A nomogram for predicting neonatal apnea: a retrospective analysis based on the MIMIC database.

Introduction: The objective of this study is to develop a model based on indicators in the routine examination of neonates to effectively predict neonatal apnea. Methods: We retrospectively analysed 8024 newborns from the MIMIC IV database, building logistic regression models and decision tree models. The performance of the model is examined by decision curves, calibration curves and ROC curves. Variables were screened by stepwise logistic regression analysis and LASSO regression. Results: A total of 7 indicators were ultimately included in the model: gestational age, birth weight, ethnicity, gender, monocytes, lymphocytes and acetaminophen. The mean AUC (the area under the ROC curve) of the 5-fold cross-validation of the logistic regression model in the training set and the AUC in the validation set are 0.879 and 0.865, respectively. The mean AUC (the area under the ROC curve) of the 5-fold cross-validation of the decision tree model in the training set and the AUC in the validation set are 0.861 and 0.850, respectively. The calibration and decision curves in the two cohorts also demonstrated satisfactory predictive performance of the model. However, the logistic regression model performs relatively well. Discussion: Our results proved that blood indicators were valuable and effective predictors of neonatal apnea, which could provide effective predictive information for medical staff.

Exposure to thimerosal induces behavioral abnormality in the early life stages of zebrafish via altering amino acid homeostasis.

Thimerosal (THI) has become a significant source of organic mercury pollutants in aquatic ecosystems, but there is limited information regarding its adverse effects on fish. In this study, zebrafish embryos were exposed to THI at 0 (control), 5.0, and 50 ng/L from 0-5 days post fertilization (dpf), and variations in their survival, development, behavior, free amino acid contents, and the biochemical responses involved in monoaminergic systems were examined. Although THI exposure did not significantly affect the survival, heart rate, or hatching time of zebrafish embryos, it substantially increased swimming velocity (136-154 % of the control) and reduced exploratory behavior (141-142 % of the control) in zebrafish larvae at 5 dpf. Exposure also significantly altered the amino acid contents (51-209 % of the control) and monoamine levels (70-154 % of the control) in zebrafish larvae, some of which displayed significant correlations with behavioral traits. THI significantly elevated dopamine receptor gene expression and monoamine oxidase activity in zebrafish larvae. Adding extra phenylalanine or tryptophan to the E3 medium facilitates the recovery of zebrafish larvae from the abnormal behaviors induced by THI. These findings reveal for the first time that THI exposure at the level of ng/L is sufficient to induce neurobehavioral toxic effects in the early life stages of zebrafish, and disrupting amino acid homeostasis is a critical underlying mechanism. This study provides valuable insights into the toxicity of THI to fish and highlights the importance of assessing its potential risks to aquatic ecosystems.

Clinical and Imaging Features of Pulmonary Nodular Lymphoid Hyperplasia.

PURPOSE: To investigate the clinical and radiographic features of PNLH and the relationship with pathologic features. MATERIALS AND METHODS: A total of 11 patients in whom PNLH was confirmed in our department were retrospectively studied. The clinical and radiographic features were extracted and analyzed, and we also discussed the relationship between radiologic and pathologic features. RESULTS: Of the 11 patients with PNLH, 5 were discovered incidentally, while 4 presented with chest symptoms. Laboratory tests showed no specificity and the lesions were located under the pleura with an adjacent pleural indentation. Most lesions were solid, with some showing signs of spiculation or spiculate protuberance. In some cases, hypodense areas and vocules were visible. The enhanced scan showed marked enhancement, but most had no lymph node enlargement, and there was no pleural effusion. CONCLUSIONS: The clinical manifestations of PNLH are nonspecific and the imaging features overlap with those of malignant lung tumors, and the diagnosis depends on pathologic examination.

A transcriptomics-based analysis of mechanisms involved in the sex-dependent effects of diazepam on zebrafish.

Diazepam (DZP) is a universally detected emerging pollutant in aquatic ecosystems. Although the sex-dependent effects of DZP on fish have been properly established, the underlying mechanisms remain unclear. In this study, zebrafish of both sexes were separately exposed to DZP (8 µg/L) for 21 days, and the alteration of the behaviors, brain amino acid neurotransmitter contents, and transcriptomic profiles were investigated. Although DZP exposure showed a sedative effect on both sexes, significantly reduced cumulative duration of high mobility and willingness to encounter the opposite sex were only observed in females. However, DZP significantly enhanced the brain levels of glutamate and glutamine in males but not in females. Transcriptome analysis identified more different expression genes (DEGs) in females (322 up-regulated and 311 down-regulated) than in males (138 up-regulated genes and 38 down-regulated). The DEGs in both sexes were significantly enriched in the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway of the synaptic vesicle cycle, indicating a possible pathway for the sedative effects of DZP on zebrafish. DZP exhibited different or even opposing regulatory patterns on gene expression in the brains of females and males, providing some insights into its sex-dependent impacts on the behaviors and brain neurotransmitter contents in zebrafish. Moreover, enrichment analysis also suggested that DZP exposure may affect the oocyte maturation in female zebrafish, which highlights the need to study its reproductive and transgenerational toxicity to fish species.

Circadian clock component PER2 negatively regulates CD4+ T cell IFN-γ production in ulcerative colitis.

Period circadian clock 2 (PER2) is involved in the pathogenesis of various inflammatory and autoimmune diseases. However, there are gaps in our understanding of the role of PER2 in regulating CD4+ T cells beyond its time-keeping function in ulcerative colitis (UC) pathogenesis. Our findings revealed PER2 was predominantly expressed in CD4+ T cells, while it was significantly decreased in the inflamed mucosa and peripheral blood CD4+ T cells of UC patients compared with that in Crohn's disease (CD) patients and healthy controls (HC). Notably, PER2 expression was significantly recovered in UC patients in remission (R-UC) compared to that in active UC patients (A-UC) but not in CD patients. It was negatively correlated with the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Crohn's Disease Activity Index (CDAI), Simple Endoscopic Score for Crohn's disease (SES-CD), and C-reactive protein (CRP), respectively. Overexpression of PER2 markedly inhibited IFN-γ production in UC CD4+ T cells. RNA-seq analysis showed that overexpression of PER2 could repress the expression of a disintegrin and metalloproteinase 12 (ADAM12), a costimulatory molecule that determines Th1 cell fate. Mechanistically, cleavage under targets and tagmentation (CUT&Tag) analysis revealed that PER2 down-regulated ADAM12 expression by reducing its binding activity, thereby suppressing IFN-γ production in UC CD4+ T cells. Additionally, our data further demonstrated that ADAM12 was upregulated in CD4+ T cells and inflamed mucosa of A-UC patients compared to HC. Our study reveals a critical role of PER2 in regulating CD4+ T cell differentiation and highlights its potential as a therapeutic target for UC treatment.

Emamectin benzoate-induced toxicity affects intestinal epithelial integrity involving apoptosis.

The frequency presence of emamectin benzoate in agricultural production highlights the need for studying their toxicity against human intestinal epithelial barrier (IEB). Herein, we combined a Caco-2 cell model with transcriptome analysis to assess the intestinal toxicity of emamectin benzoate and its disease-causing potential. Results showed that the half maximal inhibitory concentration (IC50) of emamectin benzoate on Caco-2 cell viability after 24, 48, and 72 h of exposure were 18.1, 9.9, and 8.3 µM, respectively. Emamectin benzoate exposure enhanced the Caco-2 monolayer paracellular permeability, damaged the IEB, and increased cellular apoptosis. Key driver gene analysis of 42 apoptosis - related DEGs, identified 10 genes (XIAP, KRAS, MCL1, NRAS, PIK3CA, CYCS, MAPK8, CASP3, FADD, and TNFRSF10B) with the strongest correlation with emamectin benzoate - induced apoptosis. Transcriptomics identified 326 differentially expressed genes (DEGs, 204 upregulated and 122 downregulated). The functional terms of neurodegeneration - multiple diseases was enriched with the most number of DEGs, and the Parkinson disease pathway had the highest enrichment degree. Our findings provided support for environmental toxicology studies and the health risk assessment of emamectin benzoate.

Time-series variation in the locomotor behavior and vocal traits of Japanese medaka (Oryzias latipes) acutely exposed to organophosphorus pesticide chlorpyrifos.

Organophosphorus pesticides (OPs), such as chlorpyrifos (CPF), are the most commonly used pesticides worldwide. Considering that OPs will eventually enter aquatic ecosystems due to runoff from agricultural lands, accidental leakage, and other unforeseen emergencies, monitoring water pollution of those substances is crucial for environmental protection and public health. In this study, Japanese medaka (Oryzias latipes) were exposed to CPF (0.03, 0.06, and 0.12 mg/L) for 6 h, and the time-series variations in their locomotor behavior and vocal traits were investigated. Compared with that measured before exposure, significantly changed locomotor behavior and vocal traits in Japanese medaka exposed to CPF could be observed at 4 h after exposure and thereafter, and the pattern of behavioral changes depends on the CPF concentrations. Exposure to CPF also changed the frequency-sound pressure level curve of Japanese medaka at 6 h after exposure, especially at 0.12 mg/L. Moreover, CPF exposure could significantly inhibit the acetylcholinesterase (AChE) activity in the brains and eyes of medaka, which exhibited significant correlations with the variation of locomotor behavioral and vocal traits. Considering that inhibiting the AChE activity is the primary mechanism underlying the neurobehavioral toxicity of all OPs, our finding suggested that simultaneously monitoring changes in the locomotor behavioral and vocal traits has a high potential to reflect the pollution of organophosphorus substances.

Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn's disease.

Background: Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial. Objectives: To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram. Design: Cross-sectional study. Methods: The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed. Results: The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (p < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (p < 0.001), CDAI (p < 0.001), and C-reactive protein (CRP) (p < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 µg/mL) and ADA (8.80 µg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort. Conclusion: This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.

Therapeutic drug monitoring-based nomogram predicts primary endoscopic response in Crohn's disease The present study established a therapeutic drug monitoring-based nomogram, which exhibits an exceptional predictive value, remarkable accuracy, and discrimination. This algorithmic nomogram holds the potential to enhance clinicians' comprehension of the underlying mechanisms contributing to individual patients' failure in achieving expected efficacy. Such approach is crucial for optimizing therapy options and facilitating biologic switching in refractory Crohn's disease.

Postoperative subphenotypes modified the hepatoma arterial-embolization prognostic score: A novel smHAP-II nomogram.

Background: Three subphenotypes were identified for unresectable hepatocellular carcinoma (uHCC) after frontline transarterial chemoembolization (TACE). This study aimed to develop an individual smHAP-Ⅱ nomogram for uHCC patients after TACE. Methods: Between January 2007 to December 2016, 1517 uHCC patients undergoing TACE were included from four hospitals in China (derivation cohort: 597 cases; validation cohort: 920 cases). Multivariable Cox proportion regression analysis was used to develop a nomogram, incorporating postoperative subphenotypes (Phenotype 1, 2, 3) and HAP score (Score 0 to 4). The model was validated by a 1000-time bootstrap resampling procedure. The performance of the model was compared with existing ones by Harrell's C-index and Area Under Curve (AUC). Results: Postoperative subphenotypes modified the HAP score (smHAP-Ⅱ nomogram) was developed and validated, with the Harrell's C-index of the nomogram was 0.679 (SD: 0.029) for the derivation cohort and 0.727(SD:0.029) for the external cohort. The area under curves of the nomogram for 1-, 3-, and 5-year OS were 0.750, 0.710, and 0.732 for the derivation cohort, respectively (0.789, 0.762, and 0.715 for the external cohort). In the calibration curves stratified by treatment after TACE, the lines for re-TACE and stop-TACE cross at 0.23, indicating that patients with a 3-year predicted survival >23% would not benefit from TACE. Conclusions: The addition of postoperative subphenotypes significantly improved the prognostic performance. The smHAP-Ⅱ nomogram can be used for accurate prognostication and selection of optimal candidates for TACE, with the value to guide sequential treatment strategy.

Sex-specific impacts of thimerosal on the behaviors and brain monoaminergic systems in zebrafish (Danio rerio).

Thimerosal (THI) is the most widely used form of organic mercury in pharmaceutical and personal care products, and has become a major source of ethylmercury pollution in aquatic ecosystems. However, knowledge about its potential risk to aquatic species is limited. In this study, zebrafish were exposed to THI for 7 days, and variations in their behavioral traits, brain monoaminergic neurotransmitter contents, and related gene expression were investigated. After the 7-day exposure, THI reduced locomotor activity and thigmotaxis in males but not females. Exposure to THI increased the social interaction between females but decreased that between males. The THI exposure also significantly reduced the serotonin (5-HT), 5-hydroxyindoleacetic acid, dopamine (DA), and 3,4-dihydroxyphenylacetic acid contents in the brain of males, but only significantly decreased the DA content in females. Correlation analysis revealed that the neurochemical alterations in the brain of zebrafish play critical roles in the behavioral abnormalities induced by THI exposure. Moreover, THI also significantly altered the expression of some genes associated with the synthesis, metabolism, and receptor binding of 5-HT and DA in the brain of zebrafish. The differences in these gene expressions between female and male zebrafish exposed to THI seem to be an important mechanism underlying their sex-specific responses to this chemical. This is the first report on the sex-specific effects of THI on behaviors and brain monoaminergic neurotransmitter contents in zebrafish, which can further improve our understanding of its toxic effects on teleost.

Directed Differentiation of Neurons from Human iPSCs for Modeling Neurological Disorders.

Human-induced pluripotent stem cell (hiPSC) technology has enabled comprehensive human cell-based disease modeling in vitro. Due to limited accessibility of primary human neurons as well as species-specific divergence between human and rodent brain tissues, hiPSC-derived neurons have become a popular tool for studying neuronal biology in a dish. Here, we provide methods for transcription factor-driven directed differentiation of neurons from hiPSCs via a neural progenitor cell (NPC) intermediate. Doxycycline-inducible expression of neuron fate-determining transcription factors neurogenin 2 (NGN2) and achaete-scute homolog 1 (ASCL1) enables rapid and controllable differentiation of human neurons for disease modeling applications. The provided method is also designed to improve the reproducibility of human neuron differentiation by reducing the batch-to-batch variation of NPC differentiation and lentiviral transduction.

Generating Homogeneous Brain Organoids from Human iPSCs.

There is a high demand for the development of in vitro models for human brain development and diseases due to the inaccessibility of human brain tissues. The human iPSC-derived brain organoids provide a promising in vitro model for studying human brain development and disorders. However, it is challenging to generate a large number of brain organoids with high consistency for modeling human neurological diseases. Here, we describe a method for generating high-yield brain organoids with high consistency by combining large-scale embryoid body (EB) generation and incorporating a quality control screening step during differentiation. The method described in this chapter provides a robust way to generate brain organoids for studying human brain development and modeling neurological diseases.

Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications.

The induced pluripotent stem cell (iPSC) technology has transformed in vitro research and holds great promise to advance regenerative medicine. iPSCs have the capacity for an almost unlimited expansion, are amenable to genetic engineering, and can be differentiated into most somatic cell types. iPSCs have been widely applied to model human development and diseases, perform drug screening, and develop cell therapies. In this review, we outline key developments in the iPSC field and highlight the immense versatility of the iPSC technology for in vitro modeling and therapeutic applications. We begin by discussing the pivotal discoveries that revealed the potential of a somatic cell nucleus for reprogramming and led to successful generation of iPSCs. We consider the molecular mechanisms and dynamics of somatic cell reprogramming as well as the numerous methods available to induce pluripotency. Subsequently, we discuss various iPSC-based cellular models, from mono-cultures of a single cell type to complex three-dimensional organoids, and how these models can be applied to elucidate the mechanisms of human development and diseases. We use examples of neurological disorders, coronavirus disease 2019 (COVID-19), and cancer to highlight the diversity of disease-specific phenotypes that can be modeled using iPSC-derived cells. We also consider how iPSC-derived cellular models can be used in high-throughput drug screening and drug toxicity studies. Finally, we discuss the process of developing autologous and allogeneic iPSC-based cell therapies and their potential to alleviate human diseases.

Development and Validation of Deep Learning Model for Intermediate-Stage Hepatocellular Carcinoma Survival with Transarterial Chemoembolization (MC-hccAI 002): a Retrospective, Multicenter, Cohort Study.

Background: There are few effective prediction models for intermediate-stage hepatocellular carcinoma (IM-HCC) patients treated with transarterial chemoembolization (TACE) to predict overall survival (OS) is available. The learning survival neural network (DeepSurv) was developed to showed a better performance than cox proportional hazards model in prediction of OS. This study aimed to develop a deep learning-based prediction model to predict individual OS. Methods: This multicenter, retrospective, cohort study examined data from the electronic medical record system of four hospitals in China between January 1, 2007, to December 31, 2016. Patients were divided into a training set(n=1075) and a test set(n=269) at a ratio of 8:2 to develop a deep learning-based algorithm (deepHAP IV). The deepHAP IV model was externally validated on an independent cohort(n=414) from the other three centers. The concordance index, the area under the receiver operator characteristic curves, and the calibration curve were used to assess the performance of the models. Results: The deepHAP IV model had a c-index of 0.74, whereas AUROC for predicting survival outcomes of 1-, 3-, and 5-year reached 0.80, 0.76, and 0.74 in the training set. Calibration graphs showed good consistency between the actual and predicted OS in the training set and the validation cohort. Compared to the other five Cox proportional-hazards models, the model this study conducted had a better performance. Patients were finally classified into three groups by X-tile plots with predicted 3-year OS rate (low: ≤ 0.11; middle: > 0.11 and ≤ 0.35; high: >0.35). Conclusion: The deepHAP IV model can effectively predict the OS of patients with IM-HCC, showing a better performance than previous Cox proportional hazards models.

Construction of Uniform LiF Coating Layers for Stable High-Voltage LiCoO2 Cathodes in Lithium-Ion Batteries.

Stabilizing LiCoO2 (LCO) at 4.5 V rather than the common 4.2 V is important for the high specific capacity. In this study, we developed a simple and efficient way to improve the stability of LiCoO2 at high voltages. After a simple sol-gel method, we introduced trifluoroacetic acid (TA) to the surface of LCO via an afterwards calcination. Meanwhile, the TA reacted with residual lithium on the surface of LCO, further leading to the formation of uniform LiF nanoshells. The LiF nanoshells could effectively restrict the interfacial side reaction, hinder the transition metal dissolution and thus achieve a stable cathode-electrolyte interface at high working-voltages. As a result, the LCO@LiF demonstrated a much superior cycling stability with a capacity retention ratio of 83.54% after 100 cycles compared with the bare ones (43.3% for capacity retention), as well as high rate performances. Notably, LiF coating layers endow LCO with excellent high-temperature performances and outstanding full-cell performances. This work provides a simple and effective way to prepare stable LCO materials working at a high voltage.

Inhalation bioaccessibility of imidacloprid in particulate matter: Implications for risk assessment during spraying.

Adverse health outcomes due to the inhalation of pesticide residues in atmospheric particulate matter (PM) are gaining global attention. Quantitative health risk assessments of pesticide inhalation exposure highlight the need to understand the bioaccessibility of pesticide residues. Herein, the inhalation bioaccessibility of imidacloprid in PM was determined using three commonly used in vitro lung modeling methods (Artificial Lysosomal Fluid, Gamble Solution, and Simulated Lung Fluid). To validate its feasibility and effectiveness, we evaluated the bioavailability of imidacloprid using a mouse nasal instillation assay. The in vitro inhalation bioaccessibility of imidacloprid was extracted using Gamble Solution with a solid-liquid ratio of 1/1000, an oscillation rate of 150 r/min, and an extraction time of 24 h, showed a strong linear correlation with its in vivo liver-based bioavailability (R2 =0.8928). Moreover, the margin of exposure was incorporated into the inhalation exposure risk assessment, considering both formulations and nozzles. The inhalation unit exposure of imidacloprid for residents was 0.95-4.09 ng/m3. The margin of exposure for imidacloprid was determined to be acceptable when considering inhalation bioaccessibility. Taken together, these results indicate that the inhalation bioaccessibility of pesticides should be incorporated into assessments of human health risks posed by PM particles.

In vitro inhalation bioaccessibility and health risk assessment of difenoconazole in the atmosphere.

BACKGROUND: Assessment of the risk of pesticide inhalation in populations around farmland is necessary because inhalation is one of the ways in which pesticides can risk human health. This study aimed to identify the inhalation risk of difenoconazole on humans by using dose-response and exposure assessments. RESULTS: In the field simulation application, respiratory exposure in populations around farmland ranged from 71 to 430 ng/m3 . Using response surface methodology, the maximum bioaccessibility of difenoconazole in three simulated lung fluids was 35.33% in Gamble's solution (GS), 34.12% in artificial lysosomal fluid (ALF), and 42.06% in simulated interstitial lung fluid (SLF). Taking the proliferation activity of the A549 cell model as the endpoint, the benchmark dose limit and benchmark dose of difenoconazole on A549 cells were 16.36 and 5.60 mg/kg, respectively. The margin of exposure to difenoconazole in GS, ALF and SLF were, respectively, 8.66 × 105 to 5.28 × 106 , 8.97 × 105 to 5.47 × 106 and 7.28 × 105 to 4.44 × 106 . CONCLUSION: The risk assessment results indicate that under all circumstances, applying difenoconazole is safe for populations around farmland. However, a fan-shaped nozzle, suspension concentrate and greater inhalation height increase the risk of inhalation. © 2023 Society of Chemical Industry.

Effects of parental exposure to amitriptyline on the survival, development, behavior, and gene expression in zebrafish offspring.

In mammals, parental exposure to amitriptyline (AMI) has been proven to contribute to congenital disabilities in their offspring. However, no studies have paid attention to the adverse effects of parental exposure to amitriptyline on fish offspring. In this study, we exposed adult zebrafish (F0) to AMI (0.8 µg/L) for 21 days. Subsequently, these zebrafish (F0) were allowed to mate, and their offspring (F1) were collected to culture in clean water for 5 days. The mortality rate, average hatching time, and heart rate at 48 h post-fertilization (hpf) of F1 were investigated. Our results showed that parental exposure to AMI induced tachycardia and increased mortality in F1 zebrafish. Under a light/dark transition test, F1 larvae born from AMI-exposed parents exhibited lower locomotor activity in the dark period and decreased thigmotaxis in the light period. The transcriptome analysis showed that parental AMI exposure dysregulated some key pathways in their offspring. Through the prediction of key driver analysis, six differentially expressed genes (DEGs) were revealed as key driver genes involved in protein processing in endoplasmic reticulum (hspa5, hsp70.1, hsp90a), ribosome (rps27a) and PPAR signaling pathway (pparab and fabp2). Considering that the concentration of AMI residual components in natural water bodies may be over our test concentration (0.8 µg/L), our findings suggested that toxicity of parental exposure to the offspring of fish should receive greater attention.

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.

Effects of chronic diazepam exposure on the behaviors and oxidative stress homeostasis in the eyes and brains of female Japanese medaka.

Diazepam (DZP) residue has been frequently detected in wastewater, surface water, and groundwater due to its extensive use over the decades. In this study, we exposed female Japanese medaka (Oryzias latipes) to environmentally relevant doses of DZP (800 and 8000 ng/L) for 4 weeks, aimed to investigate their behavioral responses and possible links with ocular and brain oxidative stress homeostasis. As a result, DZP exposure could significantly reduce swimming activity (800 ng/L) and anxiety (800 and 8000 ng/L), indicating a sedative effect on medaka. The DZP exposure also significantly increased the social interaction in medaka at 8000 ng/L. Furthermore, exposure to DZP could alter the ocular and brain oxidative stress homeostasis in medaka. The ocular CAT activities significantly increased in the 800 ng/L-DZP groups, and the brain SOD, CAT, GST and MDA levels also significantly increased in both DZP exposure groups. Correlation analysis revealed that the ocular and brain oxidative stress induced by DZP exposure might play an important role in their behavioral toxicity to medaka. Our findings highlight the necessity to clarify the exact link between DZP exposure-induced oxidative stress in the neural and sensor systems and its behavioral toxicity to better assess the risks on nontarget aquatic species.