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1.  Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets 
Science (New York, N.Y.)  2012;337(6093):477-481.
Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD)6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with X-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens, and may explain the conservation of HD6 throughout Hominidae evolution.
doi:10.1126/science.1218831
PMCID: PMC4332406  PMID: 22722251
2.  Genome-Wide Analysis of MicroRNAs and Their Target Genes Related to Leaf Senescence of Rice 
PLoS ONE  2014;9(12):e114313.
Grain production of rice (Oryza sativa L.) is a top priority in ensuring food security for human beings. One of the approaches to increase yield is to delay leaf senescence and to extend the available time for photosynthesis. MicroRNAs (miRNAs) are key regulators of aging and cellular senescence in eukaryotes. Here, to help understand their biological role in rice leaf senescence, we report identification of miRNAs and their putative target genes by deep sequencing of six small RNA libraries, six RNA-seq libraries and two degradome libraries from the leaves of two super hybrid rice, Nei-2-You 6 (N2Y6, age-resistant rice) and Liang-You-Pei 9 (LYP9, age-sensitive rice). In total 372 known miRNAs, 162 miRNA candidates and 1145 targets were identified. Compared with the expression of miRNAs in the leaves of LYP9, the numbers of miRNAs up-regulated and down-regulated in the leaves of N2Y6 were 47 and 30 at early stage of grain-filling, 21 and 17 at the middle stage, and 11 and 37 at the late stage, respectively. Six miRNA families, osa-miR159, osa-miR160 osa-miR164, osa-miR167, osa-miR172 and osa-miR1848, targeting the genes encoding APETALA2 (AP2), zinc finger proteins, salicylic acid-induced protein 19 (SIP19), auxin response factors (ARF) and NAC transcription factors, respectively, were found to be involved in leaf senescence through phytohormone signaling pathways. These results provided valuable information for understanding the miRNA-mediated leaf senescence of rice, and offered an important foundation for rice breeding.
doi:10.1371/journal.pone.0114313
PMCID: PMC4257594  PMID: 25479006
3.  Cross-strait parasitological research priorities arrived at by historical tracking and advanced dialogue 
To further enhance dialogue and promote cross-strait cooperation in the prevention and control of parasitic diseases, this paper reviewed the progress and current challenges in the cross-strait control and research of parasitic infections, based on three cross-strait meetings on parasitological research in the last decade. The major outcome of the 3rd Meeting of Cross-Strait Parasitological Research held in April 2013 was identifying the research priorities for parasitological research.
Electronic supplementary material
The online version of this article (doi:10.1186/2049-9957-3-40) contains supplementary material, which is available to authorized users.
doi:10.1186/2049-9957-3-40
PMCID: PMC4322646  PMID: 25671120
Cross-strait meeting; Parasitological research priorities; Epidemiology
4.  Deep Sequencing Identifies Tissue-Specific MicroRNAs and Their Target Genes Involving in the Biosynthesis of Tanshinones in Salvia miltiorrhiza 
PLoS ONE  2014;9(11):e111679.
Salvia miltiorrhiza is one of the most popular traditional medicinal herbs in Asian nations. Its dried root contains a number of tanshinones, protocatechuic aldehyde, salvianolic acid B and rosmarinic, and is used for the treatment of various diseases. The finding of microRNAs (miRNAs) and their target genes will help understand their biological role on the biosynthesis of tanshinones in S. miltiorrhiza. In the present study, a total of 452 known miRNAs corresponding to 589 precursor miRNAs (pre-miRNAs), and 40 novel miRNAs corresponding to 24 pre-miRNAs were identified in different tissues of S. miltiorrhiza by high-throughput sequencing, respectively. Among them, 62 miRNAs express only in root, 95 miRNAs express only in stem, 19 miRNAs express only in leaf, and 71 miRNAs express only in flower, respectively. By the degradome analysis, 69 targets potentially cleaved by 25 miRNAs were identified. Among them, acetyl-CoA C-acetyltransferase was cleaved by miR5072, and involved in the biosynthesis of tanshinones. This study provided valuable information for understanding the tissue-specific expression patterns of miRNAs in S. miltiorrhiza, and offered a foundation for future studies of the miRNA-mediated biosynthesis of tanshinones.
doi:10.1371/journal.pone.0111679
PMCID: PMC4218800  PMID: 25365305
5.  Evidence of Type-II Band Alignment in III-nitride Semiconductors: Experimental and theoretical investigation for In0.17Al0.83N/GaN heterostructures 
Scientific Reports  2014;4:6521.
Type-II band alignment structure is coveted in the design of photovoltaic devices and detectors, since it is beneficial for the transport of photogenerated carriers. Regrettably, for group-III-nitride wide bandgap semiconductors, all existing devices are limited to type-I heterostructures, owing to the unavailable of type-II ones. This seriously restricts the designing flexibility for optoelectronic devices and consequently the relevant performance of this material system. Here we show a brandnew type-II band alignment of the lattice-matched In0.17Al0.83N/GaN heterostructure from the perspective of both experimental observations and first-principle theoretical calculations. The band discontinuity is dominated by the conduction band offset ΔEC, with a small contribution from the valence band offset ΔEV which equals 0.1 eV (with being above). Our work may open up new prospects to realize high-performance III-Nitrides optoelectronic devices based on type-II energy band engineering.
doi:10.1038/srep06521
PMCID: PMC4185379  PMID: 25283334
6.  An Integrated Model for Robust Multisensor Data Fusion 
Sensors (Basel, Switzerland)  2014;14(10):19669-19686.
This paper presents an integrated model aimed at obtaining robust and reliable results in decision level multisensor data fusion applications. The proposed model is based on the connection of Dempster-Shafer evidence theory and an extreme learning machine. It includes three main improvement aspects: a mass constructing algorithm to build reasonable basic belief assignments (BBAs); an evidence synthesis method to get a comprehensive BBA for an information source from several mass functions or experts; and a new way to make high-precision decisions based on an extreme learning machine (ELM). Compared to some universal classification methods, the proposed one can be directly applied in multisensor data fusion applications, but not only for conventional classifications. Experimental results demonstrate that the proposed model is able to yield robust and reliable results in multisensor data fusion problems. In addition, this paper also draws some meaningful conclusions, which have significant implications for future studies.
doi:10.3390/s141019669
PMCID: PMC4239917  PMID: 25340445
multisensors; data fusion; Dempster-Shafer theory; extreme learning machine
7.  Band offsets of non-polar A-plane GaN/AlN and AlN/GaN heterostructures measured by X-ray photoemission spectroscopy 
Nanoscale Research Letters  2014;9(1):470.
The band offsets of non-polar A-plane GaN/AlN and AlN/GaN heterojunctions are measured by X-ray photoemission spectroscopy. A large forward-backward asymmetry is observed in the non-polar GaN/AlN and AlN/GaN heterojunctions. The valence-band offsets in the non-polar A-plane GaN/AlN and AlN/GaN heterojunctions are determined to be 1.33 ± 0.16 and 0.73 ± 0.16 eV, respectively. The large valence-band offset difference of 0.6 eV between the non-polar GaN/AlN and AlN/GaN heterojunctions is considered to be due to piezoelectric strain effect in the non-polar heterojunction overlayers.
doi:10.1186/1556-276X-9-470
PMCID: PMC4167304  PMID: 25258600
GaN/AlN; Heterostructure; X-ray photoemission spectroscopy; Non-polar
8.  Association between gastro-intestinal symptoms and menstruation in patients with ileal pouches 
Gastroenterology Report  2014;2(3):207-214.
Background and aims: Gastro-intestinal (GI) symptoms are often experienced by healthy women during menstruation. An increased frequency of GI symptoms during menses has also been reported in women with irritable bowel syndrome or inflammatory bowel disease (IBD); however, IBD patients with restorative proctocolectomy and ileal pouch-anal anastomoses (IPAA) have not been studied. We aimed to examine the association between GI symptoms before and during menses in patients with IPAA, and to assess factors for exacerbation of GI symptoms in those patients.
Methods: Adult women recorded in the Pouchitis Registry were invited to participate in a mailed survey. Participants reported on GI symptoms 1–5 days prior to- (pre-menses) and during the days of their menses in recent months. Demographic and clinical variables were obtained through the survey and chart review.
Results: One hundred and twenty-eight (21.3%) out of 600 women with IPAA responded to the survey questionnaire. Forty-three (33.5%) were excluded for reasons including post-menopausal (n = 25), hysterectomy (n = 14) and use of contraceptives (n = 4). Abdominal pain (P = 0.001), diarrhea (P = 0.021), and urgency (P = 0.031) were more commonly reported during menses than pre-menses by the participants. Only a history of painful menses was significantly associated with increased GI symptoms during menses for patients with ileal pouch (odds ratio = 5.67; 95% confidence interval: 1.41–22.88; P = 0.015).
Conclusion: GI symptoms such as abdominal pain, diarrhea, and urgency are commonly associated with menses in patients with ileo-anal pouch. Painful menses may be associated with worsening of GI symptoms.
doi:10.1093/gastro/gou042
PMCID: PMC4124275  PMID: 25016379
inflammatory bowel disease; ileal pouch-anal anastomosis; menstruation; symptomatology; restorative proctocolectomy
9.  New, goal-directed approach to renal replacement therapy improves acute kidney injury treatment after cardiac surgery 
Aim
The aim of this study was to compare the efficacies of goal-directed renal replacement therapy (GDRRT) and daily hemofiltration (DHF) for treating acute kidney injury (AKI) patients after cardiac surgery.
Methods
In our retrospective study, we included 140 cardiac surgery AKI patients who were treated with renal replacement therapy (RRT) from 2002 to 2010. Two patient groups, which comprised 70 patients who received DHF from January 2002 to September 2008 and 70 patients treated with GDRRT from October 2009 to September 2010 were pair-wise compared regarding clinical outcomes, as well as the incidence of adverse events.
Results
In-hospital and 30-day mortality rates were 45.7% and 41.4% in the GDRRT and 48.6% and 54.3% in the DHF group, respectively, but without statistically significant differences. GDRRT patients needed statistically significantly shorter hospital and intensive care unit (ICU) stays, less frequent RRT, and shorter RRT sessions, whereas, of 11 analyzed renal outcome parameters, 6 values, including percentage of complete renal recovery and time for complete renal recovery, were significantly superior in the GDRRT group at the time of discharge. There was no significant difference in the incidence of adverse events within the initial 72 treatment hours between the 2 groups. Hospitalization expenses were less in GDRRT group than in DHF group.
Conclusion
The GDRRT approach is superior to DHF for improving renal outcome, as well as reducing the time and cost of RRT therapy, for cardiac surgery AKI patients.
doi:10.1186/1749-8090-9-103
PMCID: PMC4075594  PMID: 24947162
Cardiac surgery; Acute kidney injury; Goal-directed renal replacement therapy; Daily hemofiltration
10.  Identification of Helicity-Dependent Photocurrents from Topological Surface States in Bi2Se3 Gated by Ionic Liquid 
Scientific Reports  2014;4:4889.
Dirac-like surface states on surfaces of topological insulators have a chiral spin structure with spin locked to momentum, which is interesting in physics and may also have important applications in spintronics. In this work, by measuring the tunable helicity-dependent photocurrent (HDP), we present an identification of the HDP from the Dirac-like surface states at room temperature. It turns out that the total HDP has two components, one from the Dirac-like surface states, and the other from the surface accumulation layer. These two components have opposite directions. The clear gate tuning of the electron density as well as the HDP signal indicates that the surface band bending and resulted surface accumulation are successfully modulated by the applied ionic liquid gate, which provides a promising way to the study of the Dirac-like surface states and also potential applications in spintronic devices.
doi:10.1038/srep04889
PMCID: PMC4013928  PMID: 24809330
11.  A directional switch of integrin signaling and a new anti-thrombotic strategy 
Nature  2013;503(7474):10.1038/nature12613.
Integrins are critical in thrombosis and hemostasis1. Antagonists of the platelet integrin αIIbβ3 are potent anti-thrombotic drugs, but also have the life-threatening adverse effect of bleeding2,3. It is thus desirable to develop new antagonists that do not cause bleeding. Integrins transmit signals bidirectionally4,5. Inside-out signaling activates integrins via a talin-dependent mechanism6,7. Integrin ligation mediates thrombus formation and outside-in signaling8,9, which requires Gα13 and greatly expands thrombi. Here we show that Gα13 and talin bind to mutually exclusive, but distinct sites within the integrin β3 cytoplasmic domain in opposing waves. The first talin binding wave mediates inside-out signaling and also “ligand-induced integrin activation”, but is not required for outside-in signaling. Integrin ligation induces transient talin dissociation and Gα13 binding to an ExE motif, which selectively mediates outside-in signaling and platelet spreading. The second talin binding wave is associated with clot retraction. An ExE motif-based inhibitor of Gα13-integrin interaction selectively abolishes outside-in signaling without affecting integrin ligation, and suppresses occlusive arterial thrombosis without affecting bleeding time. Thus, we have discovered a novel mechanism for the directional switch of integrin signaling and, based on this mechanism, we designed a potent new anti-thrombotic that does not cause bleeding.
doi:10.1038/nature12613
PMCID: PMC3823815  PMID: 24162846
12.  A case of horizontal gene transfer from Wolbachia to Aedes albopictus C6/36 cell line 
Mobile Genetic Elements  2014;4:e28914.
Horizontal gene transfer plays an essential role in evolution and ecological adaptation, yet this phenomenon has remained controversial, particularly where it occurs between prokaryotes and eukaryotes. There are a handful of reported examples of horizontal gene transfer occurring between prokaryotes and eukaryotes in the literature, with most of these documented cases pertaining to invertebrates and endosymbionts. However, the vast majority of these horizontally transferred genes were either eventually excluded or rapidly became nonfunctional in the recipient genome. In this study, we report the discovery of a horizontal gene transfer from the endosymbiont Wolbachia in the C6/36 cell line derived from the mosquito Aedes albopictus. Moreover, we report that this horizontally transferred gene displayed high transcription level. This finding and the results of further experimentation strongly suggest this gene is functional and has been expressed and translated into a protein in the mosquito host cells.
doi:10.4161/mge.28914
PMCID: PMC4013104  PMID: 24812591
horizontal gene transfer; endosymbiont; Wolbachia; mosquito; Aedes Albopictus; C6/36 cell line
13.  Ribosomal Protein S29 Regulates Metabolic Insecticide Resistance through Binding and Degradation of CYP6N3 
PLoS ONE  2014;9(4):e94611.
Background
Many diseases are transmitted by mosquitoes, including malaria, dengue fever, yellow fever, filariasis, and West Nile fever. Chemical control plays a major role in managing mosquito-borne diseases. However, excessive and continuous application of insecticides has caused the development of insecticide resistance in many species including mosquito, and this has become the major obstacle to controlling mosquito-borne diseases. Insecticide resistance is the result of complex polygenic inheritance, and the mechanisms are not well understood. Ribosomal protein RPS29 was found to be associated with DM resistance in our previous study. In this study, we aim to further investigate the involvement of RPS29 in deltamethrin resistance.
Methodology and Principal Findings
In this study, tandem affinity purification was used to identify proteins that can interact with RPS29. Among the candidate proteins, CYP6N3, a member of the CYP450 superfamily, was identified, and binding to RPS29 was confirmed in vitro and in vivo by GST pull-down and immunofluorescence. CCK-8 assay was used to investigate the RPS29-CTP6N3 interaction in relation to DM resistance. CYP6N3 overexpression significantly enhanced DM resistance and insect cell viability, but this was reversed by RPS29 overexpression. Western blot was used to study the mechanism of interaction between RPS29 and CYP6N3. RPS29 increases CYP6N3 protein degradation through the proteasome.
Conclusions and Significance
These observations indicate that CYP6N3, a novel RPS29-interacting partner, could stimulate deltamethrin resistance in mosquito cells and RPS29 overexpression targeted CYP6N3 for proteosomal degradation, abrogating the CYP6N3-associated resistence to deltamethrin. Our findings provide a novel mechanism associated with CYP450s mediated DM resistance.
doi:10.1371/journal.pone.0094611
PMCID: PMC3984272  PMID: 24728095
14.  Trypsin-Catalyzed Deltamethrin Degradation 
PLoS ONE  2014;9(3):e89517.
To explore if trypsin could catalyze the degradation of non-protein molecule deltamethrin, we compared in vitro hydrolytic reactions of deltamethrin in the presence and absence of trypsin with ultraviolet-visible (UV/Vis) spectrophotometry and gas chromatography-mass spectrometry (GC/MS). In addition, acute oral toxicity of the degradation products was determined in Wistar rats. The results show that the absorption peak of deltamethrin is around 264 nm, while the absorption peaks of deltamethrin degradation products are around 250 nm and 296 nm. In our GC setting, the retention time of undegraded deltamethrin was 37.968 min, while those of deltamethrin degradation products were 15.289 min and 18.730 min. The LD50 of deltamethrin in Wistar rats is 55 mg/kg, while that of deltamethrin degradation products is 3358 mg/kg in female rats and 1045 mg/kg in male rates (61-fold and 19-fold reductions in toxicity), suggesting that trypsin could directly degrade deltamethrin, which significantly reduces the toxicity of deltamethrin. These results expand people's understanding of the functions of proteases and point to potential applications of trypsin as an attractive agent to control residual pesticides in the environment and on agricultural products.
doi:10.1371/journal.pone.0089517
PMCID: PMC3940599  PMID: 24594869
15.  Spin transport study in a Rashba spin-orbit coupling system 
Scientific Reports  2014;4:4030.
One of the most important topics in spintronics is spin transport. In this work, spin transport properties of two-dimensional electron gas in AlxGa1-xN/GaN heterostructure were studied by helicity-dependent photocurrent measurements at room temperature. Spin-related photocurrent was detected under normal incidence of a circularly polarized laser with a Gaussian distribution. On one hand, spin polarized electrons excited by the laser generate a diffusive spin polarization current, which leads to a vortex charge current as a result of anomalous circular photogalvanic effect. On the other hand, photo-induced spin polarized electrons driven by a longitudinal electric field give rise to a transverse current via anomalous Hall Effect. Both of these effects originated from the Rashba spin-orbit coupling. By analyzing spin-related photocurrent varied with laser position, the contributions of the two effects were differentiated and the ratio of the spin diffusion coefficient to photo-induced anomalous spin Hall mobility Ds/μs = 0.08 V was extracted at room temperature.
doi:10.1038/srep04030
PMCID: PMC3916788  PMID: 24504193
16.  Ribose-phosphate pyrophosphokinase 1 (PRPS1) associated with deltamethrin resistance in Culex pipiens pallens 
Parasitology research  2012;112(2):847-854.
Ribose-phosphate pyrophosphokinase 1 (PRPS1) was identified and isolated as a differentially expressed gene between deltamethrin-susceptible (DS) and deltamethrin-resistant (DR) Culex pipiens pallens and Aedes albopictus C6/36 cell line through microarray and 2D-Gel. An open reading frame of PRPS1 cloned from C. pipiens pallens has 1,011 bp and encodes for a 336 amino acids protein which shares high homology with Culex quinquefasciatus. Real-time polymerase chain reaction was used to determine the transcript expression level of PRPS1 in DS and DR strains. The expression levels of PRPS1 were higher in DR laboratory strains and natural population JXZ-DR, JXZ-LDR. PRPS1 was also detected and expressed at all developmental stages of C. pipiens pallens and increased expression level in DR3 strain than DS strain in the third and fourth instar larvae, female and male stages. In addition, to further investigate the role of PRPS1 in deltamethrin resistance, PRPS1 was transiently expressed in A. albopictus C6/36 cells and detected by western blotting. Cells transfected with PRPS1 had an increased resistance to deltamethrin compared with control cells. These results suggested that the increased expression level of PRPS1 may play roles in the regulation of deltamethrin resistance.
doi:10.1007/s00436-012-3205-2
PMCID: PMC3720864  PMID: 23250545
17.  Genome sequence of Anopheles sinensis provides insight into genetics basis of mosquito competence for malaria parasites 
BMC Genomics  2014;15:42.
Background
Anopheles sinensis is an important mosquito vector of Plasmodium vivax, which is the most frequent and widely distributed cause of recurring malaria throughout Asia, and particularly in China, Korea, and Japan.
Results
We performed 454 next-generation sequencing and obtained a draft sequence of A. sinensis assembled into scaffolds spanning 220.8 million base pairs. Analysis of this genome sequence, we observed expansion and contraction of several immune-related gene families in anopheline relative to culicine mosquito species. These differences suggest that species-specific immune responses to Plasmodium invasion underpin the biological differences in susceptibility to Plasmodium infection that characterize these two mosquito subfamilies.
Conclusions
The A. sinensis genome produced in this study, provides an important resource for analyzing the genetic basis of susceptibility and resistance of mosquitoes to Plasmodium parasites research which will ultimately facilitate the design of urgently needed interventions against this debilitating mosquito-borne disease.
doi:10.1186/1471-2164-15-42
PMCID: PMC3901762  PMID: 24438588
Genome; Anopheles sinensis; Malaria
18.  Serum microRNA-499 and microRNA-208a as biomarkers of acute myocardial infarction 
Objective: Acute myocardial infarction (AMI) is a most serious cardiovascular disease with high morbidity and mortality. Novel biomarkers for AMI are explored continuous. MicroRNAs (miRNAs, miRs) are present in the circulation in a consistent, stable, and reproducible manner, attracting major interest of using circulating miRNAs as biomarkers. In plasma, miR-208a and miR-499 are considered to be the best candidate for AMI diagnosis. However, serum has slightly higher miRNA yields compared to plasma and the majority of archived samples are stored in form of serum, marking interesting to determine whether miR-208a and miR-499 in serum can be used as biomarkers for AMI. Methods: AMI was induced by coronary ligation and the serum and heart tissues were collected. The levels of miR-208a and miR-499 in serum and heart tissues were determined using TaqMan-based miRNA quantitative real-time polymerase chain reactions (qRT-PCRs). Results: Serum miR-208a was increased by 36-fold and 51-fold while miR-499 was elevated by 103-fold and 95-fold at 4 h and 24 h after AMI. Moreover, the expression level of miR-499 was significantly decreased in the myocardial infarct zone comparing to the remote zone or the sham group while miR-208a remained unchanged. Conclusion: Serum miR-499 and miR-208a might be potential biomarkers for AMI. miR-499 might be released from damaged heart to the circulation.
PMCID: PMC3902251  PMID: 24482699
Serum; microRNA; acute myocardial infarction; biomarker
19.  Risk factors of lymphatic metastasis complement poor radiological detection in gallbladder cancer 
AIM: To explore risk factors of lymphatic metastasis (LM) in gallbladder cancer, and their potential to complement unsatisfactory radiological detection.
METHODS: Radiological detection of LM by computed tomography (CT) was reported to fail in more than 60% of patients with pathological LM. In order to find risk factors highly suggestive of LM other than radiological manifestations, the documents of 63 patients were analyzed statistically. Except for 4 patients having T1a disease, in whom cholecystectomy is enough for radical resection, 59 patients underwent lymphadenectomy with at least 3 lymph nodes dissected. Fifty point eight percent (32/63) of patients were found to have LM during pathological examination. The median number of dissected lymph nodes was 6 (range 3-20).
RESULTS: Only 31.3% (10/32) of patients with LM were detected by CT. Through multivariate analysis, two risk factors of LM were discovered as age < 60 years (OR = 6.24; P < 0.01) and carbohydrate antigen (CA) 19-9 elevation (OR = 5.70; P < 0.05). By analysis of patients with pathological LM but failed to be detected by CT, 81.8% (18/22) of patients had at least one risk factor, including 31.3% (10/32) who had the risk factor of age < 60 years, and 37.5% (12/32) who had the risk factor of CA 19-9 elevation. Besides, among patients with LM (n = 32), those whose age were younger than 60 years (OR = 3.41; P < 0.05) were more likely to have 3 or more positive lymph nodes.
CONCLUSION: Age < 60 years and CA 19-9 elevation could complement radiological detection of LM. Patients aged < 60 years are at higher risk of multiple positive nodes.
doi:10.3748/wjg.v20.i1.290
PMCID: PMC3886021  PMID: 24415884
Gallbladder cancer; Multidetector computed tomography; Lymphatic metastasis; Lymph node excision; Carbohydrate antigen 19-9; Age
20.  Norcantharidin Induced DU145 Cell Apoptosis through ROS-Mediated Mitochondrial Dysfunction and Energy Depletion 
PLoS ONE  2013;8(12):e84610.
Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/ time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5‘-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.
doi:10.1371/journal.pone.0084610
PMCID: PMC3868658  PMID: 24367681
21.  Pregnancy-induced physiological hypertrophy protects against cardiac ischemia-reperfusion injury 
Objective: Cardiac hypertrophy is a compensatory response of the heart to maintain its pumping capacity. Cardiac hypertrophy can be divided into pathological hypertrophy and physiological hypertrophy. The major forms of physiological hypertrophy include developing in response to developmental maturation, exercise, and pregnancy, which is adaptive and beneficial. Exercise has well-known beneficial cardiovascular effects and has recently been shown to be protective for myocardial ischemia-reperfusion injury. However, there are conflicting reports for the cardiac protective effects of pregnancy-induced hypertrophy. In the present study, we investigated the effects of pregnancy-induced physiological hypertrophy in cardiac ischemia-reperfusion injury and if cardiac progenitor cells were activated during pregnancy. Methods: Physiological hypertrophy was induced in pregnancy and the mRNA levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined by real-time polymerase chain reactions (RT-PCRs) analysis. Triphenyltetrazolium chloride staining was used to determine the cardiac ischemia-reperfusion injury. c-Kit and Nkx2.5 levels were determined by RT-PCRs, western blot and immunofluorescent staining. Results: Heart weight (HW) and the ratio of HW to tibia length were increased while mRNA levels of ANP and BNP remained unchanged. Pregnancy-induced physiological hypertrophy protected against cardiac ischemia-reperfusion injury. In pregnancy, c-Kit positive cardiac progenitor cells were activated. Conclusion: This study presents that pregnancy-induced physiological hypertrophy activates cardiac progenitor cells and thereafter protects against cardiac ischemia-reperfusion injury.
PMCID: PMC3885477  PMID: 24427343
Pregnancy; hypertrophy; physiological; ischemia/reperfusion; cardiac progenitor cells
22.  Bone loss in patients with the ileostomy and ileal pouch for inflammatory bowel disease 
Gastroenterology Report  2013;1(3):159-165.
Low bone mineral density (BMD) or low bone mass is common in patients with inflammatory bowel disease (IBD). Studies have shown that low BMD is also common in patients with ulcerative colitis (UC) even after colectomy and ileal pouch–anal anastomosis (IPAA). The reported frequency of osteopenia ranged from 26–55% and that of osteoporosis ranged from 13–32% in patients with IPAA. Increasing age, low body mass index, lack of calcium supplementation and high inflammatory activity with villous atrophy in the ileo-anal pouch are risk factors for low bone mass in pouch patients. Bone loss is also common in patients with IBD and ostomy. Current professional society guidelines do not specifically address the need for surveillance in patients with ileal pouches or ostomy. A growing body of evidence suggests that patients with ileal pouch or ostomy are at an increased risk of bone loss. Pending prospective studies, screening and surveillance using dual energy X-ray absorptiometry (DEXA) along with calcium/vitamin D supplementation may be beneficial in those patients.
doi:10.1093/gastro/got030
PMCID: PMC3937994  PMID: 24759961
Bone loss; Crohn’s disease; inflammatory bowel disease; ulcerative colitis
23.  Co-infections with Babesia microti and Plasmodium parasites along the China-Myanmar border 
Background
Babesiosis is an emerging health risk in several parts of the world. However, little is known about the prevalence of Babesia in malaria-endemic countries. The area along the China-Myanmar border in Yunnan is a main endemic area of malaria in P.R. China, however, human infection with Babesia microti (B. microti) is not recognized in this region, and its profile of co-infection is not yet clear.
Methods
To understand its profile of co-infections with B. microti, our investigation was undertaken in the malaria-endemic area along the China-Myanmar border in Yunnan between April 2012 and June 2013. Four parasite species, including B. microti, Plasmodium falciparum (P. falciparum), P. vivax, and P. malariae, were identified among 449 suspected febrile persons detected by nested polymerase chain reaction (PCR) assay based on small subunit ribosomal ribonucleic acid (RNA) genes of B. microti and Plasmodium spp.
Results
Of all the collected samples from febrile patients, mono-infection with B. microti, P. vivax, P. falciparum, and P. malariae accounted for 1.8% (8/449), 9.8% (44/449), 2.9% (13/449), and 0.2% (1/449), respectively. The rate of mixed infections of B. microti with P. falciparum or P. vivax are both 0.2% (1/449), and mixed infections of P. falciparum and P. vivax accounted for 1.1% (5/449).
Conclusions
This report supports the hypothesis that babesiosis caused by B. microti is emerging along the China-Myanmar border in the Yunnan province, P.R. China, but it was ignored because of low parasitemia or mixed infection with Plasmodium spp. More sensitive and specific diagnosis methods are needed to find the rapid response mechanism of emergency for babesiosis and malaria co-prevalence areas.
doi:10.1186/2049-9957-2-24
PMCID: PMC3819642  PMID: 24090043
Babesia; Plasmodium; Co-infection; China-Myanmar border
24.  Inside-out, outside-in, and inside-outside-in: G protein signaling in integrin-mediated cell adhesion, spreading, and retraction 
Current opinion in cell biology  2012;24(5):600-606.
The integrin family of cell adhesion receptors mediates bi-directional signaling: “inside-out” signaling activates the ligand binding function of integrins and “outside-in” signaling mediates cellular responses induced by ligand binding to integrins leading to cell spreading, retraction, migration, and proliferation. Integrin signaling requires both heterotrimeric G proteins and monomeric small G proteins. This review focuses on recent development in the roles of G proteins in integrin outside-in signaling. The finding of direct interaction between the heterotrimeric G protein subunit Gα13 and integrin β subunits reveals a new mechanism for integrin signaling, and also uncovers a crosstalk between the signaling pathways initiated by G protein-coupled receptors (GPCRs) and integrins. This crosstalk, which may be referred to as “inside-outside-in” signaling, dynamically regulates contractility and greatly promotes integrin outside-in signaling
doi:10.1016/j.ceb.2012.08.011
PMCID: PMC3479359  PMID: 22980731
25.  Enantioselective Synthesis of α-Oxy Amides via Umpolung Amide Synthesis 
Journal of the American Chemical Society  2012;134(37):15233-15236.
α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes, and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids.
doi:10.1021/ja306225u
PMCID: PMC3477818  PMID: 22967461

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