Exposure to PM2.5 during pregnancy causes lung inflammation in the offspring: Mechanism of action of mogrosides.

Epidemiological and toxicological studies have demonstrated that exposure to fine particulate matter (PM2.5) during pregnancy is harmful to the tissues of the offspring. However, the mechanism by which PM2.5 exposure causes lung damage in the offspring or potential dietary therapy for this condition remains unclear. Mogrosides (MGs) are derived from the traditional plant Siraitia grosvenorii and are used medicinally, where they can moisten the lungs and relieve coughing. In this study, pregnant rats were exposed to PM2.5 by intratracheal instillation and treated with MGs by gavage to model the effect of PM2.5 in the offspring and the interventional effect of MGs on lung tissue. We then used transcriptomics, metabolomics, and RT-qPCR as tools to look for metabolite and genetic changes in the offspring. We found that when compared to the control group, the mRNA levels of the inflammatory mediator Pla2g2d and the metabolites lysophosphatidylcholines (LysoPCs) and arachidonic acid (AA) were up-regulated in the lung tissues of PM2.5 group. In contrast, these inflammatory changes were restored after treatment with MGs during pregnancy. In addition, the levels of AA, LPC 15:0 and LPC 18:0 were elevated in the PM2.5 group compared with control group. This increase was inhibited by co-administration of MGs. The change of PGA1 was adverse. In conclusion, even a relatively low exposure to PM2.5 in rats during pregnancy produces inflammation in the lungs of the male offspring, and an intervention with MGs could significantly alleviate this effect. Furthermore, Pla2g2d may represent a potential target for MGs resulting in the improvement of PM2.5-induced lung injury.

MWPCR: Multiscale Weighted Principal Component Regression for High-dimensional Prediction.

We propose a multiscale weighted principal component regression (MWPCR) framework for the use of high dimensional features with strong spatial features (e.g., smoothness and correlation) to predict an outcome variable, such as disease status. This development is motivated by identifying imaging biomarkers that could potentially aid detection, diagnosis, assessment of prognosis, prediction of response to treatment, and monitoring of disease status, among many others. The MWPCR can be regarded as a novel integration of principal components analysis (PCA), kernel methods, and regression models. In MWPCR, we introduce various weight matrices to prewhitten high dimensional feature vectors, perform matrix decomposition for both dimension reduction and feature extraction, and build a prediction model by using the extracted features. Examples of such weight matrices include an importance score weight matrix for the selection of individual features at each location and a spatial weight matrix for the incorporation of the spatial pattern of feature vectors. We integrate the importance score weights with the spatial weights in order to recover the low dimensional structure of high dimensional features. We demonstrate the utility of our methods through extensive simulations and real data analyses of the Alzheimer's disease neuroimaging initiative (ADNI) data set.

Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes.

Skeletal muscle atrophy is often caused by catabolic conditions including fasting, disuse, aging and chronic diseases, such as chronic obstructive pulmonary disease. Atrophy occurs when the protein degradation rate exceeds the rate of protein synthesis. Therefore, maintaining a balance between the synthesis and degradation of protein in muscle cells is a major way to prevent skeletal muscle atrophy. Ginsenoside Rg1 (Rg1) is a primary active ingredient in Panax ginseng, which is considered to be one of the most valuable herbs in traditional Chinese medicine. In the current study, Rg1 was observed to inhibit the expression of MuRF-1 and atrogin-1 in C2C12 muscle cells in a starvation model. Rg1 also activated the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT), and forkhead transcription factor O, subtypes 1 and 3a. This phosphorylation was inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. These data suggest that Rg1 may participate in the regulation of the balance between protein synthesis and degradation, and that the function of Rg1 is associated with the AKT/mTOR/FoxO signaling pathway.

Melittin inhibits the invasion of MCF-7 cells by downregulating CD147 and MMP-9 expression.

Tumor invasion and metastasis are the critical steps in determining the aggressive phenotype of human cancers. Melittin, a major component of bee venom, has been reported to induce apoptosis in several cancer cells. However, the mechanisms of melittin involvement in cancer invasion and metastasis remain unclear. Our previous study indicated that melittin inhibits cyclophilin A (CypA), a ubiquitously distributed peptidylprolyl cis-trans isomerase, in macrophage cells. In the present study, the Transwell assay results showed that melittin may downregulate the invasion level of MCF-7 cells in a dose-dependent manner. Additionally, it was also found, using flow cytometry and reverse transcription-polymerase chain reaction, that melittin decreased the expression of cluster of differentiation (CD)147 and matrix metallopeptidase-9 (MMP-9), whereas CypA upregulated the expression of CD147 and MMP-9. Overall, the present study indicated that melittin decreased the invasion level of MCF-7 cells by downregulating CD147 and MMP-9 by inhibiting CypA expression. The results of the present study provide an evidence for melittin in anticancer therapy and mechanisms.

eHUGS: Enhanced Hierarchical Unbiased Graph Shrinkage for Efficient Groupwise Registration.

Effective and efficient spatial normalization of a large population of brain images is critical for many clinical and research studies, but it is technically very challenging. A commonly used approach is to choose a certain image as the template and then align all other images in the population to this template by applying pairwise registration. To avoid the potential bias induced by the inappropriate template selection, groupwise registration methods have been proposed to simultaneously register all images to a latent common space. However, current groupwise registration methods do not make full use of image distribution information for more accurate registration. In this paper, we present a novel groupwise registration method that harnesses the image distribution information by capturing the image distribution manifold using a hierarchical graph with its nodes representing the individual images. More specifically, a low-level graph describes the image distribution in each subgroup, and a high-level graph encodes the relationship between representative images of subgroups. Given the graph representation, we can register all images to the common space by dynamically shrinking the graph on the image manifold. The topology of the entire image distribution is always maintained during graph shrinkage. Evaluations on two datasets, one for 80 elderly individuals and one for 285 infants, indicate that our method can yield promising results.

Apelin-13 induces MCF-7 cell proliferation and invasion via phosphorylation of ERK1/2.

Apelin-13 is extensively expressed in various tissues, particularly breast tissue. Apelin­13 has been shown to promote tumor proliferation in various types of cancer, including hepatocellular, lung and ovarian cancer. However, the effect and molecular mechanism of apelin­13 in breast cancer cells remains unclear. The present study investigated the effect of apelin­13 on MCF­7. Therefore, cell proliferation was determined by MTT and flow cytometry analysis. The results revealed that apelin­13 markedly increased cell proliferation. Transwell assays demonstrated that apelin­13 increased MCF­7 cell invasion. Apelin­13 also markedly increased the expression of cyclin D1, extracellular matrix metalloproteinase­1 and amplified in breast cancer 1 (AIB1) in a dose­dependent manner by polymerase chain reaction assays. To study the molecular mechanism, cell proliferation, invasion and cyclin D1 were inhibited by pre­treatment with 10 µM of PD98059 (ERK(1/2) inhibitor). Western blotting results suggested that apelin­13 significantly enhances the expression of p­ERK(1/2) in a concentration­dependent manner. In conclusion, the results suggest that apelin­13 promoted MCF-7 cell proliferation and invasion via the ERK1/2/AIB1 signaling pathway.

Behavior of stable carbon isotope of phthalate acid esters during photolysis under ultraviolet irradiation.

The photolysis of three phthalic acid esters (PAEs) (dimethyl (DMP), di-n-butyl (DBP), and di-n-octyl (DOP) phthalates) under ultraviolet (UV) irradiation at 254nm in laboratory experiments was investigated by gas chromatography coupled with isotope ratio mass spectrometry through a combustion interface (GC-C-IRMS). The degradation processes of DMP, DBP and DOP were well described by a first-order kinetic, with rate constants of 0.02636, 0.1005 and 0.958h(-1) for DMP, DBP and DOP, respectively, indicating that the photolysis rate of PAEs is related to the number of carbon atoms in molecule. The results of TOC analysis indicated that PAEs could not be completely mineralized under UV irradiation. Stable carbon isotope fractionation of the three PAEs produced during photolysis was evaluated with compound-specific isotope analysis (CSIA). Pronounced (13)C-enrichment, with maximum δ(13)C shifts of Δδ(13)CDMP=10.04±0.13‰ (f=0.09), Δδ(13)CDBP=7.4±0.19‰ (f=0.06) and Δδ(13)CDOP=2.9±0.17‰ (f=0.25) in the residual DMP, DBP and DOP, respectively, were clearly a direct evidence for photolysis of three PAEs. The order of stable carbon isotope fractionation of the three PAEs during photolysis, DMP>DBP>DOP, is an inverse function of the number of carbon atoms in molecule. The kinetic isotope effects (KIE) values, from 1.0018 to 1.0045 for the three PAEs, were consistent with the KIE values (1.00-1.03) of the C-O bond cleavage reported in literature.

Pathway of diethyl phthalate photolysis in sea-water determined by gas chromatography-mass spectrometry and compound-specific isotope analysis.

The degradation mechanism of diethyl phthalate (DEP) in natural seawater under UV irradiation was investigated using a combination of intermediates detection and determination of stable carbon isotopic fractionation. Typical intermediates identified with gas chromatography-mass spectrometry (GC-MS) were mono-ethyl phthalate (MEP) and phthalic anhydride. Stable carbon isotope signature was determined by gas chromatography coupled with isotope ratio mass spectrometry through a combustion interface (GC-C-IRMS). A profound (13)C enrichment, with a δ(13)C isotope shift of 12.3±0.3‰ (f=0.09) in residual DEP molecule, was clearly an indicator to its photolysis. The reactive position isotope enrichment factor (ε(reactive position)) and apparent kinetic isotope effects (AKIE) were -35.25±2.26‰ and 1.075, respectively, indicating that the initial reaction step was cleavage of a CO bond in DEP photolysis. Based on these observations, a degradation pathway was proposed. First, a CO bond in DEP molecule was broken to form MEP. Then, MEP was further degraded to phthalic anhydride. Our work demonstrates that compound-specific isotope analysis (CSIA), when combined with intermediates analysis, is a reliable measure to deduce the mechanism of DEP photolysis. This approach might be extended as a reference for mechanism investigation in complicated environment systems.

Compound-specific isotope analysis for aerobic biodegradation of phthalate acid esters.

The degradation of three phthalic acid esters (PAEs) (dimethyl phthalate (DMP), diethyl phthalate (DEP) and di-n-butyl phthalate (DBP)) by natural microbial community under aerobic condition and their isotope fractionation were compared by using a laboratory microcosm system with natural marine sediment overlying with natural seawater. The results showed that the degradation of the three tested PAEs followed a first-order kinetics, with rate constants of 0.0541, 0.0352 and 0.00731 day(-1) for DMP, DBP and DOP, respectively, indicating that the degradation rate of PAEs is a inverse function of the length of the alkyl side chain: the longer the side chain, the slower the rate is. (13)C isotope enrichment of the three residual PAEs were evaluated with compound-specific isotope analysis (CSIA). A relatively obvious (13)C enrichment, with maximum δ(13)C shifts of Δδ(13)C(DMP)=2.05±0.21‰ (f=0.17) and Δδ(13)C(DBP)=1.92±0.23‰ (f=0.08) in the residual DMP and DBP, respectively, was observed at an advanced stage of biodegradation. No significant (13)C enrichment occurred in the residual DOP (Δδ(13)C(DOP)=0.55±0.21‰, f=0.16) within the accuracy and reproducibility for GC-C-IRMS (±0.5‰). The experimental results indicated that the degree of isotopic fractionation in the three residual PAEs appeared to be related to the number of carbon atoms, which is in the order of DMP>DBP>DOP.

Wearable electromagnetic apparatus for endoscope localization.

Endoscope localization is important as it provides location information for disease diagnosis and treatment. Here, we describe a simple and highly accurate electromagnetic method for endoscope localization. The system includes an emitter circuit, a receiver circuit, and a signal acquisition and processing circuit. A new receiver apparatus was designed to improve the sensitivity and accuracy of localization. A virtual colon imaging method is also presented.

Quantitative determination of enzyme activity in single cells by scanning microelectrode coupled with a nitrocellulose film-covered microreactor by means of a scanning electrochemical microscope.

An electrochemical method for quantitative determination of enzyme activity in single cells was developed by scanning a microelectrode (ME) over a nitrocellulose film-covered microreactor with micropores by means of a scanning electrochemical microscope (SECM). Peroxidase (PO) in neutrophils was chosen as the model system. The microreactor consisted of a microwell with a solution and a nitrocellulose film with micropores. A single cell perforated by digitonin was injected into the microwell. After the perforated cell was lysed and allowed to dry, physiological buffer saline (PBS) containing hydroquinone (H2Q) and H2O2 as substrates of the enzyme-catalyzed reaction was added in the microwell. The microwell containing the extract of the lysed cell and the enzyme substrates was covered with Parafilm to prevent evaporation. The solution in the microwell was incubated for 20 min. In this case, the released PO from the cell converted H2Q into benzoquinone (BQ). Then, the Parafilm was replaced by a nitrocellulose film with micropores to fabricate the microreactor. The microreactor was placed in an electrochemical cell containing PBS, H2Q, and H2O2. After a 10-microm-radius Au ME was inserted into the electrochemical cell and approached down to the microreactor, the ME was scanned along the central line across the microreactor by means of a SECM. The scan curve with a peak was obtained by detecting BQ that diffused out from the microreactor through the micropores on the nitrocellulose film. PO activity could be quantified on the basis of the peak current on the scan curve using a calibration curve. This method had two obvious advantages: no electrode fouling and no oxygen interference.