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Li Xing

Publications and source records attributed to Li Xing.

At least 19 recordsLinked to original sources
PubMed2026

Efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis: a multicenter, randomized, open-label, active-controlled, phase III trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). METHODS: In this phase III, multicenter, randomized, open-label, non-inferiority trial, patients with hyperphosphatemia on maintenance hemodialysis were randomly assigned to receive either ferric citrate or sevelamer carbonate tablets for 12 weeks. The primary endpoint was the change in serum phosphorus levels from baseline to week 12, with a non-inferiority margin of 0.32 mmol/L. Secondary endpoints included changes in serum calcium, intact parathyroid hormone, and safety assessments. RESULTS: A total of 239 patients were randomized to the ferric citrate group (n = 119) or the sevelamer carbonate group (n = 120). The mean change in serum phosphorus levels was -0.70 ± 0.50 mmol/L in the ferric citrate group and -0.61 ± 0.59 mmol/L in the sevelamer carbonate group (least squares mean difference, -0.09 mmol/L; 95% CI, -0.24 to 0.05 mmol/L; non-inferiority margin, 0.32 mmol/L). No significant inter-group differences were found in the percentage of patients achieving target phosphorus levels (49.09% vs. 48.28%, p = 0.902). Ferric citrate significantly improved iron-related parameters and hemoglobin levels. Most treatment-emergent adverse events were mild, with gastrointestinal disorders being the most common. CONCLUSIONS: Ferric citrate tablets were non-inferior to sevelamer carbonate in reducing serum phosphorus levels in hyperphosphatemia patients on maintenance hemodialysis, with the added benefit of improving iron-related anemia and a favorable safety profile.

Adult↗
PubMed2006

The dynamic envelope of a fusion class II virus. Prefusion stages of semliki forest virus revealed by electron cryomicroscopy.

Semliki Forest virus is among the prototypes for Class II virus fusion and targets the endosomal membrane. Fusion protein E1 and its envelope companion E2 are both anchored in the viral membrane and form an external shell with protruding spikes. In acid environments, mimicking the early endosomal milieu, surface epitopes in the virus rearrange along with exposure of the fusion loop. To visualize this transformation into a fusogenic stage, we determined the structure of the virus at gradually lower pH values. The results show that while the fusion loop is available for external interaction and the shell and stalk domains of the spike begin to deteriorate, the E1 and E2 remain in close contact in the spike head. This unexpected observation points to E1 and E2 cooperation beyond the fusion loop exposure stage and implies a more prominent role for E2 in guiding membrane close encounter than has been earlier anticipated.

Cryoelectron Microscopy↗
PubMed2006

Immunological equivalence between mouse brain-derived and Vero cell-derived Japanese encephalitis vaccines.

The persistent spread via animal reservoirs urges expanding vaccination programs against pathogens like the Japanese encephalitis virus, JEV. The JEV is spreads to new areas by domestic as well as by wild animals. Although there is a safe and efficient vaccine on the market, this is derived from infected mouse brains, why today's situation requires overcoming the potential risk caused by using animal tissues. To meet this demand we have developed a Vero cell-derived JEV vaccine, using the same virus strain as in the established one. A phase III clinical study of the new vaccine has recently been completed with positive outcome. Like the established mouse brain-derived vaccine, the Vero cell-derived one is a formalin inactivated whole virus vaccine. We here demonstrate the very good agreement in immunological tests between the two antigens. The study includes analyses with two neutralizing monoclonal antibodies that blocks cell entry at a late stage in infection, assumedly interfering with fusion-related refolding in the virus fusion protein. It is obvious that the formalin inactivation treatment, with both virus preparations, retains these essential vaccine epitopes.

Adolescent↗
PubMed2006

Multiple assembly states of lumazine synthase: a model relating catalytic function and molecular assembly.

Lumazine synthases have been observed in the form of pentamers, dimers of pentamers, icosahedral capsids consisting of 60 subunits and larger capsids with unknown molecular structure. Here we describe the analysis of the assembly of native and mutant forms of lumazine synthases from Bacillus subtilis and Aquifex aeolicus at various pH values and in the presence of different buffers using small angle X-ray scattering and electron microscopy. Both wild-type lumazine synthases are able to form capsids with a diameter of roughly 160 A and larger capsids with diameters of around 300 A. The relative abundance of smaller and larger capsids is strongly dependent on buffer and pH. Both forms can co-exist and are in some cases accompanied by other incomplete or deformed capsids. Several mutants of the B. subtilis lumazine synthase, in which residues in or close to the active site were replaced, as well as an insertion mutant of A. aeolicus lumazine synthase form partially or exclusively larger capsids with a diameter of about 300 A. The mutations also reduce or inhibit enzymatic activity, suggesting that the catalytic function of the enzyme is tightly correlated with its quaternary structure. The data show that multiple assembly forms are a general feature of lumazine synthases.

Bacillus subtilis↗
PubMed2006

E1A promoter of bovine adenovirus type 3.

Conserved motifs of eukaryotic gene promoters, such as TATA box and CAAT box sequences, of E1A of human adenoviruses (e.g human adenovirus 5) lie between the left inverted terminal repeat (ITR) and the ATG of E1A. However, analysis of the left end of the bovine adenovirus 3 (BAdV-3) genome revealed that the conserved sequences of the E1A promoter are present only in the ITR. As such, the promoter activity of ITR was tested in the context of a BAdV-3 vector or a plasmid-based system. Different regions of the left end of the BAdV-3 genome initiated transcription of the red fluorescent protein gene in a plasmid-based system. Moreover, BAdV-3 mutants in which the open reading frame of E1A was placed immediately downstream of the ITR produced E1A transcript and could be propagated in non-E1A-complementing Madin-Darby bovine kidney cells. These results suggest that the left ITR contains the sole BAdV-3 E1A promoter.

5' Flanking Region↗
PubMed2005

Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2'-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury.

BACKGROUND: Mercury is a ubiquitous and highly toxic environmental pollutant. In this study, we evaluated the relationship between mercury exposure and oxidative stress, serum and urinary mercury concentrations, oxidative DNA damage, and serum redox status in chronically mercury-exposed persons compared with healthy controls. METHODS: We measured urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), which we used as a biomarker of oxidative DNA damage in the mercury-exposed persons, by HPLC with electrochemical detection (ECD). We evaluated antioxidant status by measuring the activities of superoxide dismutase and glutathione peroxidase and the concentrations of total reduced glutathione and protein-bound thiols in serum. RESULTS: The significant increase in 8-OHdG concentrations in urine indicated that mercury-induced oxidative damage to DNA occurred in vivo. Differences in body mercury burden and antioxidant enzyme activities were statistically significant between the mercury-exposed persons and controls. Serum and urinary mercury concentrations in the mercury-exposed persons were more than 40-fold higher than in controls. CONCLUSIONS: Mercury exposure can induce oxidative DNA damage, whereas the antioxidative repair systems can be expected to minimize DNA lesions caused by mercury. Measurement of urinary 8-OHdG could be useful for evaluating in vivo oxidative DNA damage in mercury-exposed populations.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Multihydroxylated [Gd@C82(OH)22]n nanoparticles: antineoplastic activity of high efficiency and low toxicity.

[Gd@C82(OH)22]n particles (22 nm in a saline solution) of a dose level as low as 10(-7) mol/kg exhibit a very high antineoplastic efficiency ( approximately 60%) in mice. A dose increment of 1 x 10(-7) mol/kg increases the tumor inhibition rate 26%. [Gd@C82(OH)22]n particles have a strong capacity to improve immunity and interfere with tumor invasion in normal muscle cells, nearly without toxicity in vivo and in vitro. Unlike conventional antineoplastic chemicals, the high antitumor efficiency of nanoparticles is not due to toxic effects to cells because they do not kill the tumor cells directly and only about 0.05% of the used dose is found in the tumor tissues. Results suggest that fullerene derivatives with proper surface modifications and sizes may help realize the dream of tumor chemotherapeutics of high-efficacy and low-toxicity.

Animals↗
PubMed2005

Essential elements of the capsid protein for self-assembly into empty virus-like particles of hepatitis E virus.

Hepatitis E virus (HEV) is a noncultivable virus that causes acute liver failure in humans. The virus's major capsid protein is encoded by an open reading frame 2 (ORF2) gene. When the recombinant protein consisting of amino acid (aa) residues 112 to 660 of ORF2 is expressed with a recombinant baculovirus, the protein self-assembles into virus-like particles (VLPs) (T.-C. Li, Y. Yamakawa, K. Suzuki, M. Tatsumi, M. A. Razak, T. Uchida, N. Takeda, and T. Miyamura, J. Virol. 71:7207-7213, 1997). VLPs can be found in the culture medium of infected Tn5 cells but not in that of Sf9 cells, and the major VLPs have lost the C-terminal 52 aa. To investigate the protein requirement for HEV VLP formation, we prepared 14 baculovirus recombinants to express the capsid proteins truncated at the N terminus, the C terminus, or both. The capsid protein consisting of aa residues 112 to 608 formed VLPs in Sf9 cells, suggesting that particle formation is dependent on the modification process of the ORF2 protein. In the present study, electron cryomicroscopy and image processing of VLPs produced in Sf9 and Tn5 cells indicated that they possess the same configurations and structures. Empty VLPs were found in both Tn5 and Sf9 cells infected with the recombinant containing an N-terminal truncation up to aa residue 125 and C-terminal to aa residue 601, demonstrating that the aa residues 126 to 601 are the essential elements required for the initiation of VLP assembly. The recombinant HEV VLPs are potential mucosal vaccine carrier vehicles for the presentation of foreign antigenic epitopes and may also serve as vectors for the delivery of genes to mucosal tissue for DNA vaccination and gene therapy. The results of the present study provide useful information for constructing recombinant HEV VLPs having novel functions.

Animals↗
PubMed2005

Structure and assembly of a T=1 virus-like particle in BK polyomavirus.

In polyomaviruses the pentameric capsomers are interlinked by the long C-terminal arm of the structural protein VP1. The T=7 icosahedral structure of these viruses is possible due to an intriguing adaptability of this linker arm to the different local environments in the capsid. To explore the assembly process, we have compared the structure of two virus-like particles (VLPs) formed, as we found, in a calcium-dependent manner by the VP1 protein of human polyomavirus BK. The structures were determined using electron cryomicroscopy (cryo-EM), and the three-dimensional reconstructions were interpreted by atomic modeling. In the small VP1 particle, 26.4 nm in diameter, the pentameric capsomers form an icosahedral T=1 surface lattice with meeting densities at the threefold axes that interlinked three capsomers. In the larger particle, 50.6 nm in diameter, the capsomers form a T=7 icosahedral shell with three unique contacts. A folding model of the BKV VP1 protein was obtained by alignment with the VP1 protein of simian virus 40 (SV40). The model fitted well into the cryo-EM density of the T=7 particle. However, residues 297 to 362 of the C-terminal arm had to be remodeled to accommodate the higher curvature of the T=1 particle. The loops, before and after the C-terminal short helix, were shown to provide the hinges that allowed curvature variation in the particle shell. The meeting densities seen at the threefold axes in the T=1 particle were consistent with the triple-helix interlinking contact at the local threefold axes in the T=7 structure.

BK Virus↗
PubMed2005

Protection of mammalian cells from severe acute respiratory syndrome coronavirus infection by equine neutralizing antibody.

The aetiological agent for severe acute respiratory syndrome (SARS) has been determined to be a new type of coronavirus (SARS-CoV) that infects a wide range of mammalian hosts. Up to now, there have been no specific drugs to protect against SARS-CoV infection, thus developing effective strategies against this newly emerged viral infection warrants urgent efforts. Adoptive immune therapy with pathogen-specific heterologous immunoglobulin has been successfully used to control the dissemination of many viral infections. To investigate whether a neutralizing antibody against SARS-CoV raised in an artiodactylous host can have a protective role on primate cells, we prepared serum IgGs and their pepsin-digested F(ab')2 fragments from horses inoculated with purified SARS-CoV (BJ-01 strain). The protective effect of the F(ab')2 fragments against SARS-CoV infection was determined in cultured Vero E6 cells by cytopathic effect (CPE), MTT and plaque-forming assays and in a Balb/c mouse model by CPE and quantitative RT-PCR. The results showed the neutralization titres of F(ab')2 from three horses all reached at least 1:1600, and 50 microg of the F(ab')2 fragments could completely neutralize 1x10(4) TCID50- SARS-CoV in vivo. Additionally, we observed that F(ab')2, against BJ-01 strain could also protect cells from infection by the variant GZ-01 strain in vitro and in vivo. Our work has provided experimental support for testing the protective equine immunoglobulin in future large primate or human trials.

Animals↗
PubMed2004

Promoter activity of left inverted terminal repeat and downstream sequences of porcine adenovirus type 3.

Early region 1 (E1) of porcine adenovirus type 3 (PAdV-3) consists of E1A and E1B transcription units. The authentic promoter region of E1A contains a TATA box at nucleotide position (nt) 449 and a bifunctional regulatory element between nt 374 and 431, which enhances the transcription of E1A, but represses that of E1B. Here, we investigated the role of the left inverted terminal repeat (ITR) and its downstream sequences (between nt 151 and 312) in the transcription of early viral genes, and viral replication. Mutant PAdV-3s without the authentic E1A promoter region could be rescued by transfection of mutant genomic DNA into fetal porcine retina cells. Moreover, the mutant PAdV-3s produced E1A-specific mRNA and remained viable in swine testis (ST) cells suggesting that the left-terminal 151 bp including the ITR, can serve as a promoter for E1A expression. However, mutant PAdV-3s containing deletion including authentic E1A promoter region, displayed both reduced steady-state levels of early gene mRNAs (E1A, E1B, E2A, E3, and E4) and decreased rate of viral replication in ST cells. Interestingly, mutant PAdV-3s containing the left-terminal 312 bp displayed increased transcription of early genes including E1A. Our results suggest that the left ITR of PAdV-3 contain the promoter like elements and the sequences (between nt 151 and 312) downstream of left ITR can enhance its promoter activity.

Adenovirus E1A Proteins↗
PubMed2004

Influence of molecular flexibility and polar surface area metrics on oral bioavailability in the rat.

The relationship of rotatable bond count (N(rot)) and polar surface area (PSA) with oral bioavailability in rats was examined for 434 Pharmacia compounds and compared with an earlier report from Veber et al. (J. Med. Chem. 2002, 45, 2615). N(rot) and PSA were calculated with QikProp or Cerius2. The resulting correlations depended on the calculation method and the therapeutic class within the data superset. These results underscore that such generalizations must be used with caution.

Administration, Oral↗
PubMed2004

cis-Acting packaging motifs of porcine adenovirus type 3.

The cis-acting packaging domain is required for selective encapsidation of adenovirus DNA into preformed empty capsids late in the viral life cycle. Earlier, it was demonstrated that the cis-acting packaging domain of porcine adenovirus type (PAdV)-3 is located between nucleotide position (nt) 212 and 531 at the left end genome which contains six AT/GC rich motifs. Removal of packaging domain from left end to the right end of the genome produced a viable mutant virus suggesting that the identified cis-acting packaging domain represents the DNA sequences required for selective packaging of PAdV-3 DNA, whose position and orientation appear to be flexible. Here, by constructing and analyzing a panel of virus mutants carrying deletions or linker scanning mutations in AT/GC rich sequences, we examined the significance of the continuous A/T or G/C sequences individually in the viral packaging process. In contrast to consensus bipartite structure (5'-TTTGN8CG-3') described for most of packaging motifs of human adenovirus type 5 (HAdV-5), the packaging motifs I, II, III, and IV of PAdV-3 displayed a tripartite structure in which the continuous A/T nucleotides were flanked by G/C-rich sequences. Mutations in both continuous A/T nucleotides and its flanking GC-rich sequences reduced the packaging efficiency of mutants to varying degrees. In addition, although the continuous A/T sequences were present in all of the packaging motifs, their significance in the packaging process appears to vary within each packaging motif.

Adenoviruses, Human↗
PubMed2004

Viral RNAs detected in virions of porcine adenovirus type 3.

It has been demonstrated that cellular and viral RNAs were packaged in the virions of human cytomegalovirus (CMV) and herpes simplex virus 1 (HSV 1), members of the Herpesviridae family, both of which are enveloped double-stranded DNA viruses. Here, we provide evidence suggesting that RNAs are packaged in the virions of porcine adenovirus type 3 (PAdV-3), which is a member of the Adenoviridae family, a non-enveloped double-stranded DNA virus. The RNAs packaged in PAdV-3 virions were enriched in the size range of 300-1000 bases long. By reverse transcription (RT) of RNAs isolated from purified PAdV-3 virions, PCR amplification, and DNA sequence analysis of PCR products, we determined the identities of some viral RNAs contained in PAdV-3 virions. The results indicated that the RNAs representing transcripts from E1A, E1B, DNA binding protein (DBP), DNA polymerase (POL), E4 and some of the late genes including pIIIA, pIII, pV, Hexon, 33 K, and fiber were detected from purified PAdV-3 virions. In contrast, we could not detect the RNAs representing transcripts of precursor terminal protein (pTP), 52 kDa, pX, or 100-kDa protein genes in purified virions. Because the transcripts of pIX, IVa2, E3, protease, pVI, pVII, and pVIII overlap with those of other genes in PAdV-3, we could not definitely conclude that RNAs representing these transcripts were packaged in virions although the expected DNA fragments were produced by RT-PCR in the RNAs isolated from purified virions.

Adenovirus E1A Proteins↗
PubMed2004

Porcine adenovirus type 3 E1 transcriptional control region contains a bifunctional regulatory element.

We identified a bifunctional regulatory element located between nt 374 and 431 upstream of TATA box of porcine adenovirus (PAV) 3 E1A promoter. Deletion of the element dramatically reduced the steady-state level of E1A mRNA, but increased that of E1B, which lies immediately downstream of E1A. The mutant virus displayed defective replication at early times of infection, but replicated nearly as efficiently as wild-type PAV-3 at late times of infection. This defect was complemented with coinfecting wild-type virus in a mixed infection. The results indicated that the upstream activation sequences (UAS) of E1A overlap the upstream repression sequences (URS) of E1B, although both transcription units are transcribed from different promoters.

Adenovirus E1A Proteins↗
PubMed2004

Evaluation and application of multiple scoring functions for a virtual screening experiment.

In order to identify novel chemical classes of factor Xa inhibitors, five scoring functions (FlexX, DOCK, GOLD, ChemScore and PMF) were engaged to evaluate the multiple docking poses generated by FlexX. The compound collection was composed of confirmed potent factor Xa inhibitors and a subset of the LeadQuest screening compound library. Except for PMF the other four scoring functions succeeded in reproducing the crystal complex (PDB code: 1FAX). During virtual screening the highest hit rate (80%) was demonstrated by FlexX at an energy cutoff of -40 kJ/mol, which is about 40-fold over random screening (2.06%). Limited results suggest that presenting more poses of a single molecule to the scoring functions could deteriorate their enrichment factors. A series of promising scaffolds with favorable binding scores was retrieved from LeadQuest. Consensus scoring by pair-wise intersection failed to enrich the hit rate yielded by single scorings (i.e. FlexX). We note that reported successes of consensus scoring in hit rate enrichment could be artificial because their comparisons were based on a selected subset of single scoring and a markedly reduced subset of double or triple scoring. The findings presented in this report are based upon a single biological system and support further studies.

Animals↗
PubMed2004

Enhanced cellular receptor usage by a bioselected variant of coxsackievirus a21.

Decay-accelerating factor (DAF) functions as cell attachment receptor for a wide range of human enteroviruses. The Kuykendall prototype strain of coxsackievirus A21 (CVA21) attaches to DAF but requires interactions with intercellular cell adhesion molecule 1 (ICAM-1) to infect cells. We show here that a bioselected variant of CVA21 (CVA21-DAFv) generated by multiple passages in DAF-expressing, ICAM-1-negative rhabdomyosarcoma (RD) cells acquired the capacity to induce rapid and complete lysis of ICAM-1-deficient cells while retaining the capacity to bind ICAM-1. CVA21-DAFv binding to DAF on RD cells mediated lytic infection and was inhibited by either antibody blockade with a specific anti-DAF SCR1 monoclonal antibody (MAb) or soluble human DAF. Despite being bioselected in RD cells, CVA21-DAFv was able to lytically infect an additional ICAM-1-negative cancer cell line via DAF interactions alone. The finding that radiolabeled CVA21-DAFv virions are less readily eluted from surface-expressed DAF than are parental CVA21 virions during a competitive epitope challenge by an anti-DAF SCR1 MAb suggests that interactions between CVA21-DAFv and DAF are of higher affinity than those of the parental strain. Nucleotide sequence analysis of the capsid-coding region of the CVA21-DAFv revealed the presence of two amino acid substitutions in capsid protein VP3 (R96H and E101A), possibly conferring the enhanced DAF-binding phenotype of CVA21-DAFv. These residues are predicted to be embedded at the interface of VP1, VP2, and VP3 and are postulated to enhance the affinity of DAF interaction occurring outside the capsid canyon. Taken together, the data clearly demonstrate an enhanced DAF-using phenotype and expanded receptor utilization of CVA21-DAFv compared to the parental strain, further highlighting that capsid interactions with DAF alone facilitate rapid multicycle lytic cell infection.

Animals↗