Search

Nonconventional biomacromolecular luminogens have attracted extensive interest due to their fundamental importance and potential applications in diverse areas. To explore novel luminogens and, moreover, to gain deeper insights into their emission mechanism, we study the emission behaviors of sodium alginate (SA), a natural anionic polysaccharide composed of mannuronic (M) and guluronic acids (G). We find that the luminescence from aqueous SA solutions exhibits distinct concentration enhanced emission and aggregation-induced emission (AIE) characteristics. Meanwhile, the ratio of M/G also matters. Rheological measurements reveal the distinct regimes of the solutions, which are consistent with the observed emission, indicative of strong association between the chain entanglement and emission. Moreover, we observe persistent room temperature phosphorescence (RTP) in the amorphous SA solids, which is a rare case even in pure organic aromatic luminogens. Such unique emission can be remarkably enhanced via coordination with Ca2+ ions. These emission behaviors can be well rationalized by the clustering-triggered emission (CTE) mechanism. Namely, the emission is caused by the electron cloud overlap due to the clustering of oxygen atoms and carboxylate units, together with conformation rigidification. Owing to its biocompatibility, intrinsic emission, and, moreover, persistent RTP, SA shows great potential for anticounterfeiting, encryption, intracellular imaging, and so on. [ABSTRACT FROM AUTHOR]

Trypanosoma brucei causes sleeping sickness in humans and nagana in cattle in sub-Saharan Africa and alternates between its mammalian hosts and its insect vector, the tsetse fly. T. brucei uses a flagellum for motility, cell division, and cell- cell communication. Proper positioning and attachment of the newly assembled flagellum rely on the faithful duplication and segregation of flagellum-associated cytoskeletal structures. These processes are regulated by the polo-like kinase homolog TbPLK, whose activity and abundance are under stringent control to ensure spatiotemporally regulated phosphorylation of its substrates. However, it remains unclear whether a protein phosphatase that counteracts TbPLK activity is also involved in this regulation. Here, we report that a putative kinetoplastid-specific protein phosphatase, named KPP1, has essential roles in regulating flagellum positioning and attachment in T. brucei. KPP1 localized to multiple flagellum-associated cytoskeletal structures and co-localized with TbPLK in several cytoskeletal structures at different cell-cycle stages. KPP1 depletion abolished basal body segregation, inhibited the duplication of the centrin arm and the hook complex of the bilobe structure, and disrupted the elongation of the flagellum attachment zone, leading to flagellum misplacement and detachment and cytokinesis arrest. Importantly, KPP1-depleted cells lacked dephosphorylation of TbCentrin2, a TbPLK substrate, at late cell-cycle stages. Together, these results suggest that KPP1-mediated protein dephosphorylation regulates the duplication and segregation of flagellum-associated cytoskeletal structures, thereby promoting flagellum positioning and attachment. These findings highlight the requirement of reversible protein phosphorylation, mediated by TbPLK and KPP1, in regulating flagellum inheritance in T. brucei. [ABSTRACT FROM AUTHOR]

The role of the Kerguelen plume in breaking up eastern Gondwana is so far unclear. Recently, the initial magmatic record of the plume has been identified in the Comei igneous province, Tethyan Himalaya. In this contribution, we investigated a group of basaltic intrusions (Juelongpu and Zhaxikang) and felsic lavas (Sangxiu) from the Comei igneous province. Laser ablation-inductively coupled plasma-mass spectrometry zircon U-Pb dating indicates that these mafic and felsic rocks were emplaced in the Early Cretaceous (ca. 140-137 Ma). Probably originating from the Kerguelen plume, the Juelongpu and Zhaxikang mafic rocks are characterized by high incompatible element abundances, high Nb/Y ratios, and oceanic-island basalt-like rare earth element and trace-element patterns. The Sangxiu felsic samples share A-type affinities and were derived by partial melting of crustal rocks. These mafic and felsic rocks represent a magmatic response to the initial activity of the Kerguelen plume. Their ages (ca. 140-137 Ma) are older than the timing of initial breakup of eastern Gondwana (ca. 137-136 Ma), indicating that the plume must have been incubating underneath the supercontinent before the breakup. Recent plate reconstructions coupled with our geochemical and geochronological constraints suggest that the Kerguelen plume head was resident under the Comei area of Greater India at ca. 140 Ma. Our results, in conjunction with previous studies, support the viewpoint that the Kerguelen plume played an active role in breaking up eastern Gondwana. [ABSTRACT FROM AUTHOR]

Reinforced concrete (RC) moment frames supported on two ground levels have been widely constructed in mountainous areas with medium to high seismicity in China. In order to investigate the seismic collapse behavior and risk, a scaled frame model was tested under constant axial load and reversed cyclic lateral load. Test results show that the failure can be induced by the development of story yielding at the first story above the upper ground. The strong column and weak beam mechanism can be well realized at stories below the upper ground. Numerical analysis model was developed and calibrated with the test results. Three pairs of six case study buildings considering various structural configurations were designed and analyzed, showing similar dynamic characteristics between frames on two ground levels and flat ground of each pair. Incremental dynamic analyses (IDA) were then conducted to obtain the seismic collapse fragility curves and collapse margin ratios of nine analysis cases designated based on the case study buildings, considering amplification of earthquake effect and strengthening measures. Analysis results indicate that the seismic collapse safety is mainly determined by the stories above the upper ground. The most probable collapse mechanism may be induced by the story yielding of the bottom story on the upper ground level. The use of tie beam and column strengthening can effectively enhance the seismic collapse safety of frames on two ground levels. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the most common malignant tumours. Competitive endogenous RNA (ceRNA) networks have been hypothesized, in which various RNAs regulate each other's expression using microRNA response elements (MREs). Recent evidence has highlighted the crucial regulatory roles of ceRNA networks in colorectal cancer. In this review, we summarize the present research methods as well as the currently known ceRNA competitors and targets in colorectal cancer. In addition, we discuss the significance of ceRNA and shortcomings of current studies of colorectal cancer. [ABSTRACT FROM AUTHOR]

This particle-in-cell simulation study finds that the system of a long relativistic electron beam passing through an overdense plasma can produce high harmonic terahertz electromagnetic radiation. In this process, the electron beam is self-modulated to create a periodic electromagnetic structure which will resonate with the plasma wakefield and excite the electromagnetic instability in the nonlinear stage of the self-modulation. The study also finds that when the radiation is achieved, the self-modulated electron beam will be destroyed due to the self-consistent interaction among the radiation, the electron beam, and the plasma. Meanwhile, the radiation will gradually attenuate, which also coincides with the physical explanation of the radiation. [ABSTRACT FROM AUTHOR]

Increasing research has shown a link between viruses and miRNAs, such as miRNA-146a, in regulating virus infection and replication. In the current study, the association between miR-146a and hantaan virus (HTNV) infection in human umbilical vein endothelial cells (HUVECs) was investigated, with a focus on examining the expression of pro-inflammatory cytokines. The results showed that HTNV infection promoted the production of miR-146a in HUVECs and activated nuclear factor-κB (NF-κB) signaling, along with the upregulation of pro-inflammatory cytokines, including interleukin 8 (IL-8), C-C Motif Chemokine Ligand 5 (CCL5, also RANTES), interferon-inducible protein-10 (IP-10) and interferon beta (IFN-β). Moreover, miR-146a exhibited a negative regulatory effect on the NF-κB pathway. Accordingly, a miR-146a inhibitor increased the expression of IL-8, CCL5, IP-10 and IFN-β, whereas a miR-146a mimic reduced the levels of these cytokines. Consequently, exogenous transduction of miR-146a significantly enhanced HTNV replication in HUVEC cells. We also discovered that viral proteins (NP/GP) contributed to miR-146a expression via enhancement the activity of miR-146a promoter. In conclusion, these results imply the negative regulation of miR-146a on the production of HTNV-induced pro-inflammatory cytokines contributes to virus replication, which suggest that miR-146a may be regarded as a novel therapeutic target for HTNV infection. [ABSTRACT FROM AUTHOR]

Current strategies of gene transfection are not efficient at achieving a notable therapeutic effect. The aim of the present study was to combine ultrasound‑targeted microbubble destruction (UTMD) with a polyethylenimine/pEGFP‑N3 plasmid/nuclear localization sequence (PEI/DNA/NLS) complex gene delivery system, and evaluate the transfection efficiency of enhanced green fluorescent protein (EGFP) gene delivery to 293T cells using this system. The formation of PEI/DNA/NLS complexes and the protective effects of PEI/NLS were verified by gel electrophoresis. Solutions consisting of the plasmid alone, PEI/DNA complexes, PEI/DNA/NLS complexes, UTMD+DNA, UTMD+PEI/DNA complexes, and UTMD+PEI/DNA/NLS complexes were transduced into 293T cells via ultrasound irradiation. The expression of GFP was observed using an inverted microscope and transfection efficiency was detected by flow cytometry following 24 h incubation in vitro. Cell activity was detected using a Cell Counting kit (CCK)‑8 assay. Gel electrophoresis confirmed the formation of PEI/DNA/NLS complexes and demonstrated that PEI/NLS exhibited protective effects on plasmid integrity for a limited time. Inverted microscope observations revealed that a greater GFP signal was observed with the combined action of PEI/DNA/NLS complexes with UTMD, and flow cytometry analysis demonstrated the highest level of transfection efficiency in this group. In addition, the viability of the cells detected by CCK‑8 and treated with PEI/DNA/NLS complexes with UTMD was >80%. In conclusion, the combination of UTMD and PEI/DNA/NLS complexes was highly effective for the efficient transfection of 293T cells without causing excessive cell damage. This method may provide a novel and effective gene transduction system to be applied in clinical treatments. [ABSTRACT FROM AUTHOR]

The treatment paradigm of non-small cell lung cancer (NSCLC) has evolved into oncogene-directed precision medicine. Identifying actionable genomic alterations is the initial step towards precision medicine. An important scientific progress in molecular profiling of NSCLC over the past decade is the shift from the traditional piecemeal fashion to massively parallel sequencing with the use of next-generation sequencing (NGS). Another technical advance is the development of liquid biopsy with great potential in providing a dynamic and comprehensive genomic profiling of NSCLC in a minimally invasive manner. The integration of NGS with liquid biopsy has been demonstrated to play emerging roles in genomic profiling of NSCLC by increasing evidences. This review summarized the potential applications of NGS-based liquid biopsy in the diagnosis and treatment of NSCLC including identifying actionable genomic alterations, tracking spatiotemporal tumor evolution, dynamically monitoring response and resistance to targeted therapies, and diagnostic value in early-stage NSCLC, and discussed emerging challenges to overcome in order to facilitate clinical translation in future. [ABSTRACT FROM AUTHOR]

The poloidal electric filed, which is the drive field of poloidal rotation, has been observed and increases obviously after the injection of electron cyclotron resonance wave in HL-2A experiment, and the amplitude of the poloidal electric field is in the order of 103 V/m. Through theoretical analysis using Stringer rotation model, the observed poloidal electric field is of the same order as the theoretical calculation value. In addition, the magneticpumpdamping whichwould damp the poloidal rotation is calculated numerically and the calculation results showthat the closer to the core plasmas, the stronger the magnetic pump damping will be. Meanwhile, according to the value of the calculated magnetic pump damping, the threshold of the poloidal electric field which could overcome magnetic pump damping and drive poloidal rotation in tokamak plasmas is given out. Finally, the poloidal rotation velocity over time at different minor radius is studied theoretically. [ABSTRACT FROM AUTHOR]

Based on a property that in dilute hydrochloric acid hydrogen peroxide oxidizes Ponceau S to fade and cerium(IV) has a catalytic effect on the reaction, a new spectrophotometric method was developed for the determination of trace cerium(IV). At 450 nm, the cerium(IV) concentration presents a good linear relationship over the range of 0.08-4 μg/mL with the fading degree Δ A. Its linear regression equation is Δ A = 0.0475 c (μg/mL) + 0.0007, with a correlation coefficient of 0.9991. The detection limit of method is 0.05 μg/mL. The method has been successfully applied to the determination of cerium in water and molecular sieve samples with good results. The relative standard deviations of eleven determinations were 0.97-1.11 and 0.19-1.01%, respectively. The recoveries of standard additions were 99.4-99.9 and 99.2-101.0%, respectively. The reliability of this method was certified by parallel determination against the dibromo- p-chlorochlorophosphonazo spectrophotometry. [ABSTRACT FROM AUTHOR]

Background: Reoperative cardiac valve surgery via sternotomy is associated with a substantial morbidity and mortality. This study evaluated the right anterolateral thoracotomy for high-risk patients undergoing mitral and tricuspid valve redo procedures.Methods: Out of a series of 173 patients undergoing redo cardiac valve surgery, 24 patients were reoperative via the right anterolateral thoracotomy as the high-risk group on the basis of the proximity of the heart and great vessels to the sternum and the presence and location of patent bypass grafts.Results: In all cases, sternotomy was avoided. The mitral valve and tricuspid valve were replaced in 4 and 19 patients and repaired in 1 and 2 patients, respectively. Moreover, left atrial folding was performed in 5 patients. Mortality was 8.3%. All other patients had uneventful outcomes and normal valve function at follow-up.Conclusions: Reoperative cardiac valve surgery can be performed safely using the right anterolateral thoracotomy in high-risk patients. It offers enough exposure. It minimizes the need for cardiac dissection, and thus, the risk for injury. Avoiding a high-risk resternotomy increases patients comfort and safety of redo mitral and tricuspid valve surgery. [ABSTRACT FROM AUTHOR]

Quantifying the uncertainty in penalized regression under group sparsity is an important open question. We establish, under a high-dimensional scaling, the asymptotic validity of a modified parametric bootstrap method for the group lasso, assuming a Gaussian error model and mild conditions on the design matrix and the true coefficients. Simulation of bootstrap samples provides simultaneous inferences on large groups of coefficients. Through extensive numerical comparisons, we demonstrate that our bootstrap method performs much better than popular competitors, highlighting its practical utility. The theoretical results generalize to other block norm penalization and sub-Gaussian errors, which further broadens the potential applications. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) play a key role in a variety of biological processes, such as the perception of abiotic stress, the integration of different environmental signals, and the activation of stress response networks. Salt stress could induce an increased ROS accumulation in plants, disrupting intracellular redox homeostasis, leading to posttranslational modifications (PTMs) of specific proteins, and eventually causing adaptive changes in metabolism. Here, we performed an iodoTMT-based proteomic approach to identify the sulfenylated proteins in B. napus root responsing to salt stress. Totally, 1 348 sulfenylated sites in 751 proteins were identified and these proteins were widely existed in different cell compartments and processes. Our study revealed that proteins with changed abundance and sulfenylation level in B. napus root under salt stress were mainly enriched in the biological processes of ion binding, glycolysis, ATP binding, and oxidative stress response. This study displays a landscape of sulfenylated proteins response to salt stress in B. napus root and provides some theoretical support for further understanding of the molecular mechanisms of redox regulation under salt stress in plants. [ABSTRACT FROM AUTHOR]

Background: In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China.Methods: Patients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment. Patient data (demographics, NSCLC histologic type, Eastern Cooperative Oncology Group [ECOG] Performance Status [PS], gene aberration test and results [if performed], and first-line anticancer treatment regimen) were extracted from medical charts and entered into Medical Record Abstraction Forms (MERAFs), which were collated for analysis.Results: Overall, 1041 MERAFs were collected and data from 932 MERAFs were included for analysis. Patients with unresectable Stage IIIB/IV nonsquamous NSCLC had a median age of 59 years, 56.4% were male, 58.2% were never smokers, 95.0% had adenocarcinoma, and 92.9% had an ECOG PS ≤1. A total of 665 (71.4%) patients had gene aberration tests; 46.5% (309/665) had epidermal growth factor receptor (EGFR) gene mutations, 11.5% (48/416) had anaplastic lymphoma kinase (ALK) gene fusions, and 0.8% (1/128) had a c-ros oncogene 1 gene fusion. The most common first-line treatment regimen for unresectable Stage IIIB/IV nonsquamous NSCLC was chemotherapy (72.5%, 676/932), followed by tyrosine kinase inhibitors (TKIs; 26.1%, 243/932), and TKIs plus chemotherapy (1.4%, 13/932). Most chemotherapy regimens were platinum-doublet regimens (93.5%, 631/676) and pemetrexed was the most common nonplatinum chemotherapy-backbone agent (70.2%, 443/631) in platinum-doublet regimens. Most EGFR mutation-positive patients (66.3%, 205/309) were treated with EGFR-TKIs.Conclusions: Findings from our survey of 12 tertiary hospitals throughout China showed an increased rate of gene aberration testing, compared with those rates reported in previous surveys, for patients with advanced nonsquamous NSCLC. In addition, pemetrexed/platinum-doublet chemotherapy was the predominant first-line chemotherapy regimen for this population. Most patients were treated based on their gene aberration test status and results. [ABSTRACT FROM AUTHOR]

Ultrasound-targeted microbubble destruction (UTMD) can promote the entry of plasmid DNA (pDNA) into the cell cytoplasm, by increasing the permeability of the cell membrane. But the transfection efficiency remains low due to inability of the pDNA to enter the nucleus. Various methods have been explored to improve the UTMD transfection efficiency, but with little success. In cells, the classic nuclear localization signal (cNLS) peptide is an amino acid sequence that signals proteins that are due for nuclear transport. The present study aimed to investigate whether binding of a cNLS peptide to the pDNA may improve the transfection efficiency of UTMD. Four experimental groups were analyzed: Control group (UTMD + pDNA), group with cNLS (UTMD + pDNA + cNLS), group with mutated NLS (mNLS; UTMD + pDNA + mNLS), and group with cNLS and the nuclear import blocker, wheat germ agglutinin (WGA; UTMD + pDNA + cNLS + WGA). The NLS was labeled by fluorescein isothiocyanate, whereas pDNA was labeled with Cy3. Different molar ratios were tested for the NLS and pDNA combination in order to achieve optimal binding of the two molecules. Human umbilical vein endothelial cells were then transfected using the optimum ultrasonic irradiation parameters and NLS/pDNA molar ratio. At 6 h post-transfection, the rates of Cy3-labeled pDNA inside the cells and their nuclei were detected by flow cytometry and laser confocal microscopy, and the cellular vs. nuclear uptake of pDNA was calculated. In order to further evaluate the effect of NLS on UTMD-mediated gene transfection, the transfection efficiency and relative expression levels of mRNA and protein were detected at 48 h post-transfection. The results demonstrated that the optimal molar ratio of NLS with pDNA was 104:1. The rates of pDNA successful entry into the cell and nucleus were significantly higher in the cNLS group compared with the control group. The transfection efficiency, and relative expression levels of mRNA and protein from the plasmid were significantly increased in the cNLS group compared with the control group. The mNLS group displayed no significant difference compared with the control group, while the WGA group exhibited significant inhibition in most indicators of transfection efficiency compared to the cNLS group. These results suggest that combining a cNLS peptide with pDNA during UTMD-mediated transfection significantly improved transfection efficiency. Thus, a cNLS peptide may be an important mediator and a new strategy in enhancing the efficiency of UTMD-mediated gene transfection. [ABSTRACT FROM AUTHOR]

The present study aimed to construct targeted cationic microbubbles (TCMBs) by synthesizing cationic microbubbles conjugated to an intercellular adhesion molecule-1 (ICAM-1) antibody, and then to use the TCMBs to deliver the angiopoietin-1 (Ang-1) gene into infarcted heart tissue using ultrasound-mediated microbubble destruction. It was hypothesized that the TCMBs would accumulate in higher numbers than non-targeted cationic microbubbles (CMBs) in the infarcted heart, and would therefore increase the efficiency of targeted Ang-1 gene transfection and promote angiogenesis. The results of the study demonstrated that the ability of TCMBs to target inflammatory endothelial cells was 18.4-fold higher than that of the CMBs in vitro. The accumulation of TCMBs was greater than that of CMBs in TNF-α-stimulated human umbilical cord veins, indicated by a 212% higher acoustic intensity. In vivo, the TCMBs specifically accumulated in the myocardial infarct area in a rabbit model. Three days after ultrasound microbubble-mediated gene transfection, Ang-1 protein expression in the TCMB group was 2.7-fold higher than that of the CMB group. Angiogenesis, the thickness of the infarct region and the heart function of the TCMB group were all significantly improved compared with those in the CMB and control groups at 4 weeks following gene transfection (all P<0.01). Therefore, the results of the current study demonstrate that ultrasound-mediated TCMB destruction effectively delivered the Ang-1 gene to the infarcted myocardium, resulting in improved cardiac morphology and function in the animal model. Ultrasound-mediated TCMB destruction is a promising strategy for improving gene therapy in the future. [ABSTRACT FROM AUTHOR]

Objective: Inflammation and autoimmune responses play an important role in recurrence of atrial fibrillation (AF). Serum globulin levels are a commonly used clinical index that represents inflammation and autoimmune response. This study aimed to determine the relationship between baseline serum globulin levels and the risk of recurrence after ablation in lone AF patients. Methods: We enrolled 348 lone AF patients undergoing radiofrequency catheter ablation for the first time for whom complete follow-up data were available. Pre-ablation peripheral venous blood samples were obtained for measurement of serum globulin levels. Results: During the follow-up period of 22 months (range, 6–62), AF recurred in 129 patients (37.1%). Recurrence was associated with a low level of pre-ablation serum globulins. Multiple Cox proportional hazard regression analysis showed that persistent AF, AF duration, left atrial diameter, no amiodarone after ablation, and the serum globulin level in particular were independent predictors of AF recurrence. According to receiver operating characteristic curve analysis, the best diagnostic cut-off serum globulin level was 25.4 g/L, which showed 74.4% sensitivity, 71.3% specificity, and 73.3% accuracy. Conclusion: The baseline low serum globulin level is associated with AF recurrence after first-time ablation in lone AF patients. Therefore, it may be used as a predictor of AF recurrence in these patients. [ABSTRACT FROM AUTHOR]

Abnormally pulsatile umbilical artery (UA) Doppler ultrasound velocity waveforms are a hallmark of severe or early onset placental-mediated intrauterine growth restriction (IUGR), whereas milder late onset IUGR pregnancies typically have normal UA pulsatility. The diagnostic utility of these waveforms to detect placental pathology is thus limited and hampered by factors outside of the placental circulation, including fetal cardiac output. In view of these limitations, we hypothesized that these Doppler waveforms could be more clearly understood as a reflection phenomenon and that a reflected pulse pressure wave is present in the UA that originates from the placenta and propagates backward along the UA. To investigate this, we developed a new ultrasound approach to isolate that portion of the UA Doppler waveform that arises from a pulse pressure wave propagating backward along the UA. Ultrasound measurements of UA lumen diameter and flow waveforms were used to decompose the observed flow waveform into its forward and reflected components. Evaluation of CD1 and C57BL/6 mice at embryonic day (E)15.5 and E17.5 demonstrated that the reflected waveforms diverged between the strains at E17.5, mirroring known changes in the fractal geometry of fetoplacental arteries at these ages. These experiments demonstrate the feasibility of noninvasively measuring wave reflections that originate from the fetoplacental circulation. The observed reflections were consistent with theoretical predictions based on the area ratio of parent to daughters at bifurcations in fetoplacental arteries suggesting that this approach could be used in the diagnosis of fetoplacental vascular pathology that is prevalent in human IUGR. Given that the proposed measurements represent a subset of those currently used in human fetal surveillance, the adaptation of this technology could extend the diagnostic utility of Doppler ultrasound in the detection of placental vascular pathologies that cause IUGR. [ABSTRACT FROM AUTHOR]

Most cellular functions involve proteins' features based on their physical interactions with other partner proteins. Sketching a map of protein-protein interactions (PPIs) is therefore an important inception step towards understanding the basics of cell functions. Several experimental techniques operating in vivo or in vitro have made significant contributions to screening a large number of protein interaction partners, especially high-throughput experimental methods. However, computational approaches for PPI predication supported by rapid accumulation of data generated from experimental techniques, 3D structure definitions, and genome sequencing have boosted the map sketching of PPIs. In this review, we shed light on in silico PPI prediction methods that integrate evidence from multiple sources, including evolutionary relationship, function annotation, sequence/structure features, network topology and text mining. These methods are developed for integration of multi-dimensional evidence, for designing the strategies to predict novel interactions, and for making the results consistent with the increase of prediction coverage and accuracy. [ABSTRACT FROM AUTHOR]

Objective: Many previous reports have demonstrated significant neural anatomy changes in the brain of high myopic (HM) patients, whereas the spontaneous brain activity changes in the HM patients at rest are not well studied. Our objective was to use amplitude of low-frequency fluctuation (ALFF) method to investigate the changes in spontaneous brain activity in HM patients and their relationships with clinical features. Methods: A total of 38 patients with HM (17 males and 21 females) and 38 healthy controls (HCs) (17 males and 21 females) closely matched in age, sex, and education underwent restingstate functional magnetic resonance imaging scans. The ALFF method was used to assess local features of spontaneous brain activity. The relationship between the mean ALFF signal values in many brain regions and the clinical features in HM patients was calculated by correlation analysis. Results: Compared with HCs, the HM patients had significantly lower ALFF in the right inferior and middle temporal gyrus, left middle temporal gyrus, left inferior frontal gyrus/putamen, right inferior frontal gyrus/putamen/insula, right middle frontal gyrus, and right inferior parietal lobule and higher ALFF values in the bilateral midcingulate cortex, left postcentral gyrus, and left precuneus/inferior parietal lobule. However, no relationship was found between the mean ALFF signal values of the different areas and the clinical manifestations in HM. Conclusion: The HM patients were affected with brain dysfunction in many regions, which may indicate the presence of neurobiological changes involving deficits in language understanding and attentional control in HM patients. [ABSTRACT FROM AUTHOR]

Cry1C is one of the emerging toxin proteins produced by the Bacillus thuringiensis in the genetically modified crops for pest control in agriculture; thus, it is vital to measure the Cry1C level in crops for the healthy and environmental concerns. Current detections of Cry1C mainly rely on instrumental analysis such as high-performance liquid chromatography, which are time-consuming and are generally cost-prohibitive. Herein, a simple nanobodies (Nbs)-based electrochemical immunosensor has been first proposed for highly selective and sensitive detection of Cry1C. The Nbs pair, i.e., Nb51 and Nb54, which bind to different epitopes on Cry1C, was screened out from an immunized Bactrian camel, with an extra benefit of higher stability compared with conventional antibodies. Further, by using a π–π stacked graphene oxide/thionine assembly that had fast electron transfer kinetics as an electroactive label, the immunoreaction that occurred between the two Nbs and Cry1C can be highly sensitively quantified by square wave voltammetry. The linear detection range was from 0.01 to 100 ng•Ml-1, and the low detection limit was 3.2 pg•mL-1. This method was further successfully applied for sensing Cry 1C in spiked samples with recoveries ranging from 100.17% to 106.69% and relative standard deviation less than 4.62%. This proposed assay would provide a simple highly sensitive and selective approach for the Cry1C toxin detection and be applicable to be extended to other toxin proteins sensing in foods. [ABSTRACT FROM AUTHOR]

Background: Detecting epidermal growth factor receptor (EGFR) activating mutations in plasma could guide EGFRtyrosine kinase inhibitor (EGFR-TKI) treatment for advanced non-small cell lung cancer (NSCLC). However, dynamic quantitative changes of plasma EGFR mutations during the whole course of EGFR-TKI treatment and its correlation with clinical outcomes were not determined. The aim of this study was to measure changes of plasma EGFR L858R mutation during EGFR-TKI treatment and to determine its correlation with the response and resistance to EGFR-TKI. Methods: This study was a pre-planned exploratory analysis of a randomized phase III trial conducted from 2009 to 2014 comparing erlotinib with gefitinib in advanced NSCLC harboring EGFR mutations in tumor (CTONG0901). Totally, 256 patients were enrolled in CTONG0901 and randomized to receive erlotinib or gefitinib. One hundred and eight patients harbored L858R mutation in their tumors and 80 patients provided serial blood samples as pre-planned scheduled. Serial plasma L858R was detected using quantitative polymerase chain reaction. Dynamic types of plasma L858R were analyzed using Ward's hierarchical clustering method. Progression-free survival (PFS) and overall survival (OS) were compared between different types. Results: As a whole, the quantity of L858R decreased and reached the lowest level at the time of best response to EGFR-TKI. After the analysis of Ward's hierarchical clustering method, two dynamic types were found. In 61 patients, L858R increased to its highest level when disease progressed (ascend type), while in 19 patients, L858R maintained a stable level when disease progressed (stable type). Median PFS was 11.1 months (95% CI, 6.6-15.6) and 7.5 months (95% CI, 1.4-13.6) in patients with ascend and stable types, respectively (P = 0.023). Median OS was 19.7 months (95% CI, 16.5-22.9) and 16.0 months (95% CI, 13.4-18.5), respectively (P = 0.050). Conclusions: This is the first report finding two different dynamic types of plasma L858R mutation during EGFR-TKI treatment based on a prospective randomized study. Different dynamic types were correlated with benefits from EGFR-TKI. The impact of plasma L858R levels at disease progression on subsequent treatment strategy needs further exploration. [ABSTRACT FROM AUTHOR]

Systemic autoinflammatory diseases are caused by mutations in genes that function in innate immunity. Here, we report an autoinflammatory disease caused by loss-of-function mutations in OTULIN (FAM105B), encoding a deubiquitinase with linear linkage specificity. We identified two missense and one frameshift mutations in one Pakistani and two Turkish families with four affected patients. Patients presented with neonatal-onset fever, neutrophilic dermatitis/panniculitis, and failure to thrive, but without obvious primary immunodeficiency. HEK293 cells transfected with mutated OTULIN had decreased enzyme activity relative to cells transfected with WT OTULIN, and showed a substantial defect in the linear deubiquitination of target molecules. Stimulated patients' fibroblasts and peripheral blood mononuclear cells showed evidence for increased signaling in the canonical NF-κB pathway and accumulated linear ubiquitin aggregates. Levels of proinflammatory cytokines were significantly increased in the supernatants of stimulated primary cells and serum samples. This discovery adds to the emerging spectrum of human diseases caused by defects in the ubiquitin pathway and suggests a role for targeted cytokine therapies. [ABSTRACT FROM AUTHOR]

DNA damage-inducing agents are among the most effective treatment regimens in clinical chemotherapy. However, drug resistance and severe side effects caused by these agents greatly limit their efficacy. Sensitizing malignant cells to chemotherapeutic agents has long been a goal of chemotherapy. In the present study, suppression of STN1, a gene important for safeguarding genome stability, potentiated the anticancer effect of chemotherapeutic agents in tumor cells. Using multiple cancer cells from a variety of origins, it was observed that downregulation of STN1 resulted in a significant decrease in the half maximal inhibitory concentration values of several conventional anticancer agents. When cells are treated with anticancer agents, STN1 suppression leads to a decline in colony formation and diminished anchorage-independent growth. Furthermore, it was additionally observed that STN1 knockdown augmented the levels of DNA damage caused by damage-inducing agents. The present study concluded that suppression of STN1 enhances the cytotoxicity of damage-inducing chemotherapeutic agents by increasing DNA damage in cancer cells. [ABSTRACT FROM AUTHOR]

Trypanosoma brucei undergoes cytokinesis uni-directionally from the anterior tip of the new flagellum attachment zone (FAZ) toward the posterior end of the cell. We recently delineated a novel signaling pathway composed of polo-like kinase, cytokinesis initiation factor 1 (CIF1), and aurora B kinase that acts in concert at the new FAZ tip to regulate cytokinesis initiation. To identify new cytokinesis regulators, we carried out proximity-dependent biotin identification and identified many CIF1 binding partners and near neighbors. Here we report a novel CIF1-binding protein, named CIF2, and its mechanistic role in cytokinesis initiation. CIF2 interacts with CIF1 in vivo and co-localizes with CIF1 at the new FAZ tip during early cell cycle stages. RNAi of CIF2 inhibited the normal, anterior-toposterior cytokinesis but activated an alternative, posterior-toanterior cytokinesis. CIF2 depletion destabilized CIF1 and disrupted the localization of polo-like kinase and auroraBkinase to the new FAZ tip, thus revealing the mechanistic role of CIF2 in cytokinesis initiation. Surprisingly, overexpression of CIF2 also inhibited the normal, anterior-to-posterior cytokinesis and triggered the alternative, posterior-to-anterior cytokinesis, suggesting a tight control of CIF2 protein abundance. These results identified a new regulator in the cytokinesis regulatory pathway and reiterated that a backup cytokinesis pathway is activated by inhibiting the normal cytokinesis pathway. [ABSTRACT FROM AUTHOR]

The simulation study finds that the relativistic electron beam propagating through the plasma background can produce electromagnetic (EM) radiation. With the propagation of the electron beam, the oscillations of the beam electrons in transverse and longitudinal directions have been observed simultaneously, which provides the basis for the electromagnetic radiation. The simulation results clearly show that the electromagnetic radiation frequency can reach up to terahertz (THz) wave band which may result from the filter-like property of plasma background, and the electromagnetic radiation frequency closely depends on the plasma density. To understand the above simulation results physically, the dispersion relation of the beam-plasma system has been derived using the field-matching method, and the dispersion curves show that the slow wave modes can couple with the electron beam effectively in THz wave band, which is an important theoretical evidence of the EM radiation. [ABSTRACT FROM AUTHOR]

Cytokinesis in Trypanosoma brucei, an early branching protozoan, occurs along its longitudinal axis uni-directionally from the anterior tip of the new flagellum attachment zone filament toward the cell's posterior end. However, the underlying mechanisms remain elusive. Here we report that cytokinesis in T. brucei is regulated by a concerted action of Polo-like kinase, Aurora B kinase, and a trypanosome-specific protein CIF1. Phosphorylation of CIF1 by Polo-like kinase targets it to the anterior tip of the new flagellum attachment zone filament, where it subsequently recruits Aurora B kinase to initiate cytokinesis. Consistent with its role, CIF1 depletion inhibits cytokinesis initiation from the anterior end of the cell, but, surprisingly, triggers cytokinesis initiation from the posterior end of the cell, suggesting the activation of an alternative cytokinesis from the opposite cell end. Our results reveal the mechanistic roles of CIF1 and Polo-like kinase in cytokinesis initiation and elucidate the mechanism underlying the recruitment of Aurora B kinase to the cytokinesis initiation site at late anaphase. These findings also delineate a signaling cascade controlling cytokinesis initiation from the anterior end of the cell and uncover a backup cytokinesis that is initiated from the posterior end of the cell when the typical anterior-to-posterior cytokinesis is compromised. [ABSTRACT FROM AUTHOR]

Dual-specificity phosphatase 14 (Dusp14), an important negative modulator of mitogen-activated protein kinase (MAPK) signaling pathways, has been implicated in inflammatory immune response, cancers, cell differentiation and proliferation. The role of Dusp14 in chronic pressure overload-induced cardiac hypertrophy has not been explored. Here we have shown that Dusp14−/− knockout mice and cardiac-specific Dusp14 transgenic mice were generated and subjected to aortic banding (AB) for 4 weeks. Our results demonstrated that genetic loss of Dusp14 significantly aggravated cardiac hypertrophy, fibrosis, ventricular dilation and dysfunction, whereas transgenic cardiac-specific Dusp14 overexpression significantly attenuated AB-induced cardiac dysfunction and remodeling. In vitro, adenoviral overexpression of constitutive Dusp14 blocked angiotensin II-induced hypertrophic growth of cardiomyocytes, while Dusp14 knockdown led to opposite effects. Mechanistically, excessive phosphorylation of TAK1, P38MAPK and JNK1/2 was evidenced in Dusp14−/− knockout mice post-AB and inactivation of TAK1-P38MAPK and -JNK1/2 signaling using TAK1 inhibitor 5Z-7-ox shares similar antihypertrophic effect as Dusp14 overexpression. Moreover, we show that Dusp14 directly interacted with TAK1. Results from present experiments indicate that Dusp14 protects the heart from AB-induced cardiac hypertrophy and dysfunction possibly through inactivation of TAK1-P38MAPK/-JNK1/2 signaling pathway. Future studies are warranted to test the feasibility of overexpressing Dusp14 as a therapeutic strategy to attenuate cardiac hypertrophy and failure. [ABSTRACT FROM AUTHOR]

Background: According to the literature and our experience, the most common sites of non-small cell lung cancer (NSCLC) metastases include the brain, bone, liver, adrenal glands, contralateral lung and distant lymph nodes. Metastases to other organs are relatively rare. There have been numerous case reports and a few small case series of uncommon metastases derived from NSCLC.Methods: We defined all organs except the common metastatic sites mentioned above as uncommon sites of metastasis. Patients with uncommon metastases among 2,872 consecutive NSCLC patients with stage IV disease at the Guangdong Lung Cancer Institute (GLCI) from 2006 to 2012 were included in this study. The diagnosis of uncommon metastases was based on pathology or imaging studies.Results: Uncommon metastases were diagnosed in 193 cases at anatomical sites such as the soft tissue, kidney, pancreas, spleen, peritoneum, intestine, bone marrow, eye, ovary, thyroid, heart, breast, tonsil and nasal cavity. Uncommon metastases were identified as independent poor prognostic factors through a multivariate analysis with a HR (hazard ratio) of 1.29 [95% confidence interval (CI) 1.09-1.52, P < 0.01]. Those patients who received systemic therapy plus local treatment had a better survival rate than did those who received systemic therapy only (P < 0.01); all patients received best supportive care.Conclusions: Metastases to the above mentioned sites are infrequent. The presentation of uncommon metastases tends to indicate a poor outcome, and selected patients may benefit from local treatment. [ABSTRACT FROM AUTHOR]

Abstract: A new catalytic kinetic spectrophotometric method was proposed for determining trace oxalic acid based on the catalytic effect of oxalate on the oxidation of potassium dichromate with rhodamin B in 0.10M of sulfuric acid. Good linearity is obtained over the concentration range 0.40–6.0μg/mL of oxalic acid. After the reactions of the catalytic and non-catalytic systems were terminated by using 2.00mL of 4M sodium hydroxide solution, they can be stable for 3h at room temperature. The apparent activation energy of the catalytic reaction is 12.44kJ/mol. The effect of 50 coexisting substances was observed. The method was used to determine trace oxalic acid in tea, spinach and urine samples with satisfactory results. [Copyright &y& Elsevier]

The evolutionarily conserved centriole/basal body protein SAS-4 regulates centriole duplication in metazoa and basal body duplication in flagellated and ciliated organisms. Here, we report that the SAS-4 homolog in the flagellated protozoan Trypanosoma brucei, TbSAS-4, plays an unusual role in controlling life cycle transitions by regulating the length of the flagellum attachment zone (FAZ) filament, a specialized cytoskeletal structure required for flagellum adhesion and cell morphogenesis. TbSAS-4 is concentrated at the distal tip of the FAZ filament, and depletion of TbSAS-4 in the trypomastigote form disrupts the elongation of the new FAZ filament, generating cells with a shorter FAZ associated with a longer unattached flagellum and repositioned kinetoplast and basal body, reminiscent of epimastigote-like morphology. Further, we show that TbSAS-4 associates with six additional FAZ tip proteins, and depletion of TbSAS-4 disrupts the enrichment of these FAZ tip proteins at the new FAZ tip, suggesting a role of TbSAS-4 in maintaining the integrity of this FAZ tip protein complex. Together, these results uncover a novel function of TbSAS-4 in regulating the length of the FAZ filament to control basal body positioning and life cycle transitions in T. brucei. [ABSTRACT FROM AUTHOR]

Grain boundary diffusion using rare earth (RE)-containing compounds has recently become an effective approach for improving the coercivity and reducing the heavy RE content in sintered NdFeB magnets. Here we report the enhancement of magnetic properties and corrosion resistance of NdFeB magnets by a non-RE compound diffusion process. The Dy-free sintered NdFeB magnets were coated with an MgO layer by magnetron sputtering, followed by solid diffusion heat treatment. With the successful diffusion of MgO into the magnet, the coercivity increasing from 1094 to 1170 kA/m and the maximum energy product increasing from 240 to 261 kJ/m³, together with the enhanced temperature stability and corrosion resistance, have been demonstrated. The underlying mechanisms for these enhancements have been analyzed. Microstructural investigations show that MgO entered mainly into the intergranular regions and modified the composition and structure of the grain boundary phase. The intergranular Nd-O-Fe-Mg phases observed in the MgO diffused magnet contribute to the improved performance. The current non-RE compound grain boundary diffusion process has significance in further minimizing the use of rare earth (RE). [ABSTRACT FROM AUTHOR]

The distribution of coseismic landslides triggered by the 2014 Ludian, Yunnan, China Mw6.1 earthquake exhibits a particular pattern. They do not concentrate linearly along a fault (e.g., the causative fault) or a tectonic zone, instead mostly appear in the southeast and west of the epicenter of the main shock in a relatively clustering manner, 5-9 km distant. Majority of them occur at the river reaches with cliffs, including the unusually large-scale landslide at the Hongshiyan village, north bank of the Njiulanjiang River. Such a phenomenon implies that local conditions of terrain of the river valley might control the distribution of coseismic landslides induced by the Ludian event, which is of a moderate magnitude. To verify quantitatively this intuitive conjecture, this study proposes a parameter of the relative landslide area ratio, with which a statistics is made for landslide area ratios and local terrain conditions. The results demonstrate that this ratio value is highly correlated with the three terrain variables, i.e., slope angle, local relief, and slope aspect (facing direction of the slope). In the study area, most coseismic landslides occur at loci with slope angle greater than 30°-40°, particularly the river reaches with slope angle exceeding 50°. Localized distribution of the landslides is positively correlated with terrain relief, of which majority lies at places with altitude differences over 400 m. The side slopes facing south and southeast are most prone to occurrence of coseismic landslides, which may be explained by the mainshock process that the seismogenic fault ruptured from northwest to southeast and from deep to shallow. It may also be an account on which there is no coseismic landslide southwest of the epicenter, though there also exist river reaches with steep slopes. It means that the seismic source process can pose a constraint on the control of local terrain conditions on the distribution pattern of earthquake-induced landslides. [ABSTRACT FROM AUTHOR]

We develop a penalized likelihood estimation framework to learn the structure of Gaussian Bayesian networks from observational data. In contrast to recent methods which accelerate the learning problem by restricting the search space, our main contribution is a fast algorithm for score-based structure learning which does not restrict the search space in any way and works on high-dimensional data sets with thousands of variables. Our use of concave regularization, as opposed to the more popular l0 (e.g. BIC) penalty, is new. Moreover, we provide theoretical guarantees which generalize existing asymptotic results when the underlying distribution is Gaussian. Most notably, our framework does not require the existence of a so-called faithful DAG representation, and as a result, the theory must handle the inherent nonidentifiability of the estimation problem in a novel way. Finally, as a matter of independent interest, we provide a comprehensive comparison of our approach to several standard structure learning methods using open-source packages developed for the R language. Based on these experiments, we show that our algorithm obtains higher sensitivity with comparable false discovery rates for high-dimensional data and scales effciently as the number of nodes increases. In particular, the total runtime for our method to generate a solution path of 20 estimates for DAGs with 8000 nodes is around one hour. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the possible cardioprotective effects and potential pharmacological mechanism of genistein. Methods: Six-week old ZDF and lean rats were randomized into 4 groups (8 rats/group), including group 1 (control lean rats); group 2 (lean rats treated with genistein, 2.5 mg/kg); group 3 (control ZDF rats); and group 4 (ZDF treated with genistein). Two groups (2 and 4) were treated with genistein for 12 weeks, and cardiac functions and metabolic alterations were determined. Macrophage/monocyte chemo-attractant protein-1 (MCP-1), vascular cellular adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) secretion and their messenger RNA transcription level also were observed. Results: Genistein attenuated diabetes-induced cardiac dysfunction and pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signalling pathways. In addition, genistein treatment markedly reduced diabetic-induced MCP-1 (83.33 %), VCAM-1 (74.66 %) and ICAM-1 (71.42 %) secretion and mRNA transcription in ZDF rats. Conclusion: The results demonstrate the putative effects of genistein against cardiovascular dysfunction by improving glucose homeostasis, attenuating oxidative stress and reduced diabeticinduced endothelial dysfunction in ZDF rats. Thus, genistein is a potential candidate for the prevention of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The Polo-like kinase (PLK) in Trypanosoma brucei plays multiple roles in basal body segregation, flagellum attachment, and cytokinesis. However, the mechanistic role of TbPLK remains elusive, mainly because most of its substrates are not known. Here, we report a new substrate of TbPLK, SPBB1, and its essential roles in T. brucei. SPBB1 was identified through yeast twohybrid screening with the kinase-dead TbPLK as the bait. It interacts with TbPLK in vitro and in vivo, and is phosphorylated by TbPLK in vitro. SPBB1 localizes to both the mature basal body and the probasal body throughout the cell cycle, and co-localizes with TbPLK at the basal body during early cell cycle stages. RNAi against SPBB1 in procyclic trypanosomes inhibited basal body segregation, disrupted the new flagellum attachment zone filament, detached the new flagellum, and caused defective cytokinesis. Moreover, RNAi of SPBB1 confined TbPLK at the basal body and the bilobe structure, resulting in constitutive phosphorylation of TbCentrin2 at the bilobe. Altogether, these results identified a basal body protein as a TbPLK substrate and its essential role in promoting basal body segregation and flagellum attachment zone filament assembly for flagellum adhesion and cytokinesis initiation. [ABSTRACT FROM AUTHOR]

The present study examined 2 measures of Chinese American immigrant parents' emotional expression in the family context: self-reported emotional expressivity and observed emotional expression during a parent-child interaction task. Path analyses were conducted to examine the concurrent associations between measures of emotional expression and (a) parents' American and Chinese cultural orientations in language proficiency, media use, and social affiliation domains, and (b) parents' and teachers' ratings of children's emotion-related regulation. Results suggested that cultural orientations were primarily associated with parents' self-reported expressivity (rather than observed emotional expression), such that higher American orientations were generally associated with higher expressivity. Although parents' self-reported expressivity was only related to their own reports of children's regulation, parents' observed emotional expression was related to both parents' and teachers' reports of children's regulation. These results suggest that self-reported expressivity and observed emotional expression reflect different constructs and have differential relations to parents' cultural orientations and children's regulation. [ABSTRACT FROM AUTHOR]

Epigallocatechin-3-gallate (EGCG) is an active and major constituent of green tea. As a non-nucleoside inhibitor of DNA methylation, EGCG is able to inhibit the hypermethylation of newly synthesised DNA, resulting in the reversal of hypermethylation and recovery in expression of the silenced genes. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel tumour suppressor gene, which negatively regulates matrix metalloproteinases, and inhibits tumour invasion, angiogenesis and metastasis. The present study aimed to examine the effects of EGCG on the methylation status of the RECK gene and tumour invasion in a salivary adenoid cystic carcinoma (SACC) cell line in vitro. Marked levels of methylated and weak levels of unmethylated RECK promoter were detected in the SACC83 cells, which was determined using methylation-specific polymerase chain reaction (PCR). In addition, the treatment of SACC83 cells with EGCG partially reversed the hypermethylation status of the RECK gene. Western blot analysis and reverse transcription-PCR demonstrated that EGCG significantly enhanced the protein and mRNA expression levels of RECK, and significantly reduced the invasive ability of the SACC83 cells, as determined using a Transwell assay. These results suggested that EGCG possesses novel anti-metastatic therapeutic potential for the treatment of SACC. [ABSTRACT FROM AUTHOR]

We develop a penalized likelihood estimation framework to learn the structure of Gaussian Bayesian networks from observational data. In contrast to recent methods which accelerate the learning problem by restricting the search space, our main contribution is a fast algorithm for score-based structure learning which does not restrict the search space in any way and works on high-dimensional data sets with thousands of variables. Our use of concave regularization, as opposed to the more popular ℓ0 (e.g. BIC) penalty, is new. Moreover, we provide theoretical guarantees which generalize existing asymptotic results when the underlying distribution is Gaussian. Most notably, our framework does not require the existence of a so-called faithful DAG representation, and as a result, the theory must handle the inherent nonidentifiability of the estimation problem in a novel way. Finally, as a matter of independent interest, we provide a comprehensive comparison of our approach to several standard structure learning methods using open-source packages developed for the R language. Based on these experiments, we show that our algorithm obtains higher sensitivity with comparable false discovery rates for high-dimensional data and scales efficiently as the number of nodes increases. In particular, the total runtime for our method to generate a solution path of 20 estimates for DAGs with 8000 nodes is around one hour. [ABSTRACT FROM AUTHOR]

[Display omitted] • Proliferatin A-C (1 – 3), three previously undescribed trichosetin analogs were isolated and their absolute configurations were elucidated. • 1 – 3 attenuate the production of inflammatory signal messengers in vitro and in vivo. • Transcriptome analyses revealed that 1 – 3 suppress inflammation through inhibiting NF-κB and MAPK signaling pathways. • Western blot experiments revealed that 1 – 3 inhibit the phosphorylation of key proteins in NF-κB and MAPK signaling pathways. • SPR assays revealed that 1 – 3 present affinity for TLR4 protein with K D values of 6.9–61.5 μM. Three previously undescribed polyketides [proliferatin A-C (1 – 3)] with anti-inflammatory activity were isolated from Fusarium proliferatum. 1 – 3 attenuated the production of inflammatory signal messengers including nitric oxide (NO), reactive oxygen species, proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as the related proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the potential anti-inflammatory mechanism of 1 – 3 involved in the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinases (MAPKs) signaling pathways. Experimental evaluation of the protein levels revealed that 1 – 3 can inhibit the phosphorylation of IκB kinase (IKK), the degradation of NF-κB Inhibitor-α (IκBα), the phosphorylation of nuclear factor-κB (NF-κB) and can reduce NF-κB transportation to the nucleus. Interestingly, 1 – 3 decreased the phosphorylation of MAPKs including p-p38, p-ERK, and p-JNK. Molecular docking models suggest that binding of 1 – 3 to TLR4-MD-2 complex may lead to inhibition of NF-κB and MAPK signaling pathways, which was confirmed in vitro by surface plasmon resonance (SPR) assays. 1 – 3 can thus constitute potential therapeutic candidates for the treatment of inflammation-associated diseases. [ABSTRACT FROM AUTHOR]

The enantioselective N-allylic alkylation of N-propargylsulfonamides with racemic Morita-Baylis-Hillman (MBH) carbonates catalyzed by modified cinchona alkaloids has been investigated. The alkylation products from MBH carbonates with a 4-methoxyphenyl group underwent ipso-iodocyclization to give optically active azaspirocyclohexadienones via electrophilic activation of alkyne group with iodine monochloride. In contrast, orthoselective intramolecular Friedel-Crafts reaction occurred for intermediates from MBH carbonates with other electronrich or neutral aryl or heteroaryl substitutions via the same activation strategy, delivering multifunctional 2-benzazepine frameworks in a highly enantioenriched form. [ABSTRACT FROM AUTHOR]

Mouse models are an important way for exploring relationships between blood hemodynamics and eventual plaque formation. We have developed a mouse model of aortic regurgitation (AR) that produces large changes in plaque burden with charges in hemodynamics [Zhou et al., 2010, "Aortic Regurgitation Dramatically Alters the Distribution of Atherosclerotic Lesions and Enhances Atherogenesis in Mice," Arterioscler. Thromb. Vase. Biol., 30(6), pp. 1181-1188], In this paper, we explore the amount of detail needed for realistic computational fluid dynamics (CFD) calculations in this experimental model. The CFD calculations use inputs based on experimental measurements from ultrasound (US), micro computed tomography (CT), and both anatomical magnetic resonance imaging (MRI) and phase contrast MRI (PC-MRI). The adequacy of five different levels of model complexity (a) subject-specific CT data from a single mouse; (b) subject-specific CT centerlines with radii from US; (c) same as (b) but with MRI derived centerlines; (d) average CT centerlines and averaged vessel radius and branching vessels; and (e) same as (d) but with averaged MRI centerlines) is evaluated by demonstrating their impact on relative residence time (RRT) outputs. The paper concludes by demonstrating the necessity of subject-specific geometry and recommends for inputs the use of CT or anatomical MRI for establishing the aortic centerlines, M-mode US for scaling the aortic diameters, and a combination of PC-MRI and Doppler US for estimating the spatial and temporal characteristics of the input wave forms. [ABSTRACT FROM AUTHOR]

In this study, a magnetic hypercrosslinked microsphere (Q150) was prepared and used for organic micropollutants (OMPs) removal. Q150 has a high surface area (1103.6 m²/g) with a narrow particle size distribution (10-30 μm). The high saturation magnetization (9.6 emu/g) of Q150 demonstrates its excellent separation ability. The adsorption behaviors of a typical OMPs, atrazine, were studied and a commercial powdered activated carbon, 1240AC, was selected as comparison. Q150 and 1240AC both displayed fast adsorption kinetics, and the adsorption followed a pseudo-second-order equation (R² > 0.99). Q150 exhibited a slightly larger adsorption capacity (107.1 mg/g) for atrazine than 1240AC (101.8 mg/g). The most cost-effective adsorbent dose was 0.06 g/L at an initial atrazine concentration of 20 μg/L, resulting in an atrazine removal efficiency that was higher than 99.5%. Q150 could treat 600 ml more of the atrazine solution than 1240AC in a single batch before reaching a breakthrough point (3 μg/L). In the presence of dissolved organic matter (DOM), the water treatment volume of Q150 decreased by 29.2%, which is less than that observed for 1240AC (47.6%). 1240AC completely lost its adsorption capability after 3 adsorption-desorption cycles, whereas Q150 maintained approximately 50% of the initial adsorption capacity after 6 repeated uses. NDMP (magnetic anion exchange resin) pretreatment removed 45.2% of DOM, which improved the atrazine treatment capability of Q150 by 20.8% and enhanced the reusability. [ABSTRACT FROM AUTHOR]

A new form of two-photon exchange (TPE) effect is studied to explain the discrepancy between unpolarized and polarized experimental data in elastic ep scattering. The mechanism is based on a simple idea that apart from the usual TPE effects from box and crossed-box diagrams, the mesons may also be exchanged in elastic ep scattering by two-photon coupling at loop level. The detailed study shows such contributions to reduced unpolarized cross section (σun) and polarized observables (Pt,Pl) at fixed Q² are only dependent on proton's electromagnetic form factors GE,M and a new unknown universal parameter g. After combining this contribution with the usual TPE contributions from box and crossed-box diagrams, the ratio μpGE/GM extracted from the recent precise unpolarized and polarized experimental data can be described consistently. [ABSTRACT FROM AUTHOR]

This study was to evaluate the flow distribution in the mouse fetal circulation at late gestation using high frequency ultrasound. Twelve fetuses (E17.5) from twelve pregnant CD1 mice were studied using 40MHz ultrasound to assess the flow in eleven vessels based on Doppler measurements of blood velocity and M-mode measurements of diameter. Specifically, the intra-hepatic umbilical vein (UVIH), ductus venosus (DV), foramen ovale (FO), ascending aorta (AA), main pulmonary artery (MPA), ductus arteriosus (DA), descending thoracic aorta (DTA), common carotid artery (CCA), inferior vena cava (IVC), and right and left superior vena cavae (RSVC, LSVC) were examined, and anatomically confirmed by micro-CT. The mouse fetal circulatory system was found similar to that of the humans in terms of the major circuit and three shunts, but characterized by bilateral superior vena cavae and a single umbilical artery. The combined cardiac output (CCO) was 1.22±0.05 ml/min, with the left ventricle (flow in AA) contributing 47.8±2.3% and the right ventricle (flow in MPA) 52.2±2.3%. Relative to the CCO, the flow percentages were 13.6±1.0% for the UVIH, 10.4±1.1% for the DV, 35.6±2.4% for the DA, 41.9±2.6% for the DTA, 3.8±0.3% for the CCA, 29.5±2.2% for the IVC, 12.7±1.0% for the RSVC and 9.9±0.9% for the LSVC. The calculated flow percentage was 16.6±3.4% for the pulmonary circulation and 31.2±5.3% for the FO. In conclusion, the flow in mouse fetal circulation can be comprehensively evaluated with ultrasound. The baseline data of the flow distribution in normal mouse fetus serves as the reference range for future studies. [ABSTRACT FROM AUTHOR]

Eichhornia crassipes (Mart.) Solms is effective in assimilating nutrients from eutrophic waters. However, it is not clear whether E. crassipes has an adverse impact on the waters in which heavy blooms of Microcystis aeruginosa occur. The objective of this study was to understand the interactions of E. crassipes with toxigenic M. aeruginosa and the consequences on environmental safety. Thus, the growth, physiological characteristics, microcystin production and release of M. aeruginosa influenced by E. crassipes were investigated using a co-existence experiment. The risk of microcystin-LR (MC-LR) accumulation in E. crassipes was also evaluated. Our results indicated that the cell death of M. aeruginosa occurred at a quicker pace due to the presence of E. crassipe. But the caspase-3 activity of M. aeruginosa, as the proxy for programmed cell death, was suppressed significantly by E. crassipes. Photosystem (PS) II-Hill reaction in M. aeruginosa was not significantly interrupted by E. crassipes, but a direct positive relationship between phycocyanin (PC) and algae biomass (R² = 0.661, P < 0.01) and a consistent relationship between phycocyanin/allophycocyanin (PC/APC) ratio in M. aeruginosa and algae biomass (R² = 0.598, P < 0.01) were found to be statistically significant. These results suggested that the energy harvest and electron transfer processes in the photosystem of M. aeruginosa might be disturbed by E. crassipes due to its damage of PC and a change in the PC/APC ratio. After this 12-day experiment, the level of extracellular MC-LR was significantly eliminated from 212.68 ± 25.05 µg L-1 to 18.98 ± 0.35 µg L-1 and the MC-LR production in M. aeruginosa was not stimulated by the influence of E. crassipes. The MC-LR level in the whole plants of E. crassipes was 3.88 ± 0.49 ng g-1 FW. [ABSTRACT FROM AUTHOR]

The interlayer structure of wet organoclays has attracted great interest due to its close relation with adsorption process but still remains ambiguous at the atomic level. In this study, the structure and dynamics of cetyltrimethylammonium (CTMA+) intercalated montmorillonite (Mt) in the water saturated condition were investigated by molecular dynamics (MD) simulations. Two Mt models with different cation exchange capacity (CEC) were selected and various amounts of CTMA+ were added to achieve different loading levels based on experiments. The simulation results show that as the surfactant loading level increases, the arrangement of CTMA+ transforms from bilayer to inclined paraffin-type with a large amount of water in the interlayer space, indicating a different configuration from dry systems. The conformations of CTMA+ are influenced by water molecules and surfactant loading level. Compared to the dry models, the percentage of gauche conformations of CTMA+ decreases in the water saturated condition. In the cases of incomplete cation exchange, the confinement from silicate surface may lead to more ordered structure of alkyl chains. In the cases of excessive surfactant loading, the percentage of gauche conformation decreases due to the steric hindrance. Moreover, the ammonium head groups of CTMA+ are found to locate close to the center of six-member ring of silicate surface and coordinated with 4-6 water molecules. Their mobility is low due to the electrostatic interactions while the alkyl chains show higher mobility. Mt with a higher CEC has a stronger confining effect on both alkylammonium and water, which then reduces the mobility of alkyl chains and water molecules within the interlayer space. [ABSTRACT FROM AUTHOR]