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1.  Solution-processed small-molecule solar cells: breaking the 10% power conversion efficiency 
Scientific Reports  2013;3:3356.
A two-dimensional conjugated small molecule (SMPV1) was designed and synthesized for high performance solution-processed organic solar cells. This study explores the photovoltaic properties of this molecule as a donor, with a fullerene derivative as an acceptor, using solution processing in single junction and double junction tandem solar cells. The single junction solar cells based on SMPV1 exhibited a certified power conversion efficiency of 8.02% under AM 1.5 G irradiation (100 mW cm−2). A homo-tandem solar cell based on SMPV1 was constructed with a novel interlayer (or tunnel junction) consisting of bilayer conjugated polyelectrolyte, demonstrating an unprecedented PCE of 10.1%. These results strongly suggest solution-processed small molecular materials are excellent candidates for organic solar cells.
PMCID: PMC3842540  PMID: 24285006
2.  Expression, purification and crystallization of the FP domain of the human F-box protein Fbxo7 
The 155 amino-acid FP domain of the human F-box protein Fbxo7 was successfully expressed in bacteria, purified and crystallized. Native and single-wavelength anomalous dispersion data sets have been collected.
Fbxo7 is a conserved protein in higher eukaryotes that belongs to the F-box protein family. Fbxo7 is the substrate-recognition component of the SCFFbxo7 (Skp1-Cul1-Fbox protein) E3 ubiquitin ligase. Besides the F-box motif, Fbxo7 also contains a C-terminal proline-rich region, an N-terminal ubiquitin-like domain and a novel FP (Fbxo7/PI31) domain preceding the F-box motif. The FP domains of Fbxo7 and the PI31 proteasome inhibitor mediate interaction between the two proteins. For structure determination of the FP domain of Fxbo7, a protein construct (amino acids 181–335) corresponding to the FP domain was expressed, purified and crystallized. The native and selenomethionine-labeled proteins crystallized in different crystal forms. Native and single-wavelength anomalous dispersion data sets with diffraction to 2.1 and 2.0 Å resolution, respectively, have been collected and structure determination is in progress.
PMCID: PMC3792664  PMID: 24100556
F-box; Fbxo7; PI31 proteasome inhibitor; Fbxo7/PI31 domain; SCF E3 ubiquitin ligase
3.  Fibroblast activation protein protects bortezomib-induced apoptosis in multiple myeloma cells through β-catenin signaling pathway 
Cancer Biology & Therapy  2014;15(10):1413-1422.
Multiple myeloma (MM) is a malignant plasma cells proliferative disease. The intricate cross-talk of myeloma cells with bone marrow microenvironment plays an important role in facilitating growth and survival of myeloma cells. Bone marrow mesenchymal stem cells (BMMSCs) are important cells in MM microenvironment. In solid tumors, BMMSCs can be educated by tumor cells to become cancer-associated fibroblasts (CAFs) with high expression of fibroblast activation protein (FAP). FAP was reported to be involved in drug resistance, tumorigenesis, neoplastic progression, angiogenesis, invasion, and metastasis of tumor cells. However, the expression and the role of FAP in MM bone marrow microenvironment are still less known. The present study is aimed to investigate the expression of FAP, the role of FAP, and its relevant signaling pathway in regulating apoptosis induced by bortezomib in MM cells. In this study, our data illustrated that the expression levels of FAP were not different between the cultured BMMSCs isolated from MM patients and normal donors. The expression levels of FAP can be increased by tumor cells conditioned medium (TCCM) stimulation or coculture with RPMI8226 cells. FAP has important role in BMMSCs mediated protecting MM cell lines from apoptosis induced by bortezomib. Further study showed that this process may likely through β-catenin signaling pathway in vitro. The activation of β-catenin in MM cell lines was dependent on direct contact with BMMSCs other than separated by transwell or additional condition medium from BMMSCs and cytokines.
PMCID: PMC4130734  PMID: 25046247
apoptosis; bone marrow mesenchymal stem cells; cancer-associated fibroblast; fibroblast activation protein; multiple myeloma; signaling pathway; β-catenin
4.  Fstl1 is involved in the regulation of radial glial scaffold development 
Molecular Brain  2015;8:53.
Radial glial cells (RGCs), the instructive scaffolds for neuronal migration, are well characterized by their unique morphology and polarization; these cells extend elongated basal processes to the pial basement membrane (BM) and parallel to one another. However, little is known about the mechanisms that underlie the developmental regulation and maintenance of this unique morphology.
Here, by crossing Fstl1fl/fl mice with an EIIa-Cre line, we identified a new role for the secreted glycoprotein Follistatin like-1 (FSTL1). The ablation of Fstl1 in both of its cortical expression domains, the ventricular zone (VZ) and the pia mater, resulted in RGC morphologic disruption; basal processes were not parallel to each other, and endfeet exhibited greater density and branching. However, Fstl1 deletion in only the VZ in the Emx1IREScre; Fstl1fl/fl line did not affect RGC morphology, indicating that FSTL1 derived from the pia mater might be more important for RGC morphology. In addition, upper-layer projection neurons, not deeper-layer projection neurons, failed to reach their appropriate positions. We also found that BMP, AKT/PKB, Cdc42, GSK3β, integrin and reelin signals, which have previously been reported to regulate RGC development, were unchanged, indicating that Fstl1 may function through a unique mechanism.
In the present study, we identified a new role for FSTL1 in the development of radial glial scaffolds and the neuronal migration of upper-layer projection neurons. Our findings will improve understanding of the regulation of RGC development and neuronal migration.
Electronic supplementary material
The online version of this article (doi:10.1186/s13041-015-0144-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4573935  PMID: 26382033
5.  Arachidonate 12-lipoxygenase may serve as a potential marker and therapeutic target for prostate cancer stem cells 
International journal of oncology  2011;38(4):1041-1046.
The presence of arachidonate 12-lipoxygenase (12-LOX) potentiates prostate cancer (PCa) progression and therefore may be a good therapeutic target and/or a potential diagnostic predictor for PCa. In this study, we examined the expression of 12-LOX in PCa stem cells (PCa SCs) to test if it can serve as a unique marker and therapeutic target for PCa SCs. To this end, we isolated the cancer stem cell-like side population (SP) cells from the human PCa cell line DU-145 by a flow cytometry-based SP technique. The isolated DU-145 SP cells comprised a small population of the DU-145 cells. The SP cells had an up-regulation of ATP-binding cassette sub-family G member 2 (ABCG2) which enables these cells to efflux vital dyes and chemotherapeutic drugs. Furthermore, we detected a strong up-regulation of 12-LOX in these DU-145 SP cells compared to the parental DU-145 cells by RT-PCR and Western blot approaches. We also detected 12-LOX overexpression in PCa SCs in human PCa tissue samples by paraffin-section based immunofluorescent 4-channel confocal microscopy. However, no 12-LOX was detected in normal prostate epithelial SCs in normal prostate tissue samples. These multiple lines of evidence support the possibility that 12-LOX may serve as a unique marker and therapeutic target for PCa SCs.
PMCID: PMC4560359  PMID: 21225230
arachidonate 12-lipoxygenase; prostate cancer; stem cells; cancer stem cells; side population
6.  Geographical variations in risk factors associated with HIV infection among drug users in a prefecture in Southwest China 
Previous studies have shown inconsistent or even contradictory results for some risk factors associated with HIV infection among drug users, and these may be partially explained by geographical variations.
Data were collected from 11 methadone clinics in the Liangshan Yi Autonomous Prefecture from 2004 to 2012. A non-spatial logistical regression model and a geographically weighted logistic regression model were fitted to analyze the association between HIV infection and specific factors at the individual level.
This study enrolled 6,458 patients. The prevalence of HIV infection was 25.1 %. The non-spatial model indicated that being divorced was positively associated with HIV infection. The spatial model also showed that being divorced was positively associated with HIV infection, but only for 49.4 % of individuals residing in some northern counties. The non-spatial model suggested that service sector work was negatively associated with HIV infection. However, the spatial model indicated that service work was associated with HIV infection, but only for 23.0 % of patients living in some western counties. The non-spatial model did not show that being married was associated with HIV infection in our study field, but the spatial model indicated that being married was negatively associated with HIV infection for 12.0 % of individuals living in some western counties. For other factors, the non-spatial and spatial models showed similar results.
The spatial model may be useful for improving understanding of geographical heterogeneity in the relationship between HIV infection and individual factors. Spatial heterogeneity may be useful for tailoring intervention strategies for local regions, which can consequently result in a more efficient allocation of limited resources toward the control of HIV transmission.
Electronic supplementary material
The online version of this article (doi:10.1186/s40249-015-0073-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4557839  PMID: 26329887
Human immunodeficiency virus; Drug users; Geographically weighted logistic regression; Geographical variation; Ethnic epidemiology
7.  Four Carbapenem-Resistant Gram-Negative Species Carrying Distinct Carbapenemases in a Single Patient 
Journal of Clinical Microbiology  2014;53(3):1031-1033.
Carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, and Acinetobacter baumannii were isolated from a single patient, each producing different carbapenemases (NDM-1, KPC-2, IMP, and OXA-23, respectively). The NDM-1-producing E. coli strain was preceded by a clonally related carbapenem-susceptible strain a month earlier, suggesting in vivo acquisition of blaNDM-1.
PMCID: PMC4390643  PMID: 25552359
8.  Support and challenges to the melanosomal casing model based on nanoscale distribution of metals within iris melanosomes detected by X-ray fluorescence analysis 
Pigment cell & melanoma research  2014;27(5):831-834.
Melanin within melanosomes exists as eumelanin or pheomelanin. Distributions of these melanins have been studied extensively within tissues, but less often within individual melanosomes. Here, we apply X-ray fluorescence analysis with synchrotron radiation to survey the nanoscale distribution of metals within purified melanosomes of mice. The study allows a discovery-based characterization of melanosomal metals, and, because Cu is specifically associated with eumelanin, a hypothesis-based test of the “casing model” predicting that melanosomes contain a pheomelanin core surrounded by a eumelanin shell. Analysis of Cu, Ca, and Zn shows variable concentrations and distributions, with Ca/Zn highly correlated, and at least three discrete patterns for the distribution of Cu vs. Ca/Zn in different melanosomes – including one with a Cu-rich shell surrounding a Ca/Zn-rich core. Thus, the results support predictions of the casing model, but also suggest that in at least some tissues and genetic contexts, other arrangements of melanin may co-exist.
PMCID: PMC4150745  PMID: 24903463
Melanosome; metal; eumelanin; pheomelanin; X-ray fluorescence analysis; synchrotron-based imaging
9.  Highly Selective Palladium-Catalyzed Cross-Coupling of Secondary Alkylzinc Reagents with Heteroaryl Halides 
Organic Letters  2014;16(17):4638-4641.
The highly selective palladium-catalyzed Negishi coupling of secondary alkylzinc reagents with heteroaryl halides is described. The development of a series of biarylphosphine ligands has led to the identification of an improved catalyst for the coupling of electron-deficient heterocyclic substrates. Preparation and characterization of oxidative addition complex (L)(Ar)PdBr provided insight into the unique reactivity of catalysts based on CPhos-type ligands in facilitating challenging reductive elimination processes.
PMCID: PMC4156254  PMID: 25153332
10.  The Inability of Wild-Type Rabies Virus To Activate Dendritic Cells Is Dependent on the Glycoprotein and Correlates with Its Low Level of the De Novo-Synthesized Leader RNA 
Journal of Virology  2014;89(4):2157-2169.
Dendritic cells (DCs) are the most efficient antigen-presenting cells, playing a key role in the adaptive immune responses to viral infections. Our studies demonstrate that wild-type (wt) rabies virus (RABV) does not activate DCs. Adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate virus neutralizing antibodies (VNA), or protect recipients against challenge. However, adoptive transfer of DCs primed with laboratory-attenuated RABV resulted in DC activation, production of VNA, and protection against challenge. In vitro studies with recombinant RABV (laboratory-attenuated RABV expressing the glycoprotein or the phosphoprotein from wt RABV) demonstrate that DC activation is dependent on the glycoprotein and involves the IPS-1 pathway. Furthermore, binding to and entry into DCs by wt RABV is severely blocked, and the copy number of de novo-synthesized leader RNA was two logs lower in DCs infected with the wt than in DCs treated with laboratory-attenuated RABV. However, transient transfection of DCs with synthesized leader RNA from either wt or attenuated RABV is capable of activating DCs in a dose-dependent manner. Thus, the inability of wt RABV to activate DCs correlates with its low level of the de novo-synthesized leader RNA.
IMPORTANCE Rabies remains a public health threat, with more than 55,000 fatalities each year around the world. Since DCs play a key role in the adaptive immune responses to viral infections, we investigated the ability of rabies virus (RABV) to activate DCs. It was found that the adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate VNA, or protect mice against lethal challenge. However, laboratory-attenuated RABV mediates the activation of DCs via the IPS-1 pathway and is glycoprotein dependent. We further show that wt RABV evades DC-mediated immune activation by inefficient binding/entry into DCs and as a result of a reduced level of de novo-synthesized leader RNA. These findings may have important implications in the development of efficient rabies vaccines.
PMCID: PMC4338874  PMID: 25473057
11.  Copper-Catalyzed Regioselective ortho C–H Cyanation of Vinylarenes** 
A copper-based catalytic technique for the regioselective ortho C–H cyanation of vinylarenes has been developed. This method provides an effective means for the selective functionalization of vinylarene derivatives. A copper-catalyzed cyanative dearomatization mechanism is proposed to account for the regiochemical course of this reaction.
PMCID: PMC4127133  PMID: 24801708
C–H activation; copper; cyanation; difunctionalization; dearomatization
12.  A Pathway EM-Algorithm for Estimating Vaccine E cacy with a Non-Monotone Validation Set 
Biometrics  2014;70(3):568-578.
Here we consider time-to-event data where individuals can experience two or more types of events that are not distinguishable from one another without further confirmation, perhaps by laboratory test. The event type of primary interest can occur only once. The other types of events can recur. If the type of a portion of the events is identified, this forms a validation set. However, even if a random sample of events are tested, confirmations can be missing nonmonotonically, creating uncertainty about whether an individual is still at risk for the event of interest. For example, in a study to estimate e cacy of an influenza vaccine, an individual may experience a sequence of symptomatic respiratory illnesses caused by various pathogens over the season. Often only a limited number of these episodes are confirmed in the laboratory to be influenza-related or not. We propose two novel methods to estimate covariate e ects in this survival setting, and subsequently vaccine e cacy. The first is a pathway Expectation-Maximization (EM) algorithm that takes into account all pathways of event types in an individual compatible with that individual’s test outcomes. The pathway EM iteratively estimates baseline hazards that are used to weight possible event types. The second method is a non-iterative pathway piecewise validation method that does not estimate the baseline hazards. These methods are compared with a previous simpler method. Simulation studies suggest mean squared error is lower in the e cacy estimates when the baseline hazards are estimated, especially at higher hazard rates. We use the pathway EM-algorithm to reevaluate the e cacy of a trivalent live-attenuated influenza vaccine during the 2003-2004 influenza season in Temple-Belton, Texas, and compare our results with a previously published analysis.
PMCID: PMC4209209  PMID: 24766139
EM algorithm; Missing data; Vaccine efficacy; Validation set
13.  Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum 
Marine Drugs  2015;13(8):4733-4753.
Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple tumor types. Among them, the human malignant melanoma cell A-375 was confirmed to be the most sensitive. Morphologic evaluation, apoptosis rate analysis, Western blot and real-time quantitative PCR (RT-qPCR) results showed penicitrinine A could significantly induce A-375 cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. Moreover, we investigated the anti-metastatic effects of penicitrinine A in A-375 cells by wound healing assay, trans-well assay, Western blot and RT-qPCR. The results showed penicitrinine A significantly suppressed metastatic activity of A-375 cells by regulating the expression of MMP-9 and its specific inhibitor TIMP-1. These findings suggested that penicitrinine A might serve as a potential antitumor agent, which could inhibit the proliferation and metastasis of tumor cells.
PMCID: PMC4557002  PMID: 26264002
penicitrinine A; marine-derived fungus; human malignant melanoma cell A-375; anticancer activity; apoptosis; anti-metastatic
14.  Study on the Antifibrotic Effects of Recombinant Shark Hepatical Stimulator Analogue (r-sHSA) in Vitro and in Vivo 
Marine Drugs  2015;13(8):5201-5218.
Hepatic fibrosis is an effusive wound healing process, characterized by an excessive deposition of extracellular matrix (ECM), as the consequence of chronic liver injury of any etiology. Current therapeutic repertoire for hepatic fibrosis is limited to withdrawal of the noxious agent, which is not always feasible. Hence, in this article, the antifibrotic effects and possible mechanisms of r-sHSA, a recombinant protein with hepatoprotection potential, were investigated. Using NIH/3T3 (mouse embro-fibroblast cell line), skin fibroblasts (human skin fibroblasts, SFBs) and HSC-T6 (rat hepatic stellate cell line), the in vitro effect of r-sHSA was evaluated by measuring the expression levels of alpha-1 Type I collagen (Col1A1) and α-smooth muscle actin (α-SMA). It turned out those fibrosis indicators were typically inhibited by r-sHSA, suggesting its capacity in HSCs inactivation. The antifibrotic activity of r-sHSA was further investigated in vivo on CCl4-induced hepatic fibrosis, in view of significant improvement of the biochemical and histological indicators. More specifically, CCl4-intoxication induced a significant increase in serological biomarkers, e.g., transaminase (AST, ALT), and alkaline phosphatase (ALP), as well as disturbed hepatic antioxidative status; most of the parameters were spontaneously ameliorated to a large extent by withdrawal of CCl4, although the fibrotic lesion was observed histologically. In contrast, r-sHSA treatment markedly eliminated fibrous deposits and restored architecture of the liver in a dose dependent manner, concomitantly with the phenomena of inflammation relief and HSCs deactivation. To sum up, these findings suggest a therapeutic potential for r-sHSA in hepatic fibrosis, though further studies are required.
PMCID: PMC4557020  PMID: 26295240
r-sHSA; hepatic fibrosis; antifibrosis; carbon tetrachloride; hepatic stellate cells
15.  Therapeutic potential of digitoflavone on diabetic nephropathy: nuclear factor erythroid 2-related factor 2-dependent anti-oxidant and anti-inflammatory effect 
Scientific Reports  2015;5:12377.
Nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a therapeutic target in many diseases, because it can induce antioxidant enzymes and other cytoprotective enzymes. Moreover, some Nrf2 activators have strong anti-inflammatory activities. Oxidative stress and inflammation are major components involved in the pathology of diabetic nephropathy. In the present study, we evaluated the Nrf2-dependent anti-oxidative and anti-inflammatory effects of digitoflavone in streptozotocin-induced diabetic nephropathy. The molecular mechanisms of digitoflavone were investigated in vitro using SV40-transformed mouse mesangial cells (SV40-Mes13). For the in vivo experiment, diabetes was induced in Nrf2+/+ and Nrf2−/− mice by STZ injection, and digitoflavone was administered 2 weeks after the STZ injection. Digitoflavone induced Nrf2 activation and decreased oxidative damage, inflammation, TGF-β1 expression, extracellular matrix protein expression, and mesangial cell hyperplasia in SV40-Mes13 cells. Digitoflavone-treated Nrf2+/+ mice, but not Nrf2−/− mice, showed attenuated common metabolic disorder symptoms, improved renal performance, minimized pathological alterations, and decreased oxidative damage, inflammatory gene expression, inflammatory cell infiltration, TGF-β1 expression, and extracellular matrix protein expression. Our results show that the anti-oxidative and anti-inflammatory effects of digitoflavone are mediated by Nrf2 activation and that digitoflavone can be used therapeutically to improve metabolic disorders and relieve renal damage induced by diabetes.
PMCID: PMC4513300  PMID: 26205695
16.  De Novo Assembly of the Donkey White Blood Cell Transcriptome and a Comparative Analysis of Phenotype-Associated Genes between Donkeys and Horses 
PLoS ONE  2015;10(7):e0133258.
Prior to the mechanization of agriculture and labor-intensive tasks, humans used donkeys (Equus africanus asinus) for farm work and packing. However, as mechanization increased, donkeys have been increasingly raised for meat, milk, and fur in China. To maintain the development of the donkey industry, breeding programs should focus on traits related to these new uses. Compared to conventional marker-assisted breeding plans, genome- and transcriptome-based selection methods are more efficient and effective. To analyze the coding genes of the donkey genome, we assembled the transcriptome of donkey white blood cells de novo. Using transcriptomic deep-sequencing data, we identified 264,714 distinct donkey unigenes and predicted 38,949 protein fragments. We annotated the donkey unigenes by BLAST searches against the non-redundant (NR) protein database. We also compared the donkey protein sequences with those of the horse (E. caballus) and wild horse (E. przewalskii), and linked the donkey protein fragments with mammalian phenotypes. As the outer ear size of donkeys and horses are obviously different, we compared the outer ear size-associated proteins in donkeys and horses. We identified three ear size-associated proteins, HIC1, PRKRA, and KMT2A, with sequence differences among the donkey, horse, and wild horse loci. Since the donkey genome sequence has not been released, the de novo assembled donkey transcriptome is helpful for preliminary investigations of donkey cultivars and for genetic improvement.
PMCID: PMC4514889  PMID: 26208029
17.  MAD1L1 Arg558His and MAD2L1 Leu84Met interaction with smoking increase the risk of colorectal cancer 
Scientific Reports  2015;5:12202.
The spindle assembly checkpoint (SAC) has been established as an important mechanism of driving aneuploidy, which occurs at a high frequency in the colorectal tumorigenesis. Two important components of SAC are MAD1L1 and MAD2L1, which function together in an interactive manner to initiate the checkpoint signal. We hypothesize that genetic variants in the binding domains of MAD1L1 and MAD2L1 may modulate protein structures and eventually contribute to CRC susceptibility. A case-control study including 710 CRC cases and 735 controls was performed to examine MAD1L1 Arg558His and MAD2L1 Leu84Met’s conferring susceptibility to CRC. Cytokinesis-block micronucleus cytome assays were applied to assess the effect of two functional variants on chromosomal instability (CIN). Significant associations with CRC risk were observed for MAD1L1 Arg558His (OR = 1.38,95% CI: 1.09–1.75) and MAD2L1 Leu84Met in a dominant model (OR = 1.48,95% CI: 1.09–2.01). Moreover, significant multiplicative gene-smoking interactions were found in MAD1L1 Arg558His (P = 0.019) and MAD2L184 Leu/Met (P = 0.016) to enhance CRC risk. Additionally, the frequencies of lymphocytic micro-nucleated binucleated cells for MAD1L1 Arg558His polymorphism were significantly different in the exposed group (P = 0.013), but not in the control group. The study emphasized that MAD1L1 Arg558His and MAD2L1 Leu84Met can significantly interact with smoking to enhance CRC risk, and the genetic effects of MAD1L1Arg558His on CIN need to be further clarified in follow-up studies.
PMCID: PMC4505328  PMID: 26183163
18.  Total Syntheses of Lyconadins: Finding Efficiency and Diversity 
Lyconadins A–C are important members of the Lycopodium alkaloid family with challenging structural features and interesting biological profile. Herein, various synthetic strategies and methods for their preparation are summarized with the focus on constructive bond formation and our efficient and divergent synthesis based on functional group pairing (FGP) strategy.
PMCID: PMC4389785  PMID: 25866447
alkaloid; total synthesis; natural product; cyclization; neurodegeneration
19.  Survival Benefits of Western and Traditional Chinese Medicine Treatment for Patients With Pancreatic Cancer 
Medicine  2015;94(26):e1008.
Traditional Chinese medicine (TCM) is one of the most common complementary and alternative medicines used in the treatment of patients with cancer worldwide. However, the clinical effect of TCM on patients with pancreatic cancer remains unclear. This study was aimed to explore the efficacy of TCM on selected patients with pancreatic cancer and to study the usefulness of multimodality treatment, including TCM and western medicine (WM), in pancreatic cancer.
From January 2009 to October 2013, 107 patients with pancreatic cancer were included in this study. Kaplan–Meier curves were used to assess the differences in survival time. Cox regression analysis was performed to determine survival trends adjusted for clinical and demographic factors.
Cox regression analysis suggested that elevated CA19-9 levels (P = 0.048), number of cycles of chemotherapy (P = 0.014), and TCM were independent prognostic factors (P < 0.001). The survival hazards ratio of TCM was 0.419 (95% confidence interval [CI], 0.261–0.671). The median overall survival (OS) was 19 months for patients with TCM treatment, while the median OS was 8 months for those without TCM treatment (P < 0.001). Patients who received multimodality treatment using TCM and WM had the best prognosis with a median OS of 19 months (P < 0.001). Patients with heat-clearing, diuresis-promoting and detoxification TCM treatment had a longer survival time (32.4 months) than those with blood-activating and stasis-dissolving (9.8 months) and tonifying qi and yang treatment (6.1 months; P = 0.008).
These results indicate that TCM has an important potential value for improving the prognosis of patients with pancreatic cancer, and multimodality treatment, including TCM and WM, leads to the best prognosis. More importantly, we suggest that heat-clearing, diuresis-promoting, and detoxification TCM treatment may improve the efficacy of TCM in pancreatic cancer.
PMCID: PMC4504629  PMID: 26131801
20.  Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line 
PLoS ONE  2015;10(7):e0133169.
Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA), which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS), down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.
PMCID: PMC4503735  PMID: 26177078
21.  Glycan based Detection and Drug Susceptibility of Influenza Virus 
Analytical Chemistry  2014;86(16):8238-8244.
We have developed a panel of synthetic glycans as receptor mimics for the specific capture of influenza viruses. The glycans were printed onto commercial glass slides using a free amine at the end of a spacer to generate a small focused microarray. The microarray was evaluated for its ability to capture three different strains of influenza A virus, two H1N1, A/Brisbane/59/2007 and A/Solomon Islands/3/2006 and one H3N2, A/Aichi/2/1968. We observed an excellent detection ability with some compounds exhibiting clinically relevant (101 plaque forming units) limit of detection. We also tested the drug susceptibility of current antivirals, Zanamivir and Ostelamivir using this microarray and could determine antiviral resistance for these strains.
PMCID: PMC4139186  PMID: 25007351
22.  A Unique Human Norovirus Lineage with a Distinct HBGA Binding Interface 
PLoS Pathogens  2015;11(7):e1005025.
Norovirus (NoV) causes epidemic acute gastroenteritis in humans, whereby histo-blood group antigens (HBGAs) play an important role in host susceptibility. Each of the two major genogroups (GI and GII) of human NoVs recognizes a unique set of HBGAs through a distinct binding interface that is conserved within a genogroup, indicating a distinct evolutionary path for each genogroup. Here, we characterize a Lewis a (Lea) antigen binding strain (OIF virus) in the GII.21 genotype that does not share the conserved GII binding interface, revealing a new evolution lineage with a distinct HBGA binding interface. Sequence alignment showed that the major residues contributing to the new HBGA binding interface are conserved among most members of the GII.21, as well as a closely related GII.13 genotype. In addition, we found that glycerol inhibits OIF binding to HBGAs, potentially allowing production of cheap antivirals against human NoVs. Taken together, our results reveal a new evolutionary lineage of NoVs selected by HBGAs, a finding that is important for understanding the diversity and widespread nature of NoVs.
Author Summary
Human norovirus (huNoV) has diverged into two major lineages (GI and GII) selected by the host histo-blood group antigens (HBGAs). Both lineages further diverge into various sub-lineages (genotypes) that recognize different ABH and Lewis antigens through a common HBGA binding interface shared among strains within each genogroup. In this study, through X-ray crystallography of the P domain of a GII.21 huNoV (OIF) we identified a unique lineage in GII consisting of GII.13 and GII.21 genotypes that recognize HBGAs through a binding interface distinct from the GII conventional binding interface. While the mechanism remains unknown, our finding raises an alert on future emergence of new lineages by the same way via developing new receptor binding interfaces, as well as further divergence of this new lineage into more sub-lineages recognizing different HBGAs, which may impact future epidemiology and strategies for disease control and prevention against huNoVs.
PMCID: PMC4493018  PMID: 26147716
23.  The optoelectronic role of chlorine in CH3NH3PbI3(Cl)-based perovskite solar cells 
Nature Communications  2015;6:7269.
Perovskite photovoltaics offer a compelling combination of extremely low-cost, ease of processing and high device performance. The optoelectronic properties of the prototypical CH3NH3PbI3 can be further adjusted by introducing other extrinsic ions. Specifically, chlorine incorporation has been shown to affect the morphological development of perovksite films, which results in improved optoelectronic characteristics for high efficiency. However, it requires a deep understanding to the role of extrinsic halide, especially in the absence of unpredictable morphological influence during film growth. Here we report an effective strategy to investigate the role of the extrinsic ion in the context of optoelectronic properties, in which the morphological factors that closely correlate to device performance are mostly decoupled. The chlorine incorporation is found to mainly improve the carrier transport across the heterojunction interfaces, rather than within the perovskite crystals. Further optimization according this protocol leads to solar cells achieving power conversion efficiency of 17.91%.
Chlorine incorporation into CH3NH3PbI3 improves solar cell performance, but its optoelectronic role is still unclear. Here the authors present a strategy that decouples the morphological impact, to reveal that chlorine incorporation affects carrier transport across the heterojunction interface rather than within the perovskite crystal.
PMCID: PMC4490385  PMID: 26068804
24.  Adenosine Stress Cardiovascular Magnetic Resonance With Variable Density Spiral Pulse Sequences Accurately Detects Coronary Artery Disease: Initial Clinical Evaluation 
Adenosine stress CMR perfusion imaging can be limited by motion-induced dark-rim artifacts (DRA), which may be mistaken for true perfusion abnormalities. A high-resolution variable-density spiral (VDS) pulse sequence with a novel density compensation strategy has been shown to reduce DRA in first-pass perfusion imaging. We aimed to assess the clinical performance of adenosine stress CMR using this new perfusion sequence to detect obstructive coronary artery disease (CAD).
Methods and Results
CMR perfusion imaging was performed during adenosine stress (140μg/kg-min) and at rest on a Siemens 1.5T Avanto scanner in 41 subjects with chest pain scheduled for coronary angiography (CA). Perfusion images were acquired during injection of 0.1mmol/kg Gd-DTPA at 3 short-axis locations using a saturation recovery (SR) interleaved VDS pulse sequence. Significant stenosis was defined as >50% by quantitative CA (QCA). Two blinded reviewers evaluated the perfusion images for the presence of adenosine-induced perfusion abnormalities and assessed image quality using a 5 point scale (1 – poor to 5- excellent). The prevalence of obstructive CAD by QCA was 68%. The average sensitivity, specificity, and accuracy were 89%, 85%, and 88% respectively with a positive predictive value and negative predictive value of 93% and 79% respectively. The average image quality score was 4.4±0.7 with only one study with more than mild DRA. There was good inter-reader reliability with a kappa statistic of 0.67.
Spiral adenosine stress CMR results in high diagnostic accuracy for the detection of obstructive CAD with excellent image quality and minimal DRA.
PMCID: PMC4102611  PMID: 24759900
CMR; adenosine stress perfusion; coronary artery disease
25.  Semantic Processing Persists despite Anomalous Syntactic Category: ERP Evidence from Chinese Passive Sentences 
PLoS ONE  2015;10(6):e0131936.
The syntax-first model and the parallel/interactive models make different predictions regarding whether syntactic category processing has a temporal and functional primacy over semantic processing. To further resolve this issue, an event-related potential experiment was conducted on 24 Chinese speakers reading Chinese passive sentences with the passive marker BEI (NP1 + BEI + NP2 + Verb). This construction was selected because it is the most-commonly used Chinese passive and very much resembles German passives, upon which the syntax-first hypothesis was primarily based. We manipulated semantic consistency (consistent vs. inconsistent) and syntactic category (noun vs. verb) of the critical verb, yielding four conditions: CORRECT (correct sentences), SEMANTIC (semantic anomaly), SYNTACTIC (syntactic category anomaly), and COMBINED (combined anomalies). Results showed both N400 and P600 effects for sentences with semantic anomaly, with syntactic category anomaly, or with combined anomalies. Converging with recent findings of Chinese ERP studies on various constructions, our study provides further evidence that syntactic category processing does not precede semantic processing in reading Chinese.
PMCID: PMC4488374  PMID: 26125621

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