Institution
Xiamen University
Education•Amoy, Fujian, China•
About: Xiamen University is a education organization based out in Amoy, Fujian, China. It is known for research contribution in the topics: Catalysis & Population. The organization has 50472 authors who have published 54480 publications receiving 1058239 citations. The organization is also known as: Amoy University & Xiàmén Dàxué.
Topics: Catalysis, Population, Graphene, Raman spectroscopy, Anode
Papers published on a yearly basis
Papers
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TL;DR: It is proposed that the signaling events after the RIP1–RIP3 amyloid complex assembly are the recruitment of free RIP3 by the RIP3 in the amyloids scaffold followed by autophosphorylation of RIP3 and subsequent recruitment of MLKL by RIP3 to execute necroptosis.
Abstract: Necroptosis is mediated by a signaling complex called necrosome, containing receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like (MLKL). It is known that RIP1 and RIP3 form heterodimeric filamentous scaffold in necrosomes through their RIP homotypic interaction motif (RHIM) domain-mediated oligomerization, but the signaling events based on this scaffold has not been fully addressed. By using inducible dimer systems we found that RIP1–RIP1 interaction is dispensable for necroptosis; RIP1–RIP3 interaction is required for necroptosis signaling, but there is no necroptosis if no additional RIP3 protein is recruited to the RIP1–RIP3 heterodimer, and the interaction with RIP1 promotes the RIP3 to recruit other RIP3; RIP3–RIP3 interaction is required for necroptosis and RIP3–RIP3 dimerization is sufficient to induce necroptosis; and RIP3 dimer-induced necroptosis requires MLKL. We further show that RIP3 oligomer is not more potent than RIP3 dimer in triggering necroptosis, suggesting that RIP3 homo-interaction in the complex, rather than whether RIP3 has formed homo polymer, is important for necroptosis. RIP3 dimerization leads to RIP3 intramolecule autophosphorylation, which is required for the recruitment of MLKL. Interestingly, phosphorylation of one of RIP3 in the dimer is sufficient to induce necroptosis. As RIP1–RIP3 heterodimer itself cannot induce necroptosis, the RIP1–RIP3 heterodimeric amyloid fibril is unlikely to directly propagate necroptosis. We propose that the signaling events after the RIP1–RIP3 amyloid complex assembly are the recruitment of free RIP3 by the RIP3 in the amyloid scaffold followed by autophosphorylation of RIP3 and subsequent recruitment of MLKL by RIP3 to execute necroptosis.
241 citations
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TL;DR: Program for Changjiang Scholars and Innovative Research Team in University, China and Science-Technology Project of Fujian Provence, China.
241 citations
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TL;DR: The pharmacological modulation of MST1/2 kinase activities provides a novel approach to potentiate tissue repair and regeneration, with XMU-MP-1 as the first lead for the development of targeted regenerative therapeutics.
Abstract: Tissue repair and regenerative medicine address the important medical needs to replace damaged tissue with functional tissue. Most regenerative medicine strategies have focused on delivering biomaterials and cells, yet there is the untapped potential for drug-induced regeneration with good specificity and safety profiles. The Hippo pathway is a key regulator of organ size and regeneration by inhibiting cell proliferation and promoting apoptosis. Kinases MST1 and MST2 (MST1/2), the mammalian Hippo orthologs, are central components of this pathway and are, therefore, strong target candidates for pharmacologically induced tissue regeneration. We report the discovery of a reversible and selective MST1/2 inhibitor, 4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino)benzenesulfonamide (XMU-MP-1), using an enzyme-linked immunosorbent assay-based high-throughput biochemical assay. The cocrystal structure and the structure-activity relationship confirmed that XMU-MP-1 is on-target to MST1/2. XMU-MP-1 blocked MST1/2 kinase activities, thereby activating the downstream effector Yes-associated protein and promoting cell growth. XMU-MP-1 displayed excellent in vivo pharmacokinetics and was able to augment mouse intestinal repair, as well as liver repair and regeneration, in both acute and chronic liver injury mouse models at a dose of 1 to 3 mg/kg via intraperitoneal injection. XMU-MP-1 treatment exhibited substantially greater repopulation rate of human hepatocytes in the Fah-deficient mouse model than in the vehicle-treated control, indicating that XMU-MP-1 treatment might facilitate human liver regeneration. Thus, the pharmacological modulation of MST1/2 kinase activities provides a novel approach to potentiate tissue repair and regeneration, with XMU-MP-1 as the first lead for the development of targeted regenerative therapeutics.
241 citations
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TL;DR: The data demonstrate that necroptosis is a major mechanism of proximal tubular cell death in cisplatin-induced nephrotoxic AKI, and a positive feedback loop involving these genes and inflammatory cytokines that promotes ne croptosis progression.
Abstract: Cell death and inflammation in the proximal tubules are the hallmarks of cisplatin-induced AKI, but the mechanisms underlying these effects have not been fully elucidated. Here, we investigated whether necroptosis,atypeofprogrammednecrosis,hasaroleincisplatin-inducedAKI.Wefoundthatinhibitionof any of the core components of the necroptotic pathway—receptor-interacting protein 1 (RIP1), RIP3, or mixed lineage kinase domain-like protein (MLKL)—by gene knockout or a chemical inhibitor diminished cisplatin-induced proximal tubule damage in mice. Similar results were obtained in cultured proximal tubular cells. Furthermore, necroptosis of cultured cells could be induced by cisplatin or by a combination ofcytokines(TNF-a,TNF-relatedweakinducerofapoptosis, andIFN-g)thatwereupregulatedinproximal tubules of cisplatin-treated mice. However, cisplatin induced an increase in RIP1 and RIP3 expression in cultured tubular cells in the absence of cytokine release. Correspondingly, overexpression of RIP1 or RIP3 enhanced cisplatin-induced necroptosis in vitro. Notably, inflammatory cytokine upregulation in cisplatintreatedmicewaspartiallydiminishedinRIP3-orMLKL-deficientmice,suggestingapositivefeedbackloop involving these genes and inflammatory cytokines that promotes necroptosis progression. Thus, our data demonstrate that necroptosis is a major mechanism of proximal tubular cell death in cisplatin-induced nephrotoxic AKI.
240 citations
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TL;DR: This work demonstrates with experimental and theoretical evidence that it is DMAB which contributes to the characteristic SERS behavior in the SERS spectra of PATP and analyzes some important experimental phenomena in the framework of the surface reaction instead of the contribution "b2 modes".
Abstract: p-aminothiophenol (PATP) is an important molecule for surface-enhanced Raman spectroscopy (SERS). It can strongly interact with metallic SERS substrates and produce very strong SERS signals. It is a molecule that has often been used for mechanistic studies of the SERS mechanism as the photon-driven charge transfer (CT) mechanism is believed to be present for this molecule. Recently, a hot debate over the SERS behavior of PATP was triggered by our finding that PATP can be oxidatively transformed into 4,4′-dimercaptoazobenzene (DMAB), which gives a SERS spectra of so-called “b2 modes”. In this perspective, we will give a general overview of the SERS mechanism and the current status of SERS studies on PATP. We will then demonstrate with our experimental and theoretical evidence that it is DMAB which contributes to the characteristic SERS behavior in the SERS spectra of PATP and analyze some important experimental phenomena in the framework of the surface reaction instead of the contribution “b2 modes”. We will then point out the existing challenges of the present system. A clear understanding of the reaction mechanism for nitrobenzene or aromatic benzene will be important to not only understand the SERS mechanism but to also provide an economic way of producing azo dyes with a very high selectivity and conversion rate.
240 citations
Authors
Showing all 50945 results
Name | H-index | Papers | Citations |
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Zhong Lin Wang | 245 | 2529 | 259003 |
Lei Jiang | 170 | 2244 | 135205 |
Yang Gao | 168 | 2047 | 146301 |
William A. Goddard | 151 | 1653 | 123322 |
Rui Zhang | 151 | 2625 | 107917 |
Xiaoyuan Chen | 149 | 994 | 89870 |
Fuqiang Wang | 145 | 1518 | 95014 |
Galen D. Stucky | 144 | 958 | 101796 |
Shu-Hong Yu | 144 | 799 | 70853 |
Wei Huang | 139 | 2417 | 93522 |
Bin Liu | 138 | 2181 | 87085 |
Jie Liu | 131 | 1531 | 68891 |
Han Zhang | 130 | 970 | 58863 |
Lei Zhang | 130 | 2312 | 86950 |
Jian Zhou | 128 | 3007 | 91402 |