Hepatocytes are epithelial cells with highly specialized polarity. The disorder and loss of hepatocyte polarity leads to a weakness of cell adhesion and connection, the induction of ...epithelial–mesenchymal transition, and eventually the occurrence of hepatocellular carcinoma (HCC). Cluster of differentiation 147 (CD147), a tumor‐related glycoprotein, promotes epithelial–mesenchymal transition and the invasion of HCC. However, the function of CD147 in hepatocyte depolarization is unknown. Here we identified that CD147 was basolaterally polarized in hepatocyte membrane of liver tissues and HepG2 cells. CD147 not only promoted transforming growth factor‐β1–mediated hepatocyte polarity loss but also directly induced endocytosis and down‐regulation of E‐cadherin which contributed to hepatocyte depolarization. Overexpression of CD147 induced Src activation and subsequently recruited ubiquitin ligase Hakai for E‐cadherin ubiquitination and lysosomal degradation, leading to decreases of partitioning defective 3 expression and β‐catenin nuclear translocation. This signal transduction was initiated by competitive binding of CD147 with integrin β1 that interrupted the interaction between the Arg‐Gly‐Asp motif of fibronectin and integrin β1. The specific antibodies targeting integrin α5 and β1 reversed the decrease of E‐cadherin and partitioning defective 3 levels induced by CD147 overexpression. In human liver tissues, CD147 polarity rates significantly declined from liver cirrhosis (71.4%) to HCC (10.4%). CD147‐polarized localization negatively correlated with Child‐Pugh scores in human liver cirrhosis (r = –0.6092, P < 0.0001) and positively correlated with differentiation grades in HCC (r = 0.2060, P = 0.004). HCC patients with CD147‐polarized localization had significantly better overall survival than patients with CD147 nonpolarity (P = 0.021). Conclusion: The ectopic CD147‐polarized distribution on basolateral membrane promotes hepatocyte depolarization by activation of the CD147–integrin α5β1–E‐cadherin ubiquitination–partitioning defective 3 decrease and β‐catenin translocation signaling cascade, replenishing a molecular pathway in hepatic carcinogenesis. (Hepatology 2018;68:317‐332).
We study the optimal selling scheme when a seller sells a product/service with a positive consumption externality, and customers are uncertain about the product's/service's value. Because early ...adopters learn this value, we consider the customers' intrinsic signaling incentives and positive feedback effects. Allowing the seller to choose the sequence of customers' decisions (as an endogenous hierarchy) implies that signaling takes place in multiple rounds. To tackle this hierarchical signaling problem, we develop a novel dynamic‐programming approach that yields analytical expressions of the equilibrium outcomes. The profit‐maximizing structure turns out to be a chain in which the seller sells to the customers one by one. The sequential selling scheme is not only profitable for the seller but also beneficial to the society. The profit‐maximizing pricing exhibits a cream‐skimming property–decreasing prices along the sequence. The lack of seller's commitment is detrimental to the social welfare; nonetheless, the sequential selling still boosts up the seller's profit. When customers are allowed to freely disclose their quantity decisions to others, they willingly comply with the seller's plan of information transmissions. Despite the inherent value uncertainty, the optimal usage of information transmissions requires deliberate restricted access to information among customers. Our result also suggests some congruence between the profit and welfare maximization.
•High cycle fatigue properties of laser powder bed fusion stainless steel 316L.•Effects of build orientation, annealing and hot isostatic pressing.•Roles of defect, microstructure and cyclic ...plasticity on fatigue failure mechanism.•Stress-based fatigue modelling considering the effects of cyclic plasticity.
Variations in the physical and mechanical properties of parts made by laser power bed fusion (L-PBF) could be affected by the choice of processing or post-processing strategies. This work examined the influence of build orientation and post-processing treatments (annealing or hot isostatic pressing) on the fatigue and fracture behaviours of L-PBF stainless steel 316L in the high cycle fatigue region, i.e. 104–106 cycles. Experimental results show that both factors introduce significant changes in the plastic deformation properties, which affect fatigue strength via the mechanism of fatigue-ratcheting interaction. Cyclic plasticity is characterised by hardening, which promotes mean stress insensitivity and improved fatigue resistance. Fatigue activities, involving the initiation of crack at defects and microstructural heterogeneities, are of greater relevance to the longer life region where the global deformation mode is elastic. As the simultaneous actions of ratcheting and fatigue generate complex nonlinear interactions between the alternating stress amplitude and mean stress, the fatigue properties could not be effectively predicted using traditional stress-based models. A modification to the Goodman relation was proposed to account for the added effects of cyclic plasticity and was demonstrated to produce good agreement with experimental results for both cyclic hardening and softening materials.
Medical rumors have become a threat to modern society. To study the spread and control of rumors, nonlinear differential equations modeling with the well‐mixed assumption is commonly used. However, ...this approach ignores the underlying network structure which plays an important role in information spreading. We establish a generalized differential equations model to study the spread and control of medical rumors in a highly asymmetric social network. In our model, each node represents a group of people and a “weighted” and “directed” network describes the communications between these nodes. This network can be generated from real‐world data by community detection algorithms. We provide methods to numerically calculate the final size of a rumor in each node and its derivatives with respect to each parameter. With these methods, if the government has resources to influence the parameters subject to certain constraints or cost functions, one can obtain the optimal resources allocation easily through nonlinear programming algorithms. We show that the implications on the government's resources allocation from the well‐mixed special case in the literature or conventional wisdom may become inapplicable in the general situation. Therefore, the underlying network should not be ignored. Because the final size of a medical rumor is not always the best measure of its damage, we extend our results to a wide class of objectives and show that different objectives result in very different implications. While the lack of a rule of thumb may sound negative, our flexible framework provides a powerful workhorse for interested parties to work out the details in their specific situations. Finally, we provide a sufficient condition for no outbreak of rumors. This condition can serve as a heuristic that a government with abundant resources can use to prevent the outbreak of rumors.
The path-following problem for four-wheel independently actuated autonomous ground vehicles is investigated in this paper. A novel output constraint controller is proposed to deal with the lateral ...offset control in path following and maintain the vehicle lateral stability in the presence of tire sliding effects. The innovations of this work lie in the following two aspects: 1) A novel output constraint control strategy, namely, the hyperbolic projection method, is proposed to strictly bound the lateral offset to prevent the vehicle from transgressing the safety bound in path following; 2) an adaptive and robust linear quadratic regulator controller is adopted to obtain the optimal active front-wheel steering and direct yaw-moment control inputs with vehicle lateral stability consideration and to eliminate the effect of parameter uncertainties. CarSim-Simulink joint simulation results indicate that the proposed controller can compactly bound the lateral offset to avoid transgressing the safe boundary during path following, particularly in extreme driving conditions, in the presence of tire sliding effects and system uncertainties.
The main purpose of the paper is to investigate the relationship between technological innovation and income inequality for China based on the financial Kuznets curve (FKC) hypothesis. The study uses ...time-series data from 1985 to 2019. We employ the Johansen cointegration, ARDL model and VECM Granger causality techniques to analyze the links between the variables. We also use the DOLS, FMOLS and CCR mechanisms to estimate the long-run parameters. The paper finds that the FKC is valid for China's economy in the long run. Technological innovation positively affects the urban-rural income gap, while there is an inverted-U shaped between financial development and the urban-rural income gap. The relationship between financial development and the urban-rural income gap is bi-directional causality. Technological innovation and the urban-rural income gap cause each other. Empirical results suggest a twofold policy meaning: i) to further the financial system and ii) to eliminate the adverse impacts of technological innovations on income distribution.
Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. ...LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown.
Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24.
LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD.
Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.
Summary Background The prevalence of chronic kidney disease is high in developing countries. However, no national survey of chronic kidney disease has been done incorporating both estimated ...glomerular filtration rate (eGFR) and albuminuria in a developing country with the economic diversity of China. We aimed to measure the prevalence of chronic kidney disease in China with such a survey. Methods We did a cross-sectional survey of a nationally representative sample of Chinese adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1·73 m2 or the presence of albuminuria. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples taken. Serum creatinine was measured and used to estimate glomerular filtration rate. Urinary albumin and creatinine were tested to assess albuminuria. The crude and adjusted prevalence of indicators of kidney damage were calculated and factors associated with the presence of chronic kidney disease analysed by logistic regression. Findings 50 550 people were invited to participate, of whom 47 204 agreed. The adjusted prevalence of eGFR less than 60 mL/min per 1·73 m2 was 1·7% (95% CI 1·5–1·9) and of albuminuria was 9·4% (8·9–10·0). The overall prevalence of chronic kidney disease was 10·8% (10·2–11·3); therefore the number of patients with chronic kidney disease in China is estimated to be about 119·5 million (112·9–125·0 million). In rural areas, economic development was independently associated with the presence of albuminuria. The prevalence of chronic kidney disease was high in north (16·9% 15·1–18·7) and southwest (18·3% 16·4–20·4) regions compared with other regions. Other factors independently associated with kidney damage were age, sex, hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area of residence, and economic status. Interpretation Chronic kidney disease has become an important public health problem in China. Special attention should be paid to residents in economically improving rural areas and specific geographical regions in China. Funding The Ministry of Science and Technology (China); the Science and Technology Commission of Shanghai; the National Natural Science Foundation of China; the Department of Health, Jiangsu Province; the Sichuan Science and Technology Department; the Ministry of Education (China); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation.
Noncommunicable diseases (NCDs) are among the largest health emergencies nowadays. Although a large proportion of NCDs can be prevented effectively via good life habits, these remain ubiquitous and ...one main reason is people's self‐control problem caused by time‐inconsistent, present‐biased preferences. In this situation, we wonder whether a “long‐term” conditional cash transfer (CCT) program, which is known to be effective in shaping people's behaviors but expensive, can be a viable solution. We establish a model which can be fine‐tuned by many parameters, and show that our results are robust in a wide range of parameters. We identify the optimal CCT scheme which helps people achieve their long‐term plan while generating the lowest cash flow. Our results suggest interesting managerial insights like that the amount of necessary financial incentives can depend on people's age, and that the government's optimal CCT scheme does not depend on the level of people's naivete. Also, it is profitable for companies to hold such a program and sell enrollment to customers as self‐commitment devices. However, companies may exploit customers’ naivete to maximize their profit while hurting social welfare. We also examine situations that people's behaviors can only be monitored indirectly through inaccurate signals and that people are heterogeneous in how present‐biased they are.
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