Emerging plasmid-mediated quinolone resistance associated with the qnrA gene in Enterobacter cloacae clinical isolates in China.
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China↗
Biomedical subjects
C X Wang
Publications and source records attributed to C X Wang.
Assessment of chronic toxicity and carcinogenicity in an accelerated cancer bioassay in rats of Nifurtimox, an antitrypanosomiasis drug.
The chronic toxicity and carcinogenicity of Nifurtimox (NFX), a 5-nitrofuran derivative used in the treatment of American trypanosomiasis, were studied in male and female Wistar rats in an accelerated cancer bioassay (ACB). The ACB is a mechanistic initiation/promotion chronic toxicity and carcinogenicity bioassay designed to assess potential carcinogenic activity of a test substance in critical organs and tissues of rodents in which human carcinogens are active. The organs studied were liver, lungs, urinary bladder (UB), mammary gland (MG), bone marrow, spleen, kidneys, colon, stomach and any grossly observed lesions. NFX is a genotoxin which has been reported previously to exert a variable degree of carcinogenic activity in rat liver, kidney, UB and MG. The present study was undertaken to assess whether NFX has initiating activity in these four named target sites. In the initiation phase, groups of 20 Wistar rats were given NFX daily in the diet at 0.2% for the first 12 weeks of the study to assess initiating activity, followed by promoters (PROs) for four organs for an additional 24 weeks. NFX was compared to the following known initiators (INs) for each of these four tissues: diethylnitrosamine (DEN) for liver and kidney, N-butyl-N(4-hydroxybutyl)nitrosamine (BBN) for UB and 7,12-dimethylbenz(a)anthracene (DMBA) for MG. PROs included phenobarbital (PB) for liver and kidney, nitrilotriacetic acid (NTA) for UB, and diethylstilbestrol (DES) for MG. NFX was also administered continuously without PROs for 40 weeks. At the end of dosing (40 weeks) and at the end of recovery (52 weeks), animals were sacrificed and subjected to complete gross and histopathological examinations, along with evaluations of body weight gain over time and terminal body weights. Mortality was highest with DEN+PB (group 6) (40%), followed by BBN+NTA (group 7) (15%) and NFX+DES (group 5) and DMBA+DES (group 8) (10% each). The same groups also showed significant reductions in body weight gain over time and terminal body weights at sacrifice. In these groups, the expected preneoplastic, neoplastic and metastatic neoplastic lesions were produced, demonstrating the sensitivity of the model. In groups given NFX+PROs (groups 3-5), either no neoplasms occurred (group 4) or only single neoplasms (groups 3 and 5). In contrast, the PROs all elicited tumors in groups given INs (groups 6-8). Also, NFX given alone for 40 weeks did not produce any chronic toxicity, preneoplastic or neoplastic lesions. Thus, in this study, NFX did not demonstrate chronic toxicity or carcinogenicity. Moreover, in four target sites, i.e., liver, kidney, UB and MG, it exhibited no neoplastic initiating activity manifested by PROs for these four target sites.
Animals↗
Characteristics of neoplasm occurrence and the therapeutic effect of sirolimus in South Chinese kidney transplant recipients.
Kidney transplantation (KTx) recipients are at a higher risk of oncogenesis when compared to the general population. Sirolimus (SRL), a potent immunosuppressant, has shown promising antineoplastic effects in vitro and in vivo. This study retrospectively analyzed the neoplasm occurrence and the efficiency of SRL on unresectable malignancies in South Chinese KTx recipients. Thirty-three (1.64%) of 2017 patients who received KTx from January 1984 to December 2004 developed neoplasms at 4 to 117 months posttransplant, mostly in digestive organs (33.3%), the hematologic system (15.2%), or the skin (12.1%). The most common type was liver cancer (24.2%), followed by skin cancer, lymphoma, and thyroid cancer (9.1%). The median survival times were 41.5 and 6.0 months for those who did (n = 10) receive radical surgery or did not (n = 23), respectively. The 20-month survival rates were 70.0% versus 13.0% (P < .01). For unresectable patients, the median survival time of those treated with SRL (n = 8) was 14.5 months compared to 3.0 months for those who did not (n = 15). The survival rates at 12(th) and 20(th) months were 75.0% and 37.5% in the SRL group and 6.7% and 0% in the non-SRL group (P < .05). In conclusion, when compared with Western studies, a lower incidence and unique location pattern (liver cancer-dominant) are characteristics of de novo posttransplant neoplasms in South Chinese KTx recipients. Early diagnosis and feasible radical surgery are favorable for prognosis, and SRL is a treatment of choice for KTx recipients with neoplasms.
China↗
Origin of diameter-dependent growth direction of silicon nanowires.
A nucleation thermodynamic model was developed to clarify the diameter-dependent crystallographic orientation of silicon nanowires (SiNWs) grown via the vapor-liquid-solid (VLS) mechanism with an Au catalyst. The calculated critical energies (E(r*)) and corresponding critical radii (r*) of the SiNWs with <111> and <110> orientations as a function of Au-catalyst size (D(Au)) revealed that the 110-oriented SiNW with r is preferred below D(Au) = approximately 25 nm, but the preferred direction changes to <111> above D(Au) = approximately 25 nm. The model indicated that the nucleated SiNW with a radius (r) above r is stable and continues to grow until the diameter becomes equal to D(Au) but that the crystallographic orientation is maintained. Thus, the predicted growth direction of the final SiNW with a size of D(Au) is <110> for D(Au) < approximately 25 nm and <111> for D(Au) > approximately 25 nm, which is in excellent agreement with reported experimental results.
Catalysis↗
Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2.
Cyclin-dependent kinase-5 (Cdk5) is required for neuronal survival, but its targets in the apoptotic pathways remain unknown. Here, we show that Cdk5 kinase activity prevents neuronal apoptosis through the upregulation of Bcl-2. Treatment of SH-SY5Y cells with retinoid acid (RA) and brain-derived neurotrophic factor (BDNF) generates differentiated neuron-like cells. DNA damage triggers apoptosis in the undifferentiated cells through mitochondrial pathway; however, RA/BDNF treatment results in Bcl-2 upregulation and inhibition of the mitochondrial pathway in the differentiated cells. RA/BDNF treatment activates Cdk5-mediated PI3K/Akt and ERK pathways. Inhibition of Cdk5 inhibits PI3K/Akt and ERK phosphorylation and Bcl-2 expression, and thus sensitizes the differentiated cells to DNA-damage. Inhibition of ERK, but not PI3K/Akt, abrogates Cdk5-medidated Bcl-2 upregulation and the protection of the differentiated cells. This study suggests that ERK-mediated Bcl-2 upregulation contributes to BDNF-induced Cdk5-mediated neuronal survival.
Apoptosis↗
Thermodynamics of diamond nucleation on the nanoscale.
To have a clear insight into the diamond nucleation upon the hydrothermal synthesis and the reduction of carbide (HSRC), we performed the thermodynamic approach on the nanoscale to elucidate the diamond nucleation taking place in HSRC supercritical-fluid systems taking into account the capillary effect of the nanosized curvature of the diamond critical nuclei, based on the carbon thermodynamic equilibrium phase diagram. These theoretical analyses showed that the nanosize-induced interior pressure of diamond nuclei could drive the metastable phase region of the diamond nucleation in HSRC into the new stable phase region of diamond in the carbon phase diagram. Accordingly, the diamond nucleation is preferable to the graphite phase formation in the competing growth between diamond and graphite upon HSRC. Meanwhile, we predicted that 400 MPa should be the threshold pressure for the diamond synthesis by HSRC in the metastable phase region of diamond, based on the proposed thermodynamic nucleation on the nanoscale.
Journal Article↗
Pre-steady-state kinetics of RB69 DNA polymerase and its exo domain mutants: effect of pH and thiophosphoryl linkages on 3'-5' exonuclease activity.
DNA polymerases from the A and B families with 3'-5' exonucleolytic activity have exonuclease domains with similar three-dimensional structures that require two divalent metal ions for catalysis. B family DNA polymerases that are part of a replicase generally have a more potent 3'-5' exonuclease (exo) activity than A family DNA polymerases that mainly function in DNA repair. To investigate the basis for these differences, we determined pH-activity profiles for the exonuclease reactions of T4, RB69, and phi29 DNA polymerases as representatives of B family replicative DNA polymerases and the Klenow fragment (KF) as an example of a repair DNA polymerase in the A family. We performed exo assays under single-turnover conditions and found that excision rates exhibited by the B family DNA polymerases were essentially independent of pH between pH 6.5 and 8.5, whereas the exo activity of KF increased 10-fold for each unit increase in pH. Three exo domain mutants of RB69 polymerase had much lower exo activities than the wild-type enzyme and exhibited pH-activity profiles similar to that of KF. On the basis of pH versus activity data and elemental effects obtained using short double-stranded DNA substrates terminating in phosphorothioate linkages, we suggest that the rate of the chemical step is reduced to the point where it becomes limiting with RB69 pol mutants K302A, Y323F, and E116A, in contrast to the wild-type enzyme where chemistry is faster than the rate-determining step that precedes it.
Alanine↗
Modelling the mechanical properties of single suspension-cultured tomato cells.
BACKGROUND AND AIMS: The relationship between composition and structure of plant primary cell walls, and cell mechanical properties is not fully understood, partly because intrinsic properties of walls such as Young's modulus cannot be obtained readily. The aim of this work is to show that Young's modulus of walls of single suspension-cultured tomato cells can be determined by modelling force-deformation data. METHODS: The model simulates the compression of a cell between two flat surfaces, with the cell treated as a liquid-filled sphere with thin compressible walls. The cell wall and membrane were taken to be permeable, but the compression was so fast that water loss could be neglected in the simulations. Force-deformation data were obtained by compressing the cells in micromanipulation experiments. RESULTS: Good fits were obtained between the model and low-strain experimental data, using the modulus and initial inflation of the cell as adjustable parameters. The mean Young's modulus for 2-week-old cells was found to be 2.3 +/- 0.2 GPa at pH 5. This corresponds to an instantaneous bulk modulus of elasticity of approx. 7 MPa, similar to a value found by the pressure probe method. However, Young's modulus is a better parameter, as it should depend only on the composition and structure of the cell wall, not on bulk cell behaviour. This new method has been used to show that Young's modulus of cultured tomato cell walls is at its lowest at pH 4.5, the pH optimum for expansin activity. CONCLUSIONS: The linear elastic model is very suitable for estimating wall Young's modulus from micromanipulation experiments on single tomato cells. This is a powerful method for determining cell wall material properties.
Biomechanical Phenomena↗
NXY-059: a neuroprotective agent in acute stroke.
Free radicals play an important role in secondary processes in ischaemic brain injury. Disodium 4-[(tert-butylimino) methyl] benzene-1,3-disulphonate N-oxide (NXY-059) is a nitrone-based free radical trapping agent. Findings from animal stroke models showed that NXY-059 is a potent neuroprotective agent that has a large window of therapeutic opportunity and long-lasting effects. Therefore, NXY-059 may be used as a monotherapy agent for treatment of acute stroke. NXY-059 may also be used as an adjunct agent to thrombolytic therapy, as it can reduce tissue plasminogen activator-induced haemorrhage in ischaemic stroke.
Animals↗
Mechanism of apatite formation on pure titanium treated with alkaline solution.
The mechanism of bone-like apatite formation on the surface of pure titanium pretreated with NaOH solution is still being investigated. The apatite formation may depend on the solution that is used. In the present study, several types of solutions such as simulated body fluid (SBF), calcium aqueous solution (CAS), and phosphate aqueous solution (PAS) were used to investigate bone-like apatite formation on alkali-treated titanium. In order to observe the effect of hydrolysis on the apatite formation, experiments of pretreated titanium immersed in distilled water before the immersion in SBF were also conducted. The results showed that the mechanism of apatite formation was the hydrolysis reaction of sodium titanate which induced the apatite formation. The pre-precipitation of either calcium or phosphate could prevent the apatite formation on the surface of alkaline treated titanium.
Adsorption↗
The transportation, time-dependent distribution of heavy metals in paddy crops.
Sixteen experimenmtal plots (5 m x 6 m = 30 m2) were designed with four different levels of heavy metals (HMs) concentration in soil. The concentrations of heavy metals in soils, and paddy plant during the different periods of growth were investigated. A relationship between the total HM content in plants and the HM level in soil was found for a wide range of concentrations. The exchangeable fraction of HMs extracted with 1 M MgCl2 solution according to Tessier's method increased correlation with the dosage of supplemented HMs, then decreased as time went on. The time-related variation of exchangeable HMs in soil demonstrated that the amount of effective HMs taken up by paddy differed at various growth phases. The amount of HMs accumulated in different parts of paddy followed the order of root > stem > grain, leaf. The transportation potential of the HMs in paddy in present study followed the order of Zn, Cr > Cd, Cu > Pb. The HM content in root, stem and leaf of paddy plant (dry weight) was low at time of seedling. The concentration in the root increased sharply at time of tillering, decreased thereafter. The concentrations in stem and leaf reached the highest at time of tillering, then decreased, while rose slightly at following time.
Biological Transport↗
Nucleation and growth of apatite on chemically treated titanium alloy: an electrochemical impedance spectroscopy study.
Bone-like apatite formed on the surface of Ti6Al4V pretreated with NaOH solution after having been immersed in simulated body fluid (SBF), while no apatite formed on the surface of untreated Ti6Al4V. In the present study, electrochemical impedance spectroscopy (EIS) measurement was used to investigate the nucleation and growth of apatite on chemically treated Ti6Al4V immersed in the SBF solution, and the difference between the behaviors of treated and untreated Ti6Al4V. Appropriate equivalent circuit models were constructed to describe the nucleation and growth of apatite, and thin oxide film formed on the surface of untreated Ti6Al4V. It was found that EIS is a useful method for investigating the nucleation and growth of bone-like apatite on Ti6Al4V pretreated with NaOH solution.
Alloys↗
Self-setting kinetics of new type calcium phosphate bioactive bone cement: a thermokinetics study.
Thermokinetics method was used to study the self-setting kinetics of a new kind of calcium phosphate cement (CPC) in the present study. A calcium-deficient hydroxyapatite CPC was developed by using alpha-TCP and other calcium phosphate bioceramics. The mixing liquids used were deionized water and 0.25 M NaH2PO4/Na2HPO4, respectively. The calorimetric curves, heat evolution curves and total heat evolution in the setting and hardening process of CPC were determined. It has been found that mixing liquids, reaction temperature had influences on the calorimetric curves and heat evolution, and mixing liquids exhibited the greatest influence on the kinetics of CPC during the self-setting and hardening process. Based on the calorimetric curves obtained, the kinetic model equation was simulated, and the reaction control step was determined.
Bone Cements↗
Fizzy-related RNA expression patterns in mammalian development and cell lines.
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Animals↗
Fabrication and characterization of bioactive glass coatings produced by the ion beam sputter deposition technique.
Ion beam sputtering and ion beam sputtering/mixing deposition techniques were used to produce thin bioactive glass coatings on titanium substrate. It was found that as-deposited coatings were amorphous. Scanning electron microscopical examination showed that the coatings had a uniform and dense structure and that fabrication parameters affected the surface morphology of the coatings. The surface Ca/P ratio of the coatings, which varied from 5.9 to 8.6 according to semi-quantitative EDX analyses, was correlated with the fabrication condition. Depth profiling of the coatings revealed four distinct zones: the top surface, the thin coating zone, the intermixed zone of coating and substrate, and the substrate. Scratch tests showed that the coatings adhered well to the substrate.
Journal Article↗
LAS, a novel selective estrogen receptor modulator with chemopreventive and therapeutic activity in the N-nitroso-N-methylurea-induced rat mammary tumor model.
The N-nitroso-N-methylurea-induced rat mammary tumor model was used to conduct two types of studies: a prevention study designed to test the ability of the novel selective estrogen receptor modulator lasofoxifene (LAS) to inhibit the development of mammary tumors, and a treatment study designed to test the inhibitory effect of LAS on the growth of established tumors. The prevention study indicated that LAS markedly delayed the emergence of N-nitroso-N-methylurea-induced tumors to an extent similar to that obtained by the established antiestrogen tamoxifen (TAM). At the highest dose administered, both TAM and LAS reduced tumor incidence by 75% and total tumor number by 90% relative to the controls. LAS also reduced the multiplicity of tumors, i.e., the mean number of tumors per rat, and resulted in substantially smaller total tumor burden. In the treatment study, LAS significantly inhibited tumor growth compared with the controls. In addition, whereas none of the untreated tumors regressed completely over the experimental period, 40% of LAS-treated tumors regressed by >50% at the highest dose (10 mg/kg daily). The results of this study in a rat mammary tumor model indicate that LAS has both chemopreventive and chemotherapeutic effects quantitatively comparable with those of TAM.
Animals↗
An improved version of embolic model of brain ischemic injury in the rat.
A modified version of focal embolic stroke model has been developed in rats. Ischemic injury was induced by injection of a pre-formed clot into the middle cerebral artery (MCA). In the first series of experiments, the model was validated. Embolizing a pre-formed clot resulted in an infarction in the territory irrigated by the MCA. At 48 h after embolization, 2,3,5-triphenyltetrazolium chloride (TTC) staining showed that infarction volume was 42.1+/-15.6% (mean+/-S.D.) when 5 microl clot was injected (n=8) and 28.4+/-8.6% in the animals received 3.5 microl clot (n=8). The infarction volume between these two groups showed a significant difference (P<0.05). In the second series of experiments, the natural dissolution of the clot in the MCA was studied. Five min after embolization (n=6), clots were observed in the MCA of all the animals. Clots in the MCA were seen in 68 and 29% of the animals at 1 and 3 h, respectively, after embolization. These results suggest that the procedure described here produces a reliable and reproducible ischemic injury. The clots injected were dissolved in the MCA in relatively short period of time. The model shows a close similarity to thromboembolic stroke in human, and it provides a useful tool to investigate mechanisms and test thrombolytic agents in ischemic brain injury.
Animals↗
3'-5' Exonucleolytic activity of DNA polymerases: structural features that allow kinetic discrimination between ribo- and deoxyribonucleotide residues.
We have determined rates for the excision of nucleotides from the 3' termini of chimeric DNA-RNA oligonucleotides using the Klenow fragment (KF) and two other DNA polymerases, from phages T4 and T7. For these studies, we synthesized DNA-RNA chimeric oligonucleotides with RNA residues in defined positions. When a ribonucleotide residue was placed at the 3' terminus, all three DNA polymerases removed it at the same rate as they did for substrates composed solely of deoxynucleotide residues. There was a decrease in the excision rate, however, when a ribonucleotide residue was located at the second or third position from the 3' terminus. When both the second and third positions were occupied by ribonucleotide residues, the excision rate for the 3' terminal nucleotide was reduced even further and was almost identical to the rate observed when the DNA polymerases encountered single-stranded RNA. The magnitude of the effect of ribonucleotide residues on the excision rate was lower when Mn(2+) replaced Mg(2+) as the essential divalent cation. Two KF mutations, Y423A and N420A, selectively affected the excision rates for the chimeric substrates. Specifically, Y423A totally abolished the rate reduction when there was a single ribonucleotide residue immediately preceding the 3' terminus, whereas N420A diminished, but did not eliminate, the rate reduction relative to that of wild-type KF when the single ribonucleotide residue occupied either the second or third position from the 3' terminus. These results are consistent with the structure of a KF-ss DNA complex from which it can be deduced, by modeling, that a 2' OH group on the second sugar from the 3' terminus would sterically clash with the Tyr 423 side chain, and a 2' OH group on the third sugar would clash with the side chain of Asn 420. The corresponding mutations in T4 DNA polymerase did not affect the rate of hydrolysis of the chimeric oligonucleotides. Thus, there appears to be a major difference in the kinetic behavior of KF and T4 DNA polymerase with respect to the exonuclease reaction. These results are discussed with respect to their possible biological relevance to DNA replication.
Bacteriophage T4↗