Search

The proposed study was to develop the preparation of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) modified with citric acid, with surface conjugated with lactoferrin (Lf), which used as a potential targeted contrast agent for magnetic resonance imaging (MRI) of brain glioma. USPIONs were prepared by the thermal decomposition method. The hydrophobic USPIONs were coated with citric acid by the ligand exchange method. Then, Lf was conjugated into the surface of USPIONs. The obtained Lf-USPIONs were analyzed by fourier transform infrared (FTIR) spectroscopy and polyacrylamide gel electrophoresis. The size, size distribution, shape and superparamagnetic property of Lf-USPIONs were investigated with TEM and vibrating sample magnetometer (VSM). Both FTIR and electrophoresis analysis demonstrated the successful conjugation of Lf to the surface of USPIONs. The average size of Lf-USPIONs was about 8.4 ± 0.5 nm, which was determined using the statistics of measured over 100 nanoparticles in the TEM image, with a negative charge of −7.3 ± 0.2 mV. TEM imaging revealed that Lf-USPIONs were good in dispersion and polygonal in morphology. VSM results indicated that Lf-USPIONs were superparamagnetic and the saturated magnetic intensity was about 69.8 emu/g. The Lf-USPIONs also showed good biocompatibility in hemolysis, cytotoxicity, cell migration and blood biochemistry studies. MR imaging results in vitro and in vivo indicated that Lf-USPIONs exhibited good negative contrast enhancement. Taken together, Lf-USPIONs hold great potential for brain gliomas MR imaging as a nanosized targeted contrast agent.

Bone cancer pain (BCP) is induced by primary bone cancer and secondary bone metastasis. During BCP pathogenesis, activated spinal astrocytes release proinflammatory cytokines, which participate in pain information transmission. In this study, we found that BCP rats showed disruption of trabecular bone structure, mechanical allodynia, and spinal inflammation. Moreover, reduced adenosine monophosphate-activated protein kinase (AMPK) activity, increased mitochondrial fission-associated protein Drp1 GTPase activity accompanied by the dysfunction of mitochondrial function, and abnormal BAX and Bcl-2 expression were found in the spinal cord of BCP rats. Notably, these alterations are reversed by resveratrol (Res) administration. Cell experiment results demonstrated that Res promotes mitochondrial function by activating AMPK, decreasing Drp1 activity, and inhibiting tumor necrosis factor-α-induced mitochondrial membrane potential reduction. Taken together, these results indicate that Res suppresses BCP in rats by attenuation of the inflammatory responses through the AMPK/Drp1 signaling pathway.

Due to the low bioavailability and severe toxic side effects caused by the lack of selectivity of traditional chemotherapy drugs, the targeted delivery of chemotherapy drugs has become the key to tumor treatment. The activity and transmembrane potential of mitochondria in cancer cells were significantly higher than that of normal cells, making them a potential target for chemotherapeutic drug delivery. In this study, triphenylphosphine (TPP) based mitochondria targeting polylactic acid (PLLA) nanoparticles (TPP-PLLA NPs) were synthesized to improve the delivery efficiency of anticancer drugs. The carrier material was characterized by 1H NMR and FT-IR and 7-hydroxyl coumarin (7-HC) was successfully loaded into TPP-PLLA to form 7-HC/TPP-PLLA NPs. Further studies showed that TPP-PLLA NPs were primarily accumulated in the mitochondrial and 7-HC/TPP-PLLA NPs had higher antitumor activity. Taken together, our results indicated that TPP-PLLA NPs could be a promising mitochondria-targeted drug delivery system for cancer therapy.

Eco-Civilization Construction has gone through 8 years since it has been included in the “five-in-one” overall layout in the 18th National Congress of the Communist Party of China. As an important part of Eco-Civilization Construction, Marine Eco-Civilization Construction (MECC) has also made great achievement in China. This paper was the first attempt to evaluate the performance of Marine Eco-Civilization Construction at county scale. Selecting 20 specific indicators from six subsystems, including resource, ecology, culture, governance, economy and society, we developed an evaluation system for MECC. With the combination of analytic hierarchy process (AHP) and the entropy method, we measured the MECC performance of all 32 coastal counties in Zhejiang Province from 2010 to 2016 and calculated the coordination degree among six subsystems. Temporally, the performance level of coastal districts and counties in Zhejiang was increased steadily, and spatially, the coordination degree however was relatively low in some counties indicating the spatial discordance. Our study could provide important insights for further promoting MECC in China at local scale as well as for other coastal regions’ sustainability.

Although doxorubicin has become a key drug in cancer treatment, the resistance of colorectal carcinoma to doxorubicin is a major problem in clinical practice. F-box and WD repeat domain-containing 7 (FBXW7) plays important roles in human cancers and is one of the major causes of drug resistance. The miR-223/FBXW7 pathway has been reported to be a crucial clue to the mechanism of chemoresistance in many human cancers, such as gastric cancer, breast cancer, and non-small cell lung cancer. However, it is unclear whether similar mechanisms of doxorubicin resistance are involved in colorectal cancer (CRC). The aim of the current study was to evaluate the role of miR-223/FBXW7 pathway in chemosensitivity in different CRC cell lines and to investigate the relevant underlying mechanisms. We found that high levels of FBXW7 expression were associated with increased doxorubicin sensitivity in different CRC cell lines, and FBXW7 was regulated by miR-223. Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of CRC cells to doxorubicin, while suppression of miR-223 had the opposite effect. Moreover, epithelial-mesenchymal transition (EMT) was proved to be regulated by miR-223/FBXW7 pathway and involved in the drug resistance. In conclusion, miR-223/FBXW7 axis regulates doxorubicin sensitivity through EMT in CRC, which may lead to the development of individualized treatment in clinical practice.

China needs to balance between current population pressures and a vulnerable marine environment, creating a national, political outline or management strategy dubbed an ecological civilization construction. The nation's effort to protect and maintain a sustainable ocean and address the relevant economic, resource and environmental issues relies on Marine Ecological Civilization (MEC) construction. The quantification of MEC progress is essential to track the management performance and guide the subsequent development and implementation. This study evaluates the performance of China's MEC from 2006 to 2016 based on a comprehensive index system. Our findings are as follows: During 2006-2016, the overall MEC performance score increased from 0.3426 to 0.4850 nationwide. Large space-time variations exist among the eleven coastal regions. The Shandong and Guangdong regions showed relatively good performances, whereas the Jiangsu, Guangxi and Shanghai regions had low scores. A decade long change in MEC scores showed that Hebei achieved the largest increase ratio. Marine management was improved by implementing various conservation strategies by China's government. Marine education and human talent introduction deserve more attention in less developed areas such as Hainan and Guangxi, and poor marine environmental quality was an urgent issue of the Yangtze river estuary economic zone. More accessible marine monitoring dataset are needed to track future space-time progress dynamics towards MEC construction. Our results provide a decade long retrospect of China's MEC achievements, and the quantified evaluation for each coastal region can provide valuable insight to policy-makers.

Myocardial hypertrophy is an independent risk factor for cardiac morbidity and mortality. The antiaging protein klotho reportedly possesses a protective role in cardiac diseases. However, the precise mechanisms underlying the cardioprotective effects of klotho remain unknown. This study was aimed to determine the effects of klotho on angiotensin II (Ang II)-induced hypertrophy in neonatal rat cardiomyocytes and the possible mechanism of actions. We found that klotho significantly inhibited Ang II-induced hypertrophic growth of neonatal cardiomyocytes, as evidenced by decreased [(3)H]-Leucine incorporation, cardiomyocyte surface area and β-myosin heavy chain (β-MHC) mRNA expression. Meanwhile, klotho inhibited Ang II-stimulated activation of the Wnt/β-catenin pathway in cardiomyocytes, as evidenced by decreased protein expression of active β-catenin, downregulated protein and mRNA expression of the β-catenin target genes c-myc and cyclin D1, and increased β-catenin phosphorylation. Inhibition of the Wnt/β-catenin pathway by the specific inhibitor XAV939 markedly attenuated Ang II-induced cardiomyocyte hypertrophy. The further study revealed that klotho treatment significantly downregulated protein expression of Ang II receptor type I (AT1R) but not type II (AT2R). The AT1R antagonist losartan inhibited Ang II-stimulated activation of the Wnt/β-catenin pathway and cardiomyocyte hypertrophy. Our findings suggest that klotho inhibits Ang II-induced cardiomyocyte hypertrophy through suppression of the AT1R/β-catenin signaling pathway, which may provide new insights into the mechanism underlying the protective effects of klotho in heart diseases, and raise the possibility that klotho may act as an endogenous antihypertrophic factor by inhibiting the Ang II signaling pathway.

Finite element method (FEM) is an effective and popular tool for predicting the welding deformation and residual stress to help process optimization. But it is difficult to calculate welding deformation and residual stress without reasonable simplification, because the calculation is extremely time-consuming and difficult to converge. In this study, the inherent strain model (ISM), the large heat source model (LHM) and moving heat source model (MHM) are developed to simulate the welding deformations and residual stresses in a large welded structure of underframe. The simulation results from three models show that the underframe has obvious structural shrinkage and wide distribution range of the residual stress after welding. Calculation time indicates that ISM has the highest efficiency and it shows that MHM has the highest precision by comparing simulation results with experimental measurements. Finally, a simulation framework is proposed which will provide a reference for the selection of the finite element models for complex large welded structure in the future.

Bone cancer pain (BCP) is the pain induced by primary bone cancer or tumor metastasis. Increasing evidence and our previous studies have shown that mammalian silent information regulator 2 homolog (SIRT1) is involved in periphery sensitization and central sensitization of BCP, and the underlying mechanism of SIRT1 in bone cancer pain may provide clues for pain treatment. Dynamin-related protein 1 (Drp1) is an essential regulator for mitochondrial fission. In this research, BCP model rats were established by injecting MRMT-1 rat mammary gland carcinoma cells into the left tibia of female Sprague-Dawley rats and validated by tibia radiographs, histological examination and mechanical pain test. As a result BCP rats exhibited bone destruction and sensitivity mechanical pain. BCP increased inflammatory cells infiltration and apoptosis, reduced SIRT1 protein expression and phosphorylation, and elevated Drp1 expression in spinal cord. An agonist of SIRT1 named SRT1720 intrathecal treatment in BCP rats increased SIRT1 phosphorylation, reduced the up-regulated Drp1 expression, and reversed pain behavior. SRT1720 also regulated Bcl-2/BAX and cleaved caspase-3 expressions, and inhibited mitochondrial apoptosis in spinal cord of BCP rats. For in vitro research, SRT1720 treatment decreased Drp1 expression in a dose-dependent manner, blocked CCCP-induced mitochondrial membrane potential change, consequently reduced apoptosis and promoted proliferation. These data suggest that SIRT1 activation by SRT1720 attenuated bone cancer pain via preventing Drp1-mediated mitochondrial fission. Our results provide new targets for therapeutics of bone cancer pain.

Although doxorubicin has become a key drug in cancer treatment, the resistance of colorectal carcinoma to doxorubicin is a major problem in clinical practice. F-box and WD repeat domain-containing 7 (FBXW7) plays important roles in human cancers and is one of the major causes of drug resistance. The miR-223/FBXW7 pathway has been reported to be a crucial clue to the mechanism of chemoresistance in many human cancers, such as gastric cancer, breast cancer, and non-small cell lung cancer. However, it is unclear whether similar mechanisms of doxorubicin resistance are involved in colorectal cancer (CRC). The aim of the current study was to evaluate the role of miR-223/FBXW7 pathway in chemosensitivity in different CRC cell lines and to investigate the relevant underlying mechanisms. We found that high levels of FBXW7 expression were associated with increased doxorubicin sensitivity in different CRC cell lines, and FBXW7 was regulated by miR-223. Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of CRC cells to doxorubicin, while suppression of miR-223 had the opposite effect. Moreover, epithelial-mesenchymal transition (EMT) was proved to be regulated by miR-223/FBXW7 pathway and involved in the drug resistance. In conclusion, miR-223/FBXW7 axis regulates doxorubicin sensitivity through EMT in CRC, which may lead to the development of individualized treatment in clinical practice.

Bone cancer pain (BCP) is one of the most common pains in patients with malignant cancers. The mechanism underlying BCP is largely unknown. Our previous studies and the increasing evidence both have shown that acid-sensing ion channels 3 (ASIC3) is an important protein in the pathological pain state in some pain models. We hypothesized that the expression change of ASIC3 might be one of the factors related to BCP. In this study, we established the BCP model through intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone destruction, increased mechanical pain sensitivities and up-regulated ASIC3 protein expression levels in L4-L6 dorsal root ganglion. Then, resveratrol, which was intraperitoneally injected into the BCP rats on post-operative Day 21, dose-dependently increased the paw withdrawal threshold of BCP rats, reversed the pain behavior, and had an antinociceptive effect on BCP rats. In ASIC3-transfected SH-SY5Y cells, the ASIC3 protein expression levels were regulated by resveratrol in a dose- and time-dependent manner. Meanwhile, resveratrol also had an antinociceptive effect in ASIC3-mediated pain rat model. Furthermore, resveratrol also enhanced the phosphorylation of AMPK, SIRT1, and LC3-II levels in ASIC3-transfected SH-SY5Y cells, indicating that resveratrol could activate the AMPK-SIRT1-autophagy signal pathway in ASIC3-transfected SH-SY5Y cells. In BCP rats, SIRT1 and LC3-II were also down-regulated. These findings provide new evidence for the use of resveratrol as a therapeutic treatment during BCP states.

In this paper, a TiC reinforcement metal matrix composite coating is produced using nickel and graphite mixing powder on the surface ofTi-6Al-4V alloy by laser radiation. The microstructure of the coatings is investigated by XRD, SEM and EDS. Results show that most of the TiC phase is granular, with a size of several micrometers, and a few of the TiC phases are petals or flakes. At the cross-section of the coatings, a few special TiC patterns are found and these TiC patterns do not always occur at the observed cross-section. The even distribution of the TiC phase in the coatings confirms that the convection of the laser-melted pool leads to the homogenization of titanium atoms from the molten substrate, and carbon atoms from the preplace powder layer, by the mass transfer. The characteristics of the TiC pattern confirm that the morphology and distribution of the primary TiC phase could be influenced by convection. Two main reasons for this are that the density of the TiC phase is lower than the liquid melt, and that the primary TiC phase precipitates from the pool with a high convection speed at high temperature.

Recent studies have revealed critical roles of transforming growth factor-β1 (TGF-β1) and microRNA-132 (miR-132), a downstream mediator of TGF-β1, in the pathogenesis of cardiac remodeling. In this study, we tested whether the antiaging protein klotho modifies angiotensin II (Ang II)-induced cardiac remodeling through regulating TGF-β1-miR-132 axis. We found that both klotho and the TGF-β1 inhibitor LY364947 significantly inhibited cardiac hypertrophy, fibrosis, and dysfunction in Ang II-infused mice, as evidenced by the ratios of heart weight to body weight (HW/BW), heart weight to tibial length (HW/TL), cardiomyocyte cross-sectional area, fibrotic area, and expression of prohypertrophic genes (ANP, β-MHC) and fibrotic marker genes (α-SMA, collagen I), echocardiographic parameters. Meanwhile, klotho also significantly inhibited Ang II-induced protein expression of TGF-β1 and phosphorylated Smad2/3 in the heart tissues and cultured cardiomyocytes and cardiac fibroblasts. In vitro experiments demonstrated that Ang II-induced cardiomyocyte hypertrophy and proliferation and activation of cardiac fibroblasts were markedly inhibited by klotho, LY364947 or the miR-132 inhibitor anti-miR-132. Both klotho and the TGF-β1 inhibitor LY364947 downregulated the miR-132 expression. Additionally, klotho decreased Ang II-induced protein expressions of cardiac fibroblast growth factor (FGF)23 in vivo and in vitro. The decreased protein levels of klotho in serum and renal tissues of Ang II-infused mice were elevated by klotho. Klotho downregulated the protein levels of TGF-β1 in renal tissues of Ang II-infused mice. In conclusion, our results suggest that klotho prevents Ang II-induced cardiac remodeling and dysfunction through modifying the TGF-β1-miR-132 axis, providing an experimental basis for clinical treatment on cardiac remodeling.

This paper presents an improved frontend algorithm of RGB-D SLAM, that is, Extend-RGBD-ICP algorithm. After introducing the existing frontend algorithm and analyzing its drawbacks, we present three improvement aspects: point cloud data down-sampling, matching points' selection and elimination of cumulative error of consecutive frames splicing. From the experiments on different complexities scenarios and the evaluation on benchmark dataset, it can be seen that the Extend-RGBD-ICP algorithm can achieve both accuracy and efficiency.