区域频谱资源数据融合方法

为实现高效的数据融合,提出了一种多源频谱资源数据融合方法.该方法将多个监测节点的频谱可用资源评估信息进行融合,利用意见形成理论,对关心地域的频谱资源可用性进行评估,为频谱动态管理提供资源状态信息.通过对不同网络规模的仿真分析,结果表明：在意见形成理论的基础上,通过设定“骨干”节点,缩减了50%的融合时间;在网络节点不超过100个的情况下,通过30轮次的沟通即可完成频谱资源数据的融合.     

一种基于社交网络社区的组推荐框架

面向用户群组的推荐主要面临如何有意义地对群组进行定义并识别,以及向群组内用户进行有效推荐两大问题。该文针对已有研究在用户群组定义解释性不强等存在的问题,提出一种基于社交网络社区的组推荐框架。该框架利用社交网络结构信息发现重叠网络社区结构作为用户群组,具有较强的可解释性,并根据用户与群组间的隶属度制定了考虑用户对群组贡献与用户从群组获利的4种聚合与分配策略,以完成组推荐任务。通过在公开数据集上与已有方法的对比实验,验证了该框架在组推荐方面的有效性和准确性。     

Capacity calculation for freight transportation network under comprehensive transportation system

为科学确定城市交通的发展规模,在分析关键交叉口转向能力的基础上,提出了基于超级节点的城市交通网络构建方法;考虑公交资源以及公交优先发展战略的因素,构建了城市交通发展规模与交通资源适应性的数学模型,并设计了基于反馈的免疫克隆算法. 以城市内某一区域为例对模型和算法进行验证,结果表明:模型及算法具有较好的实用性,能够为城市交通规划部门提供良好的决策支持.

     

Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing

Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1β than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1β in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.     

Sensory Neuron-Specific Deletion of Tropomyosin Receptor Kinase A (TrkA) in Mice Abolishes Osteoarthritis (OA) Pain via NGF/TrkA Intervention of Peripheral Sensitization

Tropomyosin receptor kinase A (TrkA/NTRK1) is a high-affinity receptor for nerve growth factor (NGF), a potent pain mediator. NGF/TrkA signaling elevates synovial sensory neuronal distributions in the joints and causes osteoarthritis (OA) pain. We investigated the mechanisms of pain transmission as to whether peripheral sensory neurons are linked to the cellular plasticity in the dorsal root ganglia (DRG) and are critical for OA hyperalgesia. Sensory neuron-specific deletion of TrkA was achieved by tamoxifen injection in 4-week-old TrkA^fl/fl;Na_V1.8^CreERT2 (Ntrk1 ^fl/fl;Scn10a^CreERT2) mice. OA was induced by partial medial meniscectomy (PMM) in 12-week-old mice, and OA-pain-related behavior was analyzed for 12 weeks followed by comprehensive histopathological examinations. OA-associated joint pain was markedly improved without cartilage protection in sensory-neuron-specific conditional TrkA knock-out (cKO) mice. Alleviated hyperalgesia was associated with suppression of the NGF/TrkA pathway and reduced angiogenesis in fibroblast-like synovial cells. Elevated pain transmitters in the DRG of OA-induced mice were significantly diminished in sensory-neuron-specific TrkA cKO and global TrkA cKO mice. Spinal glial activity and brain-derived neurotropic factor (BDNF) were significantly increased in OA-induced mice but were substantially eliminated by sensory-neuron-specific deletion. Our results suggest that augmentation of NGF/TrkA signaling in the joint synovium and the peripheral sensory neurons facilitate pro-nociception and centralized pain sensitization.     

Comparison of the Chemical Components,Efficacy and Mechanisms of Action of Chrysanthemum morifolium Flower and Its Wild Relative Chrysanthemum indicum Flower against Liver-Fire Hyperactivity Syndrome of Hypertension via Integrative Analyses

To clarify the differences in the clinical application scope of Chrysanthemum morifolium flower (CMF) and Chrysanthemum indicum flower (CIF), two herbs of similar origin, an integrated strategy of network pharmacology, molecular pharmacology, and metabolomics was employed, with a view to investigating the commonalities and dissimilarities in chemical components, efficacy and mechanisms of action. Initial HPLC-Q-TOF-MS analysis revealed that CMF and CIF had different flavonoid constituents. The biological processes underlying the therapeutic effects of CMF and CIF on liver-fire hyperactivity syndrome of hypertension (LFHSH) were predicted to be related to inflammatory response, fatty acid production, and other pathways based on network pharmacology analysis. ELISA, molecular docking, Western blot, and metabolomics techniques showed similar effects of CMF and CIF in lowering blood pressure, resistance to tissue, organ and functional damage, and dyslipidemia. However, distinct effects were found in the regulation of inflammatory response, PI3K-Akt and NF-κB signaling pathways, lipid anabolism, renin-angiotensin system, and metabolic abnormalities. The comparable efficacies of CMF and CIF, despite having distinct mechanisms of action, may be attributed to the integration and counteraction of their different regulating capabilities on the above anti-LFHSH mechanisms. This study offers a vital platform for assessment of differential and precise applications of herbs of close origin with similar but slightly different medicinal properties, and provides a research strategy for bridging Chinese medicine and modern precision medicine.     

A Novel Antithrombocytopenia Agent,Rhizoma cibotii,Promotes Megakaryopoiesis and Thrombopoiesis through the PI3K/AKT,MEK/ERK,and JAK2/STAT3 Signaling Pathways

Background: Cibotii rhizoma (CR) is a famous traditional Chinese medicine (TCM) used to treat bleeding, rheumatism, lumbago, etc. However, its therapeutic effects and mechanism against thrombocytopenia are still unknown so far. In the study, we investigated the effects of aqueous extracts of Cibotii rhizoma (AECRs) against thrombocytopenia and its molecular mechanism.Methods: Giemsa staining, phalloidin staining, and flow cytometry were performed to measure the effect of AECRs on the megakaryocyte differentiation in K562 and Meg-01 cells. A radiation-induced thrombocytopenia mouse model was constructed to assess the therapeutic actions of AECRs on thrombocytopenia. Network pharmacology and experimental verification were carried out to clarify its mechanism against thrombocytopenia. Results: AECRs promoted megakaryocyte differentiation in K562 and Meg-01 cells and accelerated platelet recovery and megakaryopoiesis with no systemic toxicity in radiation-induced thrombocytopenia mice. The PI3K/AKT, MEK/ERK, and JAK2/STAT3 signaling pathways contributed to AECR-induced megakaryocyte differentiation. The suppression of the above signaling pathways by their inhibitors blocked AERC-induced megakaryocyte differentiation. Conclusions: AECRs can promote megakaryopoiesis and thrombopoiesis through activating PI3K/AKT, MEK/ERK, and JAK2/STAT3 signaling pathways, which has the potential to treat radiation-induced thrombocytopenia in the clinic.     

Identifying Drug Targets of Oral Squamous Cell Carcinoma through a Systems Biology Method and Genome-Wide Microarray Data for Drug Discovery by Deep Learning and Drug Design Specifications

In this study, we provide a systems biology method to investigate the carcinogenic mechanism of oral squamous cell carcinoma (OSCC) in order to identify some important biomarkers as drug targets. Further, a systematic drug discovery method with a deep neural network (DNN)-based drug–target interaction (DTI) model and drug design specifications is proposed to design a potential multiple-molecule drug for the medical treatment of OSCC before clinical trials. First, we use big database mining to construct the candidate genome-wide genetic and epigenetic network (GWGEN) including a protein–protein interaction network (PPIN) and a gene regulatory network (GRN) for OSCC and non-OSCC. In the next step, real GWGENs are identified for OSCC and non-OSCC by system identification and system order detection methods based on the OSCC and non-OSCC microarray data, respectively. Then, the principal network projection (PNP) method was used to extract core GWGENs of OSCC and non-OSCC from real GWGENs of OSCC and non-OSCC, respectively. Afterward, core signaling pathways were constructed through the annotation of KEGG pathways, and then the carcinogenic mechanism of OSCC was investigated by comparing the core signal pathways and their downstream abnormal cellular functions of OSCC and non-OSCC. Consequently, HES1, TCF, NF-κB and SP1 are identified as significant biomarkers of OSCC. In order to discover multiple molecular drugs for these significant biomarkers (drug targets) of the carcinogenic mechanism of OSCC, we trained a DNN-based drug–target interaction (DTI) model by DTI databases to predict candidate drugs for these significant biomarkers. Finally, drug design specifications such as adequate drug regulation ability, low toxicity and high sensitivity are employed to filter out the appropriate molecular drugs metformin, gefitinib and gallic-acid to combine as a potential multiple-molecule drug for the therapeutic treatment of OSCC.     

分流制雨水管网滞留污染物的估算研究

为了定量研究降雨时分流制雨水管网滞留污染物占总污染物的比例,对某研究区域雨水管网中的滞留污染物定期取样检测,并根据研究区域的基础数据建立SWMM模型。同时,提出了一种雨水管网滞留污染物的计算方法,即以检测到的雨水管网污染物浓度及充满度计算滞留污染物质量。将滞留污染物数据输入SWMM模型中,分析对比有无滞留污染物的管网排放口污染物浓度的变化情况。模拟结果表明,在1年一遇的降雨条件下,雨水系统内的滞留污染物对COD、NH3-N、TP总污染负荷的贡献率分别为43. 30%、92. 75%、58. 83%,雨水管网滞留污染物占雨水管网总污染物的比例较大。