Cavitation-on-a-Chip Enabled Size-Specific Liposomal Drugs for Selective Pharmacokinetics and Pharmacodynamics.

The size of liposomal drugs has been demonstrated to strongly correlate with their pharmacokinetics and pharmacodynamics. While the microfluidic method successfully achieves the production of liposomes with well-controlled sizes across various buffer/lipid flow rate ratio (FRR) settings, any adjustments to the FRR inevitably influence the concentration, encapsulation efficiency (EE), and stability of liposomal drugs. Here we describe a controllable cavitation-on-a-chip (CCC) strategy that facilitates the precise regulation of liposomal drug size at any desired FRR. The CCC-enabled size-specific liposomes exhibited striking differences in uptake and biodistribution behaviors, thereby demonstrating distinct antitumor efficacy in both tumor-bearing animal and melanoma patient-derived organoid (PDO) models. Intriguingly, as the liposome size decreased to approximately 80 nm, the preferential accumulation of liposomal drugs in the liver transitioned to a predominant enrichment in the kidneys. These findings underscore the considerable potential of our CCC approach in influencing the pharmacokinetics and pharmacodynamics of liposomal nanomedicines.

One-Step Formation of Targeted Liposomes in a Versatile Microfluidic Mixing Device.

Targeted liposomes, as a promising carrier, have received tremendous attention in COVID-19 vaccines, molecular imaging, and cancer treatment, due to their enhanced cellular uptake and payload accumulation at target sites. However, the conventional methods for preparing targeted liposomes still suffer from limitations, including complex operation, time-consuming, and poor reproducibility. Herein, a facile and scalable strategy is developed for one-step construction of targeted liposomes using a versatile microfluidic mixing device (MMD). The engineered MMD provides an advanced synthesis platform for multifunctional liposome with high production rate and controllability. To validate the method, a programmed death-ligand 1 (PD-L1)-targeting aptamer modified indocyanine green (ICG)-liposome (Apt-ICG@Lip) is successfully constructed via the MMD. ICG and the PD-L1-targeting aptamer are used as model drug and targeting moiety, respectively. The Apt-ICG@Lip has high encapsulation efficiency (89.9 ± 1.4%) and small mean diameter (129.16 ± 5.48 nm). In vivo studies (PD-L1-expressing tumor models) show that Apt-ICG@Lip can realize PD-L1 targeted photoacoustic imaging, fluorescence imaging, and photothermal therapy. To verify the versatility of this approach, various targeted liposomes with different functions are further prepared and investigated. These experimental results demonstrate that this method is concise, efficient, and scalable to prepare multifunctional targeted liposomal nanoplatforms for molecular imaging and disease theranostics.

Application of laminarin as a novel coagulant aid to improve coagulation-ultrafiltration efficiency.

Polyacrylamide (PAM) is the most commonly used coagulant aid in coagulation-ultrafiltration (C-UF) systems; however, its hydrolyzed monomer is harmful to the human nervous system. In this study, laminarin (LA), was extracted from Laminaria japonica and used as a novel coagulant aid to improve coagulation efficiency and reduce membrane fouling during the C-UF process. Optimal LA usage conditions were systematically examined and compared with those of PAM to evaluate their potential for industrial applications. The results revealed that coagulation efficiency could be enhanced by 15-35% with moderate LA addition, which exhibited comparable aid effects to PAM. LA exhibited the highest coagulation aid effect at pH 8-9, and under this condition, turbidity and natural organic matter (NOM) removal achieved 82% and 54%, respectively. Compared with a one-time LA dosing strategy, the pollutant removal capacity of batch dosing was superior. Even in lower water temperatures (5-15 °C), coagulation efficiency was still satisfied, which exhibited a good practical application perspective. The coagulation aid role of LA should be attributed to its long-chain molecular structure, which enhances the bridging role between micro flocs and assists floc growth, thus facilitating the formation of large flocs. In addition, LA adsorption on floc surface was conducive to the direct electrostatic repulsion effect of electronegative membrane, which resulted in a more porous cake layer and higher membrane flux. Therefore, LA exhibits excellent application potential for eliminating NOM while simultaneously reducing membrane fouling through the C-UF process.

Dual-Modal Immunochromatographic Test for Sensitive Detection of Zearalenone in Food Samples Based On Biosynthetic Staphylococcus aureus-Mediated Polymer Dot Nanocomposites.

The rapid detection of toxins is of great significance to food security and human health. In this work, a dual-modality immunochromatographic test (DICT) mediated by Staphylococcus aureus (SA)-biosynthesized polymer dots (SABPDs) was constructed for sensitive monitoring of zearalenone (ZEN) in agro products. The SABPDs as potent microorganism nanoscaffolds with excellent solubility, brightness, and stability were ingeniously fabricated employing hydroquinone and SA as precursors in the Schiff base reaction and a self-assembly technique. Thanks to the fact that they not only preserved an intact microsphere for loading Fc regions of monoclonal antibodies (mAbs) and the affinity of their labeled mAbs to antigen but also generated superb colorimetric-fluorescent dual signals, the versatile SABPDs manifested unique possibilities as the new carriers for dual-readout ICT with remarkable enhancement in sensitivity in ZEN screening (limit of detection = 0.036 ng/mL, which was 31-fold lower than that of traditional gold nanoparticle-based ICT). Ultimately, the proposed immunosensor performed well in millet and corn samples with satisfactory recoveries, demonstrating its potential for point-of-care testing. This work offers a bio-friendly strategy for biosynthesizing cell-based PD vehicles with bimodal signals for food safety analysis.

Hydrophilicity gradient in covalent organic frameworks for membrane distillation.

Desalination can help to alleviate the fresh-water crisis facing the world. Thermally driven membrane distillation is a promising way to purify water from a variety of saline and polluted sources by utilizing low-grade heat. However, membrane distillation membranes suffer from limited permeance and wetting owing to the lack of precise structural control. Here, we report a strategy to fabricate membrane distillation membranes composed of vertically aligned channels with a hydrophilicity gradient by engineering defects in covalent organic framework films by the removal of imine bonds. Such functional variation in individual channels enables a selective water transport pathway and a precise liquid-vapour phase change interface. In addition to having anti-fouling and anti-wetting capability, the covalent organic framework membrane on a supporting layer shows a flux of 600 l m-2 h-1 with 85 °C feed at 16 kPa absolute pressure, which is nearly triple that of the state-of-the-art membrane distillation membrane for desalination. Our results may promote the development of gradient membranes for molecular sieving.

Rod-like hybrid nanomaterial with tumor targeting and pH-responsive for cancer chemo/photothermal synergistic therapy.

The development of chemo/photothermal nanotherapeutic systems with excellent photothermal performance, stable drug loading, tumor targeting and strong membrane penetration still remains a challenge. To address this problem, herein a rod-like nanocomposite system (AuNR@FA-PR/PEG) forming from folic acid (FA) terminated carboxylated cyclodextrin (CD) pseudopolyrotaxane (FA-PR) and polyethylene glycol (PEG) modifying gold nanorods (AuNR) was reported. Cisplatin (CDDP) was loaded in AuNR@FA-PR/PEG via coordination bonds to prepare a rod-like pH-responsive nanosystem (AuNR@FA-PR/PEG/CDDP) with chemotherapy/photothermal therapy. The rod-like morphology of AuNR@FA-PR/PEG was characterized by transmission electron microscope. In vitro drug release experiments showed the pH-responsive of AuNR@FA-PR/PEG/CDDP. In vivo real-time imaging assays proved AuNR@FA-PR/PEG/CDDP could rapidly enrich in the tumor area and stay for a long time because of folate targeting and their rod-like morphology. In vivo photothermal imaging assays showed AuNR@FA-PR/PEG/CDDP excellent photothermal performance, the average temperature of tumor region could reach 63.5 °C after 10 min irradiation. In vitro and in vivo experiments also demonstrated that the combined therapy of chemotherapy and photothermal therapy had an outstandingly synergistic effect and improved the therapeutic efficacy comparing with chemotherapy and photothermal therapy alone. Therefore, the prepared rod-like AuNR@FA-PR/PEG/CDDP will provide a new strategy for the effective treatment of cancer.

Hollow mesoporous polydopamine nanospheres: synthesis, biocompatibility and drug delivery.

Various polydopamine (PDA) nanospheres were synthesized by utilizing triblock copolymer Pluronic F127 and 1,3,5-trimethylbenzene (TMB) as soft templates. Precise morphology control of polydopamine nanospheres was realized from solid polydopamine nanospheres to hollow polydopamine nanospheres, mesoporous polydopamine nanospheres and hollow mesoporous polydopamine nanospheres (H-MPDANSs) by adjusting the weight ratio of TMB to F127. The inner diameter of the prepared H-MPDANSs can be controlled in the range of 50-100 nm, and the outer diameter is about 180 nm. Furthermore, the thickness of hollow mesoporous spherical shell can be adjusted by changing the amount of dopamine (DA). The H-MPDANSs have good biocompatibility, excellent photothermal properties, high drug loading capacity, and outstanding sustainable drug release properties. In addition, both NIR laser irradiation and acid pH can facilitate the controlled release of doxorubicin (DOX) from H-MPDANSs@DOX.

Influence of Hydrophobic Chains in Nanocarriers on Antitumor Efficacy of Docetaxel Nanoparticles.

The composition of amphiphilic nanocarriers can affect the antitumor efficacy of drug-loaded nanoparticles and should be researched systematically. In this paper, to study the influence of hydrophobic chains, an amphiphilic copolymer (PEG45PCL17) and hydrophilic PEG (PEG45) were utilized as nanocarriers to prepare docetaxel-loaded nanoparticles (DTX/PEG45PCL17 nanoparticles and DTX/PEG45 nanoparticles) through an antisolvent precipitation method. The two DTX nanoparticles presented a similar drug loading content of approximately 60% and a sheet-like morphology. During the preparation procedure, the drug loading content affected the morphology of DTX nanoparticles, and the nanocarrier composition influenced the particle size. Compared with DTX/PEG45 nanoparticles, DTX/PEG45PCL17 nanoparticles showed a smaller mean diameter and better in vitro and in vivo antitumor activity. The cytotoxicity of DTX/PEG45PCL17 nanoparticles against 4T1 cells was 1.31 µg mL-1, 3.4-fold lower than that of DTX/PEG45 nanoparticles. More importantly, DTX/PEG45PCL17 nanoparticles showed significantly higher antitumor activity in vivo, with an inhibition rate over 80%, 1.5-fold higher than that of DTX/PEG45 nanoparticles. Based on these results, antitumor activity appears to be significantly affected by the particle size, which was determined by the composition of the nanocarrier. In summary, to improve antitumor efficacy, the amphiphilic structure should be considered and optimized in the design of nanocarriers.

Partially Melted Ti6Al4V Particles Increase Bacterial Adhesion and Inhibit Osteogenic Activity on 3D-printed Implants: An In Vitro Study.

BACKGROUND: A porous Ti6Al4V implant that is manufactured using selective laser melting (SLM) has broad potential applications in the field of orthopaedic implants. The pore structure of the SLM porous Ti6Al4V implant allows for cell migration and osteogenic differentiation, which is favorable for bone ingrowth and osseointegration. However, it is unclear whether the pore structure and partially melted Ti6Al4V particles on a SLM porous Ti6Al4V implant will increase bacterial adhesion and, perhaps, the risk of implant-related infection. QUESTIONS/PURPOSES: (1) Is there more bacterial adhesion and colonization on SLM porous Ti6Al4V implants than on polished orthopaedic implants? (2) Do partially melted Ti6Al4V particles on SLM porous Ti6Al4V implants reduce human bone mesenchymal stem cells (hBMSCs) adhesion, viability, and activity? METHODS: To determine bacterial adhesion and biofilm formation, we incubated five different Ti6Al4V discs (polished, grit-blasted, plasma-sprayed, particle SLM porous, and nonparticle SLM porous discs) with methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Bacterial coverage on the surface of the five different Ti6Al4V discs were evaluated based on scanning electron microscopy (SEM) images quantitatively. In addition, a spread-plate method was used to quantitatively evaluate the bacterial adhesion on those implants. The biofilm formation was stained with crystal violet and semi-quantitatively determined with a microplate reader. The morphology and adhesion of hBMSCs on the five Ti6Al4V discs were observed with SEM. The cell viability was quantitatively evaluated with a Cell Counting Kit-8 assay. In addition, the osteogenic activity was determined in vitro with a quantitatively alkaline phosphatase activity assay and alizarin-red staining. For semiquantitative analysis, the alizarin-red stained mineralized nodules were dissolved and determined with a microplate reader. RESULTS: The polished discs had the lowest MRSA adhesion (8.3% ± 2.6%) compared with grit-blasted (19.1% ± 3.9%; p = 0.006), plasma-sprayed (38.5% ± 5.3%; p < 0.001), particle (23.1% ± 2.8%; p < 0.001), and nonparticle discs (15.7% ± 2.5%; p = 0.003). Additionally, when comparing the two SLM discs, we found that particle discs had higher bacterial coverage than nonparticle discs (23.1% ± 2.8% versus 15.7% ± 2.5%; p = 0.020). An E. coli analysis showed similar results, with the higher adhesion to particle SLM discs than to nonparticle discs (20.7% ± 4.2% versus 14.4% ± 3.6%; p = 0.011). In addition, on particle SLM porous discs, bacterial colonies were localized around the partially melted Ti6Al4V particles, based on SEM images. After a 7-day incubation period, the cell viability in the particle group (optical density value 0.72 ± 0.05) was lower than that in the nonparticle groups (optical density value: 0.87 ± 0.08; p = 0.003). Alkaline phosphatase activity, as a marker of osteogenic differentiation, was lower in the particle group than in the nonparticle group (1.32 ± 0.12 U/mL versus 1.58 ± 0.09 U/mL; p = 0.012). CONCLUSION: Higher bacterial adhesion was observed on SLM porous discs than on polished discs. The partially melted Ti6Al4V particles on SLM porous discs not only enhanced bacterial adhesion but also inhibited the osteogenic activity of hBMSCs. Postprocessing treatment is necessary to remove partially melted Ti6Al4V particles on an SLM implant before further use. Additional studies are needed to determine whether an SLM porous Ti6Al4V implant increases the risk of implant-related infection in vivo. CLINICAL RELEVANCE: As implants with porous Ti6Al4V made using SLM are being designed, our preliminary findings suggest that postprocessing treatment is needed to remove partially melted Ti6Al4V particles before further use. In addition, the depth of the porous structure of the SLM implant should not exceed the maximum depth of bone ingrowth because the host immune defense cannot prevent bacterial adhesion without integration.

Amphiphilic Hybrid Dendritic-Linear Molecules as Nanocarriers for Shape-Dependent Antitumor Drug Delivery.

Nanoparticles based on hybrid block copolymers had been expected as effective nanocarriers for hydrophobic drug delivery. Herein, the novel dendritic-linear molecules from OEG dendron conjugated with octadecylamine (G2-C18) was designed, synthesized, and further applied as nanocarrier to prepare 10-hydroxycamptothecin (HCPT) nanoparticles via antisolvent precipitation method. It seemed that the feed weight ratio of HCPT vs G2-C18 not only affected the drug-loading content of nanoparticles but also influenced the morphology of HCPT nanoparticles; the morphology of HCPT nanoparticles was changed from nanosphere (NSs) to nanorod (NRs) with increasing the feed weight ratio. Both of HCPT nanoparticles presented good stability and similar drug release profiles, but different anticancer efficacy and cellular uptake mechanism. The cytotoxicity of HCPT NRs was enhanced significant comparing with HCPT NSs, the IC50 value was 2-fold lower than HCPT NSs ( p < 0.05). More importantly, HCPT NRs showed apparently higher antitumor activity in vivo, the inhibition rate of HCPT NRs was 1.3-fold higher than HCPT NSs. Based on these results, it suggested that the antitumor activity could be influenced significantly by particle morphology, which should be considered and optimized during the nanocarrier design.

The model binary/ternary mixtures for actual EPS solution extracted from the activated sludge in MBR using dead-end membrane filtration cell.

In order to find a model solution to simulate actual extracellular polymeric substances (EPS) solution in terms of filterability behavior, a series of experiments were conducted in a dead-end unstirred cell with 0.1 µm polyvinylidene fluoride membranes using binary/ternary mixtures consisting of sodium alginate (SA), bovine serum albumin (BSA) and humic acid (HA). Three target parameters (cumulative filtrate volume (CFV), specific cake resistance (αc) and rejection (R)) were compared and the roles of mixture components were investigated. The order of degree of influence on CFV, αc and R in ternary mixture was SA (94.5%, 85.6% and 88.2%, respectively) > BSA (5.2%, 10.3% and 8.0%) > HA (0.3%, 4.1% and 3.8%). Meanwhile, when the composition of ternary mixture was SA/BSA/HA = 285.1/150.1/10.2 mg·L-1, the deviation for CFV, αc and R was 7.65%, 19.6% and 7.27%, respectively, while the corresponding values for the most suitable binary solution (SA/BSA = 140.4/50.35 mg·L-1) were -12%, 1% and 164% respectively. This indicated that the ternary solution demonstrated a more accurate estimation than the binary solution for imitating the filterability of actual EPS solution. Therefore, the ternary mixture could be employed efficiently to replace the actual EPS solution in terms of three target parameters in practice applications.

Effect of exogenous pulmonary surfactants on mortality rate in neonatal respiratory distress syndrome: A network meta-analysis of randomized controlled trials.

BACKGROUND: The utilization of multiple natural and synthetic products in surfactant replacement therapies in treatment of neonatal respiratory distress syndrome (NRDS) prompted us to take a closer looks at these various therapeutic options and their efficacies. The purpose of our study was to evaluate the effects of six exogenous pulmonary surfactants (EPS) (Survanta, Alveofact, Infasurf, Curosurf, Surfaxin and Exosurf) on mortality rate in NRDS by a network meta-analysis. METHODS: An exhaustive search of electronic databases was performed in PubMed, Ovid, EBSCO, Springerlink, Wiley, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang and VIP databases (last updated search in October 2014) to retrieve randomized controlled trials (RCTs) relevant to our study topic. Published clinical trials were screened based on the following inclusion criteria: (1) study design: RCTs; (2) interventions: treatment with Survanta, Alveofact, Infasurf, Curosurf, Surfaxin or Exosurf for NRDS; (3) study subject: infants with NRDS confirmed by clinical diagnosis; (4) outcome: the mortality rate of infants with NRDS. Statistical analysis was performed using Stata 12.0 software (Stata Corporation, College Station, TX, USA) and Comprehensive Meta-analysis (CMA 2.0) software. RESULTS: From the 1840 studies initially retrieved through database searches, a total of 17 high quality RCTs were selected for this network meta-analysis. The selected studies included a combined total of 57,223 infants with NRDS treated with various EPS (Survanta, 27,017; Alveofact, 159; Infasurf, 20,377; Curosurf, 20,911; Surfaxin, 646; Exosurf, 1640). Network meta-analysis results showed that the mortality rates in NRDS infants treated with Alveofact, Infasurf, Curosurf, Surfaxin, Exosurf were not significantly different compared to Survanta (Alveofact: OR = 1.163, 95% CI = 0.645-2.099, P = 0.616; Infasurf: OR = 0.985, 95% CI = 0.777-1.248, P = 0.897; Curosurf: OR = 0.789, 95% CI = 0.619-1.007, P = 0.056; Surfaxin: OR = 0.728, 95% CI = 0.477-1.112, P = 0.142; Exosurf: OR = 0.960, 95% CI = 0.698-1.319, P = 0.799). Notably, the surface under the cumulative ranking curves (SUCRA) value in Surfaxin group was significantly higher than the other five groups (Surfaxin: 80.4%; Survanta: 37.0%; Alveofact: 24.4%; Infasurf: 40.0%; Curosurf: 73.9%; Exosurf: 44.2%), suggesting that infant mortality rate in Surfaxin group was the lowest among the six EPS groups. CONCLUSION: Our study demonstrated that Surfaxin could effectively reduce the mortality rate of infants with NRDS and may have a better efficacy in NRDS treatment, compared to Survanta, Alveofact, Infasurf, Curosurf and Exosurf.

Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance.

To overcome the P-glycoprotein (P-gp)-induced multidrug resistance (MDR) of cancer cells, a novel copolymer, chitosan-graft-D-α-tocopheryl polyethylene glycol 1000 (TPGS) (CT) was synthesized for doxorubicin (DOX) delivery by the P-gp inhibiting virtue of TPGS. DOX-loaded CT nanoparticles (NPs) were fabricated by a modified solvent extraction/evaporation method combined with ionic cross-linking to form a uniform particle size of 140-180 nm with ∼40% DOX loading efficiency. These drug-loaded CT NPs demonstrated a pH-responsive release behavior, and DOX was released more quickly under low pH values. Significant cell cytotoxicity was observed on the human hepatocarcinoma cells (HepG2 and BEL-7402) and human breast adenocarcinoma cells (MCF-7). The cell cytotoxicity and apoptosis of drug-resistant cells (MCF-7/DOX and BEL-7402/5-Fu), was greatly enhanced as compared to Adriamycin. The IC50 value showed that DOX-loaded CT NPs could be 1.5-199-fold more effective than Adriamycin. This can be attributed to the P-gp blocking and down-regulation of ATP levels by the CT NPs. The potential of these NPs to act as an oral delivery system was also investigated. Both the pharmacokinetic properties and in vivo antitumor activity of DOX-loaded CT NPs were improved compared with Adriamycin.

Efficient, quick, and low-carbon removal mechanism of microplastics based on integrated gel coagulation-spontaneous flotation process.

To address the problems of unstable efficiency, long treatment period, and high energy consumption during microplastics (MPs) removal by traditional coagulation-flotation technology, a gel coagulation-spontaneous flotation (GCSF) process is proposed that employs laminarin (LA) as the crosslinker and polyaluminum chloride (PAC)/polyaluminum ferric chloride (PAFC) as the coagulant to remove MPs. Herein, the effects of GCSF chemical conditions on microplastic-humic acid composite pollutants (MP-HAs) removal were investigated, and the removal mechanisms were analyzed through theoretical calculations and floc structure characterization. Results showed that an LA to PAC/PAFC ratio of 2.5:1 achieved the highest removal of HA (86 %) and MPs (93 %-99 %) in short coagulation (< 1 min) and spontaneous flotation (< 9 min) period. PAC-LA exhibited strong removal ability for MP-HAs while PAFC-LA induced fast flotation speed. The peak intensity and peak shift in Fourier-transformed infrared and X-ray photo-electron spectra indicated that the removal mechanisms of MPs include hydrogen bond adsorption and the sweeping effect, mainly relying on -OH/-C = O on the MPs surface and entrapment of gel flocs with a high degree of aggregation, respectively. The extended Derjaguin-Landau-Verwey-Overbeek calculation also revealed that interactions between PAC/PAFC-LA and MP-HAs were mainly polar interaction (hydrogen bonding) and intermolecular attraction interaction (Lifshitz-van der Waals force), and the sweep effect was reflected by intermolecular interaction. In addition, density function theory calculations indicated that -OH in LA mainly adsorbs DO through a double hydrogen bond configuration, and the crosslinking ligand FeO6/AlO6 assists in DO absorption by -OH.

Dialysis-functionalized microfluidic platform for in situ formation of purified liposomes.

Continuous-flow microfluidic devices have been extensively used for producing liposomes due to their high controllability and efficient synthesis processes. However, traditional methods for liposome purification, such as dialysis, gel chromatography, and ultrafiltration, are incompatible with microfluidic devices, which would dramatically restrict the efficiency of liposome synthesis. In this study, we developed a dialysis-functionalized microfluidic platform (DFMP) for in situ formation of purified drug-loaded liposomes. The device was successfully fabricated by using a high-resolution projection micro stereolithography (PµSL) 3D printer. The integrated DFMP consists of a microfluidic mixing unit, a microfluidic dialysis unit, and a dialysis membrane, enabling the liposome preparation and purification in one device. The purified ICG-loaded liposomes prepared by DFMP had a smaller size (264.01±5.34 nm to 173.93±10.71 nm) and a higher encapsulation efficiency (EE) (43.53±0.07% to 46.07±0.67%). In vivo photoacoustic (PA) imaging experiment demonstrated that ICG-loaded liposomes purified with microfluidic dialysis exhibited a stronger penetration and accumulation (2-3 folds) in tumor sites. This work provides a new strategy for one-step production of purified drug-loaded liposomes.

The pollution characteristics and risk assessment of microplastics in mollusks collected from the Bohai Sea.

Microplastics (MPs) pollution in the marine environment has become a global problem. In this study, a number of 21 mollusk species (n = 2006) with different feeding habits were collected from 11 sites along the Bohai Sea for MPs uptake analysis. The MPs in mollusk samples were isolated and identified by micro-Fourier Transform Infrared Spectroscopy (µ-FTIR), and an assessment of the health risks of MPs ingested by mollusk consumption is also conducted. Approximately 91.9 % of the individuals among all the collected species inhaled MPs, and there was an average abundance of 3.30 ± 2.04 items·individual-1 or 1.04 ± 0.74 items·g-1 of wet weight. The shape of MPs was mainly fiber, and a total number of 8 polymers were detected, of which rayon had the highest detection rate (58.3 %). The highest abundance, uptake rate and polymer composition of MPs was observed in creeping types, suggesting that they might ingest these MPs from their food. The gastropod Siphonalia subdilatata contains the highest levels of MPs, which may increase the risk of human exposure if consumed whole without removing the digestive gland. The polymer risk level of MPs in these mollusks was Level III (H = 299), presenting harmful MPs such as polyvinyl chloride. In terms of human exposure risk, the average risk of human exposure to MPs through consumption of Bohai mollusks is estimated to be 3399 items·(capita·year)-1 (424-9349 items·(capita·year)-1). Overall, this study provides a basis for the ecological and health Risk assessment of MPs in mollusks collected from the coastline of China.

pH-sensitive docetaxel-loaded D-α-tocopheryl polyethylene glycol succinate-poly(ß-amino ester) copolymer nanoparticles for overcoming multidrug resistance.

Multidrug resistance (MDR) is one of the major obstacles to successful chemotherapy. Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) is an important factor responsible for MDR. Herein, a novel copolymer, D-α-tocopheryl polyethylene glycol 1000-block-poly(ß-amino ester) (TPGS-b-PBAE, TP), was synthesized for overcoming multidrug resistance by the synergistic effect of the pH-sensitive behavior of PBAE and P-gp inhibiting activity of TPGS. Docetaxel (DTX) was chosen as the model drug. The resulting DTX-loaded nanoparticles were stable at pH 7.4, while they dissociated in a weakly acidic environment (pH 5.5) and released the incorporated DTX quickly. The DTX-loaded TP nanoparticles increased the cell cytotoxicity against both drug-sensitive human ovarian A2780 and drug-resistant A2780/T cells. The IC(50) of DTX-loaded TP against A2780/T cells was 100-fold lower than that of commercial DTX. This was associated with enhanced DTX-induced apoptosis and cell arrest in the G2/M phase. Furthermore, P-gp inhibition assays, including enhancement of the fluorescence intensity of rhodamine 123 and reduction of the intracellular ATP levels, confirmed the P-gp inhibition nature of the TP copolymer. The use of the TP copolymer is a new approach to improve the therapeutic effect of anticancer drugs in MDR tumors.

Aptamer functionalized cell membrane for brain and nerve cell sensing with high sensitivity and stability.

Accurate dopamine (DA) monitoring with high stability is essential for investigating the chemical basis of brain function and pathology. Electrochemical-based tissue-implantable carbon fiber electrodes (CFEs) show great potential in sensing the dynamics of neurochemicals at a sub-second timescale. However, their anti-fouling property, selectivity, and stability pose challenges. Here, we presented a novel strategy to enhance electrode biocompatibility and stability by modifying CFE with a chitosan (CS) film, brain cell membrane (M), and aptamer cholesterol amphiphiles (DNA-cho). We found that CFE was uniformly covered by a cicada-like membrane after being modified. Electrochemical characterizations indicated that DNA-cho-M-CS-CFE exhibited a wide linear range of DA concentration and showed high sensitivity, specificity, and stability. The electrode also presented excellent fouling resistance and biocompatibility. Moreover, the biosensor was used to detect DA in K+-induced brain slices and PC12 cells with a satisfactory stability and sensitivity and to prove that LPS treatment leads to the delayed and decreased release of DA. DNA-cho-M-CS-CFE showed excellent electrochemical performance and unique advantages for long-term in vivo sensing of living cells, thus providing a new feasible scheme for studying neurochemical kinetics and brain diseases.

Polyethylene glycol-mediated transformation of fused egfp-hph gene under the control of gpd promoter in Pleurotus eryngii.

Pleurotus eryngii was transformed using a polyethylene glycol-mediated method. A plasmid, pEPUGH, containing a reporter gene (enhanced green fluorescent protein gene, egfp) and a positive selectable marker gene (hygromycin phosphotransferase gene, hph) was constructed. The fused egfp-hph gene was placed under the control of the strong and constitutive native gpd promoter from P. eryngii. The recombinant plasmid was used to transform of P. eryngii protoplasts. Successful transformation was demonstrated by molecular analyses. Moreover, the mycelia of the transformants showed green epipolic dispersion on fluorescence microscopy. About 90-210 transformants were produced per µg plasmid DNA per 10(7) viable protoplasts.

A novel sustained release fluoride strip based Poly(propylene carbonate) for preventing caries.

Low-level fluoride in the oral environment for a long sustained period is more effective for preventing caries. However, the current fluoride delivery methods have a short fluoride retention time and high-dose fluoride administration may increase the risk of dental fluorosis. This study developed a novel fluoride strip based poly(propylene carbonate) (PPC), which can improve oral fluoride retention for desirable anticaries effect with minimal side effects. The fluoride strips based PPC (NaF-PPC strips) with different fluoride contents (0, 1.25, 2.5 and 5 wt.%) were developed by melt-blending method. The physico-chemical characteristics, drug loading, drug release properties, remineralization and antibacterial efficacy and biocompatibility of NaF-PPC strips were investigated. The in vitro drug release studies indicated that fluoride release in a sustained manner with no initial burst release and approximately 100% of fluoride ions were released from PPC strips over 24 days. NaF-PPC strips exhibited excellent remineralization and antibacterial potential when fluoride content up to 5%. Combination with biocompatibility, 2.5% NaF-PPC strips could be a promising fluoride application for preventing caries. This work provides an effective and novel topical fluoride delivery for general use.