Aims: The best-established mechanism of opioid dependence is the up-regulation of adenylate cyclase (AC)/cAMP pathway, which was reported to be negatively regulated by hydrogen sulfide (H2S), a novel endogenous neuromodulator. The present study was, therefore, designed to determine whether H2S is able to attenuate the development of opioid dependence via down-regulating AC/cAMP pathway. Results: We demonstrated that application of sodium hydrosulphide (NaHS) and GYY4137, two donors of H2S, significantly alleviated naloxone-induced robust withdrawal jumping (the most sensitive and reliable index of opioid physical dependence) in morphine-treated mice. Repeated treatment with NaHS inhibited the up-regulated protein expression of AC in the striatum of morphine-dependent mice. Furthermore, NaHS also attenuated morphine/naloxone-elevated mRNA levels of AC isoform 1 and 8, production of cAMP, and phosphorylation of cAMP response element-binding protein (CREB) in mice striatum. These effects were mimicked by the application of exogenous H2S or over-expression of cystathione-β-synthase, an H2S -producing enzyme, in SH-SY5Y neuronal cells on treatment with [D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin, a selective μ-opioid receptor agonist. Blockade of extracellular-regulated protein kinase 1/2 (ERK1/2) with its specific inhibitor attenuated naloxone-induced CREB phosphorylation. Pretreatment with NaHS or stimulation of endogenous H2S production also significantly suppressed opioid withdrawal-induced ERK1/2 activation in mice striatum or SH-SY5Y cells. Innovation: H2S treatment is important in prevention of the development of opioid dependence via suppression of cAMP pathway in both animal and cellular models. Conclusion: Our data suggest a potential role of H2S in attenuating the development of opioid dependence, and the underlying mechanism is closely related to the inhibition of AC/cAMP pathway. Antioxid. Redox Signal. 20, 31–41.
The complete mitochondrial (mt) genome of the snail Camaena
cicatricosa (Müller, 1774) has been sequenced and annotated in this study. The entire circular genome is 13,843 bp in size and represents the first camaenid mt genome, with content of 31.9%A, 37.9%T, 13.5%C and 16.7%G. Gene content, codon usage and base organization show similarity to a great extent to the sequenced mt genome from Stylommatophora, whereas, gene order is different from them, especially the positions of tRNACys, tRNAPhe, COII, tRNAAsp, tRNAGly, tRNAHis and tRNATrp. All protein coding genes use standard initiation codons ATN except for COII with GTG as start signal. Conventional stop codons TAA and TAG have been assigned to all protein coding genes. All tRNA genes possess the typical clover leaf structure, but the TψC arm of tRNAAsp and dihydrouridine arm of tRNASer(AGN) only form a simple loop. Shorter intergenic spacers have been found in this mt genome. Phylogenetic study based on protein coding genes shows close relationship of Camaenidae and Bradybaenidae. The presented phylogeny is consistent with the monophyly of Stylommatophora.
cicatricosa; Camaenidae; Stylommatophora; mitochondrial genome; secondary structure
Previously we found thymosin β4 (Tβ4) is up-regulated in glomerulosclerosis and required for angiotensin II-induced expression of plasminogen activator inhibitor-1 (PAI-1) in glomerular endothelial cells. Tβ4 has beneficial effects in dermal and corneal wound healing and heart disease yet its effects in kidney disease are unknown. Here we studied renal fibrosis in wild type and PAI-1 knockout mice following unilateral ureteral obstruction to explore the impact of Tβ4 and its prolyl oligopeptidase tetrapeptide degradation product, Ac-SDKP, in renal fibrosis. Additionally, we explored interactions of Tβ4 with PAI-1. Treatment with Ac-SDKP significantly decreased fibrosis in both wild type and PAI-1 knockout mice, as observed by decreased collagen and fibronectin deposition, fewer myofibroblasts and macrophages, and suppressed pro-fibrotic factors. In contrast, Tβ4 plus a prolyl oligopeptidase inhibitor significantly increased fibrosis in wild type mice. Tβ4 alone also promoted repair and reduced late fibrosis in wild type mice. Importantly, both pro-fibrotic effects of Tβ4 plus the prolyl oligopeptidase inhibitor, and late reparative effects of Tβ4 alone, were absent in PAI-1 knockout mice. Thus, Tβ4 combined with prolyl oligopeptidase inhibition, is consistently pro-fibrotic, but by itself, has anti-fibrotic effects in late stage fibrosis, while Ac-SDKP has consistent anti-fibrotic effects in both early and late stages of kidney injury. These effects of Tβ4 are dependent on PAI-1.
Chronic obstructive pulmonary disease (COPD) is characterized by a chronic inflammatory response that is worsened by acute exacerbations. Lianhuaqingwen (LHQW) has anti-inflammatory and immune regulatory functions and may inhibit the airway inflammation that occurs during an acute exacerbation of COPD. In this study, 100 participants were recruited and randomly assigned, 1 : 1, to the LHQW and the conventional groups, which were treated, respectively, with LHQW capsules and conventional Western medicine or only conventional Western medicine. The scores of the CAT scale and levels of inflammatory cytokines in blood and sputum were measured during treatment. In addition, subjects were subdivided into high-risk and low-risk subgroups. The CAT scores in the LHQW group and high-risk subgroup were clearly improved from the 5th day, but the other groups improved only after treatment was completed. Expression levels of IL-8, TNF-α, IL-17, and IL-23 in the sputum and of IL-8 and IL-17 in the blood were significantly decreased after treatment, and similar results were found in subgroups. These data suggested that LHQW capsules can accelerate the improvement of AECOPD patients, especially for the high-risk subgroup, and the mechanism of action may be related to the decreased release of inflammatory mediators.
The house dust mites are major sources of indoor allergens for humans, which induce asthma, rhinitis, dermatitis, and other allergic diseases. Der f 25 is a triosephosphate isomerase, representing the major allergen identified in Dermatophagoides farinae. The objective of this study was to predict the B and T cell epitopes of Der f 25. In the present study, we analyzed the physiochemical properties, function motifs and domains, and structural-based detailed features of Der f 25 and predicted the B cell linear epitopes of Der f 25 by DNAStar protean system, BPAP, and BepiPred 1.0 server and the T cell epitopes by NetMHCIIpan-3.0 and NetMHCII-2.2. As a result, the sequence and structure analysis identified that Der f 25 belongs to the triosephosphate isomerase family and exhibited a triosephosphate isomerase pattern (PS001371). Eight B cell epitopes (11–18, 30–35, 71–77, 99–107, 132–138, 173–187, 193–197, and 211–224) and five T cell epitopes including 26–34, 38–54, 66–74, 142–151, and 239–247 were predicted in this study. These results can be used to benefit allergen immunotherapies and reduce the frequency of mite allergic reactions.
Although the number of convincingly established genetic associations with systemic lupus erythematosus (SLE) has increased sharply over the last few years, refinement of these associations is required, and their potential roles in gene–gene interactions need to be further investigated. Recent genome-wide association studies (GWAS) in SLE have produced renewed interest in B cell/T cell responses and the NF-κB signaling pathway. The aim of this study was to search for possible gene–gene interactions based on identified single-nucleotide polymorphisms (SNPs), in using an approach based on the role of signaling pathways.
The SNPs in BLK, TNFSF4, TRAF1, TNFAIP3, and REL were replicated in order to evaluate genetic associations with SLE. TaqMan genotyping was conducted in 804 Chinese patients with SLE and 722 matched control subjects. A multiple logistic regression model was used to estimate the multiplicative interaction effect of the SNPs, and additive interactions were analyzed by 2 × 2 factorial designs. Data from a previously published GWAS conducted by the International Consortium on the Genetics of Systemic Lupus Erythematosus were derived for comparison and validation.
Single-marker analysis validated the association of BLK rs2736340 (P = 4.25 × 10–6) as well as TNFSF4 rs2205960 (P = 2.82 × 10–5) and TNFAIP3 rs5029939 (P = 1.92 × 10–3) with SLE susceptibility in Chinese. Multiplicative interaction analysis indicated that BLK had an interactive effect with TNFSF4 in Chinese patients with SLE (P = 6.57 × 10–4). Additive interaction analysis revealed interactions between TRAF1 and TNFAIP3 in both Chinese (P = 2.18 × 10–3) and Caucasians (P = 2.86 × 10–4). In addition, multiple tendencies toward interactions were observed, and an additive effect was observed as the number of risk genotypes increased.
The results of this study provide evidence of the possible gene–gene interactions of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in SLE, which may represent a synergic effect of T cells and B cells through the NF-κB pathway in determining immunologic aberration.
To estimate the prevalence of HIV and syphilis, incidence of syphilis and to identify the correlates of syphilis infection among heterosexual male attendees of sexually transmitted infection (STI) clinics (MSC).
A cohort study of one-year duration was conducted in Yangzhou and Changzhou cities in Jiangsu province of China. The baseline survey commenced in June 2009, recruited 1225 consenting adult MSCs (609 in Yangzhou and 617 in Changzhou) through STI-clinic based convenience sampling.
Baseline HIV and syphilis prevalence were 0.49% and 17.29% respectively. Syphilis incidence rate was 7.22 per 100 person-years (6.53 in Yangzhou and 7.76 in Changzhou) during the 6-month follow-up with retention fractions of 27.38% and 35.15% for Yangzhou and Changzhou respectively. Majority of the participants were middle-aged, high school educated, married, living with partners and non-migrants. Very few subjects reported recent and consistent condom-use with regular partners. Although considerable number of MSCs reported recent sexual exposure with female sex workers (FSW) and non-FSW casual partners, the proportion of reported condom use was very low during those exposures. In multivariate analyses higher age, having recent sex with FSWs and being HIV-positive were associated with higher syphilis sero-positivity while higher education was protective. In bivariate analyses, being married, divorced/widowed, official residency of the study cities and non-use of condom with regular partners predicted higher risk.
Considering the potential bridging role of MSCs between high and low-risk populations, effective intervention strategies among them targeting the correlates of syphilis infection are urgently called for in Jiangsu province of China.
The aim of this study was to test the ability of the Chinese version of the Mood Disorder Questionnaire (MDQ) to identify Bipolar Disorders (BD) in patients diagnosed with Major Depressive Disorder (MDD) or Unipolar Disorder (UD) in the clinical setting.
1,487 being treated for MDD or UD at 12 mental health centers across China, completed the MDQ and subsequently examined by the Mini International Neuropsychiatric Interview (MINI). Receiver Operating Characteristic(ROC) curves were used to determine the ability of the MDQ to differentiate between BD (BD, BD-I and BD-II) and MDD or UD and patients with BD-I from patients with BD-II.
Of the 1,487 patients, 309 (20.8%) satisfied the DSM-IV criteria for BD: 118 (7.9%) for BD-I and 191 (12.8%) for BD-II. When only part one of the MDQ was used, the best cutoff was 7 between BD and UD (sensitivity 0.66, specificity 0.88, positive predictive value 0.59, negative predictive value 0.91), 6 between BD-II and UD, and 10 between BD-I and BD-II. If all three parts of the MDQ were used, the MDQ could not distinguish between BD and UD at a cutoff of 7 (or 6), and the sensitivity was only 0.22 (or 0.24).
The Chinese version of the MDQ had good psychometric features in screening bipolar disorders from depressive patients with mood disorders when part two and part three of the MDQ were ignored.
AIM: To investigate the utility of phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) as a noninvasive test for assessment of response to interferon and ribavirin treatment in patients with different severities of hepatitis C virus infection.
METHODS: Sixty chronic hepatitis C patients undergoing antiviral therapy with interferon and ribavirin underwent 31P MRS at 3.0T before treatment, 6 mo after the start of treatment, and 1 year after the start of treatment.
RESULTS: The phosphomonoester (PME)/phosphodiester (PDE) ratio at 6 mo after the start of antiviral therapy in the Child-Pugh B and C groups were significantly higher than those before therapy, but this was not seen in the Child-Pugh A group. In the antiviral therapy group, the PME/PDE ratios had decreased on follow-up MR spectroscopy. However, in the virological nonresponder group, the PME/PDE ratios on follow-up imaging were similar to the baseline values.
CONCLUSION: 31P MRS can be used to provide biochemical information on hepatic metabolic processes. This study indicates that the PME/PDE ratio can be used as an indicator of response to antiviral treatment in chronic hepatitis C patients.
31P; Magnetic resonance spectroscopy; Hepatitis C; Antiviral therapy
Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer mortality worldwide. The development and progression of HCC is a complicated process, involving the deregulation of multiple genes that are essential to cell biological processes. Recently, microRNAs (miRNAs) have been suggested to be closely associated with tumorigenesis. Our study showed that miR-184 is upregulated in HCC cell lines and tissues. Overexpression of miR-184 in HCC cells increased cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-184 reduced cell proliferation, tumorigenicity, and cell cycle progression. Additionally, we identified SOX7 as a direct target of miR-184. Ectopic expression of miR-184 led to downregulation of the SOX7 protein, resulting in upregulation of c-Myc, Cyclin D1, and phosphorylation of Rb. Our findings suggested that miR-184 represents a potential onco-miR and plays an important role in HCC progression by suppressing SOX7 expression.
To investigate the prevalence rate of cigarette smoking and its socio-demographic and clinical correlates in Chinese schizophrenia inpatients receiving antipsychotic mono-therapy.
This study was a cross-sectional, two-site, hospital-based survey. Four hundred and twenty-nine schizophrenia patients (male/female: 66.9% vs. 33.1%) were consecutively recruited from psychosis inpatient wards of two large specialty psychiatric hospitals in mainland China. Patients were assessed using a cigarette smoking questionnaire, the Positive and Negative Symptom Scale, the Simpson Angus Scale, the Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale. Socio-demographic and other clinical data were also collected. We calculated the prevalence of current smoking in our sample as well as its indirectly standardized prevalence ratio (ISPR) using data from the 2010 Global Adult Tobacco Survey in China.
The prevalence rate of current smoking was 40.6% in our sample, and 57.5% in males and 6.3% in females. The ISPRs of all patients, men and women were 1.11(95%CI: 0.95∼1.29), 1.07(95%CI = 0.91∼1.24) and 4.64(95%CI = 2.12∼8.82), respectively. The overall and male-specific prevalence of current smoking did not differ significantly between patients and the general population. In multiple logistic regression analysis, male sex, older age, poor marital status, alcohol use, use of first-generation antipsychotics, longer duration of illness, more frequent hospitalizations, and more severe negative symptoms were independently associated with current smoking.
Male Chinese inpatients with schizophrenia who received a mono-therapy of antipsychotics were not more likely to smoke than the general population. Cigarette smoking is more common in schizophrenia patients with more severe illness.
The purpose of this study was to analyze the ultrasonic elastography features of phyllodes tumors of the breast comparing with fibroadenomas. A retrospective database was queried for the patients diagnosed as phyllodes tumors and fibroadenomas at Sun Yat-sen Memorial Hospital from January 2008 to August 2012. Three hundred and fifty lesions from 323 consecutive patients were included in the study. All the cases were examined by conventional ultrasonography and ultrasound elastography. Ultrasound elastography was used to calculate strain ratio of the lesions with bilateral breast tissue at the same depth as reference. There were 36 phyllodes tumors (27 benign, 8 borderline, 1 malignant) and 314 fibroadenomas (158 the pericanalicular type, 103 the intracanalicular type, 53 other special types). The strain ratio for phyllodes tumors (3.19±2.33) was significantly higher than for fibroadenomas (1.69±0.88) (p<0.05). The Spearman.s correlation coefficient between strain ratio of ultrasound elastography and pathological groups was significant, with a value of 0.17 (p<0.05). Ultrasound elastography could provide additional information to differentiate phyllodes tumors from fibroadenoma in breast.
To estimate the prevalence of sexually transmitted infections (STIs) among female sex workers (FSWs) in the Jiangsu Province, China and measure the association of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections with their potential correlates.
A cross-sectional study on a representative sample of FSWs in Yangzhou and Changzhou cities of Jiangsu was conducted.
185 sex-work venues in Yangzhou and 174 in Changzhou were selected by stratified random sampling. 2972 FSWs (1108 in Yangzhou and 1864 in Changzhou), aged 15 years or more, who agreed to participate and provided blood sample for HIV and syphilis testing were interviewed in these venues. Cervical specimens from 849 randomly chosen participants were then tested for CT and NG.
Proportions of young, school-educated, currently married FSWs who were living alone, migrated from other provinces and engaged in unprotected vaginal intercourse in past 3 months (UVI) were relatively high. Prevalence of HIV, syphilis, CT and NG were 0.20%, 4.88%, 14.61% and 5.42% respectively. Younger age, living alone or with persons other than partners/family members, engaging in UVI and having other STIs seemed to be associated with higher risk of CT or NG infection. Being divorced/widowed and working in middle/low-level venues were identified as additional risk factors for NG.
Based on a representative sample, this initial effort to identify the correlates of CT/NG infections among FSWs of Jiangsu revealed that focused interventions targeting high-risk FSWs are urgently required for controlling STI epidemics in Yangzhou and Changzhou where substantial number of STI cases were identified.
Prohibitin (PHB), also known as inhibin, is important in cell proliferation, differentiation and apoptosis. This protein localizes to the inner membrane of mitochondria, where it acts as a chaperone protein, and is also found in the nucleus, where it negatively regulates transcription. The tumor-suppressive role of PHB in cell proliferation appears to be contradictory. In this study, we investigated the existence, localization and alterations in the expression of PHB in the whole cell and nuclear matrix and analyzed its co-localization with the expression products of related genes. The western blot analysis results revealed that PHB exists in the composition of nuclear matrix proteins and that the expression level of PHB is significantly increased in the whole cell and markedly decreased in the nuclear matrix after curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) treatment. The laser confocal scanning microscope results demonstrated the co-localization of PHB with p53, c-Myc, Bax, and Fas in HaCaT cells, and this co-localization region was transferred as a result of curcumin treatment. In addition, the results of the GST pull-down assay demonstrated the direct interaction of PHB with p53, c-Myc and Bax but not Fas in vitro. Results of the present study confirmed that the expression and distribution of PHB, which is a nuclear matrix protein, affect the apoptosis of HaCaT cells and its co-localization with specific gene products connected with cell apoptosis.
prohibitin; nuclear matrix; curcumin; cell apoptosis; differential expression
Candida dubliniensis is an important human fungal pathogen that causes oral infections in patients with AIDS and diabetes mellitus. However, C. Dubliniensis has been frequently reported in bloodstream infections in clinical settings. Like its phylogenetically related virulent species C. albicans, C. Dubliniensis is able to grow and switch between yeast form and filamentous form (hyphae) and develops biofilms on both abiotic and biotic surfaces. Biofilms are recalcitrant to antifungal therapies and C. Dubliniensis readily turns drug resistant upon repeated exposure. More than 80% of infections are associated with biofilms. Suppression of fungal biofilms may therefore represent a viable antifungal strategy with clinical relevance. Here, we report that C. dubliniensis biofilms were inhibited by purpurin, a natural anthraquinone pigment isolated from madder root. Purpurin inhibited C. dubliniensis biofilm formation in a concentration-dependent manner; while mature biofilms were less susceptible to purpurin. Scanning electron microscopy (SEM) analysis revealed scanty structure consisting of yeast cells in purpurin-treated C. dubliniensis biofilms. We sought to delineate the mechanisms of the anti-biofilm activity of purpurin on C. Dubliniensis. Intracellular ROS levels were significantly elevated in fungal biofilms and depolarization of MMP was evident upon purpurin treatment in a concentration-dependent manner. DNA degradation was evident. However, no activated metacaspase could be detected. Together, purpurin triggered metacaspase-independent apoptosis in C. dubliniensis biofilms.
Magnetic nanoparticles have attracted much research interest in the past decades due to their potential applications in microwave devices. Here, we adopted a novel technique to tune cut-off frequency exceeding the natural resonance frequency limit of monodisperse Fe3O4 nanoparticles via superparamagnetic relaxation. We observed that the cut-off frequency can be enhanced from 5.3 GHz for Fe3O4 to 6.9 GHz forFe3O4@SiO2 core-shell structure superparamagnetic nanoparticles, which are much higher than the natural resonance frequency of 1.3 GHz for Fe3O4 bulk material. This finding not only provides us a new approach to enhance the resonance frequency beyond the Snoek's limit, but also extend the application for superparamagnetic nanoparticles to microwave devices.
Using a glutathione S-transferase pull-down liquid chromatography–coupled tandem mass spectrometry approach and immunoprecipitation/immunoblot analysis, we found that heat shock cognate protein 70 (Hsc70) was involved in the complex formed by atypical protein kinase Cι (PKCι) and LC3 in the esophageal cancer cell line KYSE30. Further study indicated that Hsc70 was targeted by autophagic degradation, and knockdown of PKCι down-regulated Hsc70 by promoting autophagy. PKCι knockdown sensitized cells to oxidative stress-induced apoptosis, whereas forced PKCι expression counteracted the oxidative stress-induced apoptosis via Hsc70.
Electronic supplementary material
The online version of this article (doi:10.1007/s12192-012-0389-4) contains supplementary material, which is available to authorized users.
PKCι; Hsc70; Oxidative stress; Autophagic degradation
The laser-induced ultrafast demagnetization of CoFeB/MgO/CoFeB magnetic tunneling junction is exploited by time-resolved magneto-optical Kerr effect (TRMOKE) for both the parallel state (P state) and the antiparallel state (AP state) of the magnetizations between two magnetic layers. It was observed that the demagnetization time is shorter and the magnitude of demagnetization is larger in the AP state than those in the P state. These behaviors are attributed to the ultrafast spin transfer between two CoFeB layers via the tunneling of hot electrons through the MgO barrier. Our observation indicates that ultrafast demagnetization can be engineered by the hot electrons tunneling current. It opens the door to manipulate the ultrafast spin current in magnetic tunneling junctions.
Most schistosome-endemic areas in China are characterized by low-intensity infections that are independent of prevalence. To establish an effective diagnostic method, we developed a magnetic affinity enzyme-linked immunoassay based on soluble egg antigens (SEA-MEIA) for diagnosing schistosomiasis in persons with low-intensity infection with Schistosoma japonicum by comparing it with a conventional enzyme-linked immunosorbent assay (ELISA). Our results showed that the SEA-MEIA had a higher sensitivity and greater precision in the diagnosis of low-intensity S. japonicum infections than the ELISA. In addition, when we used Pearson's correlation in associating SEA-MEIA with ELISA, a significant correlation existed between the two assays (r = 0.845, P < 0.001). Our data indicated that SEA-MEIA, with a higher sensitivity and greater ease of performance, would be valuable for diagnosis of schistosomiasis japonicum in persons with low-intensity infections.
Water use efficiency (WUE) is a key indicator to assess ecosystem adaptation to water stress. Rain use efficiency (RUE) is usually used as a proxy for WUE due to lack of transpiration data. Furthermore, RUE based on aboveground primary productivity (RUEANPP) is used to evaluate whole plant water use because root production data is often missing as well. However, it is controversial as to whether RUE is a reliable parameter to elucidate transpiration efficiency (TE), and whether RUEANPP is a suitable proxy for RUE of the whole plant basis. The experiment was conducted at three differently managed sites in the Inner Mongolia steppe: a site fenced since 1979 (UG79), a winter grazing site (WG) and a heavily grazed site (HG). Site HG had consistent lowest RUEANPP and RUE based on total net primary productivity (RUENPP). RUEANPP is a relatively good proxy at sites UG79 and WG, but less reliable for site HG. Similarly, RUEANPP is good predictor of transpiration efficiency based on aboveground net primary productivity (TEANPP) at sites UG79 and WG but not for site HG. However, if total net primary productivity is considered, RUENPP is good predictor of transpiration efficiency based on total net primary productivity (TENPP) for all sites. Although our measurements indicate decreased plant transpiration and consequentially decreasing RUE under heavy grazing, productivity was relatively compensated for with a higher TE. This offset between RUE and TE was even enhanced under water limited conditions and more evident when belowground net primary productivity (BNNP) was included. These findings suggest that BNPP should be considered when studies fucus on WUE of more intensively used grasslands. The consideration of the whole plant perspective and “real” WUE would partially revise our picture of system performance and therefore might affect the discussion on the C-sequestration and resilience potential of ecosystems.
Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood.
In the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells.
Our study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1.
Taken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics.
Colorectal cancer; CPE; Cell proliferation; Tumorigenicity
Crocodilians are diving reptiles that can hold their breath under water for long periods of time and are crepuscular animals with excellent sensory abilities. They comprise a sister lineage of birds and have no sex chromosome. Here we report the genome sequence of the endangered Chinese alligator (Alligator sinensis) and describe its unique features. The next-generation sequencing generated 314 Gb of raw sequence, yielding a genome size of 2.3 Gb. A total of 22 200 genes were predicted in Alligator sinensis using a de novo, homology- and RNA-based combined model. The genetic basis of long-diving behavior includes duplication of the bicarbonate-binding hemoglobin gene, co-functioning of routine phosphate-binding and special bicarbonate-binding oxygen transport, and positively selected energy metabolism, ammonium bicarbonate excretion and cardiac muscle contraction. Further, we elucidated the robust Alligator sinensis sensory system, including a significantly expanded olfactory receptor repertoire, rapidly evolving nerve-related cellular components and visual perception, and positive selection of the night vision-related opsin and sound detection-associated otopetrin. We also discovered a well-developed immune system with a considerable number of lineage-specific antigen-presentation genes for adaptive immunity as well as expansion of the tripartite motif-containing C-type lectin and butyrophilin genes for innate immunity and expression of antibacterial peptides. Multifluorescence in situ hybridization showed that alligator chromosome 3, which encodes DMRT1, exhibits significant synteny with chicken chromosome Z. Finally, population history analysis indicated population admixture 0.60-1.05 million years ago, when the Qinghai-Tibetan Plateau was uplifted.
diving hypoxia; oxidative phosphorylation; olfaction; immunity; FISH; SNP
The time-average method currently available is limited to analyzing the specific performance of the automatic gain control-proportional and integral (AGC-PI) based velocity-controlled closed-loop in a micro-electro-mechanical systems (MEMS) vibratory gyroscope, since it is hard to solve nonlinear functions in the time domain when the control loop reaches to 3rd order. In this paper, we propose a linearization design approach to overcome this limitation by establishing a 3rd order linear model of the control loop and transferring the analysis to the frequency domain. Order reduction is applied on the built linear model's transfer function by constructing a zero-pole doublet, and therefore mathematical expression of each control loop's performance specification is obtained. Then an optimization methodology is summarized, which reveals that a robust, stable and swift control loop can be achieved by carefully selecting the system parameters following a priority order. Closed-loop drive circuits are designed and implemented using 0.35 μm complementary metal oxide semiconductor (CMOS) process, and experiments carried out on a gyroscope prototype verify the optimization methodology that an optimized stability of the control loop can be achieved by constructing the zero-pole doublet, and disturbance rejection capability (D.R.C) of the control loop can be improved by increasing the integral term.
MEMS vibratory gyroscopes; velocity-controlled closed-loop; 3rd order; linear model; optimization methodology
Both microwave absorption and magnetocaloric effect (MCE) are two essential performances of magnetic materials. We observe that LaFe11.6Si1.4C0.2H1.7 intermetallic compound exhibits the advantages of both giant microwave absorption exceeding −42 dB and magnetic entropy change of −20 Jkg−1K−1. The excellent electromagnetic wave absorption results from the large magnetic loss and dielectric loss as well as the efficient complementarity between relative permittivity and permeability. The giant MCE effect in this material provides an ideal technique for cooling the MAMs to avoid temperature increase and infrared radiation during microwave absorption. Our finding suggests that we can integrate the giant microwave absorption with magnetic refrigeration in one multifunctional material. This integration not only advances our understanding of the correlation between microwave absorption and MCE, but also can open a new avenue to exploit microwave devices and electromagnetic stealth.