Xuemei Li

Institute of physics china, Peping, Beijing, China

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Publications (92)428.48 Total impact

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    ABSTRACT: Toxic ribosome-inactivating proteins (RIPs) abolish cell viability by inhibiting protein synthesis. Ricin, a member of these lethal proteins, is a potential bioterrorism agent. Despite the grave challenge posed by these toxins to public health, post-exposure treatment for intoxication caused by these agents currently is unavailable. In this study, we report the identification of baicalin extracted from Chinese herb medicine as a compound capable of inhibiting the activity of ricin. More importantly, post-exposure treatment with baicalin significantly increased the survival of mice poisoned by ricin. We determined the mechanism of action of baicalin by solving the crystal structure of its complex with the A chain of ricin (RTA) at a 2.2 Å resolution, which revealed that baicalin interacts with two RTA molecules at a novel binding site by hydrogen bond networks and electrostatic force interactions, suggesting its role as molecular glue of the RTA. Further biochemical and biophysical analyses validated the amino acids directly involved in binding the inhibitor, which is consistent with the hypothesis that baicalin exerts its inhibitory effects by inducing RTA to form oligomers in solution, a mechanism that is distinctly different from previously reported inhibitors. This work offers promising leads for the development of therapeutics against ricin and probably other RIPs. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 04/2015; DOI:10.1074/jbc.M114.632828 · 4.60 Impact Factor
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    ABSTRACT: Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as attachment factors, in which genogroup (G) I and GII huNoVs use distinct binding interfaces. The genetic and evolutionary relationships of GII huNoVs under selection by the host HBGAs have been well elucidated via a number of structural studies; however, such relationships among GI NoVs remain less clear due to the fact that the structures of HBGA-binding interfaces of only three GI NoVs with similar binding profiles are known. In this study the crystal structures of the P dimers of a Lewis-binding strain, the GI.8 Boxer virus (BV) that does not bind the A and H antigens, in complex with the Lewis b (Le(b)) and Le(y) antigens, respectively, were determined and compared with those of the three previously known GI huNoVs, i.e. GI.1 Norwalk virus (NV), GI.2 FUV258 (FUV) and GI.7 TCH060 (TCH) that bind the A/H/Le antigens. The HBGA binding interface of BV is composed of a conserved central binding pocket (CBP) that interacts with the β-galactose of the precursor, and a well-developed Le epitope-binding site formed by five amino acids, including three consecutive residues from the long P-loop and one from the S-loop of the P1 subdomain, a feature that was not seen in the other GI NoVs. On the other hand, the H epitope/acetamido binding site observed in the other GI NoVs is greatly degenerated in BV. These data explain the evolutionary path of GI NoVs selected by the polymorphic human HBGAs. While the CBP is conserved, the regions surrounding the CBP are flexible, providing freedom for changes. The loss or degeneration of the H epitope/acetamido binding site and the reinforcement of the Le binding site of the GI.8 BV is a typical example of such change selected by the host Lewis epitope.
    Protein & Cell 12/2014; 6(2). DOI:10.1007/s13238-014-0126-0 · 2.85 Impact Factor
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    ABSTRACT: Effect of rearing temperature on growth and thermal tolerance of Schizothorax (Racoma) kozlovi Nikolsky larvae and juveniles was investigated. The fish (start at 12 days post hatch) were reared for nearly 6 months at five constant temperatures of 10, 14, 18, 22 and 26 °C. Then juvenile fish being acclimated at three temperatures of 14, 18 and 22 °C were chosen to determine their critical thermal maximum (CTMax) and lethal thermal maximum (LTMax) by using the dynamic method. Growth rate of S. kozlovi larvae and juveniles was significantly influenced by temperature and fish size, exhibiting an increase with increased rearing temperature, but a decline with increased fish size. A significant ontogenetic variation in the optimal temperatures for maximum growth were estimated to be 24.7 °C and 20.6 °C for larvae and juveniles of S. kozlovi, respectively. The results also demonstrated that acclimation temperature had marked effects on their CTMax and LTMax, which ranged from 32.86 °C to 34.54 °C and from 33.79 °C to 34.80 °C, respectively. It is suggested that rearing temperature must never rise above 32 °C for its successful aquaculture. Significant temperature effects on the growth rate and thermal tolerance both exhibit a plasticity pattern. Determination of critical heat tolerance and optima temperature for maximum growth of S. kozlovi is of ecological significance in the conservation and aquaculture of this species.
    Journal of Thermal Biology 12/2014; 46. DOI:10.1016/j.jtherbio.2014.09.009 · 1.54 Impact Factor
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    ABSTRACT: Hepatitis A virus (HAV) remains enigmatic, despite 1.4 million cases worldwide annually. It differs radically from other picornaviruses, existing in an enveloped form and being unusually stable, both genetically and physically, but has proved difficult to study. Here we report high-resolution X-ray structures for the mature virus and the empty particle. The structures of the two particles are indistinguishable, apart from some disorder on the inside of the empty particle. The full virus contains the small viral protein VP4, whereas the empty particle harbours only the uncleaved precursor, VP0. The smooth particle surface is devoid of depressions that might correspond to receptor-binding sites. Peptide scanning data extend the previously reported VP3 antigenic site, while structure-based predictions suggest further epitopes. HAV contains no pocket factor and can withstand remarkably high temperature and low pH, and empty particles are even more robust than full particles. The virus probably uncoats via a novel mechanism, being assembled differently to other picornaviruses. It utilizes a VP2 'domain swap' characteristic of insect picorna-like viruses, and structure-based phylogenetic analysis places HAV between typical picornaviruses and the insect viruses. The enigmatic properties of HAV may reflect its position as a link between 'modern' picornaviruses and the more 'primitive' precursor insect viruses; for instance, HAV retains the ability to move from cell-to-cell by transcytosis.
    Nature 10/2014; 517(7532). DOI:10.1038/nature13806 · 42.35 Impact Factor
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    ABSTRACT: Mycobacterium tuberculosis (Mtb) uses maltose-1-phosphate to synthesize α-glucans that make up the major component of its outer capsular layer. Maltose kinase (MaK) catalyzes phosphorylation of maltose. The molecular basis for this phosphorylation is currently not understood. Here, we describe the first crystal structure of MtbMaK refined to 2.4 Å resolution. The bi-modular architecture of MtbMaK reveals a remarkably unique N-lobe. An extended sheet protrudes into ligand binding pocket of an adjacent monomer and contributes residues critical for kinase activity. Structure of the complex of MtbMaK bound with maltose reveals that maltose binds in a shallow cavity of the C-lobe. Structural constraints permit phosphorylation of α-maltose only. Surprisingly, instead of a Gly-rich loop, MtbMaK employs 'EQS' loop to tether ATP. Notably, this loop is conserved across all MaK homologues. Structures of MtbMaK presented here unveil features that are markedly different from other kinases and support the scaffolding role proposed for this kinase.
    Scientific Reports 09/2014; 4:6418. DOI:10.1038/srep06418 · 5.08 Impact Factor
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    ABSTRACT: AimsA study was conducted to compare the intestinal microbial compositions of two fish species with similar feeding strategy; paddlefish (Polyodon spathala) and bighead carp (Aristichthys nobilis) reared in the same pond. Methods and ResultsAge-0 paddlefish and bighead carp with mean average body lengths of 4339278 and 1933368cm, respectively, were reared with natural prey items in the same pond (20m(2)). After 30days of rearing, the intestinal microbiota of the two fish species was assessed by pyrosequencing of 16S rRNA genes. Interestingly, deviations were observed in the microbial communities of the two fish species according to the alpha- and beta-diversity measurements and detrended correspondence analysis (DCA). Shannon diversity (P=0015) and Pielou.evenness (P=0035) revealed significant lower diversity of the intestinal microbiota of paddlefish. Moreover, different core intestinal microbiota was noticed in the two fish species. Proteobacteria (573%), Firmicutes (119%), Fusobacteria (89%), Planctomycetes (73%), Actinobacteria (60%) and Verrucomicrobia (32%) were detected in bighead carp, while the dominant phyla in paddlefish intestines were Bacteroidetes (370%), Fusobacteria (351%), Firmicutes (148%) and Proteobacteria (126%). Conclusions Our results revealed that the intestinal microbiota differed between paddlefish and bighead carp reared in the same pond when fed similar nature food. The potential host factors, such as the genetic background, gut histology and physiology are assumed to be involved in the intestinal bacterial compositions. Significance and Impact of the StudyConsidering the similar feeding strategy of paddlefish and bighead carp, this study presents basic knowledge for evaluation of the importance of host factors (genetic background and gut anatomy) on intestinal microbial composition.
    Journal of Applied Microbiology 08/2014; 117(5). DOI:10.1111/jam.12626 · 2.39 Impact Factor
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    ABSTRACT: Unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses.
    Protein & Cell 07/2014; 5(9). DOI:10.1007/s13238-014-0087-3 · 2.85 Impact Factor
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    ABSTRACT: The tripartite motif-containing protein 2 (TRIM2) functions as an E3 ubiquitin ligase. Loss of function of TRIM2 has been shown to result in early-onset axonal neuropathy. As a member of the TRIM-NHL family of proteins, TRIM2 has a conserved modular architecture that includes N-terminal RING finger and B-box domains, a middle coiled-coil domain and a C-terminal NHL domain. To characterize the functional role of its NHL domain from the perspective of structural biology, a truncation of human TRIM2 (residues 465-744) was expressed, purified and crystallized. Rod-shaped crystals were obtained that diffracted X-rays to 1.7 Å resolution. The crystals belonged to space group P21, with unit-cell parameters a = 43.6, b = 76.4, c = 107.4 Å, α = 90.0, β = 94.0, γ = 90.0°. A Matthews coefficient of 1.97 Å(3) Da(-1), corresponding to a solvent content of 37.6%, indicated the presence of three molecules per asymmetric unit, which was further confirmed by the phasing solution from molecular replacement.
    05/2014; 70(Pt 5):673-5. DOI:10.1107/S2053230X14008127
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    ABSTRACT: The prokaryotic 5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH), a process that plays a key role in several metabolic pathways. Its absence in all mammalian species has implicated this enzyme as a promising target for antimicrobial drug design. Here, we report the crystal structure of BmMTAN in complex with its product adenine at a resolution of 2.6 Å determined by single-wavelength anomalous dispersion method. 11 key residues were mutated for kinetic characterization. Mutations of Tyr134 and Met144 resulted in the largest overall increase in Km, whereas mutagenesis of residues Glu18, Glu145 and Asp168 completely abolished activity. Glu145 and Asp168 were identified as active site residues essential for catalysis. The catalytic mechanism and implications of this structure for broad-based antibiotic design are discussed.
    Biochemical and Biophysical Research Communications 03/2014; 446(4). DOI:10.1016/j.bbrc.2014.03.045 · 2.28 Impact Factor
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    ABSTRACT: Enterovirus 71 (HEV71) epidemics in children and infants result mainly in mild symptoms; however, especially in the Asia-Pacific region, infection can be fatal. At present, no therapies are available. We have used structural analysis of the complete virus to guide the design of HEV71 inhibitors. Analysis of complexes with four 3-(4-pyridyl)-2-imidazolidinone derivatives with varying anti-HEV71 activities pinpointed key structure-activity correlates. We then identified additional potentially beneficial substitutions, developed methods to reliably triage compounds by quantum mechanics-enhanced ligand docking and synthesized two candidates. Structural analysis and in vitro assays confirmed the predicted binding modes and their ability to block viral infection. One ligand (with IC50 of 25 pM) is an order of magnitude more potent than the best previously reported inhibitor and is also more soluble. Our approach may be useful in the design of effective drugs for enterovirus infections.
    Nature Structural & Molecular Biology 02/2014; DOI:10.1038/nsmb.2769 · 11.63 Impact Factor
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    ABSTRACT: The removal of Pb2+ from aqueous solution by 732 cation-exchange resin in sodium type (732-CR) has been studied in batch experiments at varying pH (2.0-8.0), Pb2+ concentration (50-200 mg/L), contact time (5-300 min), temperature (288-308 K) and resin dose (0.125-0.75 g/L). The experimental data show that the ion-exchange process was dependent on pH and temperature, the optimal exchange capacity was found at pH 4.0, and higher temperature was beneficial to lead sorption. Kinetic data indicate that the ion-exchange process followed a pseudo-first order model. The equilibrium exchange capacity could be reached at approximately 4 h, and the maximum sorption capacity of Pb2+ at pH 4.0 was 396.8 mg/g resin. The equilibrium data were evaluated with Langmuir and Freundlich model, and were best fitted with Langmuir model. The thermodynamic parameters for removal of Pb2+ indicate that the reaction was spontaneous and endothermic. Additionally, column tests were conducted by using both synthetic solution and effluents from lead battery industry. The regeneration of resin was performed for two sorption-regeneration cycles by 1 M NaOH, and the results show that effective regeneration was achieved by this method.
    Applied Surface Science 10/2013; 283:660-667. DOI:10.1016/j.apsusc.2013.06.161 · 2.54 Impact Factor
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    ABSTRACT: GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells. Their importance to basic cell biology, human diseases, and pharmaceutical interventions is well established. Many crystal structures of GPCR proteins have been reported in both active and inactive conformations. These data indicate that agonist binding alone is not sufficient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins, yet other essential factors remain elusive. Based on analysis of available GPCR crystal structures, we identified a potential conformational switch around the conserved Asp2.50, which consistently shows distinct conformations between inactive and active states. Combining the structural information with the current literature, we propose an energy-coupling mechanism, in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.
    Protein & Cell 09/2013; 4(10). DOI:10.1007/s13238-013-3073-2 · 2.85 Impact Factor
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    ABSTRACT: Different causes of mortality have been described over different decades followed by description of pathogens identified from infective episodes that led to death. A retrospective review was performed in 3,831 hospitalized systemic lupus erythematosus (SLE) patients in Peking Union Medical College Hospital from January 1986 to April 2012. The primary causes of death were identified, and the constituent ratio of specific death causes during different periods was compared. Among 3,831 hospitalized SLE patients, 268 patients died, accounting for 7.0 %. No significant difference of death rate was found between men and women, P = 0.404. The three most frequent death causes according to decade were as follows: for 1986-1995, renal involvement, lupus encephalopathy, and infections; for 1996-2005, infections, lupus encephalopathy, and renal involvement; and for 2006-2012, infections, lupus encephalopathy, and pulmonary hypertension. Certain types of deaths, primarily related to lupus activity, have decreased over time, whereas infections, often attributed to the use of corticosteroid and immunosuppressant medications, have increased gradually and changed to the most frequent death causes of SLE. Early mortality (<3 years) occurred more commonly in lupus encephalopathy, while late death (>3 years) happened more frequently in renal involvement, pulmonary artery hypertension, cardiovascular events, and cancer. In SLE death cases mainly dying from infection, mixed infections were more frequent than single pathogen infection (60.5 vs. 39.5 %), including common bacteria, fungal infection, and cytomegalovirus. Aspergillus fumigatus and Pneumocystis carinii were the two most commonly infected pathogens, and Cytomegalovirus was a frequent pathogen of mixed infection. Aggressive therapy has effectively reduced the mortality related to disease activity but also was associated with life-threatening infections. Mixed and fungal infection should be considered when SLE patients have severe infection.
    Clinical Rheumatology 09/2013; DOI:10.1007/s10067-013-2383-3 · 1.77 Impact Factor
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    ABSTRACT: Coxsackievirus A16 belongs to the family Picornaviridae, and is a major agent of hand-foot-and-mouth disease that infects mostly children, and to date no vaccines or antiviral therapies are available. 2A protease of enterovirus is a nonstructural protein and possesses both self-cleavage activity and the ability to cleave the eukaryotic translation initiation factor 4G. Here we present the crystal structure of coxsackievirus A16 2A protease, which interestingly forms hexamers in crystal as well as in solution. This structure shows an open conformation, with its active site accessible, ready for substrate binding and cleavage activity. In conjunction with a previously reported "closed" state structure of human rhinovirus 2, we were able to develop a detailed hypothesis for the conformational conversion triggered by two "switcher" residues Glu88 and Tyr89 located within the bll2-cII loop. Substrate recognition assays revealed that amino acid residues P1', P2 and P4 are essential for substrate specificity, which was verified by our substrate binding model. In addition, we compared the in vitro cleavage efficiency of 2A proteases from coxsackievirus A16 and enterovirus 71 upon the same substrates by fluorescence resonance energy transfer (FRET), and observed higher protease activity of enterovirus 71 compared to that of coxsackievirus A16. In conclusion, our study shows an open conformation of coxsackievirus A16 2A protease and the underlying mechanisms for conformational conversion and substrate specificity. These new insights should facilitate the future rational design of efficient 2A protease inhibitors.
    Protein & Cell 09/2013; 4(10). DOI:10.1007/s13238-013-3914-z · 2.85 Impact Factor
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    ABSTRACT: Disulfide bond-forming (Dsb) protein is a bacterial periplasmic protein that is essential for the correct folding and disulfide bond formation of secreted or cell wallassociated proteins. DsbA introduces disulfide bonds into folding proteins, and is re-oxidized through interaction with its redox partner DsbB. Mycobacterium tuberculosis, a Gram-positive bacterium, expresses a DsbA-like protein ( Rv2969c), an extracellular protein that has its Nterminus anchored in the cell membrane. Since Rv2969c is an essential gene, crucial for disulfide bond formation, research of DsbA may provide a target of a new class of anti-bacterial drugs for treatment of M.tuberculosis infection. In the present work, the crystal structures of the extracellular region of Rv2969c (Mtb DsbA) were determined in both its reduced and oxidized states. The overall structure of Mtb DsbA can be divided into two domains: a classical thioredoxin-like domain with a typical CXXC active site, and an α-helical domain. It largely resembles its Escherichia coli homologue EcDsbA, however, it possesses a truncated binding groove; in addition, its active site is surrounded by an acidic, rather than hydrophobic surface. In our oxidoreductase activity assay, Mtb DsbA exhibited a different substrate specificity when compared to EcDsbA. Moreover, structural analysis revealed a second disulfide bond in Mtb DsbA, which is rare in the previously reported DsbA structures, and is assumed to contribute to the overall stability of Mtb DsbA. To investigate the disulphide formation pathway in M.tuberculosis, we modeled Mtb Vitamin K epoxide reductase (Mtb VKOR), a binding partner of Mtb DsbA, to Mtb DsbA.
    Protein & Cell 07/2013; 4(8). DOI:10.1007/s13238-013-3033-x · 2.85 Impact Factor
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    ABSTRACT: It remains largely mysterious how the genomes of non-enveloped eukaryotic viruses are transferred across a membrane into the host cell. Picornaviruses are simple models for such viruses, and initiate this uncoating process through particle expansion, which reveals channels through which internal capsid proteins and the viral genome presumably exit the particle, although this has not been clearly seen until now. Here we present the atomic structure of an uncoating intermediate for the major human picornavirus pathogen CAV16, which reveals VP1 partly extruded from the capsid, poised to embed in the host membrane. Together with previous low-resolution results, we are able to propose a detailed hypothesis for the ordered egress of the internal proteins, using two distinct sets of channels through the capsid, and suggest a structural link to the condensed RNA within the particle, which may be involved in triggering RNA release.
    Nature Communications 06/2013; 4:1929. DOI:10.1038/ncomms2889 · 10.74 Impact Factor
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    ABSTRACT: Gut microbiota has shown tight and coordinated connection with various functions of its host such as metabolism, immunity, energy utilization, and health maintenance. To gain insight into whether gut microbes affect the metabolism of fish, we employed fast-growing transgenic common carp (Cyprinus carpio L.) to study the connections between its large body feature and gut microbes. Metagenome-based fingerprinting and high-throughput sequencing on bacterial 16S rRNA genes indicated that fish gut was dominated by Proteobacteria, Fusobacteria, Bacteroidetes and Firmicutes, which displayed significant differences between transgenic fish and wild-type controls. Analyses to study the association of gut microbes with the fish metabolism discovered three major phyla having significant relationships with the host metabolic factors. Biochemical and histological analyses indicated transgenic fish had increased carbohydrate but decreased lipid metabolisms. Additionally, transgenic fish has a significantly lower Bacteroidetes:Firmicutes ratio than that of wild-type controls, which is similar to mammals between obese and lean individuals. These findings suggest that gut microbiotas are associated with the growth of fast growing transgenic fish, and the relative abundance of Firmicutes over Bacteroidetes could be one of the factors contributing to its fast growth. Since the large body size of transgenic fish displays a proportional body growth, which is unlike obesity in human, the results together with the findings from others also suggest that the link between obesity and gut microbiota is likely more complex than a simple Bacteroidetes:Firmicutes ratio change.
    PLoS ONE 05/2013; 8(5):e64577. DOI:10.1371/journal.pone.0064577 · 3.53 Impact Factor
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    ABSTRACT: Behçet's disease (BD) is a multi-systemic inflammatory disorder which can affect all types and sizes of blood vessels. This study aims to evaluate the prevalence and characteristics of vascular involvement in BD. Among 796 patients diagnosed with BD, 102 patients (81 male, 21 female) with vascular involvement were included, whose detailed clinical characteristics were recorded. The diagnosis of vascular lesions was made on clinical signs, by Doppler ultrasonography, and/or angiography using computed tomographic or magnetic resonance techniques. Vascular involvement occurred in 12.8 % of BD patients. Male to female ratio was 3.86:1. Mean age at onset of vascular involvement was 29.5 ± 11.3 years. Vascular lesion was the initial sign of BD in 28 patients, accounting for 27.5 %. Of 102 BD patients with vascular involvement, 72 had venous lesions (70.6 %) and 56 had arterial lesions (54.9 %), among which 26 (25.5 %) patients had both venous and arterial involvements. Female BD patients were more often involved with arterial lesions, whereas male BD patients developed venous lesions more often than females, P = 0.000. The most common type of vascular involvement was deep venous thrombosis in lower extremities (n = 49), other affected venous sites including inferior vena cava, superior vena cava, and cerebral venous. The prominent type of arterial lesions was dilatation (n = 25, including 24 cases of aneurysms); other types included eight cases of occlusion and 23 cases of stenosis. The main locations of arterial lesions were the aorta (n = 19), lower extremity arteries (n = 15), pulmonary arteries (n = 13), coronary arteries (n = 5), and subclavian arteries (n = 5). Compared with those without vascular lesions, ocular involvement, genital ulcers, and arthritis were significantly less frequent among patients with vasculo-BD (23.5 vs 35.2 %, P = 0.024; 54.9 vs 76.5 %, P = 0.000; 19.6 vs 30.5 %, P = 0.026), whereas a higher frequency of cardiac involvement was found in vasculo-BD patients (20.6 vs 3.6 %, P = 0.000). Vascular involvement is a complication in BD patients. This study illustrated that venous lesions are more frequently involved than arterial lesions. Vascular lesions correlated with a high frequency of cardiac involvement and a low incidence of ocular lesions, genital ulcers, and arthritis.
    Clinical Rheumatology 02/2013; DOI:10.1007/s10067-013-2205-7 · 1.77 Impact Factor
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    ABSTRACT: One group of Bcl-2 protein family, which shares only the BH3 domain (BH3-only), is critically involved in the regulation of programmed cell death. Herein we demonstrated a novel human BH3-only protein (designated as Bop) which could induce apoptosis in a BH3 domain-dependent manner. Further analysis indicated that Bop mainly localized to mitochondria and used its BH3 domain to contact the loop regions of voltage dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane. In addition, purified Bop protein induced the loss of mitochondrial transmembrane potential (Δψm) and the release of cytochrome c. Furthermore, Bop used its BH3 domain to contact pro-survival Bcl-2 family members (Bcl-2, Bcl-X(L), Mcl-1, A1 and Bcl-w), which could inhibit Bop-induced apoptosis. Bop would be constrained by pro-survival Bcl-2 proteins in resting cells, because Bop became released from phosphorylated Bcl-2 induced by microtubule-interfering agent like vincristine (VCR). Indeed, knockdown experiments indicated that Bop was partially required for VCR induced cell death. Finally, Bop might need to function through Bak and Bax, likely by releasing Bak from Bcl-X(L) sequestration. In conclusion, Bop may be a novel BH3-only factor that can engage with the regulatory network of Bcl-2 family members to process intrinsic apoptotic signaling.
    Protein & Cell 10/2012; 3(10):790-801. DOI:10.1007/s13238-012-2069-7 · 2.85 Impact Factor

Publication Stats

2k Citations
428.48 Total Impact Points


  • 2015
    • Institute of physics china
      Peping, Beijing, China
  • 2014
    • University of Cincinnati
      • Department of Pediatrics
      Cincinnati, Ohio, United States
  • 2013–2014
    • Chinese Academy of Fishery Sciences
      北江, Zhejiang Sheng, China
    • Huazhong University of Science and Technology
      • School of Environmental Science and Engineering
      Wu-han-shih, Hubei, China
  • 2003–2012
    • Chinese Academy of Sciences
      • • Institute of Hydrobiology
      • • Institute of Biophysics
      • • State Key Laboratory of Reproductive Biology
      • • Institute of Zoology
      Peping, Beijing, China
  • 2010–2011
    • Yunnan Academy of Agricultural Sciences
      Yün-nan, Yunnan, China
    • Nankai University
      • College of Life Sciences
      T’ien-ching-shih, Tianjin Shi, China
  • 2004–2009
    • Tsinghua University
      • Laboratory of Structural Biology
      Beijing, Beijing Shi, China
  • 2008
    • Yunnan University
      • Laboratory for Conservation and Utilization of Bio-resources
      Yün-nan, Yunnan, China
    • China Agricultural University
      • Department of Biochemistry and Molecular Biology
      Peping, Beijing, China
  • 2004–2005
    • National Tsing Hua University
      Hsin-chu-hsien, Taiwan, Taiwan