Advances in experimental models of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent articular inflammation and joint damage. RA was first described over 200 years ago; however, its etiology and pathophysiology remain insufficiently understood. The current treatment of RA is mainly empirical or based on the current understanding of etiology with limited efficacy and/or substantial side effects. Thus, the development of safer and more potent therapeutics, validated and optimized in experimental models, is urgently required. To improve the transition from bench to bedside, researchers must carefully select the appropriate experimental models as well as draw the right conclusions. Here, we summarize the establishment, pathological features, potential mechanisms, advantages, and limitations of the currently available RA models. The aim of the review is to help researchers better understand available RA models; discuss future trends in RA model development, which can help highlight new translational and human-based avenues in RA research.

Apigenin suppresses epithelial-mesenchymal transition in high glucose-induced retinal pigment epithelial cell by inhibiting CBP/p300-mediated histone acetylation.

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.

A novel imprinted locus on bovine chromosome 18 homologous with human chromosome 16q24.1.

Genomic imprinting is an epigenetic regulation mechanism in mammals resulting in the parentally dependent monoallelic expression of genes. Imprinting disorders in humans are associated with several congenital syndromes and cancers and remain the focus of many medical studies. Cattle is a better model organism for investigating human embryo development than mice. Imprinted genes usually cluster on chromosomes and are regulated by different methylation regions (DMRs) located in imprinting control regions that control gene expression in cis. There is an imprinted locus on human chromosome 16q24.1 associated with congenital lethal developmental lung disease in newborns. However, genomic imprinting on bovine chromosome 18, which is homologous with human chromosome 16 has not been systematically studied. The aim of this study was to analyze the allelic expressions of eight genes (CDH13, ATP2C2, TLDC1, COTL1, CRISPLD2, ZDHHC7, KIAA0513, and GSE1) on bovine chromosome 18 and to search the DMRs associated gene allelic expression. Three transcript variants of the ZDHHC7 gene (X1, X2, and X5) showed maternal imprinting in bovine placentas. In addition, the monoallelic expression of X2 and X5 was tissue-specific. Five transcripts of the KIAA0513 gene showed tissue- and isoform-specific monoallelic expression. The CDH13, ATP2C2, and TLDC1 genes exhibited tissue-specific imprinting, however, COTL1, CRISLPLD2, and GSE1 escaped imprinting. Four DMRs, established after fertilization, were found in this region. Two DMRs were located between the ZDHHC7 and KIAA0513 genes, and two were in exon 1 of the CDH13 and ATP2C2 genes, respectively. The results from this study support future studies on the molecular mechanism to regulate the imprinting of candidate genes on bovine chromosome 18.

Identification of Fasudil as a collaborator to promote the anti-tumor effect of lenvatinib in hepatocellular carcinoma by inhibiting GLI2-mediated hedgehog signaling pathway.

Lenvatinib is a frontline tyrosine kinase inhibitor for patients with advanced hepatocellular carcinoma (HCC). However, just 25% of patients benefit from the treatment, and acquired resistance always develops. To date, there are neither effective medications to combat lenvatinib resistance nor accurate markers that might predict how well a patient would respond to the lenvatinib treatment. Thus, novel strategies to recognize and deal with lenvatinib resistance are desperately needed. In the current study, a robust Lenvatinib Resistance index (LRi) model to predict lenvatinib response status in HCC was first established. Subsequently, five candidate drugs (Mercaptopurine, AACOCF3, NU1025, Fasudil, and Exisulind) that were capable of reversing lenvatinib resistance signature were initially selected by performing the connectivity map (CMap) analysis, and fasudil finally stood out by conducting a series of cellular functional assays in vitro and xenograft mouse model. Transcriptomics revealed that the co-administration of lenvatinib and fasudil overcame lenvatinib resistance by remodeling the hedgehog signaling pathway. Mechanistically, the feedback activation of EGFR by lenvatinib led to the activation of the GLI2-ABCC1 pathway, which supported the HCC cell's survival and proliferation. Notably, co-administration of lenvatinib and fasudil significantly inhibited IHH, the upstream switch of the hedgehog pathway, to counteract GLI2 activation and finally enhance the effectiveness of lenvatinib. These findings elucidated a novel EGFR-mediated mechanism of lenvatinib resistance and provided a practical approach to overcoming drug resistance in HCC through meaningful drug repurposing strategies.

Top-down design of high-performance V-based MBene anode for Li/Na-ion batteries.

Two-dimensional (2D) MBenes have enormous potential in energy applications. Vanadium metal, with its versatile and tunable electronic states, can further enhance the electrochemical performance of MBenes. However, most MBenes are composed of a few atomic layers as the metal boron (MB) block, e.g., M2B2, which might lead to instability and poor mechanical response. Herein, we designed and predicted 2D V4B6 associated with different terminations (T = Cl, O, S) using a top-down method and global search for parental V4AB6. Among the A element candidates, the P-glued MAB phase exhibited high stability and easy synthesizability. Moreover, 2D V4B6 was feasibly formed and easily exfoliated owing to its weak V-P bonding. Most of the surface functionalization could improve both the mechanical and electrochemical properties of the V4B6 monolayer. In particular, 2D V4B6S2 exhibited a high potential as an anode material for lithium-ion batteries (LIBs) with high theoretical capacity (297 mA h g-1), low diffusion barrier (0.166 eV), and low open circuit voltage (0.136 V), outperforming a majority of MXenes and transition metal sulfide layers. This work offers a new strategy for designing desirable 2D layers from parental materials, and tuning their properties via composition and surface functionalization, which could shed light on the development of other 2D metal-ion anodes.

Multidimensional Cell-Free DNA Fragmentomic Assay for Detection of Early-Stage Lung Cancer.

Rationale: Cell-free DNA (cfDNA) analysis holds promise for early detection of lung cancer and benefits patients with higher survival. However, the detection sensitivity of previous cfDNA-based studies was still low to suffice for clinical use, especially for early-stage tumors. Objectives: Establish an accurate and affordable approach for early-stage lung cancer detection by integrating cfDNA fragmentomics and machine learning models. Methods: This study included 350 participants without cancer and 432 participants with cancer. The participants' plasma cfDNA samples were profiled by whole-genome sequencing. Multiple cfDNA features and machine learning models were compared in the training cohort to achieve an optimal model. Model performance was evaluated in three validation cohorts. Measurements and Main Results: A stacked ensemble model integrating five cfDNA features and five machine learning algorithms constructed in the training cohort (cancer: 113; healthy: 113) outperformed all the models built on individual feature-algorithm combinations. This integrated model yielded superior sensitivities of 91.4% at 95.7% specificity for cohort validation I (area under the curve [AUC], 0.984), 84.7% at 98.6% specificity for validation II (AUC, 0.987), and 92.5% at 94.2% specificity for additional validation (AUC, 0.974), respectively. The model's high performance remained consistent when sequencing depth was down to 0.5× (AUC, 0.966-0.971). Furthermore, our model is sensitive to identifying early pathological features (83.2% sensitivity for stage I, 85.0% sensitivity for <1 cm tumor at the 0.66 cutoff). Conclusions: We have established a stacked ensemble model using cfDNA fragmentomics features and achieved superior sensitivity for detecting early-stage lung cancer, which could promote early diagnosis and benefit more patients.

Dissipation and Safety Analysis of Dimethomorph Application in Lychee by High-Performance Liquid Chromatography-Tandem Mass Spectrometry with QuEChERS.

This study presents a method for analyzing dimethomorph residues in lychee using QuEChERS extraction and HPLC-MS/MS. The validation parameters for this method, which include accuracy, precision, linearity, and recovery, indicate that it meets standard validation requirements. Following first-order kinetics, the dissipation dynamic of dimethomorph in lychee was determined to range from 6.4 to 9.2 days. Analysis of terminal residues revealed that residues in whole lychee were substantially greater than those in the pulp, indicating that dimethomorph residues are predominantly concentrated in the peel. When applied twice and thrice at two dosage levels with pre-harvest intervals (PHIs) of 5, 7, and 10 days, the terminal residues in whole lychee ranged from 0.092 to 1.99 mg/kg. The terminal residues of the pulp ranged from 0.01 to 0.18 mg/kg, with the residue ratio of whole lychee to pulp consistently exceeding one. The risk quotient (RQ) for dimethomorph, even at the recommended dosage, was less than one, indicating that the potential for damage was negligible. This study contributes to the establishment of maximum residue limits (MRLs) in China by providing essential information on the safe application of dimethomorph in lychee orchards.

Saikosaponin A triggers cell ferroptosis in hepatocellular carcinoma by inducing endoplasmic reticulum stress-stimulated ATF3 expression.

Ferroptosis is a type of nonapoptotic necrotic cell death characterized by iron-dependent lipid peroxidation. Saikosaponin A (SsA), a natural bioactive triterpenoid saponin extracted from Radix Bupleuri, has shown potent antitumor activity against various tumors. However, the underlying mechanism of the antitumor activity of SsA remains unclear. Here, we discovered that SsA induced HCC cell ferroptosis in vitro and in vivo. Using RNA-sequence analysis, we found that SsA mainly affected the glutathione metabolic pathway and inhibited the expression of cystine transporter solute carrier family 7 member 11 (SLC7A11). Indeed, SsA increased intracellular malondialdehyde (MDA) and iron accumulation, while it decreased the levels of reduced glutathione (GSH) in HCC. Deferoxamine (DFO), ferrostatin-1 (Fer-1) and GSH could rescue SsA-induced cell death, whereas Z-VAD-FMK was found ineffective in inhibiting SsA-induced cell death in HCC. Importantly, our result indicated that SsA induced the expression of activation transcription factor 3 (ATF3). SsA-induced cell ferroptosis and suppression of SLC7A11 are dependent on ATF3 in HCC. Moreover, we revealed that SsA induced ATF3 upregulation via activation of endoplasmic reticulum (ER) stress. Taken together, our findings support that ATF3-dependent cell ferroptosis mediated the antitumor effects of SsA, opening the possibility to explore SsA as a ferroptosis inducer in HCC.

YEATS2 regulates the activation of TAK1/NF-κB pathway and is critical for pancreatic ductal adenocarcinoma cell survival.

The prognosis of pancreatic ductal adenocarcinoma (PDAC) is poor despite diagnostic progress and new chemotherapeutic regimens. Constitutive activation of NF-κB is frequently observed in PDAC. In this study, we found that YEATS2, a scaffolding protein of ATAC complex, was highly expressed in human PDAC. Depletion of YEATS2 reduced the growth, survival, and tumorigenesis of PDAC cells. The binding of YEATS2 is crucial for maintaining TAK1 activation and NF-κB transcriptional activity. Of importance, our results reveal that YEATS2 promotes NF-κB transcriptional activity through modulating TAK1 abundance and directly interacting with NF-κB as a co-transcriptional factor.

GPR84 regulates pulmonary inflammation by modulating neutrophil functions.

Acute lung injury (ALI) is an acute, progressive hypoxic respiratory failure that could develop into acute respiratory distress syndrome (ARDS) with very high mortality rate. ALI is believed to be caused by uncontrolled inflammation, and multiple types of immune cells, especially neutrophils, are critically involved in the development of ALI. The treatment for ALI/ARDS is very limited, a better understanding of the pathogenesis and new therapies are urgently needed. Here we discover that GPR84, a medium chain fatty acid receptor, plays critical roles in ALI development by regulating neutrophil functions. GPR84 is highly upregulated in the cells isolated from the bronchoalveolar lavage fluid of LPS-induced ALI mice. GPR84 deficiency or blockage significantly ameliorated ALI mice lung inflammation by reducing neutrophils infiltration and oxidative stress. Further studies reveal that activation of GPR84 strongly induced reactive oxygen species production from neutrophils by stimulating Lyn, AKT and ERK1/2 activation and the assembly of the NADPH oxidase. These results reveal an important role of GPR84 in neutrophil functions and lung inflammation and strongly suggest that GPR84 is a potential drug target for ALI.

Experience in diagnosis and treatment of duodenal ulcer perforation in children.

BACKGROUND: This study aims to summarize our experience in diagnosis and treatment of pediatric duodenal ulcer perforation in a National Center for Children's Health. METHODS: Fifty-two children with duodenal perforation hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University from January 2007 to December 2021 were retrospectively collected. According to the inclusion and exclusion criteria, patients with duodenal ulcer perforation were included in the group. They were divided into the surgery group and the conservative group according to whether they received surgery. RESULTS: A total of 45 cases (35 males and 10 females) were included, with a median age of 13.0 (0.3-15.4) years. Forty cases (40/45, 88.9%) were over 6 years old, and 31 (31/45, 68.9%) were over 12 years old. Among the 45 cases, 32 cases (32/45, 71.1%) were examined for Helicobacter pylori (HP), and 25 (25/32, 78.1%) were positive. There were 13 cases in the surgery group and 32 cases in the conservative group, without a significant difference in age between the two groups (P = 0.625). All cases in the surgery group and the conservative group started with abdominal pain. The proportion of history time within 24 h in the two groups was 6/13 and 12/32 (P = 0.739), and the proportion of fever was 11/13 and 21/32 (P = 0.362). The proportion of pneumoperitoneum in the surgery group was higher than that in the conservative group (12/13 vs. 15/32, P = 0.013). The fasting days in the surgery group were shorter than those in the conservative group (7.7 ± 2.92 vs. 10.3 ± 2.78 days, P = 0.014). There was no significant difference in the total hospital stay (13.6 ± 5.60 vs14.8 ± 4.60 days, P = 0.531). The operation methods used in the surgery group were all simple sutures through laparotomy (9 cases) or laparoscopy (4 cases). All patients recovered smoothly after surgery. CONCLUSION: Duodenal ulcer perforation in children is more common in adolescents, and HP infection is the main cause. Conservative treatment is safe and feasible, but the fasting time is longer than the surgery group. A simple suture is the main management for the surgery group.

Management of complicated choledochal cyst in children: ultrasound-guided percutaneous external drainage and subsequent definitive operation.

OBJECTIVE: The purpose of this study was to analyze the outcomes of the combination of ultrasound (US)-guided percutaneous external drainage and subsequent definitive operation to manage complicated choledochal cyst in children. METHODS: This retrospective study included 6 children with choledochal cyst who underwent initial US-guided percutaneous external drainage and subsequent cyst excision with Roux-en-Y hepaticojejunostomy between January 2021 and September 2022. Patient characteristics, laboratory findings, imaging data, treatment details, and postoperative outcomes were evaluated. RESULTS: Mean age at presentation was 2.7 ± 2.2 (0.5-6.2) years, and 2 patients (2/6) were boys. Four patients (4/6) had a giant choledochal cyst with the widest diameter of ≥ 10 cm and underwent US-guided percutaneous biliary drainage on admission or after conservative treatments. The other 2 patients (2/6) underwent US-guided percutaneous transhepatic cholangio-drainage and percutaneous transhepatic gallbladder drainage due to coagulopathy, respectively. Five patients (5/6) recovered well after US-guided percutaneous external drainage and underwent the definitive operation, whereas 1 patient (1/6) had liver fibrosis confirmed by Fibroscan and ultimately underwent liver transplantation 2 months after external drainage. The mean time from US-guided percutaneous external drainage to the definitive operation was 12 ± 9 (3-21) days. The average length of hospital stay was 24 ± 9 (16-31) days. No related complications of US-guided percutaneous external drainage occurred during hospitalization. At 10.2 ± 6.8 (1.0-18.0) months follow-up, all patients had a normal liver function and US examination. CONCLUSIONS: Our detailed analysis of this small cohort suggests that US-guided percutaneous external drainage is technically feasible for choledochal cyst with giant cysts or coagulopathy in children, which may provide suitable conditions for subsequent definitive operation with a good prognosis. TRIAL REGISTRATION: Retrospectively registered.

Decreased cuticular penetration minimizes the impact of the pyrethroid insecticide λ-cyhalothrin on the insect predator Eocanthecona furcellata.

The use of broad-spectrum pesticides may reduce the biological control efficacy of predatory arthropods. Hence, the risks of pesticides to predators need to be evaluated. Here, we assessed the effects of a broad spectrum pyrethroid λ-cyhalothrin on a polyphagous predatory insect Eocanthecona furcellata via contact exposure route. The recommended application rate of λ-cyhalothrin was lower than the LR50 and HQ (in-field) was equal to 0.57, indicating the risk of λ-cyhalothrin to E. furcellata was low. Dried λ-cyhalothrin residue had no effect on the mortality, body weight, protein content of cuticle, or activities of major detoxification enzymes in E. furcellata. Residual of λ-cyhalothrin was only detected in the cuticle and legs of E. furcellata with a decreasing trend as time went by and no λ-cyhalothrin was detected inside the body. Additionally, a comparative transcriptome analysis was conducted to study global changes in gene expression in E. furcellata at different time points following exposure to λ-cyhalothrin-contaminated environment. A total of 57,839 unigenes with an average length of 1044 bp and an N50 of 1820 bp were obtained. In total, 118 and 109 differentially expressed genes (DEGs) at 12 h, and 60 h were identified between two groups. The DEGs were largely enriched in functional categories related to the structural constituent of cuticle. Accordingly, multiple cuticle protein-coding genes were up-regulated at 12 h after pesticide exposure. The present study stressed the importance of evaluating the compatibility between a specific pesticide (λ-cyhalothrin) and E. furcellata via simulating the releasing predators after insecticide application. The data could help optimize the pesticide use, optimizing the ecological services of E. furcellata as a BCA, and expanding its use into more areas of agriculture.

Predatory stink bug, Eocanthecona furcellata (Wolff) responses to oral exposure route of λ-cyhalothrin via sex-specific modulation manner.

The toxic effects of insecticides on predatory arthropods have closely related to their exposure routes. However, little is known about the effects of insecticide on reproductive parameters when the route of exposure occurs at a trophic level via prey intake. We therefore conducted current studies assessing whether Eocanthecona furcellata adults would be affected by feeding with λ-cyhalothrin-contaminated prey. Reproductive parameters, i.e. prolonged premating and preoviposition durations, reduced number of egg batches and egg amount, disturbed ovarian development, and suppressed expression of reproductive related genes were observed in E. furcellata females by feeding with treated prey. Moreover, reduced survival rate and altered carbohydrate metabolism parameters were detected in male bugs. Biochemical parameters, including MDA content, the activities of three antioxidant enzymes and three detoxification enzymes exhibited sex-specific responses after oral-exposure to λ-cyhalothrin in E. furcellata. The results indicate that the insecticide affects the fitness and leads to impairing reproductive potential via sex-specific modulation manner in predator insects. Taken together, our results provide a comprehensive assessment about detrimental impacts of λ-cyhalothrin-exposure on predators via prey intake, as well as a solid basis for further research to protect the predators from hazardous impacts of insecticides.

Comparative analyses of the effects of sublethal doses of emamectin benzoate and tetrachlorantraniliprole on the gut microbiota of Spodoptera frugiperda (Lepidoptera: Noctuidae).

Spodoptera frugiperda (J. E. Smith) is an important invasive pest that poses a serious threat to global crop production. Both emamectin benzoate (EB) and diamide insecticides are effective insecticides used to protect against S. frugiperda. Here, 16S rRNA sequencing was used to characterize the gut microbiota in S. frugiperda larvae exposed to EB or tetrachlorantraniliprole (TE). Firmicutes and Proteobacteria were found to be the dominant bacterial phyla present in the intestines of S. frugiperda. Following insecticide treatment, larvae were enriched for species involved in the process of insecticide degradation. High-level alpha and beta diversity indices suggested that exposure to TE and EB significantly altered the composition and diversity of the gastrointestinal microbiota in S. frugiperda. At 24 h post-EB treatment, Burkholderia-Caballeronia-Paraburkholderia abundance was significantly increased relative to the control group, with significant increases in Stenotrophobacter, Nitrospira, Blastocatella, Sulfurifustis, and Flavobacterium also being evident in these larvae. These microbes may play a role in the degradation or detoxification of EB and TE, although further work will be needed to explore the mechanisms underlying such activity. Overall, these findings will serve as a theoretical foundation for subsequent studies of the relationship between the gut microbiota and insecticide resistance in S. frugiperda (J. E. Smith) (Lepidoptera: Noctuidae).

Comparison of Glyphosate-Degradation Ability of Aldo-Keto Reductase (AKR4) Proteins in Maize, Soybean and Rice.

Genes that participate in the degradation or isolation of glyphosate in plants are promising, for they endow crops with herbicide tolerance with a low glyphosate residue. Recently, the aldo-keto reductase (AKR4) gene in Echinochloa colona (EcAKR4) was identified as a naturally evolved glyphosate-metabolism enzyme. Here, we compared the glyphosate-degradation ability of theAKR4 proteins from maize, soybean and rice, which belong to a clade containing EcAKR4 in the phylogenetic tree, by incubation of glyphosate with AKR proteins both in vivo and in vitro. The results indicated that, except for OsALR1, the other proteins were characterized as glyphosate-metabolism enzymes, with ZmAKR4 ranked the highest activity, and OsAKR4-1 and OsAKR4-2 exhibiting the highest activity among the AKR4 family in rice. Moreover, OsAKR4-1 was confirmed to endow glyphosate-tolerance at the plant level. Our study provides information on the mechanism underlying the glyphosate-degradation ability of AKR proteins in crops, which enables the development of glyphosate-resistant crops with a low glyphosate residue, mediated by AKRs.

Safety Evaluation of Chlorantraniliprole in Lychee Based on Residue and Dietary Risk Assessment.

This report presents the development of a highly effective method employing high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to investigate chlorantraniliprole's dissipation, risk assessment, and residue distribution in whole lychee fruit and its pulp. Mean recoveries of the samples ranged from 80 to 105%, exhibiting a relative standard deviation (RSD) of below 8%. The limits of quantification (LOQ) for lychee and pulp were determined as 0.001 mg/kg, and half-lives (t1/2) ranged from 8.0 to 12.2 days. Terminal residue concentrations in whole litchi and pulp were determined as 0.008-0.45 mg/kg and ≤0.001 mg/kg. These residues were treated twice and thrice at two different dosage levels with pre-harvest intervals (PHIs) of 7, 14, and 21 days. The potential chronic risk posed by chlorantraniliprole to humans was non-negligible, as indicated by the risk quotient (RQ) value not exceeding 1. Therefore, this study provides significant fresh data about the safe application of chlorantraniliprole in the production of lychee, which will help China develop maximum residual limits (MRLs).

Safe Application of 75% Trifloxystrobin-Tebuconazole as Water-Dispersible Granules in Paddy Based on Residue and Dietary Risk Assessment.

The present study describes the development of a highly effective approach for determining the residue distribution and dissipation of trifloxystrobin and tebuconazole, and their risk assessment in brown rice, husk, straw, and grain using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The current study provides considerable novel information regarding the safe utilization of a mixture of trifloxystrobin and tebuconazole in paddy production. The samples demonstrated a range of mean recoveries between 72% and 86%, with a 1.1-9.2% relative standard deviation (RSD). The limits of quantification (LOQ) and half-lives (t1/2) for brown rice, husk, straw, and grain were, respectively, established to be 0.001-0.01 mg/kg and 4.1-7.7 days. The concentrations of terminal residues in the brown rice, husk, straw, and grain were, respectively, found to be 0.02-0.05, 0.03-0.11, 0.02-0.07, and 0.02-0.05 mg/kg after being treated twice at 168.75 g a.i./ha with 21 and 28 days of pre-harvest intervals (PHIs). Trifloxystrobin and tebuconazole presented a non-negligible chronic risk to human subjects, as evidenced by a risk quotient (RQ) value of less than 1.

Dissipation Dynamic, Residue Distribution and Risk Assessment of Emamectin Benzoate in Longan by High-Performance Liquid Chromatography with Fluorescence Detection.

A derivatization method combined with high-performance liquid chromatography-fluorescence detection (HPLC-FLD) was used to evaluate the dissipation, residue distribution and risk assessment of emamectin benzoate in whole longan and pulp. The average recoveries were 82-111% with relative standard deviation (RSD) less than 11%. The limit of quantification (LOQ) was 0.001 mg/kg in longan and pulp. The half-lives were 3.3-4.2 days. The terminal residues in whole longan were <0.001-0.025 mg/kg applied two and three times at two levels of dosage with PHIs of 10, 14, and 21 days. The residues in whole longan had a higher quantity than those in the pulp, and the terminal residues of pulp were all lower than LOQ (0.001 mg/kg). The chronic risk of emamectin benzoate was not negligible to humans depending on ADI% value, which was higher than 1; and the acute risk was acceptable to the consumer. This study could provide guidance for the safe use of emamectin benzoate in longan and serve as a reference for the establishment of maximum residue limits (MRLs) in China.

Analysis of the fungicidal efficacy, environmental fate, and safety of the application of a mefentrifluconazole and pyraclostrobin mixture to control mango anthracnose.

BACKGROUND: Mango anthracnose is among the most severe diseases impacting mango yields and quality. While this disease can be effectively controlled through chemical means, it is vital that appropriate field efficacy and fate determination studies be conducted when applying pesticides to crops in order to appropriately gauge the ecological and health risks associated with the use of these agents. RESULTS: GAP field trials were conducted to explore the efficacy, dissipation, and terminal residues associated with the application of mefentrifluconazole and pyraclostrobin to mango crops in six locations throughout China. These analyses revealed that three applications of mefentrifluconazole [160 mg active ingredient (a.i.) kg-1 ] in combination with pyraclostrobin mixture achieved satisfactory disease control efficacy. To simultaneously detect mefentrifluconazole and pyraclostrobin residues on mangoes, a 'quick, easy, cheap, effective, rugged and safe' (QuEChERS) high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based approach was established. The initial mefentrifluconazole and pyraclostrobin concentrations ranged from 0.18 to 0.34 mg kg-1 , and these two compounds exhibited respective half-lives of 5.6 to 10.8 days and 5.5 to 9.0 days. At 21 days following foliage application, the terminal mefentrifluconazole and pyraclostrobin residue concentrations were 0.02-0.04 and 0.01-0.04 mg kg-1 , with these concentrations being below the maximum residue limit (MRL) established for pyraclostrobin. Both short-term [acute reference dose percent (ARfD%) 0.78-2.36% and 2.0-6.08%] and chronic [acceptable daily intake percent (ADI%) 0.08-0.47% and 0.09-0.55%] dietary intake risk assessments for mefentrifluconazole and pyraclostrobin indicated that these terminal residue concentrations are acceptable for the general population. CONCLUSION: Mefentrifluconazole and pyraclostrobin in mango was rapidly degraded following first-order kinetics models. The dietary risk of mefentrifluconazole and pyraclostrobin through mango was negligible to consumers. The application of a 400 g L-1 mefentrifluconazole-pyraclostrobin suspension concentrate mixture represents a highly efficacious fungicidal approach to controlling mango anthracnose that exhibits significant potential for development as it is easily degraded and associated with low residual concentrations after application. © 2022 Society of Chemical Industry.