Dihydrotanshinone,a Natural Diterpenoid,Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.     

Crystal-field engineering of ultrabroadband mid-infrared emission in Co2+-doped nano-chalcogenide glass composites

Tunable and ultrabroadband mid-infrared (MIR) emissions in the range of 2.5–4.5 μm are firstly reported from Co²⁺-doped nano-chalcogenide (ChG) glass composites. The composites embedded with a variety of binary (ZnS, CdS, ZnSe) and ternary (ZnCdS, ZnSSe) ChG nanocrystals (NCs) can be readily obtained by a simple one-step thermal annealing method. They are highly transparent in the near- and mid-infrared wavelength region. Low-cost and commercially available Er³⁺-doped fiber lasers can be used as the excitation source. By crystal-field engineering of the embedded NCs through cation- or anion-substitution, the emission properties of Co²⁺ including its emission peak wavelength and bandwidth can be tailored in a broad spectral range. The phenomena can be accounted for by crystal-field theory. Such nano-ChG composites, perfectly filling the 3–4 μm spectral gap between the oscillations of Cr²⁺ and Fe²⁺ doped IIVI ChG crystals, may find important MIR photonic applications (e.g., gas sensing), or can be used directly as an efficient pump source for Fe²⁺: IIVI crystals which are suffering from lack of pump sources.     

An approach to measure infill matric suction of irregular infilled rock joints under constant normal stiffness shearing

Rock joints infilled with sediments can strongly influence the strength of rock mass. As infilled joints often exist under unsaturated condition, this study investigated the influence of matric suction of infill on the overall joint shear strength. A novel technique that allows direct measurement of matric suction of infill using high capacity tensiometers (HCTs) during direct shear of infilled joints under constant normal stiffness (CNS) is described. The CNS apparatus was modified to accommodate the HCT and the procedure is explained in detail. Joint specimens were simulated by gypsum plaster using three-dimensional (3D) printed surface moulds, and filled with kaolin and sand mixture prepared at different water contents. Shear behaviours of both planar infilled joints and rough joints having joint roughness coefficients (JRCs) of 8–10 and 18–20 with the ratios of infill thickness to asperity height (t/a) equal to 0.5 were investigated. Matric suction shows predominantly unimodal behaviour during shearing of both planar and rough joints, which is closely associated with the variation of unloading rate and volumetric changes of the infill material. As expected, two-peak behaviour was observed for the rough joints and both peaks increased with the increase of infill matric suction. The results suggest that the contribution of matric suction of infill on the joint peak normalised shear stress is relatively independent of the joint roughness.     

湿式摩擦副滑摩过程温度场分析及实验验证

湿式摩擦副滑摩过程温度场与应力场相互耦合作用,温度场分布受到多种因素影响,其中压力、旋转速度、润滑流量作为湿式摩擦副工作参数对其温度场的影响尤为显著。在理论分析基础上,采用有限元数值模拟分析与实验研究相结合的方法,对摩擦界面温度场时空分布特性进行研究,同时研究界面温度场在摩擦副工作压力、相对转速和润滑流量作用下的变化规律。研究表明:在对偶钢片和摩擦片近外径侧更易出现高温和应力集中区,且对偶钢片相对于摩擦片更易出现温度和应力分布不均匀情况;温度场中高温集中区与应力场中应力集中区相对应,最大温度随着压力增加、相对转速增大、润滑流量减少而显著上升,该结果得到试验结果的验证。     

Temperature cycling and its effect on mechanical behaviours of highporosity chalks

Temperature history can have a significant effect on the strength of water-saturated chalk.In this study,hydrostatic stress cycles are applied to understand the mechanical response of chalk samples exposed to temperature cycling between each stress cycle,compared to the samples tested at a constant temperature.The total accumulated strain during a stress cycle and the irreversible strain are reported.Chalk samples from Kansas(USA)and Mons(Belgium),with different degrees of induration(i.e.amount of contact cementation),were used.The samples were saturated with equilibrated water(polar)and nonpolar Isopar H oil to quantify water weakening.All samples tested during 10 stress cycles with varying temperature(i.e.temperature cycled in between each stress cycle)accumulated more strain than those tested at constant temperatures.All the stress cycles were performed at 30℃.The two chalk types behaved similarly when saturated with Isopar H oil,but differently when saturated with water.When saturated with water,the stronger Kansas chalk accumulated more total strain and more irreversible strain within each stress cycle than the weaker Mons chalk.     

The Crosstalk of Adipose-Derived Stem Cells (ADSC), Oxidative Stress,and Inflammation in Protective and Adaptive Responses

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs is a major goal in repair medicine. Stem cells are classified by their potential to differentiate into functional cells. Compared with other sources, adipose-derived stem cells (ADSCs) have the advantage of being abundant and easy to obtain. ADSCs are considered to be tools for replacing, repairing, and regenerating dead or damaged cells. The capacity of ADSCs to maintain their properties depends on the balance of complex signals in their microenvironment. Their properties and the associated outcomes are in part regulated by reactive oxygen species, which mediate the oxidation-reduction state of cells as a secondary messenger. ADSC therapy has demonstrated beneficial effects, suggesting that secreted factors may provide protection. There is evidence that ADSCs secrete a number of cytokines, growth factors, and antioxidant factors into their microenvironment, thus regulating intracellular signaling pathways in neighboring cells. In this review, we introduce the roles of ADSCs in the protection of cells by modulating inflammation and immunity, and we develop their potential therapeutic properties.     

Effects of sintering in a high magnetic field on properties of vitrified bond and vitrified CBN composites

Vitrified bond CBN grinding wheels are being widely used due to their superior performance. Also, advantages of vitrified grinding wheels are high elastic modulus, stable chemical property, and low thermal expansion coefficient. Brittleness and low strength are key factors restricting the development of vitrified bond CBN grinding wheels. In this paper, the sintering in a high magnetic field was innovatively introduced into the manufacturing of vitrified bond CBN grinding wheels, and the effects of sintering in a high magnetic field on properties on vitrified bond and vitrified CBN composites were systematically investigated. Vitrified bond was characterized using three-point bending, scanning electron microscopy, X-ray diffraction. It was observed that microstructure of vitrified bond could be changed, grain orientation could be controlled and average grain size could be decreased in a high magnetic field, while vitrified bond strength could be simultaneously improved. High quality vitrified bond could be obtained by appropriately adjusting the strength and direction of high magnetic field. Results demonstrated that vitrified bond properties were improved when the magnetic field strength was 6?T. In order to highlight the high magnetic field effect on the vitrified CBN composites, the ordinary CBN abrasives and nickel plated CBN abrasives were used respectively. Microstructures, bending strengths of vitrified CBN composites were compared in different high magnetic fields. When the magnetic field strength was appropriate (less than 6?T), the binding characteristic of vitrified bond CBN composites with nickel plated CBN abrasives was greatly improved. The highest bending strength value of vitrified CBN composites was 79.5?MPa in 6?T high magnetic field.