Murine MPDZ-linked hydrocephalus is caused by hyperpermeability of the choroid plexus.

Though congenital hydrocephalus is heritable, it has been linked only to eight genes, one of which is MPDZ Humans and mice that carry a truncated version of MPDZ incur severe hydrocephalus resulting in acute morbidity and lethality. We show by magnetic resonance imaging that contrast medium penetrates into the brain ventricles of mice carrying a Mpdz loss-of-function mutation, whereas none is detected in the ventricles of normal mice, implying that the permeability of the choroid plexus epithelial cell monolayer is abnormally high. Comparative proteomic analysis of the cerebrospinal fluid of normal and hydrocephalic mice revealed up to a 53-fold increase in protein concentration, suggesting that transcytosis through the choroid plexus epithelial cells of Mpdz KO mice is substantially higher than in normal mice. These conclusions are supported by ultrastructural evidence, and by immunohistochemistry and cytology data. Our results provide a straightforward and concise explanation for the pathophysiology of Mpdz-linked hydrocephalus

Metabolomics-based discovery of XHP as a CYP3A4 inhibitor against pancreatic cancer

Background: Xihuang Wan (XHW), a purgative and detoxifying agent, is commonly utilized in modern medicine as a treatment and adjuvant therapy for various malignancies, including breast cancer, liver cancer, and lung cancer. A clinical study demonstrated the potential usefulness of the combination of XHW and gemcitabine as a therapy for pancreatic cancer (PC), indicating that XHW’s broad-spectrum antitumor herbal combination could be beneficial in the treatment of PC. However, the precise therapeutic efficacy of XHW in treating pancreatic cancer remains uncertain.Aim: This study assessed the biological activity of XHW by optimizing the therapeutic concentration of XHW (Xihuang pills, XHP). We performed cell culture and developed an animal test model to determine whether XHP can inhibit pancreatic cancer (PC). We also applied the well-known widely targeted metabolomics analysis and conducted specific experiments to assess the feasibility of our method in PC therapy.Materials and Methods: We used UPLC/Q-TOF-MS to test XHP values to set up therapeutic concentrations for the in vivo test model. SW1990 pancreatic cancer cells were cultured to check the effect the anti-cancer effects of XHP by general in vitro cell analyses including CCK-8, Hoechst 33258, and flow cytometry. To develop the animal model, a solid tumor was subcutaneously formed on a mouse model of PC and assessed by immunohistochemistry and TUNEL apoptosis assay. We also applied the widely targeted metabolomics method following Western blot and RT-PCR to evaluate multiple metabolites to check the therapeutic effect of XHP in our cancer test model.Results: Quantified analysis from UPLC/Q-TOF-MS showed the presence of the following components of XHP: 11-carbonyl-β-acetyl-boswellic acid (AKBA), 11-carbonyl-β-boswellic acid (KBA), 4-methylene-2,8,8-trimethyl-2-vinyl-bicyclo [5.2.0]nonane, and (1S-endo)-2-methyl-3-methylene-2-(4-methyl-3-3-pentenyl)-bicyclo [2.2.1heptane]. The results of the cell culture experiments demonstrated that XHP suppressed the growth of SW1990 PC cells by enhancing apoptosis. The results of the animal model tests also indicated the suppression effect of XHP on tumor growth. Furthermore, the result of the widely targeted metabolomics analysis showed that the steroid hormone biosynthesis metabolic pathway was a critical factor in the anti-PC effect of XHP in the animal model. Moreover, Western blot and RT-PCR analyses revealed XHP downregulated CYP3A4 expression as an applicable targeted therapeutic approach.Conclusion: The results of this study demonstrated the potential of XHP in therapeutic applications in PC. Moreover, the widely targeted metabolomics method revealed CYP3A4 is a potential therapeutic target of XHP in PC control. These findings provide a high level of confidence that XHP significantly acts as a CYP3A4 inhibitor in anti-cancer therapeutic applications

Habitual snoring, adiposity measures and risk of type 2 diabetes in 0.5 million Chinese adults:a 10-year cohort

OBJECTIVES: The present study aimed to examine whether habitual snoring was independently associated with risk of type 2 diabetes among Chinese adults, and to assess the role that adiposity measures play in the snoring-diabetes association, as well as to evaluate the joint influence of snoring and adiposity measures on diabetes. RESEARCH DESIGN AND METHODS: The China Kadoorie Biobank study recruited 512 715 adults aged 30-79 years from 10 regions in China during 2004 and 2008. Data from 482 413 participants without baseline diabetes were analyzed in the present study. Autoregressive cross-lagged panel analysis was used to assess the longitudinal relationship between adiposity measures and habitual snoring. Cox proportional hazards models were used to examine the association between habitual snoring and diabetes risk. RESULTS: Both higher body mass index and waist circumference were associated with higher risks of subsequent habitual snoring, whereas no reverse association was detected. A total of 16 479 type 2 diabetes cases were observed during a 10-year follow-up. Habitual snoring was independently associated with 12% (95% CI 6% to 18%) and 14% (95% CI 9% to 19%) higher risks of diabetes among men and women, respectively. Habitual snorers who had general obesity or central obesity were about twice as likely to develop diabetes as non-snorers at the lowest levels of adiposity measures. CONCLUSION: Habitual snoring was independently associated with a higher risk of type 2 diabetes among Chinese adults. It is important to maintain both a healthy weight and a normal waist circumference to prevent or alleviate habitual snoring and ultimately prevent diabetes among Chinese adults

Precise segmentation of densely interweaving neuron clusters using G-Cut

脑是宇宙间最为复杂的系统之一，成人的脑中有约1000亿个神经元，单个神经元通常与其它神经元有成千上万个“突触”连接节点，形成拥有百万亿级连接的极其复杂的脑神经网络。当前多数神经元三维重建和分析工具仅适用于单个神经元的形态学重建，难以从神经元簇图像中正确追踪重建出多个神经元，而神经元的重建质量又影响到量化分析神经元的形态学特征及其功能。针对这一问题，课题组提出一种新的三维神经元簇重建工具G-Cut。具体地，为了度量神经元胞体与神经突起间的关联性，课题组从已有的带有标注的大规模神经元形态学数据集统计分析得到其规律和形态学信息。然后将神经元簇的重建问题转化为神经突起之间连接所形成的拓扑连接图的图分割问题，并结合神经元形态学规律和信息，在所有的神经突起与神经元胞体的关联性中寻找重建问题的最优解。通过在不同的合成数据集以及真实的脑组织图像数据集上测试，和已有的方法相比，G-Cut在不同密度和不同规模的神经元簇图像上均获得了更高的重建正确率。该项研究工作由厦门大学，南加州大学，加州大学洛杉矶分校等高校课题组合作完成，厦门大学信息学院智能科学与技术系为第一完成单位，厦门大学博士生李睿和USC博士生Muye Zhu为论文共同第一作者，张俊松博士和南加州大学的Hong-Wei Dong教授为论文共同通讯作者。厦门大学周昌乐教授和南加州大学的Arthur Toga教授为研究提供了大力支持。【Abstract】Characterizing the precise three-dimensional morphology and anatomical context of neurons is crucial for neuronal cell type classification and circuitry mapping. Recent advances in tissue clearing techniques and microscopy make it possible to obtain image stacks of intact, interweaving neuron clusters in brain tissues. As most current 3D neuronal morphology reconstruction methods are only applicable to single neurons, it remains challenging to reconstruct these clusters digitally. To advance the state of the art beyond these challenges, we propose a fast and robust method named G-Cut that is able to automatically segment individual neurons from an interweaving neuron cluster. Across various densely interconnected neuron clusters, G-Cut achieves significantly higher accuracies than other state-of-the-art algorithms. G-Cut is intended as a robust component in a high throughput informatics pipeline for large-scale brain mapping projects.This work was supported by NIH/NIMH MH094360-01A1 (H.W.D.), MH094360-06 (H.W.D.), NIH/NCI U01CA198932-01 (H.W.D.), NIH/NIMH MH106008 (X.W.Y. and H.W.D.), National Nature Science Foundation of China No. 61772440 (J.S.Z.), and National Basic Research Program of China 2013CB329502 (J.S.Z. and C.L.Z.). We thank a support of Graduate Student International Exchange Project of Xiamen University to R.L. and State Scholarship Fund of China Scholarship Council (No. 201406315023) to J.S.Z. 该项研究得到国家自然科学基金、国家重点基础研究发展计划973项目、国家留学基金、厦门大学研究生国际交流项目、美国脑计划和NIH等课题资助

Profiling the peripheral blood T cell receptor repertoires of gastric cancer patients

Cancer driven by somatic mutations may express neoantigens that can trigger T-cell immune responses. Since T-cell receptor (TCR) repertoires play critical roles in anti-tumor immune responses for oncology, next-generation sequencing (NGS) was used to profile the hypervariable complementarity-determining region 3 (CDR3) of the TCR-beta chain in peripheral blood samples from 68 gastric cancer patients and 49 healthy controls. We found that most hyper-expanded CDR3 are individual-specific, and the gene usage of TRBV3-1 is more frequent in the tumor group regardless of tumor stage than in the healthy control group. We identified 374 hyper-expanded tumor-specific CDR3, which may play a vital role in anti-tumor immune responses. The patients with stage IV gastric cancer have higher EBV-specific CDR3 abundance than the control. In conclusion, analysis of the peripheral blood TCR repertoires may provide the biomarker for gastric cancer prognosis and guide future immunotherapy

The asymptotic Behavior of Solutions of Some Doubly Degenerate Nonlinear Parabolic Equation

In this paper we discuss the asymptotic behavior of solution of some doubly nonlinear degenerate parabolic eauations国家自然科学基

Smartphone-Based Whole-Cell Biosensor Platform Utilizing an Immobilization Approach on a Filter Membrane Disk for the Monitoring of Water Toxicants

Bioluminescent bacteria whole-cell biosensors (WCBs) have been widely used in a range of sensing applications in environmental monitoring and medical diagnostics. However, most of them use planktonic bacteria cells that require complicated signal measurement processes and therefore limit the portability of the biosensor device. In this study, a simple and low-cost immobilization method was examined. The bioluminescent bioreporter bacteria was absorbed on a filter membrane disk. Further optimization of the immobilization process was conducted by comparing different surface materials (polyester and parafilm) or by adding glucose and ampicillin. The filter membrane disks with immobilized bacteria cells were stored at −20 °C for three weeks without a compromise in the stability of its biosensing functionality for water toxicants monitoring. Also, the bacterial immobilized disks were integrated with smartphones-based signal detection. Then, they were exposed to water samples with ethanol, chloroform, and H2O2, as common toxicants. The sensitivity of the smartphone-based WCB for the detection of ethanol, chloroform, and H2O2 was 1% (v/v), 0.02% (v/v), and 0.0006% (v/v), respectively. To conclude, this bacterial immobilization approach demonstrated higher sensitivity, portability, and improved storability than the planktonic counterpart. The developed smartphone-based WCB establishes a model for future applications in the detection of environmental water toxicants

Experimental Study on the Impact of Filter Layer Permeability on Revetment Stability Under Wave Action

AbstractIn the design of revetment engineering under wave action, to resist the wave action, the pattern of Top layer - Filter layer – Core(subsoil) is often adopted. In general, the structure of top layer is usually single discrete blocks, typically accropode blocks, four-leg square hollow blocks and barrier boards, and also acropode, riprap, paved rock blocks or concrete slabs where with smaller waves. Such top layer has been provided with many research findings on its stability and is widely used in engineering. Setting a filter layer between the top layer and the lower dike core mainly has two functions: (1) giving certain permeability, to minimize the hydrodynamic load directly acting on the lower foundation soil; (2) giving certain hydraulic tightness, to prevent fine sediment of the lower foundation soil being rushed out. This paper is focused on a special filter layer with geotextile as its upper structure and coarse aggregate as its lower structure. By simulating geotextile with different permeability and coarse aggregate with different size, The pressure of top of cover layer and the down side of the geotextile is tested under wave actions, and compared with theoretical analysis, in this way, how the permeability of geotextile impacts the stability of top layer is studyed. The research shows that when the lower coarse aggregate under the geotextile has high permeability and the geotextile's permeability get poorer, the uplift force to the top layer will be increased under wave action, which will cause damage to the top layer when it si greater than the vertical component force of the block gravity under the water

Synthesis of Three-Dimensional Hierarchical Urchinlike Tungsten Trioxide Microspheres for High-Performance Supercapacitor Electrode

In this work, hierarchical three-dimensional (3D) urchinlike WO3 microspheres with a self-assembled nanorod core, and a connected and quasiconnected nanothorn network shell were synthesized with the hydrothermal method. For the surface or near-surface regions of pseudocapacitive materials that are involved in the Faradaic reaction, the urchinlike WO3 special microstructure provided more effective charge-storage area, exhibiting a high specific capacitance of 488.78 F g−1, low average equivalent-series resistance of 0.966 Ω cm−2, and excellent cycling stability (84.75% of its initial value after the 10,000 cycles). This performance indicates the urchinlike WO3 microspheres are promising electrode materials for high-performance supercapacitors