Fabricating Polymeric Micelles with Enrichment and Cavity Effect for In Situ Enzyme Imobilization from Natural Biosystems.

Metal-organic frameworks and hydrogen-organic frameworks (MOFs and HOFs) are attractive hosts for enzyme immobilization, but they are limited to immobilizing the purified enzymes, making industrial upscaling unattractive. Herein, aptamer-modified dual thermoresponsive polymeric micelles with switchable self-assembly and core-shell structure are constructed, which enable selective immobilization of trypsin directly from complex biological systems through a cascade operation of separation and immobilization. Their steric self-assembly provides a large amount of adsorption sites on the soluble micellar shell, resulting in high adsorption capacity and excellent selectivity. Meanwhile, their aptamer affinity ligand and cavity maintain the native conformations of trypsin and offer protective effects even in harsh conditions. The maximum adsorption capacity of the polymeric micelles for trypsin was determined to be 197 mg/g at 60 min, superior to those of MOFs and HOFs. 67.2 and 86.6% of its original activity was retained for trypsin immobilized in the cavity under strong alkaline and acidic conditions, respectively.

Highly Sensitive, Stable InP Quantum Dot Fluorescent Probes for Quantitative Immunoassay Through Nanostructure Tailoring and Biotin-Streptavidin Coupling.

Nontoxic, highly sensitive InP quantum dot (QD) fluorescent immunoassay probes are promising biomedical detection modalities due to their unique properties. However, InP-based QDs are prone to surface oxidation, and the stability of InP QD-based probes in biocompatible environments remains a crucial challenge. Although the thick shell can provide some protection during the phase transfer process of hydrophobic QDs, the photoluminescence quantum yield (PLQY) is generally decreased because of the contradiction between lattice stress relaxation and thick shell growth. Herein, we developed thick-shell InP-based core/shell QDs by inserting a ZnSeS alloy layer. The ternary ZnSeS intermediate shell could effectively facilitate lattice stress relaxation and passivate the defect states. The synthesized InP/ZnSe/ZnSeS/ZnS core/alloy shell/shell QDs (CAS-InP QDs) with nanostructure tailoring revealed a larger size, high PLQY (90%), and high optical stability. After amphiphilic polymer encapsulation, the aqueous CAS-InP QDs presented almost constant fluorescence attenuation and stable PL intensity under different temperatures, UV radiation, and pH solutions. The CAS-InP QDs were excellent labels of the fluorescence-linked immunosorbent assay (FLISA) for detecting C-reactive protein (CRP). The biotin-streptavidin (Bio-SA) system was first introduced in the FLISA to further improve the sensitivity, and the CAS-InP QDs-based SA-Bio sandwich FLISA realized the detection of CRP with an impressive limit of detection (LOD) of 0.83 ng/mL. It is believed that the stable and sensitive InP QD fluorescent probes will drive the rapid development of future eco-friendly, cost-effective, and sensitive in vitro diagnostic kits.

Traditional and Novel Organophosphate Esters in Plastic Greenhouse: Occurrence, Multimedia Migration, and Exposure Risk via Vegetable Consumption.

The migration and risk of organophosphate esters (OPEs) in agricultural air-soil-plant multimedia systems due to plastic film application remain unclear. This study investigates the multimedia distribution of traditional OPEs (TOPEs), novel OPEs (NOPEs), and their transformation products (POPEs) in plastic and solar greenhouses. The total concentration of OPE-associated contaminants in air and airborne particles ranged from 594 to 1560 pg/m3 and 443 to 15600 ng/g, respectively. Significant correlations between air OPE concentrations and those in polyolefin film (P < 0.01) indicate plastic film as the primary source. Contaminants were also found in soils (96.8-9630 ng/g) and vegetables (197-7540 ng/g). The primary migration pathway for NOPEs was particle dry deposition onto the soil and leaf, followed by plant accumulation. Leaf absorption was the main uptake pathway for TOPEs and POPEs, influenced by vegetable specific leaf surface area. Moreover, total exposure to OPE-associated contaminants via vegetable intake was assessed at 2250 ng/kg bw/day for adults and 2900 ng/kg bw/day for children, with an acceptable hazard index. However, a high ecological risk was identified for NOPE compounds (median risk quotient, 975). This study provides the first evidence of the multimedia distribution and potential threat posed by OPE-associated contaminants in agricultural greenhouses.

The "Microplastome" - A Holistic Perspective to Capture the Real-World Ecology of Microplastics.

Microplastic pollution, an emerging pollution issue, has become a significant environmental concern globally due to its ubiquitous, persistent, complex, toxic, and ever-increasing nature. As a multifaceted and diverse suite of small plastic particles with different physicochemical properties and associated matters such as absorbed chemicals and microbes, future research on microplastics will need to comprehensively consider their multidimensional attributes. Here, we introduce a novel, conceptual framework of the "microplastome", defined as the entirety of various plastic particles (<5 mm), and their associated matters such as chemicals and microbes, found within a sample and its overall environmental and toxicological impacts. As a novel concept, this paper aims to emphasize and call for a collective quantification and characterization of microplastics and for a more holistic understanding regarding the differences, connections, and effects of microplastics in different biotic and abiotic ecosystem compartments. Deriving from this lens, we present our insights and prospective trajectories for characterization, risk assessment, and source apportionment of microplastics. We hope this new paradigm can guide and propel microplastic research toward a more holistic era and contribute to an informed strategy for combating this globally important environmental pollution issue.

Caspase-3 and gasdermin E mediate macrophage pyroptosis in periodontitis.

BACKGROUND AND OBJECTIVES: Periodontitis is a chronic inflammatory disease linked to pyroptosis, an inflammatory cell death process. Macrophages are essential for maintaining microenvironment homeostasis, which is crucial for periodontal health. This study explores the mechanisms underlying the relationship between macrophage pyroptosis and periodontitis. METHODS: Expression of the pyroptosis marker gasdermin E (GSDME) and the macrophage surface marker CD68 was examined by immunofluorescence double staining in healthy and periodontitis gingival tissues. In an in vitro pyroptosis model, RAW264.7 cells were irritated using Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) after treatment with either a nuclear factor kappa-B (NF-κB) agonist or inhibitor. The mRNA and protein levels of NF-κB, caspase-3, GSDME, and interleukin-1ß (IL-1ß) were evaluated through qRT-PCR, western blotting, and ELISA techniques. RESULTS: GSDME and CD68 were heavily elevated in inflamed gingival tissues compared to healthy tissues and co-localized in the same region. Furthermore, exposure to P. gingivalis-LPS resulted in a significant upregulation of NF-κB, caspase-3, GSDME, and IL-1ß at both the mRNA and protein levels in RAW264.7 cells. NF-κB agonist or inhibitor pretreatment enhanced or inhibited these effects. CONCLUSIONS: GSDME-mediated macrophage pyroptosis is implicated in periodontitis. Based on in vitro experiments, P. gingivalis-LPS causes pyroptosis in RAW264.7 cells through the caspase-3/GSDME pathway. Furthermore, NF-κB regulates this pyroptotic pathway.

Citric Acid and Polyvinyl Alcohol Induced PEDOT: PSS with Enhanced Electrical Conductivity and Stretchability for Eco-Friendly, Self-Healable, Wearable Organic Thermoelectrics.

Poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT: PSS) is a promising material for organic thermoelectric (TE) applications. However, it is challenging to achieve PEDOT: PSS composites with stretchable, self-healable, and high TE performance. Furthermore, some existing self-healing TE materials employ toxic reagents, posing risks to human health and the environment. In this study, a novel intrinsically self-healable and wearable composite is developed by incorporating environmentally friendly, highly biocompatible, and biodegradable materials of polyvinyl alcohol (PVA) and citric acid (CA) into PEDOT: PSS. This results in the formation of double hydrogen bonding networks among CA, PVA, and PEDOT: PSS, inducing microstructure alignment and leading to simultaneous enhancements in both TE performance and stretchability. The resulting composites exhibit a high electrical conductivity and power factor of 259.3 ± 11.7 S·cm-1, 6.9 ± 0.4 µW·m-1·K-2, along with a tensile strain up to 68%. Furthermore, the composites display impressive self-healing ability, with 84% recovery in electrical conductivity and an 85% recovery in tensile strain. Additionally, the temperature and strain sensors based on the PEDOT: PSS/PVA/CA are prepared, which exhibit high resolution suitable for human-machine interaction and wearable devices. This work provides a reliable and robust solution for the development of environmentally friendly, self-healing and wearable TE thermoelectrics.

Constructing green superhydrophilic and superoleophobic COFs-MOFs hybrid-based membrane for efficiently emulsion separation and synchronous removal of microplastics, dyes, and pesticides.

Oil spills and micropollutants have become thorny environmental issues, posing serious threat to ecosystem and human health. To settle such dilemma, this study successfully constructed a robust and environmentally-friendly MOFs-COFs hybrid-based membrane (FS-50/COF(MATPA)-MOF(Zr)/PDA@PVDF) for the first time through solution synthesis and solvothermal method, combined with surface modification of FS-50 molecule. Importantly, we employed a simple two-step strategy to obtain the high-aspect-ratio MOFs fibers: (1) solvent regulation to generate smaller needle-like whiskers during the in-situ growth of MOFs on COFs; (2) high pressure induced directional crystallization in filtration process. The introduction of polydopamine (PDA) greatly improved the adhesion between coating and PVDF membrane. The in-situ growth of high length-diameter ratio MOFs fibers on blocky COFs greatly enhanced the specific surface area of MOFs-COFs hybrid, thus provided sufficient absorption sites. The functional groups of FS-50 endowed the hybrid membrane with superhydrophilicity and superoleophobicity, which facilitated to selectively penetrate water molecules and repel non-polar pollutants. The separation efficiency and decontamination mechanism of hybrid membrane to the simulated oily wastewater (containing various MPs, dyes, and pesticides) were investigated through experiments and theoretical calculations. The hybrid membrane could selectively and synchronously adsorb various dyes (20 mg/L-120 mg/L, almost 100% removal) and pesticides (10 mg/L for DIF and TET, adsorption rates 93.2% and 90.9%, respectively) from oil-water emulsion (50 mL). The large-scale coated sponge (6 cm × 4.5 cm × 3 cm) could quickly achieve separation of oil-water mixture (almost 100%) with a water permeability of more than 162 L m-2·h-1·bar-1, and simultaneously remove various MPs (PP-2000, PP-100, PE-2000, PS-100, 0.2 g/300 mL for each), Sudan Ⅲ (C0 = 200 mg/L), and DIF (C0 = 10 mg/L) from a simulant oily wastewater (300 mL), with the removal rates of almost 100% for MPs, 99.7% for Sudan Ⅲ, and 95.8% for DIF. Furthermore, we elucidated the removal mechanism of pesticide and dyes through simulating the theoretical adsorption energy and potential adsorption sites. The hybrid membrane not only provides a promising candidate for the removal of multiple pollutants from oil-water emulsion, but also opens a new strategy for achieving efficient and clean aquatic environment restoration.

Retrieval analysis of PEEK rods pedicle screw system: three cases analysis.

PURPOSE: To analyze the characteristics of PEEK rods retrieved in vivo, specifically their wear and deformation, biodegradability, histocompatibility, and mechanical properties. METHOD: Six PEEK rods were retrieved from revision surgeries along with periprosthetic tissue. The retrieved PEEK rods were evaluated for surface damage and internal changes using Micro-CT, while light and electron microscopy were utilized to determine any histological changes in periprosthetic tissues. Patient history was gathered from medical records. Two intact and retrieved PEEK rods were used for fatigue testing analysis by sinusoidal load to the spinal construct. RESULTS: All implants showed evidence of plastic deformation around the screw-rod interface, while the inner structure of PEEK rods appeared unchanged with no visible voids or cracks. Examining images captured through light and electron microscopy indicated that phagocytosis of macrophages around PEEK rods was less severe in comparison to the screw-rod interface. The results of an energy spectrum analysis suggested that the distribution of tissue elements around PEEK rods did not differ significantly from normal tissue. During fatigue testing, it was found that the retrieved PEEK rods cracked after 1.36 million tests, whereas the intact PEEK rods completed 5 million fatigue tests without any failure. CONCLUSION: PEEK rods demonstrate satisfactory biocompatibility, corrosion resistance, chemical stability, and mechanical properties. Nevertheless, it is observed that the indentation at the junction between the nut and the rod exhibits relatively weak strength, making it susceptible to breakage. As a precautionary measure, it is recommended to secure the nut with a counter wrench, applying the preset torque to prevent overtightening.

Interdependent recruitment of CYC8/TUP1 and the transcriptional activator XYR1 at target promoters is required for induced cellulase gene expression in Trichoderma reesei.

Cellulase production in filamentous fungus Trichoderma reesei is highly responsive to various environmental cues involving multiple positive and negative regulators. XYR1 (Xylanase regulator 1) has been identified as the key transcriptional activator of cellulase gene expression in T. reesei. However, the precise mechanism by which XYR1 achieves transcriptional activation of cellulase genes is still not fully understood. Here, we identified the TrCYC8/TUP1 complex as a novel coactivator for XYR1 in T. reesei. CYC8/TUP1 is the first identified transcriptional corepressor complex mediating repression of diverse genes in Saccharomyces cerevisiae. Knockdown of Trcyc8 or Trtup1 resulted in markedly impaired cellulase gene expression in T. reesei. We found that TrCYC8/TUP1 was recruited to cellulase gene promoters upon cellulose induction and this recruitment is dependent on XYR1. We further observed that repressed Trtup1 or Trcyc8 expression caused a strong defect in XYR1 occupancy and loss of histone H4 at cellulase gene promoters. The defects in XYR1 binding and transcriptional activation of target genes in Trtup1 or Trcyc8 repressed cells could not be overcome by XYR1 overexpression. Our results reveal a novel coactivator function for TrCYC8/TUP1 at the level of activator binding, and suggest a mechanism in which interdependent recruitment of XYR1 and TrCYC8/TUP1 to cellulase gene promoters represents an important regulatory circuit in ensuring the induced cellulase gene expression. These findings thus contribute to unveiling the intricate regulatory mechanism underlying XYR1-mediated cellulase gene activation and also provide an important clue that will help further improve cellulase production by T. reesei.

Alumina inorganic molecularly imprinted polymer modified multi-walled carbon nanotubes for uric acid detection in sweat.

Alumina inorganic molecularly imprinted polymer (MIP) modified multi-walled carbon nanotubes (MWCNTs) on a glassy carbon electrode (MWCNTs-Al2O3-MIP/GCE) was firstly designed and fabricated by one-step electro deposition technique for the detection of uric acid (UA) in sweat. The UA templates were embedded within the inorganic MIP by co-deposition with Al2O3. Through the evaluation of morphology and structure by Field Emission Scanning Electron Microscope (SEM), Energy Dispersive X-ray Spectroscopy (EDS), X-ray Photoelectron Spectroscopy (XPS) and Transmission Electron Microscopy (TEM), it was verified that the specific recognition sites can be fabricated in the electrodeposited Al2O3 molecular imprinted layer. Due to the high selectivity of molecular imprinting holes, the MWCNTs-Al2O3-MIP/GCE electrode demonstrated an impressive imprinting factor of approximately 2.338 compared to the non-molecularly imprinted glassy carbon electrode (MWCNTs-Al2O3-NIP/GCE) toward uric acid detection. Moreover, it exhibited a remarkable limit of detection (LOD) of 50 nM for UA with wide detection range from 50 nM to 600 µM. The MWCNTs-Al2O3-MIP/GCE electrode also showed strong interference resistance against common substances found in sweat. These results highlight the excellent interference resistance and selectivity of MWCNTs-Al2O3-MIP/GCE sensor, positioning it as a novel sensing platform for non-invasive uric acid detection in human sweat.

Application of Oral Retractor for Lip Injury Protection in Oral and Maxillofacial Surgeries: A Randomized Controlled Trial.

PURPOSE: Iatrogenic lip injury may occur during oral and maxillofacial surgical procedures. This study aimed to evaluate the effect of oral retractors on iatrogenic lip injury prevention during intraoral procedures of oral and maxillofacial surgery. METHODS: We conducted a randomized controlled trial and included patients who underwent intraoral procedures of oral and maxillofacial surgery. Patients were randomly allocated to receive oral retractor (intervention group) or traditional procedure without lip protection (control group). The incidence of lip injury was the outcome variable. Other study variables included surgical time and satisfaction of patients and surgeons with treatment experience evaluated by visual analog scale (VAS). Student t test and χ 2 test were used to compare both groups' variables and measure the relationship between the predictor variable and the outcome variable. P <0.05 was considered significant for all analyses. RESULTS: A total of 114 patients were included, with 56 allocated to intervention group and 58 to control group. The results showed that the application of an oral retractor did not significantly increase surgical time ( P =0.318). A total of 12 patients had lip injury, with 1 in the intervention group and 11 in the control group ( P =0.003). For the assessment of satisfaction with treatment experience, the intervention group had significantly higher VAS scores for doctors and patients ( P <0.05). CONCLUSIONS: We found that the oral retractor was a good tool for iatrogenic lip injury prevention in oral and maxillofacial surgical procedures and could be considered in clinical treatment.

Genome-Wide Characterization and Expression Analyses of Major Latex Protein Gene Family in Populus simonii × P. nigra.

Major latex proteins, or MLPs, are crucial to plants' capacity to grow, develop, and endure biotic and abiotic stresses. The MLP gene family has been found in numerous plants, but little is known about its role in Populus simonii × P. nigra. This study discovered and assessed 43 PtMLP genes that were unevenly dispersed throughout 12 chromosomes in terms of their physicochemical characteristics, gene structure, conserved motifs, and protein localization. Based on their phylogeny and protein structural characteristics, three separate subclasses of PtMLP family were identified. Segmental and tandem duplication were found to be essential variables in the expansion of the PtMLP genes. The involvement of the PtMLP genes in growth and development, as well as in the responses to different hormones and stresses, was demonstrated by cis-regulatory element prediction. The PtMLP genes showed varying expression patterns in various tissues and under different conditions (cold, salt, and drought stress), as demonstrated in RNA-Seq databases, suggesting that PsnMLP may have different functions. Following the further investigation of the genes demonstrating notable variations in expression before and after the application of three stresses, PsnMLP5 was identified as a candidate gene. Subsequent studies revealed that PsnMLP5 could be induced by ABA treatment. This study paves the way for further investigations into the MLP genes' functional mechanisms in response to abiotic stressors, as well as the ways in which they can be utilized in poplar breeding for improved stress tolerance.

Function Analysis of a Maize Endo-1,4-ß-xylanase Gene ZmHSL in Response to High-Temperature Stress.

Rising temperature is a major threat to the normal growth and development of maize, resulting in low yield production and quality. The mechanism of maize in response to heat stress remains uncertain. In this study, a maize mutant Zmhsl-1 (heat sensitive leaves) with wilting and curling leaves under high temperatures was identified from maize Zheng 58 (Z58) mutant lines generated by ethyl methanesulfonate (EMS) mutagenesis. The Zmhsl-1 plants were more sensitive to increased temperature than Z58 in the field during growth season. The Zmhsl-1 plants had lower plant height, lower yield, and lower content of photosynthetic pigments. A bulked segregant analysis coupled with whole-genome sequencing (BSA-seq) enabled the identification of the corresponding gene, named ZmHSL, which encodes an endo-ß-1,4-xylanase from the GH10 family. The loss-of-function of ZmHSL resulted in reduced lignin content in Zmhsl-1 plants, leading to defects in water transport and more severe leaf wilting with the increase in temperature. RNA-seq analysis revealed that the differentially expressed genes identified between Z58 and Zmhsl-1 plants are mainly related to heat stress-responsive genes and unfolded protein response genes. All these data indicated that ZmHSL plays a key role in lignin synthesis, and its defective mutation causes changes in the cell wall structure and gene expression patterns, which impedes water transport and confers higher sensitivity to high-temperature stress.

Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells.

Dimethyl fumarate (DMF), originally proposed to treat multiple sclerosis, is considered to have a spectrum of anti-inflammatory effects that effectively control periodontitis, mainly when applied with a hydrogel delivery system. Chemokine expression by gingival fibroblasts is a significant driver of periodontitis; thus, hydrogel-based strategies to deliver DMF, which in turn dampen chemokine expression, are of potential clinical relevance. To test this approach, we have established a bioassay where chemokine expression is induced by exposing gingival fibroblast to IL1ß and TNFα, or with saliva. We show herein that DMF effectively reduced the expression of CXCL8, CXCL1, CXCL2, and CCL2-and lowered the phosphorylation of ERK and JNK-without affecting cell viability. This observation was confirmed by immunoassays with CXCL8. Consistently, the forced chemokine expression in HSC2 oral squamous epithelial cells was greatly diminished by DMF. To implement our hydrogel-based delivery system, gingival fibroblasts were cocultured with gellan gum hydrogels enriched for DMF. In support of our strategy, DMF-enriched gellan gum hydrogels significantly reduced the forced chemokine expression in gingival fibroblasts. Our data suggest that DMF exerts its anti-inflammatory activity in periodontal cells when released from gellan gum hydrogels, suggesting a potential clinical relevance to control overshooting chemokine expression under chronic inflammatory conditions.

Fluoride removal from coal mining water using novel polymeric aluminum modified activated carbon prepared through mechanochemical process.

Defluoridation of coal mining water is of great significance for sustainable development of coal industry in western China. A novel one-step mechanochemical method was developed to prepare polymeric aluminum modified powder activated carbon (PAC) for effective fluoride removal from coal mining water. Aluminum was stably loaded on the PAC through facile solid-phase reaction between polymeric aluminum (polyaluminum chloride (PACl) or polyaluminum ferric chloride (PAFC)) and PAC (1:15 W/W). Fluoride adsorption on PACl and PAFC modified PAC (C-PACl and C-PAFC) all reached equilibrium within 5 min, at rate of 2.56 g mg-1 sec-1 and 1.31 g mg-1 sec-1 respectively. Larger increase of binding energy of Al on C-PACl (AlF bond: 76.64 eV and AlFOH bond: 77.70 eV) relative to that of Al on C-PAFC (AlF bond: 76.52 eV) explained higher fluoride uptake capacity of C-PACl. Less chloride was released from C-PACl than that from C-PAFC due to its higher proportion of covalent chlorine and lower proportion of ionic chlorine. The elements mapping and atomic composition proved the stability of Al loaded on the PAC as well as the enrichment of fluoride on both C-PACl and C-PAFC. The Bader charge, formation energy and bond length obtained from DFT computational results explained the fluoride adsorption mechanism further. The carbon emission was 7.73 kg CO2-eq/kg adsorbent prepared through mechanochemical process, which was as low as 1:82.3 to 1:8.07 × 104 compared with the ones prepared by conventional hydrothermal methods.

Water-Triggered Segment Orientation of Long-Lasting Anti-Biofouling Polyurethane Coatings on Biomedical Catheters via Solvent Exchange Strategy.

The formation of biofilm and thrombus on medical catheters poses a significant life-threatening concern. Hydrophilic anti-biofouling coatings upon catheter surfaces with complex shapes and narrow lumens are demonstrated to have the potential in reducing complications. However, their effectiveness is constrained by poor mechanical stability and weak substrate adhesion. Herein, a novel zwitterionic polyurethane (SUPU) with strong mechanical stability and long-term anti-biofouling is developed by controlling the ratio of sulfobetaine-diol and ureido-pyrimidinone. Once immersed in water, as-synthesized zwitterionic coating (SUPU3 SE) would undergo a water-driven segment reorientation to obtain much higher durability than its direct drying one, even under various extreme treatments, including acidic solution, abrasion, ultrasonication, flushing, and shearing, in PBS at 37 °C for 14 days. Moreover, SUPU3 SE coating could achieve a 97.1% of exceptional reducing protein fouling, complete prevention of cell adhesion, and long-lasting anti-biofilm performance even after 30 days. Finally, the good anti-thrombogenic formations of SUPU3 SE coating with bacterial treatment are validated in blood circulation through an ex vivo rabbit arteriovenous shunt model. This work provides a facile approach to fabricating stable hydrophilic coating through a simple solvent exchange to reduce thrombosis and infection of biomedical catheters.

Activation of CYP3A by Accelerated Blood Clearance Phenomenon Potentiates the Hepatocellular Carcinoma-Targeting Therapeutic Effects of PEGylated Anticancer Prodrug Liposomes.

Reduced enzyme activity in hepatocellular carcinoma (HCC) and poor targeting limit the application of enzyme-activating prodrugs, which is also detrimental to the effective treatment of HCC. Here, we investigated whether accelerated blood clearance (ABC) phenomenon occurs in HCC models following repeated injections of PEGylated liposomes (PEG-L), thus inducing prodrug accumulation and activation in the liver and exerting highly effective and low-toxicity therapeutic effects on HCC. First, PEGylated liposomal cyclophosphamide was prepared by solvent injection and characterized. Importantly, preinjection of PEG-L induced the ABC phenomenon and activation of CYP3A in both HCC rats and HCC mice by studying the effects of repeated injections of PEG-L on pharmacokinetics and tissue distribution. Next, the efficacy and toxicity of repeated injections of PEG-L in HCC mice were examined, and our data indicate that repeated injections are administered in a manner that significantly enhances the antitumor effect compared with controls, with little or no toxicity to other organs. To further reveal the pharmacokinetic mechanism of PEG-L repeated administration for the treatment of HCC, the protein expression of hepatic CYP3A and the concentration of cyclophosphamide in the liver and spleen of HCC mice by inhibiting CYP3A were analyzed. These results revealed that inducing CYP3A to accelerate the rapid conversion of prodrugs that accumulate significantly in the liver is a key mechanism for the treatment of HCC with repeated injections of PEG-L. Collectively, this work taps into the application potential of the ABC phenomenon and provides new insights into the clinical application of PEGylated nanoformulations. SIGNIFICANCE STATEMENT: This study revealed that repeated injections of PEGylated liposomes could induce the accelerated blood clearance (ABC) phenomenon characterized by hepatic accumulation and CYP3A activation based on hepatocellular carcinoma (HCC) rats and HCC mice. Furthermore, it was verified that induction of the ABC phenomenon dependent on hepatic accumulation and CYP3A activation could enhance the antihepatocellular carcinoma effects of PEGylated anticancer prodrugs in HCC mice. This elucidated the relevant pharmacokinetic mechanisms and unearthed new clues for solving the clinical application of PEGylated nanoparticles.

Engineered and Durable Antimicrobial Polymer via Controllable Immobilization of Ionic Liquids onto the Poly(lactic acid) Chains.

Nowadays, the development of effective modification methods for PLA has gained significant interest because of the wide application of antimicrobial PLA materials in the medical progress. Herein, the ionic liquid (IL) 1-vinyl-3-butylimidazolium bis(trifluoromethylsulfonyl)imide, has been grafted onto the PLA chains successfully in the PLA/IL blending films via electron beam (EB) radiation for the miscibility between PLA and IL. It was found that the existence of IL in the PLA matrix can significantly improve the chemical stability under EB radiation. The Mn of PLA-g-IL copolymer did not change obviously but was just decreased from 6.80 × 104 g/mol to 5.20 × 104 g/mol after radiation with 10 kGy. The obtained PLA-g-IL copolymers showed excellent filament forming property during electrospinning process. The spindle structure on the nanofibers can be completely eliminated after feeding only 0.5 wt % ILs for the improvement of ionic conductivity. Specially, the prepared PLA-g-IL nonwovens exhibited outstanding and durable antimicrobial activity for the enrichment of immobilized ILs on the nanofiber surface. This work provides a feasible strategy to realize the modification of functional ILs onto PLA chains with low EB radiation doses, which may have huge potential application in the medical and packaging industry.

Identification of Poly(ethylene terephthalate) Nanoplastics in Commercially Bottled Drinking Water Using Surface-Enhanced Raman Spectroscopy.

Micro/nanoplastics have emerged as global contaminants of serious concern to human and ecosystem health. However, identification and visualization of microplastics and particularly nanoplastics have remained elusive due to the lack of feasible and reliable analytical approaches, particularly for trace nanoplastics. Here, an efficient surface-enhanced Raman spectroscopy (SERS)-active substrate with triangular cavity arrays is reported. The fabricated substrate exhibited high SERS performance for standard polystyrene (PS) nanoplastic detection with size down to 50 nm and a detection limit of 0.001% (1.5 × 1011 particles/mL). Poly(ethylene terephthalate) (PET) nanoplastics collected from commercially bottled drinking water were detected with an average mean size of ∼88.2 nm. Furthermore, the concentration of the collected sample was estimated to be about 108 particles/mL by nanoparticle tracking analysis (NTA), and the annual nanoplastic consumption of human beings through bottled drinking water was also estimated to be about 1014 particles, assuming water consumption of 2 L/day for adults. The facile and highly sensitive SERS substrate provides more possibilities for detecting trace nanoplastics in an aquatic environment with high sensitivity and reliability.

Nontarget Identification of Novel Organophosphorus Flame Retardants and Plasticizers in Rainfall Runoffs and Agricultural Soils around a Plastic Recycling Industrial Park.

Plastic recycling and reprocessing activities may release organophosphate ester (OPE) flame retardants and plasticizers into the surrounding environment. However, the relevant contamination profiles and impacts remain not well studied. This study investigated the occurrence of 28 OPEs and their metabolites (mOPEs) in rainfall runoffs and agricultural soils around one of the largest plastic recycling industrial parks in North China and identified novel organophosphorus compounds (NOPs) using high-resolution mass spectrometry-based nontarget analysis. Twenty and twenty-seven OPEs were detected in runoff water and soil samples, with total concentrations of 86.0-2491 ng/L and 2.53-199 ng/g dw, respectively. Thirteen NOPs were identified, of which eight were reported in the environment for the first time, including a chlorine-containing OPE, an organophosphorus heterocycle, a phosphite, three novel OPE metabolites, and two oligomers. Triphenylphosphine oxide and diphenylphosphinic acid occurred ubiquitously in runoffs and soils, with concentrations up to 390 ng/L and 40.2 ng/g dw, respectively. The downwind areas of the industrial park showed elevated levels of OPEs and NOPs. The contribution of hydroxylated mOPEs was higher in soils than in runoffs. These findings suggest that plastic recycling and reprocessing activities are significant sources of OPEs and NOPs and that biotransformation may further increase the ecological and human exposure risk.