Lysosome Targeting Chimaeras for Glut1-Facilitated Targeted Protein Degradation.

Targeted protein degradation technology holds great potential in biomedicine, particularly in treating tumors and other protein-related diseases. Research on intracellular protein degradation using molecular glues and PROTAC technology is leading, while research on the degradation of membrane proteins and extracellular proteins through the lysosomal pathway is still in the preclinical stage. The scarcity of useful targets is an immense limitation to technological advancement, making it essential to explore novel, potentially effective approaches for targeted lysosomal degradation. Here, we employed the glucose transporter Glut1 as an innovative lysosome-targeting receptor and devised the Glut1-Facilitated Lysosomal Degradation (GFLD) strategy. We synthesized potential Glut1 ligands via reversible addition-fragmentation chain transfer (RAFT) polymerization and acquired antibody-glycooligomer conjugates through bioorthogonal reactions as lysosome-targeting protein degradation molecules, utilized in the management of PD-L1 high-expressing triple-negative breast cancer. The glucose transporter Glut1 as a lysosome-targeting receptor exhibits potential for the advancement of a broader array of medications in the future.

Does the use of chlorantraniliprole during queen development adversely impact health and viability?

The queen is the sole reproductive individual and the maturing brood replenishes the shorter-lived worker bees. Production of many crops relies on both pesticides and bee pollination to improve crop quantity and quality. Despite the certain knowledge on chemical pesticides caused damage to worker bee physiology and behavior, our understanding of the relationship between honeybee queen development and chemical pesticides remains weak. Here, we comprehensive investigate the effects of the widely used insecticide chlorantraniliprole on the growth, hormone levels, and detoxifying enzyme activity of queen larvae. It has been determined that chlorantraniliprole present a chronic toxic effect on queen larvae and also reduced the fitness of queen, and that these effects are positively correlated with pesticide levels. It has been found that queen larvae began to show reduced capping and emergence rates when exposed to 2 ng/larva of chlorantraniliprole. At 20 ng/larva, queen capping and emergence rates were the lowest, and there were significant reductions in larval hormone level. Chlorantraniliprole have an effect on detoxification enzyme activity and hormone levels in queen larvae. In conclusion, chlorantraniliprole can adversely affect the growth and development of queen larvae. Our findings may guide the scientifically sound use of chemical pesticides to reduce potential risks to queen larvae.

Assessing spatiotemporal population density dynamics from 2000 to 2020 in megacities using urban and rural morphologies.

Rapid urbanization has resulted in the substantial population growth in metropolitan areas. However, existing research on population change of the cities predominantly draws on grid statistical data at the administrative level, overlooking the intra-urban variegation of population change. Particularly, there is a lack of attention given to the spatio-temporal change of population across different urban forms and functions. This paper therefore fills in the lacuna by clarifying the spatio-temporal characteristics of population growth in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 2000 to 2020 through the methods of local climate zone (LCZ) scheme and urban-rural gradients. The results showed that: (1) High population density was observed in the compact high-rise (LCZ 1) areas, with a noticeable decline along urban-rural gradients. (2) The city centers of GBA experienced the most significant population growth, while certain urban fringes and rural areas witnessed significant population shrinkage. (3) The rate of growth tended to slow down after 2010, but the uneven development of population-based urbanization was also noticeable, as urbanization and industrialization varied across different LCZ types and cities in GBA. This paper therefore contributes to a deeper understanding of population change and urbanization by clarifying their spatio-temporal contingences at landscape level.

Protocol to synthesize sequence-controlled glycooligomers for tumor targeting in mice.

Due to the higher and more rapid consumption of carbohydrates by cancer cells compared to normal cells, carbohydrates can be effectively employed as a targeted therapeutic strategy for tumor treatment. Here, we present a protocol for synthesizing sequence-controlled glycooligomers using both solution-phase and solid-phase systems. We outline detailed procedures for evaluating the safety and tumor-targeting properties of the sequence-controlled glycooligomers in vivo. For complete details on the use and execution of this protocol, please refer to Chen et al.1.

Active metabolites combination therapies: towards the next paradigm for more efficient and more scientific Chinese medicine.

Traditional Chinese medicine (TCM) formulae have been studied extensively in various human diseases and have proven to be effective due to their multi-component, multi-target advantage. However, its active metabolites are not clear and the specific mechanisms are not well established, which limits its scientific application. Recently, combination therapies are attracting increasing attention from the scientific community in the past few years and are considered as the next paradigm in drug discovery. Here, we tried to define a new concept of "active metabolites combination therapies (AMCT)" rules to elucidate how the bioactive metabolites from TCMs to produce their synergistic effects in this review. The AMCT rules integrate multidisciplinary technologies like molecular biology, biochemistry, pharmacology, analytical chemistry and pharmacodynamics, etc. Meanwhile, emerging technologies such as multi-omics combined analysis, network analysis, artificial intelligence conduce to better elucidate the mechanisms of these combination therapies in disease treatment, which provides new insights for the development of novel active metabolites combination drugs. AMCT rules will hopefully further guide the development of novel combination drugs that will promote the modernization and international needs of TCM.

Topology and giant circular dichroism of enantiomorphic Kagome bands in a designed covalent organic framework.

Covalent organic frameworks (COFs) are an emerging class of crystalline organic materials that have shown potential to be a new physical platform. In this work, a designed COF named AB-COF, which has novel enantiomorphic Kagome bands, is proposed and a feasible route to synthesize it is given. Via a combination of first-principles calculations and tight-binding analysis, we investigate the electronic structures and the phase interference of the COF. It becomes topologically nontrivial when doping one iodine atom in a unit cell. The Berry curvatures of the valence band (VB) and conduction band (CB) of the iodine-doped AB-COF show opposite values and different distributions. This provides an opportunity to study the new mechanism of circular dichroism from the different Berry curvatures of the VB and CB. Surprisingly, the circular-dichroism dissymmetry factor of AB-COF reaches a theoretical maximum value, and the oscillator strength data are in agreement with this result. When two iodine atoms are doped in a unit cell, the Berry curvatures of the VB and CB also have different values, but with more symmetry and similar distributions. This behavior enhances the circular dichroism with a wider range of dissymmetric absorption, and the circular dichroism dissymmetry factor also reaches its theoretical maximum value.

YOLOv8-RMDA: Lightweight YOLOv8 Network for Early Detection of Small Target Diseases in Tea.

In order to efficiently identify early tea diseases, an improved YOLOv8 lesion detection method is proposed to address the challenges posed by the complex background of tea diseases, difficulty in detecting small lesions, and low recognition rate of similar phenotypic symptoms. This method focuses on detecting tea leaf blight, tea white spot, tea sooty leaf disease, and tea ring spot as the research objects. This paper presents an enhancement to the YOLOv8 network framework by introducing the Receptive Field Concentration-Based Attention Module (RFCBAM) into the backbone network to replace C2f, thereby improving feature extraction capabilities. Additionally, a mixed pooling module (Mixed Pooling SPPF, MixSPPF) is proposed to enhance information blending between features at different levels. In the neck network, the RepGFPN module replaces the C2f module to further enhance feature extraction. The Dynamic Head module is embedded in the detection head part, applying multiple attention mechanisms to improve multi-scale spatial location and multi-task perception capabilities. The inner-IoU loss function is used to replace the original CIoU, improving learning ability for small lesion samples. Furthermore, the AKConv block replaces the traditional convolution Conv block to allow for the arbitrary sampling of targets of various sizes, reducing model parameters and enhancing disease detection. the experimental results using a self-built dataset demonstrate that the enhanced YOLOv8-RMDA exhibits superior detection capabilities in detecting small target disease areas, achieving an average accuracy of 93.04% in identifying early tea lesions. When compared to Faster R-CNN, MobileNetV2, and SSD, the average precision rates of YOLOv5, YOLOv7, and YOLOv8 have shown improvements of 20.41%, 17.92%, 12.18%, 12.18%, 10.85%, 7.32%, and 5.97%, respectively. Additionally, the recall rate (R) has increased by 15.25% compared to the lowest-performing Faster R-CNN model and by 8.15% compared to the top-performing YOLOv8 model. With an FPS of 132, YOLOv8-RMDA meets the requirements for real-time detection, enabling the swift and accurate identification of early tea diseases. This advancement presents a valuable approach for enhancing the ecological tea industry in Yunnan, ensuring its healthy development.

Detection Model of Tea Disease Severity under Low Light Intensity Based on YOLOv8 and EnlightenGAN.

In response to the challenge of low recognition rates for similar phenotypic symptoms of tea diseases in low-light environments and the difficulty in detecting small lesions, a novel adaptive method for tea disease severity detection is proposed. This method integrates an image enhancement algorithm based on an improved EnlightenGAN network and an enhanced version of YOLO v8. The approach involves first enhancing the EnlightenGAN network through non-paired training on low-light-intensity images of various tea diseases, guiding the generation of high-quality disease images. This step aims to expand the dataset and improve lesion characteristics and texture details in low-light conditions. Subsequently, the YOLO v8 network incorporates ResNet50 as its backbone, integrating channel and spatial attention modules to extract key features from disease feature maps effectively. The introduction of adaptive spatial feature fusion in the Neck part of the YOLOv8 module further enhances detection accuracy, particularly for small disease targets in complex backgrounds. Additionally, the model architecture is optimized by replacing traditional Conv blocks with ODConv blocks and introducing a new ODC2f block to reduce parameters, improve performance, and switch the loss function from CIOU to EIOU for a faster and more accurate recognition of small targets. Experimental results demonstrate that YOLOv8-ASFF achieves a tea disease detection accuracy of 87.47% and a mean average precision (mAP) of 95.26%. These results show a 2.47 percentage point improvement over YOLOv8, and a significant lead of 9.11, 9.55, and 7.08 percentage points over CornerNet, SSD, YOLOv5, and other models, respectively. The ability to swiftly and accurately detect tea diseases can offer robust theoretical support for assessing tea disease severity and managing tea growth. Moreover, its compatibility with edge computing devices and practical application in agriculture further enhance its value.

Functional analysis of three odorant receptors in Plutella xylostella response to repellent activity of 2,3-dimethyl-6-(1-hydroxy)-pyrazine.

Plutella xylostella is an important pest showing resistance to various chemical pesticides, development of botanical pesticides is an effective strategy to resolve above problem and decrease utilization of chemical pesticides. Previous study showed that 2,3-dimethyl-6-(1-hydroxy)-pyrazine has significant repellent activity to P. xylostella adult which mainly effect to the olfactory system, however the molecular targets and mechanism are still unclear. Based on the RNA-Seq and RT-qPCR data, eight ORs (Odorant receptor) in P. xylostella were selected as candidate targets response to repellent activity of 2,3-dimethyl-6-(1-hydroxy)-pyrazine. Here, most of the ORs in P. xylostella were clustered into three branches, which showed similar functions such as recognition, feeding, and oviposition. PxylOR29, PxylOR31, and PxylOR46 were identified as the potential molecular targets based on the results of repellent activity and EAG response tests to the adults which have been injected with dsRNA, respectively. Additionally, the three ORs were higher expressed in antenna of P. xylostella, followed by those in the head segment. Furthermore, it was found that the bindings between these three ORs and 2,3-dimethyl-6-(1-hydroxy)-pyrazine mainly depend on the hydrophobic effect of active cavities, and the binding to PxylOR31 was more stabler and easier with an energy of -16.34 kcal/mol, together with the π-π T-shaped interaction at PHE195 site. These findings pave the way for the complete understanding of pyrazine repellent mechanisms.

Light-mediated intracellular polymerization.

The synthesis of synthetic intracellular polymers offers groundbreaking possibilities in cellular biology and medical research, allowing for novel experiments in drug delivery, bioimaging and targeted cancer therapies. These macromolecules, composed of biocompatible monomers, are pivotal in manipulating cellular functions and pathways due to their bioavailability, cytocompatibility and distinct chemical properties. This protocol details two innovative methods for intracellular polymerization. The first one uses 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) as a photoinitiator for free radical polymerization under UV light (365 nm, 5 mW/cm2). The second method employs photoinduced electron transfer-reversible addition-fragmentation chain-transfer polymerization with visible light (470 nm, 100 mW/cm2). We further elaborate on isolating these intracellular polymers by streptavidin/biotin interaction or immobilized metal ion affinity chromatography for polymers tagged with biotin or histidine. The entire process, from polymerization to isolation, takes ~48 h. Moreover, the intracellular polymers thus generated demonstrate significant potential in enhancing actin polymerization, in bioimaging applications and as a novel avenue in cancer treatment strategies. The protocol extends to animal models, providing a comprehensive approach from cellular to systemic applications. Users are advised to have a basic understanding of organic synthesis and cell biology techniques.

Identification and functional characterization of two antenna-specifc odorant-binding proteins in Plutella xylostella response to 2,3-dimethyl-6-(1-hydroxy)-pyrazine.

Plutella xylostella is an important cruciferous crop pest with a serious resistance to multiple insecticides, a novel natural compound, 2,3-dimethyl-6-(1-hydroxy)-pyrazine were isolated, that showed significant repellent activity against P. xylostella with olfactory system as a potential target. Eight odorant-binding proteins (OBPs) were determined as candidate target genes using RT-qPCR (Quantitative reverse transcription PCR), most of them were clustered with OBPs from Spodoptera frugiperda. Fluorescence competitive binding assays showed that PxylPBP2 (Pheromone binding protein) and PxylOBP3 had Ki values of 7.13 ± 0.41 µM and 9.56 ± 0.35 µM, indicating a high binding affinity to the pyrazine. Moreover, the binding style between these two OBPs and the pyrazine was determined as a hydrophobic interaction by using molecular docking. The binding between PxylPBP2 and the pyrazine was found to be more stable, and the carbon atoms of C-2 and C-3 in this pyrazine showed potential optimization characteristics. Both PxylPBP2 and PxylOBP3 were highly expressed in the antennae of both sexes. These results can be used to design and develop novel green pesticides with the pyrazine as the active or lead compound to reduce the utilization of chemical pesticides and postpone development of resistance.

Ecological Toxicity of Cyantraniliprole against Procambarus clarkii: Histopathology, Oxidative Stress, and Intestinal Microbiota.

Cyantraniliprole is a novel insecticide recently introduced for rice pest control that may cause potential threats to the red swamp crayfish (Procambarus clarkii) in rice-crayfish coculture systems. In this study, we investigated the acute toxicity of cyantraniliprole against P. clarkii with a LC50 value of 149.77 mg/L (96 h), first. Some abnormal behaviors of P. clarkii treated with 125 mg/L cyantraniliprole, including incunabular hyperexcitability, imbalance, inactivity, and increased excretion were observed. Moreover, it was observed that exposure to 5 mg/L cyantraniliprole for 14 days resulted in histopathological alterations in abdominal muscle, gills, hepatopancreas, and intestines. Furthermore, exposure to 0.05 and 5 mg/L cyantraniliprole induced increased activities of several oxidative stress-related enzymes, which was verified by the upregulation of related genes. Additionally, dysregulation of the intestinal microbiota was determined via 16S rRNA sequencing. These results will provide the basis for the utilization of cyantraniliprole in the fields of rice-crayfish integrated system.

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION: Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Residue Behavior of Chiral Fungicide Prothioconazole and Its Major Chiral Metabolite in Flour Product Processing.

This study systematically investigates the stereoselective metabolism and residue behavior of chiral pesticide prothioconazole enantiomers during the steaming, baking, and frying of steamed buns, bread, and deep-fried dough sticks. The results show that steaming, baking, and frying can significantly promote the degradation of the prothioconazole enantiomers. In low- and high-concentration treatments, the degradation rates of prothioconazole enantiomers were over 96.0% and 45.4%, respectively, and the residual concentration of prothioconazole-desthio enantiomers was less than 32.7 µg/kg (excluding fried processing). During the processing of steamed buns, bread, and deep-fried dough sticks, the enantiomer fraction (EF) value of the prothioconazole enantiomer was close to 0.5, and the stereoselectivity was not significant. During the processing of steamed buns (low concentration), bread (low and high concentrations), and deep-fried dough sticks (low concentration), the stereoselectivity of prothioconazole-desthio was significant, and preferential enantiomer degradation occurred. Following the analysis of 120 flour product samples, the residual risk.

Enantiomorphic kagome bands in a two-dimensional covalent organic framework with non-trivial magnetic and topological properties.

The kagome lattice is one of the most intriguing topics to study. It has a frustrated flat band touching a set of Dirac bands and can possess various promising properties, such as ferromagnetism, superconductivity, and a non-trivial topology. Covalent organic frameworks (COFs) are a rare type of inorganic material, however, they can provide a platform for generating certain required lattices. Based on first-principles density functional theory calculations, we show that a newly synthesized two-dimensional COF named COF-SH has novel enantiomorphic kagome bands, which include two sets of flat bands touching the Dirac bands around the Fermi level. The Bloch wave of the flat-valence band at the K-point shows the kagome nature of the phase interference. Under charge doping, the COF-SH exhibits a ferromagnetic ground state. Moreover, when COF-SH is doped with iodine atoms, a sizable gap in the system is opened between the flat bands and the Dirac bands due to the spin-orbit coupling (SOC) effect. Meanwhile, the spin degeneracy is lifted since the organic layer loses electrons due to the oxidizing property of iodine. In addition, our tight-binding analysis with the SOC effect shows that the flat valence band separates from the Dirac bands and holds a nonzero Chern number. Consequently, this I-doped COF can give rise to a quantum anomalous Hall effect.

Effect of novel botanical synergist on the effectiveness and residue behavior of prothioconazole in wheat field.

Fusarium head blight (FHB) is a critical fungal disease causes serious grain yield losses and mycotoxin contaminations. Currently, utilization of chemical fungicides is the main control method which has led to serious resistance. Development of novel synergist is an important strategy to reduce the usage of chemical fungicides and postpone the development of resistance, while natural components are interesting resources. In this study, the synergistic effect of Taxodium 'zhongshansha' essential oil (TZEO) was determined and the best synergistic ratio (SR) of 3.96 in laboratory which was observed when the weight ratio of TZEO and prothioconazole was 1 : 1 with the corresponding EC50 (half maximal effective concentration) value of Fusarium graminearum was 0.280 mg L-1. Subsequently, an increase of 6.31% on the control effect to FHB index in field test was observed when compared to the treatment with prothioconazole alone, though there was no significant difference between these treatments. Furthermore, we established an effective method to detect the mycotoxin contaminations in wheat grain with the limits of quantifications (LOQs) value of 5 µg kg-1 (DON, ZEN, 3-DON, and 15-DON) and 1 µg kg-1 (OTA) and the contents were less to the maximum residue limit (MRL) values. It was also shown that the application of 20% TZEO EW led to a 20% reduction in the use of prothioconazole, which was calculated based on the control effect values of 86.41% and 90.20% between the treatments of 30% prothioconazole OD (225 g a.i ha-1, recommend dosage) and 30% prothioconazole OD (180 g a.i ha-1) + 20% TZEO EW (225 mL ha-1), significantly. The initial residue of prothioconazole and prothioconazole-desthio was increased in the treatment with TZEO, which may play an important role in the synergistic effect on FHB. Moreover, none of the treatments posed a prothioconazole residue risk in the wheat grain and the environment. In addition, the essential oil has no any negative influence on wheat growth, which was revealed by a study of the chlorophyll content. These results provide an important botanical synergist for use with prothioconazole to control Fusarium head blight, and in-depth study to the synergistic mechanism of this oil is necessary in our future research.

Risk assessment of honeybee larvae exposure to pyrethroid insecticides in beebread and honey.

Honeybee is an essential pollinator to crops, evaluation to the risk assessment of honeybee larvae exposure to pesticides residue in the bee bread and honey is an important strategy to protect the bee colony due to the mixture of these two matrices is main food for 3-day-old honeybee larvae. In this study, a continuous survey to the residue of five pyrethroid insecticides in bee bread and honey between 2018 and 2020 from 17 major cultivation provinces which can be determined as Northeast, Northwest, Eastern, Central, Southwest, and Southern of China, there was at least one type II pyrethroid insecticide was detected in 54.7 % of the bee bread samples and 43.4 % of the honey. Then, we assayed the acute toxicity of type II pyrethroid insecticides based on the detection results, the LD50 value was 0.2201 µg/larva (beta-cyhalothrin), 0.4507 µg/larva (bifenthrin), 2.0840 µg/larva (fenvalerate), 0.0530 µg/larva (deltamethrin), and 0.1640 µg/larva (beta-cypermethrin), respectively. Finally, the hazard quotient was calculated as larval oral ranged from 0.046 × 10-3 to 2.128 × 10-3. Together, these empirical findings provide further insight into the accurate contamination of honey bee colonies caused by chemical pesticides, which can be used as a valuable guidance for the beekeeping industry and pesticide regulation.

Identification and characterization of odorant receptors in Plutella xylostella antenna response to 2,3-dimethyl-6-(1-hydroxy)-pyrazine.

Diamondback moth (Plutella xylostella), a worldwide migratory pest that is developing strong resistance to various chemical insecticides. It has been determined that four natural pyrazines isolated from Allium tuberosum showed significant repellent activity to P. xylostella, but the molecular target still unknown. In the present study, a novel synthetic route for 2,3-dimethyl-6-(1-hydroxy)-pyrazine which has the most significant repellent activity with a purity of 90.60% was established. Simultaneously, the bioassay result declared that the repellent grade was IV at a dosage of 0.01 mg which was the same as to the published data. Transcriptomics analysis detected 1643 upregulated and 3837 downregulated genes in P. xylostella antennae following this pyrazine exposure. Then, 2142 differentially expressed genes were annotated using Gene Ontology and 2757 genes were annotated by Kyoto Encyclopedia of Genes and Genomes. Moreover, this procedure identified 84 odour perception-related genes, 58 odorant receptor (OR) genes including 57 conventional ORs and the odorant receptor co-receptor (Orco, atypical odorant receptor) gene, and 26 odorant-binding protein (OBP) genes. Based on quantitative real time PCR (RT-qPCR) and differential expression results, 9 OR genes including the Orco were cloned and characterised. In summary, this study provides important basis for the utilization of pyrazines as the main active ingredients or lead compounds to developing new botanical pesticides, which will reduce application of chemical pesticides and postpone the development of resistance.

Ultrasound-responsive glycopolymer micelles for targeted dual drug delivery in cancer therapy.

Controlled drug release of nanoparticles was achieved by irreversibly disrupting polymer micelles through high-intensity focused ultrasound (HIFU) induction. An ultrasound-responsive block copolymer was synthesized, comprising an end-functional Eosin Y fluorophore, 2-tetrahydropyranyl acrylate (THPA), and acrylate mannose (MAN). The block copolymer was then self-assembled to produce micelles. The chemotherapy drug dasatinib (DAS) and the sonodynamic therapy agent methylene blue (MB) were encapsulated by the self-assembly of the block copolymer. This targeted nanoparticle enables sonodynamic therapy through high-intensity focused ultrasound while triggering nanoparticle disassembly for controlled drug release. The ultrasound-mediated, non-invasive strategy provides external spatiotemporal control for targeted tumour treatment.

Digestion dynamics of acetamiprid during royal jelly formation and exposure risk assessment to honeybee larva based on processing factor.

Previous studies to the exposure effects of acetamiprid on honeybees were based on the analysis of bee pollen and honey sacs from field trials or of beebread and honey in the hive, which overestimate or underestimate the risk of exposure to pesticide residues. It was believed that the processing factor (PF) is an important variable to determine the final pesticide residue during royal jelly formation and the actual risk to honeybee larva. Hence, a QuEChERS method to determine acetamiprid contents in honeybee samples was established in this study. Then, the PFs for acetamiprid in beebread fermentation, honey brewing, and royal jelly formation were determined to be 0.85, 0.76, and 0.16, respectively. The PF for royal jelly formation was 0.04 when acetamiprid was detected in beebread alone, and it was 0.12 when acetamiprid was only detected in honey. Finally, the predicted exposure concentration of acetamiprid in royal jelly was calculated to be 2.05 µg/kg using the PF without significant difference with the 90th percentile value (3.64 µg/kg) in the actual sample. However, the value was 16.62 µg/kg without considering the PF. This study establishes a methodology for the correct evaluation of the risk to bee larva of acetamiprid residues in bee pollen and honey sac contents and the residual levels in royal jelly.