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1.  Chiropractic identity, role and future: a survey of North American chiropractic students 
The literature pertaining to chiropractic students’ opinions with respect to the desired future status of the chiropractic physician is limited and is an appropriate topic worthy of study. A previous pilot study was performed at a single chiropractic college. This current study is an expansion of this pilot project to collect data from chiropractic students enrolled in colleges throughout North America.
The purpose of this study is to investigate North American chiropractic students’ opinions concerning professional identity, role and future.
A 23-item cross-sectional electronic questionnaire was developed. A total of 7,455 chiropractic students from 12 North American English-speaking chiropractic colleges were invited to complete the survey. Survey items encompassed demographics, evidence-based practice, chiropractic identity and setting, and scope of practice. Data were collected and descriptive statistical analysis was performed.
A total of 1,247 (16.7% response rate) questionnaires were electronically submitted. Most respondents agreed (34.8%) or strongly agreed (52.2%) that it is important for chiropractors to be educated in evidence-based practice. A majority agreed (35.6%) or strongly agreed (25.8%) the emphasis of chiropractic intervention is to eliminate vertebral subluxations/vertebral subluxation complexes. A large number of respondents (55.2%) were not in favor of expanding the scope of the chiropractic profession to include prescribing medications with appropriate advanced training. Most respondents estimated that chiropractors should be considered mainstream health care practitioners (69.1%). Several respondents (46.8%) think that chiropractic research should focus on the physiological mechanisms of chiropractic adjustments.
The chiropractic students in this study showed a preference for participating in mainstream health care, report an exposure to evidence-based practice, and desire to hold to traditional chiropractic theories and practices. The majority of students would like to see an emphasis on correction of vertebral subluxation, while a larger percent found it is important to learn about evidence-based practice. These two key points may seem contradictory, suggesting cognitive dissonance. Or perhaps some students want to hold on to traditional theory (e.g., subluxation-centered practice) while recognizing the need for further research to fully explore these theories. Further research on this topic is needed.
Electronic supplementary material
The online version of this article (doi:10.1186/s12998-014-0048-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4313466  PMID: 25646145
Chiropractic; Cross-sectional survey
2.  Impact of enteral nutrition on energy metabolism in patients with Crohn’s disease 
AIM: To investigate the impact of enteral nutrition (EN) on the body composition and metabolism in patients with Crohn’s disease (CD).
METHODS: Sixty-one patients diagnosed with CD were enrolled in this study. They were given only EN (enteral nutritional suspension, TPF, non-elemental diet) support for 4 wk, without any treatment with corticosteroids, immunosuppressive drugs, infliximab or by surgical operation. Body composition statistics such as weight, body mass index, skeletal muscle mass (SMM), fat mass, protein mass and inflammation indexes such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and CD activity index (CDAI) were recorded before and after EN support.
RESULTS: The 61 patients were divided into three groups according to CDAI before and after EN support: A (active phase into remission via EN, n = 21), B (remained in active phase before and after EN, n = 19) and C (in remission before and after EN, n = 21). Patients in group A had a significant increase in SMM (22.11 ± 4.77 kg vs 23.23 ± 4.49 kg, P = 0.044), protein mass (8.01 ± 1.57 kg vs 8.44 ± 1.45 kg, P = 0.019) and decrease in resting energy expenditure (REE) per kilogram (27.42 ± 5.01 kcal/kg per day vs 22.62 ± 5.45 kcal/kg per day, P < 0.05). There was no significant difference between predicted and measured REE in active CD patients according to the Harris-Benedict equation. There was no linear correlation between the measured REE and CRP, ESR or CDAI in active CD patients.
CONCLUSION: EN could decrease the hypermetabolism in active CD patients by reducing the inflammatory response.
PMCID: PMC4306176  PMID: 25632205
Crohn’s disease; Enteral nutrition; Body composition; Metabolism
3.  Overexpression, crystallization and preliminary X-ray crystallographic analysis of the phosphotriesterase from Mycobacterium tuberculosis  
Crystals of the phosphotriesterase from M. tuberculosis were obtained and diffraction data were collected and processed to 2.27 Å resolution. An analytical ultracentrifugation experiment suggested that mPHP exists as dimers in solution.
Organophosphates (OPs) are extremely toxic compounds that are used as insecticides or even as chemical warfare agents. Phosphotriesterases (PHPs) are responsible for the detoxification of OPs by catalysing their degradation. Almost 100 PHP structures have been solved to date, yet the crystal structure of the phosphotriesterase from Mycobacterium tuberculosis (mPHP) remains unavailable. This study reports the first crystallization of mPHP. The crystal belonged to space group C2221, with unit-cell parameters a = 68.03, b = 149.60, c = 74.23 Å, α = β = γ = 90°. An analytical ultracentrifugation experiment suggested that mPHP exists as a dimer in solution, even though one molecule is calculated to be present in the asymmetric unit according to the structural data.
PMCID: PMC3539705  PMID: 23295488
Mycobacterium tuberculosis; phosphotriesterases
4.  Discovery of Invasion Routes for Nasopharyngeal Adenoid Cystic Carcinoma 
Journal of Cancer  2015;6(1):90-97.
The aim of this study is to discover regional invasion routes for nasopharyngeal adenoid cystic carcinoma (NACC) through analyses of the magnetic resonance (MR) images and comparison with keratinizing squamous cell carcinoma (KSCC). Both MR results and clinical records were retrospectively reviewed for 18 patients with NACC and 182 patients with KSCC. The metastasis routes of NACC were identified by analysis of MR images of patients who underwent magnetic resonance imaging (MRI). There were significant differences in skull base invasion and cavernous sinus invasion (p = 0.020 and 0.028, respectively) while parapharyngeal space invasion rate was not. The laryngopharynx invasion rate and external pterygoid muscle invasion rate were higher in NACC patients than that in KSCC patients (16.7% vs. 0.5 %, p = 0.002; 27.8% vs. 11.0%, p = 0.040, respectively). Paralysis of the cranial nerves had a significant higher incidence in the NACC group compared to the KSCC group (66.7% vs. 8.2%, p < 0.001). There was significant difference in invasion to the neural foramen between the NACC and KSCC groups (66.7% vs. 36.3%, p = 0.020). Foramen ovale was a common invasion site, significantly higher in NACC patients than in KSCC patients (50.0% vs. 24.1%, p = 0.018). Based on the MRI findings, a regional invasion model of NACC with two possible routes has been built, including aggressive local infiltration along submucosa to laryngopharynx or external pterygoid muscle, and extension from pharyngonasal cavity, through cranial nerve canal to cavernous sinus. The significant difference in overall survival (OS) time between the two different invasion routs and the recurrent rates in different regions also supported the validity of the invasion model.
PMCID: PMC4278919  PMID: 25553093
nasopharyngeal adenoid cystic carcinoma; keratinizing squamous cell carcinoma; invasion routes; MRI; paralyzed cranial nerve.
5.  Current level and determinants of inappropriate admissions to township hospitals under the new rural cooperative medical system in China: a cross-sectional study 
The increased funding and reimbursement for the New Rural Cooperative Medical System (NRCMS) have provided residents in rural China with better access to inpatient services. This research aims to examine the level of inappropriate admissions to township hospitals under NRCMS, and the determinants that influence inappropriate admissions.
A total of 2,044 medical records in 10 township hospitals were collected from five counties in Midwestern China by stratified cluster sampling and evaluated using the Appropriateness Evaluation Protocol (AEP), which was developed by a Delphi expert consultation of 32 experts. A two-level logistic regression model by MLwiN 2.30 was used to examine the determinants of inappropriate admissions.
Township hospitals had an average inappropriate admission rate of 26.5%. The highest rate of inappropriate admission was among patients aged more than 59 years old (30.1%). Inappropriate admissions mostly occurred for respiratory and circulatory diseases. Township hospital similarity and clustering were observed. Two-level logistic regression analysis showed that age, treating department, and disease were determinants of inappropriate admission.
Township hospitals have a high rate of inappropriate admissions. Explicit diagnostic criteria and a standardized supervision system should be developed to reduce this.
PMCID: PMC4310202  PMID: 25519885
Appropriateness evaluation protocol; Inappropriate admission; New Rural Cooperative Medical System; Rural China; Township hospital
6.  Adult hepatic cavernous hemangioma with highly elevated α-fetoprotein: A case report and review of the literature 
Oncology Letters  2014;9(2):637-640.
A 47-year-old male presented with a six-month history of fatigue and a four-month history of alanine and aspartate aminopherase elevation. Laboratory examination revealed that the serum α-fetoprotein (AFP) level was 371.51 μg/l (normal range, 0–20 μg/l), and a computed tomography scan revealed a hypodense lesion in the left hepatic lobe. During laparotomy, a dark red-colored soft tumor (1.5×1.7 cm in diameter) was found in segment eight of the liver. Intra-operative pathology and post-operative histopathology examinations revealed that the tumor was a hepatic cavernous hemangioma. The serum AFP level was decreased to 24.45 μg/l by the second post-operative week. The literature was searched and only three similar cases were found. A brief review of this rare disease entity was produced, which attempted to explain this appearance reasonably.
PMCID: PMC4301549  PMID: 25624892
hepatic cavernous hemangioma; α-fetoprotein; cancer stem cell
7.  Thoracoscopic left upper lobectomy with systematic lymph nodes dissection under left pulmonary artery clamping 
Journal of Thoracic Disease  2014;6(12):1855-1860.
Video-assisted thoracoscopic surgery (VATS) has become a routine procedure for stage I and II lung cancers. However, in the presence of multiple metastasized lymph nodes invading the pulmonary artery or its major branches, the pulmonary artery have to be resected partially or sleeve resected, which could be extremely risky under thoracoscopic conditions. In order to reduce the risk of bleeding, an experienced thoracic surgeon would occlude the inflow and outflow of the pulmonary artery before anatomically dissecting the area of the pulmonary artery with tumor invasion. Different centers may use different clamping techniques and devices. Here, we report our technique of totally thoracoscopic left upper lobectomy with systematic lymph nodes dissection under pulmonary artery clamping for a 49-year-old woman with left upper lobe carcinoma. The video demonstrates our thinking and surgical process.
PMCID: PMC4283299  PMID: 25589991
Video-assisted thoracoscopic surgery (VATS); left pulmonary artery clamping; left lower lobe pulmonary artery; left upper lobectomy; systematic lymph node dissection
8.  Real-Time qPCR Identifies Suitable Reference Genes for Borna Disease Virus-Infected Rat Cortical Neurons 
Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) is the most commonly-used technique to identify gene expression profiles. The selection of stably expressed reference genes is a prerequisite to properly evaluating gene expression. Here, the suitability of commonly-used reference genes in normalizing RT-qPCR assays of mRNA expression in cultured rat cortical neurons infected with Borna disease virus (BDV) was assessed. The expressions of eight commonly-used reference genes were comparatively analyzed in BDV-infected rat cortical neurons and non-infected control neurons mainly across 9 and 12 days post-infection. These reference genes were validated by RT-qPCR and separately ranked by four statistical algorithms: geNorm, NormFinder, BestKeeper and the comparative delta-Ct method. Then, the RankAggreg package was used to construct consensus rankings. ARBP was found to be the most stable internal control gene at Day 9, and ACTB at Day 12. As the assessment of the validity of the selected reference genes confirms the suitability of applying a combination of the two most stable references genes, combining the two most stable genes for normalization of RT-qPCR studies in BDV-infected rat cortical neurons is recommended at each time point. This study can contribute to improving BDV research by providing the means by which to obtain more reliable and accurate gene expression measurements.
PMCID: PMC4284680  PMID: 25431926
Borna disease virus; BDV; reference gene; RT-qPCR; cortical neuron
9.  Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling 
The AAPS Journal  2013;16(1):101-113.
Licorice has been shown to affect the activities of several cytochrome P450 enzymes. This study aims to identify the key constituents in licorice which may affect these activities. Bioactivity assay was combined with metabolic profiling to identify these compounds in several complex licorice extracts. Firstly, the inhibition potencies of 40 pure licorice compounds were tested using an liquid chromatography/tandem mass spectrometry cocktail method. Significant inhibitors of human P450 isozymes 1A2, 2C9, 2C19, 2D6, and 3A4 were then selected for examination of their structural features by molecular docking to determine their molecular interaction with several P450 isozymes. Based on the present in vitro inhibition findings, along with our previous in vivo metabolic studies and the prevalence of individual compounds in licorice extract, we identified several licorice constituents, viz., liquiritigenin, isoliquiritigenin, together with seven isoprenylated flavonoids and arylcoumarins, which could be key components responsible for the herb–drug interaction between cytochrome P450 and licorice. In addition, hydrophilic flavonoid glycosides and saponins may be converted into these P450 inhibitors in vivo. These studies represent a comprehensive examination of the potential effects of licorice components on the metabolic activities of P450 enzymes.
Electronic supplementary material
The online version of this article (doi:10.1208/s12248-013-9544-9) contains supplementary material, which is available to authorized users.
PMCID: PMC3889530  PMID: 24254844
CYP450; herb–drug interaction; isoliquiritigenin; licorice; liquiritigenin
10.  Hemangioendothelioma arising from the spleen: A case report and literature review 
Oncology Letters  2014;9(1):209-212.
Primary hemangioendotheliomas (HEs) of the spleen are rare, low-grade borderline-malignant vascular tumors. To date, only a few splenic HE cases have been reported in adults. In infants, one 9-year-old male patient has previously been reported, and the patient succumbed to the disease shortly following surgery. Currently, the clinical treatment and prognosis of the disease remains challenging to define, due to the extremely low number of cases reported. The current report presents the case of a 9-year-old pediatric patient with splenic HE, who survived with no recurrence or complications following a partial splenectomy. Additionally, a literature review was conducted to analyze the treatment and prognosis of the disease.
PMCID: PMC4246698  PMID: 25435960
hemangioendotheliomas; spleen; partial splenectomy
11.  Novel phosphatidylinositol 3-kinase inhibitor NVP-BKM120 induces apoptosis in myeloma cells and shows synergistic anti-myeloma activity with dexamethasone 
NVP-BKM120 is a novel phosphatidylinositol 3-kinase (PI3K) inhibitor and is currently being investigated in phase I clinical trials in solid tumors. This study aimed to evaluate the therapeutic efficacy of BKM120 in multiple myeloma (MM). BKM120 induces cell growth inhibition and apoptosis in both MM cell lines and freshly isolated primary MM cells. However, BKM120 only shows limited cytotoxicity toward normal lymphocytes. The presence of MM bone marrow stromal cells, insulin-like growth factor, or interleukin-6 does not affect BKM120-induced tumor cell apoptosis. More importantly, BKM120 treatment significantly inhibits tumor growth in vivo and prolongs the survival of myeloma-bearing mice. In addition, BKM120 shows synergistic cytotoxicity with dexamethasone in dexamethasone-sensitive MM cells. Low doses of BKM120 and dexamethasone, each of which alone has limited cytotoxicity, induce significant cell apoptosis in MM.1S and ARP-1. Mechanistic study shows that BKM120 exposure causes cell cycle arrest by upregulating p27 (Kip1) and downregulating cyclin D1 and induces caspase-dependent apoptosis by downregulating antiapoptotic XIAP and upregulating expression of cytotoxic small isoform of Bim, BimS. In summary, our findings demonstrate the in vitro and in vivo anti-MM activity of BKM120 and suggest that BKM120 alone or together with other MM chemotherapeutics, particularly dexamethasone, may be a promising treatment for MM.
PMCID: PMC4212830  PMID: 22207485
Multiple myeloma; PI3K; BKM120; Apoptosis; Chemotherapy
12.  Genome-wide DNA Methylation Profiles and Their Relationships with mRNA and the microRNA Transcriptome in Bovine Muscle Tissue (Bos taurine) 
Scientific Reports  2014;4:6546.
DNA methylation is a key epigenetic modification in mammals and plays important roles in muscle development. We sampled longissimus dorsi muscle (LDM) from a well-known elite native breed of Chinese Qinchuan cattle living within the same environment but displaying distinct skeletal muscle at the fetal and adult stages. We generated and provided a genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA for fetal and adult muscle studies. Integration analysis revealed a total of 77 and 1,054 negatively correlated genes with methylation in the promoter and gene body regions, respectively, in both the fetal and adult bovine libraries. Furthermore, we identified expression patterns of high-read genes that exhibit a negative correlation between methylation and expression from nine different tissues at multiple developmental stages of bovine muscle-related tissue or organs. In addition, we validated the MeDIP-Seq results by bisulfite sequencing PCR (BSP) in some of the differentially methylated promoters. Together, these results provide valuable data for future biomedical research and genomic and epigenomic studies of bovine skeletal muscle that may help uncover the molecular basis underlying economically valuable traits in cattle. This comprehensive map also provides a solid basis for exploring the epigenetic mechanisms of muscle growth and development.
PMCID: PMC4194443  PMID: 25306978
13.  Experimental Comparison of the Reproductive Outcomes and Early Development of the Offspring of Rats Given Five Common Types of Drinking Water 
PLoS ONE  2014;9(10):e108955.
Tap water (unfiltered), filtered tap water and processed bottled water (purified water, artificial mineralized water, or natural water) are now the five most widely consumed types of drinking water in China. However, the constituents (organic chemicals and inorganic ingredients) of the five waters differ, which may cause them to have different long-term health effects on those who drink them, especially sensitive children. In order to determine which type of water among the five waters is the most beneficial regarding reproductive outcomes and the developmental behaviors of offspring, two generations of Sprague–Dawley rats were given these five waters separately, and their reproductive outcomes and the developmental behaviors of their offspring were observed and compared. The results showed that the unfiltered tap water group had the lowest values for the maternal gestation index (MGI) and offspring's learning and memory abilities (OLMA); the lowest offspring survival rate was found in the purified water group; and the highest OLMA were found in the filtered tap water group. Thus, the best reproductive and offspring early developmental outcomes were found in the group that drank filtered tap water, which had the lowest levels of pollutants and the richest minerals. Therefore, thoroughly removing toxic contaminants and retaining the beneficial minerals in drinking water may be important for both pregnant women and children, and the best way to treat water may be with granular activated carbon and ion exchange by copper zinc alloy.
PMCID: PMC4184831  PMID: 25279561
14.  Cytochrome C oxidase subunit I barcodes provide an efficient tool for Jinqian Baihua She (Bungarus parvus) authentication 
Pharmacognosy Magazine  2014;10(40):449-457.
To test the feasibility of DNA barcoding for accurate identification of Jinqian Baihua She and its adulterants.
Materials and Methods:
Standard cytochrome C oxidase subunit I (COI) gene fragments were sequenced for DNA barcoding of 39 samples from 9 snake species, including Bungarus multicinctus, the officially recognized origin animal by Chinese Pharmacopoeia, and other 8 adulterate species. The aligned sequences, 658 base pairs in length, were analyzed for divergence using the Kimura-2-parameter (K2P) distance model with MEGA5.0.
The mean intraspecific K2P distance was 0.0103 and the average interspecific genetic distance was 0.2178 in B. multicinctus, far greater than the minimal interspecific genetic distance of 0.027 recommended for species identification. A neighbor-joining (NJ) tree was constructed, in which each species formed a monophyletic clade with bootstrap supports of 100%. All the data were submitted to Barcode of Life Data system version 3.0 (BOLD, under the project title “DNA barcoding Bungarus multicinctus and its adulterants”. Ten samples of commercially available crude drugs of JBS were identified using the identification engine provided by BOLD. All the samples were clearly identified at the species level, among which five were found to be the adulterants and identified as Dinodon rufozonatum.
DNA barcoding using the standard COI gene fragments provides an effective and accurate means for JBS identification and authentication.
PMCID: PMC4239722  PMID: 25422545
Bungarus multicinctus; cytochrome C oxidase subunit I; DNA barcodes; identification
15.  Combination use of platelets and recombinant activated factor VII for increased hemostasis during acute type a dissection operations 
Refractory blood loss is a common problem in surgeries for acute type A aortic dissections. Significant evidence has supported the benefit of using recombinant activated factor VII (rFVIIa) to control of intractable bleeding in patients after cardiac surgery. In this prospective clinical study, we present a novel method to achieve intraoperative hemostasis by using a combination of platelets and rFVIIa during operations for acute type A aortic dissections.
Between May 2009 and August 2012, 71 patients with acute type A dissections who underwent emergency surgery were prospectively included and allocated to one of the following two intervention groups for hemostasis: 3 units platelets combined with 2.4 mg rFVIIa (n = 25), and conventional methods (n = 46).
The patients who received the combination of platelets and rFVIIa required fewer transfusions of red blood cells (6.2 ± 3.1 units vs 9.8 ± 2.8 units; p < 0.05), fresh frozen plasma (736.9 ± 178.3 ml vs 1264.3 ± 245.2 ml, p < 0.05), platelet concentrates (3 units vs 5.0 ± 1.8 units, p < 0.001), and cryoprecipitate (2.8 ± 0.9 units vs 8.2 ± 2.3 units, p < 0.05). These patients also required less time for sternal closure (76.9 ± 17.2 min vs 102.3 ± 10.7 min, p < 0.05) compared with the conventional therapy patients. There was no statistically significant difference in the incidence of serious adverse events between these two groups.
Using a combination of platelets and rFVIIa is an effective strategy for achieving hemostasis during acute type A dissection surgery. This hemostatic strategy does not appear to be associated with an increase in postoperative adverse events.
PMCID: PMC4156631  PMID: 25179738
Platelets; Recombinant activated factor VII (rFVIIa); Acute type A dissection; Hemostatic strategy
16.  Clinical outcomes of a novel combination of lenalidomide and rituximab followed by stem cell transplantation for relapsed/refractory aggressive B-cell non-hodgkin lymphoma 
Oncotarget  2014;5(17):7368-7380.
We retrospectively compared outcomes of patients with relapsed/refractory non-Hodgkin lymphoma (NHL) who underwent stem cell transplantation (SCT) with stable disease or better following a novel combination of lenalidomide and rituximab (LR) treatment and did not undergo SCT in a phase I/II clinical trial. We retrospectively compared outcomes of patients who underwent SCT with that of patients who had stable disease or better following LR treatment and did not undergo SCT. Twenty-two patients enrolled in LR clinical trial and undergone SCT were identified, 13 with mantle cell lymphoma (MCL) and nine with large B-cell lymphoma (LBCL). All patients who underwent SCT achieved complete response. In the MCL subset, there were no significant differences between SCT and non-SCT groups except that non-SCT patients were older and had a higher mantle-cell international prognostic index score. There was no difference between SCT-group and non-SCT-group in response duration (P=0.3), progression-free survival (PFS) (P=0.304) and overall survival (OS) (P=0.87). In LBCL subgroup, there were no significant differences between two groups except that non-SCT group had a higher international prognostic index score. Patients with LBCL who underwent SCT had significantly longer response duration (P=0.001), PFS (P=0.000), and OS (P=0.003) than the non-SCT group. The novel therapeutic combination offers a bridge to SCT in patients with relapsed/refractory aggressive B-cell NHL.
PMCID: PMC4202129  PMID: 25228589
Clinical outcomes; Lenalidomide; Relapsed lymphoma; Rituximab; Stem cell transplantation
17.  Motion Field Estimation for a Dynamic Scene Using a 3D LiDAR 
Sensors (Basel, Switzerland)  2014;14(9):16672-16691.
This paper proposes a novel motion field estimation method based on a 3D light detection and ranging (LiDAR) sensor for motion sensing for intelligent driverless vehicles and active collision avoidance systems. Unlike multiple target tracking methods, which estimate the motion state of detected targets, such as cars and pedestrians, motion field estimation regards the whole scene as a motion field in which each little element has its own motion state. Compared to multiple target tracking, segmentation errors and data association errors have much less significance in motion field estimation, making it more accurate and robust. This paper presents an intact 3D LiDAR-based motion field estimation method, including pre-processing, a theoretical framework for the motion field estimation problem and practical solutions. The 3D LiDAR measurements are first projected to small-scale polar grids, and then, after data association and Kalman filtering, the motion state of every moving grid is estimated. To reduce computing time, a fast data association algorithm is proposed. Furthermore, considering the spatial correlation of motion among neighboring grids, a novel spatial-smoothing algorithm is also presented to optimize the motion field. The experimental results using several data sets captured in different cities indicate that the proposed motion field estimation is able to run in real-time and performs robustly and effectively.
PMCID: PMC4208193  PMID: 25207868
3D LiDAR; motion field estimation; motion sensing; spatial smoothing
18.  Chemical Interference with Iron Transport Systems to Suppress Bacterial Growth of Streptococcus pneumoniae 
PLoS ONE  2014;9(8):e105953.
Iron is an essential nutrient for the growth of most bacteria. To obtain iron, bacteria have developed specific iron-transport systems located on the membrane surface to uptake iron and iron complexes such as ferrichrome. Interference with the iron-acquisition systems should be therefore an efficient strategy to suppress bacterial growth and infection. Based on the chemical similarity of iron and ruthenium, we used a Ru(II) complex R-825 to compete with ferrichrome for the ferrichrome-transport pathway in Streptococcus pneumoniae. R-825 inhibited the bacterial growth of S. pneumoniae and stimulated the expression of PiuA, the iron-binding protein in the ferrichrome-uptake system on the cell surface. R-825 treatment decreased the cellular content of iron, accompanying with the increase of Ru(II) level in the bacterium. When the piuA gene (SPD_0915) was deleted in the bacterium, the mutant strain became resistant to R-825 treatment, with decreased content of Ru(II). Addition of ferrichrome can rescue the bacterial growth that was suppressed by R-825. Fluorescence spectral quenching showed that R-825 can bind with PiuA in a similar pattern to the ferrichrome-PiuA interaction in vitro. These observations demonstrated that Ru(II) complex R-825 can compete with ferrichrome for the ferrichrome-transport system to enter S. pneumoniae, reduce the cellular iron supply, and thus suppress the bacterial growth. This finding suggests a novel antimicrobial approach by interfering with iron-uptake pathways, which is different from the mechanisms used by current antibiotics.
PMCID: PMC4149436  PMID: 25170896
19.  A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation 
Nature chemical biology  2013;10(2):93-95.
N6-methyladenosine (m6A) is the most prevalent and reversible internal modification in mammalian messenger and non-coding RNAs. We report here that human METTL14 catalyzes m6A RNA methylation. Together with METTL3, the only previously known m6A methyltransferase, these two proteins form a stable heterodimer core complex of METTL3-14 that functions in cellular m6A deposition on mammalian nuclear RNAs. WTAP, a mammalian splicing factor, can interact with this complex and affect this methylation.
PMCID: PMC3911877  PMID: 24316715
20.  Atomistic Simulation of Tensile Deformation Behavior of ∑5 Tilt Grain Boundaries in Copper Bicrystal 
Scientific Reports  2014;4:5919.
Experiments on polycrystalline metallic samples have indicated that Grain boundary (GB) structure can affect many material properties related to fracture and plasticity. In this study, atomistic simulations are employed to investigate the structures and mechanical behavior of both symmetric and asymmetric ∑5[0 0 1] tilt GBs of copper bicrystal. First, the equilibrium GB structures are generated by molecular statics simulation at 0K. The results show that the ∑5 asymmetric GBs with different inclination angles (φ) are composed of only two structural units corresponding to the two ∑5 symmetric GBs. Molecular dynamics simulations are then conducted to investigate the mechanical response and the underlying deformation mechanisms of bicrystal models with different ∑5 GBs under tension. Tensile deformation is applied under both ‘free’ and ‘constrained’ boundary conditions. Simulation results revealed different mechanical properties of the symmetric and asymmetric GBs and indicated that stress state can play an important role in the deformation mechanisms of nanocrystalline materials.
PMCID: PMC4118255  PMID: 25082227
21.  Hypoxia Adaptations in the Grey Wolf (Canis lupus chanco) from Qinghai-Tibet Plateau 
PLoS Genetics  2014;10(7):e1004466.
The Tibetan grey wolf (Canis lupus chanco) occupies habitats on the Qinghai-Tibet Plateau, a high altitude (>3000 m) environment where low oxygen tension exerts unique selection pressure on individuals to adapt to hypoxic conditions. To identify genes involved in hypoxia adaptation, we generated complete genome sequences of nine Chinese wolves from high and low altitude populations at an average coverage of 25× coverage. We found that, beginning about 55,000 years ago, the highland Tibetan grey wolf suffered a more substantial population decline than lowland wolves. Positively selected hypoxia-related genes in highland wolves are enriched in the HIF signaling pathway (P = 1.57E-6), ATP binding (P = 5.62E-5), and response to an oxygen-containing compound (P≤5.30E-4). Of these positively selected hypoxia-related genes, three genes (EPAS1, ANGPT1, and RYR2) had at least one specific fixed non-synonymous SNP in highland wolves based on the nine genome data. Our re-sequencing studies on a large panel of individuals showed a frequency difference greater than 58% between highland and lowland wolves for these specific fixed non-synonymous SNPs and a high degree of LD surrounding the three genes, which imply strong selection. Past studies have shown that EPAS1 and ANGPT1 are important in the response to hypoxic stress, and RYR2 is involved in heart function. These three genes also exhibited significant signals of natural selection in high altitude human populations, which suggest similar evolutionary constraints on natural selection in wolves and humans of the Qinghai-Tibet Plateau.
Author Summary
Understanding the genetic mechanisms that allow some individuals to live at high altitudes under hypoxic conditions can provide insight into the evolutionary constraints of adaptation to extreme conditions and the development of hypoxia-related disease in humans. The Tibetan grey wolf (Canis lupus chanco) has long existed on the Qinghai-Tibet Plateau, where low oxygen tension exerts unique selection pressure on individuals. Comparing the complete genome sequences of 4 grey wolves from high altitude and 5 from low altitude, we identify three candidate genes for high-altitude adaptation (EPAS1, ANGPT1, and RYR2) that show strong signals of selection. The three genes potentially enhance function under hypoxic conditions by increasing oxygen delivery (EPAS1 and ANGPT1) and heart (RYR2) function. These genes also appear under selection in high altitude human populations, which suggesting there may be limited pathways for adapting to high altitude existence.
PMCID: PMC4117439  PMID: 25078401
22.  Effects of Extract from Cole Pollen on Lipid Metabolism in Experimental Hyperlipidemic Rats 
The Scientific World Journal  2014;2014:982498.
In order to evaluate the effects of extract by SCE (supercritical carbon dioxide extraction) from cole pollen on lipid metabolism in hyperlipidemic rats, the experimental hyperlipidemic rats were established by providing with high fat diets, and randomized into six groups. After four weeks of perfusion diets into stomach, the rats were executed, and lipid levels of serum and hepatic tissue were detected. The serum levels of TC and TG were significantly lower in the pollen extract groups and MC group than in HFC group. Hepatic TC levels were decreased in rats fed pollen extract and lovastatin compared with HFC group. A higher concentration of HDL-C and apoAI in hepatic tissue was measured after intake of the pollen extract compared to the HFC group (P < 0.05). LCAT activity in serum of pollen extract groups was significantly higher than that in HFC group, and also HMG-CoA reductase showed decreasing tendency in pollen extract groups. The contents of DHA in pollen extract groups were found higher than those in HFC group. Cole pollen extract enriched in alpha-linolenic acid is likely to be a novel source of ALA which is probably responsible for favorable lipid changes through promoting transportation, excretion, and metabolism of cholesterol in hepatic tissue and serum.
PMCID: PMC4134780  PMID: 25152932
23.  Aqueous extract of post-fermented tea reverts the hepatic steatosis of hyperlipidemia rat by regulating the lipogenic genes expression and hepatic fatty acid composition 
Post-fermented tea has been used for the prevention of metabolic syndrome in Western China. Present study reports the biochemical mechanism of lipid-lowering effects of Jing-wei fu tea (JWFT), a variety of post-fermented tea on high-fat diet-induced hyperglycemia and obesity in rats.
Aqueous extract of JWFT was prepared by putting them in boiling water, and then concentrated under reduced pressure. The major compounds of JWFT were determined by high performance liquid chromatography (HPLC). High-fat diet fed rats were orally administered different doses of JWFT aqueous extract (0.5, 1.0 and 2.0 g/kg) for four weeks. At the end of this experiment, hepatic lipids, serum leptin and lipids levels were determined using enzyme-linked immunosorbent assay (ELISA). The hepatic fatty acid composition was analyzed using gas chromatography mass (GC-MS). The relative expression of lipids metabolism genes was analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR).
The results showed that JWFT inhibited the increase in the body weight, abdominal adipose weight, serum lipids and hepatic lipids, and decreased serum leptin levels of high-fat diet fed rats. JWFT normalized hepatic fatty acid composition of hyperlipidemia rats by up-regulating hepatic acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase 1 (SCD1) and fatty acid synthase (FAS) gene expression, and down-regulating carnitine palmitoyl transferase-1 (CPT1). Furthermore, the results showed that JWFT inhibited the absorption of lipids.
JWFT could mitigate the obesity-induced hepatic steatosis by regulating hepatic lipogenesis and lipolysis.
PMCID: PMC4122764  PMID: 25055996
Post-fermented tea; Lipids; Absorption; Lipogenic genes; Leptin
24.  Bioactive proteins and peptides isolated from Chinese medicines with pharmaceutical potential 
Chinese Medicine  2014;9:19.
Some protein pharmaceuticals from Chinese medicine have been developed to treat cardiovascular diseases, genetic diseases, and cancer. Bioactive proteins with various pharmacological properties have been successfully isolated from animals such as Hirudo medicinalis (medicinal leech), Eisenia fetida (earthworm), and Mesobuthus martensii (Chinese scorpion), and from herbal medicines derived from species such as Cordyceps militaris, Ganoderma, Momordica cochinchinensis, Viscum album, Poria cocos, Senna obtusifolia, Panax notoginseng, Smilax glabra, Ginkgo biloba, Dioscorea batatas, and Trichosanthes kirilowii. This article reviews the isolation methods, molecular characteristics, bioactivities, pharmacological properties, and potential uses of bioactive proteins originating from these Chinese medicines.
PMCID: PMC4110622  PMID: 25067942
25.  Meta-Analysis of EGFR Tyrosine Kinase Inhibitors Compared with Chemotherapy as Second-Line Treatment in Pretreated Advanced Non-Small Cell Lung Cancer 
PLoS ONE  2014;9(7):e102777.
Since efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy in the treatment of patients with pretreated advanced non-small cell lung cancer (NSCLC) remain controversial, we performed a meta-analysis to compare them.
An internet search of several databases was performed, including PubMed, Embase, and the Cochrane database. Randomized trials that compared an EGFR-TKI with chemotherapy in the second-line setting were included. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade 3–4 toxicities. The PFS, OS for the EGFR mutation-positive (EGFR M+) and EGFR mutation-negative (EGFR M−) subgroups were pooled. The pooled hazard ratios (HRs) and odds ratios (ORs) with their corresponding confidence intervals (CIs) were calculated on the STATA software.
Our meta-analysis combined 3,825 patients from 10 randomized trials. Overall, EGFR-TKIs and second-line chemotherapy have equivalent efficacy in terms of PFS (HR, 1.03; 95%CI, 0.87–1.21; P = 0.73; I2 = 78.7%, Pheterogeneity<0.001), OS (HR, 1.00; 95%CI, 0.92–1.08; P = 0.90; I2 = 0.0%, Pheterogeneity = 0.88), and ORR (OR, 1.34; 95%CI, 0.86–2.08; P = 0.20; I2 = 73.1%, Pheterogeneity<0.001). However, subgroup analysis based on EGFR mutation status showed that second-line chemotherapy significantly improved PFS (HR, 1.35; 95%CI, 1.09–1.66; P = 0.01; I2 = 55.7%, Pheterogeneity = 0.046) for EGFR M− patients, whereas OS was equal (HR, 0.96; 95%CI, 0.77–1.19; P = 0.69; I2 = 0.0%, Pheterogeneity = 0.43); EGFR-TKIs significantly improved PFS (HR, 0.28; 95%CI, 0.15–0.53; P<0.001; I2 = 4.1%, Pheterogeneity = 0.35) for EGFR M+ patients, whereas OS was equal (HR, 0.86; 95%CI, 0.44–1.68; P = 0.65; I2 = 0.0%, Pheterogeneity = 0.77). Compared with chemotherapy, EGFR-TKIs led to more grade 3–4 rash, but less fatigue/asthenia disorder, leukopenia and thrombocytopenia.
Our analysis suggests that chemotherapy in the second-line setting can prolong PFS in EGFR M− patients, whereas it has no impact on OS. EGFR-TKIs seem superior over chemotherapy as second-line therapy for EGFR M+ patients. Our findings support obtaining information on EGFR mutational status before initiation of second-line treatment.
PMCID: PMC4100920  PMID: 25029199

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