[Adiponectin ameliorated pancreatic islet mitochondrial injury induced by chronic intermittent hypoxia].

Objective: To explore the effect of adiponectin (APN) on islet injury induced by chronic intermittent hypoxia (CIH). Methods: Thirty-six SD rats were randomly divided into three groups: Normal control (NC), CIH, and CIH + APN groups. The rats in the CIH and CIH+APN groups received an intermittent hypoxia exposure while the rats in NC group received the room air only. The rats in CIH+APN group received the intravenous injection of APN. The intermittent hypoxia events persisted 8 hours a day and last for 35 days. The fasting blood glucose and fasting insulin were detected at the time of 0, 7, 14, 21, 28, and 35 day. After 35 days, the level of serum adiponectin, and adenosine triphosphate (ATP) level, superoxide dismutase (SOD), malondialdehyde (MDA), the mRNA levels of mitochondrial oxidative phosphorylation function and mitochondrial synthesis gene, and the protein level of mitochondrial and cytoplasmic cytochrome C of pancreatic islet were detected. Results: The glucose and insulin level had no statistically differences among three groups at different time points (all P>0.05). However, compared with NC and CIH+APN groups, CIH reduced the serum adiponectin [(7 265±2 209) ng/ml, (6 536±1 678) ng/ml vs (4 923±1 742) ng/ml, both P<0.05], ATP levels [(30.92±1.12) nmol/mg, (26.55±0.72) nmol/mg vs (20.22±1.47) nmol/mg, both P<0.05], mRNA levels of mitochondria oxidative phosphorylation function and mitochondrial synthesis gene, the activity of SOD, and the rate of mitochondrial/cytoplasmic cytochrome C protein level while increased the MDA level in pancreatic islet. Compared with NC group, the MDA level increased (P<0.05) and the APN level had no statistically difference, while the level of other indicators decreased in CIH+APN group (all P<0.05). Conclusion: APN ameliorates the pancreatic islet injury induced by CIH through inhibition of oxidative stress.

Survival prediction with score model based on clinical characteristics in advanced HCC patients receiving oxaliplatin-containing regimens.

A score model based on clinical characteristics in advanced hepatocellular carcinoma (HCC) patients treated with systemic chemotherapy of oxaliplatin-containing regimens was established to evaluate progression-free survival (PFS) and overall survival (OS). Thirty HCC patients eligible for radical resection were involved in the retrospective study, and these were divided into the good response group (complete response (CR)/partial response (PR) and the poor response group (stable disease (SD)/progression disease (PD). The median PFS and OS were compared in the two groups. PFS and OS combined with clinical characteristics were evaluated by univariate and multivariate analyses. The score model was defined with 1 score for each characteristic, and score model cut-off values were determined by the receiver operating characteristic curve (ROC) which describes treatment response. The median PFS was 10 and 2 months (p<0.001), and the median OS was 13 and 4 months (p=0.011) for the CR/PR and SD/PD groups, respectively. The score of 1 was the optimal cutoff value, with sensitivity ranging from 52.6 to 63.2% and specificity from 81.8 to 100% (AUC= 0.773, p=0.014). The median PFS for good and poor response groups was 9 months and 1month (p<0.001) and the median OS was 22 and 3months at p<0.001, respectively. Patients with scores above 1 had poor response, with median 3 months OS and 1 month PFS, and patients with scores of 0 and 1 established good response, with median 22 months OS and 9 months PFS, respectively.

[Risk factors of central neck lymph node metastasis in cN0 papillary thyroid carcinoma].

Objective:To investigate the risk factors of central neck lymph node metastasis (CNLNM) in cN0 papillary thyroid carcinoma. Method:Retrospective analysis of 114 patients with papillary thyroid carcinoma in stage of cN0 who underwent primary treatment. Collected the clinical and pathological data, used the univariate and multivariate analysis to investigate the risk factors of central neck lymph node metastasis and high volume central neck lymph node metastasis.Result:In the univariate analysis, age (48.2% in<45 years vs 27.6% in≥45 years), multifocal (51% with vs 27.7% without), nodular goiter (58.8% with vs 28.7% without), showed significant difference in prevalence of CNLNM. Age (14.3% in<45 years vs 1.7% in≥45 years), tumor size (19.2% >1 cm vs 4.5%≤1 cm) showed significant difference in prevalence of high volume CNLNM. Inmultivariate analysis, age (RR= 0.304), multifocal (RR= 3.637) and nodular goiter (RR= 4.132) showed the independent risk factor of CNLNM.Conclusion:For cN0 patients with thyroid papillary carcinoma, if the age is younger than 45 years old, the tumor is multifocal, or associatedwith nodular goiter, the surgery should be more aggressive in the prophylactic central neck dissection.

[Laryngeal undifferentiated soft-tissue sarcoma: a case report and review of literature].

Patient presented as a 74-year-old male complaining of hoarseness. Electronic laryngoscope showed a neoplasm whose size was about 1.0 cm×0.5 cm×0.5 cm at anterior commissure. A surgery was conducted to excise the neoplasm en bloc. The histopathological and immunohistochemistry examination suggested inflammatory myofibroblastic tumor. A month later, the patient presented with dyspnea and blood-stained sputum. CT scan of neck showed an occupation lesions under glottis. A tracheotomy and a CO2 laser surgery was conducted due to patient's will. The histopathological and immunohistochemistry examination suggested undifferentiated sarcoma. We advised him keeping a tracheal cannula to receive further treatment such as radiotherapy or chemotherapy in oncology department, but the patient was not compliant with care instructions for personal reason. He was readmitted 2 months later for dyspnea after plugging the tube. Electronic laryngoscope showed a large neoplasm occupied the laryngeal vestibule, covering the glottis. CT and MRI scan showed the lesion involved spaces of supraglottic, glottic, subglottic and soft tissue around larynx. Hence, a total laryngotomy and bilateral functional neck dissection was conducted. The histopathological examination agreed with the former one. Three weeks later, the skin around his tracheal cannula swelled,ulcerated and pyorrheal. After 10 days of dressing change, patient died of uncontrolled infection.

Bayesian tomography and integrated data analysis in fusion diagnostics.

In this article, a Bayesian tomography method using non-stationary Gaussian process for a prior has been introduced. The Bayesian formalism allows quantities which bear uncertainty to be expressed in the probabilistic form so that the uncertainty of a final solution can be fully resolved from the confidence interval of a posterior probability. Moreover, a consistency check of that solution can be performed by checking whether the misfits between predicted and measured data are reasonably within an assumed data error. In particular, the accuracy of reconstructions is significantly improved by using the non-stationary Gaussian process that can adapt to the varying smoothness of emission distribution. The implementation of this method to a soft X-ray diagnostics on HL-2A has been used to explore relevant physics in equilibrium and MHD instability modes. This project is carried out within a large size inference framework, aiming at an integrated analysis of heterogeneous diagnostics.

Inversion of infrared imaging bolometer based on one-dimensional and three-dimensional modeling in HL-2A.

Linear regularization has been applied to the HL-2A infrared imaging bolometer to reconstruct local plasma emission with one-dimensional (1D) and three-dimensional (3D) modeling under the assumption of toroidal symmetry. In the 3D modeling, a new method to calculate the detector point response function is introduced. This method can be adapted to an arbitrarily shaped pinhole. With the full 3D treatment of the detector geometry, up to 50% of the mean-squared error is reduced compared with the 1D modeling. This is attributed to the effects of finite detector size being taken into account in the 3D modeling. Meanwhile, the number of the bolometer pixels has been optimized to 20 × 20 by making a trade-off between the number of bolometer pixels and the sensitivity of the system. The plasma radiated power density distributions have been calculated as a demonstration using 1D modeling and 3D modeling, respectively.

QTL verification of grain protein content and its correlation with oil content by using connected RIL populations of high-oil maize.

Maize with high grain protein and oil contents offers great advantages for human food and animal feed. In this study, grain protein contents of 282 and 263 F7:8 recombinant inbred lines (RILs) of 2 crosses were evaluated in 4 environments within and between populations. The RILs were developed from crosses between an inbred high-oil maize line and 2 normal dent inbred maize lines. A total of 16 single-population QTLs and 19 joint-population QTLs were identified for protein content, and 21 QTLs were detected for protein-oil in each of the 4 environments tested and in combination. Most of the QTLs for protein content were greatly influenced by variation among populations and environments. Seven QTLs showed generational consistency compared with QTLs detected in the 2 F2:3 populations. However, 7 and 6 QTLs were detected in only the RIL and F2:3 populations, respectively. Protein and protein-oil QTLs with the same parental effects were detected at bins 3.03-3.05, 5.04-5.06, 6.03-6.05, 8.03-8.04, and 8.04-8.06, demonstrating that tightly linked and/or pleiotropic QTLs are controlling both traits at these bins. Four single-population QTLs and 11 joint-population QTLs identified at bins 3.02-3.03, 3.05, 7.01, 8.02, 8.03, 8.04-8.05, 8.05, 9.03, and 9.05 with intervals <5 cM could be used in marker-assisted selection. Along with the previously detected QTLs qPRO1-8-1 and qPRO1-5-1 at bins 8.03-8.04 and 5.02-5.04, the QTLs detected herein could be used to develop near isogenic lines and chromosome segment substitution lines in future studies.

Genome-wide multilocus analysis of intraspecific differentiation in Oryza rufipogon Griff. from China and the influence of introgression from O. sativa L.

Twenty-five populations of Oryza rufipogon from China and 144 cultivars of Oryza sativa were selected for this study. Based on the DNA fragment of Ehd1-4 and subspecies-specific sequence-tagged site markers in different chromosomes, intraspecific differentiation in O. rufipogon from China was analyzed. The introgression from O. sativa to O. rufipogon was also analyzed based on simple sequence repeat markers. The results revealed that the DNA fragment of Ehd1-4 could distinguish the O. sativa subspecies japonica and indica. Furthermore, although significant indica-japonica differentiation did not occur in most O. rufipogon populations from China, O. rufipogon varieties from Hainan Island and from the mainland of China showed differentiation tendencies. Japonica-like O. rufipogon varieties were predominant in Mainland China. However, more indica-like O. rufipogon varieties were found in Hainan Island. Finally, although cultivar-specific alleles were found in most of the O. rufipogon varieties from Hainan Island and Guangdong Province, some varieties remain pure and non-introgressive.

Minimum Fisher regularization of image reconstruction for infrared imaging bolometer on HL-2A.

An infrared imaging bolometer diagnostic has been developed recently for the HL-2A tokamak to measure the temporal and spatial distribution of plasma radiation. The three-dimensional tomography, reduced to a two-dimensional problem by the assumption of plasma radiation toroidal symmetry, has been performed. A three-dimensional geometry matrix is calculated with the one-dimensional pencil beam approximation. The solid angles viewed by the detector elements are taken into account in defining the chord brightness. And the local plasma emission is obtained by inverting the measured brightness with the minimum Fisher regularization method. A typical HL-2A plasma radiation model was chosen to optimize a regularization parameter on the criterion of generalized cross validation. Finally, this method was applied to HL-2A experiments, demonstrating the plasma radiated power density distribution in limiter and divertor discharges.

Time-frequency analysis for microwave reflectometry data processing in the HL-2A tokamak.

The Choi-Williams distribution (CWD) technique is introduced as a time-frequency tool for processing data measured from the new developed homodyne and the fixed frequency reflectometry in the HL-2A tokamak. The comparison between spectrogram and CWD for the simulated signal is presented. It indicates that the CWD can greatly improve the representation of the time-frequency content of the multi-components signal. Its effectiveness is demonstrated through two applications in HL-2A, which are the extraction of beat frequencies from the frequency modulated-continuous wave reflectometry (FM-CW) and the characterizing of the fluctuations. The density profile inversed from the group delay of the FM-CW and the density fluctuations deduced from the fixed-frequency reflectometry would be more reliable and accurate by using the CWD technique.

Observation of turbulence suppression after electron-cyclotron-resonance-heating switch-off on the HL-2A tokamak.

The formation of a transient internal transport barrier (ITB) is observed after the electron-cyclotron-resonance-heating (ECRH) switch-off in the HL-2A plasmas, characterized by transient increase of central electron temperature. The newly developed correlation reflectometer provided direct measurements showing reduction of turbulence in the region of steepened gradients for the period of ITB formation triggered by the ECRH switch-off. Furthermore, the reduction of core turbulence is correlated in time with the appearance of a low-frequency mode with a spectrally broad poloidal structure that peaks near zero frequency in the core region. These structures have low poloidal mode number, high poloidal correlation, and short radial correlation and are strongly coupled with high-frequency ambient turbulence. Observation indicates that these structures play important roles in the reduction of the core turbulence and in improvements of the core transport after the off-axis ECRH is turned off.

Identification of trait-improving quantitative trait loci for grain yield components from a dent corn inbred line in an advanced backcross BC2F2 population and comparison with its F2:3 population in popcorn.

Normal maize germplasm could be used to improve the grain yield of popcorn inbreds. Our first objective was to locate genetic factors associated with trait variation and make first assessment on the efficiency of advanced backcross quantitative trait locus (AB-QTL) analysis for the identification and transfer of favorable QTL alleles for grain yield components from the dent corn inbred. A second objective was to compare the detection of QTL in the BC2F2 population with results using F(2:3) lines of the same parents. Two hundred and twenty selected BC2F2 families developed from a cross between Dan232 and an elite popcorn inbred N04 were evaluated for six grain yield components under two environments, and genotyped by means of 170 SSR markers. Using composite interval mapping (CIM), a total of 19 significant QTL were detected. Eighteen QTL had favorable alleles contributed by the dent corn parent Dan232. Sixteen of these favorable QTL alleles were not in the same or near marker intervals with QTL for popping characteristics. Six QTL were also detected in the F(2:3) population. Improved N04 could be developed from 210 and 208 families with higher grain weight per plant and/or 100-grain weight, respectively, and 35 families with the same or higher popping expansion volume than N04. In addition, near isogenic lines containing detected QTL (QTL-NILs) for grain weight per plant and/or 100-grain weight could be obtained from 12 families. Our study demonstrated that the AB-QTL method can be applied to identify and manipulate favorable QTL alleles from normal corn inbreds and combine QTL detection and popcorn breeding efficiently.

Diagnostic strategies in CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited autosomal dominant condition characterized by migraine, recurrent stroke, and dementia. It results from mutations in the notch3 gene but mutations may occur at multiple sites making molecular diagnosis time consuming. It has been suggested that the presence of granular osmiophilic material (GOM) on skin biopsy and involvement of the anterior temporal lobe and external capsule on MRI may help in diagnosis. METHODS: The authors identified 83 potential index cases from the British population and screened exons 2 to 23 of notch3. MRI scans were scored using a modified Scheltens scale. Skin biopsy was performed in a subgroup. RESULTS: Fifteen different point mutations were identified in 48 families, 73% of which were in exon 4, 8% in exon 3, and 6% in each of exons 5 and 6. Moderate or severe involvement of the anterior temporal pole on MRI had a sensitivity of 89% and specificity of 86% for diagnosis of CADASIL, whereas external capsule involvement had a high sensitivity of 93% but a low specificity of 45%. Skin biopsy, performed in 18 cases, had a sensitivity of 45% and specificity of 100%. CONCLUSIONS: The spectrum of mutations in this study can be used to plan appropriate screening protocols; a suggested protocol is to screen exon 4, and proceed to exons 3, 5, and 6 where indicated. GOM on skin biopsy is diagnostic but can be negative. Anterior temporal pole involvement on MRI is a useful diagnostic marker.

T594M mutation of the beta-subunit of the epithelial sodium channel in Ghanaian populations from Kumasi and London and a possible association with hypertension.

We have tested 186 individuals from Ghana, 95 indigenous and 91 who have settled in the United Kingdom, for the presence of the T594M mutation in the beta-subunit of the epithelial sodium channel, which is associated with hypertension in black populations. The group living in Ghana had a mean age of 27 years and were normotensive, but had an increased frequency of the T allele compared to the London-based population. If this is reflected in larger studies, and the link with hypertension is maintained in the Ghanaian population, this mutation could be a significant cause of hypertension in Ghana.

E2F-1 up-regulates c-Myc and p14(ARF) and induces apoptosis in colon cancer cells.

Although overexpression of E2F-1 can induce apoptosis in a variety of tumor cell lines, the mechanisms by which E2F-1 induces apoptosis remain ambiguous. In this study, we examine the ability of E2F-1 to induce apoptosis in colon cancer and the molecular mechanisms underlying E2F-1-mediated apoptosis. HT-29 and SW-620 colon adenocarcinoma cells (both mutant p53) were treated by mock infection or adenoviral vectors Ad5CMV (empty vector), Ad5CMVLacZ (beta-galactosidase), and Ad5CMVE2F-1 (E2F-1) at multiplicity of infection of 100. Western blot analysis confirmed marked overexpression of E2F-1 in both cell lines. By 5 days after infection, E2F-1 overexpression resulted in >25-fold reduction in cell growth and >90% loss of cell viability in both cell lines. Cell cycle analysis of Ad-E2F-1-infected cells revealed an increase in G(2)/M and sub-G(1) populations. By in situ terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling analysis, evidence of apoptosis was observed including internucleosomal DNA fragmentation and the formation of apoptotic bodies. In addition, caspase-3 and poly(ADP-ribose) polymerase apoptotic fragments were detected by 48 h after treatment with Ad-E2F-1. Of mechanistic importance, overexpression of E2F-1 caused a G(2)/M arrest followed by increased levels of c-Myc and p14(ARF) proteins. Additionally, expression of the antiapoptotic Bcl-2 family member Mcl-1 was down-regulated in E2F-1-overexpressing cells. In conclusion, E2F-1 overexpression initiates apoptosis and suppresses growth in HT-29 and SW620 colon adenocarcinoma cells. Overexpression of E2F-1 triggers apoptosis and is associated with up-regulation of c-Myc and p14(ARF) proteins and down-regulation of Mcl-1. Therefore, E2F-1 is a potentially active gene therapy agent for the treatment of colon cancer.

T594M and G442V polymorphisms of the sodium channel beta subunit and hypertension in a black population.

Polymorphisms of the epithelial sodium channel may raise blood pressure by increasing renal sodium reabsorption. This study examines frequency distributions and associations with hypertension of the T594M and of the G442V polymorphisms of the beta subunit of the epithelial sodium channel in a population-based sample. We studied a stratified random sample of 459 subjects (279 women), aged 40-59 years, of black African origin from general practices' lists within a defined area of South London. All were first generation immigrants. The polymorphic variants were detected using single strand conformational polymorphism technique (SSCP). The prevalence of hypertension (BP > or =160 and/or 95 mm Hg or on drug therapy) was 43%; of these, 76% were on drug therapy. The main analysis was carried out by three ordered blood pressure categories (I to III) according to increasing blood pressure and presence or absence of drug therapy. The frequency of the 594M variant (heterozygotes and homozygotes) was 4.6%; the frequency of the 442V variant was higher (27.0%). The frequency of the 594M variant increased with increasing blood pressure category (P = 0.05) and was more common in hypertensives than normotensives. By contrast the frequency of the 442V variant did not vary across increasing blood pressure categories (P = 0.62). No gender difference was observed. Adjustment for age, sex and body mass index did not alter these findings. These results suggest that the 594M variant may contribute to high blood pressure in black people of African origin whereas the G442V polymorphism is unlikely to influence blood pressure in this population.

Additive effect of adenovirus-mediated E2F-1 gene transfer and topoisomerase II inhibitors on apoptosis in human osteosarcoma cells.

Recently, it has been demonstrated that Etoposide, a topoisomerase II inhibitor, can induce apoptosis in MDM2-overexpressing tumor cells by inhibition of MDM2 synthesis. We have previously shown that E2F-1 overexpression induces apoptosis of MDM2-overexpressing sarcoma cells, which is related to the inhibition of MDM2 expression. Therefore, the present study was designed to investigate the in vitro and in vivo effect of combined treatment of adenovirus-mediated E2F-1 and topoisomerase II inhibitors on the growth inhibition and apoptosis in human sarcoma cells. Two human sarcoma cell lines, OsACL and U2OS, were treated with topoisomerase II inhibitors (Etoposide and Adriamycin), alone or in combination with adenoviral vectors expressing beta-galactosidase (Ad-LacZ) or E2F-1 (Ad-E2F-1). E2F-1 expression was confirmed by Western blot analysis. Ad-E2F-1 gene transfer at a low dose (multiplicity of infection, 2) markedly increased the sensitivity of human sarcoma cells to topoisomerase II inhibitor treatment. This cooperative effect of E2F-1 and topoisomerase II inhibitors was less marked in SAOS-2 cells (p53 and pRb null). Topoisomerase II inhibitors also cooperated with E2F-1 overexpression to enhance tumor cell killing in an in vivo model using xenografts in nude mice. When combined with Adriamycin or Etoposide, E2F-1 adenovirus therapy resulted in approximately 95% and 85% decrease in tumor size, respectively, compared to controls (P<.05). These results suggest a new chemosensitization strategy that is effective in MDM2-overexpressing tumors and may have clinical utility.

Two versatile N,N'-bipyridine-type ligands for preparing organic-inorganic coordination polymers: new cobalt- and nickel-containing framework materials.

The Schiff base ligands 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene (L1, monoclinic, P2(1)/c, a = 3.856(1) A, b = 11.032(2) A, c = 12.738(3) A, beta = 92.21(3) degrees, Z = 2) and 2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene (L2, monoclinic, P2(1)/c, a = 10.885(2) A, b = 4.613(1) A, c = 14.978(3) A, beta = 92.827(4) degrees, Z = 2) were used in the synthesis of four new organic-inorganic coordination polymers, each of them adopting a different structural motif. Synthesis, X-ray structural determinations, and spectroscopic and thermogravimetric analyses are presented. The reaction between Co(NO(3))(2).6H(2)O and L1 afforded a two-dimensional noninterpenetrating brick-wall structure, [Co(C(12)N(4)H(10))(1.5)(NO(3))(2)(H(2)O)(CH(2)Cl(2))(2)](n)() (1, triclinic, P1; a = 10.242(7) A, b = 10.802(7) A, c = 15.100(1) A, alpha = 70.031(1), beta = 75.168(11), gamma = 76.155(11), Z = 2), while Ni(NO(3))(2).6H(2)O combined with L1 yielded an interpenetrating three-dimensional rhombus-grid polymer, [Ni(C(12)N(4)H(10))(2)(NO(3))(2)(OC(4)H(8))(1.66)(H(2)O)(0.33)](n) (2, monoclinic, C2/c; a = 20.815(8) A, b = 23.427(8) A, c = 17.291(6) A, beta = 116.148(6), Z = 8). The reaction of Co(NO(3))(2).6H(2)O and L2 was found to be solvent-sensitive and resulted in the formation of two different noninterpenetrating compounds: [Co(C(14)N(4)H(14))(2)(NO(3))(2)(C(6)H(6))(1.5)](n)() (3, monoclinic, C2/c; a = 22.760(2) A, b = 21.010(3) A, c = 25.521(2) A, beta = 97.151(2), Z = 8), which adopts a two-dimensional square-grid motif formed by propeller-type modules, and [Co(C(14)N(4)H(14))(1.5)(NO(3))(2)(CH(2)Cl(2))(2)](n)() (4, monoclinic, P2(1)/n; a = 14.432(2) A, b = 14.543(8) A, c = 15.448(4) A, beta = 96.968(0), Z = 4), consisting of T-shaped building blocks assembled into a one-dimensional ladder-type structure. These four coordination polymers all exhibit impressive thermal stability. Thermogravimetric studies showed that after complete removal of the solvents, the frameworks are stable to temperatures between 234 degrees C and 260 degrees C.