Norsesquiterpenes from the Latex of Euphorbia dentata and Their Chemical Defense Mechanisms against Helicoverpa armigera.

Euphorbia dentata (Euphorbiaceae), an invasive weed, is rarely eaten by herbivorous insects and could secrete a large amount of white latex, causing a serious threat to local natural vegetation, agricultural production and human health. In order to prevent this plant from causing more negative effects on humans, it is necessary to understand and utilize the chemical relationships between the latex of E. dentata and herbivorous insects. In this study, three new norsesquiterpenes (1-3), together with seven known analogues (4-10), were isolated and identified from the latex of E. dentata. All norsesquiterpenes (1-10) showed antifeedant and growth-inhibitory effects on H. armigera with varying levels, especially compounds 1 and 2. In addition, the action mechanisms of active compounds (1-3) were revealed by detoxifying enzyme (AchE, CarE, GST and MFO) activities and corresponding molecular docking analyses. Our findings provide a new idea for the development and utilization of the latex of E. dentata, as well as a potential application of norsesquiterpenes in botanical insecticides.

Tumor Microenvironment Stimuli-Responsive Polymeric Prodrug Micelles for Improved Cancer Therapy.

PURPOSE: The discovery of nano drug delivery system has rendered a great hope for improving cancer therapy. However, there are some inevitable obstacles that constrain its development, such as the physical and biological barriers, the toxicity of carrier materials and the physiological toxicity of drugs. Here, we report a polymeric prodrug micelle (PPM) with pH/redox dual-sensitivity, which was prepared using methoxy poly (ethylene glycol) (mPEG) with favorable biosafety to improve cancer therapy. METHOD: The tumor microenvironment stimuli-responsive PPMs were prepared and characterized in vitro and in vivo. RESULTS: Our data displayed that the PPMs with excellent biocompatibility exhibited the stimuli-responsive drug release behavior under the microenvironment of cancer cells, superior cellular internalization and lower cytotoxicity. A new method to control drug release behavior was proposed by comparing the release behavior of PPMs formed by PEG of different molecular weight. Furthermore, the fabricated PPMs exhibited the "oral-like" blood concentration curve, improved biodistribution, reduced tissue toxicity and excellent antitumor efficiency in vivo. Consistently, these results indicated that PPMs improved chemotherapeutic efficiency and reduced side effects of the model drug doxorubicin (DOX). CONCLUSION: The prepared pH/redox dual-sensitive PPM enhanced the chemotherapy effect on the tumor site while reducing the physiological toxicity of DOX. Graphical Abstract.

Fine-tuning DETR: Toward holistic process in plastic waste sorting system.

Every year human discharges about 350 million tons of plastic waste into the environment and can be projected to triple in 2060 without any attempts to change situation. From 1970 to 2019, an estimation of 130 million tons of plastic waste was accumulated into the rivers, lakes and sea, while only 27 % is recycled and utilized. Moreover, waste treatment plants in most places around the world are using out-of-date technology, may pose a threat to the health of the workers. Therefore, it is essential to modernize these systems for protecting human health. This paper proposes fine-tuning DETR, which applies Artificial Intelligent in plastic waste sorting system. Consequently, this study analyzed the applicability of fine-tuning DETR in the domain of plastic waste categorization and its potential drawbacks. For fair experiment and evaluation, model candidates were trained and evaluated on an industrial plastic waste dataset. The fine-tuning DETR outperformed other candidates in the context of critical indicators, from accuracy (25.1 mAP), processing speed (28 FPS) to computational cost (GFLOPs 86). Furthermore, fine-tuning DETR possesses the capability of autonomous operation without requiring human intervention, distinguishing this candidate from other prevalent algorithms. Our research demonstrates that, fine-tuning DETR specifically and Transformer-based algorithms in general, are entirely suitable and hold significant potential for large-scale application in holistic plastic waste sorting systems.

Different responses of mesophilic and thermophilic anaerobic digestion of waste activated sludge to PVC microplastics.

The effect of microplastics (MPs) retained in waste activated sludge (WAS) on anaerobic digestion (AD) performance has attracted more and more attention. However, their effect on thermophilic AD remains unclear. Here, the influence of polyvinyl chloride (PVC) MPs on methanogenesis and active microbial communities in mesophilic (37 °C) and thermophilic (55 °C) AD was investigated. The results showed that 1, 5, and 10 mg/L PVC MPs significantly promoted the cumulative methane yield in mesophilic AD by 5.62%, 7.36%, and 8.87%, respectively, while PVC MPs reduced that in thermophilic AD by 13.30%, 18.82%, and 19.99%, respectively. Moreover, propionate accumulation was only detected at the end of thermophilic AD with PVC MPs. Microbial community analysis indicated that PVC MPs in mesophilic AD enriched hydrolytic and acidifying bacteria (Candidatus Competibacter, Lentimicrobium, Romboutsia, etc.) together with acetoclastic methanogens (Methanosarcina, Methanosaeta). By contrast, most carbohydrate-hydrolyzing bacteria, propionate-oxidizing bacterium (Pelotomaculum), and Methanosarcina were inhibited by PVC MPs in thermophilic AD. Network analysis further suggested that PVC MPs significantly changed the relationship of key microorganisms in the AD process. A stronger correlation among the above genera occurred in mesophilic AD, which may promote the methanogenic performance. These results suggested that PVC MPs affected mesophilic and thermophilic AD of WAS via changing microbial activities and interaction.

Design, synthesis and performance evaluation of mPEG-PR: A novel non-absorbable marker.

The aim of the present study was to develop a new marker for correcting water flux in the in situ single-pass intestinal perfusion (SPIP) model. The new marker was designed and synthesized based on the application of both polyethylene glycol-4000 (PEG-4000) and phenol red as non-absorbable markers. The new marker mPEG-PR was obtained by combining phenol red with polyethylene glycol monomethyl ether-4000 (mPEG-4000) and verified by nuclear magnetic resonance (NMR), ultraviolet (UV) spectra, gel permeability chromatograph (GPC) and differential scanning calorimetry (DSC). mPEG-PR fully took the advantages of phenol red and PEG including the low permeability and the simple measuring method which were assessed by the in vitro and the in situ models. In the everted gut sac (EGS) studies, the permeability of mPEG-PR was significantly reduced by nearly 4 times compared with phenol red, and the absorptive percentage of mPEG-PR was <0.1% in 105 min. In addition, the solution with verapamil or without Ca2+ could help improve the absorption of phenol red but did not influence the absorption of mPEG-PR. The results of isosorbide dinitrate as a model drug in the in situ SPIP study showed that both the mPEG-PR marker and the gravimetric method were useful for correcting water flux, which had smaller coefficients of variation than the phenol red marker and the non-corrected method. In conclusion, mPEG-PR could potentially be applied as an accurate and convenient marker for correcting water volume in the intestinal perfusion study.

Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(ß-amino ester)/poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma.

Stepwise pH-responsive nanoparticle system containing charge reversible pullulan-based (CAPL) shell and poly(ß-amino ester) (PBAE)/poly(lactic-co-glycolic acid) (PLAG) core is designed to be used as carriers of paclitaxel (PTX) and combretastatin A4 (CA4) for combining antiangiogenesis and chemotherapy to treat hepatocellular carcinoma (HCC). CAPL-coated PBAE/PLGA (CAPL/PBAE/PLGA) nanoparticles displayed step-by-step responses to weakly acidic tumor microenvironment (pH ≈6.5) and endo/lysosome (pH ≈5.5) respectively through the cleavage of ß-carboxylic amide bond in CAPL and the "proton-sponge" effect of PBAE, thus realized the efficient and orderly releases of CA4 and PTX. In human HCC HepG2 cells and human umbilical vein endothelial cells, CAPL/PBAE/PLGA nanoparticles significantly enhanced synergistic effects of PTX and CA4 on cell proliferation and cell migration. In HepG2 tumor-bearing mice, CAPL/PBAE/PLGA nanoparticles showed excellent tumor-targeting capability and remarkably increased inhibitory effects of PTX and CA4 on tumor growth and angiogenesis. In conclusion, this novel nanoparticle system is a promising candidate as carrier for drugs against HCC.

Lactosylated PLGA nanoparticles containing ϵ-polylysine for the sustained release and liver-targeted delivery of the negatively charged proteins.

The acidic internal pH environment, initial burst release and lack of targeting property are main limitations of poly(lactide-co-glycolide) (PLGA) nanoparticles for carrying proteins. In this study, ϵ-polylysine (ϵ-PL) was used as an anti-acidic agent and a protein protectant to prepare PLGA nanoparticles for the protein delivery. To obtain the liver-targeting capability, lactosylated PLGA (Lac-PLGA) was synthesized by conjugation of lactose acid to PLGA at both ends, and then used to prepare nanoparticles containing ϵ-PL by the nanoprecipitation method. Bovine serumal bumin (BSA), a negatively charged protein, was efficiently loaded into Lac-PLGA/ϵ-PL nanoparticles and exhibited significant decreased burst release in vitro, sustained release in the blood and increased liver distribution in mice after intravenous injections. The enhanced stability of BSA was due to its electrical interaction with ϵ-PL and the neutralized internal environment of nanoparticles. In conclusion, Lac-PLGA/ϵ-PL nanoparticle system can be used as a promising carrier for the negatively charged proteins.

Core-shell nanoparticles based on pullulan and poly(ß-amino) ester for hepatoma-targeted codelivery of gene and chemotherapy agent.

This study designs a novel nanoparticle system with core-shell structure based on pullulan and poly(ß-amino) ester (PBAE) for the hepatoma-targeted codelivery of gene and chemotherapy agent. Plasmid DNA expressing green fluorescent protein (pEGFP), as a model gene, was fully condensed with cationic PBAE to form the inner core of PBAE/pEGFP polycomplex. Methotrexate (MTX), as a model chemotherapy agent, was conjugated to pullulan by ester bond to synthesize polymeric prodrug of MTX-PL. MTX-PL was then adsorbed on the surface of PBAE/pEGFP polycomplex to form MTX-PL/PBAE/pEGFP nanoparticles with a classic core-shell structure. MTX-PL was also used as a hepatoma targeting moiety, because of its specific binding affinity for asialoglycoprotein receptor (ASGPR) overexpressed by human hepatoma HepG2 cells. MTX-PL/PBAE/pEGFP nanoparticles realized the efficient transfection of pEGFP in HepG2 cells and exhibited significant inhibitory effect on the cell proliferation. In HepG2 tumor-bearing nude mice, MTX-PL/PBAE/pEGFP nanoparticles were mainly distributed in the tumor after 24 h postintravenous injection. Altogether, this novel codelivery system with a strong hepatoma-targeting property achieved simultaneous delivery of gene and chemotherapy agent into tumor at both cellular and animal levels.