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  • 1
    Publication Date: 2018-10-18
    Description: The work investigated the effect of sepiolite nanofibres on mechanical properties and sintering behaviour of shellfish porcelain. Samples of shellfish porcelain reinforced by sepiolite nanofibres were fired in an electric furnace at 1150, 1200 and 1250°C for a period of 80, 100, 120 and 140 min. Sintered samples were characterized by flexural strength, fracture toughness, scanning electron microscopy, transmission electron microscopy and X-ray diffraction. The results showed that 2 wt% sepiolite nanofibres could increase the flexural strength and fracture toughness of the porcelain bodies through the fibre pullout and the weak interface mechanisms. Sintering activation energies were determined according to the linear shrinkage results. It is found that the liquid-phase sintering mechanism of shellfish porcelain with sepiolite nanofibres is a diffusion mechanism. Porcelain without sepiolite is controlled by volume diffusion, and eventually, the grain boundary diffusion began to appear with the increase of sepiolite addition.
    Keywords: inorganic chemistry, materials science
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 2
    Publication Date: 2018-01-03
    Description: Skeletal muscle atrophy due to excessive protein degradation is the main cause for muscle dysfunction, fatigue, and weakening of athletic ability. Endurance exercise is effective to attenuate muscle atrophy, but the underlying mechanism has not been fully investigated. α-Ketoglutarate (AKG) is a key intermediate of tricarboxylic acid cycle, which is generated during endurance exercise. Here, we demonstrated that AKG effectively attenuated corticosterone-induced protein degradation and rescued the muscle atrophy and dysfunction in a Duchenne muscular dystrophy mouse model. Interestingly, AKG also inhibited the expression of proline hydroxylase 3 (PHD3), one of the important oxidoreductases expressed under hypoxic conditions. Subsequently, we identified the β 2 adrenergic receptor (ADRB2) as a downstream target for PHD3. We found AKG inhibited PHD3/ADRB2 interaction and therefore increased the stability of ADRB2. In addition, combining pharmacologic and genetic approaches, we showed that AKG rescues skeletal muscle atrophy and protein degradation through a PHD3/ADRB2 mediated mechanism. Taken together, these data reveal a mechanism for inhibitory effects of AKG on muscle atrophy and protein degradation. These findings not only provide a molecular basis for the potential use of exercise-generated metabolite AKG in muscle atrophy treatment, but also identify PHD3 as a potential target for the development of therapies for muscle wasting.—Cai, X., Yuan, Y., Liao, Z., Xing, K., Zhu, C., Xu, Y., Yu, L., Wang, L., Wang, S., Zhu, X., Gao, P., Zhang, Y., Jiang, Q., Xu, P., Shu, G. α-Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
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  • 3
    Publication Date: 2018-06-30
    Description: Rotaviruses (RVs), which cause severe gastroenteritis in infants and children, recognize glycan ligands in a genotype-dependent manner via the distal VP8* head of the spike protein VP4. However, the glycan binding mechanisms remain elusive for the P[II] genogroup RVs, including the widely prevalent human RVs (P[8], P[4], and P[6]) and a rare P[19] RV. In this study, we characterized the glycan binding specificities of human and porcine P[6]/P[19] RV VP8*s and found that the P[II] genogroup RV VP8*s could commonly interact with mucin core 2, which may play an important role in RV evolution and cross-species transmission. We determined the first P[6] VP8* structure, as well as the complex structures of human P[19] VP8*, with core 2 and lacto- N -tetraose (LNT). A glycan binding site was identified in human P[19] VP8*. Structural superimposition and sequence alignment revealed the conservation of the glycan binding site in the P[II] genogroup RV VP8*s. Our data provide significant insight into the glycan binding specificity and glycan binding mechanism of the P[II] genogroup RV VP8*s, which could help in understanding RV evolution, transmission, and epidemiology and in vaccine development. IMPORTANCE Rotaviruses (RVs), belonging to the family Reoviridae , are double-stranded RNA viruses that cause acute gastroenteritis in children and animals worldwide. Depending on the phylogeny of the VP8* sequences, P[6] and P[19] RVs are grouped into genogroup II, together with P[4] and P[8], which are widely prevalent in humans. In this study, we characterized the glycan binding specificities of human and porcine P[6]/P[19] RV VP8*s, determined the crystal structure of P[6] VP8*, and uncovered the glycan binding pattern in P[19] VP8*, revealing a conserved glycan binding site in the VP8*s of P[II] genogroup RVs by structural superimposition and sequence alignment. Our data suggested that mucin core 2 may play an important role in P[II] RV evolution and cross-species transmission. These data provide insight into the cell attachment, infection, epidemiology, and evolution of P[II] genogroup RVs, which could help in developing control and prevention strategies against RVs.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 4
    Publication Date: 2018-01-03
    Description: A genomic variant in the human ADTRP [androgen-dependent tissue factor (TF) pathway inhibitor (TFPI) regulating protein] gene increases the risk of coronary artery disease, the leading cause of death worldwide. TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that adtrp and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vasculogenesis. In zebrafish, there are 2 paralogues for adtrp ( i.e. , adtrp1 and adtrp2 ). Knockdown of adtrp1 expression inhibits the specification of hemangioblasts, as shown by decreased expression of the hemangioblast markers, etsrp , fli1a , and scl ; blocks primitive hematopoiesis, as shown by decreased expression of pu.1 , mpo , and l-plastin ; and disrupts the specification of hematopoietic stem cells (definitive hematopoiesis), as shown by decreased expression of runx1 and c-myb . However, adtrp1 knockdown does not affect erythropoiesis during primitive hematopoiesis (no effect on gata1 or h-bae1 ) or vasculogenesis (no effect on kdrl , ephb2a, notch3 , dab2 , or flt4 ). Knockdown of adtrp2 expression does not have apparent effects on all markers tested. Knockdown of adtrp1 reduced the expression of tfpi , and hematopoietic defects in adtrp1 morphants were rescued by tfpi overexpression. These data suggest that the regulation of tfpi expression is one potential mechanism by which adtrp1 regulates primitive myelopoiesis and definitive hematopoiesis.—Wang, L., Wang, X., Wang, L., Yousaf, M., Li, J., Zuo, M., Yang, Z., Gou, D., Bao, B., Li, L., Xiang, N., Jia, H., Xu, C., Chen, Q., Wang, Q. K. Identification of a new adtrp1-tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
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  • 5
    Publication Date: 2018-06-02
    Description: Introduction Approximately 1.4%–2.2% of the global population suffers from chronic migraine. Acupuncture may serve as an alternative management for chronic migraine, where pharmacological prophylaxis is not suitable. However, the effects of acupuncture as migraine prophylaxis have not been confirmed. This study is designed as a single-blinded, double-dummy randomised controlled trial to evaluate the efficacy and safety of acupuncture compared with topiramate in patients with chronic migraine. Methods and analysis A total of 60 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and real medicine (topiramate). All participants will receive a 12-week treatment and then be followed up for another 12 weeks. The primary outcome is the reduction of monthly headache days, and the secondary outcomes include the reduction of the number of days with acute headache medications, and changes of Migraine Disability Assessment, Migraine-Specific Quality of Life Questionnaire, Headache Impact Test, State-Trait Anxiety Inventory-trait, and Beck Depression Inventory-II scores from baseline to endpoints. Ethics and dissemination Ethical approval of this study was granted by the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University (2017BL-045-01). Written informed consent will be obtained from all participants. Outcomes of the trial will be disseminated through peer-reviewed publications. Trial registration number ISRCTN13563102; Pre-results .
    Keywords: Open access, Complementary medicine
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 6
    Publication Date: 2018-07-20
    Description: Atmospheric new particle formation (NPF) is an important global phenomenon that is nevertheless sensitive to ambient conditions. According to both observation and theoretical arguments, NPF usually requires a relatively high sulfuric acid (H 2 SO 4 ) concentration to promote the formation of new particles and a low preexisting aerosol loading to minimize the sink of new particles. We investigated NPF in Shanghai and were able to observe both precursor vapors (H 2 SO 4 ) and initial clusters at a molecular level in a megacity. High NPF rates were observed to coincide with several familiar markers suggestive of H 2 SO 4 –dimethylamine (DMA)–water (H 2 O) nucleation, including sulfuric acid dimers and H 2 SO 4 -DMA clusters. In a cluster kinetics simulation, the observed concentration of sulfuric acid was high enough to explain the particle growth to ~3 nanometers under the very high condensation sink, whereas the subsequent higher growth rate beyond this size is believed to result from the added contribution of condensing organic species. These findings will help in understanding urban NPF and its air quality and climate effects, as well as in formulating policies to mitigate secondary particle formation in China.
    Keywords: Geochemistry, Geophysics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2018-10-06
    Description: High-energy lithium metal batteries (LMBs) are expected to play important roles in the next-generation energy storage systems. However, the uncontrolled Li dendrite growth in liquid electrolytes still impedes LMBs from authentic commercialization. Upgrading the traditional electrolyte system from liquid to solid and quasi-solid has therefore become a key issue for prospective LMBs. From this premise, it is particularly urgent to exploit facile strategies to accomplish this goal. We report that commercialized liquid electrolyte can be easily converted into a novel quasi-solid gel polymer electrolyte (GPE) via a simple and efficient in situ gelation strategy, which, in essence, is to use LiPF 6 to induce the cationic polymerization of the ether-based 1,3-dioxolane and 1,2-dimethoxyethane liquid electrolyte under ambient temperature. The newly developed GPE exhibits elevated protective effects on Li anodes and has universality for diversified cathodes including but not restricted to sulfur, olivine-type LiFePO 4 , and layered LiNi 0.6 Co 0.2 Mn 0.2 O 2 , revealing tremendous potential in promoting the large-scale application of future LMBs.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 8
    Publication Date: 2018-04-26
    Description: UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response, Published online: 25 April 2018; doi:10.1038/s41375-018-0141-x UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response
    Print ISSN: 0887-6924
    Electronic ISSN: 1476-5551
    Topics: Medicine
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  • 9
    Publication Date: 2018-02-16
    Description: Objectives To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China. Design This was a multicentre, retrospective, observational study. Setting 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 Participants Information on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms. Primary and secondary outcome measures Resource use for CAP management. Results Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0–1 and Pneumonia Severity Index risk class I–II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%. Conclusions These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China. Trial registration number NCT02489578 ; Results.
    Keywords: Open access, Infectious diseases
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 10
    Publication Date: 2018-05-25
    Description: Introduction There are two approaches for the treatment of intracranial aneurysm (IA): interventional therapy and craniotomy, both of which have their advantages and disadvantages in terms of treatment efficacy. To avoid overtreatment of unruptured aneurysms (UIA), to save valuable medical resources and to reduce patient mortality and disability rate, it is vital that neurosurgeons select the most appropriate type of treatment to provide the best levels of care. In this study, we propose a refined, prospective, multicentre study for the Chinese population with strictly defined patient inclusion criteria, along with the selection of representative clinical participating centres. Methods and analysis This report describes a multicentre, prospective cohort study. As IA is extremely harmful if it ruptures, ethical issues need to be taken into account with regard to this study. Researchers are therefore not able to use randomised controlled trials. The study will be conducted by 12 clinical centres located in different regions of China. The trial recruitment programme begins in 2016 and is scheduled to be completed in 2020. We expect 1500 participants with UIA to be included. Clinical information relating to the participants will be recorded objectively. The primary endpoints are an evaluation of the safety and efficiency of interventional treatment and craniotomy for 6 months after surgery, with each participant completing at least 1 year of follow-up. The secondary endpoint is the evaluation of safety and efficacy of interventional therapy and craniotomy clipping when participants are treated for 12 months. We also address the success of treatment and the incidence of adverse events. Ethics and dissemination The research protocol and the informed consent form for participants in this study were approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University (2017-SJWK-001). The results of this study are expected to be disseminated in peer-reviewed journals in 2021. Trial registration number NCT03133598 .
    Keywords: Open access, Neurology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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