Mechanism insights into the histopathological changes of polypropylene microplastics induced gut and liver in zebrafish.

Microplastics (MPs), emerging as significant pollutants, have been consistently detected in aquatic environments, with the Yangtze River experiencing a particularly severe level of microplastic pollution, exceeding all other watersheds in China. Polypropylene (PP), the plastic most abundantly found in the middle and lower reaches of the Yangtze River Basin, has less comprehensive research results into its toxic effects. Consequently, the present investigation employed zebrafish as a model organism to delve into the toxicological impacts of polypropylene microplastics (PP-MPs) with a diameter of 5 µm across varying concentrations (300 mg/L and 600 mg/L). Using histopathological, microbiota profiling, and transcriptomic approaches, we systematically evaluated the impact of PP-MPs exposure on the intestine and liver of zebrafish. Histopathological analysis revealed that exposure to PP-MPs resulted in thinner intestinal walls, damaged intestinal mucosa, and hepatic cellular damage. Intestinal microbiota profiling demonstrated that, the richness, uniformity, diversity, and homogeneity of gut microbes significantly increased after the PP-MPs exposure at high concentration. These alterations were accompanied by shifts in the relative abundance of microbiota associated with intestinal pathologies, suggesting a profound impact on the intestinal microbial community structure. Concurrently, hepatic transcriptome analysis and RT-qPCR indicated that the downregulation of pathways and genes associated with cell proliferation regulation and DNA damage repair mechanisms contributed to hepatic cellular damage, ultimately exerting adverse effects on the liver. Correlation analysis between the intestinal microbiota and liver transcriptome profiles further highlighted significant associations between intestinal microbiota and the downregulated hepatic pathways. Collectively, these results provide novel insights into the subacute toxicological mechanisms of PP-MPs in aquatic organisms and highlight the need for further research on the ecological and health risks associated with PP-MPs pollution.

Post COVID-19 pandemic: Disposable face masks as a potential vector of antibiotics in freshwater and seawater.

With the outbreak and widespread of the COVID-19 pandemic, large numbers of disposable face masks (DFMs) were abandoned in the environment. This study first investigated the sorption and desorption behaviors of four antibiotics (tetracycline (TC), ciprofloxacin (CIP), sulfamethoxazole (SMX), and triclosan (TCS)) on DFMs in the freshwater and seawater. It was found that the antibiotics in the freshwater exhibited relatively higher sorption and desorption capacities on the DFMs than those in the seawater. Here the antibiotics sorption processes were greatly related to their zwitterion species while the effect of salinity on the sorption processes was negligible. However, the desorption processes were jointly dominated by solution pH and salinity, with greater desorption capacities at lower pH values and salinity. Interestingly, we found that the distribution coefficient (Kd) of TCS (0.3947 L/g) and SMX (0.0399 L/g) on DFMs was higher than those on some microplastics in freshwater systems. The sorption affinity of the antibiotics onto the DFMs followed the order of TCS > SMX > CIP > TC, which was positively correlated with octanol-water partition coefficient (log Kow) of the antibiotics. Besides, the sorption processes of the antibiotics onto the DFMs were mainly predominated by film diffusion and partitioning mechanism. Overall, hydrophobic interaction regulated the antibiotics sorption processes. These findings would help to evaluate the environmental behavior of DFMs and to provide the analytical framework of their role in the transport of other pollutants.

Enhanced heavy metal adsorption on microplastics by incorporating flame retardant hexabromocyclododecanes: Mechanisms and potential migration risks.

Microplastics (MPs) are known to act as carriers of heavy metals; however, little is known about the intrinsic chemical additives of MPs, such as hexabromocyclododecane (HBCD), in terms of the adsorption behaviors and migration risks of heavy metals on MPs. Here, we reported the potential mechanisms and risks of HBCD inherent in polystyrene (PS) MPs with Cu(II), Ni(II), and Zn(II) adsorption/desorption. A comparison of the adsorption capacity of the metals onto HBCD/PS composites (HBCD/PS) MPs (10.31-20.76 µmol/g), pure MPs (0-3.60 µmol/g), and natural minerals (0.11-13.88 µmol/g) showed that the addition of HBCD significantly promoted the metals adsorption onto the HBCD/PS MPs, and even exceeded that of natural particles. Isotherms and thermodynamic data suggested that the adsorption process of the metals onto the HBCD/PS MPs was spontaneous and endothermic, and that the adsorption was a mainly multi-ion process with an inclined direction. Furthermore, the results of SEM-EDS, FTIR, and XPS analyses, as well as density functional theory well explained that the metals were mainly adsorbed on the -O and -Br groups of the HBCD/PS MPs via electrostatic interactions and surface complexation. More importantly, by comparing the desorption activity with natural river water and seawater, HBCD inherent in MPs can enhance the long-range transfer of metals carried by the HBCD/PS MPs from contamination sources to potential sink like oceans. Thus, the HBCD/PS MPs with high loading of Cu(II), Ni(II), and Zn(II) could be potential secondary sources of these metals in seawater. Overall, these findings revealed the potential risks of flame retardant in MPs associated with metal migration, and advocated that flame retardant-related waste MPs should be included in coastal sustainable development.

Exploration of possible binding sites of nanoparticles on protein by cross-linking chemistry coupled with mass spectrometry.

For the first time, the possible binding site of nanoparticles on protein was revealed by cross-linking chemistry coupled with mass spectrometry. The peptides located very close to the poly(acrylic acid) (PAA)-coated Fe(3)O(4) nanoparticles (NPs) during interaction with human serum albumin (HSA) were cross-linked to the surface of NPs. Following protease digestion, the attached peptides were cleaved off the particle surface and identified by matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). The peptides were found to be part of the so-called drug binding site 2 of HSA; and the competitive binding to HSA between the corresponding drug, ibuprofen, and the NPs was observed. Our results demonstrated that cross-linking chemistry coupled with MS was a quick and simple method for locating the possible binding sites of NPs on protein. Information on NP-protein binding interface will benefit the study of how the interactions are governed by the physicochemical properties of NPs, for guiding the design of functional bionano constructs. It can also help to predict the biological consequence of protein adsorption on NPs, for obtaining more knowledge on nanotoxicity.

Effective treatment of drug-resistant lung cancer via a nanogel capable of reactivating cisplatin and enhancing early apoptosis.

Cisplatin resistance is a daunting obstacle in cancer therapy and one of the major causes for treatment failure due to the inadequate drug activity and apoptosis induction. To overcome cisplatin resistance, we proposed a multifunctional nanogel (designated as Valproate-D-Nanogel) capable of reactivating cisplatin and enhancing early apoptosis. This Valproate-D-Nanogel was prepared through copolymerizing carboxymethyl chitosan with diallyl disulfide and subsequent grafting with valproate to reverse the drug-resistance in cisplatin-resistant human lung adenocarcinoma cancer. It can significantly increase the proportion of G2/M phase (up to 3.2-fold enhancement) to reactivate cisplatin via high level of G2/M arrest induced by valproate. Meanwhile, the intracellular ROS-P53 crosstalk can be upregulated by diallyl disulfide (up to 8-fold increase of ROS) and valproate (up to 18-fold increase of P53) to enhance early apoptosis. The synchronization of enhanced G2/M arrest and ROS-P53 crosstalk devotes to reverse the cisplatin resistance with a high level of resistance reversion index (50.22). As a result, improved in vivo tumor inhibition (up to 15-fold higher compared to free cisplatin) and decreased systemic toxicity was observed after treatment with Valproate-D-Nanogels. Overall, this nanogel can effectively inhibit cisplatin-resistance cancer through combined pathways and provides an effective approach for overcoming cisplatin-resistance in cancer treatment.

Hybrid micelles based on Pt (IV) polymeric prodrug and TPGS for the enhanced cytotoxicity in drug-resistant lung cancer cells.

Multidrug resistance (MDR) is a primary cause of failure in oncotherapy and interest is growing in the design of multi-stimuli responsive nano-carriers to synergistically deliver chemotherapeutic agents and P-gp inhibitors to reverse MDR. The hybrid micelles based on a Platinum (IV)-coordinate polymeric prodrugs and TPGS were developed to improve chemotherapy and reduce side effects. The pH/redox dual-sensitive polymers were synthesized by condensation polymerization using ortho ester monomer and diamminedichlorodisuccinatoplatinum (DSP). The hybrid micelles possessed uniform size (38 nm) and displayed good stability in various physiological conditions. In contrast, in vitro drug release profiles indicated that these micelles could be completely depolymerized under acidic and reducing environment, thereby more than 80 % cisplatin were released within 12 h at pH 5.0 plus 10 mM DTT. More importantly, a large amount of TPGS released simultaneously could effectively inhibit the function of drug efflux pumps, which significantly enhanced the cytotoxicity of cisplatin against A549/DDP cells. The growth inhibition rate of micelles on A549/DDP multicellular spheroids was 79.5 %, while that of free cisplatin was only 6.8 %. Therefore, these hybrid micelles are promising in overcoming tumor MDR and worth doing further research in vivo and extend to other therapeutic agents.

Magnetochromatic microspheres: rotating photonic crystals.

Magnetochromatic microspheres have been fabricated through instant assembly of superparamagnetic (SPM) colloidal particles inside emulsion droplets of UV curable resin followed by an immediate UV curing process to polymerize the droplets and fix the ordered structures. When dispersed in the liquid droplets, superparamagnetic Fe(3)O(4)@SiO(2) core/shell particles self-organize under the balanced interaction of repulsive and attractive forces to form one-dimensional chains, each of which contains periodically arranged particles diffracting visible light and displaying field-tunable colors. UV initiated polymerization of the oligomers of the resin fixes the periodic structures inside the droplet microspheres and retains the diffraction property. Because the superparamagnetic chains tend to align themselves along the field direction, it is very convenient to control the orientation of such photonic microspheres and, accordingly, their diffractive colors, by changing the orientation of the crystal lattice relative to the incident light using magnetic fields. The excellent stability together with the capability of fast on/off switching of the diffraction by magnetic fields makes the system suitable for applications such as color display, rewritable signage, and sensors. As a simple demonstration, we have fabricated a display unit that has on/off bistable states by embedding the magnetochromatic microspheres in a matrix that can thermally switch between solid and liquid phases.

Acid-breakable TPGS-functionalized and diallyl disulfide-crosslinked nanogels for enhanced inhibition of MCF-7/ADR solid tumours.

Herein, a diallyl disulfide (DADS)-crosslinked nanogel (NG) and an ortho ester-conjugated TPGS (T-OE) were synthesized using free radical copolymerization and transesterification, respectively. Then, T-OE was grafted onto the NG to fabricate a dual-functionalized nanogel (TNG), and both the NG and TNG possessed a uniform diameter (∼160 nm) and excellent stability. The DOX-loaded nanogel (NG/D and TNG/D) displayed appropriate release properties under reducing conditions. MCF-7/ADR cell experiments showed that although both the NG/D and TNG/D could increase the production of reactive oxygen species (ROS), only the TNG could effectively overcome the drug efflux by inducing mitochondrial depolarization and by interfering with the metabolism of ATP. Both the cell cytotoxicity and the MCF-7/ADR solid cancer assay indicated that TNG/D possessed a long-acting drug enrichment and enhanced the inhibition, resulting from the combined action of the high ROS level and the suppressed drug efflux. These results demonstrated that the T-OE-functionalized and the DADS-crosslinked NG had a great potential for use in the treatment of MCF-7/ADR tumours.

TPGS-grafted and acid-responsive soy protein nanogels for efficient intracellular drug release, accumulation, penetration in 3D tumor spheroids of drug-resistant cancer cells.

The frequent occurrence of multidrug resistance (MDR) in solid tumors is the major obstacle for nano-drug delivery systems (nDDS) to realize the successful cancer chemotherapy. Herein, we had prepared pH-responsive nanogels via cross-linking TPGS-grafted soy protein with an acid-labile ortho ester cross-linker (OEAM) to realize the efficient intracellular drugs release and accumulation, and subsequently enhance therapeutic effect in MDR tumor cells. These nanogels displayed a uniform size (~200 nm) and morphology, and the introduction of ortho ester bonds endowed nanogels stability in neutral environment and acid-degradability in acidic conditions. Cisplatin (CDDP) was successfully loaded into nanogels, which exhibited an accelerated drug release at low pH. The modification of TPGS efficiently improved cellular internalization and drug accumulation in A549/DDP cells by inhibiting the function of drug efflux pumps (MRP2 and ATP7A/7B), leading to higher cytotoxicity and apoptosis. Moreover, TPGS-grafted nanogels also showed better drug accumulation and penetration in tumor-like spheroids, and then remarkably inhibited tumor growth owing to the rapid drug release in acidic organelles. As a result, the TPGS-grafted and pH-sensitive soy protein nanogels have a great potential as a drugs carrier for the efficient cancer treatment.

Co-delivery of DOX and PDTC by pH-sensitive nanoparticles to overcome multidrug resistance in breast cancer.

Chemotherapeutic drugs have a series of limitations in the conventional clinical treatments, mainly including serious adverse effects and multidrug resistance (MDR). Herein, we developed a pH-sensitive polymeric nanoparticle with using poly(ortho ester urethanes) copolymers for co-delivering doxorubicin (DOX) and pyrrolidinedithiocarbamate (PDTC) to settle these problems. Dual-drug-loaded nanoparticles were nano-sized (˜220 nm) with the spherical morphology and excellent physiological stability. Both drugs both could be quickly released in the mild acidic conditions due to the cleavage of ortho ester bonds. Monolayer cultured cells (2D) and multicellular spheroids (3D) experiments proved that PDTC could reverse multidrug resistance (MDR), improve intracellular drugs accumulation and enhance tumor penetration by down-regulating the expression of P-gp, then resulting in higher DOX-induced cytotoxicity and apoptosis in MCF-7 and MCF-7/ADR cells. Besides, in vivo experiments further demonstrated that co-encapsulated nanoparticles had higher DOX accumulation and superiorer tumor growth inhibition (TGI 82.9%) than free drugs or single-drug-loaded nanoparticles on MCF-7/ADR bearing-mice. Accordingly, the pH-sensitive co-delivery systems possess a promising potential to overcome MDR in cancer therapy.

Hybrid pH-sensitive nanogels surface-functionalized with collagenase for enhanced tumor penetration.

Densely extracellular matrix (ECM) is one of the main barriers that hinder the penetration of drug into tumor parenchyma, compromising the therapeutic activity. In this work, alginic acid was copolymerized with an acid-labile monomer to give the acid-degradable nanogels (ALG NG), which was then immobilized with collagenase to obtain the surface-functionalized nanogels (Co@ALG NG). The introduction of collagenase would enhance the diffusion ability of nanogels in tumor parenchyma based on the hydrolytic activity to tumor ECM. The stability of these nanogels in various physiological environment and the pH-triggered degradation and drug release at different pH were then investigated. Monolayer cell and tumor-like spheroids were used to illustrate the penetration and drug delivery. In vivo drug distribution and antitumor efficiency of these nanogels were investigated using H22 tumor-bearing mice. The immobilization of collagenase significantly enhance the nanogels' penetration and diffusion ability in tumor area upon the digestion of tumor ECM, leading to higher drug concentration and superior antitumor effect.

Magnetochromatic thin-film microplates.

A new type of magnetochromatic material is developed based on thin-film interference of microplates self-assembled from super-paramagnetic nanocrystals. Dynamic optical tuning can be achieved through orientational manipulation of free-standing super-paramagnetic thin-film microplates using external magnetic fields.

[External ear reconstruction using expanded postauricular scar flap and Medpor framework].

OBJECTIVE: To investigate the possibility of external ear reconstruction using expanded postauricular scar flap and Medpor framework in burn cases. METHODS: External ear reconstruction using expanded postauricular scar flap in combination with Medpor framework was performed in 17 cases whose ear had burn injury. RESULTS: Of the 17 cases, 15 cases achieved success; 2 cases experienced partial exposure of the framework due to inadequate wrapping of the subcutaneous fascia flap and later injury. The longest follow-up was three years, and the final result was satisfactory. CONCLUSIONS: External ear reconstruction using expanded postauricular scar flap in combination with Medpor framework is a reliable method for adult (over 25 years) who has ear defect from burn injury.