Bioengineered Platelets Combining Chemotherapy and Immunotherapy for Postsurgical Melanoma Treatment: Internal Core-Loaded Doxorubicin and External Surface-Anchored Anti-PD-L1 Antibody Backpacks.

The pivotal factors affecting the survival rate of patients include metastasis and tumor recurrence after the resection of the primary tumor. Anti-PD-L1 antibody (aPD-L1) has promising efficacy but with some side effects for the off-target binding between aPD-L1 and normal tissues. Here, inspired by the excellent targeting capability of platelets with respect to tumor cells, we propose bioengineered platelets (PDNGs) with inner-loaded doxorubicin (DOX) and outer-anchored aPD-L1-cross-linked nanogels to reduce tumor relapse and metastatic spread postoperation. The cargo does not impair the normal physiological functions of platelets. Free aPD-L1 is cross-linked to form nanogels with a higher drug-loading efficiency and is sustainably released to trigger the T-cell-mediated destruction of tumor cells, reversing the tumor immunosuppressive microenvironment. PDNGs can reduce the postoperative tumor recurrence and metastasis rate, prolonging the survival time of mice. Our findings indicate that bioengineered platelets are promising in postsurgical cancer treatment by the tumor-capturing and in situ microvesicle-secreting capabilities of platelets.

Eco-Corona vs Protein Corona: Effects of Humic Substances on Corona Formation and Nanoplastic Particle Toxicity in Daphnia magna.

Despite many studies on the toxicity of nanoplastic particles (NPPs) to aquatic invertebrates, the effects of ecological constituents such as humic substances (HSs) are often neglected. In our study, Daphnia magna was used to evaluate the effects of three HSs, natural organic matter (NOM), fulvic acid (FA), and humic acid (HA), on NPP toxicity and corona formation. Acute toxicities of NPPs were reduced by all HSs at environmentally relevant concentrations. NPPs elicited the upregulation of all genes related to detoxification, oxidative stress, and endocrine activity after 7 days of exposure. The presence of NOM or HA resulted in the mitigation of gene expression, whereas significantly higher upregulation of all of the genes was observed with FA. The presence of FA led to increased protein adsorption on NPPs in D. magna culture medium (eco-corona, EC) and homogenates (protein corona, PC), while there was less adsorption in the presence of HA. The highly abundant proteins identified in EC are involved in immune defense, cell maintenance, and antipredator response, while those in PC are responsible for lipid transport, antioxidant effects, and estrogen mediation. Our findings revealed the key influence of HSs on the toxicity of NPPs and provide an analytical and conceptual foundation for future study.

A ubiquitous tire rubber additive induced serious eye injury in zebrafish (Danio rerio).

Previous studies have indicated that tire wear particles (TWPs) leachate exposure induced serious eye injury in fish through inhibiting the thyroid peroxidase (TPO) enzyme activity. However, the main TPO inhibitors in the leachate were still unknown. In this study, we identified 2-Mercaptobenzothiazole (MBT) as the potential TPO inhibitor in the TWPs leachate through references search, model prediction based on Danish QSAR and ToxCast database, molecular docking, and in vivo assay. We further explored the toxic mechanism of MBT under environmentally relevant concentrations. The decreased eye size of zebrafish larvae was mainly caused by the decreased lens diameter and cell density in the inner nuclear layer (INL) and outer nuclear layer (ONL) of the retina. Transcriptomics analysis demonstrated that the eye phototransduction function was significantly suppressed by inhibiting the photoreceptor cell proliferation process after MBT exposure. The altered opsin gene expression and decreased opsin protein levels were induced by weakening thyroid hormone signaling after MBT treatment. These results were comparable to those obtained from a known TPO inhibitor, methimazole. This study has identified MBT as the primary TPO inhibitor responsible for inducing eye impairment in zebrafish larvae exposed to TWPs leachate. It is crucial for reducing the toxicity of TWPs leachate in fish.

Mechanistic insight into the adverse outcome of tire wear and road particle leachate exposure in zebrafish (Danio rerio) larvae.

Tire wear particles (TWP) have become the major microplastic pollution in China. Road runoff containing TWP leachate can decrease the eye size and even induced mortality in the aquatic organisms. However, the toxic mechanism of TWP and road particles (RP) leachate on aquatic organisms is still unclear. In this study, the zebrafish embryos were exposed to TWP or RP leachate for 5 days at both environmental relevant and high concentrations. The adverse outcome pathways (AOPs) were screened from individual to molecular levels. The morphological and behavioral analysis demonstrated that the leachate exposure mainly impaired the eye development of zebrafish larvae and inhibited the larval swim behavior and phototactic response, which are the adverse outcomes. The phototransduction modulated by zebrafish retina was significantly down-regulated through transcriptomics and metabolomics analysis. The eye histopathological analysis showed that the decreased thickness of the retinal outer nuclear layer (ONL) and retinal pigmented epithelium (RPE) after leachate exposure were caused by the decreased photoreceptor cells. Moreover, the expression of NR2E3 and TPO genes showed concentration-dependent down-regulation after leachate exposure. The inhibition of photoreceptor cell proliferation was identified as the main reason for photoreceptor cell decrease in zebrafish larval eye. This study, for the first time, uncovered the underlying toxic mechanism of TWP and RP on zebrafish larval eyes.

[Effects of Wastewater Treatment Processes on the Removal Efficiency of Microplastics Based on Meta-analysis].

Microplastics (MPs) are ubiquitous emerging pollutants that have been found in the marine, freshwater, air, and soil environments. Wastewater treatment plants (WWTPs) play an important role in releasing MPs to the environment. Therefore, understanding the occurrence, fate, and removal mechanism of MPs in WWTPs is of great importance towards microplastic control. In this review, the occurrence characteristics and removal rates of MPs in 78 WWTPs from 57 studies were discussed based on Meta-analysis. Specifically, the key aspects regarding MPs removal in WWTPs, such as wastewater treatment processes and MPs shapes, sizes, and polymer compositions were analyzed and compared. The results showed that:① the abundances of MPs in the influent and effluent were 1.56×10-2-3.14×104 n·L-1 and 1.70×10-3-3.09×102 n·L-1, respectively. The abundance of MPs in the sludge ranged from 1.80×10-1 to 9.38×103 n·g-1. ② The total removal rate (>90%) of MPs by WWTPs using oxidation ditch, biofilm, and conventional activated sludge treatment processes was higher than that using sequencing batch activated sludge, anaerobic-anoxic-aerobic, and anoxic-aerobic processes. ③ The removal rate of MPs in primary, secondary, and tertiary treatment process were 62.87%, 55.78%, and 58.45%, respectively. The combination process of "grid+ sedimentation tank+primary sedimentation tank" had the highest removal rate towards MPs in primary treatment processes, and the membrane bioreactor had the highest one beyond other secondary treatment processes. Filtration was the best process in tertiary treatment. ④ The film, foam, and fragment MPs were easier to remove (>90%) than fiber and spherical (<90%) MPs by WWTPs. The MPs with particle size larger than 0.5 mm were easier to remove than those with particle size smaller than 0.5 mm. The removal efficiencies of polyethylene (PE), polyethylene terephthalate (PET), and polypropylene (PP) MPs were higher than 80%.

Microplastics from consumer plastic food containers: Are we consuming it?

Microplastic (MP) accumulation in the environment has become an issue of human and environmental importance. Great efforts were made recently to identify the sources of MP exposure to humans and their release into the environment. Here, we employed spectroscopic techniques to identify and characterize MP in consumer plastic food containers that are, in huge quantity, used for food delivery and disposable plastic cups for daily drinking. We determined the average weight of isolated MP per pack to be 12 ± 5.12 mg, 38 ± 5.29 mg, and 3 ± 1.13 mg for the round-shaped, rectangular-shaped plastic container and disposable plastic cups, respectively, with various morphological features including cubic, spherical, rod-like as well as irregular shapes, which may either be consumed by humans or released into the environment. This study demonstrates that new plastic containers can be an important source of direct human and environmental exposure to microplastics. Most importantly, our results indicated that necessary attention must be given to morphological features of realistic MPs when evaluating their risks to humans and the environment.

[Synthesis and fluorescence properties of thermo-responsive microgel nanoparticles].

In the present paper, the preparation and properties of Eu(III) on poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-co-AAc)) were described. At first, P(NIPAM-co-AAc) microgel nanoparticles were prepared by the precipitation copolymerization of N-isopropylacrylamide with acrylic acid in the presence of N, N-methylenebisacrylamide in water. The morphology and size of the P(NIPAM-co-AAc) nanoparticles were characterized by the scanning electron microscope (SEM) method. The result of SEM shows that the sample is uniformly sized spherical particle and the average particle size of the P(NIPAM-co-AAc) is about 365 nm. Then, EuCl3 was chosen to interact with P(NIPAM-co-AAc) nanoparticles and formed the complex of P(NIPAM-co-AAc)-Eu(III). The complex was characterized by Fourier transform infrared spectroscopy, ultraviolet-visible and fluorescence spectroscopy. It was found that the complex shows thermo-responsive fluorescence from the experimental results. There exists a energy transfer between the polymer ligand and the Eu(III), which can enhance fluorescence emission of the polymer ligand and Eu(III) at the same time. The LCST of P(NIPAM-co-AAc) containing Eu(III) has changed little after the formation of the complex of P(NIPAM-co-AAc)-Eu(III). Therefore, the complex can be used for developing the new applications in biomedical and fluorescence field.

[Screening and characteristics of normal temperature lignocellulose-degradation microbial community].

A normal temperature lignocellulose-degrading microflora has been constructed by our laboratory. We researched the degradation activity and compose of the community in 28 degrees C fermentation condition. The results showed that the microbial community could degrade 39.6% of rice stew gross weight within five days.The volatile products were detected using CP-Chirasil-Dex CB capillary column by GC-MS, propionic acid, ethanol, isopropyl alcohol, 4-amino-1-butanol, butanoic acid, diethoxydimethyl-silane, lactic acid, ethanol,2,2'-oxybis-, diethyl phthalate and glycerin,more than 10 kinds of volatile products were detected. The state volatile products of changed largely along with the process of decompose, the productions gradually increase, and the content changes much with the process of decompose. Denaturing gradient gel electrophoresis (DGGE) detected the dynamic change of bacterium compose, the bacterium changes much in different period,the result of Blast from 16S rDNA sequence was found that the closest relative in community belong to Clostridium sp., Brevibacillus sp., Rhizobium sp., Bacterium sp. four genera.

[Degradation of cassava residue by the cellulose degradation composite microbial system MC1].

The lignocelluloses of cassava residue are good biomass resources. They are mainly used to produce feeds and alcohol. It is a promising approach to utilize them to produce methane. But it is difficult to use cassava residue for producing methane because of its dispersive solid matter and much water. A cellulose degradation composite microbial system MC1 was applied to degrade cassava residue discarded from cassava starch manufactory, and the composition of the lignocelluloses and the soluble ingredients of cassava residue were analyzed. After 18 days' cultivation, the total weight of the cassava residue was reduced by 47.3%, the cellulose, hemi-cellulose and lignin of the cassava residue were reduced by 22.7%, 90.4% and 11.3%, respectively, and 85% of the whole weight relief was made by MC1 within 6 days. The soluble ingredients of the cassava residue were increased from the incipient 18% to 33% in the third day which was the peak value in the process. The total amount of the volatile products, analyzed by GC-MS, came to a maximum in the sixth day. Twelve kinds of volatile products in the fermentation broth were determined, in which ethanol, acetic acid, 1, 2-ethanediol, butanoic acid and glycerine were the major compounds, and they can be utilized by methanogenic organism directly or be changed into compounds that can be utilized by methanogens organism directly. Accordingly, it is very hopeful to use MC1 to degrade cassava residue as a method of prefermentation in methane fermentation.

Tissue distribution of a plasmid DNA containing epitopes of foot-and-mouth disease virus in mice.

It is known that only the minority of plasmid DNAs effect a cure or prevention after intramuscular injection into host. But what is the fate of the majority? And indeed how many of the injected DNAs work? Till now, little is known about it. To answer these questions, two methods including PCR and autoradiography were used in distribution study in mice that had received a single muscular inoculation of plasmid DNA containing antigenic epitopes of foot-and-mouth disease virus. The results showed that the plasmid DNAs were distributed by blood circulation and degraded soon. The degradation ratio of super coiled plasmid DNA was 20.9% in 10 min, 34.1% in 1h, 86.8% in 1 day and 97.8% in 1 week in sera in vivo. And over a half of the whole were output in urine and faeces. The rest resided most in muscles as 'antigen pool', next in immune organs, kidney, liver, heart, lung and little in brain or gonad. About 40% or 0.5% of total plasmid DNAs, inferring to be effective, resided in muscles or immune organs, respectively. Collective results suggested that 'nude' DNA, as water injection, was characterized as quick absorbent, extensive distribution, but low utilization rate. Finally, the immune mechanism for the DNA vaccine was discussed.