A case of using the Semantic Interoperability Framework for custom orthopedic implants manufacturing

The efficiency and effectiveness of the daily practice in orthopedic surgery depend on the availability, interoperability and unique access to a wide set of information, related to the patient’s medical record and diagnosis, domain knowledge and available resources and staff. The most important of the tangible resources, needed for the therapeutic or preventive actions are orthopedic implants. In some cases, the implants may be highly complex and customized products, which need to be manufactured (assembled) on basis of the above information in a shortest possible timeframe. In this paper, the case of the custom orthopedic implants manufacturing is described from the perspective of the collaborative enterprising, with special consideration of the interoperability issues of the involved enterprise collaboration. It is shown how the previously developed Semantic Interoperability Framework can be used to improve the efficiency of the manufacturing and other relevant processes.     

基于Newsvendor型产品特性的FJSP问题研究

针对新时代环境下Newsvendor型产品销售期短、期末未出售产品价值递减的产品特点,生产链要求位于上游的供应商必须快速加工出所需的工件,否则将面临着线性递增的拖期惩罚。在面对基于Newsvendor型产品的柔性作业车间调度问题时,设计了一种加入禁忌搜索的混合遗传算法,扩大了解的搜索范围,避免了传统遗传算法容易陷于局部最优的缺陷。最后利用混合遗传算法对一个仿真案例进行求解。     

CRISPR/Cas9-Mediated Generation of Pathogen-Resistant Tomato against Tomato Yellow Leaf Curl Virus and Powdery Mildew

Tomato is one of the major vegetable crops consumed worldwide. Tomato yellow leaf curl virus (TYLCV) and fungal Oidium sp. are devastating pathogens causing yellow leaf curl disease and powdery mildew. Such viral and fungal pathogens reduce tomato crop yields and cause substantial economic losses every year. Several commercial tomato varieties include Ty-5 (SlPelo) and Mildew resistance locus o 1 (SlMlo1) locus that carries the susceptibility (S-gene) factors for TYLCV and powdery mildew, respectively. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) is a valuable genome editing tool to develop disease-resistant crop varieties. In this regard, targeting susceptibility factors encoded by the host plant genome instead of the viral genome is a promising approach to achieve pathogen resistance without the need for stable inheritance of CRISPR components. In this study, the CRISPR/Cas9 system was employed to target the SlPelo and SlMlo1 for trait introgression in elite tomato cultivar BN-86 to confer host-mediated immunity against pathogens. SlPelo-knockout lines were successfully generated, carrying the biallelic indel mutations. The pathogen resistance assays in SlPelo mutant lines confirmed the suppressed accumulation of TYLCV and restricted the spread to non-inoculated plant parts. Generated knockout lines for the SlMlo1 showed complete resistance to powdery mildew fungus. Overall, our results demonstrate the efficiency of the CRISPR/Cas9 system to introduce targeted mutagenesis for the rapid development of pathogen-resistant varieties in tomato.     

Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells

We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.     

The Role of Chronic Inflammation in Various Diseases and Anti-inflammatory Therapies Containing Natural Products

Chronic inflammation represents a long-term reaction of the body's immune system to noxious stimuli. Such a sustained inflammatory response sometimes results in lasting damage to healthy tissues and organs. In fact, chronic inflammation is implicated in the development and progression of various diseases, including cardiovascular diseases, respiratory diseases, metabolic diseases, neurodegenerative diseases, and even cancers. Targeting nonresolving inflammation thus provides new opportunities for treating relevant diseases. In this review, we will go over several chronic inflammation-associated diseases first with emphasis on the role of inflammation in their pathogenesis. Then, we will summarize a number of natural products that exhibit therapeutic effects against those diseases by acting on different markers in the inflammatory response. We envision that natural products will remain a rich resource for the discovery of new drugs treating diseases associated with chronic inflammation.     

陕北±800 kV换流站高填方湿陷性黄土地基处理方案研究

陕北±800 kV换流站用地为原循环工业经济园区挖黄土梁卯、填深沟给出的一块台阶式场地,场地覆盖一层厚度0~50 m的素填土,密实度差异较大,土质极不均匀,填土完成约5年半时间,是一种欠固结土,在其自身重度和大气降水的入渗作用下有自行密实的特点,影响位于填方区建(构)筑物地基的承载力和稳定性。基于该工程特殊的岩土地质情况,除挖方区采用天然地基外,从处理填方区大面积欠固结土和消除部分地基土湿陷性、提高地基土承载力、减小场地沉降变形的角度,对不同地基处理及桩基方案进行技术经济综合比选,提出适合本工程的经济合理的地基处理方案。     

基于主成分分析与Wasserstein距离的低压用户相别识别

负载不平衡会导致电能质量差、功率损耗增加、变压器使用寿命缩短等问题,而准确识别用户相别可调整部分用户相别,尽可能达到三相负载平衡,因此提出一种基于主成分分析与Wasserstein距离的低压用户相别识别方法.首先利用主成分分析提取低压用户电压主成分进行聚类,然后计算聚类中值与关口各相电压Wasserstein距离进行相别归属.实测数据证明该方法对相别识别准确性较高,且相较于传统相似度算法在判别相别时具有明显区分度.     

Design,Synthesis, and Biological Evaluation of Novel 6H-Benzo[c]chromen-6-one Derivatives as Potential Phosphodiesterase II Inhibitors

Urolithins (hydroxylated 6H-benzo[c]chromen-6-ones) are the main bioavailable metabolites of ellagic acid (EA), which was shown to be a cognitive enhancer in the treatment of neurodegenerative diseases. As part of this research, a series of alkoxylated 6H-benzo[c]chromen-6-one derivatives were designed and synthesized. Furthermore, their biological activities were evaluated as potential PDE2 inhibitors, and the alkoxylated 6H-benzo[c]chromen-6-one derivative 1f was found to have the optimal inhibitory potential (IC₅₀: 3.67 ± 0.47 μM). It also exhibited comparable activity in comparison to that of BAY 60-7550 in vitro cell level studies.