VEGF-induced vascular permeability is mediated by FAK

Endothelial cells (ECs) form cell-cell adhesive junctional structures maintaining vascular integrity. This barrier is dynamically regulated by vascular endothelial growth factor (VEGF) receptor signaling. We created an inducible knockin mouse model to study the contribution of the integrin-associated focal adhesion tyrosine kinase (FAK) signaling on vascular function. Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation, rapid FAK localization to cell-cell junctions, binding of the FAK FERM domain to the vascular endothelial cadherin (VE-cadherin) cytoplasmic tail, and direct FAK phosphorylation of β-catenin at tyrosine-142 (Y142) facilitating VE-cadherin-β-catenin dissociation and EC junctional breakdown. Kinase inhibited FAK is in a closed conformation that prevents VE-cadherin association and limits VEGF-stimulated β-catenin Y142 phosphorylation. Our studies establish a role for FAK as an essential signaling switch within ECs regulating adherens junction dynamics.     

Adsorption of Ni2+ and Cu2+ using Bio-Mineral: Adsorption Isotherms and Mechanisms

Heavy metal pollution has become one of the most serious environmental pollution problems. This study aimed to determine the adsorption and desorption characteristics of Ni²⁺ and Cu²⁺ by bio-mineral which was induced by Bacillus subtilis, and to explore the effect of pH on adsorption characteristics. The results showed that the Langmuir model gave a better fit to the experimental data than the Freundlich model, which demonstrated the adsorption was of a single-molecule layer form. The maximum adsorption capacities of the bio-mineral for Ni²⁺ and Cu²⁺ were determined as 67.114 mg/g and 69.930 mg/g, respectively. The desorption rates of Ni²⁺ and Cu²⁺ were very low, especially for Ni²⁺ which was almost 0. Besides, the bio-mineral maintained high adsorption capability for metals ions within a wide pH range (pH ≥ 3). It did not show any new phases after adsorption of Ni²⁺ and Cu²⁺ tested by FTIR, indicating that the bio-mineral and heavy metal ions might mainly physically be adsorbed. The bio-mineral has a larger internal and external specific surface area, pore volume and colloidal properties which are beneficial for the adsorption of metals ions, but shows limits in desorption. This study provides a theoretical basis for the utilization of bio-mineral and opens a new perspective for the remediation of heavy metals pollution.     

污染预测的非线性参数模型

本文探索了Cr~（3 ）,Cr~（6 ）溶液浓度与绿豆幼苗根过氧化物酶活性之间的相关关系,建立了线性与非线性的数学模型,经相关指数,剩余标准差检验,找出了拟合度比较高的非线性参数模型．本文的结果为利用过氧化物酶活性增长率作为水环境受重金属污染的生物监测指标提供了理论依据．     

By-Products of Zea mays L.: A Promising Source of Medicinal Properties with Phytochemistry and Pharmacological Activities: A Comprehensive Review

Zea mays (Z. mays) is one of the main cereal crops in the world, and it′s by-products have exhibited medicinal properties to explore. This article intends to review the chemical compositions and pharmacological activities of by-products of Z. mays (corn silks, roots, bract, stems, bran, and leaves) which support the therapeutic potential in the treatment of different diseases, with emphasis on the natural occurring compounds and detailed pharmacological developments. Based on this review, 231 natural compounds are presented. Among them, flavonoids, terpenes, phenylpropanoids, and alkaloids are the most frequently reported. The by-products of Z. mays possess diuretic effects, hepatoprotective, anti-diabetic, antioxidant, neuroprotective, anti-inflammatory, anti-cancer, plant protection activity, and other activities. This article reviewed the phytochemistry and pharmacological activities of Z. mays for comprehensive quality control and the safety and effectiveness to enhance future application.     

Excessive rainfall leads to maize yield loss of a comparable magnitude to extreme drought in the United States

Increasing drought and extreme rainfall are major threats to maize production in the United States. However, compared to drought impact, the impact of excessive rainfall on crop yield remains unresolved. Here, we present observational evidence from crop yield and insurance data that excessive rainfall can reduce maize yield up to ?34% (?17 ± 3% on average) in the United States relative to the expected yield from the long‐term trend, comparable to the up to ?37% loss by extreme drought (?32 ± 2% on average) from 1981 to 2016. Drought consistently decreases maize yield due to water deficiency and concurrent heat, with greater yield loss for rainfed maize in wetter areas. Excessive rainfall can have either negative or positive impact on crop yield, and its sign varies regionally. Excessive rainfall decreases maize yield significantly in cooler areas in conjunction with poorly drained soils, and such yield loss gets exacerbated under the condition of high preseason soil water storage. Current process‐based crop models cannot capture the yield loss from excessive rainfall and overestimate yield under wet conditions. Our results highlight the need for improved understanding and modeling of the excessive rainfall impact on crop yield.     

Does in vitro activation of postsynaptic alpha 2-adrenoceptor utilize intracellular Ca2+ for contraction in dog saphenous vein?

Dog saphenous vein spiral strips were employed to determine whether an intracellular source of Ca2+ is used for contraction upon activation of the alpha 2-adrenoceptor by B-HT 920 in Ca2+-free Krebs solution containing 50 microM EGTA. The studies were carried out in parallel with the activation of the alpha 1-adrenoceptor by phenylephrine (Phe) under the condition that B-HT 920 (10(-5) M) and Phe (2 x 10(-6) M) gave rise to a similar level of responses in Ca2+-containing Krebs solution. A similar level of responses to these agonists at equieffective concentrations in Ca2+-free medium were also observed. Such responses to Phe and B-HT 920 were inhibited by 10(-7) M rauwolscine and 10(-7) M prazosin, respectively, and were not affected by 10(-7) M nifedipine or 5 mM Mn2+. The responses to B-HT 920 (10(-5) M) and submaximal concentration of Phe (2 x 10(-6) M) in Ca2+-free medium were additive. However, if the vascular strips were first contracted maximally with 10(-4) M Phe in Ca2+-free medium to deplete the intracellular Ca store, subsequent addition of B-HT 920 failed to induce additional response. Our results strongly suggest that activation of alpha 2-adrenoceptor in dog saphenous vein in Ca2+-free medium indeed utilizes intracellular Ca2+ for contraction. We also found that the failure of earlier studies to demonstrate the contractile effects of B-HT 920 in dog saphenous vein was due to experimental artifacts derived from the use of high concentration of EGTA and artificial pH-buffering reagent.     

化学修饰提高胰岛素口服降血糖作用的研究

本文探索了用小分子化合物对胰岛素进行化学修饰,以增加口服降血糖的可能性.制备了乙酰胰岛素、琥珀酰胰岛素和半乳糖酰胰岛素.这些胰岛素不仅较好地保持了天然胰岛素的活性,而且其口服降血糖作用也较天然胰岛素明显增加,其中琥珀酰胰岛素是天然胰岛素的口服降血糖作用的二倍以上.这为口服或肛门给药的胰岛素新剂型的研制提供了科学依据.     

Type I Interferons Function as Autocrine and Paracrine Factors to Induce Autotaxin in Response to TLR Activation

Lysophosphatidic acid (LPA) is an important phospholipid mediator in inflammation and immunity. However, the mechanism of LPA regulation during inflammatory response is largely unknown. Autotaxin (ATX) is the key enzyme to produce extracellular LPA from lysophosphatidylcholine (LPC). In this study, we found that ATX was induced in monocytic THP-1 cells by TLR4 ligand lipopolysaccharide (LPS), TLR9 ligand CpG oligonucleotide, and TLR3 ligand poly(I:C), respectively. The ATX induction by TLR ligand was abolished by the neutralizing antibody against IFN-β or the knockdown of IFNAR1, indicating that type I IFN autocrine loop is responsible for the ATX induction upon TLR activation. Both IFN-β and IFN-α were able to induce ATX expression via the JAK-STAT and PI3K-AKT pathways but with different time-dependent manners. The ATX induction by IFN-β was dramatically enhanced by IFN-γ, which had no significant effect on ATX expression alone, suggesting a synergy effect between type I and type II IFNs in ATX induction. Extracellular LPA levels were significantly increased when THP-1 cells were treated with IFN-α/β or TLR ligands. In addition, the type I IFN-mediated ATX induction was identified in human monocyte-derived dendritic cells (moDCs) stimulated with LPS or poly(I:C), and IFN-α/β could induce ATX expression in human peripheral blood mononuclear cells (PBMCs) and monocytes isolated form blood samples. These results suggest that, in response to TLR activation, ATX is induced through a type I INF autocrine-paracrine loop to enhance LPA generation.