ANP and BNP Exert Anti-Inflammatory Action via NPR-1/cGMP Axis by Interfering with Canonical,Non-Canonical,and Alternative Routes of Inflammasome Activation in Human THP1 Cells

Dysregulated inflammasome activation and interleukin (IL)-1β production are associated with several inflammatory disorders. Three different routes can lead to inflammasome activation: a canonical two-step, a non-canonical Caspase-4/5- and Gasdermin D-dependent, and an alternative Caspase-8-mediated pathway. Natriuretic Peptides (NPs), Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP), binding to Natriuretic Peptide Receptor-1 (NPR-1), signal by increasing cGMP (cyclic guanosine monophosphate) levels that, in turn, stimulate cGMP-dependent protein kinase-I (PKG-I). We previously demonstrated that, by counteracting inflammasome activation, NPs inhibit IL-1β secretion. Here we aimed to decipher the molecular mechanism underlying NPs effects on THP-1 cells stimulated with lipopolysaccharide (LPS) + ATP. Involvement of cGMP and PKG-I were assessed pre-treating THP-1 cells with the membrane-permeable analogue, 8-Br-cGMP, and the specific inhibitor KT-5823, respectively. We found that NPs, by activating NPR-1/cGMP/PKG-I axis, lead to phosphorylation of NLRP3 at Ser295 and to inflammasome platform disassembly. Moreover, by increasing intracellular cGMP levels and activating phosphodiesterases, NPs interfere with both Gasdermin D and Caspase-8 cleavage, indicating that they disturb non-canonical and alternative routes of inflammasome activation. These results showed that ANP and BNP anti-inflammatory and immunomodulatory actions may involve the inhibition of all the known routes of inflammasome activation. Thus, NPs might be proposed for the treatment of the plethora of diseases caused by a dysregulated inflammasome activation.     

计算机与建筑:非欧几里得空间的产生过程

首先做个假设,总体来说,讨论一个思想的起源几乎是不可能的。无论其是抽象或是具体的,它的产生过程总是被不确定性所掩盖。本文的主旨在于了解计算机如何生成建筑空间的一种新理念。特别是我们关注的非欧几里得空间,因为利用电子工具我们有可能借助软件容易地处理复杂的形状．从而释放出设计师的创造性。     

可持续理念下的风景园林评价体系研究

随着可持续理念在20多年的发展中被广泛接受和认可,城市风景园林的可持续性也受到广泛关注,各国都在探索可持续理念下的城市景观的建设与发展。对不同国家和中国台湾地区现阶段已经建立的可持续风景园林的评价体系,按照定性、定量及综合评价方法的方式进行分类,分别进行阐述与比较,并提出了中国建立可持续风景园林评价体系的建议。     

Catalysts for the Ethoxylation of Esters

The intermediates for the production of nonionic surfactants can be derived from petrochemicals and/or from renewable raw materials. In both, the role of catalysis is fundamental. In this paper the main results reported in the literature related with the catalysis for ethoxylation of fatty esters will be reviewed. The main open challenges for these technologies will be outlined.     

Oncogenic MicroRNAs Characterization in Clear Cell Renal Cell Carcinoma

A key challenge for the improvement of clear cell renal cell carcinoma (ccRCC) management could derive from a deeper characterization of the biology of these neoplasms that could greatly improve the diagnosis, prognosis and treatment choice. The aim of this study was to identify specific miRNAs that are deregulated in tumor vs. normal kidney tissues and that could impact on the biology of ccRCC. To this end we selected four miRNAs (miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p) and their expression has been evaluated in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues from 20 ccRCC patients who underwent surgical nephrectomy resection. miR-21-5p and miR-210-3p resulted the most significantly up-regulated miRNAs in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in ccRCC tumorigenesis. Thus, this study reports the identification of specific oncogenic miRNAs that are altered in ccRCC tissues and suggests that they might be useful biomarkers in ccRCC management.     

基于古村落宅间元素模式的村落景观 设计优化策略——以徽州地区为例

新村空间设计语汇模块化是村落景观设计较为普遍的现象,也是地域特征弱化和空间不契合空间行为等问题的主要原因之一。古村落宅间元素是村民日常生活与村落环境在相互影响下长期适应性发展的结果,宅间元素模式研究可促进丰富新村空间设计语汇。以徽州地区古村落为例,从宅间元素的分类、图示、与空间行为的关联3个方面论述了古村落宅间元素模式研究方法论。通过徽州茆田新村景观设计阐述了宅间元素模式的应用,论述了基于古村落宅间元素模式的村落景观设计优化策略,有益于形成并推广地方空间设计语汇,避免过度依赖和使用既有的、来自城市的广场、草坪、树池等元素造成的全国村落的无差别设计。     

Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.     

Anisotropic molecular packing of soluble C60 fullerenes in hexagonal nanocrystals obtained by solvent vapor annealing

We describe the self-assembly of soluble, chemically modified fullerene [6,6]-phenyl C₆₁ butyric acid methyl ester (PCBM) into a new crystalline phase where the C₆₀ moieties are arranged in parallel layers. Minimum C₆₀ center-to-center distance is 10 Å within the layers, and up to 15 Å perpendicular to the layers. Highly anisotropic, mesoscopic hexagonal crystals of this material, with a lateral size of many microns and a thickness below 1 μm, are obtained from chloroform solution by solvent vapor annealing, and characterized by optical microscopy and X-ray diffraction. The crystalline structure is deduced combining experimental data with molecular modeling and ab initio calculations. The large difference in C₆₀–C₆₀ spacing indicates a high anisotropy in electrical and charge transport properties of this new phase.