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Background: Due to the short biological half-life and serious side effects (especially for heart and kidney), the application of Doxorubicin (Dox) in clinical therapy is strictly limited. To overcome these shortcomings, a novel sustained release formulation of doxorubicin-loaded dextran-coated superparamagnetic iron oxide nanoparticles (Dox-DSPIONs) was prepared. Objective: The purpose of this study was to evaluate the intracellular uptake behavior of Dox-DSPIONs and to investigate their pharmacokinetics and biodistribution properties. Method: Confocal laser scanning microscopy was employed to study the intracellular uptake and release properties of Dox from Dox-DSPIONs in SMMC-7721 cells. Simple high-performance liquid chromatography with fluorescence detection (HPLC-FLD) method was established to study the pharmacokinetics and biodistribution properties of Dox-DSPIONs in vivo after intravenous administration and compared with free Dox. Results: Intracellular uptake experiment indicated that Dox could be released sustainedly from Dox-DSPIONs over time. The pharmacokinetics parameters displayed that the T1/2and AUC0-24h of Dox-DSPIONs were higher than those of free Dox, while the Cmax of Dox-DSPIONs was significantly lower than that of free drug. The biodistribution behaviors of the drug were altered by Dox-DSPIONs in mice, which showed obvious liver targeting, and significantly reduced the distribution of the drug in the heart and kidney. Conclusion: Dox-DSPIONs have the sustained-release property in vitro and in vivo, which could significantly prolong blood circulation time, improve bioavailability, and reduce the side effects of Dox. Therefore, the novel formulation of the Dox-DSPIONs has the potential as a promising drug delivery system in cancer therapy.

Histone acetylation is a well-characterized epigenetic modification controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalanced histone acetylation has been observed in many primary cancers. Therefore, efforts have been made to find drugs or small molecules such as HDAC inhibitors that can revert acetylation levels to normal in cancer cells. We observed dose-dependent reduction in the endogenous and exogenous protein expression levels of KAT8 (also known as human MOF), a member of the MYST family of HATs, and its corresponding histone acetylation at H4K5, H4K8, and H4K16 in chemotherapy drug gemcitabine (GEM)-exposed T24 bladder cancer (BLCA) cells. Interestingly, the reduction in MOF and histone H4 acetylation was inversely proportional to GEM-induced γH2AX, an indicator of chemotherapy drug effectiveness. Furthermore, pGL4-MOF-Luc reporter activities were significantly inhibited by GEM, thereby suggesting that GEM utilizes an MOF-mediated anti-BLCA mechanism of action. In the CCK-8, wound healing assays and Transwell® experiments, the additive effects on cell proliferation and migration were observed in the presence of exogenous MOF and GEM. In addition, the promoted cell sensitivity to GEM by exogenous MOF in BLCA cells was confirmed using an Annexin V-FITC/PI assay. Taken together, our results provide the theoretical basis for elucidating the anti-BLCA mechanism of GEM.

To explore possible approaches to differentiating rat bone marrow mesenchymal stem cells (BMSCs) into retinal ganglion-like cells and to demonstrate the dynamic changes in protein expression profiles of BMSCs throughout the differentiation. BMSCs were isolated from adult rats and cultured in medium conditioned by neonatal rat retinal cells to induce BMSC differentiation into retinal ganglion-like cells. Immunostaining for neurofilament, nestin, Map2, and Thy1.1 was used to follow the differentiation process. Two types of protein arrays were employed to profile the BMSCs, the differentiated retinal ganglion-like cells, and the primary retinal ganglion cells (RGCs) using the Biomarker Wizard System. After 7 days of culture in conditioned medium, cells showing a neural-cell-like modality appeared. The differentiated retinal ganglion-like cells showed that network-like connections were positive for nestin, neurofilament, Map2, and Thy1.1. In total, 16 marker proteins were highly expressed in both retinal ganglion-like cells and RGCs and no obvious expression was observed in BMSCs. Among them, nine proteins were expressed more highly in RGCs than in retinal ganglion-like cells. BMSCs can be induced to differentiate into retinal ganglion-like cells by neonatal rat retinal cells, and the induced cells show protein profiles resembling those of isolated RGCs.

Acid treated P25 catalysts (HP25-x, x represents the treatment temperature) were successfully fabricated via a simple soaking and drying process for photocatalytic H2 production. After acid treatment, a substantial number of –OH groups were obtained on the surface of HP25-60, which can act as Bronsted acid sites providing hydrogen protons for H2 generation. Besides, more oxygen vacancies and Ti3+ sites were also created on the HP25-60 surface after acid treatment, which could enhance the carrier separation and transfer efficiency by capturing more electrons and holes, respectively. The H2 production over HP25-60 reached 4853 μmol h−1 with Pt as a co-catalyst, which is 7.1 times higher than 679 μmol h−1 of bare TiO2. Three favorable factors for H2 photogeneration, i.e. Bronsted acid sites, oxygen vacancies and Ti3+ sites, can be introduced on a catalyst surface via a simple one-step acid strategy, which can be applied as a universally-applicable modification method for valence-alternative metal oxide semiconductors for enhanced H2 photogeneration.

Understanding the soil fertility status and heavy metal pollution is of great significance for targeted environmental management and governance in a basin. The Dawen River Basin (DRB), a sub-basin in the lower Yellow River area in China, was taken as the study area. A total of 107 surface soil samples were collected in the DRB in October 2019, and the sampling points were mainly located within 10 km of the mainstream of the Dawen River. Based on the measured soil nutrient indicators (organic matter, total nitrogen, total phosphorus, and total potassium) and heavy metal contents (As, Hg, Cd, Cr, and Pb), the status and spatial distribution of soil fertility and heavy metal pollution in the DRB were evaluated by combining the use of the Nemerow index method, the land accumulation index method, and the general Kriging interpolation method. The results showed that the soil fertility in the DRB was generally at a normal level or below, while some areas of Taian City, Xintai City, and Ningyang County had relatively high soil nutrient content. The content of heavy metals in the soil of the DRB was mainly at a safe level, but the single pollution index and geo-accumulation index implied that there was light to moderate pollution of heavy metals in individual samples, and the content of heavy metals in urban and industrial agglomerations is relatively high.

Cell embedment into a solid support matrix is considered essential for the culture of intestinal epithelial organoids and tumoroids, but this technique presents challenges that impede scalable culture expansion, experimental manipulation, high-throughput screening and diagnostic applications. We have developed a low-viscosity matrix (LVM) suspension culture method that enables efficient establishment and propagation of organoids and tumoroids from the human large intestine. Organoids and tumoroids cultured in LVM suspension recapitulate the morphological development observed in solid matrices, with tumoroids reflecting the histological features and genetic heterogeneity of primary colorectal cancers. We demonstrate the utility of LVM suspension culture for organoid and tumoroid bioreactor applications and biobanking, as well as tumoroid high-throughput drug sensitivity testing. These methods provide opportunities for the study and use of patient-derived organoids and tumoroids from the large intestine., Given the practical limitations of solid matrix-based protocols in organoid culture, Yumiko Hirokawa et al. assess the ability of low-concentration Matrigel conditions to promote intestinal organoid growth. Their results suggest that a low-viscosity culture system can improve live cell yield compared to the existing dome method, while maintaining similar morphology, and represents a useful approach for high-throughput applications of organoids.

Purpose Vascular endothelial growth factor (VEGF) plays implicated roles in diabetic retinopathy (DR). The role of roundabout 4 (Robo 4) in angiogenesis and vasculogenesis is controversial; however, the interdependent relationship between these two factors has not been studied in DR. This study determined the colocalization of VEGF and Robo4 in fibrovascular membranes (FVM) from patients with proliferative diabetic retinopathy (PDR). MicroRNA (miRNA)-mediated modulation of VEGF and Robo4 was explored in diabetic rats and ARPE-19 tissue culture cells under hyperglycemia. Methods VEGF and Robo4 co-expression in the FVM was analyzed using immunofluorescence. VEGF and Robo4 levels were determined in diabetic retinas and ARPE-19 tissue culture cells under high glucose using western blotting and RT-qPCR. MicroRNA agomir was intraocularly injected to increase miR-15a expression and downregulate VEGF and Robo4 levels in diabetic retinas. Results VEGF and Robo4 colocalization in FVM vessels was observed. Increased VEGF levels were consistent in diabetic retinas and ARPE-19 tissue culture cells cultured under hyperglycemia. Robo4 decreased in ARPE-19 tissue culture cells exposed to hyperglycemia for 72 h, whereas it increased in diabetic rat retinas. Several miRNAs were differentially expressed during DR progression. Furthermore, miR-15a agomir injection inhibited high levels of VEGF and Robo4 in diabetic retinas. Conclusions VEGF and Robo4 were co-expressed in FVMs from PDR patients. In the early stages of DR, VEGF was upregulated and contributed to DR development, whereas, in the late stage of DR, VEGF and Robo4 worked together to aggravate DR progression. However, miR-15a could downregulate VEGF and Robo4 to ameliorate DR development.

Converting lignin into value-added products in current lignocellulosic biorefineries has been challenging, which in turn restricts the commercialization of many lignocellulosic biorefineries. In this work, a two-stage alkali-oxygen assisted liquid hot water pretreatment (AlkOx) was proposed as the first step of biorefinery. This alkali-oxygen pretreatment facilitated biomass fractionation by solubilizing majority of lignin in water-soluble fraction, while remaining most of cellulose and hemicellulose in water-insoluble fraction. As a result, biomass saccharification was significantly improved by selective removal and oxidative modification of lignin through alkali-oxygen pretreatment. Moreover, lignin residues from both pretreatment hydrolysate and enzymatic hydrolysate were shown to be favorable adsorbents for Pb(II) ions, with adsorption capacity of 263.16 and 90.91 mg/g, respectively. Results demonstrated that this integrated process could not only improve biomass saccharification but also enable lignin valorization, which encouraged the holistic utilization of lignin residues as part of an integrated biorefinery.

Herein we report an isostructural solid solution of Mg2(Ti1-xSnx)O4:0.002Mn (0 ≤ x ≤ 1) in which cation substitution leads to the presence of two different Mn luminescence centers. When Mn sources of different valance states (MnCO3/MnO2/Mn3O4) were introduced into Mg2TiO4, the self-redox reaction of MnCO3 occurred in air that can be proved by experimental results, from Mn2+→ Mn4+→ Mn3+ and eventually Mn3O4 can be obtained. Low valance state Mn2+/3+ ions in Mn3O4 can be further oxidized to Mn4+ ions by O2 in Mg2TiO4:Mn. Mn4+ red emission can be observed along with oxygen defects-induced blue emission in Mg2(Ti1-xSnx)O4:Mn (0 ≤ x V o • ) to Mn3+. This is the first time that compositional-tunability that induces Mn ions of different valance states luminescent behaviors and further interprets its spectral transition mechanism.

This work proposed a two-stage pretreatment with alkaline sulphonation and steam treatment, and investigated its efficiency for converting Eucalyptus woody biomass to fermentable sugars and bioethanol. Comparing with steam pretreatment and subsequent sulphonation, this alkaline sulphonation-steam pretreatment improved carbohydrate recovery by maintaining a more neutral pH throughout the pretreatment process, while promoting the enzymatic digestibility of biomass through lignin removal and modification. Results showed that the alkaline sulphonation-steam pretreatment caused lignin removal of 69.37% and 120.28 mmol/kg acid groups incorporation into substrate, both of which could lead to significantly improved cellulose accessibility. About 80% of the sugars present in the original carbohydrate (cellulose and hemicellulose) were released, which could be recovered after pretreatment and enzymatic hydrolysis. The sugars released from enzymatic hydrolysis of substrate pretreated by alkaline sulphonation-steam pretreatment could be efficiently converted to ethanol, indicating that alkaline sulphonation-steam two-stage pretreatment is a promising pretreatment approach of lignocellulosic biomass for the production of biofuels.

In this study, acrylamide-containing crosslinking agents 2,4-diacrylamidebenzenesulfonic acid (AC-DABS1) and 2,5-diacrylamidebenzenesulfonic acid (AC-DABS2) were synthesized and applied to cotton fabric as durable press finishing agents under alkaline conditions. The target products were characterized by high-performance liquid chromatography (HPLC) and proton nuclear magnetic resonance. The stability of the acrylamide group in alkaline solution was investigated by model compound para-acrylamidebenzenesulfonic acid. The efficiency of AC-DABS1 and AC-DABS2 as durable press finishing agents was examined and compared by testing the wrinkle recovery angle (WRA), tearing strength retention (TSR) and washing durability under different conditions using the steaming process. The performance of fabric treated with 1,3,5-triacroylaminohexahydro-s-triazine (FAP) was also investigated and compared with those treated with acrylamide-containing crosslinking agents. The results showed that the anti-crease effects of FAP were better than those of the new synthesized agents. However, the new synthesized agents have the advantage of water solubility and low cost. The fabric treated with new synthesized agents presented satisfactory WRA and TSR, indicating that AC-DABS1 and AC-DABS2 can be utilized as effective alkaline crosslinking agents. In addition, the different performance of the FAP-treated fabric and fabric treated with the new synthesized agents was illustrated by the HPLC method.

The chemical heat sink of endothermic hydrocarbon fuels (EHFs) is generally dependent on its thermal cracking in the cooling channel, which is accompanied and limited by the formation of carbon deposit. In this work, HF-1 (a kerosene-based EHF) was electrically heated in the rectangular, square, and circular channels with the same cross-sectional area under 3.5 MPa to study the effect of cooling channel geometric structures on the thermal cracking and carbon deposition behaviors. It was found that under similar conditions (inlet flow rate of fuel, pressure, outlet temperature), conversions of HF-1 in both rectangular and square channels were slightly higher than that in the circular one with high selectivity to methane but lower selectivities to the primary cracking products (such as 1-hexene and 1-heptene, etc.). In addition, more carbon deposits were formed in the rectangular and square channels, especially around the corners of channels. Based on the CFD simulation, the possible reasons should be ascri...

Background Glutamate oxaloacetate transaminase 1 (GOT1) regulates cellular metabolism through coordinating the utilization of carbohydrates and amino acids to meet nutrient requirements. KRAS mutated cancer cells were recently shown to rely on GOT1 to support long-term cell proliferation. The aim of the present study was to address the role of GOT1 in the metabolic adaption of cancer cells. Methods GOT1-null and knockdown cell lines were established through CRISPR/Cas9 and shRNA techniques. The growth properties, colony formation ability, autophagy and selected gene expression profiles were analysed. Glucose deprivation decreased the viability of the GOT1-null cells and rescue experiments were conducted with selected intermediates. The redox NADH/NAD+ homeostasis as well as lactate secretion were determined. GOT1 expression levels and correlation with survival rates were analysed in selected tumor databases. Results Inhibition of GOT1 sensitized the cancer cells to glucose deprivation, which was partially counteracted by oxaloacetate and phosphoenol pyruvate, metabolic intermediates downstream of GOT1. Moreover, GOT1-null cells accumulated NADH and displayed a decreased ratio of NADH/NAD+ with nutrient depletion. The relevance of GOT1 as a potential target in cancer therapy was supported by a lung adenocarcinoma RNA-seq data set as well as the GEO:GSE database of metastatic melanoma where GOT1 expression was increased. High levels of GOT1 were further linked to poor survival as analysed by the GEPIA web tool, in thyroid and breast carcinoma and in lung adenocarcinoma. Conclusions Our study suggests an important role of GOT1 to coordinate the glycolytic and the oxidative phosphorylation pathways in KRAS mutated cancer cells. GOT1 is crucial to provide oxaloacetate at low glucose levels, likely to maintain the redox homeostasis. Our data suggest GOT1 as a possible target in cancer therapy. Electronic supplementary material The online version of this article (10.1186/s12885-018-4443-1) contains supplementary material, which is available to authorized users.

Insights into reaction mechanism were vital to direct naphtha catalytic cracking process to produce light olefins. In order to reveal influences of reaction pathways modulation on light olefins production, Zr-ZSM-5, Ag-ZSM-5, and the regenerated HZSM-5 (ZSM-5(R2)) were prepared and employed in n -pentane catalytic cracking. It was found that light olefins yield obtained over Zr-ZSM-5, Ag-ZSM-5, and ZSM-5(R2) at 500 °C was 58%, 81%, and 113% higher than that over the parent HZSM-5 (12.0%), respectively. Promotion on light olefins production caused by Zr-incorporation can be attributed to the enhancement of hydride transfer reactions increasing the utilization of Bronsted acid sites and the catalytic activity accompanied with the proximate stability compared to the parent HZSM-5. Different from Zr-ZSM-5, Ag-ZSM-5 and ZSM-5(R2) respectively introduced dehydrogenation cracking and redox cracking to n -pentane catalytic cracking, which selectively promoted the formation of light olefins and significantly enhanced n -pentane protolytic cracking. However, both Ag-ZSM-5 and ZSM-5(R2) went through a rapid deactivation at 550 °C, which was probably due the selective enhancement of alkenes accelerating the side reactions to coke formation.

Somatic mosaicism is widespread among tissues and could indicate distinct tissue origins of circulating cell-free DNA (cfDNA), DNA fragments released by lytic cells into the blood. By investigating the alignment patterns of whole genome sequencing reads with the genomic DNA of different tissues, we found that the read distributions formed type-specific patterns in some regions as a result of somatic mosaicism. We then utilized this information to construct a tissue-of-origin mapping model and evaluated its predictive performance on whole genome sequencing data from tissue and cfDNA samples. In total, 1,545 tissue samples associated with 13 cancer types were included, and identification of the tissue of origin achieved a specificity of 82% and a sensitivity of 80%. Furthermore, a total of 30 cfDNA samples from lung cancer and liver cancer patients and healthy controls were analyzed to predict their tissues of origin with a specificity of 87% and a sensitivity of 87%. Our results show that read distribution patterns from whole genome sequencing could be used to identify cfDNA tissues of origin with high accuracy, suggesting the potential application of our model to early cancer detection and diagnosis.

Owing to the implementation of increasingly stringent water conservation policies and regulations, the pulp and paper mill industry must make increased efforts to meet the limits for pollutant emissions. The primary pretreatment and secondary biochemical treatment methods used currently generally fail to meet the country-specific environmental regulations, and the wastewater must be processed further even after being subjected to secondary biochemical treatments. In this work, we synthesized Fe3O4/MnO2 nanocomposites (FMNs) with a flower-like structure for use in the heterogeneous photocatalytic treatment of biotreated papermaking wastewater. FMNs1.25, which were formed using a KMnO4/Fe3O4 molar ratio of 1.25, could be separated readily using an external magnetic field and exhibited higher photocatalytic activity than those of the other samples as well as MnO2 and Fe3O4. The effects of various experimental parameters on the photocatalytic activity of FMNs1.25, including the initial pH of the wastewater and the catalyst dosage, were determined. The common chemical oxygen demand (CODCr) reduction rate in the case of this sample reached 56.58% within 120 min at a pH of 3, the CODCr of effluent after treatment was 52.10 mg/L. Further, even under neutral conditions, the CODCr of the treated effluent was below the current limit for discharge in China. Moreover, the nanocomposites exhibited good recyclability, and their catalytic activity did not decrease significantly even after five usage cycles. This study should serve as a platform for the fabrication of effective photocatalysts for the advanced treatment of biotreated papermaking effluent and refractory organic wastewater.

Transactivation of p21 (cyclin-dependent kinase inhibitor 1A, CDKN1A) is closely related to the recruitment of transcription cofactors at the p53 responsive elements (p53REs) in its promoter region. Human chromatin remodeling enzyme INO80 can be recruited to the p53REs of p21 promoter and negatively regulates p21. As one of the key subunits of the INO80 complex, YY1 has also been confirmed to bind to the p53RE sites of p21 promoter. Importantly, YY1 was recently reported to be bound and stabilized by BCCIP (BRCA2 and CDKN1A-interacting protein). Therefore, we hypothesized that the YY1/BCCIP complex plays an important role in regulating the transactivation of p21. Here we present evidence that the YY1/BCCIP complex coordinatively regulates p53RE-mediated p21 transactivation. We first confirmed the cross-interaction between YY1, BCCIP, and p53, suggesting an intrinsic link between three proteins in the regulation of p21 transcription. In dual luciferase assays, YY1 inhibited p53RE-mediated luciferase activity, whereas BCCIP revealed the opposite effect. More interestingly, the region 146&ndash, 270 amino acids of YY1, which bound to BCCIP, increased p53-mediated luciferase activity, indicating the complexity of the YY1/BCCIP complex in co-regulating p21 transcription. Further in-depth research confirmed the co-occupancy of YY1/BCCIP with p53 at the p53RE-proximal region of p21. Lentiviral-mediated knockdown of BCCIP inhibited the recruitment of p53 and YY1 at the p53RE proximal region of p21, however, this phenomenon was reversed by expressing exogenous YY1, suggesting the collaborative regulation of YY1/BCCIP complex in p53RE-mediated p21 transcription. These data provide new insights into the transcriptional regulation of p21 by the YY1/BCCIP complex.

Intimately coupled photocatalysis and biodegradation (ICPB) provides novel insights into the removal of refractory pollutants. However, the practical application of ICPB was limited by low bacterial loading density and low microbial activity. Herein, an environment-friendly, low-cost and renewable biocarrier was fabricated using natural loofah sponge. In comparison to polyurethane carrier, after employing loofah sponge in ICPB, the tetracycline hydrochloride (TCH) removal rate was increased by ∼6.6 %, the mineralization was increased by ∼9.2 %, and almost all photocatalytic products were degraded. Compared with conventional catalyst coating strategies, our powder spraying method enables the exterior surface of biocarrier to be firmly coated by the photocatalyst, while the inside of biocarrier was extremely clean to accumulate bacteria. The biocarrier provided a higher loading density and a higher microbial activity of bacteria than that of polyurethane carrier. Besides, it can regulate the bacterial community to have more favorable members to biodegrade the photocatalysis intermediates. In summary, using loofah sponge as biocarrier could be an effective approach for enhancing the biodegradation performance of ICPB.

To elucidate the molecular mechanisms underlying the therapeutic activity of ginsenoside Rg3 (Gs-Rg3) in the context of hepatocellular carcinoma (HCC). Methods Relevant databases were searched to identify protein targets that were both dysregulated and implicated in HCC, as well as targeted by Gs-Rg3. Generation of a protein-protein interaction network facilitated the selection of connected nodes for the construction of a shared disease- and drug-target interaction network model, and topological analysis identified the most highly connected nodes. Targets were annotated with their associated Gene Ontology terms, followed by Kyoto Encyclopedia of Genes and Genomes biological pathway enrichment analysis. In vitro experiments using 2 hours CC cell lines (Bel-7402 and HCCLM3) were performed to investigate the impact of Gs-Rg3 on cell proliferation, viability, cell cycle, cyclin D1 and sirtuin 2 (SIRT2) levels, and global cellular histone acetylation (specifically H3K18ac and H4K16ac). Results Network pharmacology suggested that Gs-Rg3 synergistically targets multiple proteins and pathways relevant to HCC pathogenesis, including those involved in cell cycle and proliferation. In vitro experiments confirmed that Gs-Rg3 dose-dependently inhibits cell proliferation and viability; induces G1 phase cell cycle arrest; decreases cyclin D1, cyclin-dependent kinase 2 (CDK2), and SIRT2 levels; and enhances global H3K18ac and H4K16ac. Conclusions Hypotheses derived from the network analysis were confirmed in vitro. Gs-Rg3 induces G1 phase cell cycle arrest, concomitant with decreased cyclin D1 and CDK2 levels, suggesting a possible mechanism for inhibiting proliferation. In addition, Gs-Rg3 decreases SIRT2 levels, concomitant with enhanced global H3K18ac and H4K16ac. These findings provide a theoretical basis and a support for further preclinical study of the safety and antineoplastic molecular mechanisms of Gs-Rg3, with the goal of eventual clinical translation.

In this paper, a series of self-crosslinking waterborne polyurethane (WPU) dispersions with side chain, which is (3-(2-Aminoethyl)aminopropyl)trimethoxysilane (AEAPTMS) as the diamine chain extender, were prepared. The characteristics of WPU with different dosages of AEAPTMS were evaluated, including particle size, crystallinity, surface performance, water resistance and thermal stability. It was demonstrated that AEAPTMS was successfully incorporated into the WPU from Fourier-transform infrared spectroscopy (FT-IR). Once the content of AEAPTMS increased to 5 %, the WPU dispersions became gelatinous. That is, the siloxane groups were hydrolyzed into a cross-linked structure during the emulsification process. The particle size enlarged with the increasing dosage of AEAPTMS in transmission electron microscopy (TEM). The X-ray photoelectron spectroscopy showed that the silane in the cross-linked WPU migrated freely towards the WPU film surface. The addition of AEAPTMS enhanced the tensile strength, hydrophobicity, water resistance and thermal stability of WPU film. Meanwhile, the elongation at break and crystallinity of WPU films were declined. Besides, interestingly, the glass transition temperature of WPU films followed the trend of first rising and then falling. By adding wetting agent, antifoaming agent, adhesion promoter and flatting agent into WPU, the water-based varnish was prepared. The pencil hardness, water resistance, adhesion and anti-adhesion of water-based varnish were best in the application on the stainless steel substrate when the WPU sample was Si-WPU-3.

Doxorubicin (Dox) is one of the most widely used chemotherapeutic agents for many types of cancer, including hepatocellular carcinoma. However, clinical applications of Dox are limited due to its non-selective cytotoxicity that results in severe adverse effects. To tackle this problem targeted delivery of Dox exclusively to tumour milieu has become clinically prioritised. In this study, we first synthesized and validated Dextran coated GoldMag Nanoparticles (DGMNs) as a potential delivery vehicle for Dox. We then evaluated the cytotoxicity of Dox-DGMNs, the drug and carrier composites, under guidance of external magnetic field (EMF) in hepatocellular carcinoma cell lines and in tumour grafts. Intriguingly, DGMNs exhibited the capacity to prolong Dox release in vitro; hence, Dox-DGMNs significantly enhanced the therapeutic efficiency of the drug in vitro and in vivo, especially under EMF. However, DGMNs were able to significantly decrease systemic adverse effects and inhibit tumour growth compared to the intravenous application of free Dox. Molecular analysis revealed that tumour cells were more affected by Dox-DGMNs with EMF than Dox-DGMNs or Dox alone in terms of apoptosis and DNA damage marker expression. Overall, DGMNs exhibited a substantial potential to serve as a promising drug delivery carrier for magnetically targeted cancer therapy.

Mouse model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) is generally accepted as an ideal object to study on the carcinogenesis mechanisms of human colorectal cancer (CRC). The genomic responses to the AOM/DSS treatment in mouse that possibly lead to elucidation of CRC pathological mechanism are still poorly understood. For the first time, we investigated the cancer genome landscape of AOM/DSS mouse model by exome sequencing, to testify its molecular faithfulness to human CRC. Of 14 neoplastic samples, 7575 somatic variants were identified, which resulted in 2507 mutant genes and exhibited a large diversity in both colorectal aberrant crypt foci (ACF) and tumors even those tissues that were gained from the similar morphology or same treatment period. Cross-species comparison of the somatic variants demonstrated the totally different patterns of variable sites, mutant genes and perturbed pathways between mouse and human CRC. We therefore come to a conclusion that the tumorigenesis at genomic level in AOM/DSS model may not be properly comparable with that in human CRC, and the molecular mechanism elicited from this animal model should be carefully evaluated.

Klebsiella pneumoniae is one of the most significant nosocomial pathogens in healthcare settings. Over the last decade, K. pneumoniae producing extended-spectrum β-lactamases (ESBLs) have been prevalent worldwide. ESBL-producing isolates are considered resistant to all penicillins, cephalosporins and aztreonam, and carbapenems are the only β-lactams that still remain consistently active.1 But owing to the overuse of carbapenems, resistant strains have become endemic in many countries as well. In addition, most carbapenem-resistant K. pneumoniae (CR-KP) are resistant to other antimicrobial classes, referred to as multidrug-resistant (MDR) and extensively drug-resistant strains.2 The lack of active antimicrobials against CR-KP continues to threaten public health.

Dextran-coated superparamagnetic iron oxide nanoparticles (DSPIONs) have gained considerable interest, because of their biocompatibility and biosafety in clinics. Doxorubicin (Dox), a widely used chemotherapeutic drug, always has limited applications in clinical therapy due to its serious side effects of dose-limiting irreversible cardiotoxicity and myelo suppression. Herein, DSPIONs were synthesized and developed as magnetic carriers for doxorubicin. The Dox-DSPION conjugates were evaluated in the in vitro test of Dox release, which showed pH-dependence with the highest release percentage of 50.3% at pH 5.0 and the lowest release percentage of 11.8% in a physiological environment. The cytotoxicity of DSPIONs and Dox-DSPIONs evaluated by the MTT assay indicated that DSPIONs had no cytotoxicity and the conjugates had significantly reduced the toxicity (IC50 = 1.36 μg mL(-1)) compared to free Dox (IC50 = 0.533 μg mL(-1)). Furthermore, confocal microscopic data of cell uptake suggest that less cytotoxicity of Dox-DSPIONs may be attributed to the cellular internalization of the conjugates and sustainable release of Dox from the formulation in the cytoplasm. More importantly, the results from the rabbit VX2 liver tumor model test under an external magnetic field showed that the conjugates had approximately twice the anti-tumor activity and two and a half times the animal survival rate, respectively, compared to free Dox. Collectively, our data have demonstrated that Dox-DSPIONs have less toxicity with better antitumor effectiveness in in vitro and in vivo applications, suggesting that the conjugates have potential to be developed into chemo-therapeutic formulations.

We propose a statistical algorithm MethylPurify that uses regions with bisulfite reads showing discordant methylation levels to infer tumor purity from tumor samples alone. MethylPurify can identify differentially methylated regions (DMRs) from individual tumor methylome samples, without genomic variation information or prior knowledge from other datasets. In simulations with mixed bisulfite reads from cancer and normal cell lines, MethylPurify correctly inferred tumor purity and identified over 96% of the DMRs. From patient data, MethylPurify gave satisfactory DMR calls from tumor methylome samples alone, and revealed potential missed DMRs by tumor to normal comparison due to tumor heterogeneity. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0419-x) contains supplementary material, which is available to authorized users.

Ozone can be used in treatment of industrial recycling cooling water. In order to guide practice more efficiently, the dynamics equation of ozone decomposition in recycling cooling water was established. The research deducted mathematical model of the decomposition. It is that: -d[O3]/[O3]dt ? k'1[OH?] + k''2[OH?]x[CODCr]. Then experiment water of different concentrations multiple was confected, adjusted alkalinty with NaHCO3, ozone of different concentrations was led into, ozone decomposition rate was mensurated. When pH was 8.0?8.5?9.0?9.5 and CODCr was 1?3?6?7 mg/L, the interrelated data was determined. The dynamics equation of ozone decomposition at the experimental condition is: ?d[O3]/[O3]dt = 75460×[OH?] +4.990×[OH?]0.228[CODCr]. Analysing the mathetics model, we can see that affecting decomposition factors are not only [OH?], but also CODCr in water, include the microbe, organic compound, reductive inorganic compound and so on. In practical using, it should monitor water quality continuously or intermittently, adjust ozone quantity according to the pH and CODCr in the water, at the same time, it also should control CODCr of the system so that it can ensure treatment effect.

Hydrophobic charge induction chromatography (HCIC) is a mixed-mode chromatography that achieves high adsorption capacity by hydrophobic interaction and facile elution by pH-induced charge repulsion between the solute and ligand. This article reports a new medium, 5-aminoindole-modified Sepharose (AI-Sepharose) for HCIC. The adsorption equilibrium and kinetics of lysozyme and bovine serum albumin (BSA) to AI-Sepharose were determined by batch adsorption experiments at different conditions to provide insight into the adsorption properties of the medium. The influence of salt type on protein adsorption to AI-Sepharose corresponded with the trend for other hydrophobicity-related properties in literature. Both ligand density and salt concentration had positive influences on the adsorption of the two proteins investigated. The adsorption capacity of lysozyme, a basic protein, decreased rapidly when pH decreased from 7 to 3 due to the increase of electrostatic repulsion, while BSA, an acidic protein, achieved maximum adsorption capacity around its isoelectric point. Dynamic adsorption experiments showed that the effective pore diffusion coefficient of lysozyme remained constant at different salt concentrations, while that of BSA decreased with increased salt concentration due to its greater steric hindrance in pore diffusion. High protein recovery by adsorption at pH 7.10 elution at pH 3.0 was obtained at a number of NaCl concentrations, indicating that the adsorbent has typical characteristics of HCIC and potentials for applications in protein purification.

cAMP and protein kinase A (PKA) are widely known as signaling molecules that are important for the induction of adipogenesis. Here we show that a strong increase in the amount of cAMP inhibits the adipogenesis of 3T3-L1 fibroblast cells. Stimulation of PKA activity suppresses adipogenesis and, in contrast, inhibition of PKA activity markedly accelerates the adipogenic process. As adipogenesis progresses, there is a significant increase in the expression level of PKA regulatory subunits and a corresponding decrease in PKA activity. Moreover, treatment of 3T3-L1 cells with epidermal growth factor (EGF) stimulates PKA activity and blocks adipogenesis. Inhibition of PKA activity abolishes this suppressive effect of EGF on adipogenesis. Moreover, activation of PKA induces serine/threonine phosphorylation, reduces tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and the association between PKA and IRS-1. Taken together, our study demonstrates that PKA has a pivotal role in the suppression of adipogenesis. cAMP at high concentrations can suppress adipogenesis through PKA activation. These findings could be important and useful for understanding the mechanisms of adipogenesis and the relevant physiological events.

Adenosine 3',5'-cyclic monophosphate (cAMP) and transforming growth factor-beta are important regulators of many biological processes. In this study we investigated the effect and its potential mechanism of cAMP on transforming growth factor-beta1- and serum deprivation-induced apoptosis in Mv1Lu cells. Transforming growth factor-beta1 treatment or serum deprivation induces apoptotic response in Mv1Lu cells. Forskolin, a cAMP-elevating agent, or 8-Bromo-cAMP (8-B-cAMP), a cell permeable cAMP analogue, inhibited the cell proliferation and markedly enhanced apoptosis induced by transforming growth factor-beta1, but completely suppressed serum deprivation-induced apoptosis. Furthermore, forskolin decreased the Akt phosphorylation, and the inhibition of phosphatidylinositol-3 kinase by LY294002 sensitized Mv1Lu cells to transforming growth factor-beta1-induced apoptosis. In addition, forskolin treatment induced tyrosine phosphorylation of epidermal growth factor receptor. Inhibition of epidermal growth factor receptor by specific inhibitor PD153035 blocked the cAMP-mediated suppression of serum deprivation-induced apoptosis. The results indicate that cAMP exerts its opposite effects in transforming growth factor-beta1- and serum deprivation-induced apoptosis via a mechanism involving the modulation of signaling components of phosphatidylinositol-3-kinase/Akt and epidermal growth factor receptor in Mv1Lu cells.