Interspecific root interaction enhances cadmium accumulation in Oryza sativa when intercropping with cadmium accumulator Artemisia argyi.

The contamination of arable land with heavy metals, such as Cd, is a serious concern worldwide. Intercropping with Cd accumulators can be used for efficient safe crop production and phytoremediation of Cd-contaminated soil. However, the effect of intercropping on Cd uptake by main crops and accumulators varies among plant combinations. Rhizosphere interaction may mediate Cd uptake by intercropped plants, but the mechanism is unclear. Thus, in the present study, we aimed to examine the effect of rhizosphere interaction on Cd uptake by intercropping rice (Oryza sativa L.) with mugwort (Artemisia argyi Levl. et Vant.) in Cd-contaminated paddy soil. We grew O. sativa and A. argyi in pots designed to allow different levels of interaction: complete root interaction (no barrier), partial root interaction (nylon mesh barrier), and no root interaction (plastic film barrier). Our results indicated that both complete and partial root interaction increased the shoot and root mass of A. argyi, but did not decrease the shoot, root, and grain mass of O. sativa. Interspecific root interaction significantly increased the Cd content in the shoots, roots, and grains of O. sativa and the shoots of A. argyi. Increased content of total organic acids in the rhizosphere, which increased the content of available Cd, was a possible mechanism of increased Cd uptake in both plants under interspecific root interaction. Our findings demonstrate that an intercropping system can extract more Cd from contaminated soil than a monocropping system of either A. argyi or O. sativa. However, the intercropping system did not facilitate safe crop production because it substantially increased grain Cd content in O. sativa.

Effects of six different microbial strains on polyphenol profiles, antioxidant activity, and bioaccessibility of blueberry pomace with solid-state fermentation.

To explore the effect of different microbial strains on blueberry pomace with solid-state fermentation (SSF), three fungi strains and three lactic acid bacteria (LAB) strains were utilized to investigate with respect to polyphenol profiles, antioxidant capacities, and bioaccessibility. Different strains exhibited different capacities for metabolizing polyphenolic compounds in blueberry pomace. The contents of 10 phenolic acids and 6 flavonoids (except (+)-catechin) were increased in blueberry pomace fermented by Lactobacillus acidophilus (LA). A similar tendency was observed in blueberry pomace fermented by Aspergillus niger (AN) and Lactobacillus plantarum (LP), where the concentration of 8 phenolic acids and 5 flavonoids was enhanced, with the following exceptions: (+)-catechin, ferulic acid, vanillic acid, and quercitrin. Chlorogenic acid and quercetin were the maximum phenolic acids and flavonoids in blueberry pomace with SSF, upgraded at 22.96 and 20.16%, respectively. Contrary to the growth of phenolic acids and flavonoid compounds, all individual anthocyanins showed a decreased trend. Only in the blueberry pomace fermented by AN, all anthocyanidins exhibit a rising trend. After SSF, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenylpicrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) radical scavenging abilities were increased by up to 33.56, 59.89, and 87.82%, respectively. Moreover, the simulated gastrointestinal digestion system revealed that SSF improved the bioaccessibility of polyphenolic compounds. Compared with other strains, LA, LP, and AN showed better excellent capacities for metabolizing polyphenolic compounds, which led to a greater increase in antioxidant activity and bioaccessibility in fermented blueberry pomace.

Soluble CD163 and CD163 Expression on Monocytes Associated with Chronic Hepatitis B Inflammation and HBsAg Loss.

Background and Aims: Monocyte/macrophage-associated CD163 is an indicator of the severity of liver inflammation and cirrhosis, but the difference of soluble CD163 (sCD163) levels in chronic hepatitis B (CHB) patients and hepatitis B surface antigen (HBsAg)-loss patients is unclear. Herein, we aimed to compare the sCD163 levels in CHB patients and HBsAg-loss patients with or without antiviral treatment. Methods: sCD163 and CD163 expression on monocytes were compared among four groups, healthy subjects, treatment-naïve CHB patients, spontaneous HBsAg-loss patients, and treatment-related HBsAg-loss patients. The correlation between sCD163 levels and clinical parameters in CHB patients was analyzed. A group of 80 patients with hepatitis B virus (HBV) infection and liver biopsy were recruited. Results: sCD163 levels were higher in the CHB group than in the other three groups. sCD163 levels were higher in treatment-related HBsAg-loss patients than in spontaneous HBsAg-loss patients. sCD163 levels were negatively correlated with hepatitis B e-antigen (HBeAg) and HBsAg levels in HBeAg-positive patients. Liver biopsy results further demonstrated that sCD163 levels were elevated in CHB patients with substantial inflammation (A≥2) or fibrosis (F≥2). The sCD163 model was more sensitive in predicting inflammation than other noninvasive models. Its levels were higher in patients with normal alanine aminotransferase levels and significant inflammation (A≥2) than in patients with no or mild inflammation. Conclusions: sCD163 and CD163 expression on monocytes were associated with CHB inflammation and HBsAg loss, and may be used as markers to predict HBV-specific immune activation.

[Effects of Iron Intensity-regulated Root Microbial Community Structure and Function on Cadmium Accumulation in Rice].

Exploring the effects of exogenous iron (Fe) on cadmium (Cd) in rice is of great significance for ensuring food security. The accumulation of Cd and the changes in the microbial community structure in rice roots under three Fe concentrations (5, 50, and 500 µmol·L-1 EDTA-Na2Fe) were studied through a hydroponic experiment. The results showed that the increase in the environmental Fe concentration promoted the formation of iron plaque on the rice roots, and both Fe-deficiency and Fe-sufficiency would enhance the adsorption and fixation of Cd on the root surface. Compared with that of normal Fe levels (50 µmol·L-1), Fe deficiency increased Cd accumulation in rice roots and shoots by 49.76% and 15.68%, respectively. Although Fe sufficiency also increased Cd accumulation in the roots by 18.39%, the Cd concentration in shoots was significantly reduced by 35.95% compared with that of the normal Fe. 16S rRNA high-throughput sequencing was used to determine the root microbial community structure, and through PCA, LEfSe, and RDA analysis, it was found that compared with normal Fe, an Fe-deficient environment reduced the abundance and uniformity of root microbes. Proteobacteria and Bacteroidetes at the phylum level were the dominant flora, Fe deficiency inhibited the increase in the relative abundance of Bacteroidetes, and high-concentration Fe reduced the relative abundance of Proteobacteria. At the genus level, the relative abundance of functional microorganisms Ensifer, Rhodopila, Bdellovibrio, and Dyella were different under different Fe environments, which may have affected the absorption and accumulation of Cd by rice by affecting the formation of Fe plaque on the root and other biochemical processes. In addition, the effect of an Fe-deficient environment on microbial functions was higher than that of the Fe sufficient environment. This study investigated the changes in the rice root microbial community structure and the ability of rice to absorb and transport Cd under different Fe environments, which provided a theoretical basis and an important reference for the inhibition of Fe on Cd accumulation in rice in Cd-polluted paddy soil in southern China.

Microribonucleic Acid-15a-5p Alters Adriamycin Resistance in Breast Cancer Cells by Targeting Cell Division Cycle-Associated Protein 4.

OBJECTIVE: Although chemotherapy is one of the first line clinical treatment of tumors, the efficacy of chemotherapy has been severely restricted by the frequent occurrence of drug resistance phenomenon. Multiple studies found that miRNAs can regulate the chemosensitivity of tumor cells. Here, this study aimed to assess the potential role of the miR-15a-5p/cell division cycle-related protein 4 (CDCA4) axis in breast cancer (BC) resistance to Adriamycin. METHODS: In the present study, the relative expression of miRNA-15a-5p in MCF-7/ADR, MCF-7 and Hs578Bst was measured by qRT-PCR. MCF-7/ADR cells underwent transfection with an miR-15a-5p mimic and inhibitor, respectively. Transwell assays, flow cytometry and CCK8 were performed to examine the potential effects of the abnormal expression of miR-15a-5p. The association of aberrant miR-15a-5p expression with Adriamycin resistance in BC was determined in cultured MCF-7/ADR cells. Bioinformatics was employed to predict the genes targeted by miR-15a-5p. Moreover, the correlation between miR-15a-5p and its target gene, CDCA4, was evaluated based on qRT-PCR data. RESULTS: The expression of miR-15a-5p was significantly downregulated in MCF/ADR cells compared with MCF-7 and Hs578Bst cell lines. In the presence of Adriamycin, miR-15a-5p overexpression significantly increased cell chemosensitivity, as well as MCF-7/ADR cell proliferation, invasion, and migration, while promoting apoptosis and inducing cell-cycle arrest in the synthesis phase. CDCA4 RNA interference enhanced these effects as shown in our previous study. Bioinformatics identified CDCA4 as an miR-15a-5p target gene. qRT-PCR further demonstrated that CDCA4 and miR-15a-5p expression levels were inversely correlated. CONCLUSION: Adriamycin resistance in BC cells was, at least in part, altered by mRNA-15a-5p via regulation of its target gene, CDCA4, by controlling the cell cycle, which may provide some novel ideas for BC chemotherapy in the future.

Cadmium and arsenic availability in soil under submerged incubation: The influence of humic substances on iron speciation.

Humic substances (HSs), as electron shuttles, are associated with iron oxide transformation, yet the manner by which HSs affect Cd/As availabilities during this process under anaerobic conditions remains unclear. Two HSs (humic sodium, HA-Na, and biochemical fulvic acid, BFA) were applied at 0, 1, 2, and 4 gCkg-1 in a submerged incubation experiment. The dissolved, extractable and fractions of Cd/As and different iron oxides in soils were monitored. The addition of both HA-Na and BFA decreased the CaCl2-extractable Cd by 12.66-93.13%, and increased the KH2PO4-extractable As by 18.81-71.38% on the 60th day of incubation. The soil Eh and crystalline iron oxides (Fed) decreased, while amorphous iron oxides (Feo) and dissolved As increased after addition of both HSs. However, the two HSs had opposite effects on soil pH and dissolved Cd at the end of the incubation. HA-Na immobilized 19.47-85.99% more available Cd than did BFA over the incubation, although the extent of immobilization was similar with the maximum application rate on the 60th day. BFA mobilized 5.22-26.12% more available As than did HA-Na. XPS data showed that FeOOH decreased while the FeO component increased over the incubation. Correlation analysis and SEM showed that the reduction in the soil Eh and Fed and relative increase in Feo increased the available Cd, while decreased the available As. Consequently, the addition of HA-Na and BFA, particularly combined with flooding irrigation management, could effectively reduce the available Cd in Cd-contaminated soil. However, this method should be used with caution in As-contaminated soil.

Meta-analysis of the effects of liming on soil pH and cadmium accumulation in crops.

Increasing cadmium (Cd) contamination in agricultural fields has resulted in a higher risk of Cd accumulation in the food chain. Lime addition can mitigate soil acidification and reduce Cd accumulation in crops cultured in Cd-contaminated soil. To determine key factors controlling the outcomes of liming in reducing Cd accumulation and enhancing soil pH, we performed a meta-analysis using previously published data from field and pot experiments. The results indicated that the liming showed positive effect sizes on the soil pH but negative effect sizes on Cd accumulation in crops, indicating the addition of different lime materials could enhance soil pH and reduce Cd accumulation in crops. The effect sizes of liming on soil pH under pot experimental conditions were higher than that under field experimental conditions, however, the effect sizes of application types and amount of limes on soil pH did not significantly differ between their individual different levels. Under a low background value of soil pH, SOM, CEC and clay, the addition of limes showed a significantly higher effect size on soil pH when compared to their individual higher soil background value, suggesting that the lower background values of soil pH, SOM, CEC and clay might facilitate the outcomes of liming to enhance soil pH. The experiment patterns, crop types and lime application amounts showed a limit effect on the outcomes of liming to reduce the shoot and grain Cd concentrations in crops. The lime types only showed a significant effect size on the shoot Cd accumulation but not on the grain Cd accumulation, in which the CaCO3 had the highest effect size (absolute value, the same below) followed by Ca(OH)2 and CaO. The low soil background values of total Cd concentration and CEC content, but a high soil SOM background content might facilitate the outcomes of liming to reduce the shoot Cd concentration in crops. However, only the background value of soil clay content showed a significantly negative effect size on the grain Cd accumulation, where a high soil clay content had a higher effect size than a low soil clay content. These findings provide useful knowledge about the effects of experiment patterns, crop types, soil conditions, lime types and lime addition amounts on the efficiency of liming in enhancing soil pH and decrease crop Cd concentration.

[Effects of Water Management on Cadmium Accumulation by Rice (Oryza sativa L.) Growing in Typical Paddy Soil].

In order to explore the effects of water management on the Cd accumulation of rice in paddy soils with different parent materials, a pot experiment with three paddy soils with different parent materials from Hunan Province (granite sandy soil, plate shale soil, and purple sandy shale soil) with different water management treatments ï¼»flooding and alternate wetting and drying (AWD)ï¼½ was performed. The soil pH, DTPA-Cd, Fe plaque in the rice roots, and heavy metal concentration in the rice were determined. The results showed that the soil pH of the three paddy soils under the flooding treatment was increased by 0.17-1.33 units. During the filling and maturity periods, compared with that under AWD, the DTPA-Cd concentration in the three paddy soils was reduced by 14.39%-36.56% under the flooding treatment, but the DTPA-Fe concentration was increased by 35.35%-347.25%. In the three growth stages, the Cd and Mn concentrations in the Fe plaque (except for DCB-Fe) were in the order of tillering stage < filling stage < mature stage. Compared with that under AWD, the brown rice Cd concentration in the three soils was reduced by 57.84%-93.79% under flooding treatment. The Cd accumulation in rice was reduced under flooding treatment by reducing the DTPA-Cd via increasing the soil pH and DTPA-Fe and by decreasing the formation of Fe plaque. According to the results of the correlation and SEM analysis, the soil pH and DCB-Cd were the main factors affecting the Cd accumulation in rice grains, although the changes in the DTPA-Cd and DTPA-Fe also impacted the Cd in rice grains. In summary, our study demonstrated that water management had a significant impact on the Cd content in rice, and there were significant differences among the three paddy soils with different parent materials. In conclusion, the Cd content in rice grains was affected by the soil parent material, soil physicochemical properties, and Fe plaque on the surface of the rice roots. The granite sandy soil and plate shale soil with different water management treatments had significant impacts on the contents of heavy metals in rice. Continuous flooding is a valuable strategy for improving soil acidity and alkalinity and minimizing soil available Cd, but the soil parent materials must be considered.

Effects of composited organic mobilizing agents and their application periods on cadmium absorption of Sorghum bicolor L. in a Cd-contaminated soil.

Organic mobilizing agents have been advocated for phytoremediation of heavy metals contaminated soils, while the effects of application period of such agents remain unclear. A pot experiment was conducted, with two composited organic agents (oxalic acid or citric acid + dissolved organic fertilizer (OA + DOF and CA + DOF)) and four application periods (seeding, jointing, flag leaf and heading stages) of sorghum (Sorghum bicolor L.), to investigate their impacts on Cd bioavailability in soil. Results indicated that application of the two composited agents increased soil dissolved organic carbon (DOC) and DTPA extractable Cd by 7.31-49.13%, Cd contents in roots and shoots by 21.49-72.10%, bioaccumulation factor (BCF) and translocation factor (TF) of shoots by 4.44-71.99%, while reduced soil pH by 0.25-0.53 units, respectively. Most of these indices increased with the application periods, and largely peaked with their application during the flag leaf to heading stages. Meanwhile, the maximum sorghum biomass (132.84 g pot-1) and Cd bioaccumulation quantity (BCQ, 0.71 mg pot-1) in shoots were obtained for the CA + DOF applied at the heading. The DTPA extractable Cd was closely related to soil pH and DOC. Similar close relationships were observed between the Cd contents in shoots and soil DTPA extractable Cd, pH and DOC. The BCQ of Cd was positively related to the shoots biomass rather than their Cd contents. Therefore, the sorghum combined with the CA + DOF may be advocated as an alternative phytoremediation mode in Cd-contaminated soils, and the mobilizing agent should be primarily applied at the heading stage.

Increasing soil moisture faciliates the outcomes of exogenous sulfate rather than element sulfur in reducing cadmium accumulation in rice (Oryza sativa L.).

Cadmium (Cd) contamination in paddy soils and the related pollution risk of rice grain have received increasing attention. Agronomic measures, such as the application of sulfur and changes in water regimes, were reported to mitigate the accumulation of Cd in rice. However, there is limited information on the combined effects of sulfur application and water regimes. Therefore, a pot experiment was conducted to investigate the effects of two sulfur forms, three water regimes and multiple sulfur application rates on Cd accumulation in rice. The sulfur was applied as SO42- (SVI, replacing the traditional fertilizers by SO42--containing fertilizers), and element S (S0) was applied at 0, 10, 20, 30 and 40 mg S kg-1 soil. The water regimes were continuous flooding (F), flooding-moist alternation (FM), and moist irrigation (M), for a total of 30 treatments. The results indicated that application of SVI exceeding 30 mg S kg-1 significantly reduced the Cd concentrations in brown rice by 31.1-56.3%, and the Cd concentrations decreased with increasing amount of irrigation water. Similar reductions in Cd concentrations in rice shoots and rice straw collected at tillering and maturity stages were observed after application of SVI. However, the effect of S0 application on Cd accumulation in grain was not significant under different water regimes. Furthermore, this study found that application of both SVI and S0 inhibited the transfer of Cd from rice roots to shoots in most cases. These findings indicate that replacing traditional fertilizers with SO42--containing fertilizers, especially combined with increased irrigation, could be a potential approach to mitigate Cd accumulation in rice growing in Cd-contaminated acidic paddy soils.

[A multicenter epidemiological investigation of brain injury in hospitalized preterm infants in Anhui, China].

OBJECTIVE: To investigate the risk factors for brain injury in preterm infants by a multicenter epidemiological investigation of brain injury in hospitalized preterm infants in Anhui, China. METHODS: Preterm infants who were hospitalized in the department of neonatology in 9 hospitals of Anhui Neonatal Collaboration Network between January 2016 and January 2017 were enrolled as subjects. The data of maternal pregnancy and clinical data of preterm infants were collected, and the logistic regression model was used to analyze the risk factors for brain injury in preterm infants. RESULTS: A total of 3 378 preterm infants were enrolled. Of the 3 378 preterm infants, 798 (23.56%) had periventricular-intraventricular hemorrhage (PVH-IVH), and 88 (2.60%) had periventricular leukomalacia (PVL). Intrauterine distress, anemia, hypoglycemia and necrotizing enterocolitis (NEC) were risk factors for PVH-IVH (OR=1.310, 1.591, 1.835, and 3.310 respectively; P<0.05), while a higher gestational age was a protective factor against PVH-IVH (OR=0.671, P<0.05). PVH-IVH, NEC and mechanical ventilation were risk factors for PVL (OR=4.017, 3.018, and 2.166 respectively; P<0.05), and female sex and use of pulmonary surfactant were protective factors against PVL (OR=0.514 and 0.418 respectively; P<0.05). CONCLUSIONS: Asphyxia/anoxia, infection/inflammation, mechanical ventilation, anemia and hypoglycemia may increase the risk of brain injury in preterm infants.

Effectiveness of simultaneous applications of lime and zinc/iron foliar sprays to minimize cadmium accumulation in rice.

Due to the large area of Cd-contaminated paddy soils worldwide, low-cost measures to reduce the accumulation of Cd in rice plant are necessary. A field experiment was therefore conducted to investigate the reducing effect of lime combined with foliar applications of Zn (ZnSO4) or Fe (EDTA·Na2Fe) on Cd concentrations in brown rice on a Cd-contaminated paddy soil. The results indicated that liming alone or in combination with foliar sprays of Zn or Fe increased the soil pH by 0.27-0.63 units. However, limited effects of lime or lime combined with foliar applications of Zn/Fe on soil DTPA-extractable Cd, rice grain and rice straw biomass were observed. Liming alone significantly reduced the Cd concentration in brown rice and rice straw by 31.8% and 42.3%, respectively. The Cd concentrations in brown rice decreased by 25.5% and 65.4% and in rice straw by 53.0% and 68.1% after liming combined with foliar applications of Fe and Zn, respectively. In contrast, liming combined with foliar spraying of Fe significantly increased the transfer ratio of Cd from the rice straw to the grain. As a low-cost technique, lime application combined with foliar application of ZnSO4 could be recommended for the remediation of Cd-contaminated paddy soils.

Distribution and availability of cadmium in profile and aggregates of a paddy soil with 30-year fertilization and its impact on Cd accumulation in rice plant.

The research was conducted to investigate the accumulation, distribution and availability of Cd in paddy soil and their relation to Cd in rice plants under 30-year fertilization regimes. Six treatments were involved in the study: control without fertilization (CK), chemical fertilizer (NPK), high nitrogen chemical fertilizer (HN), rice straw incorporation (ST), low and high dosage of manure fertilizer (LM and HM). Total and DTPA extractable concentration of Cd (T-Cd and DTPA-Cd) in bulk soils (20 cm topsoil), profiles (0-60 cm) and aggregates (>2, 1-2, 0.5-1, 0.25-0.5, 0.053-0.25 and < 0.053 mm) were investigated. The Cd concentration in relevant rice plant (roots, stems, leaves, husks and grains) were also analyzed. Manure fertilizers caused T-Cd accumulation in bulk soil with a significant increase of 36.2% in LM and 81.2% in HM. Similar impacts of manure fertilizers were observed in DTPA-Cd in the bulk soil. Further, the HM generated a further accumulation in deeper soil layers, presenting a remarkable increase of T-Cd (28.3%-225%) in 10-40 cm and DTPA-Cd (116%-158%) in 10-30 cm profiles. Moreover, the continuous application of manure fertilizers enhanced the availability of Cd in all aggregate size classes with an increase of 17.3%-87.8% in DTPA-Cd. Organic fertilizers (LM, HM and ST) heightened the content of Cd (38.0%-152%) in all parts of rice plant. The accumulation of Cd in rice plants was directly affected by fertilization regimes and Cd availability in the 10-20 cm soil layers and 0.25-0.5 mm aggregates. In conclusion, long-term application of manures resulted in increasing availability of Cd in aggregates and in topsoil and subsoil layers, which accordingly enhanced the accumulation of Cd in rice plants.

Serum M2BPGi level is a novel predictive biomarker for the responses to pegylated interferon-α treatment in HBeAg-positive chronic hepatitis B patients.

Serum Mac-2-binding protein glycosylation isomer (M2BPGi) level was found to be a useful prognostic marker for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients treated with nucleoside/nucleotide analogs (NUCs) therapy, and the aim of our study is to evaluate the clinical implementation of M2BPGi level in the prediction of antiviral responses to pegylated-interferon-α (PEG-IFN-α) treatment in HBeAg-positive CHB patients. Ninety-six CHB patients who received PEG-IFN-α treatment for at least 48 weeks were recruited. The serum M2BPGi, alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), HBeAg, and HBV DNA levels at baseline, weeks 4, 12, and 24 after PEG-IFN-α treatment were determined and their associations with antiviral responses were evaluated and the virological response (VR) rate and serological response (SR) rate after 48 weeks of treatment were 65.6% and 35.4%, respectively. Baseline serum M2BPGi level was significantly different between VR and non-VR (P = 0.002) or SR and non-SR groups (P = 0.012). Multivariate analyses suggested that baseline serum M2BPGi level was independently associated with VR and SR of PEG-IFN-α treatment at week 48. The area under the ROC curve (AUC) of baseline M2BPGi was 0.682 in predicting VR, which was superior to HBsAg (AUC = 0.566) or HBV DNA (AUC = 0.567). The AUC of baseline M2BPGi in predicting SR was 0.655, which was also higher than that of HBsAg (AUC = 0.548) or HBV DNA (AUC = 0.583). These results suggested that baseline serum M2BPGi level was a novel predictor of VR and SR for PEG-IFN-α treatment in HBeAg-positive CHB patients.

The sero-prevalence of anti-adenovirus 5 neutralizing antibodies is independent of a chronic hepatitis B carrier state in China.

We investigated the prevalence of neutralizing antibodies (NA) to human Adenovirus (Ad) 5 both in healthy subjects (HS) and Chronic Hepatitis B (CHB) patients in Shanghai. Detection of anti-Ad5 NA (percentage of detection and titers) was similar between HS and CHB patients. A high percentage of subjects harbored no detectable antibodies (32.2 %) while proportion of subjects displaying very high antibody titers was low (4 %). Neither demographic factors (gender, age, health) nor AST/ALT or HBV circulating DNA titers affected detection of Ad5-specific NA. These observations pave the ground for development of Ad5-based immunotherapeutics aiming at treating CHB patients in China.

Chemoprevention activity of 25-hydroxyvitamin D in the MMTV-PyMT mouse model of breast cancer.

Development of oncologic conditions is often accompanied by inadequate vitamin D status. The chemoprevention ability of this molecule is of high interest for breast cancer, the most common malignancy in women worldwide. Because current effective vitamin D analogues, including the naturally occurring active metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D), frequently cause hypercalcemia at pharmacologic doses, the development of safer molecules for clinical chemopreventive use is essential. This study examines whether exogenously supplied prohormone 25-hydroxycholecalciferol (25(OH)D) can delay tumor progression in vivo without hypercalcemic effects. A low vitamin D diet (25 IU/kg) in the non-immunodeficient MMTV-PyMT mouse model of metastatic breast cancer revealed a significant acceleration of mammary neoplasia compared with normal diet (1,000 IU/kg). Systemic perfusion of MMTV-PyMT mice with 25(OH)D or 1,25(OH)2D delayed tumor appearance and significantly decreased lung metastasis, and both metabolites reduced Ki-67, cyclin D1, and ErbB2 levels in tumors. Perfusion with 25(OH)D caused a 50% raise in tumor 1,25(OH)2D levels, indicating good tumor penetration and effective activation. Importantly, in contrast with 1,25(OH)2D, perfusion with 25(OH)D did not cause hypercalcemia. In vitro treatment of cultured MMTV-PyMT mammary tumor cells with 25(OH)D inhibited proliferation, confirming local activation of the prohormone in this system. This study provides an in vivo demonstration in a non-immunodeficient model of spontaneous breast cancer that exogenous 25(OH)D delays neoplasia, tumor growth, and metastasis, and that its chemoprevention efficacy is not accompanied by hypercalcemia.

Speciation and phytoavailability of cadmium in soil treated with cadmium-contaminated rice straw.

When grown on Cd-contaminated soil, rice typically accumulates considerable Cd in straw, and which may return to the soil after harvest. This work was undertaken to assess the pollution risk of Cd associated to the Cd-contaminated rice straw after incorporating into an uncontaminated soil. With the Cd-contaminated rice straw added at 0, 1, 2, 3, 4 and 5 % (w/w), an incubation experiment (28 days) with non-planting and a followed pot experiment sequent with two planting (rice and Chinese cabbage, transplanted after 28-day incubation) were carried out to investigate the changes of soil Cd speciation and phytoavailability. The results indicated that the Cd-contaminated rice straw addition significantly increased soil pH and dissolved organic carbon during the 28-day incubation. For the high availability of Cd in contaminated rice straw, diethylenetriaminepentaacetic acid (DTPA) extractable Cd significantly increased, and the percentages of acetic acid extractable and reducible Cd in soil significantly enhanced after the addition of Cd-contaminated rice straw. However, the Cd-contaminated rice straw addition inhibited the rice growth and induced the decrease of Cd in rice grain and straw by 12.8 to 70.2 % and 39.3 to 57.3 %, respectively, whereas the Cd contents increased by 13.9 to 84.1 % in Chinese cabbage that planted after rice harvest. In conclusion, Cd associated with Cd-contaminated rice straw was highly available after incorporating into the soil, and thus the Cd pollution risk via the Cd-contaminated rice straw incorporation should be evaluated in the Cd-contaminated paddy region.

Parathyroid hormone-related protein: potential therapeutic target for melanoma invasion and metastasis.

The role of PTHrP in the highly metastatic human melanoma disease is not known. This study investigates the mechanisms of action of this secreted factor through homozygous inactivation of the Pthrp gene in A375 human melanoma cells. In vitro, Pthrp-ablated cells (knockout [KO]-A375, -/-) showed decreased motility and anchorage-independent growth, rounder morphology, and a significant reduction in invasion capacity compared with nonablated A375 cells (wild-type [WT]-A375, +/+). PTHrP peptide 1-34 and conditioned medium from WT-A375 cells partially restored the invasive phenotype in KO-A375. Pthrp ablation substantially decreased actin polymerization, matrix metallopeptidase 9 expression and focal adhesion kinase phosphorylation. In vivo, green fluorescent protein-transduced ablated and nonablated A375 cells were injected intracardially or sc into nude mice to study proliferation and multiorgan metastasis. Dissemination of injected Pthrp-ablated cells to lung and liver was reduced by 85% and 50%, respectively, compared with nonablated controls (120 hours after injection). The number of metastatic lesions and the percentage of animals with metastasis were markedly lower in mice injected with Pthrp-ablated A375, and 45% of these animals survived a 7-week period compared with 15% of mice injected with nonablated WT-A375. When mice injected with WT-A375 were treated with our blocking anti-PTHrP monoclonal antibody raised against the first 33 amino acids of human PTHrP, tumor size was decreased by more than 80% over 4 weeks and survival was significantly improved over 8 months. This study provides direct evidence of the major role for PTHrP in melanoma invasion and metastasis and suggests that agents that suppress PTHrP may be beneficial against melanoma progression.

Assessment of Quantum Mechanical Methods for Copper and Iron Complexes by Photoelectron Spectroscopy.

Broken-symmetry density functional theory (BS-DFT) calculations are assessed for redox energetics [Cu(SCH3)2]1-/0, [Cu(NCS)2]1-/0, [FeCl4]1-/0, and [Fe(SCH3)4]1-/0 against vertical detachment energies (VDE) from valence photoelectron spectroscopy (PES), as a prelude to studies of metalloprotein analogs. The M06 and B3LYP hybrid functionals give VDE that agree with the PES VDE for the Fe complexes, but both underestimate it by ∼400 meV for the Cu complexes; other hybrid functionals give VDEs that are an increasing function of the amount of Hartree-Fock (HF) exchange and so cannot show good agreement for both Cu and Fe complexes. Range-separated (RS) functionals appear to give a better distribution of HF exchange since the negative HOMO energy is approximately equal to the VDEs but also give VDEs dependent on the amount of HF exchange, sometimes leading to ground states with incorrect electron configurations; the LRC-ωPBEh functional reduced to 10% HF exchange at short-range give somewhat better values for both, although still ∼150 meV too low for the Cu complexes and ∼50 meV too high for the Fe complexes. Overall, the results indicate that while HF exchange compensates for self-interaction error in DFT calculations of both Cu and Fe complexes, too much may lead to more sensitivity to nondynamical correlation in the spin-polarized Fe complexes.

Interferon gamma inhibits adipogenesis in vitro and prevents marrow fat infiltration in oophorectomized mice.

Interferon gamma (IFNγ) has been reported to induce osteoblastogenesis from mesenchymal stem cells (MSCs) both in vitro and in vivo. With ageing, adipocytes outnumber osteoblasts within the bone microenvironment leading to a decrease in bone formation. Since both osteoblasts and adipocytes are of mesenchymal origin, we hypothesized that IFNγ treatment might negatively affect adipogenesis while stimulating osteoblastogenesis in human MSC. To test this hypothesis, human MSCs were induced to differentiate into adipocytes in the presence or absence of osteogenic doses of IFNγ (1, 10, and 100 ng/ml). IFNγ-treated MSC showed a decrease in adipocyte differentiation and lipid deposition when compared with vehicle-treated controls. Additionally, adipogenic markers were significantly decreased by IFNγ treatment at the same doses that have been reported to have a strong osteogenic effect in vitro. Furthermore, DNA binding of peroxisome proliferator-activated receptor gamma was significantly lower in IFNγ-treated differentiating MSC. Subsequently, ovariectomized C57BL6 mice were treated with osteogenic doses of IFNγ three times a week for 6 weeks. In distal femur, treated mice showed significantly higher hematopoiesis concomitant with lower levels of fat volume/total volume, adipocyte number, and expression of adipogenic markers when compared with the vehicle-treated mice. Together, these findings demonstrate that, at osteogenic doses, IFNγ also acts as an inhibitor of adipogenesis in vitro and prevents marrow fat infiltration while favors hematopoiesis in ovariectomized mice.