126 research outputs found

    Luttinger-volume violating Fermi liquid in the pseudogap phase of the cuprate superconductors

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    Based on the NMR measurements on Bi2_2Sr2x_{2-x}Lax_xCuO6+δ_{6+\delta} (La-Bi2201) in strong magnetic fields, we identify the non-superconducting pseudogap phase in the cuprates as a Luttinger-volume violating Fermi liquid (LvvFL). This state is a zero temperature quantum liquid that does not break translational symmetry, and yet, the Fermi surface encloses a volume smaller than the large one given by the Luttinger theorem. The particle number enclosed by the small Fermi surface in the LvvFL equals the doping level pp, not the total electron number ne=1pn_e=1-p. Both the phase string theory and the dopon theory are introduced to describe the LvvFL. For the dopon theory, we can obtain a semi-quantitative agreement with the NMR experiments.Comment: The final version in PR

    Effects of Shenlian Extracts () on Atherosclerosis by Inhibition of the Inflammatory Response

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    ObjectiveInflammation plays a critical role in atherosclerosis, and this inflammatory reaction is being intensively studied. Shenlian Extracts (), an active ingredient of Chinese medicinal herbs, is believed to have multiple therapeutic and preventive effects against human vascular diseases, including atherosclerosis. Our work investigated whether Shenlian Extracts serves as an anti-inflammatory agent during atherogenesis.MethodsWe established a model of atherosclerosis in rabbits using balloon angioplasty and a high cholesterol diet. The effects of Shenlian Extracts on vessel structure and inflammation were assessed by hematoxylin-eosin staining of the femoral artery, measurement of inflammation-related factors in serum or vascular tissue, and radioimmunoassay. Enzyme linked immunosorbent assays (ELISA), flow cytometry and western blots were also performed.ResultsWe show that oral pre-treatment with Shenlian Extracts suppressed the pathological changes associated with atherosclerosis and that graded doses of Shenlian Extracts reduced total serum levels of cholesterol (90, 180 and 360 mg/kg), triglyceride (180 and 360 mg/kg), and LDL-c (90, 180 mg/kg). Various doses of Shenlian Extracts reduced serum content of TNF-a (180 and 360 mg/kg), CRP (90, 180 and 360 mg/kg) and IL-8 (360 mg/kg) (P<0.05), but led to no significant changes in IL-1β levels. Treatment with Shenlian Extracts also significantly reduced VCAM-1 levels (90 and 360 mg/kg) and IGF-1 levels (90 and 180 mg/kg) in vascular tissue but had no significant effect on ICAM-1 and MCP-1 levels. Finally, Shenlian Extracts significantly reduced the abnormal expression of CD18 in monocytes in a dose-dependent manner.ConclusionThese results suggest that Shenlian Extracts may play a direct role in preventing and treating atherogenesis by inhibiting the inflammatory reaction, providing insights into the possible mechanism underlying the anti-atherosclerotic actions of Shenlian Extracts

    Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancer

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    <p>Abstract</p> <p>Background</p> <p>P21<sup>(WAF1/Cip1) </sup>binds to cyclin-dependent kinase complexes and inhibits their activities. It was originally described as an inhibitor of cancer cell proliferation. However, many recent studies have shown that p21 promotes tumor progression when accumulated in the cell cytoplasm. So far, little is known about the correlation between cytoplasmic p21 and drug resistance. This study was aimed to investigate the role of p21 in the cisplatin resistance of ovarian cancer.</p> <p>Methods</p> <p>RT-PCR, western blot and immunofluorescence were used to detect p21 expression and location in cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008. Regulation of cytoplasmic p21 was performed through transfection of p21 siRNA, Akt2 shRNA and Akt2 constitutively active vector in the two cell lines; their effects on cisplatin-induced apoptosis were evaluated by flow cytometry. Tumor tissue sections of clinical samples were analyzed by immunohistochemistry.</p> <p>Results</p> <p>p21 predominantly localizes to the cytoplasm in C13* compared to OV2008. Persistent exposure to low dose cisplatin in OV2008 leads to p21 translocation from nuclear to cytoplasm, while it had not impact on p21 localization in C13*. Knockdown of cytoplasmic p21 by p21 siRNA transfection in C13* notably increased cisplatin-induced apoptosis through activation of caspase 3. Inhibition of p21 translocation into the cytoplasm by transfection of Akt2 shRNA into C13* cells significantly increased cisplatin-induced apoptosis, while induction of p21 translocation into the cytoplasm by transfection of constitutively active Akt2 in OV2008 enhanced the resistance to cisplatin. Immunohistochemical analysis of clinical ovarian tumor tissues demonstrated that cytoplasmic p21 was negatively correlated with the response to cisplatin based treatment.</p> <p>Conclusions</p> <p>Cytoplasmic p21 is a novel biomarker of cisplatin resistance and it may represent a potential therapeutic target for ovarian tumors that are refractory to conventional treatment.</p

    Research progress of hydrogels as delivery systems and scaffolds in the treatment of secondary spinal cord injury

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    Secondary spinal cord injury (SSCI) is the second stage of spinal cord injury (SCI) and involves vasculature derangement, immune response, inflammatory response, and glial scar formation. Bioactive additives, such as drugs and cells, have been widely used to inhibit the progression of secondary spinal cord injury. However, the delivery and long-term retention of these additives remain a problem to be solved. In recent years, hydrogels have attracted much attention as a popular delivery system for loading cells and drugs for secondary spinal cord injury therapy. After implantation into the site of spinal cord injury, hydrogels can deliver bioactive additives in situ and induce the unidirectional growth of nerve cells as scaffolds. In addition, physical and chemical methods can endow hydrogels with new functions. In this review, we summarize the current state of various hydrogel delivery systems for secondary spinal cord injury treatment. Moreover, functional modifications of these hydrogels for better therapeutic effects are also discussed to provide a comprehensive insight into the application of hydrogels in the treatment of secondary spinal cord injury

    Magnetic criticality-enhanced hybrid nanodiamond-thermometer under ambient conditions

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    Nitrogen vacancy (NV) centres in diamond are attractive as quantum sensors owing to their superb coherence under ambient conditions. However, the NV centre spin resonances are relatively insensitive to some important parameters such as temperature. Here we design and experimentally demonstrate a hybrid nano-thermometer composed of NV centres and a magnetic nanoparticle (MNP), in which the temperature sensitivity is enhanced by the critical magnetization of the MNP near the ferromagnetic-paramagnetic transition temperature. The temperature susceptibility of the NV center spin resonance reached 14 MHz/K, enhanced from the value without the MNP by two orders of magnitude. The sensitivity of a hybrid nano-thermometer composed of a Cu_{1-x}Ni_{x} MNP and a nanodiamond was measured to be 11 mK/Hz^{1/2} under ambient conditions. With such high-sensitivity, we monitored nanometer-scale temperature variation of 0.3 degree with a time resolution of 60 msec. This hybrid nano-thermometer provides a novel approach to studying a broad range of thermal processes at nanoscales such as nano-plasmonics, sub-cellular heat-stimulated processes, thermodynamics of nanostructures, and thermal remanent magnetization of nanoparticles.Comment: 21 pages, 6 figure

    Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors

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    <p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic efficacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells.</p> <p>Methods</p> <p>We assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID<sub>50 </sub>assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv-Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofluorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods.</p> <p>Results</p> <p>Adv-Stat3(-) amplified in MSCs and were released 4 days after infection. MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confirmed the preferential localization of MSCs in the tumor periphery 24 hours after tail vein injection, and this localization was mainly detected in the tumor parenchyma after 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice.</p> <p>Conclusions</p> <p>These results indicate that MSCs migrate to the tumor site in a time-dependent manner and could be an effective platform for the targeted delivery of CRAd and the amplification of tumor killing effects.</p

    Development and Characterization of Neutralizing Antibodies Against Zaire Ebolavirus Glycoprotein and Protein 40

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    Background/Aims: Monoclonal antibodies (mAbs) are presently the most promising treatment against Ebola virus disease (EVD), and cocktail of two or more antibodies likely confers protection through complementary mechanisms. Zaire Ebolavirus (EBOV) glycoprotein (GP) and viral protein 40 (VP40) are targets for designing neutralizing antibodies. Currently, the antiviral therapeutics of mAb-cocktails are still limited solely to anti-GP antibodies,there is no Abs cocktail against Zaire EBOV GP and VP40, which both have important interactions with host cellular membrane. Methods: We used hybridoma technology to produce anti-Zaire EBOV GP mAb against GP receptor binding domain, and anti-Zaire EBOV VP40 mAbs against the N-terminal domain, the C-terminal domain, respectively; synthesized Zaire EBOV transcription and replication competent virus like particles (trVLPs), which model even all aspects of the EBOV life cycles in order to evaluate the anti-viral effect of mAbs. Then, we characterized the anti- Zaire EBOV trVLPs effect of anti-GP and VP40 mAbs in vitro by real time-PCR, immunofluorescence assay and western blot analysis. Results: Our results demonstrate that anti-GP or anti-VP40 mAbs effectively inhibit trVLPs replication. The cocktails of anti-GP and anti-VP40 mAbs, or between anti-VP40 mAbs, had synergistic anti-trVLPs effect. Meanwhile, the detailed DNA and amino acid sequences of the mAbs were checked. Conclusion: The study verifies neutralizing efficacy of anti-GP or anti-VP40 mAb, report promising cocktail of anti-GP and anti-VP40 mAb, or cocktail of two anti-VP40 mAbs. To our knowledge, this is the first account to report the important anti-viral effect of cocktails of anti-GP and anti-VP40 mAbs in vitro

    Cortico-basal ganglia networks dysfunction associated with disease severity in patients with idiopathic blepharospasm

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    BackgroundStructural changes occur in brain regions involved in cortico-basal ganglia networks in idiopathic blepharospasm (iBSP); whether these changes influence the function connectivity patterns of cortico-basal ganglia networks remains largely unknown. Therefore, we aimed to investigate the global integrative state and organization of functional connections of cortico-basal ganglia networks in patients with iBSP.MethodsResting-state functional magnetic resonance imaging data and clinical measurements were acquired from 62 patients with iBSP, 62 patients with hemifacial spasm (HFS), and 62 healthy controls (HCs). Topological parameters and functional connections of cortico-basal ganglia networks were evaluated and compared among the three groups. Correlation analyses were performed to explore the relationship between topological parameters and clinical measurements in patients with iBSP.ResultsWe found significantly increased global efficiency and decreased shortest path length and clustering coefficient of cortico-basal ganglia networks in patients with iBSP compared with HCs, however, such differences were not observed between patients with HFS and HCs. Further correlation analyses revealed that these parameters were significantly correlated with the severity of iBSP. At the regional level, the functional connectivity between the left orbitofrontal area and left primary somatosensory cortex and between the right anterior part of pallidum and right anterior part of dorsal anterior cingulate cortex was significantly decreased in patients with iBSP and HFS compared with HCs.ConclusionDysfunction of the cortico-basal ganglia networks occurs in patients with iBSP. The altered network metrics of cortico-basal ganglia networks might be served as quantitative markers for evaluation of the severity of iBSP

    Pairing symmetry and properties of iron-based high temperature superconductors

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    Pairing symmetry is important to indentify the pairing mechanism. The analysis becomes particularly timely and important for the newly discovered iron-based multi-orbital superconductors. From group theory point of view we classified all pairing matrices (in the orbital space) that carry irreducible representations of the system. The quasiparticle gap falls into three categories: full, nodal and gapless. The nodal-gap states show conventional Volovik effect even for on-site pairing. The gapless states are odd in orbital space, have a negative superfluid density and are therefore unstable. In connection to experiments we proposed possible pairing states and implications for the pairing mechanism.Comment: 4 pages, 1 table, 2 figures, polished versio
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