Glycometabolic disorder induced by chronic exposure to low-concentration imidacloprid in zebrafish.

The health risks induced by chronic exposure to low concentrations of imidacloprid (IMI) to zebrafish were investigated in this study. The results indicated that the growth of zebrafish was inhibited after being exposed to 10, 100, and 500 µg/L of IMI for 90 days. Moreover, the blood glucose levels in the IMI-exposed groups were significantly higher compared to the control group. Investigation into the development of zebrafish larvae revealed that IMI exposure hindered the development of the liver and pancreatic islets, organs crucial for glucose metabolism. In addition, the IMI-exposed groups exhibited reduced liver glycogen and plasma insulin levels, along with changes in the activity of enzymes and the transcription levels of genes associated with liver glucose metabolism. These findings suggest that IMI induces glycometabolic disorders in zebrafish. The analysis of intestinal flora revealed that several key bacteria associated with an elevated risk of diabetes were significantly altered in IMI-exposed fish. Specifically, a remarkable decrease was found in the abundance of the genera Aeromonas and Shewanella, which have been found closely related to the development of pancreatic islets. This implies that the alteration of key bacteria in the fish gut by IMI, which in turn affects the development of organs such as the pancreatic islets, may be the initial trigger for abnormalities in glucose metabolism. Our results revealed that chronic exposure to low concentrations of IMI led to glycometabolic disorder in fish. Therefore, considering the pervasive existence of IMI residues in the environment, the health hazards posed by low-concentration IMI to fish cannot be overlooked.

[Determination of three new herbicide residues in soil, sediment and water by liquid chromatography-tandem mass spectrometry].

Herbicides play an important role in preventing and controlling weeds and harmful plants and are increasingly used in agriculture, forestry, landscaping, and other fields. However, the effective utilization rate of herbicides is only 20%-30%, and most herbicides enter the atmosphere, soil, sediment, and water environments through drift, leaching, and runoff after field application. Herbicide residues in the environment pose potential risks to ecological safety and human health. Therefore, establishing analytical methods to determine herbicide residues in environmental samples is of great importance. In this study, an analytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) in positive electrospray ionization mode (ESI+) was developed for the determination of isoxaflutole, metazachlor, and saflufenacil residues in soil, sediment, and water. The instrumental detection parameters, including electrospray ionization mode, mobile phase, and chromatographic column, were optimized. The mobile phases were methanol (A) and 0.1% formic acid aqueous solution (B). Gradient elution was performed as follows: 0-1.0 min, 60%A; 1.0-2.0 min, 60%A-90%A; 2.0-3.0 min, 90%A; 3.0-4.0 min, 90%A-60%A; 4.0-5.0 min, 60%A. The samples were salted after extraction with acetonitrile and cleaned using a C18 solid-phase extraction column. Different solid-phase extraction columns and leaching conditions were investigated during sample pretreatment. Working curves in the neat solvent and matrix were constructed by plotting the measured peak areas as a function of the concentrations of the analytes in the neat solvent and matrix. Good linearities were found for isoxaflutole, metazachlor, and saflufenacil in the solvent and matrix-matched standards in the range of 0.0005-0.02 mg/L, with r≥0.9961. The matrix effects of the three herbicides in soil, sediment, and water ranged from -10.1% to 16.5%. The limits of detection (LODs, S/N=3) for isoxaflutole, metazachlor, and saflufenacil were 0.05, 0.01, and 0.02 µg/kg, respectively. The limits of quantification (LOQs, S/N=10) for isoxaflutole, metazachlor, and saflufenacil were 0.2, 0.05, and 0.05 µg/kg, respectively. The herbicides were applied to soil, sediment, and water at spiked levels of 0.005, 0.1, and 2.0 mg/kg, respectively. The average recoveries for isoxaflutole, metazachlor, and saflufenacil in soil, sediment, and water were in the ranges of 77.2%-101.9%, 77.9%-105.1%, and 80.8%-107.1%, respectively. The RSDs for isoxaflutole, metazachlor, and saflufenacil were in the ranges of 1.4%-12.8%, 1.2%-7.7%, and 1.5%-11.5%, respectively. The established method was used to analyze actual samples collected from four different sites in Zhejiang Province (Xiaoshan, Taizhou, Dongyang, and Yuhang) and one site in Heilongjiang (Jiamusi). The proposed method is simple, rapid, accurate, stable, and highly practical. It can be used to detect isoxaflutole, metazachlor, and saflufenacil residues in soil, sediment, and water and provides a reference for monitoring the residual pollution and environmental behavior of herbicides.

A systemic study of cyenopyrafen in strawberry cultivation system: Efficacy, residue behavior, and impact on honeybees (Apis mellifera L.).

The pesticide application method is one of the important factors affecting its effectiveness and residues, and the risk of pesticides to non-target organisms. To elucidate the effect of application methods on the efficacy and residue of cyenopyrafen, and the toxic effects on pollinators honeybees in strawberry cultivation, the efficacy and residual behavior of cyenopyrafen were investigated using foliar spray and backward leaf spray in field trials. The results showed that the initial deposition of cyenopyrafen using backward leaf spray on target leaves reached 5.06-9.81 mg/kg at the dose of 67.5-101.25 g a.i./ha, which was higher than that using foliar spray (2.62-3.71 mg/kg). The half-lives of cyenopyrafen in leaves for foliar and backward leaf spray was 2.3-3.3 and 5.3-5.9 d, respectively. The residues (10 d) of cyenopyrafen in leaves after backward leaf spray was 1.41-3.02 mg/kg, which was higher than that after foliar spraying (0.25-0.37 mg/kg). It is the main reason for the better efficacy after backward leaf spray. However, the residues (10 d) in strawberry after backward leaf spray and foliar spray was 0.04-0.10 and < 0.01 mg/kg, which were well below the established maximum residue levels of cyenopyrafen in Japan and South Korea for food safety. To further investigate the effects of cyenopyrafen residues after backward leaf spray application on pollinator honeybees, sublethal effects of cyenopyrafen on honeybees were studied. The results indicated a significant inhibition in the detoxification metabolic enzymes of honeybees under continuous exposure of cyenopyrafen (0.54 and 5.4 mg/L) over 8 d. The cyenopyrafen exposure also alters the composition of honeybee gut microbiota, such as increasing the relative abundance of Rhizobiales and decreasing the relative abundance of Acetobacterales. The comprehensive data on cyenopyrafen provide basic theoretical for environmental and ecological risk assessment, while backward leaf spray proved to be effective and safe for strawberry cultivation.

Uptake, accumulation and toxicity of short chain chlorinated paraffins to wheat (Triticum aestivum L.).

Short chain chlorinated paraffins (SCCPs) are ubiquitous persistent organic pollutants. They have been widely detected in plant-based foods and might cause adverse impacts on humans. Nevertheless, uptake and accumulation mechanisms of SCCPs in plants remain unclear. In this study, the soil culture data indicated that SCCPs were strongly absorbed by roots (root concentration factor, RCF>1) yet limited translocated to shoots (translocation factor<1). The uptake mechanism was explored by hydroponic exposure, showing that hydrophobicity and molecular size influenced the root uptake and translocation of SCCPs. RCFs were significantly correlated with logKow values and molecular weights in a parabolic curve relationship. Besides, it was extremely difficult for SCCPs to translocate from shoots back to roots via phloem. An active energy-dependent process was proposed to be involved in the root uptake of SCCPs, which was supported by the uptake inhibition by the low temperature and metabolic inhibitor. Though SCCPs at environmentally relevant concentrations had no negative impacts on root morphology and chlorophyll contents, it caused obvious changes in cellular ultrastructure of root tip cells and induced a significant increase in superoxide dismutase activity. This information may be beneficial to moderate crop contamination by SCCPs, and to remedy soils polluted by SCCPs with plants.

Dissipation behavior and dietary risk assessment of cyclaniliprole and its metabolite in cabbage under field conditions.

Cyclaniliprole, a novel diamide insecticide, can successfully control Spodoptera litura (Fabricius, 1775) in cabbage. Understanding the residual level of cyclaniliprole in crops and the risk related to its dietary intake is imperative for safe application. Here, we established a simplified, sensitive method for simultaneous analysis of cyclaniliprole and its metabolite NK-1375 (3-bromo-2-((2-bromo-4H-pyrazolo[1,5-d]pyrido[3,2-b]-[1,4]oxazin-4-ylidene)amino)-5-chloro-N-(1-cyclopropylethyl)benzamide) in cabbage by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate their dissipation behavior and residual characteristics. Cyclaniliprole showed rapid dissipation in cabbage and had a half-life of 1.8-2.7 days. The highest residue of total cyclaniliprole (sum of cyclaniliprole and NK-1375) in cabbage from different pre-harvest intervals (3 and 5 days) was 0.25 mg/kg. Our results confirmed the generally low dietary risk quotient of cyclaniliprole (0.243-1.036%) among different age and gender groups in China. Therefore, cyclaniliprole did not pose an unacceptable risk to consumers. This study contributes to setting cyclaniliprole maximum residue limit in cabbage by assessing its dissipation fate and food safety risks.

In vitro assessment of the pesticide bioaccessibility in Dendrobium officinale Kimura et Migo.

Bioaccessibility (BA) is a crucial factor for evaluating the absorption of pollutants in the human digestion system, which is of vital importance for risk assessment of pollutants via food intake. Multi-pesticides were detected in Dendrobium officinale Kimura et Migo (D. officinale), a popular dual-use plant with both botanical medicine and food applications. Nevertheless, the BA of pesticides in D. officinale remains unknown, restricting its market size. Herein, the BA of 19 pesticides with varying properties was evaluated by using an in vitro digestion model, showing BA values between 27.4 and 96.8%. The BA was controlled by the hydrophobicity and water solubility of pesticides, since the significant correlation between these two factors and BA values was observed. Moreover, co-ingested food ingredients could influence the BA, wherein the effect was significant for pesticides of logKow values no less than 3. Lipids enhanced the BA by 9-66%, whereas proteins or carbohydrates decreased BA values by 6-28%. In particular, considering the BA, the risk quotient values were reduced by 3-73%. Clearly, this work suggested that traditional risk assessment without considering the BA would seriously overestimate the actual risk of pesticides in food.

Regulation of LRRK2 mRNA stability by ATIC and its substrate AICAR through ARE-mediated mRNA decay in Parkinson's disease.

Mutations in LRRK2 are the most common genetic causes of Parkinson's disease (PD). While the enzymatic activity of LRRK2 has been linked to PD, previous work has also provided support for an important role of elevated LRRK2 protein levels, independent of enzymatic activity, in PD pathogenesis. However, the mechanisms underlying the regulation of LRRK2 protein levels remain unclear. Here, we identify a role for the purine biosynthesis pathway enzyme ATIC in the regulation of LRRK2 levels and toxicity. AICAr, the precursor of ATIC substrate, regulates LRRK2 levels in a cell-type-specific manner in vitro and in mouse tissue. AICAr regulates LRRK2 levels through AUF1-mediated mRNA decay. Upon AICAr treatment, the RNA binding protein AUF1 is recruited to the AU-rich elements (ARE) of LRRK2 mRNA leading to the recruitment of the decapping enzyme complex DCP1/2 and decay of LRRK2 mRNA. AICAr suppresses LRRK2 expression and rescues LRRK2-induced dopaminergic neurodegeneration and neuroinflammation in PD Drosophila and mouse models. Together, this study provides insight into a novel regulatory mechanism of LRRK2 protein levels and function via LRRK2 mRNA decay that is distinct from LRRK2 enzymatic functions.

Residues and Dietary Risk Assessment of Prohexadione-Ca and Uniconazole in Oryza sativa L. and Citrus reticulata Blanco by Liquid Chromatography-Tandem Mass Spectrometry.

A simple and sensitive method for the simultaneous quantitation of prohexadione-Ca and uniconazole in the field experiment of Oryza sativa L. and Citrus reticulata Blanco was established using solid-phase extraction (SPE) with polymer anion exchange (PAX) and Florisil followed by LC-MS/MS. The method demonstrated excellent linearity (R2 > 0.999 0), trueness (recoveries between 95~105%), precision (CVs between 0.8~12%), sensitivity, and repeatability (LOQ of 0.05 and 0.01 mg/kg, respectively). Residue tests were conducted in the field at 12 representative sites in China, revealing final concentrations of prohexadione-Ca and uniconazole in brown rice, rice hull, and rice straw to be below 0.05 mg/kg, while in whole citrus fruit and citrus pulp, they were below 0.01 mg/kg. These were below the maximum residue limits specified in China. The chronic dietary risks of prohexadione-Ca and uniconazole in rice crops and citrus fruits were calculated to be 0.48% and 0.91%, respectively. Our research suggests that the chronic risk associated with the daily consumption of rice crops and citrus fruit at the recommended dosage is acceptable.

Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability.

MYC-driven medulloblastomas are highly aggressive childhood brain tumors, however, the molecular and genetic events triggering MYC amplification and malignant transformation remain elusive. Here we report that mutations in CTDNEP1, a CTD nuclear-envelope-phosphatase, are the most significantly enriched recurrent alterations in MYC-driven medulloblastomas, and define high-risk subsets with poorer prognosis. Ctdnep1 ablation promotes the transformation of murine cerebellar progenitors into Myc-amplified medulloblastomas, resembling their human counterparts. CTDNEP1 deficiency stabilizes and activates MYC activity by elevating MYC serine-62 phosphorylation, and triggers chromosomal instability to induce p53 loss and Myc amplifications. Further, phosphoproteomics reveals that CTDNEP1 post-translationally modulates the activities of key regulators for chromosome segregation and mitotic checkpoint regulators including topoisomerase TOP2A and checkpoint kinase CHEK1. Co-targeting MYC and CHEK1 activities synergistically inhibits CTDNEP1-deficient MYC-amplified tumor growth and prolongs animal survival. Together, our studies demonstrate that CTDNEP1 is a tumor suppressor in highly aggressive MYC-driven medulloblastomas by controlling MYC activity and mitotic fidelity, pointing to a CTDNEP1-dependent targetable therapeutic vulnerability.

Kavain ablates the radio-resistance of IDH-wildtype glioblastoma by targeting LITAF/NF-κB pathway.

BACKGROUND: Glioblastoma multiforma (GBM) is the most malignant intrinsic tumor of the central nervous system (CNS), with high morbidity of 3.19/100,000 per year and a poor 5-year survival rate (< 5%) worldwide. Numerous studies have indicated that GBM shows remarkable radioresistance and aggressive recurrence. However, the mechanisms to endow GBM cells with radioresistance are complex and unclear. METHODS: Cell growth curve and colony formation assays were used to analyze the radioresistance of GBM. Immunoprecipitation and immunoblotting experiments were carried out to analyze protein expression and interaction. RESULTS: In the present study, we found that LITAF, lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α factor, is up-regulated both in mRNA and protein in GBM tumors. Meanwhile, we observed that high LITAF expression contributes to radioresistance of GBM cell lines (including U87, U251, DK, and AM38 cells), indicated by knockout or knockdown of LITAF in cells sensitizing them to radiation treatment both in vitro and in vivo. Furthermore, we demonstrated that kavain, an active constituent of Piper methysticum Forst., effectively ablates GSC-like cells' (such as CD133 + U87, U251, DK, and AM38 populations) radioresistance in a LITAF-dependent manner. CONCLUSION: In mechanism, our results indicated that 1) the elevation of LITAF in GBM cells activates the NF-κB pathway to promote mesenchymal transition, and 2) kavain disturbs STAT6B/LITAF protein interaction and then expels LITAF from the nucleus. Therefore, we consider that kavain may be a potential candidate to develop an irradiation therapy adjuvant for GBM.

Myotubularin functions through actomyosin to interact with the Hippo pathway.

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size by integrating diverse regulatory inputs, including actomyosin-mediated cytoskeletal tension. Despite established connections between the actomyosin cytoskeleton and the Hippo pathway, the upstream regulation of actomyosin in the Hippo pathway is less defined. Here, we identify the phosphoinositide-3-phosphatase Myotubularin (Mtm) as a novel upstream regulator of actomyosin that functions synergistically with the Hippo pathway during growth control. Mechanistically, Mtm regulates membrane phospholipid PI(3)P dynamics, which, in turn, modulates actomyosin activity through Rab11-mediated vesicular trafficking. We reveal PI(3)P dynamics as a novel mode of upstream regulation of actomyosin and establish Rab11-mediated vesicular trafficking as a functional link between membrane lipid dynamics and actomyosin activation in the context of growth control. Our study also shows that MTMR2, the human counterpart of Drosophila Mtm, has conserved functions in regulating actomyosin activity and tissue growth, providing new insights into the molecular basis of MTMR2-related peripheral nerve myelination and human disorders.

Thermal-Driven Formation of Silver Clusters Inside Na/Li FAUY Zeolites for Formaldehyde Detection.

In this research, the LiY zeolite was firstly synthesized by using NaY as the parent zeolite; thereafter, the LiYAg and NaYAg zeolites created for formaldehyde gas detection were prepared with further Ag+-Li+/Na+ exchange and a mild thermal treatment at 300 °C to promote the formation of luminescent Ag CLs. The spectra experimental results indicated that Ag CLs showed stronger and blue-shifted emissions in LiYAg compared with in NaYAg, and the emission intensity of Ag CLs in both zeolites monotonously decreased when exposed to increasing formaldehyde gas content. Moreover, the linear dependence of the Ag CLs' emission intensity variation on formaldehyde content indicated a reliable method for fast and sensitive formaldehyde detection. According to the XPS, UV-vis absorption, and N2 adsorption-desorption isotherm studies, the formaldehyde-gas-induced luminescence quenching of Ag CLs is due to the formation of Ag2O and Ag NPs, in which the higher content of Ag+/Ag0 redox couples in LiYAg and larger surface area of NaYAg benefit the precise detection of formaldehyde gas in low- and high-content ranges, respectively. Furthermore, the blue-shifted peak position and widened FWHM of Ag CLs can also be used for the indication of formaldehyde gas and the detection limit of NaYAg and LiYAg, which both meet with the standards of the WHO and OSHA.

Pentagalloylglucose disrupts the PALB2-BRCA2 interaction and potentiates tumor sensitivity to PARP inhibitor and radiotherapy.

DNA damage repair plays a vital role in maintaining the genomic integrity of cells and has been exploited therapeutically in the treatment of cancer. We have previously demonstrated that the upregulation of CXorf67 in posterior fossa type A ependymoma sensitizes tumor cells to PARP inhibitors by suppressing the PALB2-BRCA2 protein-protein interaction (PPI). Here, we performed structure-based virtual screening of ∼2 million small molecular entities followed by NanoBiT-based screening, and determined that pentagalloylglucose (PGG) disrupts the PALB2-BRCA2 PPI. Structure-based molecular docking and in vitro binding affinity assays revealed that PGG occupies a well-defined binding groove in the tips of the fourth and fifth blades of the PALB2 WD40 domain. PGG reduces BRCA2 recruitment to DNA damage sites and inhibits the formation of RAD51 foci, suppressing homologous recombination repair. PGG also inhibits proliferation and survival in several cancer cell lines, including breast cancer and medulloblastoma cells, and suppresses the in vivo growth of tumor xenografts. Thus, PGG is a specific inhibitor of the PALB2-BRCA2 PPI, which has potential value in cancer treatment to sensitize tumors to PARP inhibitors and radiotherapy.

Dissipation and dietary exposure risk assessment of pyraclostrobin, fluxapyroxad, difenoconazole, and azoxystrobin in the Fritillaria field ecosystem.

Fritillaria (Beimu in Chinese) is a well-known traditional Chinese medicinal herbal and valuable health food, which has attracted more and more attention. In this study, an efficient method was developed to determine pyraclostrobin, fluxapyroxad, difenoconazole, and azoxystrobin in plants, fresh Fritillaria, dry Fritillaria, and soil via liquid chromatography-tandem mass spectrometry. The average recoveries of the method were 78.9-109.7% with relative standard deviations of 0.94-11.1%. The dissipation half-lives of the four fungicides were 4.4-7.7 days in the Fritillaria plant and 11.6-18.2 days in the soil. The terminal residues of four fungicides were 0.033-0.13 mg/kg in fresh Fritillaria, 0.096-0.42 mg/kg in dry Fritillaria, and 0.12-0.74 mg/kg in soil. In the risk assessment of dietary exposure, all the chronic hazard quotient and acute hazard quotient index values were far below 100%, which were both acceptable to consumers. Accordingly, 7 days was recommended as the pre-harvest interval for the four fungicides in Fritillaria. This work could guide the safe use of these fungicides in Fritillaria and also give a reference for the Chinese government to establish the maximum residue limits (MRLs).

The Post-COVID-19 Economic Policy Uncertainty and the Effectiveness of Monetary Policy: Evidence From China.

The outbreak of the COVID-19 pandemic has caused an upsurge economic policy uncertainty (EPU). Study on the time-varying effect of EPU is of substantial implication for the central bank in implementation of monetary policy. To empirically investigate the time-varying effect of EPU, the paper considers the shock of the monetary policy implemented by China's central bank on different economic variables including interest rate, output gap, and inflationary gap using the latent threshold time-varying parameter vector autoregressive model (LT-TVP-VAR Model). Data period is chosen to be January 2015 through April 2021. Our findings show that (i) EPU has a significant threshold effect on the shock of quantitative monetary policy instrument and the shock of price-based monetary policy, and that the two types of policy are positively correlated; (ii) the price-based monetary policy instrument has a significant counter-cyclical effect on both output gap and inflationary gap; (iii) relative to the quantitative monetary policy instrument, the price-based monetary policy instrument has a more significant counter-cyclical effect on output gap; and (iv) a higher level of EPU is associated with a more significant monetary policy effect on output gap and inflationary gap.

Dysregulation of the AP2M1 phosphorylation cycle by LRRK2 impairs endocytosis and leads to dopaminergic neurodegeneration.

Mutations in the kinase LRRK2 and impaired endocytic trafficking are both implicated in the pathogenesis of Parkinson's disease (PD). Expression of the PD-associated LRRK2 mutant in mouse dopaminergic neurons was shown to disrupt clathrin-mediated endocytic trafficking. Here, we explored the molecular mechanism linking LRRK2 to endocytosis and found that LRRK2 bound to and phosphorylated the µ2 subunit of the adaptor protein AP2 (AP2M1), a core component of the clathrin-mediated endocytic machinery. Analysis of human SH-SY5Y cells and mouse neurons and tissues revealed that loss of LRRK2 abundance or kinase function resulted in decreased phosphorylation of AP2M1, which is required for the initial formation of clathrin-coated vesicles (CCVs). In contrast, overexpression of LRRK2 or expression of a Parkinson's disease-associated gain-of-function mutant LRRK2 (G2019S) inhibited the uncoating of AP2M1 from CCVs at later stages and prevented new cycles of CCV formation. Thus, the abundance and activity of LRRK2 must be calibrated to ensure proper endocytosis. Dysregulated phosphorylation of AP2M1 from the brain but not thyroid tissues of LRRK2 knockout and G2019S-knockin mice suggests a tissue-specific regulatory mechanism of endocytosis. Furthermore, we found that LRRK2-dependent phosphorylation of AP2M1 mediated dopaminergic neurodegeneration in a Drosophila model of PD. Together, our findings provide a mechanistic link between LRRK2, AP2, and endocytosis in the pathogenesis of PD.

Guadipyr, a new insecticide, induces microbiota dysbiosis and immune disorders in the midgut of silkworms (Bombyx mori).

Guadipyr, which combines neonicotinoid and semicarbazone functional groups in one molecule, exhibits good activity on several pests and high acute and chronic toxicity to silkworms (Bombyx mori). In this report, the effects of low-dose guadipyr on the midgut microbiota and immune system of silkworms were studied. Results showed that the structure and richness of the midgut microbiota of silkworms were altered after being treated with 5.25 mg/L (1/10 of LC50) of guadipyr. The abundance of Pseudomonas was evidently increased, whereas Curvibacter was substantially reduced, which might be related to the growth and immunity of silkworms. The expression of key genes in the Toll, IMD, and JAK/STAT pathways, which ultimately led to the downregulation of antimicrobial peptide genes (AMPs), such as CecA, Defensin1, Leb, and glv2, was reduced upon guadipyr exposure. Simultaneously, the suppression of steroid hormone 20-hydroxyecdysone receptor and response genes, such as BR-C Z4, was detected in the exposed groups. The decreased expression of these immune regulatory pathway-related and 20-hydroxyecdysone signal pathway-related genes indicated that the immune system of silkworms was affected by low-dose guadipyr. Our results revealed the negative effects of guadipyr on silkworms and highlighted the unneglectable toxicity of low-dose guadipyr to this economic insect. Given the risk, it is necessary to control the application of guadipyr in or around the mulberry fields.

Residue behavior and risk assessment of validamycin a in grape under field conditions.

The dissipation and residue of validamycin A in grapes were investigated under field conditions. An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of validamycin A in grapes was established and validated. Methanol and water (90/10, v/v) were used for validamycin A extraction and purification used MCX solid-phase extraction cartridges. The average recoveries of validamycin A in grapes at 0.01, 0.50, and 5.0 mg/kg levels were between 83.8 and 91.4%, with relative standard deviations of 2.3-3.0%. The half-lives of validamycin A in grape were 4.4-6.1 days. The terminal residues in grapes over a range of harvest times (7, 14, and 21 days) were no more than 0.73 mg/kg. According to Chinese consumption data, the risk quotient (RQ) of validamycin A was 3.22%, demonstrating a low risk to consumers. The current study may offer guidance for validamycin A use and could aid the government in determining the maximum residue level (MRL) values for validamycin A in grapes.

Genomic and Transcriptomic Analyses Reveals ZNF124 as a Critical Regulator in Highly Aggressive Medulloblastomas.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor, however, the mechanisms underlying tumorigenesis in different MB subgroups remain incompletely understood. Although previous studies of MB predisposition have been conducted in tertiary referral centers primarily in Caucasian cohorts, it is not unclear clear whether there exist population-specific genetic alterations in MBs. In this study, we investigated the contribution of genomic and transcriptomic alterations to the risk of malignant MB in the Chinese population (designated as the Asian cohort). We analyze the genomic and transcriptomic alterations of the Asian MB cohort by using a combination of whole-exome sequencing (WES) and RNA-deep-sequencing. In addition, we integrate publicly available data with the Asian MB cohort and identify a subset of potential MB-driving genes specifically enriched in each of the MB subgroups. We further characterize a newly identified group-3-enriched transcriptional regulator, ZNF124, and demonstrate that ZNF124 is critical for the growth of the most aggressive group-3 MB cells. Together, our analyses indicate conserved yet distinct genetic alterations and gene expression patterns of MBs between different ethnic groups. Our studies further provide an important resource for identifying potential tumor-driving factors in MBs, enhancing our understanding of the disease process for developing ethnically targeted therapies in patients with MB.