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1.  Microinfarct disruption of white matter structure 
Neurology  2014;83(2):182-188.
To evaluate the local effect of small asymptomatic infarctions detected by diffusion-weighted imaging (DWI) on white matter microstructure using longitudinal structural and diffusion tensor imaging (DTI).
Nine acute to subacute DWI lesions were identified in 6 subjects with probable cerebral amyloid angiopathy who had undergone high-resolution MRI both before and after DWI lesion detection. Regions of interest (ROIs) corresponding to the site of the DWI lesion (lesion ROI) and corresponding site in the nonlesioned contralateral hemisphere (control ROI) were coregistered to the pre- and postlesional scans. DTI tractography was additionally performed to reconstruct the white matter tracts containing the ROIs. DTI parameters (fractional anisotropy [FA], mean diffusivity [MD]) were quantified within each ROI, the 6-mm lesion-containing tract segments, and the entire lesion-containing tract bundle. Lesion/control FA and MD ratios were compared across time points.
The postlesional scans (performed a mean 7.1 ± 4.7 months after DWI lesion detection) demonstrated a decrease in median FA lesion/control ROI ratio (1.08 to 0.93, p = 0.038) and increase in median MD lesion/control ROI ratio (0.97 to 1.17, p = 0.015) relative to the prelesional scans. There were no visible changes on postlesional high-resolution T1-weighted and fluid-attenuated inversion recovery images in 4 of 9 lesion ROIs and small (2–5 mm) T1 hypointensities in the remaining 5. No postlesional changes in FA or MD ratios were detected in the 6-mm lesion-containing tract segments or full tract bundles.
Asymptomatic DWI lesions produce chronic local microstructural injury. The cumulative effects of these widely distributed lesions may directly contribute to small-vessel–related vascular cognitive impairment.
PMCID: PMC4117171  PMID: 24920857
2.  Mechanical writing of n-type conductive layers on the SrTiO3 surface in nanoscale 
Scientific Reports  2015;5:10841.
The fabrication and control of the conductive surface and interface on insulating SrTiO3 bulk provide a pathway for oxide electronics. The controllable manipulation of local doping concentration in semiconductors is an important step for nano-electronics. Here we show that conductive patterns can be written on bare SrTiO3 surface by controllable doping in nanoscale using the mechanical interactions of atomic force microscopy tip without applying external electric field. The conductivity of the layer is n-type, oxygen sensitive, and can be effectively tuned by the gate voltage. Hence, our findings have potential applications in oxide nano-circuits and oxygen sensors.
PMCID: PMC4455303  PMID: 26042679
3.  Identification of enzymes involved in SUMOylation in Trypanosoma brucei 
Scientific Reports  2015;5:10097.
Small ubiquitin-like modifier (SUMO), a reversible post-translational protein modifier, plays important roles in diverse cellular mechanisms. Three enzymes, E1 (activating enzyme), E2 (conjugating enzyme) and E3 (ligase), are involved in SUMO modification. SUMOylation system and process in higher eukaryotes have been well studied. However, in protozoa, such as Trypanosoma brucei (T. brucei), these remain poorly understood. Herein, we identified the E1 (TbAos1/TbUba2) and E2 (TbUbc9) enzymes of SUMOylation pathway in T. brucei by sequence analysis and GST pull-down assay. Furthermore, we successfully reconstructed the SUMOylation system in vitro with recombinant enzymes. Using this system, the active site of TbUba2 and TbUbc9 was revealed to be located at Cys343 and Cys132, respectively, and a centrin homologue (TbCentrin3) was identified to be a target of SUMOylation in T. brucei. Altogether, our results demonstrate that TbAos1/TbUba2 and TbUbc9 are the bona fide E1 and E2 enzymes of the SUMOylation system in T. brucei.
PMCID: PMC4426598  PMID: 25959766
4.  Enhancing the light-driven production of d-lactate by engineering cyanobacterium using a combinational strategy 
Scientific Reports  2015;5:9777.
It is increasingly attractive to engineer cyanobacteria for bulk production of chemicals from CO2. However, cofactor bias of cyanobacteria is different from bacteria that prefer NADH, which hampers cyanobacterial strain engineering. In this study, the key enzyme d-lactate dehydrogenase (LdhD) from Lactobacillus bulgaricus ATCC11842 was engineered to reverse its favored cofactor from NADH to NADPH. Then, the engineered enzyme was introduced into Synechococcus elongatus PCC7942 to construct an efficient light-driven system that produces d-lactic acid from CO2. Mutation of LdhD drove a fundamental shift in cofactor preference towards NADPH, and increased d-lactate productivity by over 3.6-fold. We further demonstrated that introduction of a lactic acid transporter and bubbling CO2-enriched air also enhanced d-lactate productivity. Using this combinational strategy, increased d-lactate concentration and productivity were achieved. The present strategy may also be used to engineer cyanobacteria for producing other useful chemicals.
PMCID: PMC4419521  PMID: 25940225
5.  New Insights into Intracellular Locations and Functions of Heme Oxygenase-1 
Antioxidants & Redox Signaling  2014;20(11):1723-1742.
Significance: Heme oxygenase-1 (HMOX1) plays a critical role in the protection of cells, and the inducible enzyme is implicated in a spectrum of human diseases. The increasing prevalence of cardiovascular and metabolic morbidities, for which current treatment approaches are not optimal, emphasizes the necessity to better understand key players such as HMOX1 that may be therapeutic targets. Recent Advances: HMOX1 is a dynamic protein that can undergo post-translational and structural modifications which modulate HMOX1 function. Moreover, trafficking from the endoplasmic reticulum to other cellular compartments, including the nucleus, highlights that HMOX1 may play roles other than the catabolism of heme. Critical Issues: The ability of HMOX1 to be induced by a variety of stressors, in an equally wide variety of tissues and cell types, represents an obstacle for the therapeutic exploitation of the enzyme. Any capacity to modulate HMOX1 in cardiovascular and metabolic diseases should be tempered with an appreciation that HMOX1 may have an impact on cancer. Moreover, the potential for heme catabolism end products, such as carbon monoxide, to amplify the HMOX1 stress response should be considered. Future Directions: A more complete understanding of HMOX1 modifications and the properties that they impart is necessary. Delineating these parameters will provide a clearer picture of the opportunities to modulate HMOX1 in human disease. Antioxid. Redox Signal. 20: 1723–1742.
PMCID: PMC3961787  PMID: 24180287
6.  Mirror neuron therapy for hemispatial neglect patients 
Scientific Reports  2015;5:8664.
Mirror neuron system(MNS) based therapy has been employed to treat stroke induced movement disorders. However, its potential effects on patients with hemispatial neglect were uninvestigated. The present study set out to test the therapeutic efficiency of video watching of series of hand actions/movements (protocol A) in two patients with left hemispatial neglect, due to the right hemisphere stroke. The video containing dynamic landscape of natural scene or cities but not human/animals was used as the protocol B. The “ABA” training procedure for 3 weeks therefore allows us to internally control the individual differences. Before and after each week of training, the Chinese behavioral inattention test- Hongkong version (CBIT-HK) was implemented to evaluate the hemispatial neglect severity. Functional magnetic resonance imaging (fMRI) experiment was implemented in two health subjects to reveal the difference of brain activation between protocol A and B. The results showed that protocol A rather than protocol B significantly improved the CBIT-HK scores at first and third weeks, respectively. Protocol A induced more bilateral activations including right inferior parietal lobe (supramarginal gyrus), which belongs to MNS and is also critical region resulting to hemineglect. Conclusion: MNS activation can provide a novel therapy for hemispatial neglect patients.
PMCID: PMC4345335  PMID: 25727354
7.  Aurora-A kinase-inactive mutants disrupt the interaction with Ajuba and cause defects in mitotic spindle formation and G2/M phase arrest in HeLa cells 
BMB Reports  2014;47(11):631-636.
Aurora-A is a centrosome-localized serine/threonine kinase that is overexpressed in multiple human cancers. We previously reported an intramolecular inhibitory regulation of Aurora-A between its N-terminal regulatory domain (Nt, amino acids [aa] 1-128) and the C-terminal catalytic domain (Cd, aa 129-403). Here, we demonstrate that although both Aurora-A mutants (AurA-K250G and AurA-D294G/Y295G) lacked interactions between the Nt and Cd, they also failed to interact with Ajuba, an essential activator of Aurora-A, leading to loss of kinase activity. Additionally, overexpression of either of the mutants resulted in centrosome amplification and mitotic spindle formation defects. Both mutants were also able to cause G2/M arrest and apoptosis. These results indicate that both K250 and D294/Y295 are critical for direct interaction between Aurora-A and Ajuba and the function of the Aurora-A complex in cell cycle progression. [BMB Reports 2014; 47(11): 631-636]
PMCID: PMC4281342  PMID: 24499673
Ajuba; Aurora-A; Autophosphorylation; Cell cycle; Centrosome
8.  Analysis of the transcriptional responses in inflorescence buds of Jatropha curcas exposed to cytokinin treatment 
BMC Plant Biology  2014;14:318.
Jatropha curcas L. is a potential biofuel plant. Application of exogenous cytokinin (6-benzyladenine, BA) on its inflorescence buds can significantly increase the number of female flowers, thereby improving seed yield. To investigate which genes and signal pathways are involved in the response to cytokinin in J. curcas inflorescence buds, we monitored transcriptional activity in inflorescences at 0, 3, 12, 24, and 48 h after BA treatment using a microarray.
We detected 5,555 differentially expressed transcripts over the course of the experiment, which could be grouped into 12 distinct temporal expression patterns. We also identified 31 and 131 transcripts in J. curcas whose homologs in model plants function in flowering and phytohormonal signaling pathways, respectively. According to the transcriptional analysis of genes involved in flower development, we hypothesized that BA treatment delays floral organ formation by inhibiting the transcription of the A, B and E classes of floral organ-identity genes, which would allow more time to generate more floral primordia in inflorescence meristems, thereby enhancing inflorescence branching and significantly increasing flower number per inflorescence. BA treatment might also play an important role in maintaining the flowering signals by activating the transcription of GIGANTEA (GI) and inactivating the transcription of CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) and TERMINAL FLOWER 1b (TFL1b). In addition, exogenous cytokinin treatment could regulate the expression of genes involved in the metabolism and signaling of other phytohormones, indicating that cytokinin and other phytohormones jointly regulate flower development in J. curcas inflorescence buds.
Our study provides a framework to better understand the molecular mechanisms underlying changes in flowering traits in response to cytokinin treatment in J. curcas inflorescence buds. The results provide valuable information related to the mechanisms of cross-talk among multiple phytohormone signaling pathways in woody plants.
Electronic supplementary material
The online version of this article (doi:10.1186/s12870-014-0318-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4272566  PMID: 25433671
Cytokinin; Flowering; Physic nut; Phytohormone; Woody plant; Microarray
9.  Suppression of histone deacetylation promotes the differentiation of human pluripotent stem cells towards neural progenitor cells 
BMC Biology  2014;12:95.
Emerging studies of human pluripotent stem cells (hPSCs) raise new prospects for neurodegenerative disease modeling and cell replacement therapies. Therefore, understanding the mechanisms underlying the commitment of neural progenitor cells (NPCs) is important for the application of hPSCs in neurodegenerative disease therapies. It has been reported that epigenetic modifications of histones play important roles in neural differentiation, but the exact mechanisms in regulating hPSC differentiation towards NPCs are not fully elucidated.
We demonstrated that suppression of histone deacetylases (HDACs) promoted the differentiation of hPSCs towards NPCs. Application of HDAC inhibitors (HDACi) increased the expression of neuroectodermal markers and enhanced the neuroectodermal specification once neural differentiation was initiated, thereby leading to more NPC generation. Similarly, the transcriptome analysis showed that HDACi increased the expression levels of ectodermal markers and triggered the NPC differentiation related pathways, while decreasing the expression levels of endodermal and mesodermal markers. Furthermore, we documented that HDAC3 but not HDAC1 or HDAC2 was the critical regulator participating in NPC differentiation, and knockdown of HDAC3′s cofactor SMRT exhibited a similar effect as HDAC3 on NPC generation.
Our study reveals that HDACs, especially HDAC3, negatively regulate the differentiation of hPSCs towards NPCs at an earlier stage of neural differentiation. Moreover, HDAC3 might function by forming a repressor complex with its cofactor SMRT during this process. Thus, our findings uncover an important epigenetic mechanism of HDAC3 in the differentiation of hPSCs towards NPCs.
Electronic supplementary material
The online version of this article (doi:10.1186/s12915-014-0095-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4254204  PMID: 25406762
Histone deacetylation; Histone deacetylase inhibitors; Neuroectodermal specification; Neural progenitor cells; Human pluripotent stem cells
10.  Transcriptome of the inflorescence meristems of the biofuel plant Jatropha curcas treated with cytokinin 
BMC Genomics  2014;15(1):974.
Jatropha curcas, whose seed content is approximately 30–40% oil, is an ideal feedstock for producing biodiesel and bio-jet fuels. However, Jatropha plants have a low number of female flowers, which results in low seed yield that cannot meet the needs of the biofuel industry. Thus, increasing the number of female flowers is critical for the improvement of Jatropha seed yield. Our previous findings showed that cytokinin treatment can increase the flower number and female to male ratio and also induce bisexual flowers in Jatropha. The mechanisms underlying the influence of cytokinin on Jatropha flower development and sex determination, however, have not been clarified.
This study examined the transcriptional levels of genes involved in the response to cytokinin in Jatropha inflorescence meristems at different time points after cytokinin treatment by 454 sequencing, which gave rise to a total of 294.6 Mb of transcript sequences. Up-regulated and down-regulated annotated and novel genes were identified, and the expression levels of the genes of interest were confirmed by qRT-PCR. The identified transcripts include those encoding genes involved in the biosynthesis, metabolism, and signaling of cytokinin and other plant hormones, flower development and cell division, which may be related to phenotypic changes of Jatropha in response to cytokinin treatment. Our analysis indicated that Jatropha orthologs of the floral organ identity genes known as ABCE model genes, JcAP1,2, JcPI, JcAG, and JcSEP1,2,3, were all significantly repressed, with an exception of one B-function gene JcAP3 that was shown to be up-regulated by BA treatment, indicating different mechanisms to be involved in the floral organ development of unisexual flowers of Jatropha and bisexual flowers of Arabidopsis. Several cell division-related genes, including JcCycA3;2, JcCycD3;1, JcCycD3;2 and JcTSO1, were up-regulated, which may contribute to the increased flower number after cytokinin treatment.
This study presents the first report of global expression patterns of cytokinin-regulated transcripts in Jatropha inflorescence meristems. This report laid the foundation for further mechanistic studies on Jatropha and other non-model plants responding to cytokinin. Moreover, the identification of functional candidate genes will be useful for generating superior varieties of high-yielding transgenic Jatropha.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-974) contains supplementary material, which is available to authorized users.
PMCID: PMC4246439  PMID: 25400171
Biofuel; Physic nut; Cytokinin; 454 Sequencing; Flower; Cell division
11.  Multifocal hemosiderin depositions on T2*-weighted magnetic resonance imaging in a patient with pathology-proven systemic diffuse large B-cell lymphoma 
BMC Neurology  2014;14:184.
Intracranial hemorrhage in central nervous system lymphoma is extremely rare. T2*-weighted gradient-echo magnetic resonance imaging is of particularly use in detecting silent hemorrhage as hypointense signals due to the deposition of paramagnetic hemosiderin or mineralization. Multifocal hemosiderin depositions caused by chronic silent hemorrhage have not yet been identified in patients with central nervous system involvement of systemic lymphoma. We present an unexpected radiographic feature on T2*-weighted gradient-echo magnetic resonance imaging in a patient with central nervous system involvement of pathologically confirmed systemic diffuse large B-cell lymphoma.
Case presentation
A 56-year-old woman presented with lower extremities weakness and progressive cognitive decline for four months. Conventional brain magnetic resonance imaging demonstrated multiple lesions with hypointensities on T1-weighted images and hyperintensities on T2-weighted images and fluid attenuated inversion recovery in both hemispheres. She was then transferred to our hospital.
Neurological examination showed impaired cognitive functions. Contrast-enhanced magnetic resonance imaging revealed irregular spotty enhancement within the lesions. T2*-weighted gradient-echo magnetic resonance imaging revealed diffuse hemosiderin depositions with hypointensities mostly adjacent to the cortex, which are not compatible with the lesions visualized on T1-weighted images. Whole body positron emission tomography/computed tomography scanning showed multiple hyper-metabolic foci in the pelvic cavity and the spleen. The pathological diagnosis of the biopsy specimen was consistent with diffuse large B-cell lymphoma.
This is the first report of pathologically confirmed case of CNS involvement of systemic diffuse large B-cell lymphoma with multifocal silent hemosiderin depositions detected by T2*-weighted gradient-echo magnetic resonance imaging. Even though uncommon, our report offers an insight that CNS lymphoma could present with multifocal silent hemosiderin depositions on T2*-weighted gradient-echo magnetic resonance imaging. Further studies were expected for exploring the association between this radiologic feature and systemic lymphoma and their underlying mechanisms.
PMCID: PMC4180546  PMID: 25252760
Systemic lymphoma; Central nervous system; Hemosiderin deposition; T2*-weighted gradient-echo magnetic resonance imaging
12.  P300-dependent STAT3 acetylation is necessary for angiotensin II-induced pro-fibrotic responses in renal tubular epithelial cells 
Acta Pharmacologica Sinica  2014;35(9):1157-1166.
To explore the signal transducer and activator of transcription 3 (STAT3) signaling pathway, especially STAT3 acetylation, in angiotensin II (Ang II)-induced pro-fibrotic responses in renal tubular epithelial cells.
Rat renal tubular epithelial cell line (NRK-52E) was used. STAT3 acetylation and phosphorylation, as well as the expression of fibronectin, collagen IV and transforming growth factor-β1 (TGF-β1) were examined using Western blotting. The level and localization of STAT3 phosphorylation on Tyr705 were detected with fluorescence immunocytochemistry. The cells were transfected with a plasmid vector carrying p300 gene or siRNA targeting p300 to regulate p300 expression.
Overexpression of p300 significantly increased STAT3 acetylation on Lys685, STAT3 phosphorylation on Tyr705, and the expression of TGF-β1, collagen IV and fibronectin in the cells. Treatment of the cells with Ang II (1 μmol/L) significantly increased STAT3 phosphorylation on Tyr705 through JAK2 activation, and dose-dependently increased the expression of fibronectin, collagen IV and TGF-β1. Pretreatment with curcumin, an inhibitor of JAK2 and p300, blocked Ang II-induced effects. Knockdown of p300 significantly decreased STAT3 acetylation on Lys685, and abolished Ang II-stimulated STAT3 phosphorylation on Tyr705, whereas pretreatment of the cells with C646, a selective inhibitor of p300, inhibited Ang II-induced STAT3 nuclear translocation and the expression of TGF-β1, collagen IV and fibronectin. Pretreatment of the cells with AG490, a JAK2 inhibitor, markedly inhibited Ang II-induced STAT3 phosphorylation on Tyr705 and fibronectin expression.
p300-dependent STAT3 acetylation is necessary for Ang II-induced STAT3 phosphorylation and the consequent pro-fibrotic responses in renal tubular epithelial cells in vitro.
PMCID: PMC4155527  PMID: 25088002
renal fibrosis; angiotensin II; renal tubular epithelial cells; STAT3; JAK2; extracellular matrix; p300; curcumin; C646; AG490
13.  Moyamoya syndrome associated with Graves’ disease: a case series study 
The aim of this study was to describe the clinical and radiological findings of patients with moyamoya syndrome and Graves’ disease. Possible mechanisms predisposing these individuals to ischemic stroke are discussed.
We retrospectively analyzed 12 consecutive patients with both moyamoya syndrome and Graves’ disease. Moyamoya vasculopathy was diagnosed by digital subtract angiography or magnetic resonance angiography (MRA). The clinical characteristics, laboratory data, vascular radiological characteristics and outcome were reported.
All patients were female and mean age was 33.33±12.65 years. Stenosis or occlusion of bilateral terminal internal carotid artery and/or proximal anterior/middle cerebral arteries was found in nine patients. Among them, three patients displayed asymmetrical stenosis. In addition, there were three patients with probable unilateral moamoya syndrome. Eleven patients presented with ischemic stroke and/or transient ischemic attack (TIA) and one with dizziness. Thyroid function tests demonstrated elevated thyroid hormone levels and suppressed thyroid stimulating hormone levels in all the patients with ischemic events. All patients received anti-thyroid therapy and two had recurrent ischemic attack after drug withdrawal.
Moyamoya syndrome associated Graves’ disease often presented with asymmetric stenosis or occlusion. We hypothesize cerebrovascular hemodynamic changes due to thyrotoxicosis contribute to the ischemic events.
PMCID: PMC4200642  PMID: 25333052
Moyamoya syndrome; Graves’ disease; thyrotoxicosis; treatment
14.  Inhibition of STAT3 acetylation is associated with angiotesin renal fibrosis in the obstructed kidney 
Acta Pharmacologica Sinica  2014;35(8):1045-1054.
To explore the relationship between the signal transducer and activator of transcription 3 (STAT3) signaling and renal fibrosis.
Rat renal tubular epithelial NRK-52E cells were treated with angiotesin II (Ang II), nicotinamide (an inhibitor of NAD+-dependent class III protein deacetylases, SIRT1-7), or resveratrol (an activator of SIRT1). Mice underwent unilateral ureteral obstruction (UUO) were used for in vivo studies. Renal interstitial fibrosis was observed with HE and Masson's trichrome staining. STAT3 acetylation and phosphorylation, fibronectin, collagen I, collagen IV, and α-smooth muscle actin (α-SMA) levels were examined using Western blotting.
Nicotinamide (0.625–10 mmol/L) dose-dependently increased STAT3 acetylation on Lys685 and phosphorylation on Tyr705 in NRK-52E cells, accompanied by accumulation of fibronectin and collagen IV. Ang II increased STAT3 phosphorylation on Tyr705 and the expression of fibronectin, collagen IV and α-SMA in the cells. Pretreatment with resveratrol (12.5 μmol/L) blocked Ang II-induced effects in the cells. UUO induced marked STAT3 phosphorylation, fibronectin, collagen IV and α-SMA accumulation, and renal interstitial fibrosis in the obstructed kidneys, which were significantly attenuated by daily administration of resveratrol (100 mg/kg).
STAT3 acetylation plays an important role in activation of STAT3 signaling pathway and consequent renal fibrosis.
PMCID: PMC4125712  PMID: 24976155
chronic kidney disease; renal fibrosis; unilateral ureteral obstruction (UUO); angiotensin II; resveratrol; nicotinamide; STAT3; acetylation; phosphorylation
15.  Genome Sequence of Sporolactobacillus terrae DSM 11697, the Type Strain of the Species 
Genome Announcements  2014;2(3):e00465-14.
Sporolactobacillus terrae DSM 11697 is the type strain of S. terrae. Here, we present a 3.2-Mb assembly of its genome sequence. As S. terrae is one of the important lactic acid bacteria, the genome sequence may provide insights into the molecular mechanism for its further microbial investigation.
PMCID: PMC4038878  PMID: 24874673
16.  Draft Genome Sequence of the Gluconobacter oxydans Strain DSM 2003, an Important Biocatalyst for Industrial Use 
Genome Announcements  2014;2(2):e00417-14.
Gluconobacter oxydans strain DSM 2003 can efficiently produce some industrially important building blocks, such as (R)-lactic acid and (R)-2-hydroxybutyric acid. Here, we present a 2.94-Mb assembly of its genome sequence, which might provide further insights into the molecular mechanism of its biocatalysis in order to further improve its biotechnological applications.
PMCID: PMC4007994  PMID: 24786959
17.  High-resolution MRI findings in patients with capsular warning syndrome 
BMC Neurology  2014;14:16.
Capsular warning syndrome (CWS) is rare (1.5% of TIA presentations) but has a poor prognosis (7-day stroke risk of 60%). Up to date, the exact pathogenic mechanism of CWS has not been fully understood. We report the clinical presentations and high-resolution MRI (HR MRI) findings of two cases with capsular warning symptoms.
Case presentation
Case 1 was a 63-year-old man with a history of hypertension with recurrent episodes of left hemiparesis and dysarthria lasting 10 ~ 30 minutes. Case 2 was a 54-year-old woman with repetitive episodes of transient left hemiparesis and dysarthria lasting about 10 minutes. Capsular infarctions on DWI were demonstrated in the territory of a lenticulostriate artery in both 2 patients. HR MRI disclosed atherosclerotic plaques on the ventral wall of the MCA where enticulostriate arteries were arisen from, although traditional digital subtraction angiography showed normal. Aggressive medical therapy with dual antithrombotic agents and statin was effective in these two cases.
Our HR MRI data offer an insight into the pathophysiology of CWS which might be caused by atherosclerotic plaque in non-stenotic MCA wall. HR MRI might be a useful modality for characterizing atherosclerotic plaques in the MCA and detecting the pathophysiology of the CWS.
PMCID: PMC3898091  PMID: 24438445
Capsular warning syndrome; High-resolution MRI; Middle cerebral artery; Atherosclerotic plaque
18.  Intragenic Suppressor of Osiaa23 Revealed a Conserved Tryptophan Residue Crucial for Protein-Protein Interactions 
PLoS ONE  2014;9(1):e85358.
The Auxin/Indole-3-Acetic Acid (Aux/IAA) and Auxin Response Factor (ARF) are two important families that play key roles in auxin signal transduction. Both of the families contain a similar carboxyl-terminal domain (Domain III/IV) that facilitates interactions between these two families. In spite of the importance of protein-protein interactions among these transcription factors, the mechanisms involved in these interactions are largely unknown. In this study, we isolated six intragenic suppressors of an auxin insensitive mutant, Osiaa23. Among these suppressors, Osiaa23-R5 successfully rescued all the defects of the mutant. Sequence analysis revealed that an amino acid substitution occurred in the Tryptophan (W) residue in Domain IV of Osiaa23. Yeast two-hybrid experiments showed that the mutation in Domain IV prevents the protein-protein interactions between Osiaa23 and OsARFs. Phylogenetic analysis revealed that the W residue is conserved in both OsIAAs and OsARFs. Next, we performed site-specific amino acid substitutions within Domain IV of OsARFs, and the conserved W in Domain IV was exchanged by Serine (S). The mutated OsARF(WS)s can be released from the inhibition of Osiaa23 and maintain the transcriptional activities. Expression of OsARF(WS)s in Osiaa23 mutant rescued different defects of the mutant. Our results suggest a previously unknown importance of Domain IV in both families and provide an indirect way to investigate functions of OsARFs.
PMCID: PMC3893212  PMID: 24454849
19.  Pancreatic solid cystic desmoid tumor: Case report and literature review 
Desmoid tumors (DTs) are nonmetastatic, locally aggressive neoplasms with a high rate of postoperative recurrence. Pancreatic DTs are especially rare; only a few cases have been reported to date. This paper describes a case of a sporadic cystic DT of the pancreas managed successfully with central pancreatectomy, with no signs of recurrence 40 mo after surgery. According to the literature, this is the first reported case in China of a pancreatic DT presenting as a solid cystic lesion, as well as the first pancreatic DT managed with central pancreatectomy and pancreaticogastrostomy. We report the case for its rarity and emphasize disease management by concerted application of clinical, pathological, radiological and immunohistochemical analyses.
PMCID: PMC3870530  PMID: 24379602
Pancreatic tumor; Desmoid tumor; Cystic tumor; Central pancreatectomy; Pancreaticogastrostomy
20.  Successful interventional radiological management of postoperative complications of laparoscopic distal pancreatectomy 
During the past decade, laparoscopic distal pancreatectomy (LDP) has gained increasing acceptance in the surgical community as a viable treatment option for distal pancreatic lesions. However, the possible complication of post-LDP pancreatic leakage remains a challenge, because it may lead to a series of events resulting in intraperitoneal abscess formation, sepsis, pseudoaneurysm formation, and occasional fatal hemorrhage. Dealing with these complications is extremely difficult and not much experience has been reported to date. We report a case involving the aforementioned post-LDP complications successfully managed by interventional radiological techniques while avoiding reoperation. We conclude that these management options are attractive, safe and minimally invasive alternatives to standard protocols.
PMCID: PMC3857473  PMID: 24363541
Interventional radiology; Pancreatectomy; Laparoscopy; Postoperative complications
21.  Dysfunction and Post-Traumatic Stress Disorder in Fracture Victims 50 Months after the Sichuan Earthquake 
PLoS ONE  2013;8(10):e77535.
This study aimed to evaluate the effectiveness of a rehabilitation intervention on physical dysfunction (PDF) and post-traumatic stress disorder (PTSD) in fracture victims 50 months after the Sichuan earthquake of 2008 and to identify risk factors for PTSD.
This is a retrospective cohort study. Four hundred and fifty-nine earthquake-related fracture victims from Mianzhu city, Sichuan Province who did not qualify for disability pension participated. Two hundred and forty-five subjects received regular rehabilitation and 214 did not. Muscle strength, joint range of motion (ROM),sensory function, and sit-to-stand balance capacity were evaluated to assess PDF. The PTSD Checklist-Civilian Version (PCL-C) was administered to screen for PTSD. An ordinary least square regression was used to predict PTSD, and a logistic regression was used to predict PDF. In addition a Least Angle Regression (LARS) was carried out for PTSD to study the effects of rehabilitation and PDF at the same time.
Unadjusted and adjusted group differences in physical dysfunction (p<0.01) and PTSD prevalence (p<0.05) were significant in favor of the rehabilitation group. In addition, being female, average or above family income, having witnessed death and fearfulness were found risk factors for PTSD symptoms 50 months after the earthquake. Both PDF and rehabilitation were selected predictors by LARS demonstrating opposite effects.
PDF and PTSD were significantly reduced by the rehabilitation intervention. Future medical intervention strategies should consider rehabilitation in order to assist survivors in dealing with both physical and psychological effects of natural disaster.
PMCID: PMC3812228  PMID: 24204861
22.  H2S Inhibits Hyperglycemia-Induced Intrarenal Renin-Angiotensin System Activation via Attenuation of Reactive Oxygen Species Generation 
PLoS ONE  2013;8(9):e74366.
Decrease in endogenous hydrogen sulfide (H2S) was reported to participate in the pathogenesis of diabetic nephropathy (DN). This study is aimed at exploring the relationship between the abnormalities in H2S metabolism, hyperglycemia-induced oxidative stress and the activation of intrarenal renin-angiotensin system (RAS). Cultured renal mesangial cells (MCs) and streptozotocin (STZ) induced diabetic rats were used for the studies. The expressions of angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II (Ang II) type I receptor (AT1), transforming growth factor-β1 (TGF-β1) and collagen IV were measured by real time PCR and Western blot. Reactive oxygen species (ROS) production was assessed by fluorescent probe assays. Cell proliferation was analyzed by 5'-bromo-2'-deoxyuridine incorporation assay. Ang II concentration was measured by an enzyme immunoassay. AGT, ACE and AT1 receptor mRNA levels and Ang II concentration were increased in high glucose (HG) -treated MCs, the cell proliferation rate and the production of TGF-β1 and of collagen IV productions were also increased. The NADPH oxidase inhibitor diphenylenechloride iodonium (DPI) was able to reverse the HG-induced RAS activation and the changes in cell proliferation and collagen synthesis. Supplementation of H2S attenuated HG-induced elevations in ROS and RAS activation. Blockade on H2S biosynthesis from cystathione-γ-lyase (CSE) by DL-propargylglycine (PPG) resulted in effects similar to that of HG treatment. In STZ-induced diabetic rats, the changes in RAS were also reversed by H2S supplementation without affecting blood glucose concentration. These data suggested that the decrease in H2S under hyperglycemic condition leads to an imbalance between oxidative and reductive species. The increased oxidative species results in intrarenal RAS activation, which, in turn, contributes to the pathogenesis of renal dysfunction.
PMCID: PMC3772925  PMID: 24058553
23.  Recognition of Multiple Imbalanced Cancer Types Based on DNA Microarray Data Using Ensemble Classifiers 
BioMed Research International  2013;2013:239628.
DNA microarray technology can measure the activities of tens of thousands of genes simultaneously, which provides an efficient way to diagnose cancer at the molecular level. Although this strategy has attracted significant research attention, most studies neglect an important problem, namely, that most DNA microarray datasets are skewed, which causes traditional learning algorithms to produce inaccurate results. Some studies have considered this problem, yet they merely focus on binary-class problem. In this paper, we dealt with multiclass imbalanced classification problem, as encountered in cancer DNA microarray, by using ensemble learning. We utilized one-against-all coding strategy to transform multiclass to multiple binary classes, each of them carrying out feature subspace, which is an evolving version of random subspace that generates multiple diverse training subsets. Next, we introduced one of two different correction technologies, namely, decision threshold adjustment or random undersampling, into each training subset to alleviate the damage of class imbalance. Specifically, support vector machine was used as base classifier, and a novel voting rule called counter voting was presented for making a final decision. Experimental results on eight skewed multiclass cancer microarray datasets indicate that unlike many traditional classification approaches, our methods are insensitive to class imbalance.
PMCID: PMC3770038  PMID: 24078908
24.  Isolated splenic metastases from gastric carcinoma: A case report and literature review 
Isolated metastases to the spleen from gastric carcinoma is very rare. Only a few cases have been reported in the literature. We herein present a case of isolated splenic metastases in a 62-year-old man, occurring 12 mo after total gastrectomy for gastric carcinoma. The patient underwent a laparoscopic exploration, during which two lesions were found at the upper pole of the spleen, without involvement of other organs. A laparoscopic splenectomy was performed. Histological examination confirmed that the splenic tumor was a poorly differentiated adenocarcinoma similar to the primary gastric lesion. The postoperative course was uneventful and the patient has been well for 9 mo, with no tumor recurrence. The clinical data of 18 cases of isolated splenic metastases from gastric carcinoma treated by splenectomy were summarized after a literature review. To our knowledge, this is the first reported case of isolated splenic metastases undergoing laparoscopic splenectomy.
PMCID: PMC3746397  PMID: 23964159
Metastasis; Splenic neoplasms; Stomach neoplasms; Laparoscopy; Splenectomy
25.  Characterization of Two Streptomyces Enzymes That Convert Ferulic Acid to Vanillin 
PLoS ONE  2013;8(6):e67339.
Production of flavors from natural substrates by microbial transformation has become a growing and expanding field of study over the past decades. Vanillin, a major component of vanilla flavor, is a principal flavoring compound used worldwide. Streptomyces sp. strain V-1 is known to be one of the most promising microbial producers of natural vanillin from ferulic acid. Although identification of the microbial genes involved in the biotransformation of ferulic acid to vanillin has been previously reported, purification and detailed characterization of the corresponding enzymes with important functions have rarely been studied. In this study, we isolated and identified 2 critical genes, fcs and ech, encoding feruloyl-CoA synthetase and enoyl-CoA hydratase/aldolase, respectively, which are involved in the vanillin production from ferulic acid. Both genes were heterologously expressed in Escherichia coli, and the resting cell reactions for converting ferulic acid to vanillin were performed. The corresponding crucial enzymes, Fcs and Ech, were purified for the first time and the enzymatic activity of each purified protein was studied. Furthermore, Fcs was comprehensively characterized, at an optimal pH of 7.0 and temperature of 30°C. Kinetic constants for Fcs revealed the apparent Km, kcat, and Vmax values to be 0.35 mM, 67.7 s−1, and 78.2 U mg−1, respectively. The catalytic efficiency (kcat/Km) value of Fcs was 193.4 mM−1 s−1 for ferulic acid. The characterization of Fcs and Ech may be helpful for further research in the field of enzymatic engineering and metabolic regulation.
PMCID: PMC3696112  PMID: 23840666

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