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The roles of the Hippo‑Yes‑associated protein (YAP) pathway in lung injury and repair remain elusive. The present study examined the effects of systemic inhibition or stimulation of YAP activity on lung injury, repair and inflammation in a mouse model of lipopolysaccharide (LPS)‑induced lung injury. Mice were treated with or without YAP inhibitor, verteporfin, or with or without YAP stimulator, XMU‑MP‑1, and intraperitoneally injected with LPS (7.5 mg/kg). Lung injury and repair were evaluated by histological analysis and by testing for markers of lung injury. Lung inflammation was assessed by measuring tissue levels of inflammatory mediators. Lung injury was associated with a decreased, whereas lung repair was associated with an increased YAP activity evidenced by nuclear translocation. Lung injury was associated with a high level of lung inflammation and epithelial adherens junction disassembly, but not with cell proliferation or epithelial cell regeneration. The injury phase was defined as 0‑48 h post‑LPS injection, and the 48‑168 h time period was considered the repair phase. Inhibition of YAP activity at the injury phase, using verteporfin, exacerbated, whereas its stimulation, using XMU‑MP‑1, alleviated lung injury, lung inflammation and epithelial adherens junction disassembly. Inhibition or stimulation of YAP activity at the injury phase had no effects on cell proliferation or epithelial regeneration. By contrast, lung repair was associated with inflammation resolution, increased cell proliferation, epithelial regeneration and reassembly of epithelial adherens junctions. Inhibition of YAP activity at the repair phase delayed inflammation resolution, impeded lung recovery, inhibited cell proliferation and epithelial regeneration, and inhibited epithelial adherens junction reassembly. Stimulation of YAP activity at the repair phase reversed all these processes. The results of the current study demonstrated that the Hippo‑YAP activity serves a protective role against endotoxemic lung injury. The Hippo‑YAP activity alleviated lung inflammation and injury at the injury phase and promoted inflammation resolution and lung repair at the repair phase.

Joubert syndrome is characterized by unique malformation of the cerebellar vermis. More than thirty Joubert syndrome genes have been identified, including ARL13B. However, its role in cerebellar development remains unexplored. We found that knockdown or knockout of arl13b impaired balance and locomotion in zebrafish larvae. Granule cells were selectively reduced in the corpus cerebelli, a structure homologous to the mammalian vermis. Purkinje cell progenitors were also selectively disturbed dorsomedially. The expression of atoh1 and ptf1, proneural genes of granule and Purkinje cells, respectively, were selectively down-regulated along the dorsal midline of the cerebellum. Moreover, wnt1, which is transiently expressed early in cerebellar development, was selectively reduced. Intriguingly, activating Wnt signaling partially rescued the granule cell defects in arl13b mutants. These findings suggested that Arl13b is necessary for the early development of cerebellar granule and Purkinje cells. The arl13b-deficient zebrafish can serve as a model organism for studying Joubert syndrome.

To observe the changes of apolipoprotein E (apoE) protein expression of pulmonary tissue in mice with pulmonary hypertension induced by hypoxia.The animal model of hypoxic pulmonary hypertension was established by exposing the mice to isobaric hypoxic chamber for 3 weeks (23 h/d, regular chow feed).Twenty male wild type (WT) C57BL/6 mice and twenty apoE gene knockout (apoE-KO) mice were randomly divided into normoxia group and hypoxia group. The plasma concentrations of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were detected by ELISA method. The protein expression of apoE in lung and liver, and peroxisome proliferators-activated receptor gamma (PPARγ) in lung were measured by Western blot.①In WT mice, the right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group by 68% and 59% (Down-regulated expression of apoE in lung tissue participates in the pathological proceeding of pulmonary hypertension induced by hypoxia.

1-Chloro-3-buten-2-one (CBO) is an in vitro metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. CBO exhibited potent cytotoxicity and genotoxicity that have been attributed in part to its reactivity toward DNA. Previously, we have characterized the CBO adducts with 2'-deoxycytidine and 2'-deoxyguanosine. In the present study, we report on the reaction of CBO with 2'-deoxyadenosine (dA) under in vitro physiological conditions (pH 7.4, 37 °C). We used the synthesized standards and their decomposition and acid-hydrolysis products to characterize the CBO-DNA adducts formed in human cells. The fused-ring dA adducts (dA-1 and dA-2) were readily synthesized and were structurally characterized as 1,N(6)-(1-hydroxy-1-hydroxymethylpropan-1,3-diyl)-2'-deoxyadenosine and 1,N(6)-(1-hydroxy-1-chloromethylpropan-1,3-diyl)-2'-deoxyadenosine, respectively. dA-1 exhibited a half-life of 16.0 ± 0.7 h and decomposed to dA at pH 7.4 and 37 °C. At similar conditions, dA-2 decomposed to dA-1 and dA, and had a half-life of 0.9 ± 0.1 h. These results provide strong evidence for dA-1 being a degradation product of dA-2. dA-1 is formed by replacement of the chlorine atom of dA-2 by a hydroxyl group. The slow decomposition of dA-1 to dA, along with the detection of hydroxymethyl vinyl ketone (HMVK) as another degradation product, suggested equilibrium between dA-1 and a ring-opened carbonyl-containing intermediate that undergoes a retro-Michael reaction to yield dA and HMVK. Acid hydrolysis of dA-1 and dA-2 yielded the corresponding deribosylated products A-1D and A-2D, respectively. In the acid-hydrolyzed reaction mixture of CBO with calf thymus DNA, both A-1D and A-2D could be detected; however, the amount of A-2D was significantly larger than that of A-1D. Interestingly, only A-2D could be detected by LC-MS analysis of acid-hydrolyzed DNA from cells incubated with CBO, suggesting that dA-2 was stable in DNA and thus may play an important role in the genotoxicity and carcinogenicity of BD. In addition, A-2D could be developed as a biomarker of CBO formation in human cells.

Serratia marcescens are considered to be abundant and optimal resources for obtaining prodigiosin, which can be isolated from soil, water, plants and air but rarely from insects. In the present study, a strain of Serratia marcescens named WA12‑1‑18 was isolated from the gut of Periplaneta americana, which was capable of producing high levels of pigment reaching 2.77 g/l via solid fermentation and was identified as prodigiosin by ultraviolet, high performance liquid chromatography (LC), Fourier‑transform infrared spectroscopy, LC‑mass spectroscopy and nuclear magnetic resonance. The apoptotic tumor cells treated with prodigiosin were examined by 4',6‑diamidino‑2‑phenylindole (DAPI) staining assays and transmission electron microscopy. Flow cytometry (FCM) was utilized to measure the apoptotic rate with Annexin V staining and the expression levels of proteins involved in apoptosis, including B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X (Bax) and caspase‑3 were determined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The experimental results revealed that prodigiosin could inhibit the proliferation of HeLa cells and the half‑maximal inhibitory concentration values of prodigiosin in HeLa were 2.1, 1.2 and 0.5 µg/ml over 24, 48 and 72 h, respectively. Furthermore, DAPI staining assays and transmission electron microscopy clearly demonstrated that prodigiosin could induce HeLa cell apoptosis. FCM results revealed that the cell apoptotic rates were 19.7±1.4, 23.7±2.4 and 26.2±2.3% following the treatment with 0.5, 1.0 and 2.0 µg/ml prodigiosin for 48 h, respectively. Western blot analysis and RT‑qPCR revealed that prodigiosin could activate apoptosis‑associated molecules including Bcl‑2, Bax and caspase‑3. Therefore, the results of the present study demonstrated that the prodigiosin could induce apoptosis in HeLa cells, which may be associated with the upregulation of Bax and caspase‑3, the concomitant downregulation of Bcl‑2 levels and also triggering the extrinsic apoptotic signaling pathway.

To observe the role of apelin in the prevention of pulmonary hypertension induced by hypoxia in mice.Adult male apoE gene knockout (apoE-KO) mice were exposed to isobaric hypoxic chamber (9%~11% O①The right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group by 87% and 85% (Apelin attenuates hypoxia-induced pulmonary hypertension of mice through regulation of lipid metabolism.

La conversion coatings in various growth stages were obtained by immersing hot-dip galvanized (HDG) sheets in the lanthanum nitrate solution for different times from 10 s to 240 min. A growth process model of the La conversion coating on hot-dip galvanized steel was suggested. It is shown that the conversion coating grows more quickly by the zinc grain boundaries, where the cracks occur first and develop gradually on the whole surface of the conversion coating. When the immersion time is increased (more than 60 min), some rod-like precipitations containing more Zn and less La are deposited on the conversion coating. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) measurement results reveal that, with increasing immersion time, the protective property of the La conversion coatings is gradually increased in the early growth stage and then decreased when the cracks develop.

We have previously shown that 1-chloro-3-buten-2-one (CBO), a potential reactive metabolite of 1,3-butadiene (BD), exhibits potent cytotoxicity and genotoxicity that have been attributed in part to its reactivity toward DNA. In an effort to identify the DNA adducts of CBO, we characterized the CBO reactions with 2′-deoxyguanosine (dG), 2′-deoxycytidine (dC), and 2′-deoxyadenosine (dA) under in vitro physiological conditions (pH 7.4, 37 °C). In the present study, we investigated the CBO reaction with 2′-deoxythymidine (dT) and compared the rate constants of the reactions of CBO with dA, dC, dG, and dT at both individual- and mixed-nucleosides levels. We also investigated the reactions of CBO with single- and double-stranded DNA using HPLC with UV detection after adducts were released by either acid or enzymatic hydrolysis of DNA. Consistent with the results from the nucleoside reactions and the rate constant experiments, 1,N6-(1-hydroxy-1-chloromethylpropan-1,3-diyl)adenine (A-2D) was identified as the maj...

Modified lanthanum salt conversion coatings prepared by rare earth salt route based on lanthanum nitrate solution were proposed as alternatives to the process involving toxic hexavalent chromate. The structure and composition of the coating were determined with X-ray energy dispersive spectrometer and X-ray photoelectron spectroscopy. The surface morphologies of the treated samples were observed with scanning electron microscopy. The natural salt spray and electrochemical impendence spectra tests were carried out to evaluate the coating performance. The results showed that the corrosion resistance of the lanthanum salt conversion coating modified with citric acid on hot dip galvanized steel was superior to that of common lanthanum salt conversion coating.

Mordant yellow 10-pillared magnesium–aluminum layered double hydroxide (MY10-LDH) is prepared by anion exchange method. The intercalated structures and the chemical compositions of MY10-LDH are characterized by X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR), respectively. The experimental data prove that MY10 anion is successfully intercalated into the interlayer space of the LDHs. XRD patterns indicate that the MY10-LDH has the special intercalated structure of LDHs with an interlayer distance of 1.58 nm. IR spectra show that the product has the characteristic absorption bands of azo form of MY10 anion, as well as the Mg–O and Al–O vibrations of LDH layers. Furthermore, the microscopic structure of MY10-LDH is investigated by the quantum chemical method. The stable geometries of MY10 and MY10-LDH model molecules are optimized by using density functional theory of quantum chemistry at the level of B3LYP/6-31G(d,p). Through comparing the molecular size of MY10 anion in MY10-LDH with the interlayer distance of MY10-LDH from XRD data, it is determined that the MY10 anions are inclined arranging in the interlayer space of LDHs, because the gallery height is less than the size of MY10 anion.

The layered structures of hydrotalcites with Mg/Al ratio of 3 are studied by using quantum chemistry and molecular mechanics methods. The coordination structure and morphology of hydrotalcite are described by a series of molecular cluster models of lamellae. The geometries of cluster models of lamellae are fully optimized at the level of semiempirical molecular orbital methods and density functional theory, respectively. The computing results show that the lamellae of hydrotalcite with Mg/Al ratio of 3 have a special Mg–Al atomic arrangement and the stable structures of cluster models have hexagonal shapes corresponding to the experimental morphology of lamellae of hydrotalcites. The Mg/Al ratio of lamellae is found to be an alterable number variable with the size of lamella, and the ratio 3 is an utmost when lamella diameter becomes large enough. The highest occupied molecular orbitals on oxygen atom at the edge of the lamellae are easy to attract metal cations and the lowest unoccupied molecular orbitals near the Al3+ ions are fit to accept intercalated anions.

The double-bond isomerization of 1-pentene over zeolites has been investigated by using density functional theory at the B3LYP/6-31G(d,p) level. The calculated results indicate that the double-bond isomerization may proceed via either a stepwise or a concerted reaction pathway. The stepwise reaction consists of two elementary steps: firstly, the formation of an alkoxy intermediate by addition of a proton from zeolites, and then the decomposition of this alkoxy intermediate to yield an adsorbed 2-pentene. The calculated activation barriers are 17.9 and 31.5 kcal/mol for the first and second step, respectively. The concerted reaction occurs via one-shift proton transfer, which avoids the formation of highly stable alkoxide species. The resulting activation energy, 20.5 kcal/mol, is close to that of the first step of the stepwise reaction. From an energetic point of view, it is expected that at low temperatures, the concerted reaction mechanism dominates the overall isomerization reaction due to the lower activation energy, while at higher temperatures, the two reaction pathways compete against each other because the alkoxy formation will occur relatively easily. The results can well explain the experimental phenomena observed.

The double-bond isomerization of 1-pentene to cis -2-pentene on the surface of the molecular sieves has been investigated by using density functional theory with a cluster model simulating the zeolite materials. The microcosmic interaction of the pentene molecule with the Bronsted acid site of the zeolite leads to the formation of a π-complex, where the C C double bond is weakly coordinated to the proton of the Bronsted acid site. The transition state has an eight-member cyclic structure, in which two hydrogen atoms are situated between one oxygen atom of the zeolite and one carbon atom of the migrating double bond, respectively. The calculations of the intrinsic reaction coordinate indicate that the double-bond isomerization of 1-pentene proceeds via a concerted proton transfer between the Bronsted acid sites of the zeolite and the pentene molecules. The calculated activation energy of 11.74 kcal/mol is close to the experimental data.

Intercropping facilitates the efficient utilization of land, light, water and nutrients. It is, therefore, important to increase the biodiversity of farmland and to develop sustainable ecological agriculture in both theory and practice. Intercropping helps improve the mobilization and uptake of soil iron (Fe) and zinc (Zn) and corresponding nutritional status in the plants, thus achieving grain micronutrient biofortification. In this review, phenomena of the improvement of Fe and Zn nutrition in dicotyledonous plants as affected by intercropping with gramineous plants (e.g. maize/peanut intercropping) were summarized. Moreover, the possible mechanisms in relation to interspecific rhizosphere molecular and physiological processes, as well as the changes in interspecific root morphology and distribution and microorganisms in the rhizosphere were elucidated. The accumulation, transfer and distribution of Fe and Zn in the plants in intercropping systems were also reviewed. The possible affecting factors on nutrients of Fe and Zn were analyzed. Based on the present advances in the mobilization and acquisition of soil Fe and Zn, and their accumulation and distribution in plants as well as the related management and environment influence factors, some new research questions were pointed out. Quantitative analysis, dynamic and systemic researches and field studies on Fe and Zn transfer from soil to plant in intercropping systems should be strengthened in the future.

To explore the role and mechanism of microRNA185 (miR-185) on proliferation, migration and invasion of esophageal squamous cell carcinoma (ESCC).Samples were obtained from 23 ESCC patients undergoing surgery whose were confirmed by pathological diagnosis of esophageal carcinoma from 2002 to 2012,at Department of Thoracic Surgery,Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Real-time PCR was used to measure the expression of miR-185. The xCELLigence RTCA MP system and Transwell assay were performed to detect the effect of miR-185 on proliferation, migration and invasion of ESCC respectively. After transfecting of miR-185 mimic into KYSE150, the expression of Six1's downstream gene cyclin A1 was evaluated by real-time PCR. After transfection of miR-185 inhibitor into KYSE30, the expression of E-cadherin, a downstream protein of Six1, was observed under confocal microscope.The expression level of miR-185 was down-regulated in ESCC compared with adjacent normal tissue (0.006 vs 0.039,P = 0.016). After transfection of miR-185 mimic, miR-185 significantly inhibited proliferation, migration and invasion of ESCC.Transwell assay showed, in comparison with the control group, the number of KYSE150 metastatic and invasive cells was respectively decreased(146 ± 15 vs 64 ± 11, 110 ± 12 vs 67 ± 5, both P0.05). And the expression level of cyclin A1 decreased. After transfection of miR-185 inhibitor,the expression level of E-cadherin decreased.miR-185 may inhibit proliferation, migration and invasion of ESCC through its target gene Six1.

From the functional point of view, a method that employed an Immune Programming algorithm to extract rules from Neural Network (NN) was presented. According to quantifying color feature of landscape images had been marked with emotion values in China Affective Picture System (CAPS), the method clustered outputs of hidden neurons of NN, reduced the searching scale, and the mapping between color and subjective impressions was established. The result of experiment shows it can extract reasonably succinct sign rules that have high predictive accuracy rates.

AIM Vaccaria segetalis was reported anti-tumor action in vitro. In this study, the effect and mechanism of inhibiting tumor growth and improving the quality of life of Vaccaria segetalis on mouse inoculated H22 solid carcinoma were investigated. METHODS The solid carcinoma model of mouse was made by H22 cells subcutaneous injection and they were divided into four groups including model control group, 1mg/kg treatment dose, 2.5mg/kg treatment dose and 5mg/kg treatment dose groups of Vaccaria segetalis.After ig treatment for 10 days,the mice were killed,and the inhibited rate of tumor growing was calculated. The pathological morhpologic change of tumor was observed by HE staining.The apoptosis number of tumor was observed by TUNEL method. The expression of CD31 of tumor endothelial cells was measured by immunohistochemical method.RESULTS Vaccaria segetalis can improve the quality of life on mice invased by tumor, inhibite the growth of tumor.The effect of Vaccaria segetalis on the tumor morphology showed nuclear shrinkage, necrosis, and inflammatory cell infiltration on the periphery, etc. And it inhibited the expression of CD31, induced apoptosis of tumor cells and vascular endothelial cells.CONCLUSION Vaccaria segetalis can improve the the quality of life on mice invased by tumor, and inhibit the growth of tumor. The mechanisms were likely due to inhibiting the angiogenesis, and inducing the apoptosis of tumor cells and vascular endothelial cells.