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Aims Sirtuin 1 (SIRT1) inhibits nuclear factor kappa B (NF-κB) activity in response to the inflammatory cytokine tumour necrosis factor alpha (TNF-α). Smooth muscle (SM) 22α is a phosphorylation-regulated suppressor of IKK-IκBα-NF-κB signalling cascades in vascular smooth muscle cells (VSMCs). Sm22α knockout results in increased expression of pro-inflammatory genes in the aortas which are controlled by NF-κB. This study aimed to investigate the relationship between SM22α and SIRT1 in the control of vascular inflammation. Methods and results The ligation injury model of Sirt1-Tg/Sm22α-/- mice displayed an increased level of the inflammatory molecules in the carotid arteries compared with Sirt1-Tg mice, accompanied with aggravating neointimal hyperplasia. In the in vitro study, on the one hand, we showed that TNF-α induced the epigenetic silencing of SM22α transcription via EZH2-mediated H3K27 methylation in the SM22α promoter region, contributing to inflammatory response. On the other hand, TNF-α simultaneously induced SIRT1 phosphorylation via CKII and thereby protected against inflammation. Phosphorylated SIRT1 interacted with and deacetylated EZH2 and, subsequently, promoted SM22α transcription by inhibiting EZH2 activity. Increased SM22α in turn facilitated the phosphorylation and activation of SIRT1 via recruitment of CKII to SIRT1, which amplified the anti-inflammatory effect of SIRT1. Conclusion Our findings demonstrate that, in response to TNF-α stimulation, CKII-SIRT1-SM22α acts in a loop to reinforce the expression of SM22α, which limits the inflammatory response in VSMCs in vivo and in vitro. The anti-inflammatory effect of SIRT1 may be dependent on SM22α to some extent. Our data point to targeted activation of SIRT1 in VSMCs as a promising therapeutic avenue in preventing cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: The venom of predatory marine cone snails mainlycontainsadiversearrayofuniquebioactive peptides commonly referred to as conopeptides or conotoxins. These peptides have proven to be valuable pharmacological probes and potential drugs because of their high specificity and affinity to important ion channels, receptors and transporters of the nervous system. Most previous studies have focused specifically on the conopeptides from piscivorous and molluscivorous cone snails, but little attention has been devoted to the dominant vermivorous species. Results: The vermivorous Chinese tubular cone snail, Conus betulinus, is the dominant Conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in the identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including nine new superfamilies. It appeared that most of the identified conopeptides were synthesized in the venom duct, while a handful of conopeptides were identified only in the venom bulb and at very low levels. Conclusions: We identified 215 unique putative conopeptide transcripts from the combination of five transcriptomes and one EST sequencing dataset. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for the development of new pharmaceuticals, and a pathway for the discovery of new conotoxins. [ABSTRACT FROM AUTHOR]

The curvature elasticity of a polyelectrolyte brush monolayer attached to curved surface is investigated theoretically. An analytical method based on the strong-stretching theory for a Gaussian chain is developed to calculate the elastic modulus induced by a polyelectrolyte brush. In particular, the scaling relations for the bending or Gaussian modulus with respect to system parameters related to the electrostatic interaction (degree of ionization and salt concentration) are derived. Using the numerical self-consistent-field theory, the inner structural, free-energy, and elastic moduli are computed for the polyelectrolyte brush with excluded-volume interactions. Compared to the analytical result, the curvature elasticity has a weaker dependence on the system parameters, which is attributed to the linearization for the Poisson-Boltzmann equation in the analytical treatment. Furthermore, our results are compared to the curvature elasticity of a bare charged surface, where from the unique polyelectrolyte brush effect on the surface elasticity is clarified clearly. The scaling relations derived in our paper can serve as a guide to experimental studies on the related systems. [ABSTRACT FROM AUTHOR]

We have studied the phase behaviors of sphere-forming triblock copolymers in confined spaces using the mean-field dynamic density functional theory. The focus is on the morphologies induced by cylindrical nanopores. The effects of the pore diameter and the surface field strength on the phase behaviors are investigated systematically. Typical structures different from the bulk morphologies are observed, which are consistent with available experiments. A series of novel morphologies are predicted in our simulation. Furthermore, the shape effect of the pore cross section on the helical structures is studied. The results of our simulation should provide a guide for designing polymeric nanomaterials confined in cylindrical nanochannels. [ABSTRACT FROM AUTHOR]

The effect of radiation-introduced defects on the behaviour of HfO2 -based metal-insulator-metal (MIM) capacitors as a function of gamma-ray radiation dose from 10 to 1000 krad are reported. Half the capacitors studied showed no degradation after exposure to 1000 krad from a 60Co source, whilst the remaining half showed no change to parameters, such as barrier height and dielectric constant. For the good devices, the I-V characteristics are controlled by Poole-Frenkel model, at a corresponding interface trap energy of 0.39 ~ 0.46 eV before radiation and 0.37 ~ 0.44 eV after 1000 krad. The failed devices show an substantial increase in the trap density from the as fabricated level of 1019 cm-3 to in excess of 1020 cm-3, in contrast to the good devices which show almost no change. We relate this change in defect density to the failure of devices by means of a percolation model, with a trap separation of around 2 nm. [ABSTRACT FROM AUTHOR]

We consider Euclidean path integrals with higher derivative actions, including those that depend quadratically on acceleration, velocity and position. Such path integrals arise naturally in the study of stiff polymers, membranes with bending rigidity as well as a number of models for electrolytes. The approach used is based on the relation between quadratic path integrals and Gaussian fields and we also show how it can be extended to the evaluation of even higher order path integrals. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

A correction to the article "Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia" that was published in a 2011 issue is presented.

Background: Previous cases reported that oocytes were characterized by indented zone pellucida (ZP) and narrow perivitelline space (PVS) with low oocyte maturity or all metaphase I (MI) like oocytes which usually be abandoned. These MI-like oocytes can be fertilized and develop embryo. The genetic analysis of blastocyst from MI-like oocytes with indented ZP and narrow PVS is still unknown. Methods: In this report, patient collected all immature MI-like oocytes with indented ZP and narrow PVS. Intracytoplasmic sperm injection (ICSI) proceed to these oocytes directly. The MI-like oocytes can fertilization, and developed blastocyst. The patient got pregnant after transfer 2 embryo on day 3. Blastomere biopsy, genome amplification, copy number variation (CNV) and single nucleotide polymorphism (SNP) analysis was performed. Results: CNV analysis showed that genotype was 46,XX, with mosaic of multiple chromosomes and SNP results showed that part of the chromosomes belong to triploids, and some belong to quadruplicate copies based on the B-allele frequency (BAF) value combined with the LogR Ratio. It is speculated that the cell is in the early stage of the first meiosis. Conclusion: MI like oocytes with indented ZP and narrow PVS can developed blastocyst and pregnancy after ICSI. Genetic analysis of blastocyst showed mosaic of multiple chromosomes.

Proliferation inhibition of vascular smooth muscle cells (VSMCs) is governed by the activity of a transcription factor network. Krüppel-like factor 4 (KIf4), retinoic acid receptor (RARα), and platelet-derived growth factor receptor (PDGFR) are expressed in VSMCs and are components of such a network. However, the relationship among them in the regulation of VSMC proliferation remains unknown. Here, we investigated the mechanisms whereby Klf4 mediates the growth inhibitory effects in VSMCs through RARα and PDGFRβ. We demonstrated that KIf4 directly binds to the 5' regulatory region of RARα, down-regulates RARn expression, and specifically inhibits RARα-mediated phosphatidylinositol 3-kinase (PI3K) and ERK signaling in cultured VSMCs induced by the synthetic retinoid Am80. Of particular interest, KIf4 inhibits RARn and PDGFRβ expression while blocking PI3K and ERK signaling induced by Am80 and PDGF-BB, respectively. The anti-proliferative effects of KIf4 on neointimal formation depend largely on PDGFR-mediated PI3K signaling without involvement of the RARα-activated signaling pathways. These findings provide a novel mechanism for signal suppression and growth inhibitory effects of KIf4 in VSMCs. Moreover, the results of this study suggest that KIf4 is one of the key mediators of retinoid actions in VSMCs. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the gene expression profiles of rats brain tissues treated with halothane compared with untreated controls to improve current understanding of the mechanism of action of the inhaled anesthetic. The GSE357 gene expression profile was dowloaded from the Gene Expression Omnibus database, and included six gene chips of samples repeatedly exposed to halothane and 12 gene chips of untreated controls. The differentially expressed genes (DEGs) between these two groups were identified using the Limma package in R language. Subsequently, the Database for Annotation, Visualization and Integrated Discovery was used to annotate the function of these DEGs. In addition, the most significantly upregulated gene and downregulated gene were annotated, to reveal the functional interactions with other associated genes, in FuncBase database. A total of 44 DEGs were obtained between The control and halothane exposure samples. Following Gene Ontology functional classification, these DEGs were found to be involved predominantly in the circulatory system, regulation of cell proliferation and response to endogenous stimulus and corticosteroid stimulus processes. KRT31 and HMGCS2, which were identified as the most significantly downregulated and upregulated DEGs, respectively, were associated with the lipid metabolic process and T cell activation, respectively. These results provided a basis for the development of improved inhalational anesthetics with minimal side effects and are essential for optimization of inhaled anesthetic techniques for advanced surgical procedures.