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Background: CircRNAs play an important role in tumorigenesis and metastasis, and their expression is comprehensively downregulated in hepatocellular carcinoma (HCC). Previous studies have shown that the polyadenylation signal1 is critical for circRNA expression, while the 3’-end processing complex participates in circRNA cyclization. As a core executor of 3’-end cleavage, we hypothesized that CPSF3 modulates the circularization of circRNA. Methods: The clinical prognostic correlation was analyzed by TCGA database and tissue microarrays. Cytological experiments were performed to determine the role of CPSF3 in the proliferation and migration of HCC cells. The Red/GFP dual fluorescent reporter system was employed to explore the mechanism of RNA back-splicing regulated by CPSF3 protein and PAS sequences. The circRNAs regulated by CPSF3 were screened by RNA-seq and further validated by real-time PCR and dot blotting. Changes in the activity of downstream pathways were explored by various molecular experiments. Finally, the safety and efficacy of the CPSF3 inhibitor JTE-607 were verified by in vitro cytology experiments and in vivo xenograft nude mouse models. Results: CPSF3 was highly expressed in HCC cells and promoted the proliferation and migration of HCC cells. Its high level of expression predicted poor prognosis in HCC patients. Mechanistic study revealed that CPSF3 enhanced RNA cleavage, thereby reducing circRNA levels, increasing linear mRNA levels, and ultimately inhibiting miRNA-mediated gene silencing. Furthermore, the chemical inhibition of CPSF3 by JET-607 suppressed the proliferation of HCC cells both in vitro and in vivo. Conclusions: Our findings indicate that the increased expression of CPSF3 in HCC promotes the shift of pre-mRNA from circRNA to linear mRNA, thereby disrupting miRNA-mediated gene silencing and ultimately leading to uncontrolled cell proliferation. JTE-607, a CPSF3 inhibitor, exerted a therapeutic effect on HCC by blocking CPSF3 activity.

A sensitive method for the determination of nine volatile phenols in smoked meat products samples has been developed using Gas Chromatography-Tandem Mass Spectrometry(GC-MS/MS). Smoked meat sample was extracted with soaking in 0.1 mol/L sodium hydroxide solution for 12 hours.The extracting solution was acidified by injecting the excess CO2 gas and then purified using sodium chloride and acetonitrile. Good linearities (R2>0.9908) were acquired for the analytes. The limit of detection and quantification were 5–15 μg kg-1 for all the nine target compounds. The recoveries were 81.6–92.0% and the relative standard deviations values were lower than 8.2% at three spiked levels (50, 200 and 1000 μg kg-1 ). The results indicated that the method was employed for the determination of volatile phenolic compounds in smoked meat because of its accuracy, speediness, high-efficiency and inexpensiveness.

International audience; Inconsistencies in the Eocene climates of East Asia have been revealed in both geological studies and simulations. Several earlier reconstructions showed an arid zonal band in mid-latitude China, but others showed a humid climate in the same region. Moreover, previous Eocene modeling studies have demonstrated that climate models can simulate both scenarios in China. Therefore, it is essential to investigate the cause of this model spread. We conducted a series of experiments using Norwegian Earth System Model 1-F and examined the impact of mountains in Southern China on the simulated Eocene climate. These mountains, including the Gangdese and Southeast Mountains, are located along the main path of water vapor transport to East Asia. Our results reveal that the Southeast Mountains play the dominant role in controlling the simulated precipitation in Eastern China during the Eocene. When the heights of the Southeast Mountains exceed ∼2,000 m, an arid zonal band appears in mid-latitude China, whereas humid climates appear in Eastern China when the elevation of the Southeast Mountains is relatively low.

Building information modeling (BIM) can theoretically facilitate collaboration among diverse design participants in construction projects, but in practice, its implementation tends to prolong the design period. Existing literature has examined some technical and managerial causes of this problem but still lacks an overall coverage of related factors. This study aims to identify the comprehensive factors affecting the teamwork efficiency in China’s BIM-based collaborative design, and to investigate the critical factors and their interactions. Based on the input-process-output theory, this study initially established a hypothetical model. Potential factors were further identified through the literature review and semi-structured interviews. Questionnaire survey was conducted, and structural equation modeling was used for analysis. The results indicated that the team cooperation atmosphere is the most significant factor, followed by the collaborators’ learning ability, comfort of the working environment, BIM software function, and the characteristics and arrangement of the design task (CADT). Besides, the CADT negatively affects the teamwork efficiency through the human interaction process, while other factors exert positive impacts by affecting both the personal work process and the human interaction process. The findings can help design units to determine the management focus of BIM-based collaborative design and prioritize the allocation of limited resources accordingly to maximize teamwork efficiency.

Although DNA binding with one finger (Dof) constitutes a crucial plant-specific family of transcription factors (TFs) that plays important roles in a wide range of biological processes, the molecular mechanisms underlying Dof regulation of flavonoid biosynthesis in plants remain largely unknown. Here, we characterized 28 Dof genes (FhDof1-FhDof28) from the 'Hongkong' kumquat (Fortunella hindsii) cultivar genome. Promoter analysis and transcriptome profiling revealed that four FhDofs - FhDof4, FhDof9, FhDof15, and FhDof16 - may be involved in flavonoid biosynthesis through binding to the flavonoid C-glycosyltransferase (FhCGT) promoter. We cloned homologous genes of four FhDofs, designated as FcDof4, FcDof9, FcDof15, FcDof16, and a homologous gene of FhCGT, designated as FcCGT, from the widely cultivated 'HuaPi' kumquat (F. crassifolia). Quantitative reverse transcription-polymerase chain reaction analysis revealed that FcDof4 and FcDof16 were significantly correlated with FcCGT expression during development stages in the 'HuaPi' fruit (Pearson's correlation coefficient0.7) and were localized to the nucleus. Results of yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase assays indicated that the two FcDofs trigger FcCGT expression by specifically binding to its promoters. Moreover, transient overexpression of FcDof4 and FcDof16 enhances the transcription of structural genes in the flavonoid biosynthetic pathway and increases C-glycosylflavonoid content. Our results provide strong evidence that the TFs FcDof4 and FcDof16 promote flavonoid synthesis in kumquat fruit by activating FcCGT expression.

The Finite Gaussian Mixture Model (FGMM) is the most commonly used model for describing mixed density distribution in cluster analysis. An important feature of the FGMM is that it can infinitely approximate any continuous distribution, as long as the model contains enough number of components. In the clustering analysis based on the FGMM, the EM algorithm is usually used to estimate the parameters of the model. The advantage is that the computation is stable and the convergence speed is fast. However, the EM algorithm relies heavily on the estimation of incomplete data. It does not use any information to reduce the uncertainty of missing data. To solve this problem, an EM algorithm based on entropy penalized maximum likelihood estimation is proposed. The novel algorithm constructs the conditional entropy model between incomplete data and missing data, and reduces the uncertainty of missing data through incomplete data. Theoretical analysis and experimental results show that the novel algorithm can effectively adapt to the FGMM, improve the clustering results and improve the efficiency of the algorithm.

The early Eocene is a warm period with very high atmospheric CO2 levels, which receives many interests from climate modelling aspects. To simulate the early Eocene paleoclimate, a realistic reconstruction for land-sea distribution, paleotopography and paleobathymetry is the fundamental step. Here, we present global paleogeographic reconstructions for the early Eocene (~55 Ma), based on integrated paleogeographic data set, the Plate-tectonic reconstruction software (GPlates) and Geographic Information System software (ArcGIS). Comparing with previous paleogeographic reconstructions, we improve the reconstructions incorporated many latest geologic data and data set, including: (1) better representations of the Tethys Sea, some marginal or inland seas in the East and Southeast Asia, Atlantic and Arctic region, and the Drake Passage and Tasmanian Gateway; (2) integrated paleoelevation data of global high plateaus and mountains, especially the paleotopography of East Asia, and adopting the latest paleotopographic reconstruction data of the Antarctic; and (3) using the updated data set of oceanic crust paleo-age and oceanic sediment thickness to reconstruct the paleobathymetry.

In the construction stage, green buildings have increased cost input compared with traditional buildings, and their cost is threatened by numerous risk factors. Various stakeholders have an influence on construction cost that cannot be ignored. However, the existing research rarely analyzed the construction cost risk of green buildings from the perspective of stakeholders. In order to close such research gap, this study used structural equation modeling to explore key stakeholders and key risk factors that affect the construction cost of green buildings, and to conduct risk assessment on it. Initially, literature bibliometrics and semi-structured interviews were conducted to identify 31 cost risk factors related to various stakeholders and 3 components of green building construction cost. Questionnaire survey was used to collect data and structural equation modeling was then used for verifying the model hypothesis to identify key stakeholders and key risk factors. The identified key stakeholders and key risk factors were evaluated according to the impact coefficient, and finally divided into three levels. Results show that the design unit has the greatest impact on the construction cost of green buildings, followed by the construction unit, while the government sector seems to have the least impact. In addition, in the classification of risk levels, the key risk factors are mainly related to the owner, the design unit, the construction unit, and the material supplier. Findings of this study provide a theoretical basis for effective management on key risk factors for green building construction cost, which will further promotes the practical development of green buildings in China.

The northeastern Tibetan Plateau began to grow during the Eocene and it is important to understand the climatic history of Asia during this period of so-called ‘doubthouse’ conditions. However, despite major advances in the last few decades, the evolutionary history and possible mechanisms of Eocene climate change in the northeastern Tibetan Plateau remain unclear. The Xining Basin in the northeastern Tibetan Plateau contains a continuous sequence of Early to Late Eocene non-marine sediments which provides the opportunity to resolve long-term climate changes during this period. In this study, we report the results of analyses of lithofacies, sediment color and geochemistry of bulk samples collected from the Xijigou section of the Xining Basin. An abrupt lithofacies change between the Early (~52–40 Ma) and Late Eocene (~40–34 Ma) indicates a change in the depositional environment from a shallow lake to a playa lake in response to a significant climatic shift. During ~52–40 Ma, higher values of sediment redness ( a *), redness/lightness ( a */ L *) and higher modified Chemical Index of Weathering (CIW′) indicate a relatively warm and humid climate, while from ~40–34 Ma the lower values of a *, a */ L * and lower CIW′ imply sub-humid to semi-arid climatic conditions. The paleoclimatic records indicate a long-term (~52–34 Ma) trend of decreasing chemical weathering, consistent with global climate change. An abrupt sharp excursion of the proxy records during ~42–40 Ma suggests a relatively brief warm interval, corresponding to the Middle Eocene Climatic Optimum (MECO). We suggest that global cooling substantially reduced humidity in inner Asia, resulting in sub-humid to semi-arid climatic conditions after 40 Ma in the Xining Basin, which may have been responsible for the long-term trend of decreasing chemical weathering during the Eocene.

Based on related data and cluster analysis, this paper creates a mathematical model of similarity measurement based on the data set, and finally obtains the influence of different music genres on their followers and the similarity of artists of different musical genres. Here, since the study is about the similarity of music, it is divided into 2 categories according to the provided music characteristics and related indicators of music type. The data is standardized and normalized. Because there is no clear indicator to measure the similarity of music, we use spss to perform K-means clustering analysis. Here, since the similarity of music is studied, it is built on the music characteristics and music provided. Types of related indicators divide it into two categories for analysis. In order to determine the reliability of the model, this article uses meaningful learning to train 70% of the previous data, 30% to test, and finally establishes a complete mathematical model.

Unipolar pulses of kinetic Alfven waves (KAW) are first observed in the near-Earth plasma sheet (NEPS) associated with dipolarizations during substorm expansion phases. Two similar events are studied with Time History of Events and Macroscale Interactions during Substorms (THEMIS) observations during substorms on 3 February 2008 and 7 February 2008. The unipolar pulses were located at a trough-like Alfven speed profile in the northern plasma sheet at a distance of 10–11 R E from Earth. The dominant wave components consist of a southward δ E z toward the neutral plane and a +δ B y toward the dusk. The |δ E z |/|δ B y | ratio was in the range of a few times the local Alfven speed, a strong indication of KAW nature. The wave Poynting flux was earthward and nearly parallel to the background magnetic field. The pulse was associated with an earthward field-aligned current carried by electrons. These observational facts strongly indicate a KAW eigenmode that is confined by the plasma sheet but propagates earthward along the field line. The KAW eigenmode was accompanied by short timescale (1 min) dipolarizations likely generated by transient magnetotail reconnection. The observed polarity of the KAW field/current is consistent with that of the Hall field/current in magnetic reconnection, supporting the scenario that the Hall fields/current propagate out from reconnection site as KAW eigenmodes. Aurora images on the footprint of THEMIS spacecraft suggest that KAW eigenmode may power aurora brightening during substorm expansion phase.

A substorm dispersionless injection event observed during the storm recovery phase on 11 March 1998 at geosynchronous orbit is carefully studied. The event shows the notable characteristics that for energetic ions the flux enhancement ratio before and after injection increases and remains elevated with increasing energy, while for energetic electrons it tends to decrease with increasing energy. In order to explain the unique injection feature, the authors propose a possible mechanism that velocity space diffusion in common to electric acceleration adjusts the particle injection state. Spectral characteristics of four different phases (pregrowth phase, the growth phase, the substorm expansion phase, and the recovery phase) have been investigated. The differential fluxes of electrons from 50 keV to 1.5 Mev and ions from 50 keV to 1.2 MeV measured by Synchronous Orbit Plasma Analyzer (SOPA) instrument onboard LANL satellite 1991-080 are found to be best fitted with the three-parameter kappa distribution function (f similar to A(0) . E[1 + E / (kappa E-0)](-kappa-1)) by Levenberg-Marquardt and Universal Global Optimization methods. The evolutions of the three parameters in the above kappa distribution in different substorm phases have been depicted for both electrons and ions. In each phase, E-0 and kappa show an approximately linear relationship kappa(E-0) = kappa(0) + eta E-0. This linear relationship can be obtained by solving the velocity space diffusion equation with an initial superthermal kappa distribution. Ion and electron are found to have opposite trend of parameters kappa(0) and eta in each phase, which indicates that the different species of particles exert different velocity space diffusion processes so that their flux enhancement ratios before and after injection are rather different. This implies that not only electric field acceleration, but also velocity space diffusion plays a very important role in the particle injection.

[1] The Neutral Atom Detector Unit (NUADU) aboard the TC-2 spacecraft recorded energetic neutral atom (ENA) image data for >3 h during part of the main and recovery phases of a major magnetic storm on 15 May 2005. A custom designed, constrained linear inversion method was applied to retrieve ring current ion distributions in the ENA records out to L = 6.6. Comparisons were then made between the ion fluxes retrieved from these ENA data (energy ranges 50–81 keV and 81–158 keV) and complementary, contemporaneous particle fluxes measured in situ by Synchronous Orbit Particle Analyzer (SOPA) instruments aboard a series of geosynchronous satellites that were launched to encircle the equatorial plane at L ∼ 6.6 by the Los Alamos National Laboratory (LANL). The ENA data revealed the development of two emission peaks during the main phase of the storm which corresponded to the arrival from the magnetotail of a pair of particle injections. These injections reached, in each case, maximum value before the corresponding AL index amplitude peak was attained. The main phase of the storm concluded (Dst ≈ −256 nT) in the aftermath of this event pair, and the ring current ion fluxes thereafter gradually decayed over several hours (the storm recovery phase). This is the first time that the linear inversion method developed for NUADU data has been globally validated using multipoint in situ measurements made at different magnetic local times. It was found that the higher the derived flux values were on the duskside/nightside, the closer they were to the in situ measurements. The retrieved fluxes obtained on the duskside/nightside tended, however, to be still somewhat underestimated since the ENA measurements concerned were made around the outer edge of the ring current at an altitude where the magnetic field in the inner magnetosphere deviates from that dipole configuration assumed in the inversion procedure to pertain there. The two methods utilized to study ions during a large magnetic storm are complementary in that the retrieved ion fluxes provide high time resolution information concerning the changing, large-scale structure of ring current events, whereas in situ flux sampling presents “measurement truth” at particular locations within individual ring currents.