Publications by authors named "Min Guan"

86 Publications

Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas.

PLoS One 2017 27;12(6):e0179692. Epub 2017 Jun 27.

Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, United States of America.

SK-UT-1 uterine leiomyosarcomas (Ut-LMS) cells were transduced with a fatty acid synthase (FASN)-containing retroviral vector to recapitulate the "lipogenic phenotype of cancer." Consistent with this model, forced expression of FASN enhanced SK-UT-1 proliferation, migration, and cellular motion. Further investigation showed FASN promotes trimethylation of H3K9 (H3K9me3) and acetylation of H3K27 (H3K27ac) in SK-UT-1 cells. In contrast, siRNA targeting of FASN in high endogenous FASN expressing SK-LMS-1 Ut-LMS cells inhibits trimethylation of H3K9 and acetylation of H3K27. Palmitate, the predominant fatty acid product of FASN, increased H3K9me3, H3K27ac and H3K27me3 detection in SK-UT-1 cells. FASN promoted histone 3 methylation and acetylation through alteration of histone 3-modifying enzymatic activities (HDAC, HDM, HMT and HAT). ChIP-seq in SK-UT-1-FASN cells with anti-H3K9me3 antibody identified regions of enriched binding compared to vector-only cells. One differentially-enriched gene, CRISP1, was investigated further by ChIP-PCR. The transcriptionally repressive function of H3K9me3 was confirmed in CRISP1. Our results provide mechanistic insight into the pathobiology of the "lipogenic phenotype of cancer." Here, FASN reprograms the Ut-LMS epigenome through chromatin remodeling to promote the "malignant phenotype."
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179692PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487038PMC
September 2017

Aberrant Insula-Centered Functional Connectivity in Psychogenic Erectile Dysfunction Patients: A Resting-State fMRI Study.

Front Hum Neurosci 2017 16;11:221. Epub 2017 May 16.

Henan Andrological Academician Workstation of Basic and Clinical Research, Henan Provincial People's HospitalZhengzhou, China.

Most previous studies exploring the neural mechanism of psychogenic erectile dysfunction (pED) focused on brain activity under tasks. We suggest that the resting brain activity is equally important in pED studies, in that the patterns of spontaneous neural activities is independent of modalities of sensory input, therefore providing substantial information regarding the central mechanism of pED. Our previous study reported the altered baseline activity in right anterior insula (aINS) in pED patients. Also, the insula is a pivotal region in sexual behavior, which is suggested to be able to directly mediate erection. Therefore, the current study employed resting-state fMRI to examine alterations in functional connectivity (FC) of the aINS comparing pED patients with matched control subjects. After rigorous participant inclusion procedure, 27 pED patients and 27 healthy male controls were enrolled. Our results elucidated the disrupted homogeneity within the right aINS and aberrant connection patterns between the right aINS and the right dorsolateral prefrontal cortex (dlPFC), as well as the right aINS and the right temporoparietal junction (TPJ) respectively in pED group, as compared with the healthy controls. In conclusion, our results demonstrated the aberrant insula-centered FC in pED, which may be related to the abnormal representation of internal bodily state or needs in pED patients and thus further affect the inhibitory control in the sexual context. We hope that these findings may shed new light on the understanding of the central mechanism of pED.
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http://dx.doi.org/10.3389/fnhum.2017.00221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433384PMC
May 2017

Self-regulating positive emotion networks by feedback of multiple emotional brain states using real-time fMRI.

Exp Brain Res 2016 12 17;234(12):3575-3586. Epub 2016 Aug 17.

China National Digital Switching System Engineering and Technological Research Center, Zhengzhou, Henan, China.

Disordered emotion regulation may affect work efficiency, induce social disharmony, and even cause psychiatric diseases. Despite recent neurocomputing advances, whether positive and negative emotion networks can be voluntarily modulated is still unknown. In the present study, we addressed this question through multivariate voxel pattern analysis and real-time functional MRI neurofeedback (rtfMRI-nf). During a sustained emotion regulation task, participants' emotional states (positive or negative) were given to them as feedback. Participants were able to increase the percentage of positive emotional states, enhancing emotion regulation network activities. Participants showed an improvement on the positive subscale of positive and negative affect scale that came close to significance. Furthermore, the activation of several emotion-related brain regions, including insula, amygdala, anterior cingulate cortex, and dorsomedial prefrontal cortex, was also increased during rtfMRI-nf training. These findings suggest that humans are able to voluntarily modulate positive emotion networks, leading to exciting applications in the treatment of various neurological and psychiatric disorders.
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http://dx.doi.org/10.1007/s00221-016-4744-zDOI Listing
December 2016

Aging Reduces an ERRalpha-Directed Mitochondrial Glutaminase Expression Suppressing Glutamine Anaplerosis and Osteogenic Differentiation of Mesenchymal Stem Cells.

Stem Cells 2017 02 21;35(2):411-424. Epub 2016 Aug 21.

Center for Human Tissues and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.

Aging deteriorates osteogenic capacity of mesenchymal stem/stromal cells (MSCs), contributing to imbalanced bone remodeling and osteoporosis. Glutaminase (Gls) catabolizes glutamine into glutamate at the first step of mitochondrial glutamine (Gln)-dependent anaplerosis which is essential for MSCs upon osteogenic differentiation. Estrogen-related receptor α (ERRα) regulates genes required for mitochondrial function. Here, we found that ERRα and Gls are upregulated by osteogenic induction in human MSCs (hMSCs). In contrast, osteogenic differentiation capacity and glutamine consumption of MSCs, as well as ERRα, Gls and osteogenic marker genes are significantly reduced with age. We demonstrated that ERRα binds to response elements on Gls promoter and affects glutamine anaplerosis through transcriptional induction of Gls. Conversely, mTOR inhibitor rapamycin, ERRα inverse agonist compound 29 or Gls inhibitor BPTES leads to reduced Gln anaplerosis and deteriorated osteogenic differentiation of hMSCs. Importantly, overexpression of ERRα or Gls restored impairment by these inhibitors. Finally, we proved that compensated ERRα or Gls expression indeed potentiated Gln anaplerosis and osteogenic capability of elderly mice MSCs in vitro. Together, we establish that Gls is a novel ERRα target gene and ERRα/Gls signaling pathway plays an important role in osteogenic differentiation of MSCs, providing new sights into novel regenerative therapeutics development. Our findings suggest that restoring age-related mitochondrial Gln-dependent anaplerosis may be beneficial for degenerative bone disorders such as osteoporosis. Stem Cells 2017;35:411-424.
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http://dx.doi.org/10.1002/stem.2470DOI Listing
February 2017

Activation of farnesoid X receptor promotes triglycerides lowering by suppressing phospholipase A2 G12B expression.

Mol Cell Endocrinol 2016 11 25;436:93-101. Epub 2016 Jul 25.

Center for Human Tissues and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China. Electronic address:

As a novel mediator of hepatic very low-density lipoproteins (VLDL) secretion, phospholipase A2 G12B (PLA2G12B) is transcriptionally regulated by hepatocyte nuclear factor-4 alpha (HNF-4α). Farnesoid X receptor (FXR) plays a critical role in maintaining bile acids and triglycerides (TG) homeostasis. Here we report that FXR regulates serum TG level in part through PLA2G12B. Activation of FXR by chenodeoxycholic acid (CDCA) or GW4064 significantly decreased PLA2G12B expression in HepG2 cells. PLA2G12B expression was transcriptionally repressed due to an FXR-mediated up-regulation of small heterodimer partner (SHP) which functionally suppresses HNF-4α activity. We found that hepatic PLA2G12B expression was suppressed and serum TG level reduced in high fat diet mice treated with CDCA. Concurrently, CDCA treatment lowered hepatic VLDL-TG secretion. Our data demonstrate that activation of FXR promotes TG lowering, not only by decreasing de novo lipogenesis but also reducing hepatic secretion of TG-rich VLDL particles in part through suppressing PLA2G12B expression.
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http://dx.doi.org/10.1016/j.mce.2016.07.027DOI Listing
November 2016

Altered Resting-State Amygdala Functional Connectivity after Real-Time fMRI Emotion Self-Regulation Training.

Biomed Res Int 2016 21;2016:2719895. Epub 2016 Feb 21.

China National Digital Switching System Engineering and Technological Research Center, Zhengzhou, Henan 450000, China.

Real-time fMRI neurofeedback (rtfMRI-nf) is a promising tool for enhancing emotion regulation capability of subjects and for the potential alleviation of neuropsychiatric disorders. The amygdala is composed of structurally and functionally distinct nuclei, such as the basolateral amygdala (BLA) and centromedial amygdala (CMA), both of which are involved in emotion processing, generation, and regulation. However, the effect of rtfMRI-nf on the resting-state functional connectivity (rsFC) of BLA and CMA remains to be elucidated. In our study, participants were provided with ongoing information on their emotion states by using real-time multivariate voxel pattern analysis. Results showed that participants presented significantly increased rsFC of BLA and CMA with prefrontal cortex, rostral anterior cingulate cortex, and some others related to emotion after rtfMRI-nf training. The findings provide important evidence for the emotion regulation effectiveness of rtfMRI-nf training and indicate its usefulness as a tool for the self-regulation of emotion.
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http://dx.doi.org/10.1155/2016/2719895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779507PMC
December 2016

Lactose-Functionalized Gold Nanorods for Sensitive and Rapid Serological Diagnosis of Cancer.

ACS Appl Mater Interfaces 2016 Mar 26;8(9):5813-20. Epub 2016 Feb 26.

Department of Physics and Materials Science, City University of Hong Kong , Tat Chee Avenue, Kowloon, Hong Kong, China.

Timely and accurate diagnosis of cancer is crucial to cancer treatment. However, serological diagnosis of cancer still faces great challenge because the conventional methodology based on the enzyme-linked immune sorbent assay (ELISA) is costly, time-consuming, and complicated, involving multiple steps. Herein, lactose-functionalized gold nanorods (Lac-GNRs) are fabricated as efficient biosensors to detect cancerous conditions based on the unique surface plasmon resonance properties of GNRs and high specificity of lactose to the galectin-1 cancer biomarker. A trace concentration of galectin-1 as small as 10(-13) M can be detected by Lac-GNRs. The comparative study among BSA, galectin-3, and galectin-1 demonstrates the good specificity of Lac-GNRs to galectin-1 either in aqueous solutions or in the complex and heterogeneous serum specimens. Clinical tests show that the Lac-GNRs biosensors can readily distinguish the serums of cancer patients from those of healthy persons simply by using a microplate reader or even direct visual observation. The Lac-GNRs biosensing platform is highly efficient and easy to use and have great potential in rapid screening of cancer patients.
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http://dx.doi.org/10.1021/acsami.5b11192DOI Listing
March 2016

Aberrant Topological Patterns of Structural Cortical Networks in Psychogenic Erectile Dysfunction.

Front Hum Neurosci 2015 18;9:675. Epub 2015 Dec 18.

Department of Radiology, Henan Provincial People's Hospital Zhengzhou, China.

Male sexual arousal (SA) has been known as a multidimensional experience involving closely interrelated and coordinated neurobehavioral components that rely on widespread brain regions. Recent functional neuroimaging studies have shown relation between abnormal/altered dynamics in these circuits and male sexual dysfunction. However, alterations in the topological organization of structural brain networks in male sexual dysfunction are still unclear. Here, we used graph theory to investigate the topological properties of large-scale structural brain networks, which were constructed using inter-regional correlations of cortical thickness between 78 cortical regions in 40 patients with psychogenic erectile dysfunction (pED) and 39 normal controls. Compared with normal controls, pED patients exhibited a less optimal global topological organization with reduced global and increased local efficiencies. Our results suggest disrupted neural integration among distant brain regions in pED patients, consistent with previous reports of impaired white matter structure and abnormal functional integrity in pED. Additionally, disrupted global network topology in pED was observed to be primarily relevant to altered subnetwork and nodal properties within the networks mediating the cognitive, motivational and inhibitory processes of male SA, possibly indicating disrupted integration of these networks in the whole brain networks and might account for pED patients' abnormal cognitive, motivational and inhibitory processes for male SA. In total, our findings provide evidence for disrupted integrity in large-scale brain networks underlying the neurobehavioral processes of male SA in pED and provide new insights into the understanding of the pathophysiological mechanisms of pED.
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http://dx.doi.org/10.3389/fnhum.2015.00675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683194PMC
January 2016

Cortical Structural Connectivity Alterations in Primary Insomnia: Insights from MRI-Based Morphometric Correlation Analysis.

Biomed Res Int 2015 11;2015:817595. Epub 2015 Oct 11.

Department of Radiology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan 450003, China.

The etiology and maintenance of insomnia are proposed to be associated with increased cognitive and physiological arousal caused by acute stressors and associated cognitive rumination. A core feature of such hyperarousal theory of insomnia involves increased sensory processing that interferes with the onset and maintenance of sleep. In this work, we collected structural magnetic resonance imaging data from 35 patients with primary insomnia and 35 normal sleepers and applied structural covariance analysis to investigate whether insomnia is associated with disruptions in structural brain networks centered at the sensory regions (primary visual, primary auditory, and olfactory cortex). As expected, insomnia patients showed increased structural covariance in cortical thickness between sensory and motor regions. We also observed trends of increased covariance between sensory regions and the default-mode network, and the salience network regions, and trends of decreased covariance between sensory regions and the frontoparietal working memory network regions, in insomnia patients. The observed changes in structural covariance tended to correlated with poor sleep quality. Our findings support previous functional neuroimaging studies and provide novel insights into variations in brain network configuration that may be involved in the pathophysiology of insomnia.
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http://dx.doi.org/10.1155/2015/817595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619857PMC
August 2016

Surface Evolution of Nano-Textured 4H-SiC Homoepitaxial Layers after High Temperature Treatments: Morphology Characterization and Graphene Growth.

Nanomaterials (Basel) 2015 Sep 18;5(3):1532-1543. Epub 2015 Sep 18.

Key Laboratory of Semiconductor Materials Science, Institute of Semiconductors, Chinese Academy of Sciences, P.O. Box 912, Beijing 100083, China.

Nano-textured 4H-SiC homoepitaxial layers (NSiCLs) were grown on 4H-SiC(0001) substrates using a low pressure chemical vapor deposition technique (LPCVD), and subsequently were subjected to high temperature treatments (HTTs) for investigation of their surface morphology evolution and graphene growth. It was found that continuously distributed nano-scale patterns formed on NSiCLs which were about submicrons in-plane and about 100 nanometers out-of-plane in size. After HTTs under vacuum, pattern sizes reduced, and the sizes of the remains were inversely proportional to the treatment time. Referring to Raman spectra, the establishment of multi-layer graphene (MLG) on NSiCL surfaces was observed. MLG with ² disorders was obtained from NSiCLs after a high temperature treatment under vacuum at 1700 K for two hours, while MLG without ² disorders was obtained under Ar atmosphere at 1900 K.
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http://dx.doi.org/10.3390/nano5031532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304623PMC
September 2015

Structural insights into aberrant cortical morphometry and network organization in psychogenic erectile dysfunction.

Hum Brain Mapp 2015 Nov 12;36(11):4469-82. Epub 2015 Aug 12.

Department of Radiology, Henan Provincial People's Hospital, Henan, China.

Functional neuroimaging studies have revealed abnormal brain dynamics of male sexual arousal (SA) in psychogenic erectile dysfunction (pED). However, the neuroanatomical correlates of pED are still unclear. In this work, we obtained cortical thickness (CTh) measurements from structural magnetic resonance images of 40 pED patients and 39 healthy control subjects. Abnormalities in CTh related to pED were explored using a scale space search based brain morphometric analysis. Organizations of brain structural covariance networks were analyzed as well. Compared with healthy men, pED patients showed significantly decreased CTh in widespread cortical regions, most of which were previously reported to show abnormal dynamics of male SA in pED, such as the medial prefrontal, orbitofrontal, cingulate, inferotemporal, and insular cortices. CTh reductions in these areas were found to be significantly correlated with male sexual functioning degradation. Moreover, pED patients showed decreased interregional CTh correlations from the right lateral orbitofrontal cortex to the right supramarginal gyrus and the left angular cortex, implying disassociations between the cognitive, motivational, and inhibitory networks of male SA in pED. This work provides structural insights on the complex phenomenon of psychogenic sexual dysfunction in men, and suggests a specific vulnerability factor, possibly as an extra "organic" factor, that may play an important role in pED.
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http://dx.doi.org/10.1002/hbm.22925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869733PMC
November 2015

Complete mitochondrial genome of the hybrid of Acipenser schrenckii (♀) × Huso dauricus (♂).

Mitochondrial DNA A DNA Mapp Seq Anal 2016 07 30;27(4):2887-8. Epub 2015 Jun 30.

a Institute of Chinese Sturgeon, China Three Gorges Corporation , Yichang , China and.

The complete mitochondrial genome sequence of the hybrid of Acipenser schrenckii (♀) × Huso dauricus (♂) (A × H) was first determined by a PCR-based sequencing method in this study. The mitochondrial was 16 687 bp in length, including 13 protein genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one control region. All genes were encoded on the heavy strain except for ND6 and eight tRNA genes. Base composition of the heavy strain was A (29.80%), T (24.42%), C (28.94%), G (16.82%), and with A + T bias of 54.26%. Compared with the complete mitochondrial genome of the parents, results showed the hybrid sturgeon was consistent with a maternal inheritance; however, we also found ND6 and tRNA-Glu which were species-specific for the male parent H. dauricus. The complete mitochondrial genome sequence of the A × H provided an important data set for further study in mitochondrial inheritance mechanism.
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http://dx.doi.org/10.3109/19401736.2015.1060422DOI Listing
July 2016

Nelfinavir and nelfinavir analogs block site-2 protease cleavage to inhibit castration-resistant prostate cancer.

Sci Rep 2015 Apr 16;5:9698. Epub 2015 Apr 16.

1] Department of Molecular Pharmacology, Beckman Research Institute of the City of Hope, Duarte, CA, USA [2] Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.

Nelfinavir and its analogs inhibit proliferation and induce apoptosis of castration-resistant prostate cancer through inhibition of site-2 protease (S2P) activity, which leads to suppression of regulated intramembrane proteolysis. Western blotting in nelfinavir and its analog treated cells confirms accumulation of precursor SREBP-1 and ATF6. Nelfinavir and its analogs inhibit human homolog M. jannaschii S2P cleavage of an artificial protein substrate CED-9 in an in vitro proteolysis assay in a dose-dependent manner. Nelfinavir and its analogs are more potent inhibitors of S2P cleavage activity than 1,10-phenanthroline, a metalloprotease-specific inhibitor. Further, cluster analysis of gene expression from treated DU145 and PC3 cell lines demonstrate a close similarity of nelfinavir, its analogs, and 1,10-phenanthroline. These results show nelfinavir and its analogs inhibit castration-resistant prostate cancer proliferation by blocking regulated intramembrane proteolysis through suppression of S2P cleavage activity. This leads to accumulation of precursor SREBP-1 and ATF6, and development of insufficient reserves of their transcriptionally-active forms. The present results validate S2P and regulated intramembrane proteolysis as novel therapeutic targets for castration-resistant prostate cancer therapeutics. A clinical trial of nelfinavir or its analogs should be developed for castration-resistant prostate cancer.
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http://dx.doi.org/10.1038/srep09698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816264PMC
April 2015

Self-regulation of brain activity in patients with postherpetic neuralgia: a double-blind randomized study using real-time FMRI neurofeedback.

PLoS One 2015 7;10(4):e0123675. Epub 2015 Apr 7.

Department of Radiology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Background: A pilot study has shown that real-time fMRI (rtfMRI) neurofeedback could be an alternative approach for chronic pain treatment. Considering the relative small sample of patients recruited and not strictly controlled condition, it is desirable to perform a replication as well as a double-blinded randomized study with a different control condition in chronic pain patients. Here we conducted a rtfMRI neurofeedback study in a subgroup of pain patients - patients with postherpetic neuralgia (PHN) and used a different sham neurofeedback control. We explored the feasibility of self-regulation of the rostral anterior cingulate cortex (rACC) activation in patients with PHN through rtfMRI neurofeedback and regulation of pain perception.

Methods: Sixteen patients (46-71 years) with PHN were randomly allocated to a experimental group (n = 8) or a control group (n = 8). 2 patients in the control group were excluded for large head motion. The experimental group was given true feedback information from their rACC whereas the control group was given sham feedback information from their posterior cingulate cortex (PCC). All subjects were instructed to perform an imagery task to increase and decrease activation within the target region using rtfMRI neurofeedback.

Results: Online analysis showed 6/8 patients in the experimental group were able to increase and decrease the blood oxygen level dependent (BOLD) fMRI signal magnitude during intermittent feedback training. However, this modulation effect was not observed in the control group. Offline analysis showed that the percentage of BOLD signal change of the target region between the last and first training in the experimental group was significantly different from the control group's and was also significantly different than 0. The changes of pain perception reflected by numerical rating scale (NRS) in the experimental group were significantly different from the control group. However, there existed no significant correlations between BOLD signal change and NRS change.

Conclusion: Patients with PHN could learn to voluntarily control over activation in rACC through rtfMRI neurofeedback and alter their pain perception level. The present study may provide new evidence that rtfMRI neurofeedback training may be a supplemental approach for chronic clinical pain management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123675PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388697PMC
January 2016

Fast responsive and highly efficient optical upconverter based on phosphorescent OLED.

ACS Appl Mater Interfaces 2014 Nov 23;6(21):19011-6. Epub 2014 Oct 23.

Key Laboratory of Semiconductor Materials Science, Institute of semiconductors, Chinese Academy of Sciences , Beijing, China.

In this work, an organic-inorganic hybrid optical upconverter that can convert irradiated 980 nm IR light to 510 nm green phosphorescence sensitively was fabricated and studied. fac-Tris(2-phenylpyridine) iridium (Ir(ppy)3) doped 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (CBP) was used as emitting layer in the phosphorescent organic light-emitting diode (OLED) unit. The upconverter using a phosphorescent OLED as display unit can achieve a higher upconversion efficiency and a low power consumption when compared with the one using fluorescent. An upconversion efficiency of 4.8% can be achieved for phosphorescent device at 15 V, much higher than that of fluorescent one (2.0%). The upconverter's transient optical and electric response to IR pulse were also investigated for the first time. The response time was found to be influenced by IR intensity and applied voltage. It has a response time as short as 60 μs. The rapid response property of the upconverter makes it feasible to be applied to high-speed IR imaging systems.
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http://dx.doi.org/10.1021/am504721gDOI Listing
November 2014

Reduced cerebral blood flow in genetic prion disease with PRNP D178N-129M mutation: an arterial spin labeling MRI study.

J Clin Neurosci 2015 Jan 11;22(1):204-6. Epub 2014 Sep 11.

Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China. Electronic address:

The D178N mutation in the PRNP gene is associated with fatal familial insomnia and Creutzfeldt-Jakob disease (CJD). Typically, the D178N mutation associated with the 129M genotype is related to fatal familial insomnia while the same mutation associated with the 129V genotype is linked to familial CJD. We describe a D178N-129M haplotype in a patient with early, severe dementia and late-onset minor insomnia, mainly presenting as the CJD phenotype. Cerebrospinal fluid 14-3-3 protein was positive. Diffusion weighted imaging demonstrated widespread cortical ribbon-like high signal intensity, which was also seen in the basal ganglia bilaterally. Arterial spin labeling (ASL) MRI showed severe hypoperfusion in the cerebral cortex, basal ganglia and thalami but this was least marked in the thalami. Neuroimaging abnormalities were more prominent in the cerebral cortex than the thalamus, which was in line with the clinical picture of severe dementia rather than insomnia. ASL-MRI seems to be a useful tool for the detection and follow-up of perfusion changes in patients and asymptomatic carriers harboring the PRNP mutation.
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http://dx.doi.org/10.1016/j.jocn.2014.05.040DOI Listing
January 2015

Crossed cerebellar diaschisis detected by arterial spin-labeled perfusion magnetic resonance imaging in subacute ischemic stroke.

J Stroke Cerebrovasc Dis 2014 Oct 31;23(9):2378-83. Epub 2014 Aug 31.

Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, Henan, China. Electronic address:

Background: Crossed cerebellar diaschisis (CCD) was a common radiological phenomenon manifested as reduced blood flow and metabolism in the cerebellar hemisphere contralateral to a supratentorial cerebral lesion. The hypoperfusion and hypometabolism in the contralateral cerebellum in CCD was traditionally detected by positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The present prospective study aimed to assess the detection of CCD in subacute stage ischemic stroke by arterial spin-labeling (ASL) perfusion technique with a 3.0-T magnetic resonance imaging (MRI) scanner.

Methods: ASL images were obtained from 46 patients with supratentorial ischemic stroke at subacute stage. Regional cerebral blood flow values in the cerebellar hemispheres were measured on a region of interest basis.

Results: Twenty-four of 46 (52%) patients showed CCD phenomenon by ASL-MRI method, which was in line with the PET/SPECT series. Infarctions in basal ganglia areas are prone to cause CCD.

Conclusions: With advantages in easy acquisition and no radiation, ASL-MRI seems to be an ideal tool for the detection and follow-up of CCD.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.05.009DOI Listing
October 2014

3D alternating direction TV-based cone-beam CT reconstruction with efficient GPU implementation.

Comput Math Methods Med 2014 19;2014:982695. Epub 2014 Jun 19.

National Digital Switching System Engineering & Technological R&D Centre, Zhengzhou, Henan 450002, China.

Iterative image reconstruction (IIR) with sparsity-exploiting methods, such as total variation (TV) minimization, claims potentially large reductions in sampling requirements. However, the computation complexity becomes a heavy burden, especially in 3D reconstruction situations. In order to improve the performance for iterative reconstruction, an efficient IIR algorithm for cone-beam computed tomography (CBCT) with GPU implementation has been proposed in this paper. In the first place, an algorithm based on alternating direction total variation using local linearization and proximity technique is proposed for CBCT reconstruction. The applied proximal technique avoids the horrible pseudoinverse computation of big matrix which makes the proposed algorithm applicable and efficient for CBCT imaging. The iteration for this algorithm is simple but convergent. The simulation and real CT data reconstruction results indicate that the proposed algorithm is both fast and accurate. The GPU implementation shows an excellent acceleration ratio of more than 100 compared with CPU computation without losing numerical accuracy. The runtime for the new 3D algorithm is about 6.8 seconds per loop with the image size of 256 × 256 × 256 and 36 projections of the size of 512 × 512.
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http://dx.doi.org/10.1155/2014/982695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089849PMC
March 2015

Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy.

Biomaterials 2014 Jul 25;35(22):5965-76. Epub 2014 Apr 25.

Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China. Electronic address:

Developing safe and effective carriers of small interference RNA (siRNA) is a significant demand for the systemic delivery of siRNA. In this study, low-density lipoprotein (LDL) was isolated from human plasma and loaded with cholesterol-conjugated siRNA to silence the multidrug resistant gene of tumors. Chol-siRNA/LDL-coupled N-succinyl chitosan nanoparticles loaded with doxorubicin (Dox-siRNA/LDL-SCS-NPs) were then prepared and characterised. The Dox-siRNA/LDL-SCS-NPs had average particle size of 206.4 ± 9.2 nm, entrapment efficiency of 71.06% ± 1.42%, and drug-loading amount of 12.35% ± 0.87%. In vitro antitumor activity revealed that cell growth was significantly inhibited. The accumulation of Dox by fluorescence microscopy and flow cytometry showed that LDL-coupled nanoparticles were more easily taken up than Dox-SCS-NPs. Results of confocal microscopy and reverse transcription-PCR revealed the highly efficient uptake of siRNA and the decrease in mdr1 mRNA expression. LDL-coupled nanoparticles protected siRNA from macrophage phagocytosis by dynamic observation using live cell station. In vivo tumor-targeting suggested that Cy7-labelled Dox-LDL-SCS-NPs were markedly accumulated in an analyzed in situ liver tumor model. Results indicated that LDL-SCS-NPs were effective tumor-targeting vectors and that the preparation form may provide a new strategy for co-delivering siRNA and antitumor drugs.
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http://dx.doi.org/10.1016/j.biomaterials.2014.03.088DOI Listing
July 2014

Effects of Tai Chi on balance and fall prevention in Parkinson's disease: a randomized controlled trial.

Clin Rehabil 2014 Aug 11;28(8):748-753. Epub 2014 Feb 11.

Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Sichuan, China Institute for Disaster Management and Reconstruction, Sichuan University - Hong Kong Polytechnic University, Sichuan, China

Objectives: To examine the effects of Tai Chi on balance and functional mobility in people with Parkinson's disease, and determine whether fall incidence could be reduced by the Tai Chi exercise.

Design: Single blinded randomized control trial with 6 months' follow-up.

Setting: A hospital and general community.

Participants: Patients (n=76) diagnosed with idiopathic Parkinson's disease, over 40 years old, able to walk independently and fell at least one time during the past 12 months.

Interventions: The Tai Chi group (n=37) received 24-form Yang style Tai Chi exercise for 60 minutes each time, three times a week and lasted for 12 weeks. The control group (n=39) received no intervention.

Main Outcome Measures: Berg Balance Scale (BBS), Unified Parkinson's Disease Rating Scale (UPDRS) III, Timed Up&Go (TUG) and occurrences of falls.

Results: The Tai Chi group improved more than the control group on the BBS (p<0.05), but there was no difference on UPDRS III scores and Timed Up&Go (p>0.05). During the 6-month follow-up, only 8 (21.6%) out of 37 patients in the Tai Chi group had experience of falls comparing to 19 (48.7%) out of 39 patients in the control group (p<0.05). The average times of falls were 0.30±0.62 in the Tai Chi group compared with 0.64±0.74 in the control group (p<0.05).

Conclusions: Our findings suggested that Tai Chi exercise could improve the balance and decrease the fall risks in patients with Parkinson's disease.
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http://dx.doi.org/10.1177/0269215514521044DOI Listing
August 2014

Effects of low-level autonomic stimulation on prevention of atrial fibrillation induced by acute electrical remodeling.

ScientificWorldJournal 2013 20;2013:781084. Epub 2013 Jun 20.

Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.

Background: Rapid atrial pacing (RAP) can induce electrical and autonomic remodeling and facilitate atrial fibrillation (AF). Recent reports showed that low-level vagosympathetic nerve stimulation (LLVNS) can suppress AF, as an antiarrhythmic effect. We hypothesized that LLVNS can reverse substrate heterogeneity induced by RAP.

Methods And Results: Mongrel dogs were divided into (LLVNS+RAP) and RAP groups. Electrode catheters were sutured to multiple atrial sites, and LLVNS was applied to cervical vagosympathetic trunks with voltage 50% below the threshold slowing sinus rate by ≤ 30 msec. RAP induced a significant decrease in effective refractory period (ERP) and increase in the window of vulnerability at all sites, characterized by descending and elevated gradient differences towards the ganglionic plexi (GP) sites, respectively. The ERP dispersion was obviously enlarged by RAP and more significant when the ERP of GP-related sites was considered. Recovery time from AF was also prolonged significantly as a result of RAP. LLVNS could reverse all these changes induced by RAP and recover the heterogeneous substrate to baseline. Conclusions. LLVNS can reverse the electrical and autonomic remodeling and abolish the GP-central gradient differences induced by RAP, and thus it can recover the homogeneous substrate, which may be the underlying mechanism of its antiarrhythmic effect.
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http://dx.doi.org/10.1155/2013/781084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705940PMC
September 2013

Reversing bone loss by directing mesenchymal stem cells to bone.

Stem Cells 2013 Sep;31(9):2003-14

Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California, USA.

Bone regeneration by systemic transplantation of mesenchymal stem cells (MSCs) is problematic due to the inability to control the MSCs' commitment, growth, and differentiation into functional osteoblasts on the bone surface. Our research group has developed a method to direct the MSCs to the bone surface by conjugating a synthetic peptidomimetic ligand (LLP2A) that has high affinity for activated α4β1 integrin on the MSC surface, with a bisphosphonates (alendronate) that has high affinity for bone (LLP2A-Ale), to direct the transplanted MSCs to bone. Our in vitro experiments demonstrated that mobilization of LLP2A-Ale to hydroxyapatite accelerated MSC migration that was associated with an increase in the phosphorylation of Akt kinase and osteoblastogenesis. LLP2A-Ale increased the homing of the transplanted MSCs to bone as well as the osteoblast surface, significantly increased the rate of bone formation and restored both trabecular and cortical bone loss induced by estrogen deficiency or advanced age in mice. These results support LLP2A-Ale as a novel therapeutic option to direct the transplanted MSCs to bone for the treatment of established bone loss related to hormone deficiency and aging.
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http://dx.doi.org/10.1002/stem.1461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795809PMC
September 2013

Growth of Hexagonal Columnar Nanograin Structured SiC Thin Films on Silicon Substrates with Graphene-Graphitic Carbon Nanoflakes Templates from Solid Carbon Sources.

Materials (Basel) 2013 Apr 16;6(4):1543-1553. Epub 2013 Apr 16.

Key Laboratory of Semiconductor Materials Science, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083, China.

We report a new method for growing hexagonal columnar nanograin structured silicon carbide (SiC) thin films on silicon substrates by using graphene-graphitic carbon nanoflakes (GGNs) templates from solid carbon sources. The growth was carried out in a conventional low pressure chemical vapor deposition system (LPCVD). The GGNs are small plates with lateral sizes of around 100 nm and overlap each other, and are made up of nanosized multilayer graphene and graphitic carbon matrix (GCM). Long and straight SiC nanograins with hexagonal shapes, and with lateral sizes of around 200-400 nm are synthesized on the GGNs, which form compact SiC thin films.
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http://dx.doi.org/10.3390/ma6041543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452306PMC
April 2013

Phase I study of nelfinavir in liposarcoma.

Cancer Chemother Pharmacol 2012 Dec 16;70(6):791-9. Epub 2012 Sep 16.

Department of Medical Oncology, City of Hope, Duarte, CA 91010, USA.

Purpose: HIV protease inhibitors are associated with HIV protease inhibitor-related lipodystrophy syndrome. We hypothesized that liposarcomas would be similarly susceptible to the apoptotic effects of an HIV protease inhibitor, nelfinavir.

Methods: We conducted a phase I trial of nelfinavir for liposarcomas. There was no limit to prior chemotherapy. The starting dose was 1,250 mg twice daily (Level 1). Doses were escalated in cohorts of three to a maximally evaluated dose of 4,250 mg (Level 5). One cycle was 28 days. Steady-state pharmacokinetics (PKs) for nelfinavir and its primary active metabolite, M8, were determined at Levels 4 (3,000 mg) and 5.

Results: Twenty subjects (13 males) were enrolled. Median (range) age was 64 years (37-81). One subject at Level 1 experienced reversible, grade 3 pancreatitis after 1 week and was replaced. No other dose-limiting toxicities were observed. Median (range) number of cycles was 3 (0.6-13.5). Overall best responses observed were 1 partial response, 1 minor response, 4 stable disease, and 13 progressive disease. Mean peak plasma levels and AUCs for nelfinavir were higher at Level 4 (7.3 mg/L; 60.9 mg/L × h) than 5 (6.3 mg/L; 37.7 mg/L × h). The mean ratio of M8:nelfinavir AUCs for both levels was ~1:3.

Conclusions: PKs demonstrate auto-induction of nelfinavir clearance at the doses studied, although the mechanism remains unclear. Peak plasma concentrations were within range where anticancer activity was demonstrated in vitro. M8 metabolite is present at ~1/3 the level of nelfinavir and may also contribute to the anticancer activity observed.
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http://dx.doi.org/10.1007/s00280-012-1961-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904496PMC
December 2012

Improved efficiency of organic/inorganic hybrid near-infrared light upconverter by device optimization.

ACS Appl Mater Interfaces 2012 Sep 6;4(9):4976-80. Epub 2012 Sep 6.

Material Science Center, Institute of Semiconductors, Chinese Academy of Sciences, P.O. Box 912, Beijing, 100083, People's Republic of China.

An organic/inorganic hybrid up-conversion device was demonstrated in this work, which can convert near-infrared light (NIR) to visible green at high conversion efficiency. The upconverter was fabricated by integrating an In(0.12)Ga(0.88)As/GaAs multiquantum wells (MQWs) photodetector (PD) with an organic light emitting diode (OLED). The up-conversion efficiency of 4.0 W/W % was obtained at 20 V under NIR illumination of 1 mW/mm(2) at room temperature by optimizing the structure of the PD unit and adding MoO(3) doped perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) as interfacial layer of OLED. Meanwhile, the green light output induced by NIR achieved 6050 cd/m(2), which proves that the organic/inorganic hybrid upconverter an excellent candidate that can be applied in light converter field.
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http://dx.doi.org/10.1021/am301340pDOI Listing
September 2012

Photoluminescent silicon nanocrystal-based multifunctional carrier for pH-regulated drug delivery.

ACS Appl Mater Interfaces 2012 Jul 16;4(7):3424-31. Epub 2012 Jul 16.

State Key Laboratory of Applied Organic Chemistry, §School of Basic Medical Science, ⊥School of Pharmacy, Lanzhou University , Lanzhou 730000, China.

A core-shell structured multifunctional carrier with nanocrystalline silicon (ncSi) as the core and a water-soluble block copolymer as the shell based on a poly(methacrylic acid) (PMAA) inner shell and polyethylene glycol (MPEG) outer shell (ncSi-MPM) was synthesized for drug delivery. The morphology, composition, and properties of the resulting ncSi-MPM were determined by comprehensive multianalytical characterization, including (1)H NMR spectroscopy, FTIR spectroscopy, XPS spectroscopy, TEM, DLS, and fluorescence spectroscopy analyses. The size of the resulting ncSi-MPM nanocarriers ranged from 40 to 110 nm under a simulated physiological environment. The loading efficiency of model drug doxorubicin (DOX) was approximately 6.1-7.4 wt % for ncSi-MPM and the drug release was pH controlled. Cytotoxicity studies demonstrated that DOX-loaded ncSi-MPM showed high anticancer activity against Hela cells. Hemolysis percentages (<2%) of ncSi-MPM were within the scope of safe values. Fluorescent imaging studies showed that the nanocarriers could be used as a tracker at the cellular level. Integration of the above functional components may result in ncSi-MPM becoming a promising multifunctional carrier for drug delivery and biomedical applications.
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http://dx.doi.org/10.1021/am300877vDOI Listing
July 2012

Wntless functions in mature osteoblasts to regulate bone mass.

Proc Natl Acad Sci U S A 2012 Aug 28;109(33):E2197-204. Epub 2012 Jun 28.

Center for Skeletal Disease Research and Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, MI 49503, USA

Recent genome-wide association studies of individuals of Asian and European descent have found that SNPs located within the genomic region (1p31.3) encoding the Wntless (Wls)/Gpr177 protein are associated significantly with reduced bone mineral density. Wls/Gpr177 is a newly identified chaperone protein that specifically escorts Wnt ligands for secretion. Given the strong functional association between the Wnt signaling pathways and bone development and homeostasis, we generated osteoblast-specific Wls-deficient (Ocn-Cre;Wls-flox) mice. Homozygous conditional knockout animals were born at a normal Mendelian frequency. Whole-body dual-energy X-ray absorptiometry scanning revealed that bone-mass accrual was significantly inhibited in homozygotes as early as 20 d of age. These homozygotes had spontaneous fractures and a high frequency of premature lethality at around 2 mo of age. Microcomputed tomography analysis and histomorphometric data revealed a dramatic reduction of both trabecular and cortical bone mass in homozygous mutants. Bone formation in homozygotes was severely impaired, but no obvious phenotypic change was observed in mice heterozygous for the conditional deletion. In vitro studies showed that Wls-deficient osteoblasts had a defect in differentiation and mineralization, with significant reductions in the expression of key osteoblast differentiation regulators. In summary, these results reveal a surprising and crucial role of osteoblast-secreted Wnt ligands in bone-mass accrual.
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http://dx.doi.org/10.1073/pnas.1120407109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3421196PMC
August 2012

Uptake and transport of a novel anticancer drug-delivery system: lactosyl-norcantharidin-associated N-trimethyl chitosan nanoparticles across intestinal Caco-2 cell monolayers.

Int J Nanomedicine 2012 11;7:1921-30. Epub 2012 Apr 11.

Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, People's Republic of China.

In this paper, novel liver-targeting nanoparticles (NPs), lactosyl-norcantharidin (Lac-NCTD)-associated N-trimethyl chitosan (TMC) NPs (Lac-NCTD-TMC-NPs), were prepared using ionic cross-linkage. The physical properties, particle size, and encapsulation efficiency of the nanoparticles were then investigated. The continuous line of heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) cell monolayer model was used to study the transport mechanism of Lac-NCTD, and the effects of factors such as time, temperature, pH level, drug concentration, enhancers, and inhibitors. This model was also used to indicate the differences among Lac-NCTD, Lac-NCTD-associated chitosan NPs (Lac-NCTD-CS-NPs), and Lac-NCTD-TMC- NPs in the absorption and transportation of membranes. Drug concentration levels were measured using high-performance liquid chromatography. Active transport and paracellular transport were suggested to be both the primary and secondary mechanisms for Lac-NCTD absorption, respectively. Lac-NCTD uptake and absorption were not controlled by pH levels, but were positively correlated to uptake time, and negatively correlated to temperature. The basolateral to apical apparent permeability coefficients (Papps) were higher than those of the apical to basolateral values. The inhibitor of P-glycoprotein and the multidrug resistance-associated protein 2 significantly enhanced the uptake amount of Lac-NCTD. Compared with Lac-NCTD, Lac-NCTD-CS-NPs and Lac-NCTD-TMC-NPs significantly enhanced drug absorption. Additionally, the latter exhibited stronger action. Lac-NCTD-NPs could penetrate the plasma membrane of Caco-2 cells and translocate into the cytoplasm and even into the nucleus. Nanoparticles were uptaken into Caco-2 cells through the endocytosis pathway.
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http://dx.doi.org/10.2147/IJN.S30034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352694PMC
December 2012

Nelfinavir inhibits regulated intramembrane proteolysis of sterol regulatory element binding protein-1 and activating transcription factor 6 in castration-resistant prostate cancer.

FEBS J 2012 Jul 21;279(13):2399-411. Epub 2012 May 21.

Department of Molecular Pharmacology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.

Nelfinavir induces apoptosis in liposarcoma by inhibiting site-2 protease (S2P) activity, which leads to suppression of regulated intramembrane proteolysis. We postulate similar effects in castration-resistant prostate cancer because it exhibits a lipogenic phenotype. Nelfinavir inhibited androgen receptor activation in androgen-sensitive prostate cancer and the nuclear translocation of the fusion proteins sterol regulatory element binding protein-1 (SREBP-1)-enhanced green fluorescence protein (EGFP) and activating transcription factor 6 (ATF6)-EGFP in castration-resistant prostate cancer cells, viewed under confocal microscopy. Nelfinavir and site-1 protease (S1P) and S2P small interfering RNAs (siRNAs) reduced the proliferation of castration-resistant prostate cancer and induced apoptosis, which was opposed by autophagy. Inhibition of autophagy with hydroxychloroquine was additive to the apoptotic effect of nelfinavir. Western blotting of S1P and S2P siRNA knockdown and/or nelfinavir-treated cells confirmed the accumulation of precursor SREBP-1 and ATF6. 3,4-Dichloroisocoumarin, an S1P inhibitor, did not affect SREBP-1 processing. In contrast, 1,10-phenanthroline, an S2P inhibitor, reproduced the nelfinavir-treated molecular and biological phenotype. Nelfinavir-mediated inhibition of regulated intramembrane proteolysis led to the accumulation of unprocessed SREBP-1 and ATF6. This resulted in sequential endoplasmic reticulum stress, inhibition of the unfolded protein response, reduced fatty acid synthase expression and apoptosis, which was countered by autophagy. Inhibition of autophagy was at least additive to this pro-apoptotic effect. These findings provide new insights into nelfinavir-induced endoplasmic reticulum stress and cancer cell death, and lead us to propose investigating its clinical activity in castration-resistant prostate cancer. This report validates S2P as a therapeutic target in castration-resistant prostate cancer.
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http://dx.doi.org/10.1111/j.1742-4658.2012.08619.xDOI Listing
July 2012

Assembling photoluminescent silicon nanocrystals into periodic mesoporous organosilica.

J Am Chem Soc 2012 May 8;134(20):8439-46. Epub 2012 May 8.

Department of Chemistry, Lanzhou University, China.

A contemporary question in the intensely active field of periodic mesoporous organosilica (PMO) materials is how large a silsesquioxane precursor can be self-assembled under template direction into the pore walls of an ordered mesostructure. An answer to this question is beginning to emerge with the ability to synthesize dendrimer, buckyball, and polyhedral oligomeric silsesquioxane PMOs. In this paper, we further expand the library of large-scale silsesquioxane precursors by demonstrating that photoluminescent nanocrystalline silicon that has been surface-capped with oligo(triethoxysilylethylene), denoted as ncSi:(CH(2)CH(2)Si(OEt)(3))(n)H, can be self-assembled into a photoluminescent nanocrystalline silicon periodic mesoporous organosilica (ncSi-PMO). A comprehensive multianalytical characterization of the structural and optical properties of ncSi-PMO demonstrates that the material gainfully combines the photoluminescent properties of nanocrystalline silicon with the porous structure of the PMO. This integration of two functional components makes ncSi-PMO a promising multifunctional material for optoelectronic and biomedical applications.
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http://dx.doi.org/10.1021/ja209532eDOI Listing
May 2012
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