[Latest Findings on the Pathogenic Mechanisms of Thoracic Aortic Dissection].

Thoracic aortic dissection (TAD) is a cardiovascular disease entailing a high lethality between 65% and 85%. Surgery-assissed implant/interventional stenting is the prevailing treatment of TAD. However, surgical treatment can cause severe postoperative complications and patients incur a relatively higher risk of postoperative mortality. Since the pathogenic mechanism underlying TAD is not clear, effective medication therapies are still not available. In recent years, along with advances in single-cell sequencing and other molecular biological technologies, there have been prelimiary findings suggesting the special role of dysfunctional vascular smooth muscle cells (VSMCs) in the pathogenesis and development of TAD. Furthermore, the molecular mechanisms regulating the dysfunction of VSMCs have been initially explored. It is expected that these new findings will contribute to the development of new strategies to prevent TAD and lead to new ideas for the identifiction of potential drug therapeutic targets. Herein, we summarized the critical role of dysfunctional VSMCs in the pathogenesis and development of TAD and presented in detail the biological factors and the related molecular mechanisms that regulate the dysfunction of VSMCs. We hope this review will provide a reference for further investigation into the central role of dysfunctional VSMCs in the pathogenesis and development of TAD and exploration for effective molecular drug targets for TAD.

Hederagenin ameliorates cisplatin-induced acute kidney injury via inhibiting long non-coding RNA A330074k22Rik/Axin2/ß-catenin signalling pathway.

BACKGROUND: Acute kidney injury (AKI), a kidney disease with high morbidity and mortality, is characterized by a dramatic decline in renal function. Hederagenin (HDG), a pentacyclic triterpenoid saponin isolated from astragalus membranaceus, has been shown to have significant anti-inflammatory effects on various diseases. However, the effects of HDG on renal injury and inflammation in AKI has not been elucidated. METHODS: In this research, mice model of AKI was established by intraperitoneal injection of cisplatin in vivo, the inflammatory model of renal tubular epithelial cells was established by LPS stimulation in vitro, and HDG was used to intervene in vitro and in vivo models. Transcriptome sequencing was used to analyze the alterations of LncRNA and mRNA expression in AKI model and LncRNA-A330074k22Rik (A33) knockdown cells, respectively. Renal in situ electrotransfer knockdown plasmid was used to establish mice model of AKI with low expression of A33 in kidney. RESULTS: The results showed that HDG effectively alleviate cisplatin-induced kidney injury and inflammation in mice. Transcriptome sequencing results showed that multiple LncRNAs in kidney of AKI model exhibited significant changes, among which LncRNA-A33 had the most obvious change trend. Subsequent results showed that A33 was highly expressed in kidney of AKI mice and LPS-induced renal tubular cells. After in situ renal electroporation knockdown plasmid down-regulated A33 in kidney of AKI mice, it was found that inhibition of A33 could significantly relieve cisplatin-induced kidney injury and inflammation of AKI, while HDG could effectively suppress the expression of A33 in vitro and in vivo, respectively. Subsequently, transcriptome sequencing was again used to analyze the changes in mRNA expression of renal tubular cells after A33 knockdown by siRNA. The results showed that a large number of inflammation-related signaling pathways were down-regulated, Axin2 and its downstream ß-catenin signal were significantly inhibited. Cell recovery test showed that HDG inhibited Axin2/ß-catenin signal by down-regulating A33, and improved kidney injury and inflammation of AKI. CONCLUSION: Taken together, HDG significantly ameliorated cisplatin-induced kidney injury through LncRNA-A330074k22Rik/Axin2/ß-catenin signal axis, which providing a potential therapeutic approach for the treatment of AKI.

Direct Z-scheme 1D/2D WO2.72/ZnIn2S4 hybrid photocatalysts with highly-efficient visible-light-driven photodegradation towards tetracycline hydrochloride removal.

There are increasing environmental concerns of serious pollution from emission of antibiotic wastewater. Herein, a series of direct Z-scheme WO2.72/ZnIn2S4 (WOZIS) hybrid photocatalysts composed of one-dimensional (1D) WO2.72 (WO) nanorods and two-dimensional (2D) ZnIn2S4 (ZIS) nanosheets have been designed and constructed for tetracycline hydrochloride (TCH) degradation without presence of solid-state electron mediators. The crystalline phase, chemical composition, morphology, optical properties and photocatalytic activity of the as-prepared samples were characterized by the XRD, XPS, SEM, HRTEM, BET, UV-vis DRS, and PL. Obviously, all the WOZIS hybrid photocatalysts exhibited significantly enhanced photocatalytic activity towards TCH degradation. Meanwhile, WOZIS-1 sample with WO/ZIS molar ratio of 1:1 showed the highest photocatalytic activity. The significantly enhanced photoactivity of WOZIS hybrid photocatalyst was due to Z-scheme charge separation mechanism based on the build of tight interfacial contacts between WO nanorods and ZIS nanosheets, thereby driving efficient charge separation. Moreover, the high photocatalytic stability of as-prepared WOZIS-1 hybrid sample was revealed through seven successive cycling reactions.

Hierarchical CdIn2S4 microspheres wrapped by mesoporous g-C3N4 ultrathin nanosheets with enhanced visible light driven photocatalytic reduction activity.

In this investigation, a series of hierarchical CdIn2S4/g-C3N4 nanocomposites were firstly synthesized by a facile one-pot hydrothermal strategy, wherein the mesoporous g-C3N4 nanosheets were in-situ self-wrapped onto CdIn2S4 nanosheets. Systematic characterization by XRD, FT-IR, UV-vis DRS, SEM, TEM, HAAF-STEM, XPS, photoelectrochemical tests were employed to analyze the phase structure, chemical composition, morphology and photocatalytic mechanism. The application, including photo-redox reaction and photocatalytic water splitting, were used to estimate the photocatalytic activity of as-obtained CdIn2S4/g-C3N4 nanocomposites. The results indicate that CdIn2S4/g-C3N4 heterostructures exhibit more efficient improvement of the photocatalytic performances towards photo-reduction of 4-NA to corresponding 4-PDA and photocatalytic H2 generation from water splitting than these counterparts as results of construction of intimate interfacial contact, which would promote the separation of photo-generated holes and electrons. Meanwhile, benefitting from the excellent surface wrap, the CdIn2S4/g-C3N4 nanocomposites possess notable enhanced photocatalytic stability. This research may provide a promising way to fabricate highly efficient photocatalysts with excellent stability and expand the application of CdIn2S4 in fine chemical engineering.

Mesoporous transition metal oxides quasi-nanospheres with enhanced electrochemical properties for supercapacitor applications.

In this report, we obtain mesoporous transition metal oxides quasi-nanospheres (includes MnO2, NiO, and Co3O4) by utilizing mesoporous silica nanospheres as a template for high-performance supercapacitor electrodes. All samples have a large specific surface area of approximately 254-325m(2)g(-1) and a relatively narrow pore size distribution in the region of 7nm. Utilization of a nanosized template resulted in a product with a relative uniform morphology and a small particle diameter in the region of 50-100nm. As supercapacitor electrodes, MnO2, NiO, and Co3O4 exhibit an outstanding capacity as high as 838-1185Fg(-1) at 0.5Ag(-1) and a superior long-term stability with minimal loss of 3-7% after 6000 cycles at 1Ag(-1). Their excellent electrochemical performances are attributed to favorable morphologies with a large surface area and a uniform architecture with abundant pores. The associated enhancement of electrolyte ion circulation within the electrode facilitates a significant increase in availability of Faradic reaction electroactive sites.

Preparation of chitosan grafted graphite composite for sensitive detection of dopamine in biological samples.

The accurate detection of dopamine (DA) levels in biological samples such as human serum and urine are essential indicators in medical diagnostics. In this work, we describe the preparation of chitosan (CS) biopolymer grafted graphite (GR) composite for the sensitive and lower potential detection of DA in its sub micromolar levels. The composite modified electrode has been used for the detection of DA in biological samples such as human serum and urine. The GR-CS composite modified electrode shows an enhanced oxidation peak current response and low oxidation potential for the detection of DA than that of electrodes modified with bare, GR and CS discretely. Under optimum conditions, the fabricated GR-CS composite modified electrode shows the DPV response of DA in the linear response ranging from 0.03 to 20.06µM. The detection limit and sensitivity of the sensor were estimated as 0.0045µM and 6.06µA µM(-1)cm(-2), respectively.

Potential signaling pathway involved in sphingosine-1-phosphate-induced epithelial-mesenchymal transition in cancer.

The developmental process of epithelial-mesenchymal transition (EMT) occurs when epithelial cells acquire invasive mesenchymal cell characteristics, and the activation of this process has been indicated to be involved in tumor progression. EMT could be induced by growth factors, cytokines and matrix metalloproteinases (MMPs). sphingosine-1-phosphate (S1P) is a biologically-active lipid that plays an important role in cancer metastasis. S1P also contributes to the activation of EMT. However, the mechanism underlying S1P-induced EMT is unclear. Increased evidence has demonstrated that the cell surface glycocalyx is closed associated with S1P and plays an important role in tumor progression, suggesting that S1P-induced EMT could be Snail-MMP signaling-dependent. Thus, we hypothesize that an S1P-glycocalyx-Snail-MMP signaling axis mediates S1P-induced EMT. This is an essential step towards improved understanding of the underlying mechanism involved in S1P-regulted EMT, and the development of novel diagnostic and anticancer therapeutic strategies.

A simple electrochemical platform for detection of nitrobenzene in water samples using an alumina polished glassy carbon electrode.

In this work, we report a selective electrochemical sensing of nitrobenzene (NB) using an alumina (γ-Al2O3) polished glassy carbon electrode (GCE) for the first time. The scanning electron microscopy studies confirm the presence of alumina particles on the GCE surface. X-ray photoelectron spectroscopy studies reveal that the utilized alumina is γ-Al2O3. The alumina polished GCE shows an enhanced sensitivity and lower overpotential toward the reduction of NB compared to unpolished GCE. The differential pulse voltammetry response was used for the determination of NB and it shows that the reduction peak current of NB is linearly proportional to the concentrations of NB ranging from 0.5 to 145.5µM. The limit of detection is found to be 0.15µM based on 3σ. The fabricated electrode exhibits its appropriate selectivity towards NB in the presence of a range of nitro compounds and metal ions. The good practicality of the sensor in various water samples reveals that it can be a promising electrode material for practical applications. In addition, the proposed NB sensor is simple and cost effective one when compared with previously reported NB sensors in the literature.

Novel mesoporous P-doped graphitic carbon nitride nanosheets coupled with ZnIn2S4 nanosheets as efficient visible light driven heterostructures with remarkably enhanced photo-reduction activity.

In this report, we rationally designed and fabricated P-C3N4/ZnIn2S4 nanocomposites by in situ immobilizing ZnIn2S4 nanosheets onto the surface of mesoporous P-doped graphite carbon nitrogen (P-C3N4) nanosheets in a mixed solvothermal environment; their application to the photoreduction of 4-nitroaniline was used to estimate the photocatalytic performance. Different to the template route, here the mesoporous P-C3N4 nanosheets were prepared with a template-free strategy. The as-fabricated P-C3N4/ZnIn2S4 nanocomposites were systematically characterized by analyzing the phase structure, chemical components, electronic and optical properties and separation of charge carrier pairs. More importantly, these P-C3N4/ZnIn2S4 heterostructures have been proven to be highly efficient visible light responsive photocatalysts for photo-reduction, and meanwhile exhibit excellent photo-stability during recycling runs. The sufficient evidence reveals that the significantly improved photocatalytic performance is mainly attributed to the more efficient charge carrier separation based on the construction of a close heterogeneous interface. This work may provide new insights into the utilization of P-C3N4/ZnIn2S4 nanocomposites as visible light driven photocatalysts for comprehensive organic transformations in the field of fine chemical engineering.

Potential microRNA biomarkers for acute ischemic stroke.

Acute ischemic stroke is a significant cause of high morbidity and mortality in the aging population globally. However, current therapeutic strategies for acute ischemic stroke are limited. Atherosclerotic plaque is considered an independent risk factor for acute ischemic stroke. To identify biomarkers for carotid atheromatous plaque, bioinformatics analysis of the gene microarray data of plaque and intact tissue from individuals was performed. Differentially expressed genes (DEGs) were identified using the Multtest and Limma packages of R language, including 56 downregulated and 69 upregulated DEGs. Enriched microRNA (miRNA or miR) DEGs networks were generated using WebGestalt software and the STRING databases, and the miRNAs were validated using serum from acute ischemic stroke patients with reverse transcription quantitative PCR (RT­qPCR). Four confirmed differentially expressed miRNAs (miR­9, ­22, ­23 and ­125) were associated with 28 upregulated DEGs, and 7 miRNAs (miR­9, ­30, ­33, ­124, ­181, ­218 and ­330) were associated with 25 downregulated DEGs. Gene ontology (GO) function suggested that the confirmed miRNA­targeted DEGs predominantly associated with signal transduction, the circulatory system, biological adhesion, striated muscle contraction, wound healing and the immune system. The confirmed miRNA­targeted genes identified serve as potential therapeutic targets for acute ischemic stroke.

Sphingosine 1-phosphate induced synthesis of glycocalyx on endothelial cells.

Sphingosine 1-phosphate (S1P) protects glycocalyx against shedding, playing important roles in endothelial functions. We previously found that glycocalyx on endothelial cells (ECs) was shed after plasma protein depletion. In the present study, we investigated the role of S1P on the recovery of glycocalyx, and tested whether it is mediated by phosphoinositide 3-kinase (PI3K) pathway. After depletion of plasma protein, ECs were treated with S1P for another 6h. And then, the major components of glycocalyx including syndecan-1 with attached heparan sulfate (HS) and chondroitin sulfate (CS) on endothelial cells were detected using confocal fluorescence microscopy. Role of PI3K in the S1P-induced synthesis of glycocalyx was confirmed by using the PI3K inhibitor (LY294002). Syndecan-1 with attached HS and CS were degraded with duration of plasma protein depletion. S1P induced recovery of syndecan-1 with attached HS and CS. The PI3K inhibitor LY294002 abolished the effect of S1P on recovery of glycocalyx. Thus, S1P induced synthesis of glycocalyx on endothelial cells and it is mediated by PI3K pathway.

Numerical simulation of the effect of permeability on the hydrodynamics in a parallel-plate coculture flow chamber.

To study the effect of the porous membrane permeability on the hydrodynamics in a parallel-plate coculture flow chamber (PPcFC), we demonstrated the permeability of the porous membrane as a function of some parameters, such as porosity, membrane thickness, pore size and shape of the membrane. The effect of permeability on the flow in the PPcFC was analysed using the commercial software - Fluent. Results showed that the permeability was directly proportional to the thickness, the porosity and the pore size of the membrane, and inversely proportional to the surface shape factor. To ensure the best flow pattern, the inlet velocity range was limited by the membrane permeability and fluid viscosity, and then restricted the available magnitudes of shear rate on the permeable membrane. Our findings are helpful in designing and preparing the biomaterials that have adequate mechanical properties for the functional vascular grafts production, and in using of the flow chamber in various investigations.

Roles of mechanical force and CXCR1/CXCR2 in shear-stress-induced endothelial cell migration.

We previously demonstrated that CXCR1 and CXCR2 are novel mechanosensors mediating laminar shear-stress-induced endothelial cell (EC) migration (Zeng et al. in Cytokine 53:42-51, 2011). In the present study, an analytical model was proposed to further analyze the underlying mechanisms, assuming the mechanical force (MF) and mechanosensor-mediated biochemical reactions induce cell migration together. Shear stress can regulate both mechanosensor-mediated migration in the flow direction (Ms-M(FD)) and mechanosensor-mediated migration toward a wound (Ms-M(W)). Next, the migration distance, the roles of MF-induced cell migration (MF-M), and the mobilization mechanisms of mechanosensors were analyzed. The results demonstrated that MF-M plays an important role in 15.27 dyn/cm(2) shear-stress-induced EC migration but is far weaker than Ms-M(W) at 5.56 dyn/cm(2). Our findings also indicated that CXCR2 played a primary role, in synergy with CXCR1. The Ms-M(FD) was primarily mediated by the synergistic effect of CXCR1 and CXCR2. In Ms-M(W), when shear stress was beyond a certain threshold, the synergistic effect of CXCR1 and CXCR2 was enhanced, and the effect of CXCR1 was inhibited. Therefore, the retarding of EC migration and wound closure capacity under low shear flow was related to the low magnitude of shear stress, which may contribute to atherogenesis and many other vascular diseases.

Interleukin-8 induces the endothelial cell migration through the activation of phosphoinositide 3-kinase-Rac1/RhoA pathway.

Endothelial cell migration is essential for tumor angiogenesis, and interleukin-8 (IL-8) has been shown to play an important role in tumor growth, angiogenesis, and metastasis. This study aimed to investigate the molecular mechanism of IL-8 induced endothelial cell migration. Our results indicated that IL-8 induced a rapid rearrangement of the actin cytoskeleton in EA.Hy926 cells, generating extensions resembling membrane ruffling and stress fibers. These processes required parallel upregulation of the small GTPases Rac1 and RhoA. Moreover, we demonstrated that IL-8 activated PI3K following the same kinetics observed from IL-8 induction of cytoskeletal rearrangement, suggesting the participation of PI3K in these processes. Taken together, our study demonstrates that PI3K-Rac1/RhoA signaling pathway plays a vital role in IL-8 induced endothelial cell migration, and provides new insight into the molecular mechanisms by which IL-8 contributes to tumor angiogenesis and metastasis.

CXCR1 and CXCR2 are novel mechano-sensors mediating laminar shear stress-induced endothelial cell migration.

The migration of endothelial cells (ECs) plays critical roles in vascular physiology and pathology. The receptors CXCR1 and CXCR2, known as G protein-coupled receptors which are essential for migratory response of ECs toward the shear stress-dependent CXCL8 (interleukin-8), are potential mechano-sensors for mechanotransduction of the hemodynamic forces. In present study, the mRNA and protein expression of CXCR1 and CXCR2 in EA.hy926 cells was detected by RT-PCR and Western blot analysis under three conditions of laminar shear stress (5.56, 10.02 and 15.27 dyn/cm(2)) respectively. Using a scratched-wound assay, the effects of CXCR1 and CXCR2 were assessed by the percentage of wound closure while CXCR1 and CXCR2 were functional blocked by the CXCL8 receptor antibodies. The results showed that the mRNA and protein expression of CXCR1 and CXCR2 was both upregulated by 5.56 dyn/cm(2) laminar shear stress, but was both downregulated by 15.27 dyn/cm(2). The wound closure was inhibited significantly while cells were treated with those antibodies in all the conditions. It was suggested that CXCR1 and CXCR2 are involved in mediating the laminar shear stress-induced EC migration. Taken together, these findings indicated that CXCR1 and CXCR2 are novel mechano-sensors mediating laminar shear stress-induced EC migration. Understanding this expanded mechanism of laminar shear stress-induced cell migration will provide novel molecular targets for therapeutic intervention in cancer and cardiovascular diseases.

[Study of photocatalytic activity, characterization and preparation of supersuspended nano-TiO2 (II) photocatalytic activity].

The photocatalytic activity of nano-TiO2 prepared by pyrolysis method and then by cooling-treatment in silicon oil and in air respectively was studied with methyl-orange solution as model waste water. The results show that the photocatalytic activity of both products is obvious with no great difference. However, the nano-TiO2 powder modified with silicone oil can degrade harmful components more effectively on the surface of waste water with sunlight and other extra light.

Effects of steady shear flow on the deformation of leukocyte adhered to vascular endothelial surface.

OBJECTIVE: To investigate the effects of steady shear flow on the deformation properties of an adherent leukocyte and its nucleus. METHOD: A compound drop model was developed to simulate the leukocyte adhered to the inner surface of a blood vessel, and a two dimensional computational fluid dynamics (CFD) was conducted to solve the model equations. RESULT: The results show: 1) The Reynolds number of the external shear flow plays a crucial role in leukocyte deformation. Leukocyte deformation increases with Reynolds number; 2) The nucleus deforms together with the leukocyte, and the deformation index of the leukocyte is greater than that of the nucleus. The leukocyte is more deformable while the nucleus is more capable of resisting external shear flow; 3) The leukocyte and the nucleus will not deform infinitely when the Reynolds number increases beyond a certain value where the deformation index reaches its maximum; 4) Pressure distribution over the surface demonstrated that there exists a region downstream of the cell, where is high pressure produced to retard continuous deformation and to provide a positive lift force on the cell. CONCLUSION: The nucleus with high viscosity plays a particular role in leukocyte deformation under shear flow.

[Study of photocatalytic activity, characterization and preparation of supersuspended nano-TiO2. II. Study of photocatalytic activity].

From the change in the absorption of methyl-orange solution at 470 nm, the photocatalytic activity of nano-TiO2 prepared by pyrolysis method, and then by cooling treatment in silicon oil and in air respectively, was studied with methyl-orange solution as model waste water under irradiation by UV-lamp. Their photocatalytic mechanisms, the percentage of degradation in 35 min and the kinetic reactive process were also analyzed. The results show that the photocatalytic activity of both products is obvious with little difference. However, the nano-TiO2 powder modified with silicone oil can degrade harmful components more effectively on the surface of waste water with sunlight and other extra light.