40 research outputs found

    Tumor Tissue-Derived Formaldehyde and Acidic Microenvironment Synergistically Induce Bone Cancer Pain

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    Background: There is current interest in understanding the molecular mechanisms of tumor-induced bone pain. Accumulated evidence shows that endogenous formaldehyde concentrations are elevated in the blood or urine of patients with breast, prostate or bladder cancer. These cancers are frequently associated with cancer pain especially after bone metastasis. It is well known that transient receptor potential vanilloid receptor 1 (TRPV1) participates in cancer pain. The present study aims to demonstrate that the tumor tissue-derived endogenous formaldehyde induces bone cancer pain via TRPV1 activation under tumor acidic environment. Methodology/Principal Findings: Endogenous formaldehyde concentration increased significantly in the cultured breast cancer cell lines in vitro, in the bone marrow of breast MRMT-1 bone cancer pain model in rats and in tissues from breast cancer and lung cancer patients in vivo. Low concentrations (1 similar to 5 mM) of formaldehyde induced pain responses in rat via TRPV1 and this pain response could be significantly enhanced by pH 6.0 (mimicking the acidic tumor microenvironment). Formaldehyde at low concentrations (1 mM to 100 mM) induced a concentration-dependent increase of [Ca(2+)]i in the freshly isolated rat dorsal root ganglion neurons and TRPV1-transfected CHO cells. Furthermore, electrophysiological experiments showed that low concentration formaldehyde-elicited TRPV1 currents could be significantly potentiated by low pH (6.0). TRPV1 antagonists and formaldehyde scavengers attenuated bone cancer pain responses. Conclusions/Significance: Our data suggest that cancer tissues directly secrete endogenous formaldehyde, and this formaldehyde at low concentration induces metastatic bone cancer pain through TRPV1 activation especially under tumor acidic environment.Multidisciplinary SciencesSCI(E)PubMed24ARTICLE4e10234

    Inter-jurisdictional cooperation in planning and development of greenways in Pearl River Delta

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    The fragmented politics set an unavoidable barrier for the governance of a region, where jurisdictions may share collective interests to cope with regional issues like the delivery of infrastructure, environmental degradation, etc. Inter-jurisdictional cooperation is the key concept to tackle the fragmented complex through employing corresponding types of regional governance. Experiencing over thirty years’ fast economic growth, the Pearl River Delta is transforming from a single-centred region to a polycentric one. Each jurisdiction has demonstrated a strong economic competitiveness and shaped the PRD to become the most populated mega-city region. However, political decentralization roused the inter-urban competitions, and regional problems like environmental degradation occurred even though the provincial government has promoted a series of regional plans to coordinate collective issues in last decades. The PRD Greenway Scheme can be understood as a tool for implementing the concept of “Regional Green Land”, which dedicated to define the boundaries of green land to preserve the integrated ecological value. To materialise it, the provincial government adopted a multi-tier planning approach and required the jurisdictions to rise funding sources locally. To facilitate its implementation, corresponding institutional arrangements including both provincial level inter-departmental collaboration and inter-scalar coordination have been conducted. And both formal and informal tactics have been adopted. Various achievements have been observed and benefits have been generated to the whole society. Meanwhile, variations emerged between jurisdictions because of different local leaders’ ambitions, urban development contexts and the conditions of local fiscal budgets. To conclude, I have found that the PRD case has “re-invented” regional governance successfully through establishing an ad-hoc cooperation mechanism. And it did avoid the common challenges that western theories have defined because of the governments’ potent intervention. However, public perception can be a controversial issue for a top-down administrative structure. To improve the mechanism, the criteria of evaluating municipalities’ performances can be diversified to include the index of quality, innovative design like flagship sections can be beneficial to public perception, and participation of various actors can be emphasized to cultivate the lifestyle of using greenways.published_or_final_versionUrban Planning and DesignMasterMaster of Science in Urban Plannin

    A study on thermal and hydraulic performance of ultra-thin heat pipe with hybrid mesh-groove wick

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    High power electronics require ultra-thin heat pipe (UTHP) with more efficient heat transfer capabilities to meet thermal management challenges. And the design of the wick structure is crucial to the heat transfer performance improvement of the UTHP. At the present work, a thermo-hydraulic model is proposed for UTHP with composite mesh-grooved wick structure and the potential applications of the hybrid wick with non-full coverage by mesh is analyzed. According to the different mesh coverage areas, the wick structures are classified into three types, including evaporator covered, evaporator-adiabatic section covered, and full covered. The results show the flow characteristics and thermal performance of UTHPs is closely related to mesh coverage area and vapor core thickness. The reduction in mesh coverage area causes an expansion in vapor space, the vapor velocity and the vapor pressure drop both decreases, the mass flow rises with the higher vapor-liquid circulation efficiency. The liquid pressure drop is positively related to working fluid mass flow. Moreover, a theoretical model to predict the heat transfer limit of the heat pipe with composite wick was established and verified by experimental results with a maximum error of 3.63%

    Mitochondrial characteristics of Pseudohynobius flavomaculatus a protected salamander in China, and biogeographical implications for the family Hynobiidae (Amphibia, Caudata)

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    Pseudohynobius flavomaculatus a provincially-protected salamander species, inhabits mountainous areas of Chongqing and surrounding provinces in China. In the present study, the complete mitochondrial genome of P. flavomaculatus was sequenced and analyzed. The mitogenome is 16,401 bp in length and consisted of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. We performed a novel phylogenetic analysis, which demonstrated a sister relationship between P. flavomaculatus and P. jinfo. The 95% confidence interval around our new divergence date estimate suggest that Hynobiidae originated at 101.62–119.84 (mean=110.87) Ma. Species within Hynobiidae diverged successively in the Cenozoic era, and hynobiid speciation coincides primarily with geologic events. Our biogeographical inference demonstrates that nearly all early hynobiids divergences correspond to geological estimates of orogeny, which may have contributed to the notably high dN/dS ratio in this clade. We conclude that orogeny is likely a primary, dynamic factor, which may have repeatedly initiated the process of speciation in the family Hynobiidae

    Discussion on Piston-Type Phase Ambiguity in a Coherent Beam Combining System

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    Coherent beam combining (CBC) with closely arranged centrosymmetric arrays is a promising way to obtain a high-brightness laser. An essential task in CBC is to actively control the piston phases of the input beams, maintaining the correct phasing to maximize the combination efficiency. By applying the neural network, the nonlinear mapping relationship between the far-field image and the piston phase could be established, so that the piston phase can be corrected quickly with one step, which caused widespread concern. However, there exists a piston-type phase ambiguity problem in the CBC system with centrosymmetric arrays, which means that multiple different piston phases may generate the same far-field image. This will prevent the far-field image from correctly reflecting the phase information, which will result in a performance degradation of the image-based intelligent algorithms. In this paper, we make a theoretical analysis of phase ambiguity. A method to solve phase ambiguity is proposed, which requires no additional optical devices. We designed simulations to verify our conclusions and methods. We believe that our work solves the phase ambiguity problem in theory and is conducive to improving the performance of image-based algorithms
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