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  • 1
    Publication Date: 2018-09-15
    Description: Complex, three-dimensional (3D) mesostructures that incorporate advanced, mechanically active materials are of broad, growing interest for their potential use in many emerging systems. The technology implications range from precision-sensing microelectromechanical systems, to tissue scaffolds that exploit the principles of mechanobiology, to mechanical energy harvesters that support broad bandwidth operation. The work presented here introduces strategies in guided assembly and heterogeneous materials integration as routes to complex, 3D microscale mechanical frameworks that incorporate multiple, independently addressable piezoelectric thin-film actuators for vibratory excitation and precise control. The approach combines transfer printing as a scheme for materials integration with structural buckling as a means for 2D-to-3D geometric transformation, for designs that range from simple, symmetric layouts to complex, hierarchical configurations, on planar or curvilinear surfaces. Systematic experimental and computational studies reveal the underlying characteristics and capabilities, including selective excitation of targeted vibrational modes for simultaneous measurements of viscosity and density of surrounding fluids. The results serve as the foundations for unusual classes of mechanically active 3D mesostructures with unique functions relevant to biosensing, mechanobiology, energy harvesting, and others.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 2
    Publication Date: 2018-06-20
    Description: Objectives We aimed to evaluate the relation of total homocysteine (tHcy) concentrations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels, and examine the possible modifiers in the association among a general population of Chinese adults. Design A cross-sectional study. Setting The study was conducted within 21 communities in Lianyungang of Jiangsu province, China. Participants A total of 26 648 participants aged ≥35 years and with no antihypertensive drug use were included in the final analysis. Results Overall, there was a positive association between tHcy concentrations and SBP (per 5 μmol/L tHcy increase: adjusted β=0.45 mm Hg; 95% CI 0.29 to 0.61) or DBP levels (per 5 μmol/L tHcy increase: adjusted β=0.47 mm Hg; 95% CI 0.35 to 0.59). Compared with participants with tHcy 〈10 μmol/L, significantly higher SBP levels were found in those with tHcy concentrations of 10 to 〈15 (adjusted β=0.80 mm Hg; 95% CI 0.32 to 1.28) and ≥15 µmol/L (adjusted β=1.79 mm Hg; 95% CI 1.20 to 2.37; p for trend 〈0.001). Consistently, significantly higher DBP levels were found in participants with tHcy concentrations of 10 to 〈15 (adjusted β=0.86 mm Hg; 95% CI 0.49 to 1.22) and ≥15 µmol/L (adjusted β=2.01 mm Hg; 95% CI 1.57 to 2.46; p for trend 〈0.001), respectively as compared with those with 〈10 μmol/L. Furthermore, a stronger association between tHcy and SBP (p for interaction=0.009) or DBP (p for interaction=0.067) was found in current alcohol drinkers. Conclusion Serum tHcy concentrations were positively associated with both SBP and DBP levels in a general Chinese adult population. The association was stronger in current alcohol drinkers.
    Keywords: Open access, Epidemiology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 3
    Publication Date: 2018-04-24
    Description: Interleukin-10 (IL-10)-producing regulatory B (Breg) cells were found to be induced in a variety of infectious diseases. However, its importance in the regulation of immune response to malaria is still unclear. Here, we investigated the dynamics, phenotype, and function of Breg cells using Plasmodium chabaudi chabaudi AS-infected C57BL/6 and BALB/c mice. BALB/c mice were more susceptible to infection and had a stronger IL-10 response in spleen than C57BL/6 mice. Analysis of the surface markers of IL-10-producing cells with flow cytometry showed that CD19 + B cells were one of the primary IL-10-producing populations in P. c. chabaudi AS-infected C57BL/6 and BALB/c mice, especially in the latter one. The Breg cells had a heterogeneous phenotype which shifted during infection. The well-established Breg subset, CD19 + CD5 + CD1d hi cells, accounted for less than 20% of IL-10-producing B cells in both strains during the course of infection. Most Breg cells were IgG + and CD138 – from day 0 to day 8 postinfection. Adoptive transfer of Breg cells to C57BL/6 mice infected with P. c. chabaudi AS led to a transient increase of parasitemia without an impact on survival rate. Our finding reveals that B cells play an active and important regulatory role in addition to mediating humoral immunity in immune response against malaria, which should be paid more attention in developing therapeutic or vaccine strategies against malaria involving stimulation of B cells.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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  • 4
    Publication Date: 2018-02-27
    Description: The recent outbreak of Zika virus (ZIKV) has emerged as a global health concern. ZIKV can persist in human semen and be transmitted by sexual contact, as well as by mosquitoes, as seen for classical arboviruses. We along with others have previously demonstrated that ZIKV infection leads to testis damage and infertility in mouse models. So far, no prophylactics or therapeutics are available; therefore, vaccine development is urgently demanded. Recombinant chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low preexisting immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7 (AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E was sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed neutralizing antibody with high titers within 1 week postvaccination, and the elicited antiserum could cross-neutralize heterologous ZIKV strains. Additionally, ZIKV M- and E-specific T cell responses were robustly induced by AdC7-M/E. Moreover, one-dose inoculation of AdC7-M/E conferred mouse sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against ZIKV-induced testicular damage. These data demonstrate that AdC7-M/E is highly effective and represents a promising vaccine candidate for ZIKV control. IMPORTANCE Zika virus (ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. Vaccine development is a high priority for ZIKV control. In this study, to avoid preexisting anti-vector immunity in humans, a rare serotype chimpanzee adenovirus (AdC7) expressing the ZIKV M/E glycoproteins was used for ZIKV vaccine development. Impressively, AdC7-M/E exhibited exceptional performance as a ZIKV vaccine, as follows: (i) protective efficacy by a single vaccination, (ii) rapid development of a robust humoral response, (iii) durable immune responses, (iv) robust T cell responses, and (v) sterilizing immunity achieved by a single vaccination. These advantages of AdC7-M/E strongly support its potential application as a promising ZIKV vaccine in the clinic.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 5
    Publication Date: 2018-11-02
    Description: Nonclustered protocadherins (PCDH) family is a group of cell–cell adhesion molecules. We have found differentially methylated genes in the nonclustered PCDHs family associated with Helicobacter pylori ( H. pylori ) infection in prior genome-wide methylation analysis. To further investigate the methylation and expression of nonclustered PCDHs encoding genes in H. pylori- -related gastric carcinogenesis process, four candidate genes including PCDH7, PCDH10, PCDH17, and PCDH20 were selected, which were reported to be tumor suppressors for digestive cancers. A total of 747 participants with a spectrum of gastric lesions were enrolled from a high-risk population of gastric cancer. Promoter methylation levels of four genes were significantly higher in H. pylori– positive subjects than the negative group (all P 〈 0.001). Elevated methylation levels of PCDH10 and PCDH17 were observed with the increasing severity of gastric lesions (both P trend 〈 0.001). In the protein expression analysis, PCDH17 expression was inversely associated with gastric lesions; the OR [95% confidence interval (CI)] was 0.49 (0.26–0.95) for chronic atrophic gastritis (CAG), 0.31 (0.15–0.63) for intestinal metaplasia, and 0.38 (0.19–0.75) for indefinite dysplasia and dysplasia, compared with superficial gastritis. In addition, PCDH10 expression was significantly lower in CAG (OR, 0.40; 95% CI, 0.24–0.68). The inverse association between methylation and protein expression of PCDH10 and PCDH1 7 was further supported when we explored the methylation and mRNA expression in The Cancer Genome Atlas database (all P 〈 0.001). Our study found elevated promoter methylation and decreased expression of PCDH10 and PCDH17 in advanced gastric lesions, suggesting that elevated PCDH10 and PCDH17 methylation may be an early event in gastric carcinogenesis. Cancer Prev Res; 11(11); 717–26. ©2018 AACR .
    Print ISSN: 1940-6207
    Electronic ISSN: 1940-6215
    Topics: Medicine
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  • 6
    Publication Date: 2018-04-10
    Description: Myeloid-derived suppressor cells (MDSCs) are major regulators of immune responses in cancer. Both C/EBP homologous protein (CHOP) and C/EBPβ play a critical role in regulating immunosuppressive function of MDSCs. In this study, we identified a novel long noncoding RNA termed as lnc-chop in MDSCs, which may interact with CHOP and the C/EBPβ isoform liver-enriched inhibitory protein. The binding of lnc-chop with both CHOP and the C/EBPβ isoform liver-enriched inhibitory protein promoted the activation of C/EBPβ and upregulated the expression of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2, which are related to the immunosuppressive function of MDSCs in inflammatory and tumor environments. Additionally, lnc-chop also promoted the enrichment of H3K4me3 on the promoter region of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2. These findings suggest an important role of lnc-chop in controlling immunosuppressive function of MDSCs in the tumor environment.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 7
    Publication Date: 2018-11-07
    Description: Appropriate subcellular localization of regulatory factors is critical for cellular function. Pap1, a nucleocytoplasmic shuttling transcription factor of Schizosaccharomyces pombe , is redox regulated for localization and antistress function. In this study, we find that overproduction of a peptide conjugate containing the nuclear export signal of Oxs1, a conserved eukaryotic protein that, along with Pap1, regulates certain diamide responsive genes, can retain Pap1 in the nucleus before stress by competing for nuclear export. The nuclear retention of Pap1 upregulates several drug resistance genes to prime the cells for higher tolerance to disulfide stress. Overproduction of Oxs1 also upregulates these same genes, not by competing for export but by binding directly to the drug resistance gene promoters for Pap1-mediated activation. Of medical relevance is that this may suggest a gene therapy approach of using nuclear export signal conjugates to suppress the nuclear export of biomolecules.
    Print ISSN: 0016-6731
    Topics: Biology
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  • 8
    Publication Date: 2018-08-09
    Description: Upward mining of the residual coal seam over an abandoned pillar working is one of the effective measures to alleviate the contradiction between limited resources and increased consumption. Interburden stability over an abandoned pillar working plays a significant role in guaranteeing the safety of upward mining; however, it has not yet been extensively studied and understood. In this study, the vertical stress of the interburden over an abandoned pillar working was first investigated. The mechanical model of the interburden was established and the damage conditions were analysed. Then, the stability of the interburden over 38502 abandoned workings in Baijiazhuang coal mine was determined by mechanical analysis and field monitoring. The results show that: (i) Vertical stress of the interburden over abandoned mining zones is clearly lower than the initial stress, indicating the existence of a de-stressed effect. Moreover, vertical stress of the interburden over residual coal pillars is greater than the initial stress, which is the evidence of a stress concentration effect. (ii) The interburden over an abandoned pillar working should be regarded as an elastic rectangular plate supported by generalized Kelvin bodies in mechanical modelling. (iii) The interburden over abandoned mining zones may experience two damage stages. In the first stage, initial plastic damage appears at the central region of interburden. In the second stage, the plastic damage evolves from the central point to the surrounding areas. (iv) The mechanical analysis and field monitoring both indicate the initial damage occurred at the central region over 38502 abandoned workings in Baijiazhuang coal mine before upward mining. Related rock control measures should be implemented in that region to guarantee the safe mining of the residual coal seam.
    Keywords: energy
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 9
    Publication Date: 2018-08-16
    Description: Purpose: Daratumumab and its use in combination with other agents is becoming a new standard of care for the treatment of multiple myeloma. We mechanistically studied how daratumumab acts on natural killer (NK) cells. Experimental Design: Quantities of NK cells in peripheral blood and/or bone marrow of patients with multiple myeloma or healthy donors were examined by flow cytometry. NK-cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded in vitro using feeder cells. Combination treatment of daratumumab and expanded NK cells was performed using an MM.1S xenograft animal model. Results: CD38 –/low NK cells survived, whereas CD38 + NK cells were almost completely eliminated, in peripheral blood and bone marrow of daratumumab-treated multiple myeloma patients. NK-cell depletion occurred due to daratumumab-induced NK-cell fratricide via antibody-dependent cellular cytotoxicity. Consequently, CD38 –/low NK cells were more effective for eradicating multiple myeloma cells than were CD38 + NK cells in the presence of daratumumab. Blockade of CD38 with the F(ab) 2 fragments of daratumumab inhibited the antibody-mediated NK-cell fratricide. CD38 –/low NK cells displayed a significantly better potential for expansion than CD38 + NK cells, and the expanded NK cells derived from the former population were more cytotoxic than those derived from the latter against multiple myeloma cells. Therefore, infusion of ex vivo –expanded autologous NK cells from daratumumab-treated patients may improve the antibody therapy. Conclusions: We unravel a fratricide mechanism for daratumumab-mediated NK-cell depletion and provide a potential therapeutic strategy to overcome this side effect in daratumumab-treated patients with multiple myeloma. Clin Cancer Res; 24(16); 4006–17. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 10
    Publication Date: 2018-12-15
    Description: The edges of layered materials have unique properties that substantially differ from the body regions. In this work, we perform a systematic Raman study of the edges of various layered materials (MoS 2 , WS 2 , WSe 2 , PtS 2 , and black phosphorus). The Raman spectra of the edges feature newly observed forbidden Raman modes, which are originally undetectable from the body region. By selecting the edge type and the polarization directions of the incident and scattered light, all forbidden Raman modes are distinctly detected. Optical simulations show that the edges of layered materials drastically distort the electromagnetic fields of both the incident and scattered light, so that the light interacts with the edges in a distinct way, which differs from its interactions with the body regions.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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