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Background: The endothelial glycocalyx plays a pivotal role in regulating blood flow, filtering blood components, sensing and transducing mechanical signals. These functions are intimately related to its dynamics at the molecular level., Objective: The objective of this research is to establish the relationship between the functions of the endothelial glycocalyx and its dynamics at the molecular level., Methods: To establish such a relationship, large-scale molecular dynamics simulations were undertaken to mimic the dynamics of the glycocalyx and its components in the presence of flow shear stresses., Results: First, motions of the glycocalyx core protein and the pertinent subdomains were scrutinised. Three-directional movements of the glycocalyx core protein were observed, although the flow was imposed only in the x direction. Such an observation contributes to understanding the glycocalyx redistribution as reported in experiments. Unsynchronised motion of the core protein subdomains was also spotted, which provides an alternative explanation of macroscopic phenomena. Moreover, the dynamics, root-mean-square-deviations and conformational changes of the sugar chains were investigated. Based on the findings, an alternative force transmission pathway, the role of sugar chains, and potential influence on signalling transduction pathways were proposed and discussed., Conclusions: This study relates the functions of the glycocalyx with its microscopic dynamics, which fills a knowledge gap about the links between different scales.

It is widely accepted that salt intake reduction and regular exercise is a healthy lifestyle, which can prevent cardiovascular diseases (CVD). Meanwhile, there is evidence that the endothelial glycocalyx layer (EGL) is related to CVD. However, how such a healthy lifestyle helps to prevent CVD via the function of the EGL has not been scientifically established. In this research, a series of large-scale molecular dynamics simulations have been conducted to study ion transport inside the EGL under varying flow velocities. Results show that a fast blood flow velocity favors the Na + transport out of the EGL, which can explain the increase in the thickness of an exclusion layer between red blood cells and the EGL under fast blood flow situations, as witnessed in some previous experiments. Based on findings from this fundamental research, a theory is proposed, which can answer the open-ended question "Why do we need to reduce salt intake and exercise regularly". The findings may also have implications for other therapies to combat cardiovascular diseases.

Flow patterns on surfaces grafted with complex structures play a pivotal role in many engineering and biomedical applications. In this research, large-scale molecular dynamics (MD) simulations are conducted to study the flow over complex surface structures of an endothelial glycocalyx layer. A detailed structure of glycocalyx has been adopted and the flow/glycocalyx system comprises about 5,800,000 atoms. Four cases involving varying external forces and modified glycocalyx configurations are constructed to reveal intricate fluid behaviour. Flow profiles including temporal evolutions and spatial distributions of velocity are illustrated. Moreover, streamline length and vorticity distributions under the four scenarios are compared and discussed to elucidate the effects of external forces and glycocalyx configurations on flow patterns. Results show that sugar chain configurations affect streamline length distributions but their impact on vorticity distributions is statistically insignificant, whilst the influence of the external forces on both streamline length and vorticity distributions are trivial. Finally, a regime diagram for flow over complex surface structures is proposed to categorise flow patterns.

Three new Talaromyces species isolated from soil are reported here, namely T. dimorphus (ex-type strain AS3.15692 T ), T. lentulus (ex-type strain AS3.15689 T ) and T. mae (ex-type strain AS3.15690 T ). T. dimorphus is characterized by biverticillate and monoverticillate penicilli, ampulliform phialides, slimy texture with sparse mycelial funicles and absent conidiogenesis on MEA. T. lentulus is featured by vivid yellow mycelium on Cz and MEA, absent conidiogenesis on CYA, and globose smooth-walled conidia. T. mae presents sparse conidia on CYA and YES, funiculous and floccose texture on MEA, and ovoid smooth-walled conidia. Both morphological and molecular characters show that T. dimorphus is unique and has no close relatives. Although T. lentulus and T. mae resembles T. adpressus and T. pinophilus very much, phylogenetic analyses of CaM, BenA, ITS and Rpb2 sequences all support their status as novel species.

The glycocalyx has a prominent role in orchestrating multiple biological processes occurring at the plasma membrane. In this paper, an all-atom flow/glycocalyx system is constructed with the bulk flow velocity in the physiologically relevant ranges for the first time. The system is simulated by molecular dynamics using 5.8 million atoms. Flow dynamics and statistics in the presence of the glycocalyx are presented and discussed. Complex dynamic behaviours of the glycocalyx, particularly the sugar chains, are observed in response to blood flow. In turn, the motion of the glycocalyx, including swing and swirling, disturbs the flow by altering the velocity profiles and modifying the vorticity distributions. As a result, the initially one-dimensional forcing is spread to all directions in the region near the endothelial cell surface. Furthermore, the coupled dynamics exist not only between the flow and the glycocalyx but also within the glycocalyx molecular constituents. Shear stress distributions between one-dimer and three-dimer cases are also conducted. Finally, potential force transmission pathways are discussed based on the dynamics of the glycocalyx constituents, which provides new insight into the mechanism of mechanotransduction of the glycocalyx. These findings have relevance in the pathologies of glycocalyx-related diseases, for example in renal or cardiovascular conditions., (© 2017 The Authors.)

Objectives: This study was designed to assess the effects of plumbagin on isoflurane-induced neurotoxicity., Methods: Neonatal Sprague Dawley rat pups were treated with plumbagin (50, 100 or 150 mg/kg body weight, orally) from postnatal day 2. The pups on postnatal day 7 were subjected to isoflurane (0.75%) exposure for 6 h. Neuronal apoptosis in the hippocampal tissues was detected by TUNEL assay and FluroJade B staining following isoflurane exposure. Protein expressions were analysed by immunoblotting. RT-PCR was performed to assess mRNA levels of brain-derived neurotrophic factor (BDNF) and TrkB., Key Findings: We observed reduced apoptosis in hippocampal CA1, CA3 and dentate gyrus regions along with severely reduced pro-apoptotic factors (Bad, Bax and cleaved caspase-3) expression and raised levels of Bcl-2, Bcl-xL, survivin, xIAP and cIAPs (cell survival proteins) in plumbagin supplemented rats. Decrease in the levels of JNK, phospho-JNK, c-Jun and phospho-c-Jun with enhanced ERK1/2 levels was observed on plumbagin pretreatment. Down-regulated PI3K/Akt signalling following isoflurane was activated by plumbagin as evidenced by raised PI3K/Akt pathway proteins - mTORc1, Akt, phospho-Akt, GSK-3β, phospho-GSK-3β, PTEN and NF-κBp65 in the hippocampal tissues as detected by Western blotting. The mRNA levels were enhanced on plumbagin supplementation., Conclusions: Plumbagin exerted its neuroprotective effects by effectively suppressing isoflurane-induced neuronal apoptosis via regulating BDNF-TrkB-PI3/Akt and ERK/JNK signalling., (© 2017 Royal Pharmaceutical Society.)

RNA interference (RNAi)-based technology has emerged as a potential tool for controlling insect pests, however, previous studies found that the efficiency of RNAi in Bactrocera dorsalis was variable. In nature, insects often meet various challenges, such as pathogen infections, extreme temperatures, lack of nutrition and heavy metals. To better understand the association of the stressors with efficiency of RNAi, in the current study we tested the expression of three core genes, dicer2 (Bddcr2), r2d2 (Bdr2d2) and argonaute2 (Bdago2), of the small interfering RNA (siRNA) pathway of B. dorsalis upon various stressors. Our results showed that all three genes were upregulated by the infection of invertebrate iridescent virus 6, which suggested a function of the siRNA pathway against viral infection. The loading of FeCl 3 could also increase the expression of Bddcr2. The treatments of Escherichia coli, extremely high (40°C) and low (0°C) temperatures, as well as starvation, could negatively influence the expression of Bddcr2 and/or Bdago2. In total, our results showed that various stressors could influence the expression of core components of B. dorsalis siRNA pathway. This highlights further speculation on the RNAi efficiency upon these stressors. Considering the complexity and variation of RNAi efficiency in different conditions, these results provide initial aspects in possible environmental stressors to influence the activity of the siRNA pathway, but the real impact of RNAi efficiency posed by these stressors requires further studies., (© 2016 Institute of Zoology, Chinese Academy of Sciences.)

Recent discovery of the heterodimeric voltage-gated sodium channels (Na v ) in two aphid species, Acyrthosiphon pisum and Myzus persicae, aroused interest in exploring whether this kind of channel is conserved for aphids. Herewith, we aim to provide evidence for the conservation of heterodimeric Na v s in aphids and investigate whether they have unique splicing patterns. We found that the only identifiable Na v from Toxoptera citricida consisted of two subunits, forming a heterodimeric Na v , which carried an atypical "DENS" ion selectivity filter and a conventional "MFM" inactivation gate, confirming the heterodimeric Na v s' conservation within aphids. These unique heterodimeric channels may form a new Na v subfamily, specific to aphids. A more ancient member of four-domain Na v homolog was well preserved in T. citricida, carrying a typical "DEEA" and "MFL" motif. The presence of "DENS" in mammalian Na x s and "DEKT" in a fungus Na v suggested that the heterodimeric Na v s may still preserve Na + permeability. Sequencing 46 clones from nymphs and adults exposed unique splicing patterns for this heterodimeric Na v from T. citricida, revealing 7 alternatively spliced exons, evidencing that exon 5 was no longer unique to Bombyx mori, and exon k/l was semi-mutually exclusive. Two previously undescribed optional exons and a SNP site seemingly unique to aphids were identified. In conclusion, the dimeric Na v s might form a new aphids-specific heterodimeric N a v subfamily. This dimeric Na v from T. citricida was characterized with distinguishable alternative splicing modes, exemplified by the discovery of two novel alternative exons and unique usage patterns of alternative exons., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate the role of heat shock protein (HSP)-9 on the inflammation reaction present in patients with chronic prostatitis with erectile dysfunction (ED)., Patients and Methods: A total of 160 participants in the study were assigned to one of four groups of the same size. Group A had patients with chronic prostatitis and ED. Group B had patients with simple chronic prostatitis. Group C had patients with ED. And group D had healthy volunteers. The serum levels of HSP-9, CRP, TNF-a, IL-6 and CD3 in each individual's serum were tested by ELISA. Additionally, the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Index of Erectile Function-5 (IIEF-5) scores were recorded for each case., Results: The serum levels of HSP-9, CRP, TNF-a, IL-6 and CD3 in the serum of groups A and B were distinctly higher than those of groups C and D (p<0.05). While comparisons between groups A and B, or between groups C and D yielded no significant differences. Nevertheless, the NIH-CPSI scores in the group A were significantly higher (mostly moderately severe) than in the group B (mild to moderate). Furthermore, the IIEF-5 scores in the group A were also significantly higher than those in the group C., Conclusions: The serum levels of HSP-9, CRP, TNF-a, IL-6 and CD3 in the sera of patients with chronic prostatitis with ED were clearly increased, reflecting a high degree of inflammation which may be related to the clinical manifestations in patients with chronic prostatitis and ED.

Species belonging to Aspergillus section Cervini are characterised by radiate or short columnar, fawn coloured, uniseriate conidial heads. The morphology of the taxa in this section is very similar and isolates assigned to these species are frequently misidentified. In this study, a polyphasic approach was applied using morphological characters, extrolite data, temperature profiles and partial BenA , CaM and RPB2 sequences to examine the relationships within this section. Based on this taxonomic approach the section Cervini is resolved in ten species including six new species: A. acidohumus , A. christenseniae , A. novoguineensis , A. subnutans , A. transcarpathicus and A. wisconsinensis . A dichotomous key for the identification is provided.

Portable and wearable electronic devices are human-centered devices; therefore, many unique attributes are highly desirable, such as flexibility, being self-powered, and waterproof. These properties render devices excellent adaptivity in harsh operation environments. In this work, we report an integrated triboelectric tactile sensor array with flexible, transparent, self-powered, and waterproof features. Each tactile sensor is a surface nano/microtexture enhanced triboelectric nanogenerator. The sensor array can serve as a touch panel for electronic devices. Owing to a unique design of a built-in triboelectric contact pair and an electrical shielding layer, an individual pixel of the fabricated tactile sensor array can generate an open circuit voltage up to 1.613 V and a short circuit current density of 47.308 mA/m(2) under 612.5 kPa. The tactile sensors can produce stable voltage signals regardless of the materials of the touching objects, and work stably both in ambient and aqueous environments. To examine the touch panel function of a sensor array, a matrix of 10 × 10 individually addressable 4 mm × 4 mm triboelectric sensors has been integrated into a thin, transparent, and flexible film, and the 2-D touch mapping has been successfully demonstrated. The unique triboelectric tactile sensor array reported here is robust and highly versatile, and it may find broad applications in display, wearable electronics, artificial skins, Internet of Things (IoT), etc.

Background/objective: Asporin is associated with osteoarthritis and lumbar disk degeneration. Previous studies in chondrocytes showed that asporin can bind to transforming growth factor-β1 (TGF-β1) and downregulate matrix biosynthesis. However, this has not been studied in intervertebral disk (IVD) cells. This study aimed to inspect the expression of asporin under TGF-β1 stimulation and its effect on TGF-β1-induced matrix biosynthesis in human intervertebral annulus cells., Methods: Human intervertebral annulus cells were obtained from the pathological region of IVD in eight patients. After primary culture and redifferentiation in alginate beads, cells were reseeded and treated with different concentrations (5 ng/mL, 10 ng/mL, and 15 ng/mL) of TGF-β1 for up to 24 hours. Total RNA extracted from the cells and those with asporin knockdown were subjected to real-time polymerase chain reaction analysis to examine the expression of asporin and extracellular matrix genes., Results: TGF-β1 stimulation induces asporin transcription significantly in a dose- and time-dependent manner. Knockdown of endogenous asporin leads to the upregulated expression of collagen II alpha 1 and aggrecan., Conclusion: Our results have verified a functional feedback loop between TGF-β1 and asporin in human intervertebral annulus cells indicating that TGF-β1-induced annulus matrix biosynthesis can be significantly upregulated by knockdown of asporin. Therefore, asporin could be a potential new therapeutic target and inhibition of asporin could be adopted to enhance the anabolic effect of TGF-β1 in human intervertebral annulus cells in degenerative IVD diseases.

Superoxide dismutase (SOD) is a family of enzymes with multiple isoforms that possess antioxidative abilities in response to environmental stresses. Panonychus citri is one of the most important pest mites and has a global distribution. In this study, three distinct isoforms of SOD were cloned from P. citri and identified as cytoplasmic Cu-ZnSOD (PcSOD1), extracellular Cu-ZnSOD (PcSOD2), and mitochondrial MnSOD (PcSOD3). mRNA expression level analysis showed that all three isoforms were up-regulated significantly after exposure to the acaricide abamectin and to UV-B ultraviolet irradiation. In particular, PcSOD3 was up-regulated under almost all environmental stresses tested. The fold change of PcSOD3 expression was significantly higher than those of the two Cu-ZnSOD isoforms. Taken together, the results indicate that abamectin and UV-B can induce transcripts of all three SOD isoforms in P. citri. Furthermore, PcSOD3 seems to play a more important role in P. citri tolerance to oxidative stress.

The vitellogenin receptor (VgR) functions as an essential component in uptaking and transporting vitellogenin (Vg) in female adults, which is involved in ovary development and oviposition. This study aimed to clarify the molecular characteristics and function of VgR in the oriental fruit fly Bactrocera dorsalis (Hendel). Here, we identified the full-length of BdVgR (GenBank Accession No. JX469118), encoding a 1925 residue (aa) protein with a 214.72 kDa molecular mass and several typical motifs of low-density lipoprotein receptor superfamily (LDLR). Phylogenic analysis suggested that BdVgR was evolutionary conserved with other Dipteran VgRs. The expression of BdVgR was exclusively detected in the ovaries rather than head, thorax or other tissues. The developmental expression patterns showed that the signal of BdVgR was detectable in very beginning of adult stage, and positively correlated with the growth rate of ovaries and the expression levels of its ligands. In addition, we also demonstrated that the expression level of BdVgR, and ovary development were significantly suppressed after being injected with BdVgR-targeted dsRNA. Together, all of these results indicated that BdVgR was critical for yolk protein absorption and ovary maturation in B. dorsalis, playing a vital role in female reproduction.

The regulation of mRNA expression level is critical for gene expression studies. Currently, quantitative reverse transcription polymerase chain reaction (qRT-PCR) is commonly used to investigate mRNA expression level of genes under various experimental conditions. An important factor that determines the optimal quantification of qRT-PCR data is the choice of the reference gene for normalization. To advance gene expression studies in Toxoptera citricida (Kirkaldy), an important citrus pest and a main vector of the Citrus tristeza virus, we used five tools (GeNorm, NormFinder, BestKeeper, ΔCt methods, and RefFinder) to evaluate seven candidate reference genes (elongation factor-1 alpha [EF1α], beta tubulin [β-TUB], 18S ribosomal RNA [18S], RNA polymerase II large subunit (RNAP II), beta actin (β-ACT), alpha tubulin, and glyceraldhyde-3-phosphate dehydrogenase) under different biotic (developmental stages and wing dimorphism) and abiotic stress (thermal, starvation, and UV irradiation) conditions. The results showed that EF1α and 18S were the most stable genes under various biotic states, β-ACT and β-TUB during thermal stress, EF1α and RNAP II under starvation stress, and RNAP II, β-ACT, and EF1α under UV irradiation stress conditions. This study provides useful resources for the transcriptional profiling of genes in T. citricida and closely related aphid species., (© The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Esterase has been reported to be involved in malathion resistance in the oriental fruit fly, Bactrocera dorsalis (Hendel). However, the underlying molecular mechanism of the esterase-mediated resistance remains largely unknown in this species. Here, with the use of a strain selected for malathion resistance in the laboratory (MR), we found that two overexpressed α-esterase genes, namely BdCarE4 and BdCarE6, predominant in the adult midgut and fat body, function in conferring malathion resistance in B. dorsalis. Notably, these two genes were found to be mostly close to the esterase E3, which are usually implicated in detoxifying organophosphate insecticides. The transcript levels of BdCarE4 and BdCarE6 were investigated and compared between the MR and a susceptible (MS) strain of B. dorsalis. Both genes were significantly up-regulated in the MR strain, which was consistent with the enhanced esterase activity in the MR strain. However, no changes in either the coding sequence or gene copy number were observed between the two strains. Subsequently, heterologous expression combined with cytotoxicity assay in Sf9 cells demonstrated that BdCarE4 and BdCarE6 can probably detoxify malathion. Furthermore, RNA interference-mediated knockdown of each of these two genes significantly increased malathion susceptibility in the MR strain adults. In conclusion, these results expand our molecular understanding of the important role of α-esterases during the development of resistance to organophosphorous insecticides in B. dorsalis., (© 2015 The Royal Entomological Society.)

Ryanodine receptors (RyRs) play a critical role in regulating the release of intracellular calcium, which enables them to be effectively targeted by the two novel classes of insecticides, phthalic acid diamides and anthranilic diamides. However, less information is available about this target site in insects, although the sequence and structure information of target molecules are essential for designing new control agents of high selectivity and efficiency, as well as low non-target toxicity. Here, we provided sufficient information about the coding sequence and molecular structures of RyR in T. citricida (TciRyR), an economically important pest. The full-length TciRyR cDNA was characterized with an open reading frame of 15,306 nucleotides, encoding 5101 amino acid residues. TciRyR was predicted to embrace all the hallmarks of ryanodine receptor, typically as the conserved C-terminal domain with consensus calcium-biding EF-hands (calcium-binding motif) and six transmembrane domains, as well as a large N-terminal domain. qPCR analysis revealed that the highest mRNA expression levels of TciRyR were observed in the adults, especially in the heads. Alternative splicing in TciRyR was evidenced by an alternatively spliced exon, resulting from intron retention, which was different from the case of RyR in Myzus persicae characterized with no alternative splicing events. Diagnostic PCR analysis indicated that the splicing of this exon was not only regulated in a body-specific manner but also in a stage-dependent manner. Taken together, these results provide useful information for new insecticide design and further insights into the molecular basis of insecticide action.

Objective: To study the causes of orchiectomy in different age groups., Methods: We retrospectively reviewed the clinical data about 291 cases of orchiectomy performed between March 1993 and October 2014 and analyzed the causes of surgery and their distribution in different age groups., Results: The main causes of orchiectomy were testicular torsion (45.8%), cryptorchidism (32.5%) and testicular tumor (16.9%) in the patients aged 0-25 years, testicular tumor (42.4%), cryptorchidism (25.9%) and tuberculosis (10.6%) in those aged 26-50 years. Prostate cancer was the leading cause in those aged 51-75 years (77.6%) or older (84.0%)), and testicular tumor was another cause in the 51-75 years old men (10.2%). Prostate cancer, testicular tumor, cryptorchidism, and testicular torsion were the first four causes of orchiectomy between 1993 and 2009. From 2010 to 2014, however, testicular tumor rose to the top while prostate cancer dropped to the fourth place., Conclusion: The causes of orchiectomy vary in different age groups. The proportion of castration for prostate cancer patients significantly reduced in the past five years, which might be attributed to the improvement of comprehensive health care service.

Because of the noninvasive, locally selective potential of thermal energy, considerable effort has been focused on the use of an external, alternating magnetic field for conversion of magnetic work to heat with iron oxide nanoparticles. However, proper regulation of thermal energy remains a challenge because of the lack of feedback from the local temperature change to the external power supply. Here, we show development of smart magnetic nanoparticles composed of Fe and Si with intrinsically tunable heat generation capability. They were engineered to possess an adjustable magnetic transition temperature through tuning the exchange between Fe atoms by incorporation of silicon atoms. They show relatively high magnetic moment. Moreover, their biocompatibility was established in several cell lines. The nanoparticles were also combined with a thermosensitive polymer, which had the capability to release of molecules with a magnetic stimulus, thereby providing a platform for locally controlled, drug release.

Background: The citrus red mite, Panonychus citri (McGregor), is regarded as one of the most serious citrus pests in many countries and has developed high resistance to pyrethroids as a result of the intensive use of these acaricides., Results: The para sodium channel gene of P. citri (named PcNav ), containing an entire coding region of 6729 bp, was cloned in this study. Three alternative splicing sites and 12 potential RNA editing sites were identified in PcNav . Thus, exons alt 1 and alt 3-v3 were found to be unique to PcNav . Comparison of field fenpropathrin-resistant (WZ) and susceptible (LS) strains identified the point mutation F1538I in IIIS6 of the sodium channel, which is known to confer strong resistance to pyrethroids in mites. Moreover, it was also found that the PcNav mRNA was present during all life stages, and the transcript seems to be more abundant in larvae than in other developmental stages., Conclusion: These results suggest that the F1538I mutation plays an important role in fenpropathrin resistance in citrus red mites. This is the first study of the sodium channel in P. citri and provides abundant information for further research on the mechanism of pyrethroid resistance., (© 2014 Society of Chemical Industry.)

Objective: To investigate the effects of overexpression of nuclear factor E2-related factor-2 (NRF2) on lung injury in rats exposed to paraquat (PQ) poisoning., Methods: A mifepristone (RU486)-inducible recombinant adenoviral vector carrying the human NRF2 gene (Ad-RUNRF2) was constructed and transfected via airway into the rats 7 days before the administration of RU486. Rats were orally challenged with PQ at 20 mg/kg 24 h after the injection of RU486. On days 0.5, 3 and 21 after PQ poisoning, the expressions of NRF2 and cytokines related to inflammation and oxidation in lung tissue were examined., Results: RU486 remarkably enhanced NRF2 mRNA and NRF2 protein levels in Ad-RUNRF2-transfected rats in a dose-dependent manner (p < 0.01). PQ stimulated compensatory overexpression of NRF2, heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1) in lungs on days 0.5 and 3 after exposure (p < 0.05), but depleted the expression of catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH), with an increased malondialdehyde (MDA) (p < 0.05). However, pretreatment with Ad-RUNRF2 and RU486 strongly enhanced the expression levels of NRF2, HO-1, NQO-1, CAT and GSH-Px in the lungs of PQ intoxicated rats, with increased GSH and decreased MDA (p < 0.05). Pretreatment with Ad-RUNRF2 and RU486 also strongly suppressed the PQ-induced activation of nuclear factor κB (NF-κB) and decreased the levels of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). In addition, Ad-RUNRF2 and RU486 induction significantly reduced PQ-induced pathological changes in lungs and attenuated lung oedema and protein leakage caused by PQ (p < 0.05)., Conclusion: RU486-induced overexpression of NRF2 in lungs transfected with Ad-RUNRF2 can ameliorate PQ-induced lung injury by the activation of the NRF2-antioxidant response element (ARE) pathway., (© The Author(s) 2014.)

Objective: To investigate the association between testicular microlithiasis (TM) and semen parameters in Chinese adult men with fertility intention., Materials and Methods: We retrospectively reviewed the ultrasonography results of the reproductive system of 16,204 consecutive adult male patients in our hospital with fertility intention from November 2012 to October 2013. TM was diagnosed by scrotal ultrasonography. Patients with TM were divided into classic testicular microlithiasis (CTM) or limited testicular microlithiasis (LTM). The clinical data of CTM, LTM, and non-TM groups, especially of patients in whom sperms were found in semen analysis, were collected and analyzed., Results: There were 226 men (1.39%) diagnosed with TM. The mean age was 28.96 ± 5.12 years (range, 21-46 years), whereas mean testicular volume was 15.38 ± 4.90 mL (range, 1.62-31.23 mL). CTM and LTM were detected in 141 (62.39%) and 85 patients (37.61%), respectively. Among 200 patients who underwent semen analysis, sperms were found in 159 men (79.5%; 97 men with CTM and 62 men with LTM). One hundred and twenty cases without TM (ie, non-TM group) were collected in the control group. Sperm concentration, total motility, and percentage of progressively motile of CTM, LTM, and non-TM groups was (38.01 ± 31.58 million/mL vs 52.31 ± 33.26 million/mL vs 67.16 ± 36.94 million/mL; P <.001), (46.03 ± 23.69% vs 55.37 ± 24.16% vs 62.08 ± 20.45%; P <.001), and (35.88 ± 20.17% vs 43.15 ± 21.08% vs 47.10 ± 17.84%; P <.001), respectively., Conclusion: TM is associated with worse semen parameters in adult men with fertility intention. The extent of microlithiasis correlates inversely with semen parameters., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To explore the potential association between the serum levels of 25-hydroxyvitamin D [25(OH)D] and carotid atherosclerosis in patients with type 2 diabetes., Material and Methods: Three hundred and fifty patients with type 2 diabetes were enrolled in this study in Shanghai, China. B-mode ultrasound was used to detect carotid plaques as indicators of atherosclerosis and measure carotid artery intima-media wall thickness (C-IMT) at two sites of carotid artery. Subjects were divided into group A (patients with carotid plaques) and group B (patients without carotid plaques) and be assessed clinically. Serum levels of 25(OH)D and other clinical parameters were measured. Multivariate logistic regression was performed to find predictors of carotid atherosclerosis in the entire group., Results: The levels of serum 25(OH)D were lower in group A than in group B[19.60 (13.30-25.73) vs 23.19 (18.10-30.06)ng/ml, P<0.001]. The C-IMT levels [(1.00±0.17 vs 0.88±0.20)mm, Ptrend<0.001] and proportion of people with carotid plaques(44/88 vs 20/87, Ptrend<0.001) in the lowest quartile of 25(OH)D were higher than in the highest quartile. Vitamin D concentrations were inversely associated with HbA1c in women(r=-0.194, P=0.006), and C-IMT in men(r=-0.409, P<0.001). Logistic regression analysis showed age, male sex, current smoke, history of hypertension, SBP, LDL-C and lg[25(OH)D] (OR: 0.924, 95%CI: 0.893-0.955, P<0.001) were independently associated with the presence of carotid plaques in T2DM., Conclusions: Serum vitamin D level is significantly and independently associated with carotid atherosclerosis in patients with T2DM in Shanghai, China., (Copyright © 2014. Published by Elsevier Masson SAS.)

A constant ratio of ferritin heavy chain homolog (HCH) and light chain homolog (LCH) subunits seems to be required to compose the ferritin heteropolymer protein in insects. However, the mechanism by which insect LCH genes regulate protein levels remains unclear. We report that alternative promoters and alternative splicing contribute to maintaining a constant ratio of the two subunits, BdFer1HCH and BdFer2LCH (ferritin 1 HCH and ferritin 2 LCH), in Bactrocera dorsalis, a notorious quarantine pest. The genes BdFer1HCH and BdFer2LCH were identified with a series of potential transcription factor binding sites and were shown to be clustered within the genome in a "head to head" fashion. Thus, we unearthed a potential post-transcriptional mechanism to regulate the levels of LCH subunits, and confirmed that the expressions of BdFer1HCH and BdFer2LCH were induced by 20-hydroecdysone, iron overload, and immune challenge.

Ryanodine receptors (RyRs) are a distinct class of ligand-gated channels controlling the release of calcium from intracellular stores. The emergence of diamide insecticides, which selectively target insect RyRs, has promoted the study of insect RyRs. In the present study, the full-length RyR cDNA (BdRyR) was cloned and characterized from the oriental fruit fly, Bactrocera dorsalis (Hendel), a serious pest of fruits and vegetables throughout East Asia and the Pacific Rim. The cDNA of BdRyR contains a 15,420-bp open reading frame encoding 5,140 amino acids with a predicted molecular weight of 582.4 kDa and an isoelectric point of 5.38. BdRyR shows a high level of amino acid sequence identity (78 to 97%) to other insect RyR isoforms. All common structural features of the RyRs are present in the BdRyR, including a well-conserved C-terminal domain containing consensus calcium-binding EF-hands and six transmembrane domains, and a large N-terminal domain. Quantitative real-time PCR analyses revealed that BdRyR was expressed at the lowest and highest levels in egg and adult, respectively, and that the BdRyR expression levels in the third instar larva, pupa and adult were 166.99-, 157.56- and 808.56-fold higher, respectively, than that in the egg. Among different adult body parts, the highest expression level was observed in the thorax compared with the head and abdomen. In addition, four alternative splice sites were identified in the BdRyR gene, with the first, ASI, being located in the central part of the predicted second spore lysis A/RyR domain. Diagnostic PCR analyses revealed that alternative splice variants were generated not only in a tissue-specific manner but also in a developmentally regulated manner. These results lay the foundation for further understanding the structural and functional properties of BdRyR, and the molecular mechanisms for target site resistance in B. dorsalis.

Hypovitaminosis D is highly prevalent in type 2 diabetes. The aim of this study is to determine the serum levels of 25-hydroxyvitamin D [25(OH)D] in type 2 diabetic patients with and without mild cognitive impairment (MCI), and examine the relationship of 25(OH)D and MCI with other clinical factors. One hundred and sixty-five diabetic patients were enrolled in this study. Among whom, 95 patients were considered as MCI [Montreal Cognitive Assessment score (MoCA) < 26] and the other 70 as no MCI (MoCA ≥ 26). Subjects were assessed clinically. Diabetic patients with MCI had a longer duration of DM, fewer years of education, elevated fasting blood glucose (FBG), resistant index (RI) of carotid, and lower levels of 25(OH)D {[17.35 (13.02-25.92) vs 28.00 (19.67-34.30)] ng/ml, P < 0.001}. The MoCA score was positively correlated with log10[25(OH)D], education year, and inversely correlated with duration of DM, history of hypertension, intima-media thickness (IMT), FBG, max-RI, and min-RI. Log10[25(OH)D] was positively correlated with MoCA score, and inversely correlated with IMT, in multivariate regression analysis adjusted for age, sex, and education year, 25(OH)D (β = 0.210, P = 0.003), history of hypertension (β = -0.191, P = 0.007), IMT (β = -0.194, P = 0.007), and FBG (β = -0.157, P = 0.026) independently predicted MoCA score. In conclusion, our results suggest that levels of serum 25(OH)D are inversely associated with the cognitive impairment in diabetic patients. Vitamin D may be a potential protective factor for cognitive impairment in patients with type 2 diabetes.

Objectives: To investigate the effects of adenovirus-mediated inducible nitric oxide synthase gene transfection on bladder transitional cell carcinoma T24 cells, and to provide novel insights and approaches to clinical therapies against bladder transitional cell carcinoma., Methods: Firstly, construct recombinant adenovirus vector pAd-iNOS of iNOS, followed by transfection of pAd-iNOS into HECK293 packaging cells. Thirdly, harvest recombinant adenovirus rAd-iNOS after amplification and purification procedures. Finally, transfect the recombinant adenovirus rAd-iNOS into human bladder carcinoma T24 cells and examine the effect of rAd-iNOS transfection on apoptosis of T24 and possible mechanism., Results: As shown by this study, the recombinant adenovirus rAd-iNOS was constructed successfully. The virus titer was 5.8×10(8) PFU/mL and recombinant was verified by PCR analysis. Transfection of adenovirus rAd-iNOS into T24 cells could induce secretion of high NO concentration, P53 protein expression up-regulation, as well as promotion of T24 cell apoptosis., Conclusions: The transfection of human bladder carcinoma T24 cells from recombinant adenovirus rAd-iNOS was confirmed to induce intracellular iNOS over-expression, high production of NO, up-regulation of intracellular P53 expression and promotion of cell apoptosis.

Alternative splicing greatly contributes to the structural and functional diversity of voltage-gated sodium channels (VGSCs) by generating various isoforms with unique functional and pharmacological properties. Here, we identified a new optional exon 23 located in the linker between domains II and III, and four mutually exclusive exons (exons 27A, 27B, 27C, and 27D) in domains IIIS3 and IIIS4 of the sodium channel of Liposcelis bostrychophila (termed as LbVGSC). This suggested that more alternative splicing phenomena remained to be discovered in VGSCs. Inclusion of exon 27C might lead to generation of non-functional isoforms. Meanwhile, identification of three alternative exons (exons 11, 13A, and 13B), which were located in the linker between domains II and III, indicated that abundant splicing events occurred in the DSC1 ortholog channel of L. bostrychophila (termed as LbSC1). Exons 13A and 13B were generated by intron retention, and the presence of exon 13B relied on the inclusion of exon 13A. Exon 13B was specifically expressed in the embryonic stage and contained an in-frame stop codon, inclusion of which led to generation of truncated proteins with only the first two domains. Additionally, several co-occurring RNA editing events were identified in LbSC1. Furthermore, remarkable similarity between the structure and expression patterns of LbVGSC and LbSC1 were discovered, and a closer evolutionary relationship between VGSCs and DSC1 orthologs was verified. Taken together, the data provided abundant molecular information on VGSC and DSC1 orthologs in L. bostrychophila, a representative Psocoptera storage pest, and insights into the alternative splicing of these two channels.

Objective: To investigate the role of the HoxA13 gene from the HOX family in the development of hypospadias by detecting the transcription and expression of HoxA13 in the prepuce and urethral plate of hypospadias patients., Methods: We collected the tissues from the prepuce and urethral plate of 30 hypospadias patients aged 3.3 - 11.6 years, the prepuce of 10 phimosis children aged 3.1 - 10.4 years and the urethra of 10 penile carcinoma patients aged 48.1 - 75.6 years with no urethral involvement, the latter 20 taken as controls. We divided the tissue samples into a distal, an intermedial, a proximal and a control group, and detected the expressions of HoxA13 mRNA and protein in different groups by RT-PCR and immunohistochemistry., Results: RT-PCR showed that the HoxA13 mRNA expressions in the prepuce and urethral plate were significantly higher in the control group (1.409 +/- 0.441 and 1.270 +/- 0.209) than in the intermedial (0.848 +/- 0.338 and 0.684 +/- 0.228) and proximal group (0.497 +/- 0.218 and 0.464 +/- 0.164) (P < 0.05 or P < 0.01), and so were they in the distal (1.071 +/- 0.342 and 1.054 +/- 0.189) than in the proximal group (P < 0.05). Immunohistochemistry revealed that the HoxA13 protein expressions in the prepuce and urethral plate were remarkably higher in the control group (12 050 +/- 4 112 and 13 420 +/- 2 636) than in the intermedial (5 217 +/- 1 993 and 5 238 +/- 3 065) and proximal group (2 095 +/- 1 591 and 2 238 +/- 2 217) (P < 0.05 or P < 0.01), and so were they in the distal (8 223 +/- 3 212 and 10 450 +/- 2 123) than in the proximal group (P < 0.05)., Conclusion: The transcription and expression of HoxA13 in the prepuce and urethral plate of hypospadias patients are closely related with the abnormal position of the urethral meatus, and their abnormal expressions may affect the development and formation of the urethra.

Objective: To study the effects of methyl jasmonate on multidrug resistance in a mouse model of hepatocellular carcinoma., Methods: Multidrug resistant H22 (H22/FAP) hepatocellular carcinoma cells were produced in vitro by continuous exposure to increasing doses of doxorubicin, cisplatin and 5-fluorouracil (FAP regimen). Cell toxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolum bromide (MTT) assay. Survival time was calculated for BALB/c mice that received intraperitoneal injections of H22/FAP cells followed by treatment with methyl jasmonate or verapamil in combination with FAP for 7 days. Adenosine triphosphate (ATP) hydrolysis was used to measure the activity of permeability-glycoprotein (P-gp) ATPase activity in plasma membranes., Results: The MTT assay showed that methyl jasmonate significantly enhanced the cytotoxicity of the FAP regimen in multidrug resistant H22/FAP cells. Methyl jasmonate (10 mg/kg and 5 mg/kg) combined with FAP significantly increased survival time in BALB/c mice by 44.25% and 48.01%, respectively, compared with FAP. Methyl jasmonate increased P-gp ATPase activity., Conclusion: The combined use of methyl jasmonate and the FAP regimen might be a novel strategy for overcoming the multidrug resistance often observed in hepatocellular carcinoma.

As the second largest organ in insects, the insect midgut is the major tissue involved in the digestion of food and detoxification of xenobiotics, such as insecticides, and the first barrier and target for oral RNA interference (RNAi). In this study, we performed a midgut-specific transcriptome analysis in the oriental fruit fly, Bactrocera dorsalis, an economically important worldwide pest, with many populations showing high levels of insecticide resistance. Using high-throughput sequencing, 52 838 060 short reads were generated and assembled to 25 236 unigenes with a mean length of 758 bp. Interestingly, 34 unique sequences encoding digestion enzymes were newly described and these included aminopeptidase and trypsin, genes associated with Bacillus thuringiensis resistance and fitness cost. Second, 41 transcripts were annotated to particular detoxification genes such as glutathione S-transferases, carboxylesterases and cytochrome P450s, and the subsequent phylogenetic analysis indicated homology with tissue-specific and insecticide resistance-related genes of Drosophila melanogaster. Third, we identified the genes involved in the mechanism of RNAi and the uptake of double-stranded RNA. The sequences encoding Dicer-2, R2D2, AGO2, and Eater were confirmed, but SID and SR-CI were absent in the midgut transcriptome. In conclusion, the results provide basic molecular information to better understand the mechanisms of food digestion, insecticide resistance and oral RNAi in this important pest insect in agriculture. Specific genes in these systems can be used in the future as potential targets for pest control, for instance, with RNAi technology., (© 2013 Royal Entomological Society.)

Objective: To investigate the effects of angiotensin converting enzyme inhibitor (ACEI) captopril on Calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats., Methods: Thirty adult male SD rats were randomly divided into 3 groups (n = 10), normal control group (NC group), diabetes mellitus group (DM group)and captopril treated group (Cap group). Streptozocin (STZ) were used to make the model of diabetes mellitus, captopril was administrated by gavage at the dose of 50 mg/kg every day, while in NC group and DM group the same volume of normal saline was administrated. Twelve weeks later, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVDEP), maximal rise rate of left ventricular pressure (+ dp/dtmax) and maximal fall rate of left ventricular pressure (- dp/dtmax) were detected; Western blot was used to detect the expression of Calpain-1 Calpain-2, Bcl-2, Bax and total Caspase3 protein; apoptosis index (AI) were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)., Results: Compared with NC group, LVDEP was significantly higher; LVSP, + dp/dtmax and - dp/dtmax were significantly decreased (P < 0.05); Bcl-2 protein expression was decreased; the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were increased; the value of AI was significantly increased. Compared with DM group, LVDEP was significantly lower; LVSP, + dp/dtmax and - dp/dtmax were significantly increased (P < 0.05); Bcl-2 protein expression was increased, the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were decreased; the value of AI was significantly decreased (P < 0.05)., Conclusion: Captopril can protect diabetic myocardial structure through inhibiting activation of Calpain-1 and Calpain-2, up-regulating the expression of Bcl-2, down-regulating the expression of Bax to inhibit Caspase3 dependent apoptosis, thereby improving the ventricular function and myocardial structure.

Objective: To evaluate the efficacy of daily low-dose tadalafil in the treatment of erectile dysfunction (ED) following pelvic fracture-induced urethral injury (PFUI)., Methods: Based on the length of time between pelvic fracture and the patients' clinic visit, we divided 42 PFUI-caused ED patients into groups A (< 1 month), B (6-24 months) and C (> 24 months). We treated them with tadalafil at 5 mg daily for 12 weeks consecutively, followed by evaluation of the therapeutic effect using IIEF-5 questionnaire and Sexual Encounter Profile (SEP) diaries., Results: Thirty-four patients (83.3%) completed the investigation and all responded well to tadalafil medication. Group A showed significant differences from B and C in the increase of IIEF-5 scores and the positive rate of SEP., Conclusion: Daily low-dose tadalafil helps penile rehabilitation in ED patients following PFUI, and the earlier the medication is initiated, the better the effect will be.

In order to present our experience with 10 cases of renal epithelioid angiomyolipoma (EAML) and validate the applicability of Ki-67 (proliferation marker) for EAML, we reviewed medical records of 10 consecutive cases diagnosed EAML from January 2005 to February 2012 at our department. Clinical data were collected and analyzed and pathology slides were reviewed. The immunohistochemical reactions for Ki-67 were performed and tumors showed positive expression were estimated. Active follow-up was performed to investigate the association between Ki-67 expression and the prognosis. The mean age and tumor size of the patients was 43.6 years (range 32-56) and 8.2 cm (range 2-15 cm), respectively. Seven were females while three were males. Radical nephrectomy was performed in 6 patients, partial nephrectomy in 3, and renal artery ligation in 1. The immunohistochemical reactions for HMB-45 (Human Melanoma Black), SMA (Smooth Muscle Actin) were positive but for S-100 were negative. The number of patients showing positive/negative Ki-67 expression was 5/5. The survival rate of the positive group was 20% (1/5) while 100% (5/5) of the negative group during the median follow-up time of 26.75 months (range 1-53). Recurrence, metastasis and death due to disease occurred in 1 (10%), 3 (30%) and 4 (40%) patients, respectively. Higher expression (positive) of Ki-67 indicates the presence of EAML and poor prognosis of patients. Surgical excision including radical and partial nephrectomy is a considerable approach to the treatment for its malignant potential.

Objective: To investigate the significance of high sensitivity C-reactive protein (hsCRP) levels in serum for detecting type 2 diabetes mellitus (T2DM) patients at risk of developing nonalcoholic fatty liver (NAFLD)., Methods: Individuals with T2DM (n = 9489) were recruited from the Kailuan Company between 2006 and 2007 for the first phase of this community-based prospective cohort study. For the second phase of the study, the original cohort was recruited for follow-up (at two years from each subject's original enrollment date (baseline)). The total followed-up subjects (n = 2802; 2344 males, 458 females, 22-88 years old) were categorized into quartiles according to baseline measurements of serum hsCRP levels (less than or equal to 0.30, > 0.30-0.60, > 0.60-1.92 and > 1.92 mg/L) and used to determine the relationship between change in incidence rates of NAFLD and predictive value of baseline serum hsCRP levels by logistic regression analysis., Results: Twenty-nine percent (n = 813) of the followed-up subjects developed NAFLD. The incidence (%) of NAFLD at the two-year follow-up had increased in conjunction with the level of serum hsCRP detected at baseline (quartile 1: 22.5%, 2: 27.3%, 3: 32.1%, and 4: 34.3%; all, P less than 0.01). It was found that the subjects in the highest quartile had an increased risk of NAFLD (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.42-2.28, P less than 0.01), as compared with those in the lowest quartile. Moreover, when the regression model was adjusted for baseline factors of age, sex, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting serum glucose, and body mass index, the risk of NAFLD remained significantly higher for the highest quartile (vs. the lowest quartile; OR = 1.49, 95% CI: 1.16-1.91, P less than 0.01)., Conclusion: Serum hsCRP levels may be predictive of development of NAFLD in individuals with type 2 diabetes mellitus. The risk of NAFLD increases in parallel with increasing levels of serum hsCRP.

Objective: To evaluate the safety of solifenacin and tolterodine in the treatment of overactive bladder (OAB)., Methods: Studies on the solifenacin, tolterodine and OAB were searched and those fulfilling the inclusion criteria were selected. RevMan 5.0 software was used to perform meta-analysis. Three studies were included with an overall sample size of 1013 cases. The experimental group of solifenacin contained 517 cases while the control group had 496 cases., Results: The incidence rates of overall adverse event, dry mouth, constipation and blurred vision of the experimental group (solifenacin 5 mg once per day) was 26.69% (138/517), 10.64% (55/517), 5.42% (28/517) and 6.55% (26/397) while those of the control group (tolterodine 2 mg twice per day) 33.27% (165/496), 16.73% (83/496), 2.22% (11/496) and 4.20% (16/381) respectively. There was no statistically significant difference in overall adverse event (RR = 0.76, 95%CI: 0.52 - 1.12, P = 0.170) and blurred vision (RR = 1.59, 95%CI: 0.88 - 2.90, P = 0.130) between two groups. However, the incidence rate of key antimuscarinic adverse events such as dry mouth (RR = 0.63, 95%CI: 0.46 - 0.87, P = 0.005) and constipation (RR = 2.38, 95%CI: 1.21 - 4.66, P = 0.010) showed statistically significant difference., Conclusions: Dry mouth is the most common adverse event of solifenacin (5 mg once per day) and tolterodine (2 mg twice per day). Solifenacin has a lower incidence rate of dry mouth and a higher rate of constipation than tolterodine. A clinical physician should consider the incidence of adverse events during treating OAB, especially for those patients prone to constipation.

There are controversies regarding the histogenesis of stromal cells of hemangioblastoma, and no hypothesis has conclusively been proven. We report a case of unusual hemangioblastoma in a middle-aged man with von Hippel-Lindau disease. Neuroimaging revealed multifocal gadolinium-enhancing masses were located within both sides of the cerebellar hemisphere. Histologically, only small areas showing the typical morphology of hemangioblastoma were recognized in masses. Most areas of masses were composed of cohesive epithelioid tumor cells with abundant cytoplasm and distinct boundaries. Epithelioid tumor cells were arranged around blood vessels, exhibiting perivascular anuclear zone structures like ependymoma. The epithelioid tumor cells were diffusely positive for vimentin, CD99, neuron-specific enolase, GFAP and focally positive for epithelial membrane antigen (EMA) and D2-40 in a dot-like pattern. Variable-sized lipid droplets and glycogen particles were noted in the cytoplasm of epithelioid tumor cells under an electron microscope. A diagnosis of epithelioid cellular hemangioblastoma with possible ependymal differentiation (WHO grade I) was made. To our knowledge, only a few cases of hemangioblastoma show epithelioid appearance or EMA immunoreactivity. The present case indicates that the stromal cells of hemangioblastoma might originate from primitive neuroectodermal cells, and they have the capacity to show a distinctive sign of glial or ependymal differentiation., (© 2012 Japanese Society of Neuropathology.)

Objective: To observe the effect of the inducible nitric oxide synthase (iNOS) gene on androgen-independent prostate cancer DU145 cells in vitro., Methods: The iNOS gene was transfected into androgen-independent prostate cancer DU145 cells. The positive cells were selected as the transfected group for amplification, and an empty vector (EV) group and a control group were also set. The mRNA transcription of iNOS was analyzed by RT-PCR. The morphological changes of the cells were observed, the effect of iNOS transfection on the cell growth determined using the MTB method, and the apoptosis of DU145 cells detected by flow cytometry, followed by analysis of the effect of NOS inhibitors on the transfected cells., Results: DU145 cells transfected with iNOS secreted significantly more nitric oxide ([272.50 +/- 15.82] micromol/L) than those of the EV and control groups ([122.00 +/- 18.93] micromol/L and [121.00 +/- 6.98] micromol/L) (P < 0.05). The rate of cell apoptosis was markedly enhanced in the transfected group as compared with the EV and control groups ([42.78 +/- 2.01]% vs [30.65 +/- 1.46]% and [28.96 +/- 1.50]%, P < 0.05). MTP test indicated a slower growth of the DU145 cells in the former than in the latter two (P < 0.05). NOS inhibitors enhanced their growth, but with no significance (P > 0.05)., Conclusion: DU145 cells transfected with iNOS could secrete high-concentration nitric oxide, induce cell apoptosis, and suppress cell proliferation, which may provide a potentially effective gene therapy for advanced androgen-independent prostate cancer.

Objective: To analyze the influence of intravesical Pirarubicin (THP) instillation on the prediction results of European Organization for Research and Treatment of Cancer (EORTC) risk tables and to discuss the efficacy of EORTC risk tables in clinical application., Methods: We retrospectively reviewed the clinical data of 389 patients with non-muscle invasive bladder cancer after TURBT treated with intravesical pirarubicin instillation. According to the EORTC Scoring System, all the cases were divided into low risk group, intermediate risk group and high risk group. The 1-year and 5-year recurrence and progression rates of each group were calculated and compared with the prediction results of the EORTC risk tables., Results: The 1-year recurrence and progression rates of the low risk group were 8.0% and 0, those of the intermediate risk group were 31.0% and 2.8%, and those of the high risk group were 52.5% and 18.6%, respectively. The 5-year recurrence and progression rates of low risk group were 16.0% and 5.3%, those of the intermediate risk group were 42.6% and 10.7%, and those of the high risk group were 63.9% and 41.9%, respectively. The prediction results of progression rate were similar to that of the EORTC risk tables while the overall recurrence rate was lower., Conclusions: The EORTC risk tables can be effectively used to predict the recurrence rate and progression rate of non-muscle invasive bladder cancer. However, the EORTC risk tables have a tendency to overestimate the recurrence rate. Intravesical pirarubicin instillation is helpful to reduce the recurrence rate, yet has no obvious influence on the tumor progression.

Background: Bladder leiomyoma is an uncommon type of bladder neoplasms. Most publications are reports of isolated cases. The influence of tumor size on patients' early symptoms was seldom analyzed. We aim to investigate the clinical characteristics of bladder leiomyoma and the influence of tumor size on patients'symptoms in Chinese population., Methods: We reviewed the medical records of eight patients diagnosed with bladder leiomyoma at our department, collected 53 cases from Chinese National Knowledge Infrastructure (CNKI), Wangfang data base, and Chinese Biological Medicine Disk, and performed a pooled analysis. The clinical characteristics of the patients were analyzed and then classified into symptomatic and asymptomatic groups. The association between tumor size and the occurrence of symptoms was evaluated. Furthermore, Logistic regression model was constructed to discriminate variables., Results: Women comprised the majority of the patients (49/61, 80.3%). The mean age and tumor size were (42.3 ± 14.0) years and (45.0 ± 25.7) mm, respectively. Among all the symptoms, irritative symptoms occurred most frequently (37.7%, 23/61), followed by obstructive urinary symptoms (31.1%, 19/61), hematuria (24.6%, 15/61), and abdominal bulge or pain (14.8%, 9/61). In our study, patients who were 45 years old or younger tended to be asymptomatic compared with elder ones (14/36 vs. 3/25, P = 0.021). The histological, as well as anatomical, location of tumor, did not show significant differences between symptomatic and asymptomatic patients (P = 0.306 and 0.700). Tumors larger than 30 mm in the greatest diameter would cause clinical symptoms such as obstructive urinary symptoms (P = 0.048) and irritative symptoms (P = 0.037). Logistic regression confirmed the association between tumor size and the occurrence of symptoms, which was related with age., Conclusions: Bladder leiomyoma occurs mainly in women and most frequently with irritative symptoms. The occurrence of symptoms is related to tumor size rather than the location. In this setting, patients with endovesical tumors smaller than 30 mm in the greatest diameter tended to be asymptomatic, which were usually treated with transurethral resection of bladder tumor.

Purpose: To assess clinical application of Nickel-titanium(NiTi) rotary instruments Protaper in preparation of curved root canals., Methods: 281 curved canals from 169 extracted molars were instrumented by Protaper rotary instruments using crown-down technique. An analysis was carried out regarding the relationship between the broken files and canal distribution,degree of curvature of canals, and the relationship between amount of the broken files and the duration was also included. SPSS18.0 software package was used for statistical analysis., Results: A total of 43 kits files were used in the preparation of 281 curved root canals, and broken files often happened in canals with curvature of >30° and very complex canals., Conclusions: The fracture of NiTi instruments is closely related to the anatomy of the root cana1. With the use of NiTi rotary instruments Protaper, curved root canals can be prepared effectively. Meanwhile, the problem of instrument separation should be prevented.

Unlabelled: The aim of this study was to evaluate the risk factors of mild cognitive impairment (MCI) in middle-aged patients with type 2 diabetes (T2DM)., Methods: Montreal Cognitive Assessment (MoCA) was applied as cognition assessment implement. One hundred and fifty-seven middle-aged type 2 diabetic patients were enrolled in this cross-section study (age 40~69, mean age 55 ± 7). There were 93 patients with MCI (MoCA score<26) in MCI group and 64 with normal cognitive function (MoCA score ≥ 26) in control group. Information of history of disease, family history, data of BMI, WHR, HbA1c, FINS, C-Peptide (C-P), SBP, DBP, blood lipid (TG, TC, LDL-C, HDL-C and carotid ultrasound (carotid IMT, carotid resistance index [RI]) was collected., Results: There were significant differences in the rate of patients with hypertension ([40.63 vs. 58.06%], P=0.026), duration of diabetes mellitus ([3.09 ± 4.04 y vs. 4.80 ± 4.94 y], P=0.024), C-P ([2.79 ± 1.09 ng/ml vs. 2.26 ± 1.00 ng/ml], P=0.008), Max C-IMT ([0.81 ± 0.15 mm vs. 0.91 ± 0.15 mm], P<0.001), Min C-RI (0.71 ± 0.06 vs. 0.68 ± 0.06, P<0.05), and no significant differences in the duration of hypertension and hyperlipidemia, BMI, WHR, HbA1c, SBP, DBP and blood lipid between control group and MCI group. MoCA scores were positively correlated with C-P (r=0.252, P=0.005), and negatively correlated with the history of hypertension (r=-0.244, P=0.002), duration of DM (r=-0.161, P=0.044), Max C-IMT (r=-0.253, P=0.005) and Min C-RI (r=-0.183, P=0.023). Multiple regression analysis showed that history of hypertension (Beta=-0.267, P=0.002), C-P (Beta=0.281, P=0.001) and Min C-RI (Beta=-0.221, P=0.011) were significantly independent determinants for the MoCA scores., Conclusions: The longer duration of diabetes, history of hypertension, lower serum C-P levels, thickened C-IMT and higher C-RI could be risk factors of MCI in type 2 diabetic patients. This finding could have an important impact on the management of cognitive decline in diabetic patients., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the effects of tadalafil administered on demand or once a day in the treatment of erectile dysfunction (ED)., Methods: We randomly assigned 61 ED patients to three groups to receive tadalafil on demand, at 5 mg once daily, and at 10 mg once daily, respectively. After 42 days of medication, we compared the therapeutic effects among different groups using the patients' sexual encounter profile (SEP) diaries, detected the adverse reactions and assessed the safety of tadalafil., Results: Fifty-three (86.7%) of the patients completed the investigation, and all responded well to tadalafil medication, with a significantly improved success rate of sexual intercourse and a low rate of mild adverse effects. The mean positive rates of SEP were basically similar between the on-demand and once-daily groups., Conclusion: There are no significant differences in the improvement of penile erection and sexual satisfaction of ED patients treated by on-demand and once-daily administration of tadalafil.

o-Quinodimethane (o-QDM) generated from benzosultine was used to extend the pyrrole system for the preparation of octabromo-tetranaphtho[2,3]porphyrins via oxidative aromatization. The properties of these bromoporphyrins were presented and chemical transformation via Pd-catalyzed Suzuki reaction was also effectively achieved., (This journal is © The Royal Society of Chemistry 2012)

Objective: To observe the effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat (PQ)., Methods: After A549 cells transfected with Ad-RUNrf2 were treated by RU486 at the doses of 10(-10), 10(-9), 10(-8) and 10(-7) mol/L for 6 h, A549 cell cultures were exposed to 10(-3) mol/L of PQ for 48 h. Then qRT-PCR and EMSA assays were used to detect the expression of Nrf2 gene, and qRT-PCR and ELISA assays were utilized to measure the effects of Nrf2 gene on the expression of the inflammatory cytokines IL-6, IL-10 and TNF-α, apoptotic factors Caspase-3, Caspase-9 and Cytochrome C. The oxidation factors (CAT and MDA protein contents) were observed by Chemical Colorimetric Analysis., Results: Nrf2 gene relative expression and protein contents increased with RU486 concentrations, and the above expression was the highest when the concentration of RU486 was 10(-7) mol/L, which was significantly higher than those in control and PQ exposure groups (P < 0.01 or P < 0.05). The relative gene expression and protein expression of IL-6 and TNF-α enhanced with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05), while the change of IL-10 content was the opposite. The relative expression of Caspase3, Caspase9 and Cytochrome C genes also increased with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05). The content of CAT enhanced with RU486 concentration, which was the highest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.05). But the change of MDA content was the contrary., Conclusion: Nrf2 expression induced by RU486 can promote the balance of oxidation-antioxidation system in A549 cells and inhibit the inflammation and apoptosis factors, which has a protective effect on A549 cell injury induced by PQ.

Thy28 protein is conserved among plants, bacteria, and mammalian cells. Nuclear Thy28 protein is substantially expressed in testis, liver, and immune cells such as lymphocytes. Lymphocyte apoptosis plays a crucial role in homeostasis and formation of a diverse lymphocyte repertoire. In this study, we examined whether Thy28 affects induction of apoptosis in WEHI-231 B lymphoma cells following engagement of membrane immunoglobulin (mIg). Once they were established, the Thy28-overexpressing WEHI-231 cells showed similar expression levels of IgM and class I major histocompatibility complex (MHC) molecule compared with controls. The Thy28-overexpressing cells were considerably resistant to loss of mitochondrial membrane potential (ΔΨm), caspase-3 activation, and increase in annexin-positive cells upon mIg engagement. These changes were concomitant with an increase in G1 phase associated with upregulation of p27(Kip1). The anti-IgM-induced sustained activation of c-Jun N-terminal kinase (JNK), which was associated with late-phase hydrogen peroxide (H(2)O(2)) production, was partially reduced in the Thy28-expressing cells relative to controls. Taken together, the data suggest that in WEHI-231 B lymphoma cells, Thy28 regulates mIg-mediated apoptotic events through the JNK-H(2)O(2) activation pathway, concomitant with an accumulation of cells in G1 phase associated with upregulation of p27(Kip1) in WEHI-231 B lymphoma cells.

Objective: To investigate the dynamic changes of oxidative stress and nuclear factor-E2 related factor 2 (Nrf2) expression in the lung tissues of acute hydrogen sulfide (H2S) intoxicated rats and intervention effects of ulinastatin (UTI)., Methods: A total of 96 SD rats of clean grade were divided randomly into four groups: normal control group (n = 8), UTI control group (n = 8), H2S -intoxicated model group (n = 40), and UTI treatment group (n = 40). The H2S-intoxicated model group and UTI treatment group were exposed to H2S (283.515 mg/m3) by inhalation for 1h, then UTI treatment group was intraperitoneally exposed to UTI at the dose of 10(5) U/kg for 2 h. H2S-intoxicated model group and UTI treatment group were sacrificed at 2, 6, 12, 24 and 48 h after exposure, respectively. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH) in the rat lung tissues were measured. The expression levels of Nrf2 mRNA in the rat lung tissues were detected. Pathological changes of rat lung tissues were observed under a light microscope and the lung injury scores were evaluated., Results: Compared with control group, the pulmonary SOD, CAT and GSH levels at 2,6 and 12 h after exposure and the pulmonary GSH-Px levels at 2, 6, 12 and 24 h after exposure in H2S-intoxicated model group significantly decreased (P < 0.05 or P < 0.01). The levels of pulmonary MDA at 2, 6, 12 and 24 h after exposure in H2S-intoxicated model group were significantly higher than those in normal control group (P < 0.01). As compared with H2S -intoxicated model group, the pulmonary GSH-Px activities at 6 and 12 h after exposure, the pulmonary CAT activities at 2, 6 and 12 h after exposure, the pulmonary GSH levels at 2, 6, 12 and 24 h after exposure and the pulmonary SOD activities at 2, 6, 12, 24 and 48 h after exposure in UTI treatment group significantly increased (P < 0.05 or P < 0.01), the pulmonary MDA levels at 2, 6 and 12 h after exposure in UTI treatment group significantly decreased (P < 0.01). The expression levels of Nrf2 mRNA at 2, 6, 12, 24 h after exposure in H2S-intoxicated model group were 0.314 +/- 0.011, 0.269 +/- 0.010, 0.246 +/- 0.011 and 0.221 +/- 0.018, respectively, which were significantly higher than those (0.149 +/- 0.012) in control group (P < 0.01). As compared with H2S-intoxicated model group, the expression levels (0.383 +/- 0.017, 0.377 +/- 0.014, 0.425 +/- 0.017, 0.407 +/- 0.011 and 0.381 +/- 0.010) of Nrf2 mRNA at 2, 6, 12, 24 and 48 h after exposure in UTI treatment group significantly increased (P < 0.01). The lung injury at 24 h after exposure in H2S-intoxicated model group was higher than that in UTI treatment group. Histopathological examination showed that the scores of lung injury at 12, 24 and 48 h after exposure in UTI treatment group was significantly lower than those in H2S-intoxicated model group (P < 0.01)., Conclusion: Oxidative stress and Nrf2 activation may be the important factors in rat lung injury induced by H2S-intoxicated, UTI may reduce the rat lung injury and protect the rat lung from damage induced by H2S by inhibiting ROS, improving the imbalance in redox and up-regulating Nrf2 mRNA expression.