Amphiphilic branched polymer-nitroxides conjugate as a nanoscale agent for potential magnetic resonance imaging of multiple objects in vivo.

BACKGROUND: In order to address the potential toxicity of metal-based magnetic resonance imaging (MRI) contrast agents (CAs), a concept of non-metallic MRI CAs has emerged. Currently, paramagnetic nitroxides (such as (2,2,5,5-tetramethylpyrrolidine-1-oxyl, PROXYL), (2,2,6,6-tetramethylpiperidine-1-oxide, TEMPO), etc.) are being extensively studied because their good stability and imaging mechanism are similar to metal-based contrast agents (such as Gd3+ chelate-based clinical CAs). However, a lower relaxivity and rapid in vivo metabolism of nitroxides remain to be addressed. Previous studies have demonstrated that the construction of macromolecular nitroxides contrast agents (mORCAs) is a promising solution through macromolecularization of nitroxides (i.e., use of large molecules to carry nitroxides). Macromolecular effects not only increase the stability of nitroxides by limiting their exposure to reductive substances in the body, but also improve the overall 1H water relaxation by increasing the concentration of nitroxides and slowing the molecular rotation speed. RESULTS: Branched pDHPMA-mPEG-Ppa-PROXYL with a high molecular weight (MW = 160 kDa) and a nitroxides content (0.059 mmol/g) can form a nanoscale (~ 28 nm) self-assembled aggregate in a water environment and hydrophobic PROXYL can be protected by a hydrophilic outer layer to obtain strong reduction resistance in vivo. Compared with a small molecular CA (3-Carboxy-PROXYL (3-CP)), Branched pDHPMA-mPEG-Ppa-PROXYL displays three prominent features: (1) its longitudinal relaxivity (0.50 mM- 1 s- 1) is about three times that of 3-CP (0.17 mM- 1 s- 1); (2) the blood retention time of nitroxides is significantly increased from a few minutes of 3-CP to 6 h; (3) it provides long-term and significant enhancement in MR imaging of the tumor, liver, kidney and cardiovascular system (heart and aortaventralis), and this is the first report on nitroxides-based MRI CAs for imaging the cardiovascular system. CONCLUSIONS: As a safe and efficient candidate metal-free magnetic resonance contrast agent, Branched pDHPMA-mPEG-Ppa-PROXYL is expected to be used not only in imaging the tumor, liver and kidney, but also the cardiovascular system, which expands the application scope of these CAs.

Probing active microbes involved in Bt-containing rice straw decomposition.

Transgenic Bacillus thuringiensis (Bt) rice extends significant protection against insect pests and meets the increasing demands for food and energy. Many studies have been conducted investigating the impacts of Bt rice to the agricultural ecosystem, but much less attention has been given to efforts attempting to determine how the presence of Bt rice influences and shapes the microbial community, especially the active microbes. Stable isotope probing and high-throughput sequencing were employed to explore the active microbes involved in Bt-containing straw decomposition. Compared to its near isoline, the Bt straw contained higher contents of total N, total P, total K, lignin, cellulose, and Cry1Ab toxin protein. These chemical differences did not affect the decomposition rate but significantly changed the active microbial decomposer communities. During the decomposition of Bt-containing straw, fungi were more affected than bacteria. Agromyces, Terrabacter, Microbacterium, Glycomyces, and Kribbella were the most representative unique (existed only in the Bt treatments and appeared at the early stage) bacterial genera, and Trichoderma was the most representative unique fungal genus in the Bt straw decomposition. By using similarity index calculation and function prediction, the significant differences between Bt straw and non-Bt straw treatments were found to be transient for both microbial taxa and functional traits. These results suggested that Bt rice has a significant but transient impact on soil microbes in terms of microbial straw decomposition.

Fabrication of Antiswelling Loose Nanofiltration Membranes via a "Selective-Etching-Induced Reinforcing" Strategy for Bioseparation.

With diverse selectivity, higher permeance, and good antifouling property, loose polyamide nanofiltration (NF) membranes can be potentially deployed in various bioseparation applications. However, the loose NF membrane with a low crosslinking degree generally suffers from the alkali-induced pore swelling during chemical cleaning, resulting in degradation of separation performance with time. In this work, we conceive a novel strategy to tailor the separating layer through alkaline post-etching following the interfacial polymerization process, where piperazine and tannic acid (TA) were used as water-phase monomers, and trimesoyl chloride (TMC) and ferric acetylacetonate were employed as organic monomers in n-hexane. Thereinto, the polyester network formed by TA and TMC was selectively etched by alkaline treatment, thus obtaining a loose NF membrane, whose structure and performance could be facilely tailored by controlling the TA ratio and the etching pH. As a result, the well-designed loose NF membrane exhibited higher flux, better selectivity, and more stable separation performance in a long-term filtration of diluted cane molasses. Interestingly, the obtained loose NF membrane showed excellent antiswelling ability during alkaline cleaning because of network locking induced by Fe3+ chelation, decrease in the carboxyl proportion (more hydroxyl generation due to the ester bond hydrolysis), and enhanced interface interaction between the separation layer and the sublayer attributed to catechol adhesion effect. Therefore, such a "selective-etching-induced reinforcing" strategy could endow the polyamide NF membrane with both loose and antiswelling separation layer in a reliable and scalable way, which provides a new perspective for preparing highly selective and stable NF membrane for resource recovery.

Custom-Tailoring Loose Nanofiltration Membrane for Precise Biomolecule Fractionation: New Insight into Post-Treatment Mechanisms.

Loose nanofiltration (NF) membranes with diverse selectivity can meet the great demands in various bioseparation applications. Thus, a facile strategy to tune the properties such as pore size, surface charge, and hydrophilicity of the NF membrane is required to produce tailor-made loose NF membranes without changing the existing production line. Herein, we systematically investigated the post-treatment of the nascent poly(piperazine amide) NF membranes using different reagents (organic acids, weak bases, organic solvents and ionic liquid (IL)). Various characterizations revealed that the skin/separation layer became looser and permeance was promoted with the decrease of salt rejection in varying degrees. It was found that the O/N ratio did not rigorously represent the cross-linking degree of the skin layer, because besides the hydrolysis of the residual acyl chloride impeding the amido bond formation, the breaking of existing amido bonds and the grafting of free trimesoyl chloride molecules on the nascent membranes could also increase the O/N ratio during post-treatments. Then three mechanisms including hydrolysis, swelling rearrangement and capping reaction effects were proposed to better understand the membrane properties variations. All these effects resulted in larger pore size of the NF membrane, and the hydrolysis/capping effect might increase negative charge and hydrophilicity on the membrane, while the swelling rearrangement could produce less defective skin structure. These three effects might be involved together during a single treatment. Finally, the NF membrane post-treated by N-hexane could efficiently separate antibiotics and NaCl with the highest permeate flux, whereas the one post-treated by ionic liquid outperformed others for the decoloration of cane molasses (much more efficient than NF270, DL, and NTR7450 membranes). The long-term operating stability of the post-treated membranes selected was also confirmed by a continuous crossflow filtration for 15 h with regular alkaline cleaning.

Reductive microenvironment responsive gadolinium-based polymers as potential safe MRI contrast agents.

Accumulation of nano-scale contrast agents in body tissues potentially induces adverse effects associated with free Gd(iii) ion release from the nano-scale system, such as nephrogenic systemic fibrosis and gadolinium deposition in the brain tissue. A novel formulation strategy was proposed herein for Gd-based macromolecular MRI contrast agents (Gd-mCAs), which may significantly reduce Gd(iii) retention but maintain sufficient imaging contrast. Biodegradable poly[N-(1,3-dihydroxypropyl)methacrylamide] copolymers (pDHPMA) were synthesized from N-(1,3-dihydroxypropyl)methacrylamide (DHPMA) as a monomer and enzyme-responsive short peptide (GFLG) as a chain transfer agent. Small molecular Gd-chelate (Gd-DOTA) was conjugated onto the copolymer backbone through a sulfide bond or a GSH-sensitive cleavable disulfide bond to produce two novel Gd-mCAs (pDHPMA-Cy5.5-DOTA-Gd or pDHPMA-Cy5.5-SS-DOTA-Gd) for tumor diagnosis. Their relaxivities were 10.49 and 10.24 mM-1 s-1 respectively, which were significantly higher than that of DTPA-Gd (3.97 mM-1 s-1). Compared with pDHPMA-Cy5.5-DOTA-Gd, pDHPMA-Cy5.5-SS-DOTA-Gd had a shorter Gd(iii) retention time but maintained a sufficient contrast efficacy. We have demonstrated that the conjugation of small molecular Gd-chelate to biodegradable macromolecular carriers through a ROX-sensitive biocleavable disulfide bond may be an efficient strategy for formulating safe biodegradable Gd-based pDHPMA copolymers as MRI contrast agents.

Redox imbalance contributed differently to membrane damage of cucumber leaves under water stress and Fusarium infection.

Redox-associated events are important in plant development and responses to environmental stresses. In this study, we investigated spatial redox responses of cucumber (Cucumis sativus L.) leaves to biotic stress (Fusarium infection) or abiotic stress (water stress). Plants were grown under hydroponic conditions and either treated with polyethylene glycol to simulate drought or infected with Fusarium oxysporum f. sp. cucumerinum. Both water stress and Fusarium infection restricted cucumber growth and were associated with cellular plasma-membrane damage, reactive oxygen species accumulation, and changes in antioxidants; however, the responses to each stress were distinctive. Under water stress, H2O2 generation at the leaf edge increased 29.7% compared with that at the centre but with Fusarium infection there was a relative 10.4% decrease at the edge. These changes correlated with changes in antioxidants and linked enzyme activities. The key sources of variation in oxidative events were defined by principal component analysis of all of the data and redox balance evaluations. We suggest that these spatial differences under water stress and Fusarium infection arise from discrete regulatory mechanisms, reflecting either developmental effect over the leaf regions or systemic anti-oxidative events occurred following infection.

Controlled and Targeted Drug Delivery by a UV-responsive Liposome for Overcoming Chemo-resistance in Non-Hodgkin Lymphoma.

Although chemotherapy plays a vital role in treating non-Hodgkin lymphomas, the clinical applications are limited because of intolerable side-effects and multidrug resistance at the beginning or during the course of therapy. In this study, we successfully fabricated a CD20-targeting immuno-liposome based on 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC-8,9PC), which can form intermolecular cross-linking through the diacetylenic group by ultraviolet irradiation. This immuno-liposome showed appropriate size distribution, well-defined regular spherical structure, favorable biocompatibility, high serum stability, and prolonged circulation time in blood vessels. The in and ex vivo experiments demonstrate enhanced tumor suppression abilities against both wild-type and resistant non-Hodgkin lymphomas for liposomal doxorubicin when compared with free drugs. The outstanding antitumor activities are attributed to the accumulation and retention of liposomal drugs in malignant tissues and cells, which are realized by the co-operation of active targeting via antibody-antigen reaction and passive targeting via enhanced permeability and retention effect.

Continuous esterification to produce biodiesel by SPES/PES/NWF composite catalytic membrane in flow-through membrane reactor: experimental and kinetic studies.

A novel composite catalytic membrane (CCM) was prepared from sulfonated polyethersulfone (SPES) and polyethersulfone (PES) blend supported by non-woven fabrics, as a heterogeneous catalyst to produce biodiesel from continuous esterification of oleic acid with methanol in a flow-through mode. A kinetic model of esterification was established based on a plug-flow assumption. The effects of the CCM structure (thickness, area, porosity, etc.), reaction temperature and the external and internal mass transfer resistances on esterification were investigated. The results showed that the CCM structure had a significant effect on the acid conversion. The external mass transfer resistance could be neglected when the flow rate was over 1.2 ml min(-1). The internal mass transfer resistance impacted on the conversion when membrane thickness was over 1.779 mm. An oleic acid conversion kept over 98.0% for 500 h of continuous running. The conversions obtained from the model are in good agreement with the experimental data.