylate transporter 4 and lactate dehydrogenase A through the formation of a β-arrestin-1/phospho-mitogen-activated protein kinase/hypoxia-inducible factor-1α ternary complex to upregulate lactate metabolism in astrocyte-derived U251 cells. Conversely, long-term treatment with formoterol led to the desensitization of β2ARs, which was responsible for its decreased beneficial effects. Conclusions Our results not only revealed that β-arrestin-1 regulated lactate metabolism to contribute to β2AR functions in improved memory formation, but also indicated that the appropriate management of one specific stress pathway, such as through the clinical drug formoterol, may exert beneficial effects on cognitive abilities.

In this paper, the reachable set estimation problem is studied for a class of dynamic neural networks subject to polytopic uncertainties. The problem addressed here is to find a set as small as possible to bound the states starting from the origin by inputs with peak values. The maximal Lyapunov functional is proposed to derive a sufficient condition for the existence of a non-ellipsoidal bound to estimate the states of neural networks. It is theoretically shown that this method is superior to the traditional one based on the common Lyapunov function. Finally, two examples illustrate the advantages of our proposed result.

Objective: To investigate whether dietary daidzein interact with endogenous 17β-Estradiol (E2) to give rise to additive or inhibitory effects on proliferation and apoptosis in breast cancer cells. Methods: Cell cycle distribution and apoptosis induction were analyzed by using flow cytometry when breast cancer cell lines MCF-7 were cotreated with daidzein (1, 5 μmol/L) and E2 (0.1−10 nmol/L) for 5 days. Whether daidzein could alter E2-modulated mRNA expression of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ) and ERβ-estrogen response element (ERE) dependent transcription was investigated by RT-PCR and luciferase induction assays. The effects of daidzein on E2-modulated expression of proapoptotic p53, bax and antiapoptotic bcl-2 at both mRNA and protein levels were also investigated by RT-PCR and Western blot. Results: Daidzein enhanced the antiapoptotic effect in an E2 dose-dependent manner, but had no effect on E2-induced proliferation. Daidzein antagonized E2-induced ERβ mRNA expression and ERβ-ERE dependent transcription. In addition, daidzein only antagonized E2-upregulated expression of p53 and bax, but had no effect on E2-upregulated expression of bcl-2. Conclusion: Daidzein enhances the antiapoptotic effect of E2 on breast cancer cells by inhibiting E2-mediated p53-bax proapoptotic pathway. These results suggest that dietary daidzein may enhance deleterious effect of endogenous E2 in hormone-dependent breast cancer.

Here we demonstrate the copper/dielectric TDDB improvement of 8 metal layers in 28nm technology node with 90 nm pitch. After the process optimization, the Weibull slope of MOM TDDB increase from 0.85 to 1.28 that improves the estimated MOM TDDB about 200 times.

In order to remove and recover copper, zinc, cadmium, and chromium from the wastewater treatment sludge generated by an electroplating process, the heavy metal extraction kinetics was studied in a batch reactor using two different extraction agents (nitric and citric acid) at constant agitation speed (150 rpm) and solid to liquid ratio (10 g/L), but varying acid concentrations (0.02-0.10 N), temperatures (25-85 degrees C in nitric acid solution, 25-95 degrees C in citric acid solution), and sludge particle sizes. The shrinking-core model and empirical kinetic model were adopted to analyze the experimental data. Although both models could fit the experimental kinetic data well, the obtained parameters of the shrinking-core model did not show reasonable trends varying with the experimental variables while the empirical model parameters showed significant trends. The experimental and modeling results showed that the metal extraction rates increased with acid concentration, temperature, but decreased with increasing particle size. Nitric acid was found to be more effective than citric acid to extract the heavy metals from the sludge. The extraction activation energies obtained in this study suggested that both a physical diffusion process and a chemical reaction process might play important roles in the overall extraction process.

MmxMl1-xNi4.14Cu0.5Al0.3Zn0.06 (Mm=Ce-rich misch-metal, Ml=La-rich misch-metal, x=0, 0.2, 0.4, 0.6, 0.8, 1) alloys have been synthesized by the inter-media alloy method. The properties of these alloys have been systematically investigated by means of X-ray diffraction (XRD), pressure-composition isotherms (PCT), electrochemical impendence (EIS) and cyclic voltammogram (CV). The X-ray diffraction results indicated that these alloys had a CaCu5-type hexagonal crystal structure. With increasing the Mm content, the plateau pressure and volume expansion of their hydrides were increased, but the volume of unit was decreased.

Negative Tone Development (NTD) process with ArF immersion has been developed for the next generation lithography technology because it shows good resolution performance and process window for C/H and trench patterning. Because of the etch requirement, tri-layer process has been used popularly. However, most of the Si-HM materials are optimized for positive tone development process and most of them show poor lithography performance in NTD process. In this paper, we study the behaviors of Si-HM for NTD process, develop new concepts and optimize the formulation of Si-HM to match the resist for NTD process bellow N28 node device.

To explore the tk gene mutation spectrum in spontaneous and induced WTK1 mutants.After exposure to methyl methanesulfonate (MMS), mitomycin (MMC) or sodiam azide (NaN3), spontaneously-arising and induced mutants of WTK1 cell line were selected. The spectrum and hotspot of tk gene mutation were analyzed by multiplex PCR.Three chemicals used in this study induced tk mutation frequency (MF) to increase significantly in a dose-dependent manner; most of the analyzed mutants had lost exon 4 and exon 5-7.Three chemicals have mutagenic effect on WTK1 cell line, and obvious hotspot exists in tk gene mutation.

To evaluate the genotoxicity of two mitotic inhibitors vincristine and colchicine, and to compare the detecting sensitivity of tk gene mutation assay with short-and long-term treatment by them.Tk gene mutation assay was performed by microwell method with L5178Y mouse lymphoma cell line after exposing to vincristine and colchicine for 3 h and 24 h respectively, and the results of two different treating time were compared.The two chemicals didn't show positive responses in mouse lymphoma assay (MLA) with 3h treatment, but they could induce tk mutation frequency increase 1.6 to 4.8 and 2.1 to 6.2 times higher to spontaneous MF respectively after continuous treatment for 24 h.Vincristine and colchicine had mutagenic effect on tk gene with long-term treatment, which indicated that the detecting sensitivity of MLA could be enhanced by long-term treatment.

To compare the advantages and disadvantages of utilizing L5178Y and TK6 cell lines in the TK locus mutation assay.The two cell lines were used for detecting and assessing the mutability of four chemicals (MMS, EMS, MMC and KCl); the microwell method of TK locus mutation assay was adopted.The two cell lines brought about similar results in the study. The tolerance of TK6 to all four chemicals was lower than that of L5178Y, and all the relative mutation indices of TK6 were higher than those of L5178Y.Each of the two cell lines has its own strong points; nevertheless, the authors recommend the applications of TK6 cell in the assay system since this cell line comes from human.