Earth-abundant Zn-dipyrrin chromophores for efficient CO2 photoreduction.

The development of strong sensitizing and Earth-abundant antenna molecules is highly desirable for CO2 reduction through artificial photosynthesis. Herein, a library of Zn-dipyrrin complexes (Z-1-Z-6) are rationally designed via precisely controlling their molecular configuration to optimize strong sensitizing Earth-abundant photosensitizers. Upon visible-light excitation, their special geometry enables intramolecular charge transfer to induce a charge-transfer state, which was first demonstrated to accept electrons from electron donors. The resulting long-lived reduced photosensitizer was confirmed to trigger consecutive intermolecular electron transfers for boosting CO2-to-CO conversion. Remarkably, the Earth-abundant catalytic system with Z-6 and Fe-catalyst exhibits outstanding performance with a turnover number of >20 000 and 29.7% quantum yield, representing excellent catalytic performance among the molecular catalytic systems and highly superior to that of noble-metal photosensitizer Ir(ppy)2(bpy)+ under similar conditions. Experimental and theoretical investigations comprehensively unveil the structure-activity relationship, opening up a new horizon for the development of Earth-abundant strong sensitizing chromophores for boosting artificial photosynthesis.

Evolution of the ErbB gene family and analysis of regulators of Egfr expression during development of the rat spinal cord.

Egfr, a member of the ErbB gene family, plays a critical role in tissue development and homeostasis, wound healing, and disease. However, expression and regulators of Egfr during spinal cord development remain poorly understood. In this study, we investigated ErbB evolution and analyzed co-expression modules, miRNAs, and transcription factors that may regulate Egfr expression in rats. We found that ErbB family members formed via Egfr duplication in the ancient vertebrates but diverged after speciation of gnathostomes. We identified a module that was co-expressed with Egfr, which involved cell proliferation and blood vessel development. We predicted 25 miRNAs and nine transcription factors that may regulate Egfr expression. Dual-luciferase reporter assays showed six out of nine transcription factors significantly affected Egfr promoter reporter activity. Two of these transcription factors (KLF1 and STAT3) inhibited the Egfr promoter reporter, whereas four transcription factors (including FOXA2) activated the Egfr promoter reporter. Real-time PCR and immunofluorescence experiments showed high expression of FOXA2 during the embryonic period and FOXA2 was expressed in the floor plate of the spinal cord, suggesting the importance of FOXA2 during embryonic spinal cord development. Considering the importance of Egfr in embryonic spinal cord development, wound healing, and disease (specifically in cancer), regulatory elements identified in this study may provide candidate targets for nerve regeneration and disease treatment in the future.

Angiogenic and Antiangiogenic mechanisms of high density lipoprotein from healthy subjects and coronary artery diseases patients.

Normal high-density lipoprotein (nHDL) in normal, healthy subjects is able to promote angiogenesis, but the mechanism remains incompletely understood. HDL from patients with coronary artery disease may undergo a variety of oxidative modifications, rendering it dysfunctional; whether the angiogenic effect is mitigated by such dysfunctional HDL (dHDL) is unknown. We hypothesized that dHDL compromises angiogenesis. The angiogenic effects of nHDL and dHDL were assessed using endothelial cell culture, endothelial sprouts from cardiac tissue from C57BL/6 mice, zebrafish model for vascular growth and a model of impaired vascular growth in hypercholesterolemic low-density lipoprotein receptor null(LDLr-/-)mice. MiRNA microarray and proteomic analyses were used to determine the mechanisms. Lipid hydroperoxides were greater in dHDL than in nHDL. While nHDL stimulated angiogenesis, dHDL attenuated these responses. Protein and miRNA profiles in endothelial cells differed between nHDL and dHDL treatments. Moreover, nHDL suppressed miR-24-3p expression to increase vinculin expression resulting in nitric oxide (NO) production, whereas dHDL delivered miR-24-3p to inhibit vinculin expression leading to superoxide anion (O2•-) generation via scavenger receptor class B type 1. Vinculin was required for endothelial nitric oxide synthase (eNOS) expression and activation and modulated the PI3K/AKT/eNOS and ERK1/2 signaling pathways to regulate nHDL- and VEGF-induced angiogenesis. Vinculin overexpression or miR-24-3p inhibition reversed dHDL-impaired angiogenesis. The expressions of vinculin and eNOS and angiogenesis were decreased, but the expression of miR-24-3p and lipid hydroperoxides in HDL were increased in the ischemic lower limbs of hypercholesterolemic LDLr-/- mice. Overexpression of vinculin or miR-24-3p antagomir restored the impaired-angiogenesis in ischemic hypercholesterolemic LDLr-/- mice. Collectively, nHDL stimulated vinculin and eNOS expression to increase NO production by suppressing miR-24-3p to induce angiogenesis, whereas dHDL inhibited vinculin and eNOS expression to enhance O2•- generation by delivering miR-24-3p to impair angiogenesis, and that vinculin and miR-24-3p may be therapeutic targets for dHDL-impaired angiogenesis.

Circulating extracellular vesicles from patients with valvular heart disease induce neutrophil chemotaxis via FOXO3a and the inhibiting role of dexmedetomidine.

We previously demonstrated that circulating extracellular vesicles (EVs) from patients with valvular heart disease (VHD; vEVs) contain inflammatory components and inhibit endothelium-dependent vasodilation. Neutrophil chemotaxis plays a key role in renal dysfunction, and dexmedetomidine (DEX) can reduce renal dysfunction in cardiac surgery. However, the roles of vEVs in neutrophil chemotaxis and effects of DEX on vEVs are unknown. Here, we investigated the impact of vEVs on neutrophil chemotaxis in kidneys and the influence of DEX on vEVs. Circulating EVs were isolated from healthy subjects and patients with VHD. The effects of EVs on chemokine generation, forkhead box protein O3a (FOXO3a) pathway activation and neutrophil chemotaxis on cultured human umbilical vein endothelial cells (HUVECs) and kidneys in mice and the influence of DEX on EVs were detected. vEVs increased FOXO3a expression, decreased phosphorylation of Akt and FOXO3a, promoted FOXO3a nuclear translocation, and activated the FOXO3a signaling pathway in vitro. DEX pretreatment reduced vEV-induced CXCL4 and CCL5 expression and neutrophil chemotaxis in cultured HUVECs via the FOXO3a signaling pathway. vEVs were also found to suppress Akt phosphorylation and activate FOXO3a signaling to increase plasma levels of CXCL4 and CCL5 and neutrophil accumulation in kidney. The overall mechanism was inhibited in vivo with DEX pretreatment. Our data demonstrated that vEVs induced CXCL4-CCL5 to stimulate neutrophil infiltration in kidney, which can be inhibited by DEX via the FOXO3a signaling. Our findings reveal a unique mechanism involving vEVs in inducing neutrophils chemotaxis and may provide a novel basis for using DEX in reducing renal dysfunction in valvular heart surgery.

[Fluoride Removal Efficiency of Novel Material:Magnetite Core/Zirconia Shell Nanocomposite].

Magnetite core/zirconia shell nanocomposite (abbreviated as Fe3O4@ZrO2 hereafter) was obtained using one-step co-precipitation method and its performance for removal of fluoride ion from water was studied. The results showed that the Langmuir maximum adsorption capacity of fluoride ion by Fe3O4@ZrO2 was 35.46 mg·g-1, which was far higher than those of magnetite, activated alumina and activated carbon. Studies of adsorption kinetics indicated that the adsorption of fluoride ion by Fe3O4@ZrO2 was fast and could be well described by the pseudo-second-order model. The adsorption process of fluoride ion was an endothermic reaction. The adsorption of fluoride ion by Fe3O4@ZrO2 decreased with increasing pH. Chloride, nitrate and sulfate anions, which commonly coexist in drinking water, had little effect on F- adsorption, although the coexistence of HCO3- and CO32- reduced the adsorption significantly by increasing the pH of the solution system. The fluoride adsorbed by Fe3O4@ZrO2 could be successfully desorbed with 1 mol·L-1 NaOH solution as desorption agent. The desorption rate reached 99.5%-99.6%. The F--desorbed Fe3O4@ZrO2 could be reused for the removal of F- after regeneration via restoring the protonation status of surface hydroxyl groups on hydrous zirconia. The removal efficiency of fluoride by Fe3O4@ZrO2 from actual well water was lower than that from pure water, but concentration limit for fluoride in drinking water could still be attained by increasing the dosage to a sufficiently high level. Fe3O4@ZrO2 is a promising material for fluoride removal due to its good performance, simple preparation method and easy separation from water by providing an external magnetic field.

Characterization and application of droplet spray ionization for real-time reaction monitoring.

RATIONALE: The ionization source for real-time reaction monitoring has attracted tremendous interest in recent years. We have previously reported a reliable approach in which droplet spray ionization (DSI) was used for monitoring chemical reactions in real-time. Herein, we systematically investigated the characterization and application of DSI for real-time reaction monitoring. METHODS: Analyte ions are generated by loading a sample solution onto a corner of a microscope cover glass positioned in front of the MS inlet and applying a high voltage to the sample. The tolerance to positioning, solvent effect, spray angle and spray time were investigated. Extension to real-time monitoring of macromolecule reactions was also demonstrated by the charge state change of cytochrome c in the presence of acetic acid. RESULTS: The corner could be positioned within an area of approximately 10 × 6 × 5 mm (x, y, z) in front of the MS inlet. The broad polarities of solvents from methanol to PhF were suitable for DSI. It featured monitoring real-time changes in reactions on the time scale of seconds to minutes. A real-time charge state change of cytochrome c was captured. CONCLUSIONS: DSI-MS features ease of use, durability of the spray platform and reusability of the ion source. Eliminating the need for a sample transport capillary, DSI opens a new avenue for the in situ analysis and real-time monitoring of short-lived key reaction intermediates even at subsecond dead times. Copyright © 2016 John Wiley & Sons, Ltd.

[Effects of soil data and map scale on assessment of total phosphorus storage in upland soils.] / ä¸åŒåˆ¶å›¾å°ºåº¦åŠåœŸå£¤æ•°æ®å¯¹åœŸå£¤å ¨ç£·å‚¨é‡ä¼°ç®—çš„å½±å“.

Accurate assessment of total phosphorus storage in farmland soils is of great significance to sustainable agricultural and non-point source pollution control. However, previous studies haven't considered the estimation errors from mapping scales and various databases with different sources of soil profile data. In this study, a total of 393×104 hm2 of upland in the 29 counties (or cities) of North Jiangsu was cited as a case for study. Analysis was performed of how the four sources of soil profile data, namely, "Soils of County", "Soils of Prefecture", "Soils of Province" and "Soils of China", and the six scales, i.e. 1:50000, 1:250000, 1:500000, 1:1000000, 1:4000000 and1:10000000, used in the 24 soil databases established for the four soil journals, affected assessment of soil total phosphorus. Compared with the most detailed 1:50000 soil database established with 983 upland soil profiles, relative deviation of the estimates of soil total phosphorus density (STPD) and soil total phosphorus storage (STPS) from the other soil databases varied from 4.8% to 48.9% and from 1.6% to 48.4%, respectively. The estimated STPD and STPS based on the 1:50000 database of "Soils of County" and most of the estimates based on the databases of each scale in "Soils of County" and "Soils of Prefecture" were different, with the significance levels of P＜0.001 or P＜0.05. Extremely significant differences (P＜0.001) existed between the estimates based on the 1:50000 database of "Soils of County" and the estimates based on the databases of each scale in "Soils of Province" and "Soils of China". This study demonstrated the significance of appropriate soil data sources and appropriate mapping scales in estimating STPS.

Excess ROS induced by AAPH causes myocardial hypertrophy in the developing chick embryo.

BACKGROUND: The developing embryo is very sensitive to oxidative stress and excess reactive oxygen species (ROS) generation is often associated with cardiovascular malformation. However, little is known about the adverse effects of ROS during heart morphogenesis, especially during the formation of the atria and ventricles. METHODS AND RESULTS: We have treated early chick embryos with 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH) to generate free radicals in the developing heart. We established that excess ROS induced by AAPH caused cardiomegaly to develop in 4-, 14- and 17-day-old embryos. The cardiomyocytes of these AAPH-treated hearts were hypertrophic, in both the compact and trabeculated myocardium. The weight of these hearts was also significantly increased in an AAPH dose-dependent fashion. We examined and compared the functions of the AAPH-treated and untreated hearts by echocardiography and determined that the ejection fraction was shortened. BrdU incorporation assay was performed and revealed that cell proliferation was not the main cause of cardiomegaly. However, we established that the cardiomyocytes exposed to excess ROS were distinctively larger than control cardiomyocytes - indicting that cardiomegaly was attributed to hypertrophy. We have also found that excess ROS inhibited Wnt signaling but enhanced VEGF signaling. Consequently, this promoted angiogenesis and caused larger coronary arteries to develop in the AAPH-treated hearts. CONCLUSIONS: We have demonstrated that cardiomyocyte hypertrophy and changes in Wnt and VEGF signaling were the main contributing factors in the development of cardiomegaly induced by oxidative stress.

A new oxidative stress model, 2,2-azobis(2-amidinopropane) dihydrochloride induces cardiovascular damages in chicken embryo.

It is now well established that the developing embryo is very sensitive to oxidative stress, which is a contributing factor to pregnancy-related disorders. However, little is known about the effects of reactive oxygen species (ROS) on the embryonic cardiovascular system due to a lack of appropriate ROS control method in the placenta. In this study, a small molecule called 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH), a free radicals generator, was used to study the effects of oxidative stress on the cardiovascular system during chick embryo development. When nine-day-old (stage HH 35) chick embryos were treated with different concentrations of AAPH inside the air chamber, it was established that the LD50 value for AAPH was 10 µmol/egg. At this concentration, AAPH was found to significantly reduce the density of blood vessel plexus that was developed in the chorioallantoic membrane (CAM) of HH 35 chick embryos. Impacts of AAPH on younger embryos were also examined and discovered that it inhibited the development of vascular plexus on yolk sac in HH 18 embryos. AAPH also dramatically repressed the development of blood islands in HH 3+ embryos. These results implied that AAPH-induced oxidative stress could impair the whole developmental processes associated with vasculogenesis and angiogenesis. Furthermore, we observed heart enlargement in the HH 40 embryo following AAPH treatment, where the left ventricle and interventricular septum were found to be thickened in a dose-dependent manner due to myocardiac cell hypertrophy. In conclusion, oxidative stress, induced by AAPH, could lead to damage of the cardiovascular system in the developing chick embryo. The current study also provided a new developmental model, as an alternative for animal and cell models, for testing small molecules and drugs that have anti-oxidative activities.

Exploring the caffeine-induced teratogenicity on neurodevelopment using early chick embryo.

Caffeine consumption is worldwide. It has been part of our diet for many centuries; indwelled in our foods, drinks, and medicines. It is often perceived as a "legal drug", and though it is known to have detrimental effects on our health, more specifically, disrupt the normal fetal development following excessive maternal intake, much ambiguity still surrounds the precise mechanisms and consequences of caffeine-induced toxicity. Here, we employed early chick embryos as a developmental model to assess the effects of caffeine on the development of the fetal nervous system. We found that administration of caffeine led to defective neural tube closures and expression of several abnormal morphological phenotypes, which included thickening of the cephalic mesenchymal tissues and scattering of somites. Immunocytochemistry of caffeine-treated embryos using neural crest cell markers also demonstrated uncharacteristic features; HNK1 labeled migratory crest cells exhibited an incontinuous dorsal-ventral migration trajectory, though Pax7 positive cells of the caffeine-treated groups were comparatively similar to the control. Furthermore, the number of neurons expressing neurofilament and the degree of neuronal branching were both significantly reduced following caffeine administration. The extent of these effects was dose-dependent. In conclusion, caffeine exposure can result in malformations of the neural tube and induce other teratogenic effects on neurodevelopment, although the exact mechanism of these effects requires further investigation.

Anti-stress effects of carnosine on restraint-evoked immunocompromise in mice through spleen lymphocyte number maintenance.

Carnosine (ß-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK) cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU(10)/spleen) while the activity of a single NK cell (LU(10)/10(6) cells) was not changed. However, oral administration of carnosine (150 and 300 mg/kg) increased spleen index and number of spleen lymphocytes (including NK cells), and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist) treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm, increased Bcl-2/Bax mRNA ratio, as well as decreased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in spleen lymphocytes of stressed mice. The results above suggested that the maintenance of spleen lymphocyte number by carnosine was related with the inhibition of lymphocytes apoptosis caused by glucocorticoids overflow. The stimulation of lymphocyte proliferation by carnosine also contributed to the maintenance of spleen lymphocyte number in stressed mice. In view of the elevated histamine level, the anti-stress effects of carnosine on restraint-evoked immunocompromise might be via carnosine-histamine metabolic pathway. Taken together, carnosine maintained spleen lymphocyte number by inhibiting lymphocyte apoptosis and stimulating lymphocyte proliferation, thus prevented immunocompromise in restraint-stressed mice.

Caffeine interferes embryonic development through over-stimulating serotonergic system in chicken embryo.

The potential harmful effects of caffeine in pregnant women aroused public interests due to its possibility to jeopardize fetal development. Monoamine neurotransmitters are thought to regulate neural development processes through maternal-fetal interactions, which may have long term impact on mental and behavioral effects. The current study focuses on investigating the effects of caffeine on the monoamine neurotransmitter system using developmental chicken embryos. The ED(50) value of caffeine toxicity was 27.3 µmol/egg in chicken embryo. Administration of caffeine, with lower dosage than ED(50) (2.5, 5.0 and 10.0 µmol/egg), caused failure of neural tube closure. In addition, contents of 5-HT and its metabolite 5-HIAA were increased under dosage of 10.0 µmol/egg caffeine administration. Gene expression of TPH2 was also increased by caffeine treatment. Caffeine could result in defect of neural tube closure and induce disorder of serotonergic system development, which may increase teratogenic rate of embryos. Meanwhile, it is probably an underlying factor for inducing psychological and behavioral disorders in adult. Moreover, caffeine was found to be accumulated in the embryonic brain and not being metabolized, which may incur a magnification of adverse effects. This study may provide valuable data for further investigations on toxicology of caffeine during different stages of pregnancy.

Protective effect of extract of chicken meat on restraint stress-induced liver damage in mice.

In this study, we investigated the protective effects of the extract of chicken meat (EC) on liver damage in mice caused by restraint stress. Our results showed that 18 h of restraint stress-induced liver damage was marked by an increase of plasma alanine aminotransferase (ALT) and aspartate aminotransferase(AST) levels. However, oral administration of EC (0.12 and 0.24 mL/10 g per day, 7 d) was found to reduce the increased plasma ALT and AST levels in stressed mice. Meanwhile, EC significantly decreased the contents of malondialdehyde and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) in plasma or liver of stressed mice. The gene expressions of antioxidative enzymes (Cu/Zn-SOD, Mn-SOD and GPX) were also up-regulated in the EC-treated group when compared with the stressed group. In addition, EC administration was found to resist a stress-induced increase of plasma corticosterone levels and down-regulation of liver glucocorticoid receptor gene expression. These results suggested that EC could protect against restraint stress-induced liver damage by smoothing stress and promoting antioxidative processes.

Carnosine ameliorates stress-induced glucose metabolism disorder in restrained mice.

Carnosine is a natural dipeptide that has shown multiple benefits in the treatment of various diseases. This study investigated the ameliorative effects of carnosine on glucose metabolism in restraint-stressed mice. Our results showed that restraint stress could significantly influence glucose metabolism, as reflected by lowered glucose tolerance, hepatic and muscle glycogen content, and increased plasma corticosterone concentration in mice. Oral administration of carnosine (150 and 300 mg/kg) not only reverted stress-induced decline in glucose tolerance and glycogen content in liver and muscle, but also reduced plasma corticosterone level. Carnosine has also significantly suppressed mRNA expression of glucose-6-phosphatase, while elevating glycogen synthase 2, glucokinase and glucose transporter 2 expressions in the liver. The obtained results demonstrated the harmful effects induced by restraint stress, while proving that carnosine could ameliorate stress-induced glucose metabolism disturbance. It is presumable that carnosine exerts its anti-stress effects by indirectly affecting the histaminergic neuron system, modulating the stress-activated hypothalamic-pituitary-adrenal axis and improving glucose metabolism through regulation of the enzymes in the glucose metabolic pathways.

[Occult HBV infection in patients with anti-HBc positive alone].

OBJECTIVE: This study was designed to explore the incidence rate of occult HBV infection in patients with anti-HBc positive alone and analyze the possible reasons of occult infection. METHODS: Sera of 183 patients carrying anti-HBc alone(A < or = 0.1) were collected and real-time PCR was used to select samples with HBV DNA positive. HBV pre-S/S amplification products were obtained by PCR, and clonal sequencing were then used for these samples with HBV DNA positive. RESULTS: DNA quantitative results of three samples were greater than 10(3) copies/ml in 183 samples, with a fraction of 1.6%. Pre-S/S sequencing results of two samples from these three samples were obtained. Point mutations within "a" determinant with Q129R/P mutations and co-existence of the mutant type and wild type were found in the two samples. CONCLUSIONS: Occult HBV infection existed in samples with anti-HBc alone. Factors contributing to the loss of HBsAg detection by immunoassays include S gene mutations and low levels of circulating antigen which are below the assay limit of detection. Occult HBV infection not only can lead to a false clinical diagnosis, but also can result in hematological pollution due to such occult infection of blood donors.

[Effect of bacillus calmette-guerin treatment on airway inflammation and T regulatory cells in mice with asthma].

OBJECTIVE: Previous studies have shown that bacillus calmette-guerin (BCG) can deviate TH2 response toward TH1 response, resulting in a suppressive effect on the development of asthma/atopy. This study examined the effect of BCG treatment on regulatory T cells in asthmatic mice to investigate the possible mechanism. METHODS: Kunming mice were sensitized and challenged with ovalbumin (OVA) to establish asthmatic models. Asthmatic mice were injected intradermally with BCG five days before and after sensitization. After 24 hrs of last challenge, bronchoaveolar lavage fluid (BALF) and peripheral blood were collected . The total cells and eosinophils were counted in the BALF. The percentage of CD4(+) CD25(+) in peripheral blood was detected with flow cytometry. Single spleen cell suspension was prepared and cultured in 1640 medium for 48 hrs and then the cytokine IL-10 level in the supernatant was determined using ELISA. The mice which were challenged with normal saline were used as the Normal control group. RESULTS: The number of total cells and eosinophils in BALF in asthmatic mice [(27.27 +/- 5.36) x 10(7)/L and (6.59 +/- 1.32) x 10(7)/L respectively] were more than in the Normal control group [(1.52 +/- 0.36) x 10(7)/L and zero respectively] (P < 0.01). The number of total cells and eosinophils in BALF in asthmatic mice were reduced after BCG treatment [(13.71 +/- 3.17) x 10(7)/L and (1.43 +/- 0.37) x 10(7)/L respectively] (P < 0.01). The percentage of CD4(+) CD25(+) in peripheral blood of asthmatic mice [(11.59 +/- 1.33)%] was noticeably lower than that of the Control group [(13.66 +/- 1.68)%] (P < 0.01), but increased significantly in asthmatic mice after BCG treatment [(14.40 +/- 2.70)%] (P < 0.05). The IL-10 level in spleen cell supernatant in the BCG-treated group (7.79 +/- 1.34 pg/mL) also increased compared with that in the untreated asthmatic mice (5.54 +/- 0.66 pg/mL) (P < 0.01). CONCLUSIONS: BCG can markedly inhibit the airway inflammation in asthmatic mice possibly by promoting the production of regulatory T cells.