All-Aqueous Bicontinuous Structured Liquid Crystal Emulsion through Intraphase Trapping of Cellulose Nanoparticles.

Here, we describe the all-aqueous bicontinuous emulsions with cholesteric liquid crystal domains through hierarchical colloidal self-assembly of nanoparticles. This is achieved by homogenization of a rod-like cellulose nanocrystal (CNC) with two immiscible, phase separating polyethylene glycol (PEG) and dextran polymer solutions. The dispersed CNCs exhibit unequal affinity for the binary polymer mixtures that depends on the balance of osmotic and chemical potential between the two phases. Once at the critical concentration, CNC particles are constrained within one component of the polymer phases and self-assemble into a cholesteric organization. The obtained liquid crystal emulsion demonstrates a confined three-dimensional percolating bicontinuous network with cholesteric self-assembly of CNC within the PEG phase; meanwhile, the nanoparticles in the dextran phase remain isotropic instead. Our results provide an alternative way to arrest bicontinuous structures through intraphase trapping and assembling of nanoparticles, which is a viable and flexible route to extend for a wide range of colloidal systems.

A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial in Northwest China.

The nasal type of extranodal natural killer/T-cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol-asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T-cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2-year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression-free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment-related deaths. These results will require confirmation in larger prospective trials.

[Current status and prospect of translational medicine in nanotechnology].

Nowadays, nanotechnologies have shown wide application foreground in the biomedical field of medicine laboratory tests, drug delivery, gene therapy and bioremediation. However, in recent years, nanomaterials have been labeled poisonous, because of the disputes and misunderstandings of mainstream views on their safety. Besides, for the barriers of technical issues in preparation like: (1) low efficacy (poor PK & PD and low drug loading), (2) high cost (irreproducibility and difficulty in scale up), little of that research has been successfully translated into commercial products. Currently, along with the new theory of "physical damage is the origin of nanotoxicity", biodegradability and biocompatibility of nanomaterials are listed as the basic principle of safe application of nanomaterials. Combining scientific design based on molecular level with precision control of process engineering will provide a new strategy to overcome the core technical challenges. New turning point of translational medicine in nanotechnology may emerge.

Extraction and characterization of bound extracellular polymeric substances from cultured pure cyanobacterium (Microcystis wesenbergii).

Preliminary characterization of bound extracellular polymeric substances (bEPS) of cyanobacteria is crucial to obtain a better understanding of the formation mechanism of cyanobacterial bloom. However, the characterization of bEPS can be affected by extraction methods. Five sets (including the control) of bEPS from Microcystis extracted by different methods were characterized using three-dimensional excitation and emission matrix (3DEEM) fluorescence spectroscopy combined chemical spectrophotometry; and the characterization results of bEPS samples were further compared. The agents used for extraction were NaOH, pure water and phosphate buffered saline (PBS) containing cationic exchange resins, and hot water. Extraction methods affected the fluorescence signals and intensities in the bEPS. Five fluorescence peaks were observed in the excitation and emission matrix fluorescence spectra of bEPS samples. Two peaks (peaks T1 and T2) present in all extractions were identified as protein-like fluorophores, two (peaks A and C) as humic-like fluorophores, and one (peak E) as a fulvic-like substance. Among these substances, the humic-like and fulvic-like fluorescences were only seen in the bEPS extracted with hot water. Also, NaOH solution extraction could result in strong fluorescence intensities compared to the other extraction methods. It was suggested that NaOH at pH10.0 was the most appropriate method to extract bEPS from Microcystis. In addition, dialysis could affect the yields and characteristics of extracted bEPS during the determination process. These results will help us to explore the issues of cyanobacterial blooms.

Micro- and nanoplastics interact with conventional pollutants on microalgae: Synthesis through meta-analysis.

Micro- and nanoplastics (MNPs) have been found to occur intensively in aquatic environments, along with other conventional pollutants (Po) such as heavy metals, pesticides, pharmaceuticals, etc. However, our understanding of how MNPs and Po interact on aquatic primary producers is fragmented. We performed a quantitative meta-analysis based on 933 published experimental assessments from 44 studies to examine the coupled effects of MNPs and Po on microalgae. Although the results based on interaction type frequency (the proportion of each interaction type in all results) revealed dominantly additive interactions (56%) for overall physiological performance, an overall antagonistic effect was observed based on the mean interaction effect sizes. A higher proportion of antagonistic interaction type frequency was found in marine species compared to fresh species. The antagonistic effects were particularly significant for growth, oxidative responses, and photosynthesis, which could be attributed to the adsorption effect of MNPs on Po and thus the decreasing concentrations of pollutants in the medium. Larger-sized, negatively charged or uncharged and aged MNPs had higher proportions of antagonistic effects compared to smaller-sized, positively charged and virgin MNPs, due to their stronger adsorption capacity to Po. This study provides a comprehensive insight into the interactive effects of MNPs and Po on microalgae.

Genome-wide identification, characterization and expression analysis of the BMP family associated with beak-like teeth in Oplegnathus.

Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor beta (TGF-ß) family, are critical for the control of developmental processes such as dorsal-ventral axis formation, somite and tooth formation, skeletal development, and limb formation. Despite Oplegnathus having typical healing beak-like teeth and tooth development showing a trend from discrete to healing, the potential role of BMPs in the development of the beak-like teeth is incompletely understood. In the present study, 19 and 16 BMP genes were found in O. fasciatus and O. punctatus, respectively, and divided into the BMP2/4/16, BMP5/6/7/8, BMP9/10, BMP12/13/14, BMP3/15 and BMP11 subfamilies. Similar TGFb and TGF_ß gene domains and conserved protein motifs were found in the same subfamily; furthermore, two common tandem repeat genes (BMP9 and BMP3a-1) were identified in both Oplegnathus fasciatus and Oplegnathus punctatus. Selection pressure analysis revealed 13 amino acid sites in the transmembrane region of BMP3, BMP7, and BMP9 proteins of O. fasciatus and O. punctatus, which may be related to the diversity and functional differentiation of genes within the BMP family. The qPCR-based developmental/temporal expression patterns of BMPs showed a trend of high expression at 30 days past hatching (dph), which exactly corresponds to the ossification period of the bones and beak-like teeth in Oplegnathus. Tissue-specific expression was found for the BMP4 gene, which was upregulated in the epithelial and mesenchymal tissues of the beak-like teeth, suggesting that it also plays a regulatory role in the development of the beak-like teeth in O. punctatus. Our investigation not only provides a scientific basis for comprehensively understanding the BMP gene family but also helps screen the key genes responsible for beak-like tooth healing in O. punctatus and sheds light on the developmental regulatory mechanism.

Current understanding and challenges for aquatic primary producers in a world with rising micro- and nano-plastic levels.

The impacts of micro- and nanoplastics (MNPs) on aquatic animals have been intensively studied; however, the extent and magnitude of potential effects of MNPs on aquatic primary producers are poorly understood. In this study, we quantitatively analyzed the published literature to examine the impacts of MNPs on growth, photosynthesis, pigments, and metabolism of aquatic microalgae. MNPs negatively affected growth of microalgae but usually had a high EC50 (>25 mg/L). However, positively charged MNPs had a much lower EC50 (<1 mg/L). MNPs lowered maximum photochemical efficiency of photosystem II (Fv/Fm) with the effect increasing with concentration of MNPs but diminishing with exposure time, and also reduced chlorophyll a content to enhanced extent with increased MNPs concentration. MNPs induced relatively higher changes in superoxide dismutase (SOD) and malondialdehyde (MDA) levels in marine algae than in freshwater algae. Reactive oxygen species (ROS) levels increased with MNPs concentration and exposure time while SOD levels first increased and then decreased with increasing MNPs concentration. Macrophytes were found to be able to trap MNPs via multiple mechanisms. Future work should focus on the mechanisms behind MNPs impacts on primary productivity and global carbon cycle, and the combined effects of MNPs with other environmental factors.

Microplastics in bloom-forming macroalgae: Distribution, characteristics and impacts.

Macroalgal blooms and marine microplastics (MPs), as global challenges for oceans, are both showing a rising trend. However, none is known regarding the interaction of these two important issues. The Yellow Sea suffers the world's largest green tides and severe MPs pollution as well. Therefore, we tracked the trapping of MPs by drifting Ulva prolifera in the Yellow Sea during the green-tide period. The abundance of MPs in drifting U. prolifera was 595-3917 times higher than that in seawater and increased along the drifting path from south to north in the Yellow Sea. In addition, four mechanisms of trapping plastics (twining, attachment, embedment, and wrapping) on or in U. prolifera were unmasked, which explains why the plant has such strong capacity to trap MPs. Laboratory incubation experiments showed that MPs (0.025-25 mg L-1) did not affect relative growth rate, effective photochemical efficiency of photosystem II (PSII), or saturating irradiance of U. prolifera until reaching an extremely high concentration (100 mg L-1), indicating a high tolerance to MPs. Due to tremendous biomass and coverage of the green tide and increased frequency as well, the plastics trap in drifting macroalgae can alter the spatio-temporal distribution of MPs in the oceans.

Microplastics in specific tissues of wild sea urchins along the coastal areas of northern China.

Sea urchins serve as an essential niche for benthic ecosystems and are valuable seafood for humans. However, little is known about the microplastics (MPs) accumulation in sea urchins. Here, we investigated the abundances and characteristics of MPs in specific tissues of wild sea urchins for 12 sites across 2, 900 km of coastlines in northern China. Sea urchins from all sites were detected to have MPs, with a total detection rate of 89.52%. The MPs abundance in sea urchins from all sites ranged from 2.20 ± 1.50 to 10.04 ± 8.46 items/individual or 0.16 ± 0.09 to 2.25 ± 1.68 items/g wet weight. The samples from Dalian were found to have the highest value by individual, and samples from Lianyungang had the highest value by gram. Furthermore, MPs were found in different tissues of sea urchins, i.e., gut, coelomic fluid and gonads. The highest abundance of MPs was found in the gut of sea urchins, followed by coelomic fluid and gonads. The size of MPs ranged from 27 to 4742 µm, and the mean size found in gut was bigger than coelomic fluid and gonads. More interestingly, the MPs abundance increased with the decrease of anus size, shell diameter and gonad index (the wet weight ratio of gonad to total soft tissues). The MPs were dominated by fiber in shape, blue-green in colour and cellophane in composition. The high MPs abundance in sea urchins indicates the potential risks to human as they are consumed in many parts of the world, particularly in Asia and Europe.

Spatio-temporal features of microplastics pollution in macroalgae growing in an important mariculture area, China.

Macroalgae are being consumed by a growing number of people as functional food. Therefore, they are intensively cultivated to meet the rising demand. Mariculture is a potential source of microplastics (MPs). However, as a potential source of microplastics, little is known regarding the MPs pollution in macroalgae of open sea macriculture. Here we investigated the MPs characteristics in macroalgae in three sections of Haizhou Bay, an important mariculture area in China, during Pyropia culture (Pyropia yezoensis) and non-culture periods (Ulva prolifera, Sargassum horneri, Cladophora sp., Undaria pinnatifida, Ulva pertusa). It was found that P. yezoensis during the culture period had higher MPs abundance (0.17 ± 0.08 particles g-1fresh weight) than other macroalgae (0.12 ± 0.09 particles g-1 fresh weight) during the non-culture period, particularly for the nearshore sections. There were more fiber MPs in P. yezoensis (90.43%) in culture period compared to macroalgae (84.46%) in non-culture period. Highly similar spectrum of plastics in culture gears and macroalgae was verified. Pyropia culture gears released about 1, 037 tons plastics into the environment annually and the MPs abundances in seawater during the culture and non-culture periods were 1.04 ± 0.32 and 1.86 ± 0.49 particles L-1, respectively. The gap of MPs abundance between the two periods can be attributed to the tremendous trapping by massive biomass of P. yezoensis during the culture period and the continuous plastic release during the non-culture period. This study indicates that culture gears of macroalgae could be an important MPs source and the MPs can be transferred to human by edible macroalgae, and meanwhile macroalgae may be ideal biomonitors for MPs pollution in seawater due to their unbiased trapping and immovability.

The accumulation of microplastics in fish from an important fish farm and mariculture area, Haizhou Bay, China.

Marine fisheries and aquaculture can match growing demand for marine protein from an increasing population. However, the microplastics (MPs) in marine environments may pose a threat to human health through food chains by seafood consumption. The MPs have been found lodged in the digestive tracts and other tissues of various sea animals, nevertheless, little is known in regard to the accumulation of MPs in fish from major fish farms and mariculture areas, especially in non-digestive tissues of fishes. This study investigated the accumulation of MPs in six major wild fish species (including Thryssa kammalensis, Amblychaeturichthys hexanema, Odontamblyopus rubicundus, Cynoglossus semilaevis, Chaeturichthys stigmatias and Collichthys lucidus), both in digestive and non-digestive tissues, from an important fish farm and mariculture area, Haizhou Bay, China. All fishes had items that were identified as MPs. The highest abundance of MPs was 22.21±1.70items/individual or 11.19±1.28items/g in T. kammalensis, which is filter-feeding and usually inhabits in estuary. The lowest abundance of MPs was observed in C. semilaevis (13.54±2.09items/individual) and C. stigmatias (1.61±0.56items/g). The abundance of MPs exponentially increased with the decrease of MPs size. The MPs were dominated by fiber in shape, black or grey in colour and cellophane in composition. As to different tissues, the total number of MPs on skin (800) or in gills (746) was higher than that in gut (514). In terms of skin, the abundances of MPs in three species of scaleless fish with mucus (A. hexanema, C. stigmatias and O. rubicundus) were generally higher than other three fishes with scales (C. lucidus, C. semilaevis and T. kammalensis), implying the potential high risk of scaleless fish consumption for human health in Haizhou Bay. More in-depth studies need to focus on the scaleless fish through mucus adsorbing enormous MPs.

Robust, tough and anti-fatigue cationic latex composite hydrogels based on dual physically cross-linked networks.

Dual physically cross-linked hydrogels, which are triggered by cationic latexes as hydrophobic association and ionic crosslinking centers, were easily fabricated via a one-pot in situ polymerization method. First, the hydrophobic alkyl chains of hydrophobic monomers are adsorbed on the surface of latex microspheres and stabilized in the presence of surfactants, forming hydrophobic association centers as the first physical crosslinking points. Meanwhile, the anionic sulfate radicals dissociated by persulphate are attracted towards the cationic molecular chains of latex microspheres through ionic interactions, forming the secondary physical crosslinking centers, and initiate the copolymerization between acrylamide and hydrophobic vinyl monomers. The fabricated hydrogel exhibited high tensile strength of 1.32MPa, a remarkable toughness of 4.53MJm-3, excellent self-recovery properties and fatigue resistance. Therefore, the current work provides a promising strategy for designing novel hydrogels via multiple physical interactions and devoid of any chemical crosslinking. The novel design of hydrogels can enhance their mechanical properties and expand their biomedical applications.

Hydraulic connectivity and evaporation control the water quality and sources of chromophoric dissolved organic matter in Lake Bosten in arid northwest China.

Lake Bosten is the largest oligosaline lake in arid northwestern China, and water from its tributaries and evaporation control the water balance of the lake. In this study, water quality and chromophoric dissolved organic matter (CDOM) absorption and fluorescence were investigated in different seasons to elucidate how hydraulic connectivity and evaporation may affect the water quality and variability of CDOM in the lake. Mean suspended solids and turbidity were significantly higher in the upstream tributaries than in the lake, the difference being notably more pronounced in the wet than in the dry season. A markedly higher mean first principal component (PC1) score, which was significantly positively related to protein-like components, and a considerably lower fluorescence peak integration ratio - IC:IT, indicative of the terrestrial humic-like CDOM contribution percentage, were observed in the lake than in the upstream tributaries. Correspondingly, notably higher contribution percentages of terrestrial humic-like components were observed in the river mouth areas than in the remaining lake regions. Furthermore, significantly higher mean turbidity, and notably lower mean conductivity and salinity, were recorded in the southwestern Kaidu river mouth than in the remaining lake regions in the wet season. Notably higher mean salinity is recorded in Lake Bosten than in upstream tributaries. Autochthonous protein-like associated amino-acids and also PC1 scores increased significantly with increasing salinity. We conclude that the dynamics of water quality and CDOM composition in remote arid Lake Bosten are strongly driven by evaporation and also the hydraulic connectivity between the upstream tributaries and the downstream lake.

Spatial and temporal variability in the nitrogen cyclers of hypereutrophic Lake Taihu.

Harmful cyanobacterial blooms (cyanoHABs) are a major threat to freshwater ecosystems worldwide. Evidence suggests that both nitrogen and phosphorus are important nutrients in the development and proliferation of blooms, yet much less is known about nitrogen cycling dynamics in these systems. To assess the potential nitrogen cycling function of the cyanoHAB community, surface water samples were collected in Lake Tai (Taihu), China over a 5-month bloom event in 2014. The expression of six nitrogen cycling genes (nifH, hzsA, nxrB, nrfA, amoA, nosZ) was surveyed using a targeted microarray with probes designed to provide phylogenetic information. N-Cycling gene expression varied spatially across Taihu, most notably near the mouth of the Dapu River. Expression of nifH was observed across the lake and attributable to both Proteobacteria and Cyanobacteria: Proteobacteria were major contributors to nifH signal near shore. Other N transformations such as anaerobic ammonia oxidation and denitrification were evident in the surface waters as well. Observations in this study highlight the potential importance of heterotrophic bacteria in N-cycling associated with cyanoHABs.

Liposome-mediated transient transfection reduces cholesterol-dependent coxsackievirus infectivity.

Liposome-mediated gene delivery provides a powerful strategy for the study of gene function and for gene therapy. Coxsackievirus B3 is an important human pathogen associated with various diseases. Here we reported that liposome-mediated transient transfection of plasmid cDNA inhibited coxsackieviral replication at the levels of RNA, protein and viral progeny release. These inhibitory effects were observed in various cell types and by using different liposome reagents. We further showed that the inhibition was likely due to the lack of virus attachment. Moreover, we showed that addition of cholesterol restored, at least in part, the viral infectivity. Interestingly, we found that membrane cholesterol levels were unchanged during transfection, indicating that disruption rather than depletion of membrane cholesterol contributes to the inhibitory effects of transfection. Our data suggest that liposome-mediated cDNA transient transfection inhibits coxsackievirus infectivity via inhibition of viral attachment, which is likely occurring through the changes of membrane cholesterol integrity.

pH-Triggered Charge-Reversal Polyurethane Micelles for Controlled Release of Doxorubicin.

A series of pH-triggered charge-reversal polyurethane copolymers (PS-PUs) containing methoxyl-poly(ethylene glycol) (mPEG), carboxylic acid groups, and piperazine groups is presented in this work. The obtained PS-PUs copolymers can form into stable micelles at pH 7.4, which response to a narrow pH change (5.5-7.5) and show a tunable pH-triggered charge-reversal property. Doxorubicin (DOX) is encapsulated into the PS-PU micelles as a model drug. The drug release of DOX-loaded PS-PU micelles shows an obviously stepped-up with reducing the pH. Meanwhile, it is found that the charge-reversal property can improve the cellular uptake behavior and intracellular drug release in both HeLa cells and MCF-7 cells. Additionally, the time-dependent cytotoxicity of the DOX-loaded PS-PU micelles is confirmed by MTT assay. Attributed to the tunable charge-reversal property through changing the molar ratio of piperazine/carboxyl, the PS-PU micelles will be a potential candidate as an intelligent drug delivery system in future studies.

pH-Responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area.

A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM(-1) s(-1). To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic pathological tissues.

Environmental pH-sensitive polymeric micelles for cancer diagnosis and targeted therapy.

The delivery and control over the release of hydrophobic imaging markers for cancer diagnosis or pharmaceutical agents for targeted therapy are of considerable interest. Nano-sized pH-sensitive polymeric micelles that rely on the enhanced permeability and retention (EPR) of vasculature and the low-pH microenvironment in cancer tissue are emerging as stimuli-responsive targeted therapies that can simultaneously release diagnostic and therapeutic agents into a cancerous region. This review focuses on the developments of pH-sensitive polymeric micelles and their biomedical applications in cancer diagnosis and targeted therapy.

Stimulus-sensitive polymeric nanoparticles and their applications as drug and gene carriers.

Polymeric nanoparticles are promising candidates as drug and gene carriers. Among polymeric nanoparticles, those that are responsive to internal or external stimuli are of greater interest because they allow more efficient delivery of therapeutics to pathological regions. Stimulus-sensitive polymeric nanoparticles have been fabricated based on numerous nanostructures, including micelles, vesicles, crosslinked nanoparticles, and hybrid nanoparticles. The changes in chemical or physical properties of polymeric nanoparticles that occur in response to single, dual, or multiple stimuli endow these nanoparticles with the ability to retain cargoes during circulation, target the pathological region, and release their cargoes after cell internalization. This Review focuses on the most recent developments in the preparation of stimulus-sensitive polymeric nanoparticles and their applications in drug and gene delivery.