Grass-Specific EPAD1 Is Essential for Pollen Exine Patterning in Rice.

The highly variable and species-specific pollen surface patterns are formed by sporopollenin accumulation. The template for sporopollenin deposition and polymerization is the primexine that appears on the tetrad surface, but the mechanism(s) by which primexine guides exine patterning remain elusive. Here, we report that the Poaceae-specific EXINE PATTERN DESIGNER 1 (EPAD1), which encodes a nonspecific lipid transfer protein, is required for primexine integrity and pollen exine patterning in rice (Oryza sativa). Disruption of EPAD1 leads to abnormal exine pattern and complete male sterility, although sporopollenin biosynthesis is unaffected. EPAD1 is specifically expressed in male meiocytes, indicating that reproductive cells exert genetic control over exine patterning. EPAD1 possesses an N-terminal signal peptide and three redundant glycosylphosphatidylinositol (GPI)-anchor sites at its C terminus, segments required for its function and localization to the microspore plasma membrane. In vitro assays indicate that EPAD1 can bind phospholipids. We propose that plasma membrane lipids bound by EPAD1 may be involved in recruiting and arranging regulatory proteins in the primexine to drive correct exine deposition. Our results demonstrate that EPAD1 is a meiocyte-derived determinant that controls primexine patterning in rice, and its orthologs may play a conserved role in the formation of grass-specific exine pattern elements.

Emerging Health Risks of Crumb Rubber: Inhalation of Environmentally Persistent Free Radicals via Saliva During Artificial Turf Activities.

Crumb rubber (CR) is a commonly used infill material in artificial turf worldwide. However, the potential health risk associated with exposure to CR containing environmentally persistent free radicals (EPFRs) remains under investigation. Herein, we observed the widespread presence of CR particles in the range of 2.8-51.4 µg/m3 and EPFRs exceeding 6 × 1015 spins/g in the ambient air surrounding artificial turf fields. Notably, the abundance of these particles tended to increase with the number of operating years of the playing fields. Furthermore, by analyzing saliva samples from 200 participants, we established for the first time that EPFR-carrying CR could be found in saliva specimens, suggesting the potential for inhaling them through the oral cavity and their exposure to the human body. After 40 min of exercise on the turf, we detected a substantial presence of EPFRs, reaching as high as (1.15 ± 1.00) × 1016 spins of EPFR per 10 mL of saliva. Moreover, the presence of EPFRs considerably increased the oxidative potential of CR, leading to the inactivation of Ca2+, redox reactions, and changes in spatial binding of the α-1,4-chain of salivary amylase to Ca2+, all of which could influence human saliva health. Our study provides insights into a new pathway of human exposure to CR with EPFRs in artificial turf infill, indicating an increased human health risk of CR exposure.

In Vitro Assessment Reveals the Effects of Environmentally Persistent Free Radicals on the Toxicity of Photoaged Tire Wear Particles.

Tire wear particles (TWP) have been identified as one of the major sources of microplastics (MPs), and few studies have focused on their environmental behaviors and impacts. However, a thorough characteristic and toxicity assessment associated with environmentally persistent free radicals (EPFRs) on the photoaged TWP is missing. In this study, we investigated EPFRs in the process of TWP photoaging and evaluated their toxicity using in vitro bioassays. Our results showed that a total of around 1.0 × 1017 spins/g EPFRs (g-factors ranging 2.00308-2.00318) was formed on TWP with 60 days of light irradiation, which contained more than 29% of reactive EPFRs (r-EPFRs). Using macrophages as model cells for bioassays, TWP-associated EPFRs trigged endpoints, including the decrease of cell viability (27 to 45%) and the increase of oxidative stress response (46-93%) and inflammatory factor secretion. The enhancement of TWP toxicity with photoaging was confirmed to be attributed to the generated EPFRs combined with other TWP's chemical compositions (e.g., various metals and organics). Most importantly, the toxicity of photoaged TWP was closely correlated with the generated r-EPFRs, which induced reactive oxidant species (ROS) generation. This study provides direct evidence of toxicity on the photoaged TWP particles, revealing the potential contributions of EPFRs to the adverse effect on human health and highlighting the need for an improved understanding of the impacts of EPFRs on the risk assessment of TWP released into the environment.

The First Observation of the Formation of Persistent Aminoxyl Radicals and Reactive Nitrogen Species on Photoirradiated Nitrogen-Containing Microplastics.

Nitrogen-containing microplastics (N-MPs) are widely present in the atmosphere, but their potential health risks have been overlooked. In this study, the formation of persistent aminoxyl radicals (PAORs) and reactive nitrogen species (RNSs) on the N-MPs under light irradiation was investigated. After photoaging, an anisotropic triplet with the g-factor of ∼2.0044, corresponding to PAORs, was detected on the nonaromatic polyamide (PA) rather than amino resin (AmR) by electron paramagnetic resonance and confirmed by density functional theory calculations. The generated amine oxide portions on the photoaged PA were identified using X-ray photoelectron spectroscopy and Raman spectroscopy, which were considered to be the main structural basis/precursors of a PAOR. Surprisingly, RNSs were also observed on the irradiated PA. The generated ·NO due to the aphotolysis of nitrone groups simultaneously reacted with peroxide radicals and O2·- to yield ·NO2 and peroxynitrite, respectively, which were responsible for peroxyacyl nitrates (PAN) and CO3·- formation. Besides, a significantly higher oxidative potential and reductive potential were observed for the aged PA than AmR, which is assigned to the abundant RNSs, organic hydroperoxides and PANs, and a strong ability to transfer electrons from PAOR, respectively. This work provides important information for the potential risks of airborne N-MPs and may serve as a guide for future toxicological assessments.

An adjuvant compound that enhances immunogenicity at fractional doses of the Sabin-inactivated poliovirus vaccine (sIPV) with a long duration of protection in a rat model.

BACKGROUND: At the same dosage, the new generation of Sabin-inactivated poliovirus vaccine (sIPV) is less immunogenic than the traditional oral polio vaccine (OPV) dosage in China. The useful adjuvant might be a necessary strategy to strengthen the immune protective effects. METHODS: In this study, we produced an adjuvant compound (named KML05) that could promote immunogenicity and fractional doses of sIPV with a long duration of protection in a rat model. The compound adjuvant had both advantages and a function of MF59 and carbopol971P. RESULTS: The effect seroconversion of experimental animals immunized with KML05 could be extended to one-eighth of the dose. According to the result of the geometric mean titers (GMTs), KML05 adjuvant could save eight times the amount of sIPV D-antigen usage, but aluminum hydroxide adjuvant could save twice at the same titers. Additionally, it was found that there was a significant difference in the GMT titer of poliovirus type 2 between animals immunized by KML05 and alum adjuvant (P < 0.05). At 12th-month postvaccination, the neutralization titers stimulated by IPV-KML05 were maintained over a longer time period in immunized animals. CONCLUSION: Our research team developed KML05 adjuvant, which combined carbopol971P with MF59, increased antibody responses to sIPV for a longer duration of protection in a rat model.

Rice No Pollen 1 (NP1) is required for anther cuticle formation and pollen exine patterning.

Angiosperm male reproductive organs (anthers and pollen grains) have complex and interesting morphological features, but mechanisms that underlie their patterning are poorly understood. Here we report the isolation and characterization of a male sterile mutant of No Pollen 1 (NP1) in rice (Oryza sativa). The np1-4 mutant exhibited smaller anthers with a smooth cuticle surface, abnormal Ubisch bodies, and aborted pollen grains covered with irregular exine. Wild-type exine has two continuous layers; but np1-4 exine showed a discontinuous structure with large granules of varying size. Chemical analysis revealed reduction in most of the cutin monomers in np1-4 anthers, and less cuticular wax. Map-based cloning suggested that NP1 encodes a putative glucose-methanol-choline oxidoreductase; and expression analyses found NP1 preferentially expressed in the tapetal layer from stage 8 to stage 10 of anther development. Additionally, the expression of several genes involved in biosynthesis and in the transport of lipid monomers of sporopollenin and cutin was decreased in np1-4 mutant anthers. Taken together, these observations suggest that NP1 is required for anther cuticle formation, and for patterning of Ubisch bodies and the exine. We propose that products of NP1 are likely important metabolites in the development of Ubisch bodies and pollen exine, necessary for polymerization, assembly, or both.

Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro.

Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV-A71 virus. In this study, our findings were the first to demonstrate that LiCl inhibition of the FMDV replication. In this study, BHK-21 cell was dose-dependent with LiCl at various stages of FMDV. Virus titration assay was calculated by the 50% tissue culture infected dose (TCID50 ) with the Reed and Muench method. The cytotoxicity assay of LiCl was performed by the CCK8 kit. The expression level of viral mRNA was measured by RT-qPCR. The results revealed LiCl can inhibit FMDV replication, but it cannot affect FMDV attachment stage and entry stage in the course of FMDV life cycle. Further studies confirmed that the LiCl affect the replication stage of FMDV, especially the early stages of FMDV replication. So LiCl has potential as an effective anti-FMDV drug. Therefore, LiCl may be an effective drug for the control of FMDV. Based on that, the mechanism of the antiviral effect of LiCl on FMDV infection is need to in-depth research in vivo.

Occurrence of microplastics pollution in the Yangtze River: Distinct characteristics of spatial distribution and basin-wide ecological risk assessment.

The widespread presence of microplastics (MPs) in the Yangtze River, the third longest river in the world, has drawn increasing attention. Although numerous studies have been conducted recently to investigate and analyze the MPs exposure to the surface water of the river, most merely focus on a certain part of the Yangtze River, and knowledge of MPs based on the basin-wide is still scattered. This article reveals the spatial distribution characteristics of MPs in the Yangtze River from the whole watershed scale. Among the five areas in the basin, the upstream and the midstream were demonstrated to contain more MPs (3598.6 particles/m3 and 3226.8 particles/m3). The obtained results suggested the MP presented in the entire watersheds was uneven and the 'hotspots' occurred, where the MPs concentrations were relatively higher than the surrounding. The discharging of the wastewater treatment plants along the river, the locations of dams, and the stability and fragment of MPs, were demonstrated to be the important driving factors in the spatial distribution of MPs and leading to the appearance of the MP 'hotspots' in the Yangtze River, but were previously overlooked. It is the first study to evaluate the ecological risk of MPs exposure to the surface water of the Yangtze River with multiple assessment methods, taking not only abundance but also morphological characteristics, polymer composition and toxic effect into account. More importantly, based on the multiple individual MPs risk assessment methods, we developed the BetaMP method which achieves a comprehensive assessment of MP risk in basin-wide by taking multiple MP characteristics into account for the first time. This is conducive to better understanding the environmental impacts of MPs pollution in the different regions of the river.

Multistage O2-producing liposome for MRI-guided synergistic chemodynamic/chemotherapy to reverse cancer multidrug resistance.

Reduced drug uptake and elevated drug efflux are two major mechanisms in cancer multidrug resistance (MDR). In the present study, a new multistage O2-producing liposome with NAG/R8-dual-ligand and stimuli-responsive dePEGylation was developed to address the abovementioned issues simultaneously. The designed C-NAG-R8-PTXL/MnO2-lip could also achieve magnetic resonance imaging (MRI)-guided synergistic chemodynamic/chemotherapy (CDT/CT). In vitro and in vivo studies showed that C-NAG-R8-PTXL/MnO2-lip enhanced circulation time by PEG and targeted the tumor site. After tumor accumulation, endogenous l-cysteine was administered, and the PEG-attached disulfide bond was broken, resulting in the dissociation of PEG shells. The previously hidden positively charged R8 by different lengths of PEG chains was exposed and mediated efficient internalization. In addition, the oxygen (O2) generated by C-NAG-R8-PTXL/MnO2-lip relieved the hypoxic environment within the tumor, thus reducing the efflux of chemotherapeutic drug. O2 was able to burst liposomes and triggered the release of PTXL. The toxic hydroxyl radical (·OH), which was produced by H2O2 and Mn2+, strengthened CDT/CT. C-NAG-R8-PTXL/MnO2-lip was also used as MRI contrast agent, which blazed the trail to rationally design theranostic agents for tumor imaging.

Simultaneous Determination and Exposure Assessment of Antioxidants in Food-Contact Plastic Materials by HPLC-MS/MS.

Antioxidants are widely used to prevent oxidative degradation of food-contact plastics materials. However, when plastic products come into contact with food, antioxidants may contaminate food. Herein, twenty-three kinds of possible antioxidants were monitored in 257 products of seven polymers. The migration of antioxidants into the food simulants at different temperatures and times was detected by using HPLC-MS/MS. Risk assessment was performed based on the EU, U.S. FDA methods and Monte Carlo simulation. The antioxidants migrated mainly to fatty food simulant, with the highest concentration and occurrence frequency of Irgafos 168, followed byIrganox 1010, Irganox 1076, and Antioxidant LTDP in polyethylene terephthalate, polyvinyl chloride, polypropylene, polyethylene. No antioxidants were detected in polystyrene, polycarbonate, and polyvinylidene chloride. Additionally, antioxidants exhibited the highest detection rate of 0.81 in polyethylene. Risk assessment demonstrated that the antioxidants have no obvious health risk to the exposed population. However, the risk of polypropylene was relatively high compared to other polymers.

Uptake of isoprene, methacrylic acid and methyl methacrylate into aqueous solutions of sulfuric acid and hydrogen peroxide.

Multiphase acid-catalyzed oxidation by hydrogen peroxide has been suggested to be a potential route to secondary organic aerosol formation from isoprene and its gas-phase oxidation products, but the lack of kinetics data significantly limited the evaluation of this process in the atmosphere. Here we report the first measurement of the uptake of isoprene, methacrylic acid and methyl methacrylate into aqueous solutions of sulfuric acid and hydrogen peroxide. Isoprene cannot readily partition into the solution because of its high volatility and low solubility, which hinders its further liquid-phase oxidation. Both methacrylic acid and methyl methacrylate can enter the solutions and be oxidized by hydrogen peroxide, and steady-state uptake was observed with the acidity of solution above 30 wt.% and 70 wt.%, respectively. The steady-state uptake coefficient of methacrylic acid is much larger than that of methyl methacrylate for a solution with same acidity. These observations can be explained by the different reactivity of these two compounds caused by the different electron-withdrawing conjugation between carboxyl and ester groups. The atmospheric lifetimes were estimated based on the calculated steady-state uptake coefficients. These results demonstrate that the multiphase acid-catalyzed oxidation of methacrylic acid plays a role in secondary organic aerosol formation, but for isoprene and methyl methacrylate, this process is not important in the troposphere.

An enhanced risk assessment framework for microplastics occurring in the Westerscheldt estuary.

Microplastics (MPs) pollution in the aquatic environment raises considerable concerns. Freshwater system is generally considered as an important source for MPs transformation into the marine environment, however, only limited data on the MPs pollution in global freshwater systems is available at this time. In this study, we explored the abundance, characteristics and distribution of microplastics in the Scheldt River. The investigation results indicated that the abundance of microplastics in sediments (15-413 items/kg dry weight (DW)) was much higher than that in surface water (0-113 items/m3), and small size MPs (less than 500 µm) frequently appeared in sediments. Industrial activities were regarded as the major cause of MP discharging. Risk assessment models with using data of the concentration of MPs, polymer types and toxicity of MPs exposure were developed to assess the risk of MPs pollution in both surface water and sediment of the Westerscheldt estuary. Risk assessment results revealed that MPs exposure have potentially adverse effects on the aquatic ecosystem and human health. MPs tend to be transported from "Hotspots", such as urban or industries area, to remote areas. The risk assessment of MPs serves as a baseline for better understanding the distribution and characteristics of MPs and highlights the need of intensively monitoring to limit MPs release by intensively monitoring. This research provides a perspective on the risk of MPs that could be used in future studies.

Is the impact of atmospheric microplastics on human health underestimated? Uncertainty in risk assessment: A case study of urban atmosphere in Xi'an, Northwest China.

Microplastic (MP) exposure in the environment has been commonly demonstrated to have adverse effects on human health. The majority of studies on MP were related to the aquatic and terrestrial systems, its potential risk for ecosystem and human health when exposed to the atmosphere is not well-understood. The presented study, taking Xi'an, a megacity in Northwest China, as an example, first estimated the possibility of local residents bearing MPs pollution. The results figured out an average abundance of MPs in TSP, PM10, and PM2.5 was 12.5, 3.5 and 0.8 particles/L, respectively. A total of 15 polymer types of MPs were identified in the atmosphere. Although a species sensitivity distribution (SSD) approach is acknowledged to be useful to estimate the potential risk of pollutants, the result of SSD when used to evaluate the risk of MPs is debatable. In this study, SSD-based risk assessment showed that the atmospheric MP pollution in Xi'an had not yet reached the level of threatening human. However, unlike chemicals, it is unreliable to assess risk using the relationship of dose-response for MPs because toxic effects of MPs can be influenced by not only the abundance but also the characteristics, e.g., morphological size, shape and oxidative potential. Since insufficient mechanistic understanding regarding the relative relationship between MP characteristics and their toxic effects and limitation of the quality and relevance of toxicity data, the uncertainty of risk assessment of the atmospheric MPs is inevitable and the risk of the atmospheric MPs was tended to be underestimated. This poses a challenge to manufacturers and public health authorities, as well as researchers alike, however, we are already being exposed to the atmospheric MPs.

The protective layer formed by soil particles on plastics decreases the toxicity of polystyrene microplastics to earthworms (Eisenia fetida).

The recent discovery of microplastics contaminants in most ecosystems has raised major health issues, yet knowledge on their impact on soil organisms is limited, especially their toxicity evolution with aging. Herein, the toxicity of polystyrene microplastic (PS-MP) to earthworm (Eisenia fetida) along with aging was investigated. Results showed that the 28 d-LC50 (50% lethal concentration) of PS-MP was 25.67 g kg-1, whereas that increased to 96.47 g kg-1 after PS-MP initially aged in soil for 28 days, indicating the toxicity of PS-MP decreased with aging. Laser scanning confocal microscope and scanning electron microscope (SEM) found that the toxicity of PS-MP to earthworm may be due to the ingestion of PS-MP by earthworms and the physical damage (e.g., epidermis abrasion and setae loss) of PS-MP to earthworms. Similarly, the levels of reactive oxygen species, antioxidant enzyme activities and malondialdehyde content increased with PS-MP concentrations from 0.1 to 1.5 g kg-1, but decreased with aging from 7 to 28 days. The integrated biomarker response index also confirmed that the toxicity of PS-MP decreased with aging. SEM found that PS-MP were progressively covered by soil particles during soil aging, inducing the formation of protective layer and increasing the particle size of PS-MP, which prevented direct contact with earthworms and decreased the ingestion of PS-MP, in turn decreased PS-MP toxicity. Overall, our study provides valuable insights for elucidating the effect of aging on the toxicity of microplastics.

Global trends and current status of distraction osteogenesis: Bibliometric analysis of publications from 1980 to 2021.

Introduction: Distraction osteogenesis (DO) has become an important technology for the correction of various congenital and acquired skeletal ridge deformities. It is widely used in oral and maxillofacial surgery, orthopedics, and other disciplines. From 1980 to 2021, the cutting-edge research of DO has been continuously promoted, and the interaction between disciplines has also been deepening. However, the analysis on the global trend and status of DO is relatively rare. Therefore, the aim of our study was to summarize the global trends and current status of DO through bibliometrics. Materials and methods: Web of Science (WOS) core collection database and Medline were used to search DO-related literatures published during 1980-2021. The collected data are imported into Microsoft Excel, Microsoft Word, VOSviewer software for analysis and drawing figure/table. Results: A total of 7,721 publications were included in this study. The United States is the main contributing country to DO (ranking first in terms of total publications, sum of times cited and H-index). Harvard University was the main contributing institution to DO. Journal of Craniofacial Surgery is the main contributing journal of DO related articles. Buchman, SR is the main contributing author to DO related articles. DO related publications can be summarized into 7 clusters: 1) "mechanism study", 2) "limb bone distraction study", 3) "alveolar bone distraction study", 4) "temporomandibular joint ankylosis study", 5) "maxillofacial surgery study", 6) "skull distraction study" and 7) "mandible distraction study". Mandible distraction study has been a hot topic in recent years. In addition, the "management", "osteogenesis" and "reconstruction" of DO have been the research hotspots from 1980 to 2021. Conclusion: From 1980 to 2021, the total number of DO articles has increased rapidly and maintained a steady trend. The United States is the predominant country in the field. Surgery, dental, and oral surgery and orthopaedics are hot fields of DO research. The study of mandible distraction has been paid more and more attention and will become a hotspot in the future. Our study is beneficial for scientists to specify the research hotspot and development direction of DO.

Occurrence, spatial distribution, and main source identification of ten bisphenol analogues in the dry season of the Pearl River, South China.

Bisphenol analogues (BPs) including bisphenol a (BPA) have been broadly utilized as industrial feedstocks and unavoidably discharged into water bodies. However, there is little published data on the occurrence, distribution, and environmental risks of other BPs in surface water. In this study, ten BPs besides BPA were analyzed in surface water from the Pearl River, South China. Among these detected BPs, BPA, bisphenol F (BPF), bisphenol AF (BPAF), and bisphenol S (BPS) were the most frequently detected compounds. The median concentrations of the measured BPs were ranked in the order of BPA (34.9 ng/L) > BPS (24.8 ng/L) > BPAF (10.1 ng/L) > bisphenol F (BPF) (9.0 ng/L) > bisphenol B (BPB) (7.6 ng/L) > bisphenol C (BPC) (1.2 ng/L). Among them, BPA and BPS were predominant BPs, contributing 68% of the total ten BPs in surface water of the Pearl River. These results demonstrated that BPA and BPS were the most extensively utilized and manufactured BPs in this region. The source analysis of BPs suggested that the BPs may be originated from domestic wastewater, wastewater treatment plant (WWTP) effluent, and the leaching of microplastic in surface water of the Pearl River. The calculated BP-derived estrogenic activity exhibited low to medium risks in surface water, but their combined estrogenic effects with other endocrine disrupting compounds should not be ignored.

Generation of environmental persistent free radicals (EPFRs) enhances ecotoxicological effects of the disposable face mask waste with the COVID-19 pandemic.

A large amount of disposable plastic face masks (DPFs) is produced and used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which results in an inevitable consequence of the dramatic increase of DPFs waste. However, the impact of DPFs exposure to the environment on their toxicity is rarely considered. In this study, a range of 76-276 items/L microplastics (MPs) was detected in the DPFs leachates, and fibrous (> 80.3%) and polypropylene (PP, > 89.2%) MPs were dominant. Co, Cu, Ni, Sr, Ti and Zn, were commonly detected in all leachates of the tested DPFs. Organics, such as acetophenone, 2,4-Di-tert-butylphenol, benzothiazole, bisphenol-A and phthalide, were found in the DPFs leachate, which were including organic solvents and plasticizer. Besides, we first found an emerging environmental risk substance, namely environmentally persistent free radicals (EPFRs), was generated in the DPFs leachates. The characteristic g-factors of the EPFRs was in a range of 2.003-2.004, identified as mixture of carbon- and oxygen-centered radicals. By means of in vitro toxicity assay, the DPFs leachate were confirmed to cause cytotoxicity and oxidative stress. Significantly, it is found that the formed EPFRs could contribute more toxic effects. Furthermore, when compared to N95 respirators, the tested surgical masks tend to release more MPs, leach more metals and organics, and generate more EPFRs. Surgical masks were thus showed higher risk than N95 respirators after exposure to water. This work highlights the importance of understanding the chemical complexity and possible toxicity of DPFs for their risk assessment.

Inorganic anions influenced the photoaging kinetics and mechanism of polystyrene microplastic under the simulated sunlight: Role of reactive radical species.

The photo-transformation of microplastic (MP) in natural water may involve interactions with various ingredients, but the photoaging kinetics and underlying mechanism are not well understood. This work systematically explored the photoaging process of polystyrene microplastic (PS-MP) in the presence of commonly-found inorganic anions, including NO3-, HCO3-, Br- and Cl-. The addition of these ions led to more obvious changes in the morphology, functional groups and molecular weight of photoaging PS-MP. The evolution of carbonyl index value for the photoaged samples conformed to pseudo-first-order kinetic model, and the photoaging rate constant (k) in the presence of inorganic anions at their environmentally relevant concentrations of 0.6 mM, 1.2 mM, 0.1 M and 0.1 mM was calculated to be kHCO3- = 0.0074 d-1, kNO3- = 0.01001 d-1, kCl- = 0.00783 d-1, and kBr- = 0.00888 d-1, which was higher than that in ultrapure water (k=0.00705 d-1). Electron paramagnetic resonance technique and quenching experiments demonstrated that photo-transformation of PS-MP was mainly mediated by indirect photolysis, i.e., the formation of reactive radical species. The photosensitivity of NO3- promoted more •OH production, thereby accelerated the indirect photoaging of PS-MP. Meanwhile, the presence of halide ions promoted the generation of reactive halogen species, which were also involved in the indirect photoaging of PS-MP. Interestingly, as •OH scavenger, HCO3- had no inhibitory effect on PS-MP photoaging, attributing to the oxidation of CO3•-. This study provides valuable insights into the understanding of photo-transformation of MPs in natural aquatic environments.

Synthetic enzyme inhibitor: a novel targeting ligand for nanotherapeutic drug delivery inhibiting tumor growth without systemic toxicity.

Unresolved problems associated with ligand-targeting of liposomal nanoparticles (NPs) to solid tumors include variable target receptor expression due to genetic heterogeneity and insufficient target specificity, leading to systemic toxicities. This study addresses these issues by developing a novel ligand-targeting strategy for liposomal NPs using RR-11a, a synthetic enzyme inhibitor of Legumain, an asparaginyl endopeptidase. Cell-surface expression of Legumain is driven by hypoxic stress, a hallmark of solid tumors. Legumain-targeted RR-11a-coupled NPs revealed high ligand-receptor affinity, enhanced solid-tumor penetration and uptake by tumor cells. Treatment of tumor-bearing mice with RR-11a-coupled NPs encapsulating doxorubicin resulted in improved tumor selectivity and drug sensitivity, leading to complete inhibition of tumor growth. These antitumor effects were achieved while eliminating systemic drug toxicity. Therefore, synthetic enzyme inhibitors, such as RR-11a, represent a new class of compounds that can be used for highly specific ligand-targeting of NPs to solid tumors. FROM THE CLINICAL EDITOR: This study addresses the problems associated with ligand-targeting of liposomal nanoparticles to solid tumors with variable target receptor expression. A novel and efficacious targeting strategy has been developed towards a synthetic enzyme inhibitor of Legumain. The authors demonstrate successful tumor growth inhibiting effect while eliminating systemic drug toxicity in an animal model using this strategy.

[Compound erythromycin sustained release preparation and its in vitro release].

Using the weight-average molecular weight 50 000 polylactic acid (PLA) as a carrier, and a certain proportion of erythromycin (EM) and prednisone acetate (PNA) to mixed prepare the compound erythromycin sustained release preparation (sustained-release tablets). Using ultraviolet spectrophotometry and high performance liquid chromatography (HPLC) to detect separately the release amount of EM and PNA in vitro medium. The sustained-release tablets release for about 21 days, the average content of EM is 99.7 mg/table, RSD = 0.82%; and the average content of PNA is 10.03 mg/table, RSD = 0.93%. Within 21 days, the cumulative releases of EM and PNA are 86.1% and 78.3%, respectively. The drug release is steady and slow after 5 days, the burst release phenomenon in early stage is more significant. The results showed that the sustained-release tablet preparation method is feasible, the release performance is good and the clinical efficacy is significant.