Accelerated Blood Clearance of Nanoemulsions Modified with PEG-Cholesterol and PEG-Phospholipid Derivatives in Rats: The Effect of PEG-Lipid Linkages and PEG Molecular Weights.

Various types of nanocarriers modified with poly(ethylene glycol) (PEG) exhibit the accelerated blood clearance (ABC) phenomenon, resulting in reduced circulation time and abnormal increase in hepatic and splenic accumulations. Based on the abundance of esterases in the serum of rats, we developed cleavable methoxy PEG-cholesteryl methyl carbonate (mPEG-CHMC) with a carbonate linkage and noncleavable N-(carbonyl-methoxy PEG-n)-1,2-distearoyl-sn-glycero-3-phos-phoethanolamine (mPEG-DSPE) with a carbamate linkage on the surface of the nanoemulsions (CHMCE and PE, respectively). Both PEG derivatives possessed PEG with six different molecular weights (n = 350, 550, 750, 1000, 2000, and 5000). The pharmacokinetic behaviors and biodistributions of single and repeated injection of the two types of PEGylated nanoemulsions were determined to investigate the influence of cleavable linkages and PEG molecular weights on the ABC phenomenon in an attempt to find a potential strategy to eliminate the ABC phenomenon. CHMCEns (n = 1000, 2000, and 5000) exhibited the same pharmacokinetic behaviors as PE550 and PE750 and only alleviated the ABC phenomenon to a certain extent at the expense of shortened cycle time, indicating that the cleavable carbonate linkage was not an ideal strategy to eliminate the ABC phenomenon. As the molecular weights of PEG increased, the ABC phenomenon became more severe. Surprisingly, PE5000 induced a lower anti-PEG IgM level and a weaker ABC phenomenon compared with PE2000 while possessing a similar long circulation time. The results suggested that increasing the molecular weight of PEG in the PEG derivatives could be a potential strategy for eliminating the ABC phenomenon while simultaneously guaranteeing longer circulation time.

Effects of Uncleavable and Cleavable PEG-Lipids with Different Molecular Weights on Accelerated Blood Clearance of PEGylated Emulsions in Beagle Dogs.

To investigate the effect of polyethylene glycol (PEG) molecular weights on circulation time of PEGylated emulsions and the second injection of injected PEGylated emulsions, we studied the effect of molecular weights on the pharmacokinetic behavior of PEG-DSPE (modified emulsions with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy (polyethyleneglycol)]) and PEG-CHMC (modified emulsions with poly(ethyleneglycol)-cholesteryl carbonate) emulsions in beagle dogs. The "accelerated blood clearance" (ABC) phenomenon was induced. Through this study, the contribution of PEG molecular weights on the ABC phenomenon was further clarified, and the results provided guidance for lessening or eliminating the ABC phenomenon. We injected different PEG-modified emulsions with 10% PEG-modified density into beagle dogs at 2 µmol phospholipids kg-1 and the blood samples were drawn after 1 min, 3 min, 5 min, 10 min, 15 min, 30 min, 60 min, 120 min, 240 min, 360 min, 600 min, and 24 h. Then, concentrations of the drug were assayed using high-performance liquid chromatography (HPLC). The results showed that the circulation times of PEG-DSPE-modified emulsions were significantly different because of the difference in molecular weights, whereas those of the PEG-CHMC modified emulsions were not. The spatial conformation of PEG with small molecular weights (PEG400, PEG600, and PEG800) was more likely to induce a strong ABC phenomenon. The results of our work suggest the interaction of circulation time and PEG molecular weights on the ABC phenomenon, implying that the spatial conformation of PEG has advantages that alleviate the ABC phenomenon. Importantly, the results have implications for the choice of molecular weights of PEG for PEGylated formulations.

Acute Management of Hyperkalemia.

PURPOSE OF THE REVIEW: Hyperkalemia is a common electrolyte abnormality that can lead to life-threatening cardiac arrhythmia. Medical management of acute hyperkalemia revolves around three strategies-stabilizing the myocardium, intracellular shifting of serum potassium, and enhancing elimination of total body potassium via urinary or fecal excretion. In this review, we outline the current evidence behind the acute medical management of hyperkalemia. RECENT FINDINGS: Two new oral potassium-binding agents, patiromer and sodium zirconium cyclosilicate, show promise in the management of hyperkalemia. Their role in the acute setting needs further investigation. Recent investigations also suggest that the optimal dosing of intravenous insulin may be lower than previously described. Despite its prevalence, there is wide variability in the medical management of hyperkalemia in the acute setting. High-quality evidence demonstrating efficacy is lacking for many medications, though novel oral potassium-binding agents show promise. Overall, more research is necessary to establish optimal dosing strategies to manage hyperkalemia in the acute setting.

Use of Dual-Ligand Modification in Kupffer Cell-Targeted Liposomes To Examine the Contribution of Kupffer Cells to Accelerated Blood Clearance Phenomenon.

The "accelerated blood clearance (ABC) phenomenon" is known to be involved in the adaptive immune system. Regretfully, the relationship between the ABC phenomenon and innate immune system, especially with respect to Kupffer cells (KCs) has been largely unexplored. In this study, the contribution of KCs to ABC was examined using the 4-aminophenyl-α-d-mannopyranoside (APM) lipid derivative DSPE-PEG2000-APM (DPM) and the 4-aminophenyl-ß-l-fucopyranoside (APF) lipid derivative DSPE-PEG2000-APF (DPF) as ligands for mannose/fucose receptors on KCs, which were synthesized and modified on the surface of liposomes. The results of cellular liposome uptake in vitro and biodistribution in vivo indicated that DPM and DPF comodified liposomes (MFPL5-5) present the strongest capability of KC-targeting among all preparations tested. In rats pretreated with MFPL5-5 instead of PEGylated liposomes (PL), the ABC phenomenon was significantly enhanced and the distribution of liposomes in the liver was increased. Cellular uptake of the second injection of PL in vivo demonstrated that KCs was responsible for the uptake. Furthermore, compared to pretreatment with PL, the uptake of second injection of PL was more enhanced when pretreated with MFPL5-5. These findings suggest that KCs, which are considered traditional members of the innate immune system, play a crucial role in the ABC phenomenon and act as a supplement to the phenomenon.

Evaluating the Accelerated Blood Clearance Phenomenon of PEGylated Nanoemulsions in Rats by Intraperitoneal Administration.

The accelerated blood clearance (ABC) phenomenon is induced by repeated intravenous injection of stealth polyethylene glycol (PEG) nanocarriers and appears as the alteration of the pharmacokinetics and biodistribution of the second administration. Nevertheless, there is no any report about the ABC phenomenon induced by intraperitoneal administration of PEGylated nanocarriers. In this study, we firstly observed whether the ABC phenomenon is induced with PEGylated nanoemulsion at the dose of 0.5~100 µmol phospholipid·kg-1 by intraperitoneal/intravenous injections in rats. The PEG (molecule weight, 2000)-modified nanoemulsions PE-B and PE in which fluorescence indicator dialkylcarbocyanines (DiR) is encapsulated by PE-B were prepared for this work. The pharmacokinetics of the first injected PE via veins or peritoneal cavity features different variation trends. Moreover, the tissue distributions (in vivo or in vitro) of the first injected PE by intraperitoneal injection reveals that the PE gains access to the whole lymphatic circulatory system. Furthermore, our results demonstrate that the ABC phenomenon can be induced by intraperitoneal administration PE-B and present obvious changes with varying PE-B concentration 0.5~100 µmol phospholipid·kg-1. Moreover, an interesting point is that the ABC phenomenon induced by intraperitoneal injected PE-B can be significantly inhibited by intraperitoneal pre-injection of distilled water. For understanding this issue clear, we studied the production of anti-PEG IgM and the characteristic morphologies of immune cells. We observed that the mast cells in peritoneal cavity exhibit rapid depletion in response to the intraperitoneal pre-injection of distilled water, while the anti-PEG IgM secretes at the same level.

Microplastics in Hong Kong's marine waters: Impact of rainfall and Pearl River discharge.

This study provided a systematic investigation of microplastics in Hong Kong's surface marine waters during the pandemic from 2019 to 2021. Microplastics (2.07 ± 4.00 particles/m3) exhibited significant temporal variations with higher abundance in the wet season, without a consistent trend after the mandatory mask-wearing requirement was announced. The impact of pandemic restrictions on microplastic distribution was found to be relatively minor. However, significant correlations between microplastic abundances and rainfall highlighted the substantial contribution of local emissions through surface runoff. Notably, sites in closer proximity to the Pearl River Delta exhibited higher microplastic abundances, indicating their association with emission sources. The influence of rainfall and adverse weather on marine microplastic loads demonstrated different sensitivities among various locations but can generally last for one month. These results revealed the impact of seasonal rainfall on coastal microplastics and emphasized the need for efforts to reduce microplastic discharge from land-based sources.

Full factorial design, physicochemical characterization, ex vivo investigation, and biological assessment of glutathione-loaded solid lipid nanoparticles for topical application.

l-Glutathione (GSH) has exceptional antioxidant activities against UVA irradiation-induced oxidative stress and is used widely for combatting skin ageing. However, topical administration of GSH is challenging due to its inability to penetrate the stratum corneum (SC). This study aims to evaluate the solid lipid nanoparticles (SLNs) carrier system for improving the skin penetration and stability of GSH. The GSH-loaded SLNs (GSH-SLNs) were prepared by the double emulsion technique and were optimized by a full factorial design. The optimized GSH-SLNs formulation had a mean particle size of 305 ± 0.6 nm and a zeta potential of + 20.1 ± 9.5 mV, suitable for topical delivery. The ex-vivo penetration study using human skin demonstrated a 3.7-fold improvement of GSH penetration across SC with GSH-SLNs when compared with aqueous GSH. GSH-SLNs prolonged antioxidant activity on UVA irradiated fibroblast cells when compared to GSH solution, preventing UVA-induced cell death and promoting cell growth for times over 48 h. This research has illustrated that as a carrier system, SLNs were able to enhance the physicochemical stability, skin penetration, and drug deposition in the viable epidermis and dermis layers of the skin for GSH, while also maintaining the ability to protect human skin fibroblast cells against oxidative stress caused by UVA irradiation. This delivery system shows future promise as a topical delivery platform for the topical delivery of GSH and other chemically similar bioactive compounds for improving skin health.

Persistent immune response: Twice tumor exfoliation induced by sialic acid-modified vincristine sulfate liposomes.

Studies have shown that tumor-associated macrophages (TAMs) are crucial for the establishment and maintenance in immunosuppressive tumor immune microenvironment (TIME), which can help tumor cells to achieve immune escape and attenuate antitumor therapy. Siglecs, the receptors of sialic acid (SA), widely exist in TAMs, which could be targeted to disrupt TIME and inhibit tumor growth at the root. Therefore, a SA-modified VCR liposome was reported (VCR-SSAL). Cellular and pharmacodynamic experiments showed that VCR-SSAL exhibited strong TAMs targeting and tumor-killing ability. Interestingly, VCR-SSAL treatment induced a phenomenon in which the cancerous tissues were "fell off" from the growth site, after which the wound gradually healed. Three months after the wound healed, the mice whose tumors fell off were re-inoculated, and the tumor fell off again without treatment, with an exfoliation rate of 100%. We speculated that this special efficacy might be due to that VCR loaded in VCR-SSAL could activate adaptive immunity by inducing DNA damage, promoting cytotoxic T lymphocytes (CTLs) infiltration into tumor sites, and enhancing the antitumor immune response. Thus, this study might provide new insights into the application of traditional chemotherapeutic drugs.

Policy impact on microplastic reduction in China: Observation and prediction using statistical model in an intensive mariculture bay.

Plastic pollution in the environment has spurred debate among scientists, policymakers, and the general public over how industrialization and consumerism are wreaking havoc on our ecosystem, but some policies might assist to ameliorate the problem in the near future. In this study, the decision tree classifier and Bayesian Structural Time Series (BSTS) model was used to anticipate the possible sources of microplastics and their near future state in 26 surface sediment and a sediment core, respectively in Sansha Bay, which has been criticized for its intensive mariculture applications. An inventory of microplastics in the sediment core was estimated, and it was discovered that during the previous six decades, an average of 181.95 tons of microplastics were deposited, with an average deposition (by a layer of sediment) of 179.44 tons/cm. According to the DT classifier, mariculture was the primary source of microplastics, whereas urban and industrial areas were the primary sources of POPs. The Bayesian Structural Time Series (BSTS) model revealed a microplastic downward slope, indicating that regional and national strategies implemented might successfully reduce microplastic pollution regionally.

Microplastics in the Taiwan Strait and adjacent sea: Spatial variations and lateral transport.

This study investigates the distribution, structural properties, and potential impacts of oceanic processes on microplastics (MPs) in the Taiwan Strait (TWS) and surrounding seas. With an average of 174 particles/m3, the MP abundance in surface seawater ranged from 84 to 389 particles/m3. MP abundance ranged from 16 to 382 particles/kg in sediments, with a median of 121 particles/kg. Fragment and fiber were the two most frequently detected shapes. These MPs were found to be composed primarily of carbon and oxygen elements at 70-90% levels using energy-dispersive X-ray spectroscopy. Additionally, several examples had trace levels of metallic components. Black was the color that MPs saw the most often out of all the hues. The two main types of polymers are polyester and rayon, and their production is influenced by home sewage discharge and synthetic fiber production. The main routes of MP transport were land source input, riverine input, and oceanic currents. This study showed that salinity affects the distribution of MPs, with high-salinity seawater serving to saturate their presence. On the other hand, upwelling raises MP concentrations by bringing nutrients from the deep to the surface. Furthermore, it has been discovered that the dilution of the Pearl River plume increases the MP prevalence in the region. The South China Sea Warm Current had the highest lateral MPs transport flux (2.1 × 1014 particles/y), which was followed by the Taiwan Strait Current area (1.0 × 1014 particles/y) and the Guangdong coastal areas (8.6 × 1013 particles/y). In sediments, the MP prevalence was inversely correlated with particle size. Flocculation processes probably made it easier for MPs to travel down the water column and deposit themselves on the aquatic substrate. Although the relationship between MPs, total organic carbon, and total organic nitrogen was not correlated, a favorable trend showed that MPs may discreetly contribute to carbon storage in coastal sediment.

Microplastic occurrence and ecological risk assessment in the eight outlets of the Pearl River Estuary, a new insight into the riverine microplastic input to the northern South China Sea.

Estuaries are unique transition zones connecting terrestrial and coastal environments and are recognized as primary conveyors for land-derived plastics to open oceans. Riverine microplastics (MPs) have been commonly investigated using sequential sampling which might not effectively reflect the actual load. In this study, sampling at eight outlets was performed during a complete tidal cycle to estimate the MP flux to the Pearl River Estuarine (PRE) using a concurrent sampling strategy. The MP abundances ranged from 2.90 ± 0.57-5.9 ± 2.27 particles/L. A remarkable difference between tides in MP abundances suggests tidal effect should not be overlooked in assessment. The MP load through the eight outlets was estimated at 304 trillion particles or 1102 tons into the PRE annually. Additionally, similar potential ecological risk assessment among eight rivers implied that environmental threats posed by less urbanized and populated rural areas on the western side have been under-evaluating for decades.

Exploring ex vivo peptideolysis of thymopentin and lipid-based nanocarriers towards oral formulations.

The oral delivery of medicines is the most popular route of administration for patients. However, thymopentin (TP5) is only available in the market in forms for parenteral administration. In large part, this is because of extensive peptidolytic degradation in the gastrointestinal tract (GIT), which decreases the amount of TP5 available for absorption. This study aims to understand the extent of TP5 peptideolysis and determine effective inhibitors and suitable lipid-based nanocarriers to aid in the development of an effective oral delivery formulation. Enzymatic degradation kinetics of TP5 was investigated in the presence or absence of mucosal and luminal components extracted from various parts of the rat intestine, including the duodenum, jejunum, ileum, and colon. Inhibition of TP5 enzymatic peptidolysis was screened in the presence or absence of EDTA, trypsin and chymotrypsin inhibitors from soybean (SBTCI), and bestatin. TP5 with SBTCI was loaded into lipid-based nanocarriers, including microemulsions, niosomes and solid lipid nanoparticles. These TP5-loaded nanocarriers were investigated through characterization of morphology, particle size, zeta potential, entrapment efficacy (EE%), and ex vivo rat intestinal degradation studies to select a lead formulation for a future oral drug delivery study. The degradation kinetics of TP5 followed pseudo-first-order kinetics, and the biological metabolism of TP5 was displayed in the presence of luminal contents, indicating that TP5 is sensitive to luminal enzymes. Notably, a considerable decrease in TP5 peptidolysis was found in the presence of SBTCI, bestatin, and EDTA. TP5 and SBTCI were loaded into three lipid-based delivery systems, displaying superior protection under ex vivo intestinal luminal contents and mucosal homogenates for 6 h compared with the pure drug solution. These findings suggest that using select inhibitors and lipid-based nanocarriers can decrease peptide degradation and may improve oral bioavailability of TP5 following oral administration.

Impact of intensive mariculture activities on microplastic pollution in a typical semi-enclosed bay: Zhanjiang Bay.

Microplastic (MP) was investigated in Zhanjiang Bay, a semi-enclosed bay in south China and famous for considerable mariculture industry, to evaluate whether mariculture activities accelerated MP pollution. The MP abundances ranged from 0 to 2.65 n/m3 (number/m3), showing seasonal variances with higher levels in May and September and lower levels in January. In the inner part of the bay, a significantly high MP abundance and predominance of foam were found during the oyster breeding period, and pollution sources were prone to be single and extensive. This suggested that MPs were strongly influenced by the intensive plastic products for oyster culturing, especially during breeding. Moreover, plastic cages used for culturing were the main source of MPs in the central part of the bay. By conducting statistical analysis for eight representative bays, the economic growth, social development, agriculture structure, and aquaculture development were supposed to influence the local MP pollution level.

Discovery in polyethylene glycol immunogenicity: The characteristic of intergenerational inheritance of anti-polyethylene glycol IgG.

Several studies have reported the prevalence of anti-polyethylene glycol (PEG) antibodies (APAs) in healthy people, highlighting the widespread existence of APAs. The prevalence of anti-PEG immunoglobulin (Ig)G is significantly negatively correlated with age. Here, we used Wistar rats as model organism to examine whether APAs in parental rats can affect the production of antibodies in their offspring. After being pre-stimulated with blank PEGylated nanoemulsions (PE) to induce APAs production, parental rats were paired in cages. The presence of antibodies in the parents and offspring was detected using enzyme-linked immunosorbent assay. The presence of antibodies in the parental rats led to significant anti-PEG IgG positivity in their offspring, indicating that anti-PEG IgG exhibits intergenerational inheritance. Moreover, anti-PEG IgG in the offspring rats could bind to PE and accelerate its blood clearance. To the best of our knowledge, this is the first report on the intergenerational properties of APAs.

Evasion of the accelerated blood clearance phenomenon by branched PEG lipid derivative coating of nanoemulsions.

PEGylation increases the circulation time of the nanocarrier, but also triggers accelerated blood clearance (ABC) phenomenon. It is well-known that the ABC phenomenon results in shortened blood circulation and aberrant increase in liver and spleen accumulation, which greatly limits the application of PEGylated nano-preparations. For many years, researchers have been working hard to find ways to reduce or eliminate the ABC phenomenon. Previous studies have focused on PEG molecular weight and PEG alternative materials, but there has never been any research on the effect of different PEG chain types on the ABC phenomenon. Therefore, 40 kDa molecular weight of linear PEG lipid derivatives (DSPE-mPEG40k) and branched PEG lipid derivatives (DSPE-mPEG2,40k) were selected to modify nanoemulsions to explore the influence of distinct PEG chain types on avoiding the ABC phenomenon for the first time. We pioneer the use of linear and branched PEG lipid derivatives (DSPE-mPEG40k and DSPE-mPEG2,40k) to modify nanoemulsions (PE40k and PE2,40k). Upon characterization, PE40k and PE2,40k showed good physicochemical properties in the aspect of size, polydispersity index (PDI value), and zeta potential. Surprisingly, the pharmacokinetics study indicated that repeated injection of PE40k and PE2,40k did not trigger the ABC phenomenon. More importantly, PE2,40k possessed a long circulation time and did not cause ABC phenomenon after repeated injection. This may be attributed to the fact that PE2,40k induced noticeably lower anti-PEG IgM levels compared to linear PEG-modified nanocarriers and did not activate the complement system. Therefore, we speculate that DSPE-mPEG2,40k-modified nanocarriers possess promising prospects in avoiding the ABC phenomenon, which may improve the possibility of wide application of nanoformulations.

Occurrence and sources of microplastics and polycyclic aromatic hydrocarbons in surface sediments of Svalbard, Arctic.

Due to the distinct environment condition and geographic location, Svalbard has been recognized as a potential pollution reservoir in the Arctic. In this study, 8 surface sediment samples were collected from two fjords in Svalbard (Kongsfjorden and Rijpfjorden) in 2017, and they were searched for microplastics and polycyclic aromatic hydrocarbons (PAHs). PAHs were also investigated in 10 soil samples of Ny-Ålesund for local anthropogenic source analysis. The level of microplastics and other anthropogenic particles ranged from not detected (ND) to 4.936 particles/kg dry weight (DW). Fiber was the only shape of the microplastics found and three polymers (polyester, rayon and cellulose) were detected, which suggested that fisheries-related debris and textile materials were possible sources of microplastics and anthropogenic particles. For PAHs, the level of ∑26PAH was 9.2 ng/g to 67.1 ng/g (DW), and were dominated by lnP and BghiP, indicating petroleum combustion source. Further analysis revealed that traffic emissions from cars and diesel combustion from a local power plant were major sources of PAHs in soils of Ny-Alesund, while traffic emissions from ships were the dominate source of PAHs in sediments of Kongsfjorden and Rijpfjorden. A higher level of PAHs was observed in Ny-Alesund, confirming an anthropogenic input, while transport via ocean currents might contribute to the higher abundance of microplastics in Rijpfjorden. Further research and even long-term observation of pollutants are needed to fully understand the pollution status in polar regions.

Branched PEG-modification: A new strategy for nanocarriers to evade of the accelerated blood clearance phenomenon and enhance anti-tumor efficacy.

PEGylation is one of the most successful technologies for reducing immunogenicity, improving the stability and circulation time of nanocarriers, and has been applied in the clinic for over three decades. However, linear PEG-modified nanocarriers have been found to induce anti-PEG IgM at the first injection, which triggers the accelerated blood clearance (ABC) phenomenon upon repeated injections. Furthermore, clinical and research evidence has revealed that anti-PEG antibodies also cause serious complement activation-related pseudoallergies (CARPA), which greatly reduce the safety of linear PEGylated nanocarriers. In this study, as an alternative to linear PEG, branched PEG was selected owing to its low antigenicity. We pioneer the use of branched PEG lipid derivatives [DSPE-mPEG2,n (n = 2, 10, and 20 kDa)] to modify nanoemulsions (PE2,n) and liposomes (PL2,n). Upon characterization, PE2,n and PL2,n showed similar physicochemical properties to linear DSPE-mPEG2000-modified nanocarriers in terms of size, polydispersity index (PDI), and zeta potential. However, our pharmacokinetics study surprisingly indicated that PE2,n and PL2,n did not induce the ABC phenomenon after repeated injection. This may be attributed to the fact that PE2,n and PL2,n induced noticeably lower levels of anti-PEG IgM than linear PEG-modified nanocarriers and did not activate the complement system. Furthermore, we are the first to investigate the anti-tumor efficacy of DSPE-mPEG2,n-modified liposomal doxorubicin (DOX). The pharmacodynamic experiments showed that DSPE-mPEG2,n-m-modified liposomal DOX had better in vivo anti-tumor effects than linear DSPE-mPEG2000-modified liposomes. Therefore, we speculate that DSPE-mPEG2,n-modified nanocarriers possess promising prospects in avoiding the ABC phenomenon, reducing CARPA, and improving the anti-tumor efficacy of encapsulated drugs.

Microplastics in the surface waters of the South China sea and the western Pacific Ocean: Different size classes reflecting various sources and transport.

Microplastic transport in the marginal seas is a key process influencing their ultimate fate in the open oceans. In the present study, we collected seawater samples from the western Pacific Ocean (WP) and the South China Sea (SCS) to investigate the distribution, transport, and possible sources for microplastics. Generally, the range of microplastic levels were 187-1816, 146-1563, and 34.2-622 particles/m3 (averaged in 797 ± 512, 744 ± 330, and 201 ± 134 particles/m3) for the northern SCS, the western SCS, and the WP, respectively. Based on the size distribution, the highest value (390 ± 288 particles/m3) was found for 100-200 µm, followed by 200-500 µm (131 ± 155 particles/m3), and 500-1000 µm (29.7 ± 39.2 particles/m3), with the lowest for 1-5 mm (13.6 ± 14.2 particles/m3). Granule, yellow, and size <1000 µm were their most prevalent characteristics. The main polymer types of microplastics were polyester, rayon, and nylon. A negative correlation between microplastic proportion and particle size was observed in the SCS and the WP. Furthermore, the main sources of microplastics in the northern SCS probably came from the Pearl River. Surface currents and the vertical mixing processes might be two different mechanisms that affect microplastic transport from the WP and the SCS. Future comparison to measured particle size distributions data allows us to explain size-selective microplastic transport in the marine environment, and probably provide guidance on microplastic longevity.

A preliminary study of the innate immune memory of Kupffer cells induced by PEGylated nanoemulsions.

The accelerated blood clearance (ABC) phenomenon describes a dilemma of polyethylene glycol (PEG) applied in drug delivery system (DDS) caused by its immunogenicity, that results in the enhanced blood clearance rate and increased hepatic and splenic accumulation after secondary injection of PEGylated nanocarriers. However, the ABC index, as the judgement of ABC phenomenon, only describes the accelerated blood clearance rate, but ignores the enhanced hepatic and splenic accumulation. Therefore, we proposed the hepatic accumulation (HA) index and the splenic accumulation (SA) index as supplements for assessing the ABC phenomenon, to emphasize the contribution of liver and spleen, especially the liver, possessing the most population of tissue resident macrophages. By altering the first injection site from the tail vein to the liver portal vein, there was no impact on anti-PEG IgM production, and the secondary hepatic accumulation of PEGylated nanoemulsions (PE) was observed to be proportionate to the first PE stimulation strength on the liver. We also determined that Kupffer cells (KCs) were the main contributor to this enhancement. On this basis, we revealed a definite phenomenon that PE could induce innate immune memory in KCs, by enhancing the phagocytosis of KCs toward PE during the secondary stimulation. The PE-stimulated KCs could carry this memory to the naïve rats through adoptive transfer, resulting in increased hepatic accumulation in the recipient rats without antibody production. Studies examining the phagocytosis of KCs in vivo, ex vivo and in vitro revealed that the memory of KCs against PE triggered by first-stimulated PE could be maintained independently of other cells or components until 21 days after the first stimulation, and possessing specificity to PEG, which was invalid to long-circulating GE (GM1 modified nanoemulsions). The discovery of immune memory in KCs induced by PE highlights the importance of focusing on the relationship between the innate immune system and PEGylated nanocarriers during the development of DDS to improve medication safety in the clinic.

Significant riverine inputs of typical plastic additives-phthalate esters from the Pearl River Delta to the northern South China Sea.

Phthalate esters (PAEs) are representative additives used extensively in plastics. In this study, 15 PAEs were investigated at the eight riverine outlets of the Pearl River Delta (PRD). The total concentrations of Σ15PAEs, including both the dissolved and particulate phases, ranged from 562 to 1460 ng/L and 679 ng/L-2830 ng/L in the surface and bottom layers, respectively. Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) dominated in the dissolved and suspended particulate matter (SPM) phases, respectively, accounting for >50 % and > 80 % of Σ15PAEs. Riverine input of wastewater from the PRD was possibly the primary source of the contamination. Higher levels of PAEs occurred at the eastern outlets than at the western ones. The dissolved and particulate PAEs varied seasonally, with significantly higher concentrations observed in the dry season than in the wet season. However, no significant differences of PAE levels in both phases were observed among low, medium, and high tides. The partitioning results demonstrated that SPM is important in the transportation of pollutants in estuaries, where more hydrophobic DEHP was predominantly transported by the SPM phase, while those more hydrophilic ones were regularly transported by the dissolved phase. The total annual flux of Σ15PAEs through the eight outlets to the SCS reached 1390 tons.