Desmoglein 2 and desmocollin 2 depletions promote malignancy through distinct mechanisms in triple-negative and luminal breast cancer.

BACKGROUND: Aberrant expressions of desmoglein 2 (Dsg2) and desmocollin 2(Dsc2), the two most widely distributed desmosomal cadherins, have been found to play various roles in cancer in a context-dependent manner. Their specific roles on breast cancer (BC) and the potential mechanisms remain unclear. METHODS: The expressions of Dsg2 and Dsc2 in human BC tissues and cell lines were assessed by using bioinformatics analysis, immunohistochemistry and western blotting assays. Wound-healing and Transwell assays were performed to evaluate the cells' migration and invasion abilities. Plate colony-forming and MTT assays were used to examine the cells' capacity of proliferation. Mechanically, Dsg2 and Dsc2 knockdown-induced malignant behaviors were elucidated using western blotting assay as well as three inhibitors including MK2206 for AKT, PD98059 for ERK, and XAV-939 for ß-catenin. RESULTS: We found reduced expressions of Dsg2 and Dsc2 in human BC tissues and cell lines compared to normal counterparts. Furthermore, shRNA-mediated downregulation of Dsg2 and Dsc2 could significantly enhance cell proliferation, migration and invasion in triple-negative MDA-MB-231 and luminal MCF-7 BC cells. Mechanistically, EGFR activity was decreased but downstream AKT and ERK pathways were both activated maybe through other activated protein tyrosine kinases in shDsg2 and shDsc2 MDA-MB-231 cells since protein tyrosine kinases are key drivers of triple-negative BC survival. Additionally, AKT inhibitor treatment displayed much stronger capacity to abolish shDsg2 and shDsc2 induced progression compared to ERK inhibition, which was due to feedback activation of AKT pathway induced by ERK inhibition. In contrast, all of EGFR, AKT and ERK activities were attenuated, whereas ß-catenin was accumulated in shDsg2 and shDsc2 MCF-7 cells. These results indicate that EGFR-targeted therapy is not a good choice for BC patients with low Dsg2 or Dsc2 expression. Comparatively, AKT inhibitors may be more helpful to triple-negative BC patients with low Dsg2 or Dsc2 expression, while therapies targeting ß-catenin can be considered for luminal BC patients with low Dsg2 or Dsc2 expression. CONCLUSION: Our finding demonstrate that single knockdown of Dsg2 or Dsc2 could promote proliferation, motility and invasion in triple-negative MDA-MB-231 and luminal MCF-7 cells. Nevertheless, the underlying mechanisms were cellular context-specific and distinct.

NLRP3 inflammasome activation triggers severe inflammatory liver injury in N, N-dimethylformamide-exposed mice.

N,N-dimethylformamide (DMF) is a widely utilized chemical solvent with various industrial applications. Previous studies have indicated that the liver is the most susceptible target to DMF exposure, whereas the underlying mechanisms remain to be elucidated. This study aimed to investigate the role of NLRP3 inflammasome in DMF-induced liver injury in mice by using two NLRP3 inflammasome inhibitors, Nlrp3-/- mice, Nfe2l2-/- mice, and a macrophage-depleting agent. RNA sequencing revealed that endoplasmic reticulum (ER) stress and NLRP3 inflammasome-associated pathways were activated in the mouse liver after acute DMF exposure, which was validated by Western blotting. Interestingly, DMF-induced liver injury was effectively suppressed by two inflammasome inhibitors, MCC950 and Dapansutrile. In addition, knockout of Nlrp3 markedly attenuated DMF-induced liver injury without affecting the metabolism of DMF. Furthermore, silencing Nfe2l2 aggravated the liver injury and the NLRP3 inflammasome activation in mouse liver. Finally, the depletion of hepatic macrophages by clodronate liposomes significantly reduced the liver damage caused by DMF. These results suggest that NLRP3 inflammasome activation is the upstream molecular event in the development of acute liver injury induced by DMF.

The potential health risks of short-chain chlorinated paraffin: A mini-review from a toxicological perspective.

Short-chain chlorinated paraffins (SCCPs) are ubiquitously distributed in various environmental matrics due to their wide production and consumption globally in the past and ongoing production and use in some developing countries. SCCPs have been detected in various human samples including serum, milk, placenta, nail, and hair, and internal SCCP levels were found to be positively correlated with biomarkers of some diseases. While the environmental occurrence has been reported in a lot of studies, the toxicity and underlying molecular mechanisms of SCCPs remain largely unknown. The current tolerable daily intakes (TDIs) recommended by the world health organization/international programme on chemical safety (WHO/IPCS, 100 µg/kg bw/d) and the UK Committee on Toxicity (COT, 30 µg/kg bw/d) were obtained based on a no observed adverse effect level (NOAEL) of SCCP from the repeated-dose study (90 d exposure) in rodents performed nearly 40 years ago. Importantly, the health risks assessment of SCCPs in a variety of studies has shown that the estimated daily intakes (EDIs) may approach and even over the established TDI by UK COT. Furthermore, recent studies revealed that lower doses of SCCPs could also result in damage to multiple organs including the liver, kidney, and thyroid. Long-term effects of SCCPs at environmental-related doses are warranted.

[Spatial Characterization of Stable Isotope Composition of Organic Carbon from Farmland Soils in Chongqing].

Soil was sampled from 182 profiles in typical farmlands of Chongqing and analyzed for the stable carbon isotope composition of organic matter (δ13CSOC). The results showed that the values of δ13CSOC for each soil profile were gradually increasing with increasing soil depth, and the mean values were (-23.63±1.53)‰, (-22.43±1.59)‰, and (-21.42±1.90)‰ for surface, middle, and bottom layers, respectively. The δ13CSOC values in the northeastern region of Chongqing tended to be more negative, whereas those in central Chongqing were less negative. Paddy fields showed the most negative values of δ13CSOC, followed by rice-upland rotating fields and upland fields, with the average being (-25.32±0.93)‰, (-23.17±1.37)‰, and (-24.75±1.28)‰ for the surface layers, respectively. For different soil types, the δ13C values in the surface layers were in the order of paddy soil

[Effects of Biodegradable Film Raw Material Particles on Soil Properties, Wheat Growth, and Nutrient Absorption and Transportation].

Biodegradable plastic film is one of the effective ways to solve the problem of white pollution in agriculture. However, its impacts on soil-plant systems are not well documented. In order to provide a basis for the safety evaluation of large-scale application of biodegradable plastic film, pot experiments were conducted to investigate the effects of the types(H, S, and X) and doses(2.5, 10, and 40 g·kg-1) of biodegradable film raw material particles on the soil physiochemical properties, biological properties, growth, and nutrient absorption by wheat (Triticum aestivum L.). The results showed that three types of biodegradable film raw material particles significantly increased soil pH but had no significant effect on soil organic matter content; medium-high doses of H and low-medium doses of S plastic particles had a positive effect on soil nitrification and soil nitrogen availability, whereas X film particles had an inhibitory effect. H film particles increased soil available phosphorus content, and S and X had no significant effect. X film particles increased the content of soil available potassium, but S and H had no significant effect. The effects of three types of biodegradable raw material particles on soil enzyme activities varied with the types and doses of plastic film and enzyme types. With the increase in the doses of plastic film particles, the activities of three kinds of soil enzymes showed a downward trend. Except for the low and medium doses of the S treatment, the other treatments inhibited the growth of wheat, in which X film particles had the greatest inhibitory effect on the biomass of wheat roots, stems, leaves, and grain; with the increase in the doses of film particles, the inhibition effect of wheat biomass was more obvious. For wheat nutrients, the absorption of nitrogen was promoted at low doses and inhibited at high doses, and the three types of film particles inhibited the absorption of phosphorus and potassium. There were significant differences in the distribution ratio of nitrogen and phosphorus between the stems, leaves, and grains of wheat by all the film particles; however, there was no significant difference in the distribution ratio of potassium between those treatments. Correlation analysis showed that wheat biomass was the main factor affecting wheat nutrient accumulation.

[Effects of Different Organic Materials on Absorption and Translocation of Arsenic and Cadmium in Rice].

A pot experiment was carried out to study the impacts of five organic materials (rape straw, broad bean stalk, peat, pig manure compost, and biochar) on the availability of arsenic (As) and cadmium (Cd) in soil, the amount of iron plaque on the root surface, as well as the uptake and translocation of As and Cd in rice grown in an As/Cd co-contaminated yellow paddy soil. The results indicated that the application of organic materials significantly increased the contents of the soil organic matter and the yield of rice. The application of broad bean stalk, peat, pig manure compost, and biochar remarkably increased the soil pH, while the application of rape straw exerted no significant influence. The addition of organic matter reduced the available Cd content by 34.77%-82.69%. However, the effects of organic materials on the availability of As varied with the organic materials. The soil-available As content was significantly increased by the application of pig manure compost and biochar, while it was significantly decreased by adding rape straw and peat. The application of organic materials increased As and Cd contents in the Fe plaques on rice root surface by 28.49%-94.86% and 17.73%-151.03%, respectively. It also reduced the As and Cd contents in brown rice by 27.04%-82.51% and 15.87%-79.45%, respectively. The largest decrease was observed in the biochar treatment. The application of organic materials also remarkably reduced the translocation efficiency of Cd from the root-stem-leaf-grain and that of As from the stem to grain. The correlation analysis revealed that the soil pH, available Cd, and Cd content in the Fe plaques are the major factors influencing the accumulation of Cd in the rice grain. Furthermore, the soil pH, soil organic matter, and As content in the Fe plaques are the major factors influencing the accumulation of As in the rice grain. Therefore, it has been concluded that organic materials could influence the uptake and translocation of As and Cd in rice through changing the soil pH, organic matter content, and As and Cd contents in the Fe plaques.

[Effects of Water Management and Silicon Application on Iron Plaque Formation and Uptake of Arsenic and Cadmium by Rice].

To explore the effects of water management and silicon application on the bioavailability of soil arsenic (As) and cadmium (Cd), and the accumulation of As and Cd in rice, pot experiments were carried out using As/Cd co-contaminated paddy soil from a field in Kaiyang County, Guizhou Province. The experimental treatments had the following five water application modes with and without silicon addition:flooding during the entire growth period (T1); flooding for three weeks (0-105 d) after transplanting with wet irrigation (moisture content 50%-60%) during other growth periods (T2); flooding for three weeks before heading (0-65d), three weeks after heading (84-105d), and wet irrigation during other growth periods (T3); flooding from heading to three weeks after heading (84-105d) and wet irrigation during the other growth periods (T4); and wet irrigation during the entire growth period (T5). The results showed that compared with flooding and wet irrigation, flooding combined with wet irrigation was more conducive to the formation of iron plaque (DCB-Fe) on the surfaces of roots. As and Cd content increased with an increasing of content of DCB-Fe. Silicon application increased soil pH and the content of DCB-As but decreased available As and Cd in the soil and, with the exception of the flooding treatment, the DCB-Fe/Cd content. The shorter the flooding time, the higher the accumulation of Cd and the lower the accumulation of As in each part of the rice. Silicon application increased the biomass of rice but decrease the Cd content of roots, stems, leaves, and grain by 4.23%-31.06%, 11.41%-52.90%, 1.74%-35.73%, and 19.25%-39.76%, respectively. Silicon application also decreased the As content of roots, stems, leaves, and grain by 1.47%-52.60%, 6.12%-63.02%, 2.97%-28.41%, and 16.33%-61.23%, respectively. Among the five modes of water application tested, silicon application combined with the T3 mode achieved the highest rice biomass and lowest rice As and Cd contents. Therefore, it is suggested that selecting water management and silicon application regimes according to the level of As/Cd pollution can effectively decrease the bioavailability of As/Cd in the soil, thereby reducing the accumulation of As/Cd in rice.

[Effects of Organic Amendments on Microbial Biomass Carbon and Nitrogen Uptake by Corn Seedlings Grown in Two Purple Soils].

An incubation experiment and a pot experiment were carried out to investigate the effects of organic materials on microbial biomass carbon (MBC) and nitrogen (MBN) content, dry weight, and nitrogen uptake of maize seedlings grown in an acidic purple soil and a calcareous purple soil. The organic materials used included pig manure biogas residue (PM), cattle manure biogas residue (CM), sludge compost (SC), compost from rural domestic waste both with and without 20% sludge (RWC1 and RWC2, respectively). The results showed that MBC content in the acidic and calcareous purple soils increased by 53.63%-102.91% and 12.14%-137.00%, respectively. The slower the decomposition of organic materials and the higher the C/N ratio, the bigger the MBC content of the soils. Furthermore, MBN contents, which were affected by the different forms of organic, increased by 23.37%-150.08% and 35.02%-160.02%, respectively. The MBC/MBN contents of both soils decreased with the increase in the C/N ratio of the organic materials, but a higher C/N ratio was beneficial for maintaining a higher MBN content over an extended period of time. With the exception of CM, the addition of organic materials improved the biomass of maize seedlings, and their nitrogen uptake and utilization rate in both soils were also significantly enhanced, although these effects were less than that achieved through conventional fertilization. The uptake and utilization of nitrogen followed the order of SC > PM > RWC2 > RWC1. The inhibiting effect of CM was related to its higher C/N ratio, while the promoting effect of the other materials on nitrogen uptake by the corn seedlings increased as soil MBC/MBN content decreased. Therefore, the influence of organic materials on the change and supply of soil nitrogen was not only related to their properties but also to their effects on soil MBC/MBN content.

[Analysis of the Characteristics of Nitrogen and Phosphorus Emissions from Agricultural Non-point Sources on Hanfeng Lake Basin].

To understand the status of agricultural non-point source pollution and to find out the primary pollution sources and the key control areas in the Hanfeng Lake Basin, the discharges of total nitrogen (TN) and total phosphorus (TP) from farming, livestock and poultry breeding, and rural living in thirty-two counties in 2015 were estimated using the pollutant discharge coefficient method. The spatial distribution characteristics of the quality and intensity of the TN and TP emissions from these sources were investigated using the GIS spatial analysis method. Pollution evaluation and source analysis were also carried out using the equivalent pollution load method. The results show that the total loads of TN and TP in the Hanfeng Lake Basin are 2721.42 t and 492.04 t, respectively. The discharge of pollutants is the largest in the Nanhe Basin and the smallest in the area around Hanfeng Lake. The total pollutant loads from the agricultural non-point sources varied greatly, with fertilizer application and livestock and poultry breeding being the main sources. The contribution from fertilizer application is 76.92%, which represents the primary source of TN and TP pollution in the Hanfeng Lake Basin. Among the townships, the equivalent pollution loads of Dunhao, Tieqiao, and Baiqiao are higher than 350 m3·a-1; thus, these are the key control towns. According to the results of the equivalent pollution method and cluster analysis, the 32 counties were divided into four types of pollution areas. These areas are planting-livestock breeding dominant area, fertilizer-livestock breeding dominant area, fertilizer dominant area, and heavily polluted planting dominant area.

NMDA Receptor Antagonist MK801 Protects Against 1-Bromopropane-Induced Cognitive Dysfunction.

Occupational exposure to 1-bromopropane (1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BP-induced cognitive dysfunction. Male Wistar rats were administered with MK801 (0.1 mg/kg) prior to 1-BP intoxication (800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological, and immunological analyses. We found that the spatial learning and memory were significantly impaired in the 1-BP group, and this was associated with neurodegeneration in both the hippocampus (especially CA1 and CA3) and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex. Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.

Paracrine and epigenetic control of CAF-induced metastasis: the role of HOTAIR stimulated by TGF-ß1 secretion.

BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines. Chromatin immunoprecipitation and luciferase reporter assay were performed to explore the transactivation of target LncRNA by CAFs. A series of in vitro assays was performed with RNAi-mediated knockdown to elucidate the function of LncRNA. An orthotopic mouse model of MDA-MB-231 was conducted to confirm the mechanism in vivo. RESULTS: Here we reported that TGF-ß1 was top one highest level of cytokine secreted by CAFs as revealed by cytokine antibody array. Paracrine TGF-ß1 was essential for CAFs induced EMT and metastasis in breast cancer cells, which is a crucial mediator of the interaction between stromal and cancer cells. CAF-CM significantly enhanced the HOTAIR expression to promote EMT, whereas treatment with small-molecule inhibitors of TGF-ß1 attenuated the activation of HOTAIR. Most importantly, SMAD2/3/4 directly bound the promoter site of HOTAIR, located between nucleotides -386 and -398, -440 and -452, suggesting that HOTAIR was a directly transcriptional target of SMAD2/3/4. Additionally, CAFs mediated EMT by targeting CDK5 signaling through H3K27 tri-methylation. Depletion of HOTAIR inhibited CAFs-induced tumor growth and lung metastasis in MDA-MB-231 orthotopic animal model. CONCLUSIONS: Our findings demonstrated that CAFs promoted the metastatic activity of breast cancer cells by activating the transcription of HOTAIR via TGF-ß1 secretion, supporting the pursuit of the TGF-ß1/HOTAIR axis as a target in breast cancer treatment.

[Effect of Particulate Organic Matter on Cadmium Uptake and Transport in Rice].

A pot experiment was carried out to investigate the effects and mechanism of particulate organic matter (POM) on cadmium uptake of rice on purple paddy soil. Organic carbon content in soil and POM and Cd content in POM and rice were analyzed. The results showed that the contents of total soil organic carbon (SOC), dissolved organic carbon (DOC), organic carbon in POM (POM-C), Cd in POM (POM-Cd), and the Cd enrichment factor in POM increased with the application of POM. When POM was applied at a rate of 2.5 g·kg-1, the proportion of POM-C and POM-Cd in soil significantly increased. Application of POM also increased rice plant biomass and enhanced the accumulation of Cd in rice. The Cd content was reduced by 24%-42% in rice roots and increased by 9%-30% in rice shoots with POM application, whereas it was reduced by 17% and 36% in rice grains when the application of POM was 0.5 g·kg-1 and 1.0 g·kg-1, respectively, but increased by 39% when the application of POM was 2.5 g·kg-1. Application of POM had no significant effect on the distribution of Cd in rice roots and shoots, but significantly affected the distribution of Cd in rice grains. The transportation of Cd from shoots to grains was inhibited at low rates of POM, but was promoted at high rates of POM, and consequently increased the Cd content in rice grains. Correlation analyses showed that the content of soil available Cd was the main factor affecting Cd accumulation in rice shoots, and the total content of POM-Cd in soil was the main factor affecting Cd accumulation in rice grains. Therefore, the addition of POM to soil could affect the Cd uptake of rice by changing the content of SOC, DOC, POM-C, POM-Cd, and available Cd in paddy soil.

Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver.

Protein kinase B (PKB/Akt) plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that cytochrome P4502E1 (CYP2E1) plays causal roles in the pathogenesis of alcoholic fatty liver (AFL). We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver. Chronic ethanol exposure had no effects on the protein levels of phosphatidylinositol 3 kinase (PI3K) and phosphatase and tensin homologue deleted on chromosome ten (PTEN), and led to a slight decrease of phosphoinositide-dependent protein kinase 1 (PDK-1) protein level. Ethanol exposure resulted in increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ), an efficient CYP2E1 inhibitor. Interestingly, N-acetyl-L-cysteine (NAC) significantly attenuated chronic ethanol-induced hepatic fat accumulation and the decline of Akt phosphorylation at Thr308. In the in vitro studies, Akt phosphorylation was suppressed in CYP2E1-expressing HepG2 (CYP2E1-HepG2) cells compared with the negative control HepG2 (NC-HepG2) cells, and 4-HNE treatment led to significant decrease of Akt phosphorylation at Thr308 in wild type HepG2 cells. Lastly, pharmacological activation of Akt by insulin-like growth factor-1 (IGF-1) significantly alleviated chronic ethanol-induced fatty liver in mice. Collectively, these results indicate that CYP2E1-induced oxidative stress may be responsible for ethanol-induced suppression of Akt phosphorylation and pharmacological modulation of Akt in liver may be an effective strategy for the treatment of ethanol-induced fatty liver.

[Enrichment Characteristics of Heavy Metals in Particulate Organic Matter of Purple Paddy Soil].

Twenty purple paddy soil samples were collected from the Prefectures of Hechuan and Tongliang, Chongqing, and sieved into particulate organic matter (0.053-2 mm, POM), sand fraction (0.053-2 mm) and fine soil fraction (<0.053 mm). By comparing the concentration and distribution of soil organic carbon (SOC) and heavy metals among different components, the enrichment characteristics of POM for heavy metals (Cu, Zn, Pb and Zn) and its relationship with soil properties such as pH, CEC, clay content (<0.002 mm) and SOC were investigated. The result showed that the contents of POM fraction in purple paddy soils ranged from 7.31 to 44.76 g·kg-1, with an average level of 19.20 g·kg-1, while the carbon contents ranged from 96.61 to 263.17 g·kg-1, which were significantly higher than those of their original soils and other two fractions. The contribution rates of organic carbon by POM to the total organic carbon of soils ranged from 8.63% to 48.62%, which accounted for a large pool of organic carbon. The average enrichment factors of POM fraction to Cu, Zn, Pb and Cd were 3.35, 1.14, 2.88 and 2.14, respectively. Compared with sand fraction and fine soil fraction, POM fraction showed a significantly higher contribution rate to heavy metals, which were 6.02%, 2.22%, 5.24% and 3.21%. In addition, the enrichment ability and contribution rate of POM to Cu and Pb were obviously greater than those of Zn and Cd. There was a significant positive correlation between content of POM fraction and soil properties such as SOC, pH, CEC and clay content, in which SOC was the key factor. The POM-C content and total amount were significantly correlated with SOC and clay content. The pH value, SOC and POM-C amount had a significant or extremely significant correlation with the amount of heavy metals in POM, in which SOC was the most critical one. Comparing with other heavy metals, the amount of zinc in POM had the highest regression coefficient and the closest relationship with soil properties.

[Effects of Tillage on Distribution of Heavy Metals and Organic Matter Within Purple Paddy Soil Aggregates].

A long-term experiment was utilized to study the effects of tillage methods on the contents and distribution characteristics of organic matter and heavy metals (Cu, Zn, Pb, Cd, Fe and Mn) in aggregates with different sizes (including 1-2, 0.25-1, 0.05-0.25 mm and < 0.05 mm) in a purple paddy soil under two tillage methods including flooded paddy field (FPF) and paddy-upland rotation (PR). The relationship between heavy metals and organic matter in soil aggregates was also analyzed. The results showed that the aggregates of two tillage methods were dominated by 0.05-0.25 mm and < 0.05 mm particle size, respectively. The contents of organic matter in each aggregate decreased with the decrease of aggregate sizes, however, compared to PR, FPF could significantly increase the contents of organic matter in soils and aggregates. The tillage methods did not significantly affect the contents of heavy metals in soils, but FPF could enhance the accumulation and distribution of aggregate, organic matter and heavy metals in aggregates with diameters of 1-2 mm and 0.25-1 mm. Correlation analysis found that there was a negative correlation between the contents of heavy metals and organic matter in soil aggregates, but a positive correlation between the amounts of heavy metal and organic matter accumulated in soil aggregates. From the slope of the correlation analysis equations, we could found that the sensitivities of heavy metals to the changes of soil organic matters followed the order of Mn > Zn > Pb > Cu > Fe > Cd under the same tillage. When it came to the same heavy metal, it was more sensitive in PR than in FPF.

Reprogramming carcinoma associated fibroblasts by AC1MMYR2 impedes tumor metastasis and improves chemotherapy efficacy.

Carcinoma associated fibroblasts (CAFs) produce a nutrient-rich microenvironment to fuel tumor progression and metastasis. Reactive oxygen species (ROS) levels and the inflammation pathway co-operate to transform CAFs. Therefore, elucidating the mechanism mediating the activity of CAFs might identify novel therapies. Abnormal miR-21 expression was reported to be involved in the conversion of resident fibroblasts to CAFs, yet the factor that drives transformation was poorly understood. Here, we reported that high miR-21 expression was strongly associated with lymph node metastasis in breast cancer, and the activation of the miR-21/NF-кB was required for the metastatic promoting effect of CAFs. AC1MMYR2, a small molecule inhibitor of miR-21, attenuated NF-кB activity by directly targeting VHL, thereby blocking the co-precipitation of NF-кB and ß-catenin and nuclear translocation. Taxol failed to constrain the aggressive behavior of cancer cells stimulated by CAFs, whereas AC1MMYR2 plus taxol significantly suppressed tumor migration and invasion ability. Remodeling and depolarization of F-actin, decreased levels of ß-catenin and vimentin, and increased E-cadherin were also detected in the combination therapy. Furthermore, reduced levels of FAP-α and α-SMA were observed, suggesting that AC1MMYR2 was competent to reprogram CAFs via the NF-кB/miR-21/VHL axis. Strikingly, a significant reduction of tumor growth and lung metastasis was observed in the combination treated mice. Taken together, our findings identified miR-21 as a critical mediator of metastasis in breast cancer through the tumor environment. AC1MMYR2 may be translated into the clinic and developed as a more personalized and effective neoadjuvant treatment for patients to reduce metastasis and improve the chemotherapy response.

[Effect of Montmorillonite on Fractions and Availability of Phosphorus in Soils Applied with Organic Fertilizer].

An incubation experiment was carried out to study the effect of montmorillonite on pH, the fractions and availability of phosphorus in a sandy yellow soil (SY) and a mineral flavicant soil (MF) applied with biogas residues of swine manure (BSR). The rates of montmorillonite applied were 0%, 5%, 7.5% and 10%, respectively. The results indicated that soil pH was not affected by BSR, but was significantly increased by montmorillonite. In both soils, application of BSR caused an increase in the content and proportion of Al-P during the incubation, and an increase in the content but a slight decrease in the proportion of Fe-P in later period of incubation. The concentration of O-P was not markedly changed, but its proportion was decreased by applying BSR in both soils. The changes of Ca-P varied with soils. BSR had no significant influence on Ca-P content, but decreased the proportion of Ca-P in SY, meanwhile, it increased both Ca-P content and proportion in MF. Addition of montmorillonite in soils applied with BSR decreased the contents and proportions of Al-P and O-P, and the proportion of Fe-P did not change the contents of Fe-P, but increased the content and proportion of Ca-P in SY. In MF, montmorillonite could decrease the contents and proportions of Fe-P and O-P, and the proportion of Al-P did not affect the content of Al-P, but increased the contents and proportions of Ca-P greatly. The contents of available phosphorus (A-P) were enhanced by 17.9%-38.0% and 17.1%-33.7% in SY and MF respectively, and the phosphorus activation coefficient (PVC) was significantly improved in both soils by applying BSR. The contents of A-P were reduced by 8.8%-35.5% and 1.1%-11.6% in SY and MF respectively. Correlation analysis showed that montmorillonite reduced the availability of phosphorus through increasing pH and contents of Ca-P, decreasing the content of Al-P in SY, and through increasing pH and decreasing content of Fe-P in MF. The availability of phosphorus in SY was influenced more obviously than that in MF by montmorillonite.

[Emissions Characteristics of Greenhouse Gas from Sewage Sludge Composting Process in Winter].

Sludge composting is an efficient way to realize the reclamation of waste sludge, while the Green House Gas (GHG) accompanying with it has raised great concern worldwide. However, we do lack the primary data in this area and a great uncertainty of the effect and GHG emission characteristics of sludge composting process in low-temperature environment also exists. This study is aiming to investigate the emission characteristics of GHG from composting in low-temperature environment by applying two different bulking agents to dewatered urban sludge. The results showed that aerobic composting could go smoothly even in an environment with lower temperature, yet the maturity was low due to a sharp drop of pile temperature at the stage of maturing. Sawdust treatment could reduce the total nitrogen loss compared with cornstalk treatment, while its GHG emission equivalence was higher (169.45 and 133.13 kg·t-1 dry sludge, respectively). The accumulative CH4 emissions of sawdust and cornstalk were 0.648 and 0.689 kg·t-1 dry sludge, respectively, of which over 75% was from the first two weeks; total N2O emissions of sawdust and cornstalk were 0.486 and 0.365 kg·t-1 dry sludge, of which more than 90% came from the decomposting process. On the whole, because of the relatively short duration of high temperature as well as the low temperature during mature stage, the process had an especially low emission of CH4 but a relatively high discharge of N2O. For composting in low-temperature environment, necessary measures should be taken to control N2O emission in the late period in order to realize GHG reduction.

[Effect of Different Organic Materials on Nitrogen Mineralization in Two Purple Soils].

An aerobic incubation experiment was conducted at a constant temperature to investigate the differences in nitrogen mineralization between an acid purple soil and a calcareous purple soil amended with five organic materials including biogas residues of pig manure(PM), cow manure(CW), sewage sludge compost(SC), rural waste compost(RWC1)and the compost of rural waste plus 20% of sewage sludge(RWC2). The results showed that the organic nitrogen forms in these materials followed the order of amino acid N> hydrolysable unidentified N> ammonium N> non-hydrolysable N> amino sugar N. Application of organic materials could significantly improve the contents of NH4+-N and NO3--N in acid purple soil, PM and SC could significantly improve the content of NH4+-N, but CM reduced the content of NO3--N in calcareous purple soil. Except for CM, which had no significant effect on the quantity of nitrogen mineralization in acid purple soil, but decreased the quantity of nitrogen mineralization in calcareous purple soil, applying the organic materials could significantly increase the quantity of nitrogen mineralization in both soils. Correlation analysis showed that the quantity of nitrogen mineralization was significantly and positively correlated with the contents of amino acid N and ammonium N, but were significantly and negatively correlated with the content of organic matter and the C/N of organic materials. Overall, the results illustrated that the effect of organic materials on the mineralization of nitrogen varied with soil types and the characteristics of organic materials, especially the content of organic matter, C/N and the fractions of organic nitrogen in organic materials.

Changes in microRNAs associated with Twist-1 and Bcl-2 overexpression identify signaling pathways.

Epithelial-mesenchymal transition (EMT) is regulated by multiple signal transduction pathways. Twist-1 is one of the most important transcription factors in these pathways. In a previous study, we found that Bcl-2 enhanced the role of Twist-1 in EMT. Coexpression of Twist-1 and Bcl-2 may play an import role in vasculogenic mimicry (VM) through regulation of EMT. Moreover, regulators of EMT and VM are known to be important targets for microRNAs (miRNAs). To better understand how these critical pathways are induced by coexpression of Twist-1 and Bcl-2, we performed a comprehensive comparative bioinformatics analysis using microarrays on HCCs that overexpressed Twist-1 and Bcl-2. Eleven miRNAs associated with coexpression of Twist-1 and Bcl-2 were selected from the comprehensive analysis of miRNA microarray and ChIP-seq analysis. Changes in miRNAs were associated with significant differences in the expression of genes involved in signal transduction pathways related to processes including tumor invasion, metastasis, angiogenesis, and tumor cell shape. We confirmed the role of Twist-1 and Bcl-2 coexpression in HCC cells using wound healing assays, invasion assays, and 3D Matrigel assays. Furthermore, the role of miR-27a as a crucial regulator of EMT and VM was confirmed in HCC cells by RT-PCR and western blot analysis. These findings provide evidence that Bcl-2 enhances the role of Twist-1 in VM and EMT through miRNAs.