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BackgroundFibroblast-myofibroblasts transition (FMT) is one of the hallmark cellular processes in pulmonary fibrosis. This study is to investigate the effects of CMLD-2 in FMT and pulmonary fibrosis, which antagonizes HuR, a supposedly key regulatory RNA binding protein (RBP).MethodsHuR or other deferentially expressed RBPs during TGF-β1-induced FMT were analyzed by transcriptomic methods, and further validated in vitro or in fibrotic lung specimens. The effects of HuR overexpression, down-regulation or inhibition by an antagonist CMLD-2 were analyzed in FMT or bleomycin-induced experimental lung fibrosis. HuR-targeting RNA and their interactions were analyzed by CLIP-seq.ResultsHuR, hnRNPA1, hnRNPE1, TIA1 and TFRC were significantly up-regulated, while ESRP1, ESRP2 and TTP were significantly down-regulated. Cytoplasmic expression of HuR was activated in IPF lung tissue and rat lungs of bleomycin-induced fibrosis. HuR overexpression induced α-SMA and collagen I expression, increased the proliferation and migration capacities of fibroblasts with or without the stimulation of TGF-β1. HuR knockdown by shRNA inhibited the proliferation, transition, collagen production and migration properties in fibroblasts or in TGF-β1-stimulated myofibroblasts. Combinative analysis of RNA-seq and CLIP-seq data revealed major HuR binding motifs and several HuR-bound, differentially expressed mRNAs in FMT, specifically SPP1 mRNA encoding osteopontin. HuR-mediated SPP1 mRNA stabilization was further validated by RIP-PCR and half-life analysis using SPP1 mutant transcripts. Inhibiting HuR using CMLD-2 attenuated SPP1/osteopontin expression, TGF-β1-induced FMT in vitro and bleomycin-induced pulmonary fibrosis in mice. Nuclear-cytoplasmic shuttle of HuR was activated in TGF-β1-induced FMT, which was inhibited by p38MAPK (SB203580) or PKC (Go-6976) inhibition, but not associated with phosphorylation of HuR.ConclusionsFibroblast-myofibroblast transition is activated by HuR-SPP1 mRNA interactions, and CMLD-2 is potentiated to be a therapeutic agent targeting HuR for fibroblast-myofibroblast transition and pulmonary fibrosis.

We prove that the critical value of the one-dimensional Stochastic Sandpile Model is less than one. This verifies a conjecture of Rolla and Sidoravicius., Comment: 44 pages

We study the winding behavior of random walks on two oriented square lattices. One common feature of these walks is that they are bound to revolve clockwise. We also obtain quantitative results of transience/recurrence for each walk., Comment: 28 pages

We show that for small enough sleep rate, the critical density of the symmetric Activated Random Walk model on $\mathbb Z^2$ is strictly less than one.

Additional file 4. Effect of shikonin(SKN) on the cell cycle of synovial fibroblasts.

Additional file 1. SKN has no obvious hepatotoxicity and reproductive toxicity measured by HE.

Additional file 2. With the passage of time, the out-growth of FLS became more obvious.

Additional file 3. FLS was cultured with SKN and/or TNF-α for 24 h, then measured by MTT assay for cell cytotoxicity detection.

Additional file 5. Effect of shikonin(SKN) on apoptosis of synovial fibroblasts.

The new type large capacity synchronous condensers are designed to satisfy the strong demand of dynamic reactive power support for the converter station of HVDC system. However, its operating characteristics have great difference with static reactive power compensation equipment. Therefore, it is very important to study the influence of synchronous condenser on the voltage stability of the HVDC system. In this paper, the dynamic operating characteristics of synchronous condenser connected to the rectifier station are studied during the voltage sag under the different transmitted active power and reactive power reserve of sending-end system. The voltage of AC-DC systems during the voltage sag are compared under the different conditions, respectively. The ability of synchronous condenser on maintaining voltage stability and transmitted active power of DC transmission systems is analyzed. The result of this paper can provide theoretical basis on synchronous condenser applying to converter station of HVDC systems.

Large capacity synchronous condenser can provide strong dynamic reactive power demand for HVDC transmission system, and its operation characteristics are related to excitation parameters. The force excitation voltage ratio and low excitation voltage ratio of synchronous condenser can affect dynamic reactive response and HVDC system voltage. This paper studied the influence of force excitation voltage ratio on voltage stability of HVDC after voltage sag of sending and receiving end, and the influence of low excitation voltage ratio on voltage stability after overvoltage of sending-end caused by DC Bi-polar block fault. The voltage of AC-DC systems, the reactive power of synchronous condenser and transmission power of HVDC are compared under the different excitation limit, respectively. The results show that the output reactive power of synchronous condenser increases by 400MVar and the system voltage increases by 10% of rated value as the force excitation voltage ratio changing from 2 to 3.5 during the process of voltage sag. The recovered time of system voltage of AC system decreases by 3.35s and reactive power of synchronous condenser decreases by 5.14s as the force excitation voltage ratio changing from 2.5 to 3.5. The absorbed reactive power of synchronous condenser increases by 40MVar as the low excitation voltage ratio change from 10% to 0 during the process of DC Bi-polar Block Fault. The results can provide theory basis for the operation of synchronous condenser connected to HVDC.

The parameters of synchronous generator used in power system are often obtained by the empirical formula. The simulation results calculated by these parameters have a large difference from the results of testing. Some people proposed that the accuracy parameters could be obtained by parameter identification base on experiment results. However, the large disturbance testing of large synchronous generator is hard to implement. Therefore, this paper proposes that the parameters are identified based on the results calculated by Time-Stepping Finite Element Model (T-S FEM). With a 300 MW turbine generator as an example, the steady-state parameters (x d , x q ), transient parameters (x d ', x q ', T d0 ', T q0 ') and sub-transient parameters (x d ", x q ", T d0 ", T q0 ") are identified by the least square method, and compared with the results by the empirical formula. The parameters are identified in different power angle and the influences factor on different parameters are compared and analyzed. Since the rotor slot wedge has several materials to choose from, the parameters of synchronous generator with slot wedge made from aluminum and stainless steel are identified respectively. The result shows that the parameters have a great difference in different power angle. The sub-transient time constants of synchronous generator with the rotor slot wedge made from stainless steel are smaller than that made from aluminum.

This paper comprehensively analyzes the connotation and denotation of “region” and “local culture”. Combing the views and attitudes of the critical regionalism, the article proposes the revelation of this theory for the structural transformation in product innovation and further puts forward the expression steps and innovative ideas of local culture in product design. The enterprises and product designers should reinterpret the regional features in the practice of modernism, rather than superficially imitate local culture symbols and patterns. The integration of local culture, traditional crafts, modern technology and contemporary aesthetic based on deep understanding their own culture is an effective way close to the product innovation.

Scientific Abstract Hemophilia B due to deficiency of the human factor IX is a fatal hereditary disease. The transfusion of blood or concentrated factor IX is the normal way of treatment, but this ...