99 research outputs found

    Internal Governance Structure of ā€œDouble First-classā€ Universities in China

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    Universities in China have been implementing large-scale higher education reform to construct a modern university system with Chinese characteristics. The present study explores the relationships of political, administrative, and academic power based on data analysis of Chinaā€™s first batch of ā€œdouble first-classā€ universities. Internal governance structure reform has achieved good results to adapt to the scale expanding. Chinese universities need to legalize governance structures, promote the autonomous operation of universities and the democratization of governance policies, and pursue the de-administration of their academic affairs and regulate their academic power in the system

    Bisphosphonates Cause Osteonecrosis of the Jaw-Like Disease in Mice

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    Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is a morbid bone disease linked to long-term bisphosphonate use. Despite its broad health impact, mechanistic study is lacking. In this study, we have established a mouse model of BONJ-like disease based on the equivalent clinical regimen in myeloma patients, a group associated with high risk of BONJ. We demonstrate that the murine BONJ-like disease recapitulates major clinical and radiographical manifestations of the human disease, including characteristic features of osseous sclerosis, sequestra, avascular, and radiopaque alveolar bone in the jaw that persists beyond a normal course of wound healing following tooth extraction. We find that long-term administration of bisphosphonates results in an increase in the size and number of osteoclasts and the formation of giant osteoclast-like cells within the alveolar bone. We show that the development of necrotic bone and impaired soft tissue healing in our mouse model is dependent on long-term use of high-dose bisphosphonates, immunosuppressive and chemotherapy drugs, as well as mechanical trauma. Most importantly, we demonstrate that bisphosphonate is the major cause of BONJ-like disease in mice, mediated in part by its ability to suppress osseous angiogenesis and bone remodeling. The availability of this novel mouse model of BONJ-like disease will help elucidate the pathophysiology of BONJ and ultimately develop novel approaches for prevention and treatment of human BONJ. Copyright Ā© American Society for Investigative Pathology

    No evidence of xenotropic murine leukemia virus-related virus transmission by blood transfusion from infected rhesus macaques

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    The discovery of xenotropic murine leukemia virus-related virus (XMRV) in human tissue samples has been shown to be due to virus contamination with a recombinant murine retrovirus. However, due to the unknown pathogenicity of this novel retrovirus and its broad host range, including human cell lines, it is important to understand the modes of virus transmission and develop mitigation and management strategies to reduce the risk of human exposure and infection. XMRV transmission was evaluated by whole-blood transfusion in rhesus macaques. Monkeys were infected with XMRV to serve as donor monkeys for blood transfers at weeks 1, 2, and 3 into naĆÆve animals. The donor and recipient monkeys were evaluated for XMRV infection by nested PCR assays with nucleotide sequence confirmation, Western blot assays for development of virus-specific antibodies, and coculture of monkey peripheral blood mononuclear cells (PBMCs) with a sensitive target cell line for virus isolation. XMRV infection was demonstrated in the virus-injected donor monkeys, but there was no evidence of virus transmission by whole-blood transfusion to naĆÆve monkeys based upon PCR analysis of PBMCs using XMRV-specific gag and env primers, Western blot analysis of monkey plasma up to 31 to 32 weeks after transfusion, and coculture studies using monkey PBMCs from various times after transfusion. The study demonstrates the lack of XMRV transmission by whole-blood transfusion during the acute phase of infection. Furthermore, analysis of PBMC viral DNA showed extensive APOBEC-mediated G-to-A hypermutation in a donor animal at week 9, corroborating previous results using macaques and supporting the possible restriction of XMRV replication in humans by a similar mechanism

    Heat shock protein 27 is a potential indicator for response to YangZheng XiaoJi and chemotherapy agents in cancer cells

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    Heat shock protein 27 (HSP27) is a member of the heat shock protein family which has been linked to tumour progression and, most interestingly, to chemotherapy resistance in cancer patients. The present study examined the potential interplay between HSP27 and YangZheng XiaoJi, a traditional Chinese medicine used in cancer treatment. A range of cell lines from different tumour types including pancreatic, lung, gastric, colorectal, breast, prostate and ovarian cancer (both wild-type and resistant) were used. Levels and activation of HSP27 and its potential associated signalling pathways were evaluated by protein array and western blotting. Knockdown of HSP27 in cancer cells was achieved using siRNA. Localisation and co-localisation of HSP27 and other proteins were carried out by immunofluorescence. Cell growth and migration were evaluated in their response to a range of chemotherapeutic agents. The present study first identified, by way of protein array, that YangZheng XiaoJi was able to inhibit the phosphorylation of HSP27 protein in cancer cells. We further demonstrated that HSP27, which is co-localised with caspase-9, can be blocked from localising in focal adhesions and co-localising with caspase-9 by YangZheng XiaoJi. The study also demonstrated that YangZheng XiaoJi was able to sensitise cancer cells including those cells that were resistant to chemotherapy, to chemotherapeutic agents. Finally, knocking down HSP27 markedly reduced the migration of cancer cells and increased the sensitivity of cancer cells to the inhibitory effect on cellular migration by YangZheng XiaoJi. YangZheng XiaoJi can act as an agent in first sensitising cancer cells to chemotherapy and secondly to overcome, to some degree, chemoresistance when used in an appropriate fashion in patients who have active HSP2

    Boosting the performance of single-atom catalysts via external electric field polarization

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    Single-atom catalysts represent a unique catalytic system with high atomic utilization and tunable reaction pathway. Despite current successes in their optimization and tailoring through structural and synthetic innovations, there is a lack of dynamic modulation approach for the single-atom catalysis. Inspired by the electrostatic interaction within specific natural enzymes, here we show the performance of model single-atom catalysts anchored on two-dimensional atomic crystals can be systematically and efficiently tuned by oriented external electric fields. Superior electrocatalytic performance have been achieved in single-atom catalysts under electrostatic modulations. Theoretical investigations suggest a universal ā€œonsite electrostatic polarizationā€ mechanism, in which electrostatic fields significantly polarize charge distributions at the single-atom sites and alter the kinetics of the rate determining steps, leading to boosted reaction performances. Such field-induced on-site polarization offers a unique strategy for simulating the catalytic processes in natural enzyme systems with quantitative, precise and dynamic external electric fields

    Dipole-tunable interfacial engineering strategy for high-performance all-inorganic red quantum-dot light-emitting diodes

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    All-inorganic quantum dot (QD) light-emitting diodes (AI-QLEDs) with excellent stability received enormous interest in the past few years. Nevertheless, the vast energy offset and the high trap density at the NiOX/QDs interface limit hole injection leading to fluorescence quenching and hampering the performance. Here, we present self-assembled monolayers (SAMs) with phosphonic acid (PA) anchoring groups modifying NiOX hole transport layer (HTL) to tune energy level and passivate trap states. This strategy facilitates hole injection owning to the well-aligned energy level by interface dipole, downshifting the vacuum level, reducing the hole injection barrier from 0.94 eV to 0.28 eV. Meanwhile, it mitigates the interfacial recombination by passivating surface hydroxyl group (-OH) and oxygen vacancy (VO) traps in NiOX. The electron leakage from QDs toward NiOX HTL is significantly suppressed. The all-inorganic R-QLEDs exhibit one of the highest maximum luminance, external quantum efficiency and operational lifetime of 88980 cd māˆ’2, 10.3% and 335045 h (T50@100 cd māˆ’2), respectively. The as-proposed interface engineering provides an effective design principle for high-performance AI-QLEDs for future outdoor and optical projection-type display applications

    A tau fragment links depressive-like behaviors and cognitive declines in Alzheimerā€™s disease mouse models through attenuating mitochondrial function

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    IntroductionAlzheimerā€™s disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-Ī² peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear.MethodsDepressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)-derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-Ī“). Further behavioral studies investigated the role of Tau N368-PPAR-Ī“ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS.ResultsWe found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-Ī“, repressing PPAR-Ī“ā€“mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-Ī“. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-Ī“ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice.ConclusionThese results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-Ī“, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimerā€™s disease

    Community structure of endophytic fungi in roots and leaves of Fagopyrum mill and Avena sativa in a Chinese northern cold region

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    In order to explore the endophytic fungi of Fagopyrum Mill and Avena sativa, Illumina Miseq high-throughput sequencing was used to analyze the community structure and diversity of endophytic fungi in leaves and roots of buckwheat and oat at the mature stage. The results of community structure showed that there were 205 operational taxonomic units (OTUs) in buckwheat roots and 181 OTUs in buckwheat leaves based on 97% sequence similarity level. There were 152 OTUs and 127 OTUs in the root and the leaf of oat, respectively. At the phylum level, Ascomycota and Basidiomycota were the dominant endophytic fungi in buckwheat roots and leaves, while Ascomycota was the dominant endophytic fungus in oat roots and leaves. Alpha diversity analysis showed that the Ace index, Chao index and Shannon index of buckwheat roots were higher than that of buckwheat leaves, and the three indices of oat roots were also higher than that of oat leaves, indicating that the richness and diversity of endophytic fungi community in roots were higher than that in leaves. Biomarkers were found by significant difference analysis in buckwheat and oat. The endophytic functional groups of buckwheat and oat were mainly distributed in Pathotroph and Saprotroph. The results of this study laid a foundation for fully exploiting the dominant endophytic fungal resources of buckwheat and oat and further developing microbial fertilizers

    Feasibility and safety of prophylactic tentorium cerebelli hiatus incision in surgery of glioma located in lateral fissure area

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    To discuss the feasibility and safety of prophylactic tentorium cerebelli hiatus incision in surgery of glioma located in lateral fissure area. There were 80 patients with glioma located in lateral fissure area who received treatment from May 2012 to May 2015, divided into two groups, the research group (n=40) and control group (n=40), and then statistical analysis was carried out. Difference in total resection rate and subtotal resection rate of glioma between patients of the research group and those of the control group was not significant (P>0.05); intracranial pressure of patients in the research group was significantly lower than that of control group (P0.05). Prophylactic tentorium cerebelli hiatus incision in surgery of glioma located in lateral fissure area can effectively reduce patientsā€™ intracranial pressure, shorten patientsā€™ hospital stay and reduce patientsā€™ times of using mannitol without increasing the rate of patientsā€™ acute renal function damage and second surgery

    Significance and Prospect of Tryptophan Metabolism in Treatment of Tumor Immune Checkpoint Inhibitors

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    Although immune checkpoint inhibitors (ICIs) have great breakthrough in cancer treatment in recent years, most patients have not benefited from it on account of immune microenvironment. Studies have shown that tryptophan metabolism is not only involved in the formation of tumor immunosuppressive microenvironment but also plays an important role in the therapeutic application of ICIs. At present, inhibiting the kynurenine pathway of tryptophan metabolism is now in various stages of clinical trials, while the other two metabolic pathways, 5-HT and the indole pathway, also have aroused wide concern. This article reviews the latest developments in this field
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