Gd-encapsulated carbonaceous dots for accurate characterization of tumor vessel permeability in magnetic resonance imaging.

The assessment of vascular permeability of malignant tumor plays an important role in the diagnosis and treatment of cancer. Dynamic contrast-enhanced magnetic resonance image (DCE-MRI) using Gd-encapsulated carbonaceous dots and Gd-DTPA-BMA as contrast agents was performed in 4T1 mouse breast cancer and HCC827 human non-small-cell lung cancer (NSNLC) xenograft models. Histopathological parameters of tumor vascularity microvessel density (MVD), microvessel area (MVA), endothelial area (EA) and α-SMA CD31 Co-expression (α-SMA/CD31%) were compared with the DCE-MRI parameters. Results demonstrated that DCE-MRI with the new nanoparticle Gd@C-dots can noninvasively evaluate vascular permeability. Ktrans measured by DCE-MRI with Gd@C-dots is an accurate parameter for the characterization of tumor permeability. EA is a reliable microvessel parameter to evaluate vessel permeability.

BcXyl, a ß-xylosidase Isolated from Brunfelsia Calycina Flowers with Anthocyanin-ß-glycosidase Activity.

Brunfelsia calycina flowers lose anthocyanins rapidly and are therefore well suited for the study of anthocyanin degradation mechanisms, which are unclear in planta. Here, we isolated an anthocyanin-ß-glycosidase from B. calycina petals. The MS/MS (Mass Spectrometry) peptide sequencing showed that the enzyme (72 kDa) was a ß-xylosidase (BcXyl). The enzyme showed high activity to p-Nitrophenyl-ß-d-galactopyranoside (pNPGa) and p-Nitrophenyl-ß-d-xylopyranoside (pNPX), while no activity to p-Nitrophenyl-ß-d-glucopyranoside (pNPG) or p-Nitrophenyl-ß-D-mannopyranoside (pNPM) was seen. The optimum temperature of BcXyl was 40 °C and the optimum pH was 5.0. The enzyme was strongly inhibited by 1 mM D-gluconate and Ag⁺. HPLC (High Performance Liquid Chromatography) analysis showed that BcXyl catalyzed the degradation of an anthocyanin component of B. calycina, and the release of xylose and galactose due to hydrolysis of glycosidic bonds by BcXyl was detected by GC (Gas Chromatography) /MS. A full-length mRNA sequence (2358 bp) of BcXyl (NCBI No. MK411219) was obtained and the deduced protein sequence shared conserved domains with two anthocyanin-ß-glycosidases (Bgln and BadGluc, characterized in fungi). BcXyl, Bgln and BadGluc belong to AB subfamily of Glycoside hydrolase family 3. Similar to BcPrx01, an anthocyanin-degradation-related Peroxidase (POD), BcXyl was dramatically activated at the stage at which the rapid anthocyanin degradation occurred. Taken together, we suggest that BcXyl may be the first anthocyanin-ß-glycosidase identified in higher plants.

Efficient dye adsorption of mesoporous activated carbon from bamboo parenchyma cells by phosphoric acid activation.

In order to solve the environmental damage caused by the discharge of dyes as industrial wastewater, the development of efficient and sustainable adsorbents is the key, while most of the previous studies on bamboo parenchyma cells have focused on their microstructural, functional and mechanical properties, and few of the properties in adsorption have been investigated. To evaluate the role of the unique microstructure of bamboo parenchyma cells on adsorption after carbonization and activation, PC-based activated carbon (PPAC) was fabricated by the phosphoric acid activation method and tested for adsorption using methylene blue (MB). The effect of mesoporous structure on MB adsorption was investigated in detail using PPAC-30C impregnated with phosphoric acid at a concentration of 30%. The results showed that the adsorption performance was influenced by single-factor experiments (e.g., pH, activated carbon dosing). The adsorption isotherms and kinetics could conform to the Langmuir model (R2 = 0.983-0.994) and pseudo-second-order kinetic model (R2 = 0.822-0.991) respectively, and the maximum MB adsorption capacity of adsorbent was 576 mg g-1. The adsorption mechanism of MB on PPAC-30C includes physical adsorption, electrostatic attraction, hydrogen bonding, and the π-π conjugation effect, which was dominated by physical adsorption. The results of this study show that PPAC has good application prospects for cationic dye removal.

Realization of sextuple polarization states and interstate switching in antiferroelectric CuInP2S6.

Realization of higher-order multistates with mutual interstate switching in ferroelectric materials is a perpetual drive for high-density storage devices and beyond-Moore technologies. Here we demonstrate experimentally that antiferroelectric van der Waals CuInP2S6 films can be controllably stabilized into double, quadruple, and sextuple polarization states, and a system harboring polarization order of six is also reversibly tunable into order of four or two. Furthermore, for a given polarization order, mutual interstate switching can be achieved via moderate electric field modulation. First-principles studies of CuInP2S6 multilayers help to reveal that the double, quadruple, and sextuple states are attributable to the existence of respective single, double, and triple ferroelectric domains with antiferroelectric interdomain coupling and Cu ion migration. These findings offer appealing platforms for developing multistate ferroelectric devices, while the underlining mechanism is transformative to other non-volatile material systems.

Optical Modulation of MoTe2/Ferroelectric Heterostructure via Interface Doping.

Optical modulation through interface doping offers a convenient and efficient way to control ferroelectric polarization, thereby advancing the utilization of ferroelectric heterostructures in nanoelectronic and optoelectronic devices. In this work, we fabricated heterostructures of MoTe2/BaTiO3/La0.7Sr0.3MnO3 (MoTe2/BTO/LSMO) and demonstrated opposite ultraviolet (UV) light-induced polarization switching behaviors depending on the varied thicknesses of MoTe2. The thickness-dependent band structure of MoTe2 film results in interface doping with opposite polarity in the respective heterostructures. The polarization field of BTO interacts with the interface charges, and an enhanced effective built-in field (Ebi) can trigger the transfer of massive UV light-induced carriers in both MoTe2 and BTO films. As a result, the interplay among the contact field of MoTe2/BTO, the polarization field, and the optically excited carriers determines the UV light-induced polarization switching behavior of the heterostructures. In addition, the electric transport characteristics of MoTe2/BTO/LSMO heterostructures reveal the interface barrier height and Ebi under opposite polarization states, as well as the presence of inherent in-gap trap states in MoTe2 and BTO films. These findings represent a further step toward achieving multifield modulation of the ferroelectric polarization and promote the potential applications in optoelectronic, logic, memory, and synaptic ferroelectric devices.

Occurrence and prevalence of antibiotic resistance genes and pathogens in an industrial park wastewater treatment plant.

Antibiotic resistance genes (ARGs) and pathogens are emerging environmental pollutants that pose a threat to human health and ecosystem. Industrial park wastewater treatment plants (WWTPs) treat large amounts of comprehensive wastewater derived from industrial production and park human activity, which is possible a source of ARGs and pathogens. Therefore, this study investigated the occurrence and prevalence of ARGs, ARGs hosts and pathogens and assesses the ARGs health risk in the biological treatment process in a large-sale industrial park WWTP using metagenomic analysis and omics-based framework, respectively. Results show that the major ARG subtypes are multidrug resistance genes (MDRGs), macB, tetA(58), evgS, novA, msbA and bcrA and the ARGs main hosts were genus Acidovorax, Pseudomonas, Mesorhizobium. In particular, all determined ARGs genus level hosts are pathogens. The total removal percentage of ARGs, MDRGs and pathogens were 12.77 %, 12.96 % and 25.71 % respectively, suggesting that the present treatment could not efficiently remove these pollutants. The relative abundance of ARGs, MDRGs and pathogens varied along biological treatment process that ARGs and MDRGs were enriched in activated sludge and pathogens were enriched in both secondary sedimentation tank and activated sludge. Among 980 known ARGs, 23 ARGs (e.g., ermB, gadX and tetM) were assigned into risk Rank I with characters of enrichment in the human-associated environment, gene mobility and pathogenicity. The results indicate that industrial park WWTPs might serve as an important source of ARGs, MDRGs, and pathogens. These observations invite further study of the origination, development, dissemination and risk assessment of industrial park WWTPs ARGs and pathogens.

Strong Electron-Phonon Coupling Mediates Carrier Transport in BiFeO3.

The electron-phonon interaction is known as one of the major mechanisms determining electrical and thermal properties. In particular, it alters the carrier transport behaviors and sets fundamental limits to carrier mobility. Establishing how electrons interact with phonons and the resulting impact on the carrier transport property is significant for the development of high-efficiency electronic devices. Here, carrier transport behavior mediated by the electron-phonon coupling in BiFeO3 epitaxial thin films is directly observed. Acoustic phonons are generated by the inverse piezoelectric effect and coupled with photocarriers. Via the electron-phonon coupling, doughnut shape carrier distribution has been observed due to the coupling between hot carriers and phonons. The hot carrier quasi-ballistic transport length can reach 340 nm within 1 ps. The results suggest an effective approach to investigating the effects of electron-phonon interactions with temporal and spatial resolutions, which is of great importance for designing and improving electronic devices.

Antitumor effect of BPR-DC-2, a novel synthetic cyclic cyanoguanidine derivative, involving the inhibition of MDR-1 expression and down-regulation of p-AKT and PARP-1 in lung cancer.

In our previous study, a series of novel cyclic cyanoguanidine compounds, eg. 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4- pyrimidinone derivatives have been successfully synthesized and showed remarkable cytotoxicity in several cancer cell lines. In this present study, it is our aim to screen more potential candidates among the cyclic pyridyl cyanoguanidine compounds (BPR-DC-1, 2, 3) by in vitro and in vivo studies for the therapy of lung cancer, alternatively. Our results showed that BPR-DC-2 significantly inhibited proliferation of tumor cells with an IC50 of 3.60 ± 1.27 and 14.81 ± 4.23 µM in human lung carcinoma cells, H69 and A549, respectively by the MTT assay at 48 hr; BPR-DC-2 also obviously suppressed the tumor proliferation and MDR-1 gene expression, even induced cell apoptosis in the ex vivo histocultured lung tumor. We further demonstrated that, in the nude mouse model of metastatic lung cancer, BPR-DC-2 could diminish the tumor mass, retard the progression of metastasis, and prolong the survival time. In addition, it was found that BPR-DC-2 exerted its anti-tumor effects through the inhibition of MDR-1 gene expression and down-regulation of tumor anti-apoptosis signals (activated p-AKT and over-expression of PARP-1) by western blotting analysis. In conclusion, in this present study we have demonstrated that BPR-DC-2, derived from a series of novel synthetic cyclic cyanoguanidine compounds, has proved its potential as an anti-tumor drug candidate in treating lung cancer.

Affibody-Modified Gd@C-Dots with Efficient Renal Clearance for Enhanced MRI of EGFR Expression in Non-Small-Cell Lung Cancer.

PURPOSE: Gd-encapsulated carbonaceous dots (Gd@C-dots) have excellent stability and magnetic properties without free Gd leakage, therefore they can be considered as a safe alternative T1 contrast agent to commonly used Gd complexes. To improve their potential for cancer diagnosis and treatment, affibody-modified Gd@C-dots targeting non-small-cell lung cancer (NSCLC) EGFR-positive tumors with enhanced renal clearance were developed and synthesized. MATERIALS AND METHODS: Gd@C-dots were developed and modified with Ac-Cys-ZEGFR:1907 through EDC/NHS. The size, morphology, and optical properties of the Gd@C-dots and Gd@C-dots-Cys-ZEGFR:1907 were characterized. Targeting ability was evaluated by in vitro and in vivo experiments, respectively. Residual gadolinium concentration in major organs was detected with confocal imaging and inductively coupled plasma mass spectrometry (ICP-MS) ex vivo. H&E staining was used to assess the morphology of these organs. RESULTS: Gd@C-dots with nearly 20 nm in diameter were developed and modified with Ac-Cys-ZEGFR:1907. EGFR expression in HCC827 cells was higher than NCI-H520. In cell uptake assays, EGFR-expressing HCC827 cells exhibited significant MR T1WI signal enhancement when compared to NCI-H520 cells. Cellular uptake of Gd@C-dots-Cys-ZEGFR:1907 was reduced, when Ac-Cys-ZEGFR:1907 was added. In vivo targeting experiments showed that the probe signal was significantly higher in HCC827 than NCI-H520 xenografts at 1 h after injection. In contrast to Gd@C-dots, Gd@C-dots-Cys-ZEGFR:1907 nanoparticles can be efficiently excreted through renal clearance. No morphological changes were observed by H&E staining in the major organs after injection of Gd@C-dots-Cys-ZEGFR:1907. CONCLUSION: Gd@C-dots-Cys-ZEGFR:1907 is a high-affinity EGFR-targeting probe with efficient renal clearance and is therefore a promising contrast agent for clinical applications such as diagnosis and treatment of NSCLC EGFR-positive malignant tumors.

Oral delivery of peptide drugs using nanoparticles self-assembled by poly(gamma-glutamic acid) and a chitosan derivative functionalized by trimethylation.

In the study, chitosan (CS) was conjugated with trimethyl groups for the synthesis of N-trimethyl chitosan (TMC) polymers with different degrees of quaternization. Nanoparticles (NPs) self-assembled by the synthesized TMC and poly(gamma-glutamic acid) (gamma-PGA, TMC/gamma-PGA NPs) were prepared for oral delivery of insulin. The loading efficiency and loading content of insulin in TMC/gamma-PGA NPs were 73.8 +/- 2.9% and 23.5 +/- 2.1%, respectively. TMC/gamma-PGA NPs had superior stability in a broader pH range to CS/gamma-PGA NPs; the in vitro release profiles of insulin from both test NPs were significantly affected by their stability at distinct pH environments. At pH 7.0, CS/gamma-PGA NPs became disintegrated, resulting in a rapid release of insulin, which failed to provide an adequate retention of loaded insulin, while the cumulative amount of insulin released from TMC/gamma-PGA NPs was significantly reduced. At pH 7.4, TMC/gamma-PGA NPs were significantly swelled and a sustained release profile of insulin was observed. Confocal microscopy confirmed that TMC40/gamma-PGA NPs opened the tight junctions of Caco-2 cells to allow the transport of insulin along the paracellular pathway. Transepithelial-electrical-resistance measurements and transport studies implied that CS/gamma-PGA NPs can be effective as an insulin carrier only in a limited area of the intestinal lumen where the pH values are close to the p K a of CS. In contrast, TMC40/gamma-PGA NPs may be a suitable carrier for transmucosal delivery of insulin within the entire intestinal tract.

Analysis of progress and challenges for various patterns of c-MET-targeted molecular imaging: a systematic review.

BACKGROUND: Mesenchymal-epithelial transition factor also named c-MET is a receptor tyrosine kinase for the hepatocyte growth factor that plays a pivotal role in tumorigenesis. c-MET-targeted therapies have been tested in preclinical models and patients, with significant benefits for cancer treatment. In recent years, many studies have shown that the expression level and activation status of c-MET are closely correlated to c-MET-targeted therapy response and clinical prognosis, thus highlighting the importance of evaluating the c-MET status during and prior to targeted therapy. Molecular imaging allows the monitoring of abnormal alterations of c-MET in real time and in vivo. RESULTS: In this review, we initially summarize the recent advances in c-MET-targeted molecular imaging, with a special focus on the development of imaging agents ranging in size from monoclonal antibody to small molecule. The aim of this review is to report the preclinical results and clinical application of all molecular imaging studies completed until now for in vivo detection of c-MET in cancer, in order to be beneficial to development of molecular probe and the combination of molecular imaging technologies for in vivo evaluation of c-MET. Various molecular probe targeted to c-MET possesses distinctive advantages and disadvantages. For example, antibody-based probes have high binding affinity but with long metabolic cycle as well as remarkable immunogenicity. CONCLUSIONS: Although studies for c-MET-targeted molecular imaging have made many important advances, most of imaging agents specifically target to extracellular area of c-MET receptor; however, it is difficult to reflect entirely activation of c-MET. Therefore, small molecule probes based on tyrosine kinase inhibitors, which could target to intracellular area of c-MET without any immunogenicity, should be paid more attention.

Synthesis of a novel glycoconjugated chitosan and preparation of its derived nanoparticles for targeting HepG2 cells.

In the study, a novel chitosan (CS) derivative conjugated with multiple galactose residues in an antennary fashion (Gal-m-CS) was synthesized. A galactosylated CS (Gal-CS) was also prepared by directly coupling lactobionic acid on CS. Using an iontropic gelation method, CS and the synthesized Gal-CS and Gal-m-CS were used to prepare nanoparticles (CS, Gal-CS, and Gal-m-CS NPs) for targeting hepatoma cells. TEM examinations showed that the morphology of all three types of NPs was spherical in shape. No aggregation or precipitation of NPs in an aqueous environment was observed during storage for all studied groups, as a result of the electrostatic repulsion between the positively charged NPs. Little fluorescence was observed in HepG2 cells after incubation with the FITC-labeled CS NPs. The intensity of fluorescence observed in HepG2 cells incubated with the Gal-m-CS NPs was stronger than that incubated with the Gal-CS NPs. These results indicated that the prepared Gal-m-CS NPs had the highest specific interaction with HepG2 cells among all studied groups, via the ligand-receptor-mediated recognition.