Current development of high-performance transparent conductive oxide (TCO) films is limited with tradeoff between carrier mobility and concentration since none of them can be improved without sacrificing the other. In this study, we prepare fluorine doped tin oxide (FTO) films by chemical vapor deposition with inclusions of different additives and report that the mobility can be varied from 0.65 to 28.5 cm2 V−1 s−1 without reducing the achieved high carrier concentration of 4 × 1020 cm−3. Such an increase in mobility is shown to be clearly associated with the development of (200) preferred orientation (PO) but concurrent degradation of (110) PO in films. Thus, at a constant high carrier concentration, the electrical conductivity can be improved via carrier mobility simply by PO control. Such a one-step approach avoiding conventional post-deposition treatment is suggested for developing next-generation FTO as well as other TCO films with better than ever conductivities.
Twinning on the plane is a common mode of plastic deformation for hexagonal-close-packed metals. Here we report, by monitoring the deformation of submicron-sized single-crystal magnesium compressed normal to its prismatic plane with transmission electron microscopy, the reorientation of the parent lattice to a ‘twin’ lattice, producing an orientational relationship akin to that of the conventional twinning, but without a crystallographic mirror plane, and giving plastic strain that is not simple shear. Aberration-corrected transmission electron microscopy observations reveal that the boundary between the parent lattice and the ‘twin’ lattice is composed predominantly of semicoherent basal/prismatic interfaces instead of the twinning plane. The migration of this boundary is dominated by the movement of these interfaces undergoing basal/prismatic transformation via local rearrangements of atoms. This newly discovered deformation mode by boundary motion mimics conventional deformation twinning but is distinct from the latter and, as such, broadens the known mechanisms of plasticity.
Deformation twinning and dislocations are known to govern the plastic behaviour of metals at room temperature. Here the authors demonstrate a new deformation mechanism in single-crystal magnesium characterized by twin-like crystal reorientation and special interfaces.
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with a 5-year survival rate less than 15%. Understanding of the molecular mechanisms involved in the pathogenesis of ESCC becomes critical to develop more effective treatments.
Mcl-1 expression was measured by reverse transcription (RT)-PCR and Western blotting. Human Mcl-1 promoter activity was evaluated by reporter gene assay. The interactions between DNA and transcription factors were confirmed by electrophoretic mobility shift assay (EMSA) in vitro and by chromatin immunoprecipitation (ChIP) assay in cells.
Four human ESCC cell lines, TE-1, Eca109, KYSE150 and KYSE510, are revealed increased levels of Mcl-1 mRNA and protein compare with HaCaT, an immortal non-tumorigenic cell line. Results of reporter gene assays demonstrate that human Mcl-1 promoter activity is decreased by mutation of kappaB binding site, specific NF-kappaB inhibitor Bay11-7082 or dominant inhibitory molecule DNMIkappaBalpha in TE-1 and KYSE150 cell lines. Mcl-1 protein level is also attenuated by Bay11-7082 treatment or co-transfection of DNMIkappaBalpha in TE-1 and KYSE150 cells. EMSA results indicate that NF-kappaB subunits p50 and p65 bind to human Mcl-1-kappaB probe in vitro. ChIP assay further confirm p50 and p65 directly bind to human Mcl-1 promoter in intact cells, by which regulates Mcl-1 expression and contributes to the viability of TE-1 cells.
Our data provided evidence that one of the mechanisms of Mcl-1 expression in human ESCC is regulated by the activation of NF-kappaB signaling. The newly identified mechanism might provide a scientific basis for developing effective approaches to treatment human ESCC.
Esophageal squamous cell carcinoma; Gene regulation; NF-κB; Mcl-1; Cell viability
Side population (SP) cells are previously identified from bone marrow based on their capacity to efflux of the fluorescent dye Hoechst 33342. Recent studies demonstrate that SP cells isolated from various cancer cell lines and primary tumors possess stem-cell-like properties. Thus, targeting tumor SP cells may provide new strategies for treatment in clinic. We previously showed that 1,3,8-trihydroxy-6-methylanthraquinone (emodin), a reactive oxygen species (ROS) generator, enhanced sensitivity of gallbladder cancer SGC-996 cells to cisplatin (CDDP) via generation of ROS and downregulation of multidrug-resistance-associated protein 1 (MRP1). To determine whether emodin also acts effectively on cancer stem cells of gallbladder carcinoma, we use SP cells as a model of cancer stem-cell-like cells. Here, we found that emodin, via ROS-related mechanism and suppressing the function of ATP-binding cassette super-family G member (ABCG2), which is known to be associated with Hoechst dye efflux activity of SP cells, not only reduced the ratio, inhibited clone formation, and eliminated sphere formation of SP cells effectively, but also promoted obviously the intracellular accumulation of doxorubicin, the main substrate of the efflux pump ABCG2. In addition, emodin could sensitize CDDP, via inhibition of expression of ABCG2, to overcome chemoresistance of SP cells. Importantly, similar to the experiment in vitro, emodin/CDDP co-treatment in vivo suppressed the tumor growth derived from SP cells through downregulating ABCG2 expression. Our results suggest that emodin is an effective agent targeting cancer stem-like SP cells of gallbladder carcinoma, either alone or acts as a chemotherapy enhancer.
In a previous study, we generated two monoclonal antibodies (mAbs) in mice, aNogoA-N and aNogo-66 mAb, which were raised against recombinant N-terminal fragments of rat NogoA and Nogo-66, respectively. When compared with the commercial rabbit anti-rat NogoA polyclonal antibody (pAb), which can specifically recognise NogoA, the two mAbs were also specific for the NogoA antigen in immunofluorescence histochemical (IHC) staining and Western blot (WB) analysis. Serial truncations of NogoA covering the N-terminal region of NogoA (aa 570–691) and Nogo-66 (aa 1026–1091) were expressed in E. coli. The epitopes recognised by aNogoA-N and aNogo-66 are located in the aa 634–668 and aa 1026–1055 regions of NogoA, respectively. Both mAbs remarkably enhanced the axon growth and branching of cultured hippocampal neurons in vitro. These results suggest that the antibodies that bind to aa 634–668 and aa 1026–1055 of NogoA may have stimulatory effects on axon growth and branching. Additionally, the two mAbs that we generated are specific for NogoA and significantly block NogoA function. In conclusion, two sites in NogoA located within aa 634–668 and aa 1026–1055 are recognised by our two antibodies and are novel and potentially promising targets for repair after central nervous system (CNS) injury.
To use direct comparative studies or randomised controlled trials to compare the accuracy of cardiac magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) for the detection of obstructive coronary artery disease (CAD).
Materials and Methods
Various databases were searched for original articles published prior to June 2013. Studies were selected that performed both CMR and SPECT in the same or randomised patients to detect CAD and that presented sufficient data to allow construction of contingency tables. For each study, the true-positive, false-positive, true-negative, and false-negative values were extracted or derived, and 2×2 contingency tables were constructed. To reduce heterogeneity, the meta-analysis was carried out in two parts: (1) coronary territory-based analysis and (2) patient-based analysis.
10 studies (5 studies based on patient, 4 studies based on coronary territory, and 1 study based on both) were included in the meta-analysis with a total of 1727 patients. The methodological quality was moderate. For part (1), the summary estimates were as follows: for CMR based on patient–a sensitivity of 0.79 (95% confidence interval: 0.72–0.84) and a specificity of 0.75 (0.65–0.83); for SPECT based on patient–a sensitivity of 0.70 (0.59–0.79) and a specificity of 0.76 (0.66–0.83). For part (2), the summary estimates for CMR based on coronary territory were a sensitivity of 0.80 (0.73–0.85) and a specificity of 0.87 (0.81–0.91), and the summary estimates for SPECT based on coronary territory were a sensitivity of 0.67 (0.60–0.72) and a specificity of 0.80 (0.75–0.84).
Compared with SPECT, CMR is more sensitive to detect CAD on a per-patient basis. Nonetheless, large scale, well-designed trials are necessary to assess its clinical value on a per-coronary territory basis.
To investigate the amplitude of low-frequency fluctuations (ALFF) alteration of whole brain in patients with subcortical ischemic vascular dementia (SIVD).
Materials and Methods
Thirty patients with SIVD and 35 control subjects were included in this study. All of them underwent structural MRI and rs-fMRI scan. The structural data were processed using the voxel-based morphometry 8 toolbox (VBM8). The rs-fMRI data were processed using Statistical Parametric Mapping (SPM8) and Data Processing Assistant for Resting-State fMRI (DPARSF) software. Within-group analysis was performed with a one-sample Student's t-test to identify brain regions with ALFF value larger than the mean. Intergroup analysis was performed with a two-sample Student's t-test to identify ALFF differences of whole brain between SIVD and control subjects. Partial correlations between ALFF values and Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores were analyzed in the SIVD group across the parameters of age, gender, years of education, and GM volume.
Within-group analysis showed that the bilateral anterior cingulate cortex (ACC), posterior cingulate cortex, medial prefrontal cortex (MPFC), inferior parietal lobe (IPL), occipital lobe, and adjacent precuneus had significantly higher standardized ALFF values than the global mean ALFF value in both groups. Compared to the controls, patients with SIVD presented lower ALFF values in the bilateral precuneus and higher ALFF values in the bilateral ACC, left insula and hippocampus. Including GM volume as an extra covariate, the ALFF inter-group difference exhibited highly similar spatial patterns to those without GM volume correcting. Close negative correlations were found between the ALFF values of left insula and the MoCA and MMSE scores of SIVD patients.
SIVD is associated with a unique spontaneous aberrant activity of rs-fMRI signals, and measurement of ALFF in the precuneus, ACC, insula, and hippocampus may aid in the detection of SIVD.
Caspase-8 (CASP8) plays a central role in the apoptotic pathway and aberrant regulation of this pathway may cause cancers. Previous studies investigating the association between CASP8 -652 6N ins/del polymorphism and colorectal cancer (CRC) risk showed inconclusive results. We performed a meta-analysis of all available studies to investigate this association.
All studies published up to October 2013 on the association between CASP8 -652 6N ins/del polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between CASP8 -652 6N ins/del polymorphism and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).
Six studies with 6,325 cases and 6,842 controls were included in the meta-analysis. We observed that the CASP8 -652 6N ins/del polymorphism was significantly correlated with CRC risk when all studies were pooled into the meta-analysis (ins/del vs. ins/ins: OR = 0.890, 95%CI 0.821–0.964, P = 0.004; del/del + ins/del vs. ins/ins: OR = 0.899, 95%CI 0.833–0.970, P = 0.006). In stratified analyses by ethnicity, source of control, and quality score, significant association was observed in Asians (ins/del vs. ins/ins: OR = 0.862, 95%CI 0.761–0.977, P = 0.020; del/del + ins/del vs. ins/ins: OR = 0.845, 95%CI 0.749–0.953, P = 0.006), population-based studies (ins/del vs. ins/ins: OR = 0.890, 95%CI 0.813–0.975, P = 0.012; del/del + ins/del vs. ins/ins: OR = 0.901, 95%CI 0.827–0.982, P = 0.018), and high quality studies. However, in subgroup analysis according to cancer location, no significant association was detected.
The present meta-analysis suggests that the CASP8 is a candidate gene for CRC susceptibility. The CASP8 -652 6N ins/del polymorphism may play a protective role in CRC development especially among Asians. Further large and well-designed studies are needed to confirm this association.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances immune responses by inducing dendritic cell proliferation, maturation, and migration and B and T lymphocyte expansion and differentiation. The potency of DNA vaccines can be enhanced by the addition of DNA encoding cytokines, acting as molecular adjuvants. We conducted a phase I/II trial of human GM-CSF DNA in conjunction with a multipeptide vaccine (gp100 and tyrosinase) in stage III/IV melanoma patients. Nineteen human leukocyte antigen (HLA)-A*0201(+) patients were treated. Three dose levels were studied: 100, 400, and 800 mcg DNA/injection, administered subcutaneously (SQ) every month with 500 mcg of each peptide. In the dose-ranging study, 3 patients were treated at each dose level. The remaining patients were then treated at the highest dose. Most toxicities were grade 1 injection site reactions. Eight patients (42%) developed CD8+ T-cell responses, defined by a ≥3 SD increase in baseline reactivity to tyrosinase or gp100 peptide in tetramer or intracellular cytokine staining assays. There was no relationship between dose and T-cell response. Responding T cells had an effector memory cell phenotype. Polyfunctional T cells were also demonstrated. At a median of 31 months follow-up, median survival has not been reached. Human GM-CSF DNA was found to be a safe adjuvant.
This review summarizes major advances in biomarker discovery for diagnosis, differential diagnosis, and progression of Parkinson’s disease (PD), with emphasis on neuroimaging and biochemical markers. Potential strategies to develop biomarkers capable of predicting PD in the prodromal stage before the appearance of motor symptoms or correlating with nonmotor symptoms, an active area of research, are also discussed.
Parkinson disease; biomarkers; neuroimaging; proteomics; metabolomics; prodromal diagnosis
rabies; rabies virus; viruses; zoonoses; China; Henan Province
Pd(II)-catalyzed enantioselective C–H activation of phenylacetic acids followed by an intramolecular C–O bond formation afforded chiral benzofuranones. This reaction provides the first example of enantioselecctive C–H functionalizations through Pd(II)/Pd(IV) redox catalysis.
Diabetes is an ambulatory care sensitive condition that can generally be managed in outpatient settings with little or no need for inpatient care. As a preliminary step to investigate whether health disparities can be detected in the inpatient setting in China, we study how diabetic patients hospitalized without prior primary care contact or with greater severity of illness differ from other diabetic inpatients along socioeconomic and clinical dimensions.
We conduct an observational study using three years of clinical data for more than 1,800 adult patients with diabetes at two tertiary hospitals in East China. Univariate analysis and probit regression are used to characterize the differences in socioeconomic and clinical factors between patients hospitalized for diabetes with no prior primary care contact and those hospitalized with previous treatment experience. Secondarily, we use ordinary least squares regression to estimate the socioeconomic and clinical differences associated with poor serum glucose control at admission.
We find that compared with patients hospitalized after prior treatment experience, inpatients with no previous primary care contact for diabetes have worse clinical laboratory values, are more likely to be young and male, to have lower education attainment, and to have poorer blood sugar control. Insurance, urban residence, and previous use of diabetic medication are in turn negatively correlated with HbA1c levels upon admission.
Among hospitalized diabetic patients, socioeconomic factors such as lower education attainment, rural residence and lack of full insurance are associated with avoidable hospitalizations or worse indicators of health. Although we cannot definitively rule out selection bias, these findings are consistent with health disparities observable even at the inpatient level. Future studies should study the underlying mechanism by which traditionally vulnerable groups are more likely to be hospitalized for avoidable causes and with greater severity of illness.
Diabetes; China; Equity; Social gradient; Preventable hospitalizations; Ambulatory care sensitive conditions
Little is known about the clinical features and treatment of Chinese patients with Parkinson disease (PD).
A large cross-sectional survey of clinical features, medication use, and motor complications was conducted in 901 consecutive PD patients, from 42 randomly selected university-affiliated hospitals in four urban economic regions of China, between December 2006 and May 2007.
The 901 PD patients had age range 30 to 88, and median disease duration 50 months. Most (737, 81.8%) used L-dopa (median 375 mg/day), and often added low doses of other antiparkinsonian agents. Among L-dopa-treated patients, the prevalence of motor complications was low (dyskinesias: 8.5%; motor fluctuations: 18.6%), even among patients with disease duration ≥11 years (dyskinesias: 18.1%; motor fluctuations: 42.2%). Higher L-dopa use was associated with higher occurrence of dyskinesias (OR 2.44; 95% CI 1.20-5.13) and motor fluctuations (OR 2.48; 95% CI 1.49-4.14). Initiating PD treatment with L-dopa alone (OR 0.46; 95% CI 0.22-0.95) or in combination with other medications (OR 0.41; 95% CI 0.19-0.87) was associated with less dyskinesia than treatment initiated with non-L-dopa medication.
Many Chinese PD patients are treated with low-dose L-dopa and added low-dose antiparkinsonian agents, with a low prevalence of motor complications, which might be influenced by Chinese culture.
Parkinson disease; Treatment, Dyskinesias; Motor fluctuations, China
Accurately ranking docking poses remains a great challenge in computer-aided drug design. In this study, we present an integrated approach called MIEC-SVM that combines structure modeling and statistical learning to characterize protein–ligand binding based on the complex structure generated from docking. Using the HIV-1 protease as a model system, we showed that MIEC-SVM can successfully rank the docking poses and consistently outperformed the state-of-art scoring functions when the true positives only account for 1% or 0.5% of all the compounds under consideration. More excitingly, we found that MIEC-SVM can achieve a significant enrichment in virtual screening even when trained on a set of known inhibitors as small as 50, especially when enhanced by a model average approach. Given these features of MIEC-SVM, we believe it provides a powerful tool for searching for and designing new drugs.
We present a compact (130 μm cladding diameter) trench-assisted multi-orbital-angular-momentum (OAM) multi-ring fiber with 19 rings each supporting 22 modes with 18 OAM ones. Using the high-contrast-index ring and trench designs, the trench-assisted multi-OAM multi-ring fiber (TA-MOMRF) features both low-level inter-mode crosstalk and inter-ring crosstalk within a wide wavelength range (1520 to 1630 nm), which can potentially enable Pbit/s total transmission capacity and hundreds bit/s/Hz spectral efficiency in a single TA-MOMRF. Moreover, the effective refractive index difference of even and odd fiber eigenmodes induced by the ellipticity of ring and fiber bending and their impacts on the purity of OAM mode and mode coupling/crosstalk are analyzed. It is found that high-order OAM modes show preferable tolerance to the ring ellipticity and fiber bending. The designed fiber offers favorable tolerance to both small ellipticity of ring (<−22 dB crosstalk under an ellipticity of 0.5%) and small bend radius (<−20 dB crosstalk under a bend radius of 2 cm).
There is no official consensus regarding zinc therapy in pre-symptomatic children with Wilson Disease (WD); more data is needed.
To investigate the safety and efficacy of zinc gluconate therapy for Chinese children with pre-symptomatic WD.
We retrospectively analyzed pre-symptomatic children receiving zinc gluconate in a single Chinese center specialized in pediatric hepatology. Short-term follow-up data on safety and efficacy were presented, and effects of different zinc dosages were compared.
30 children (21 males) aged 2.7 to 16.8 years were followed for up to 4.4 years; 26 (87%) children had abnormal ALT at baseline. Most patients (73%) received higher than the currently recommended dose of elemental zinc. Zinc gluconate significantly reduced mean ALT (p<0.0001), AST (p<0.0001), GGT (p<0.0001) levels after 1 month, and urinary copper excretion after 6 months (p<0.0054). Mean direct bilirubin levels dropped significantly at 1 month (p = 0.0175), 3 months (p = 0.0010), and 6 months (p = 0.0036). Serum zinc levels gradually increased and reached a significantly higher level after 6 months (p<0.0026), reflecting good compliance with the therapy. Complete blood count parameters did not change throughout the analysis period. 8 children experienced mild and transient gastrointestinal side effects. The higher zinc dose did not affect treatment response and was not associated with different or increased side effects when compared to conventional zinc dose.
In our cohort, zinc gluconate therapy for Chinese children with pre-symptomatic WD was effective, and higher initial dose of elemental zinc had the same level of efficacy as the conventional dose.
Binswanger's disease (BD) is a common cause of vascular dementia in elderly patients; however, few studies have investigated the medial temporal lobe (MTL) atrophy in BD, and the differences in the atrophic patterns between BD and Alzheimer's disease (AD) remain largely unknown. Such knowledge is essential for understanding the pathologic basis of dementia. In this study, we collected structural magnetic resonance imaging (MRI) data from 16 normal controls, 14 patients with AD and 14 patients with BD. The volumes of the hippocampus and amygdala, and morphologic parameters (volume, surface area, cortical thickness and mean curvature) of the entorhinal cortex (ERC) and perirhinal cortex (PRC) were calculated using an automated approach. Volume reduction of the hippocampus, amygdala and ERC, and disturbance of the PRC curvature was found in both AD and BD patients compared with the controls (p<0.05, uncorrected). There were no significant differences among all the structural measures between the AD and BD patients. Finally, partial correlation analyses revealed that cognitive decline could be attributed to ERC thinning in AD and volume reduction of PRC in BD. We conclude that AD and BD exhibit similar atrophy patterns in the medial temporal cortices and deep gray matter but have distinct pathologic bases for cognitive impairments. Although atrophy of the MTL structures is a sensitive biomarker for AD, it is not superior for discrimination between AD and BD.
Hepatitis B virus (HBV) infection and its sequelae are now recognized as serious problems globally. Our aime is to screen hepatocellular carcinoma (HCC) from chronic hepatitis B (CHB) and identify the characteristics of proteins involved.
We affinity-purified sample serum with weak cation-exchange (WCX) magnetic beads and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis to search for potential markers. The 4210 Da protein, which differed substantially between HCC and CHB isolates, was later identified to be eukaryotic peptide chain release factor GTP-binding subunit eRF3b. Further research showed that eRF3b/GSPT2 was positively expressed in liver tissues. GSPT2 mRNA was, however differentially expressed in blood. Compared with normal controls, the relative expression of GSPT2/18s rRNA was higher in CHB patients than in patients with either LC or HCC (P = 0.035 for CHB vs. LC; P = 0.020 for CHB vs. HCC). The data of further research showed that eRF3b/GSPT2 promoted the entrance of the HepG2 cells into the S-phase and that one of the substrates of the mTOR kinase, 4E-BP1, was hyperphosphorylated in eRF3b-overexpressing HepG2 cells.
Overall, the differentially expressed protein eRF3b, which was discovered as a biomarker for HCC, could change the cell cycle and influence the phosphorylation status of 4E-BP1 on Ser65 in HepG2.
The quality of reporting in systematic reviews (SRs)/meta-analyses (MAs) of diagnostic tests published by authors in China has not been evaluated. The aims of present study are to evaluate the quality of reporting in diagnostic SRs/MAs using the PRISMA statement and determine the changes in the quality of reporting over time.
According to the inclusion and exclusion criteria, we searched five databases including Chinese Biomedical Literature Database, PubMed, EMBASE, the Cochrane Library, and Web of knowledge, to identify SRs/MAs on diagnostic tests. The searches were conducted on July 14, 2012 and the cut off for inclusion of the SRs/MAs was December 31st 2011. The PRISMA statement was used to assess the quality of reporting. Analysis was performed using Excel 2003, RevMan 5.
A total of 312 studies were included. Fifteen diseases systems were covered. According to the PRISMA checklist, there had been serious reporting flaws in following items: structured summary (item 2, 22.4%), objectives (item 4, 18.9%), protocol and registration (item 5, 2.6%), risk of bias across studies (item 15, 26.3%), funding (item 27, 28.8%). The subgroup analysis showed that there had been some statistically significant improvement in total compliance for 9 PRISMA items after the PRISMA was released, 6 items were statistically improved regarding funded articles, 3 items were statistically improved for CSCD articles, and there was a statistically significant increase in the proportion of reviews reporting on 22 items for SCI articles (P<0.050).
The numbers of diagnostic SRs/MAs is increasing annually. The quality of reporting has measurably been improved over the previous years. Unfortunately, there are still many deficiencies in the reporting including protocol and registration, search, risk of bias across studies, and funding. Future Chinese reviewers should address issues on these aspects.
It is widely known that castration has a significant effect on the accumulation of adipose tissue. microRNAs (miRNAs) are known to be involved in fat deposition and to be regulated by the androgen-induced androgen receptor (AR). However, there is little understanding of the relationship between miRNAs and fat deposition after castration. In this study, the high-throughput SOLiD sequencing approach was used to identify and characterize miRNA expression in backfat from intact and castrated full-sib male 23-week-old pigs. The patterns of adipogenesis and fat deposition were compared between castrated and intact male pigs.
A total of 366 unique miRNA genes were identified, comprising 174 known pre-miRNAs and 192 novel pre-miRNAs. One hundred and sixty-seven pre-miRNAs were common to both castrated (F3) and intact (F4) male pig small RNA libraries. The novel pre-miRNAs encoded 153 miRNAs/miRNA*s and 141 miRNAs/miRNA*s in the F3 and F4 libraries, respectively. One hundred and seventy-seven miRNAs, including 45 up- and 132 down-regulated, had more than 2-fold differential expression between the castrated and intact male pigs (p-value < 0.001). Thirty-five miRNAs were further selected, based on the expression abundance and differentiation between the two libraries, to predict their targets in KEGG pathways. KEGG pathway analyses suggested that miRNAs differentially expressed between the castrated and intact male pigs are involved in proliferation, apoptosis, differentiation, migration, adipose tissue development and other important biological processes. The expression patterns of eight arbitrarily selected miRNAs were validated by stem-loop reverse-transcription quantitative polymerase chain reaction. These data confirmed the expression tendency observed with SOLiD sequencing. miRNA isomiRs and mirtrons were also investigated in this study. Mirtrons are a recently described category of miRNA relying on splicing rather than processing by the microprocessor complex to generate the RNAi pathway. The functions of miRNAs important for regulating fat deposition were also investigated in this study.
This study expands the number of fat-deposition-related miRNAs in pig. The results also indicate that castration can significantly affect the expression patterns of fat-related miRNAs. The differentially expressed miRNAs may play important roles in fat deposition after castration.
Male pig; MicroRNA; Fat deposition; Castration
We design an ultra-compact active hybrid plasmonic ring resonator for lasing applications at deep sub-wavelength scale. The combined contributions of hybrid plasmonic mode, circular-shaped cross section of nanowire, and ring resonator structure with round-trip whispering-gallery cavity, benefit reduced metallic absorption loss, tight mode confinement, enhanced cavity feedback, achieving high quality factor (Q), small mode volume (V), high Purcell factor (Fp), low threshold gain (Gth), and ultra-small footprint with sub-micron size. The performance dependence on the geometrical parameters, including gap height (Hg), cross section radius (Rc), and ring radius (Rr), are comprehensively analyzed, showing high Q factor of 1650 (Hg = 30 nm, Rc = 100 nm, Rr = 800 nm), ultra-small mode volume of 0.0022 μm3 (Hg = 5 nm, Rc = 100 nm, Rr = 800 nm), cut off of all photonic modes for pure plasmonic mode lasing with Rc<70 nm (Hg = 10 nm, Rr = 800 nm), maximum Purcell factor of 813 and minimum threshold gain of 1407 cm−1 (Hg = 5 nm, Rc = 50 nm, Rr = 400 nm). The general design rules of the presented hybrid plasmonic ring resonator provide the potential to further extend ultra-compact sub-micron lasing applications (i.e. different lasing wavelength band) with proper choice of gain materials and geometric structures.
Accurate detection and determination of axillary lymph node metastasis are crucial for the clinical management of patients with breast cancer. Noninvasive imaging methods including ultrasound (US), computed tomography (CT), or conventional magnetic resonance imaging (MRI) are not yet accurate enough. The purpose of this study was to investigate the value of in vivo T2* in differentiating metastatic from benign axillary lymph nodes in patients with breast cancer.
In this institutional review board approved study, 35 women with breast cancer underwent multi-echo T2* weighted imaging (T2*WI) of the axillary area on a 3.0 T clinical magnetic resonance (MR) imaging system. T2* values of pathologically proven benign and metastatic axillary lymph nodes were calculated and compared. Receiver operating characteristics (ROC) analysis was conducted to evaluate the diagnostic ability. The areas under the ROC curve (AUCs) and the confidence intervals (CIs) were assessed. In total, 56 metastatic and 65 benign axillary lymph nodes were identified in this study. For metastatic lymph nodes, the average T2* value (55.96±11.87 ms) was significantly longer than that of the benign lymph nodes (26.00±5.51 ms, P<0.05). The AUC of T2* in differentiating benign from metastatic lymph nodes was 0.993. The cut-off value of 37.5 milliseconds (ms) gave a sensitivity of 94.6%, a specificity of 98.5%, a positive predictive value of 98.17 and a negative predictive value 95.54.
In vivo T2* can differentiate benign from metastatic axillary lymph nodes in patients with breast cancer. The high sensitivity and specificity as well as the easiness suggest its high potential for use in clinical practice.
Cathepsin D C224T polymorphism has been reported to associate with AD susceptibility. But the results were inconsistent. This study aimed to assess the relationship between C224T polymorphism and AD risk.
The relevant studies were identified by searching PubMed, Embase, Web of Science, Google Scholar and Wan fang electronic databases updated on July 2013. The relationship between Cathepsin D C224T polymorphism and AD risk was evaluated by ORs and 95% CIs.
A total of 25 case-control studies including 5,602 cases and 11,049 controls were included in the meta-analysis. There was no association between C224T polymorphism and AD risk with all the studies were pooled in the meta-analysis (CT vs. CC: OR = 1.125, 95% CI = 0.974-1.299, P = 0.109; CT + TT vs. CC: OR = 1.136, 95% CI = 0.978-1.320, P = 0.094). Furthermore, when stratified by ethnicity, age of onset and APOEϵ4 status, significant association did not found in all subgroups.
The present meta-analysis suggested that the Cathepsin D C224T polymorphism was not associated with AD susceptibility.
Cathepsin D; AD; Polymorphism; Meta-analysis
Gemcitabine (Gem)-based chemotherapies are the main therapeutic regimens for patients with unresectable advanced or metastatic gallbladder cancer (GBC). However, the modest ORR and mild benefit on survival demonstrates the need for finding biomarkers for sensitivity to Gem and hence improving the therapy. In present work, two GBC cell lines with vast difference in sensitivity to Gem were subjected to DNA microarray analysis. Dramatic expression difference was found in protein kinase A signaling, P2Y purigenic receptor signaling, ErbB signaling and p70S6K signaling. Predicted low expression of KRAS and inactivation of AKT/ERK signaling in Gem-resistant GBC cells was validated by quantitative PCR and immunoblotting, respectively. However, p70S6K, p38MAPK and NF-κB signaling was probably activated in Gem-resistant GBC cells, which deserves further investigation in more GBC cell lines and tissues. Our work provides potential pathway signatures for Gem sensitivity of GBC patients.
Gallbladder cancer; gemcitabine; DNA microarray analysis; KRAS; AKT signaling; ERK signaling; p38MAPK; p70S6K; NF-κB