Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrat...Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrations,are not fully elucidated.This review delves into the physiological and molecular nature of this phenomenon.To date,nitrate-dependent alleviation of ammonium toxicity is the result of cumulative consequences of the role of nitrate as a nutrient and signal in plant performance.The ability to counteract the ammonium-induced acidification through nitrate uptake and metabolism,the enhancement of potassium uptake as an essential nitrate counterion,and the nitratedependent signaling of key factors involved in ammonium assimilation,ROS scavenging,and growth hormone biosynthesis,are the most relevant hallmarks.In addition,evidence suggests that the availability of nitrate and ammonium has driven ecological selection in plants,determining current N preferences,and may have led to the selection of nitrate-dependent and ammonium-sensitive domesticated crops and the inefficient use of N fertilizers in agriculture.As ammonium toxicity limits N fertilization options and reduces agricultural yields,when it could be a more sustainable and cheaper alternative to nitrate,this review provides a better understanding of how plants use nitrate to counteract the problematic aspects of ammonium nutrition.展开更多
Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to i...Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.展开更多
Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.Howeve...Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.展开更多
BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their...BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.展开更多
The herbal drink “Attoté” has been widely used in the Abidjan district to treat a number of illnesses, notably erectile dysfunction. Despite the popularity of its therapeutic effects, very few studies have been...The herbal drink “Attoté” has been widely used in the Abidjan district to treat a number of illnesses, notably erectile dysfunction. Despite the popularity of its therapeutic effects, very few studies have been carried out on its effects on the health of users. The aim of this study was to identify the constituents contained in the phytomedicinal product and to assess their potential adverse effects in vivo. Phytochemical screening was conducted to identify the bioactive molecules in “Attoté” and to evaluate its hepatic effects in vivo. Forty (40) Wistar rats, randomly divided into 4 groups, with 10 animals per group (5 males and 5 females) were used to study potential hepatotoxic effects. Group 1 animals (control group) received distilled water. Batches I, II and III received by gavage a volume of Attoté extract corresponding to 1 ml/100 g body weight at 200 mg/kg, 400 mg/kg and 800 mg/kg, respectively. Attoté extract was administered daily at the same time for 28 days, and serum was collected every two weeks to assess hepatic biochemical markers by spectrophotometry using a Cobas C311® HITACHI biochemistry system. After one month of study, the rats were euthanized by ether overdose and the livers were harvested for morphological and histopathological analysis. Phytochemical screening revealed the presence of alkaloids, polyphenols, leucoanthocyanes, anthraquinones and quinones. Hepatic biochemical and hematological parameters such as red globular, hemoglobin, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALPs) and gamma glutamyl transferase (GGT) showed no significant change (p > 0.05) in the treated rat group compared with controls. However, these variations were moderate and transient, with values remaining almost within their standard limits. Microscopic observations of liver tissue sections from treated rats showed no liver damage or dysfunction. This study merits further investigation, with a view to gaining a better understanding of the cytotoxic mechanisms of herbal medicinal beverages, with a view to their reformulation as improved traditional medicines (ITMs).展开更多
Developmental and reproductive toxicity(DART)endpoint entails a toxicological assessment of all developmental stages and reproductive cycles of an organism.In silico tools to predict DART will provide a method to asse...Developmental and reproductive toxicity(DART)endpoint entails a toxicological assessment of all developmental stages and reproductive cycles of an organism.In silico tools to predict DART will provide a method to assess this complex toxicity endpoint and will be valuable for screening emerging pollutants as well as for m anaging new chemicals in China.Currently,there are few published DART prediction models in China,but many related research and development projects are in progress.In 2013,WU et al.published an expert rule-based DART decision tree(DT).This DT relies on known chemical structures linked to DART to forecast DART potential of a given chemical.Within this procedure,an accurate DART data interpretation is the foundation of building and expanding the DT.This paper excerpted case studies demonstrating DART data curation and interpretation of four chemicals(including 8-hydroxyquinoline,3,5,6-trichloro-2-pyridinol,thiacloprid,and imidacloprid)to expand the existing DART DT.Chemicals were first selected from the database of Solid Waste and Chemicals Management Center,Ministry of Ecology and Environment(MEESCC)in China.The structures of these 4 chemicals were analyzed and preliminarily grouped by chemists based on core structural features,functional groups,receptor binding property,metabolism,and possible mode of actions.Then,the DART conclusion was derived by collecting chemical information,searching,integrating,and interpreting DART data by the toxicologists.Finally,these chemicals were classified into either an existing category or a new category via integrating their chemical features,DART conclusions,and biological properties.The results showed that 8-hydroxyquinoline impacted estrous cyclicity,s exual organ weights,and embryonal development,and 3,5,6-trichloro-2-pyridinol caused central nervous system(CNS)malformations,which were added to an existing subcategory 8e(aromatic compounds with multi-halogen and nitro groups)of the DT.Thiacloprid caused dystocia and fetal skeletal malformation,and imidacloprid disrupted the endocrine system and male fertility.They both contain 2-chloro-5-methylpyridine substituted imidazolidine c yclic ring,which were expected to create a new category of neonicotinoids.The current work delineates a t ransparent process of curating toxicological data for the purpose of DART data interpretation.In the presence of sufficient related structures and DART data,the DT can be expanded by iteratively adding chemicals within the a pplicable domain of each category or subcategory.This DT can potentially serve as a tool for screening emerging pollutants and assessing new chemicals in China.展开更多
The extensive co-occurrence of pyrethroid insecticides such as lambda-cyhalothrin(LCT)and cypermethrin(CPM)in aquatic systems poses a potential risk,yet a significant research gap exists regarding their combined toxic...The extensive co-occurrence of pyrethroid insecticides such as lambda-cyhalothrin(LCT)and cypermethrin(CPM)in aquatic systems poses a potential risk,yet a significant research gap exists regarding their combined toxicological effects.In this study,the single and joint acute toxicity effects of lambda-cyhalothrin(LCT)and cypermethrin(CPM)on Nile tilapia fingerlings were investigated using 96-h bioassays.Results showed both were highly toxic,with LCT(96-h LC 50=66.53μg/L)being four-fold more potent than CPM(259.41μg/L).Regression analysis confirmed positive correlation(P<0.01)between pesticide concentration and observed mortality.The binary mixture exhibited synergistic effect with Additive Index(AI)>0,indicating combined effects exceeded the sum of their individual actions.This synergism likely stems from mutual inhibition of metabolic detoxification pathways,leading to increased internal concentrations and amplified neurotoxicity.Generally,this study confirmed that single-compound risk assessments dangerously underestimate pyrethroid mixture hazards,necessitating their inclusion in regulatory frameworks for accurate aquatic biodiversity protection.展开更多
In this study,the single and jiont acute toxicity effects of pendimethalin(herbicide)and fenitrothion(organophosphate insecticide)were investigated on juvenile zebrafish(Danio rerio)under semi-static conditions.Mortal...In this study,the single and jiont acute toxicity effects of pendimethalin(herbicide)and fenitrothion(organophosphate insecticide)were investigated on juvenile zebrafish(Danio rerio)under semi-static conditions.Mortality was assessed at 24,48,72,and 96 h.The study revealed that pendimethalin exhibited higher toxicity than fenitrothion.The 96-h LC 50 values were 0.477 mg/L for pendimethalin and 2.634 mg/L for fenitrothion.Joint exposure produced enhanced toxicity,with 96-h LC 50 values of 0.204 mg/L(pendimethalin equivalent)and 1.139 mg/L(fenitrothion equivalent).Regression analysis showed a significant positive correlation(p<0.05)between pesticide concentration and mortality,while toxicity indices confirmed synergistic interactions.These findings underscore the ecological risks posed by pesticide mixtures and highlight the importance of regulating pesticide use to safeguard aquatic organisms and maintain environmental sustainability.展开更多
Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration tec...Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration technique,where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea.Instillation requires minimal test material,delivers an exact dose deep into the lung,and is less labor-intensive than inhalation exposures.However,one shortcoming is that the pro-cedure may induce short-term inflammation.To minimize this,we tested different modifications of the technique to identify the potential for refinement.Methods:First,we tested whether previous findings of increased inflammation could be confirmed.Next,we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle(Disposable-syringe/steel-needle)induced less inflammation than the use of our standard set-up,a 250μL reusable glass syringe with a disposable plastic catheter(Glass-syringe/plastic-catheter).Finally,we tested if access to pelleted and liquid feed prior to instillation affected inflammation.We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.Results:Vehicle-instilled mice showed a small increase in neutrophil numbers com-pared to untreated mice.Neutrophil numbers were slightly elevated in the groups in-stilled with Disposable-syringe/steel-needle;an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pel-lets compared to liquid feed.We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.Conclusion:The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation,confirming this as a preferred instillation procedure.展开更多
This study attempted to assess the lethal concentration(96-h LC_(50))effects of imidacloprid(neonicotinoid pesticide),thiamethoxam(neonicotinoid pesticide),and their combination on juvenile Zebrafish(Danio rerio).Each...This study attempted to assess the lethal concentration(96-h LC_(50))effects of imidacloprid(neonicotinoid pesticide),thiamethoxam(neonicotinoid pesticide),and their combination on juvenile Zebrafish(Danio rerio).Each set of trials contained a control(de-chlorinated tap water),and the experiments were repeated three times.The fish(n=10)were randomly measured with an average length of(3.4±0.34)cm and weight of(1±0.1)g.The temperature was kept at 24℃.Experiments 1 and 2 were designed to investigate at the acute toxicity of imidacloprid and thiamethoxam on juvenile zebrafish(Danio rerio)respectively,whereas experiment 3 was aimed at the combined toxicity of IMI and THM on zebrafish.The tests followed the same study design,and each experiment used seven different logarithmic concentrations of imidacloprid insecticides(310.00,317.08,324.33,331.74,339.32,347.07,355.00 mg/L)and thiamethoxam(175.00,185.52,200.93,215.30,230.70,247.20,264.88 mg/L).The results show that THM is more toxic than IMI,with LC_(50)values of 190.34 mg/L for THM and 310.92 mg/L for IMI.Both individual toxicities showed a substantial positive connection(P<0.05)with confidence limits of 321.50-300.68 mg/L for IMI and 199.91-181.21 mg/L for THM.The joint toxicity test was carried out using the 96-h LC_(50)values of imidacloprid and thiamethoxam obtained in the individual acute toxicity trials at a 1:1 ratio.The Additive Index(AI)demonstrated that imidacloprid and thiamethoxam acted synergistically on D.rerio.As a matter of fact,more research is needed to better understand the impact of IMI and THM on other aquatic organisms and also create strategies to mitigate its harmful effects on aquatic life.展开更多
Background:Adult medulloblastoma(MB)represents less than 1%of central nervous system malignancies,lacking standardized therapeutic approaches due to its rarity.This retrospective single-center analysis aimed to assess...Background:Adult medulloblastoma(MB)represents less than 1%of central nervous system malignancies,lacking standardized therapeutic approaches due to its rarity.This retrospective single-center analysis aimed to assess survival outcomes and treatment-associated toxicities in adult MB patients managed with pediatric-derived protocols.Methods:Eighteen patients(≥18 years)with MB treated at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)(January 1997–January 2024)were analyzed.All received craniospinal radiotherapy with posterior fossa boost,followed by adjuvant chemotherapy utilizing pediatric regimens(PNET3,PNET4,PNET5,or high-risk protocols incorporating high-dose chemotherapy with autologous stem cell rescue).Primary outcomes included overall survival(OS)and progression-free survival(PFS).Secondary analyses focused on comprehensive toxicity assessment.Results:The cohort included 11 males and 7 females(median age:23 years).Metastatic disease was present in 6 patients(33%)at diagnosis.Histopathological distribution showed classic MB(55.5%),desmoplastic/nodular(39%),and large cell/anaplastic variants(5.5%).Molecular subgrouping(available in 6 patients)identified SHH subgroup in four cases and WNT subgroup in two.Three-year and fiveyear overall survival rates reached 94.5%and 88.8%,respectively.Treatment-related adverse events included grade 3–4 hematologic toxicities,clinically significant weight loss,and grade≥3 neurological and ototoxic complications.These toxicities necessitated treatment modifications including dose adjustments,cycle delays,and occasional early discontinuation.Conclusions:Adult MB patients treated with pediatric-adapted protocols demonstrated excellent long-termsurvival outcomes,comparable to or surpassing historical data.Despite frequent toxicity requiring treatment modifications,these regimens proved feasible with acceptable risk-benefit profiles.These results support implementing modified pediatric protocols for adult MB management.Future multicenter investigations with larger cohorts are essential for refining risk stratification,optimizing treatment intensity,and evaluating long-term outcomes in this rare malignancy.展开更多
To evaluate the subchronic and chronic toxicity of Fuyanxiao capsules,Sprague-Dawley(SD)rats were used in toxicity studies.In the subchronic toxicity study,50 female rats were randomly divided into a high-dose group(5...To evaluate the subchronic and chronic toxicity of Fuyanxiao capsules,Sprague-Dawley(SD)rats were used in toxicity studies.In the subchronic toxicity study,50 female rats were randomly divided into a high-dose group(5.4g/kg/day)and a control group,with 15 rats in each,and medium(2.7g/kg/day)and low(1.35g/kg/day)dose groups,with 10 rats in each.The test substance was administered orally(mixed with feed,twice daily)for 90 consecutive days.In the chronic toxicity study,40 female rats were randomly divided into high,medium,and low dose groups and a control group,with 10 rats in each.The test substance was administered orally in the same manner for 180 consecutive days.Clinical signs,body weight,and food consumption were observed and recorded daily.At the end of the terminal phase(the first 10 rats from each group,1 day after the last dose)and the recovery phase(the last 5 rats from the control group and the high-dose group,observed for an additional 28 days after the last dose),blood and urine samples,as well as organs,were collected.Organ coefficients were calculated,and various hematological and urinary indicators were detected,followed by pathological analysis.The results showed that there were no significant differences in body weight,food consumption,or organ coefficients between any of the dose groups and the control group in both subchronic and chronic toxicity studies(P>0.05).Histopathological examination revealed no lesions,suggesting no tissue or organ damage in any of the dose groups.The rats exhibited good mental status,and hematological and urinary physiological indicators were within normal ranges,indicating stable liver and kidney function,hematopoietic system of the bone marrow,and internal environment in all dose groups.Therefore,Fuyanxiao capsule has no obvious subchronic or chronic toxicity in SD rats,and it is safe and reliable to use at reasonable dosage in clinical practice.展开更多
Chemotherapy-induced toxicity(CIT)remains a major concern in cancer patients undergoing chemotherapy.New approaches to ameliorate the side effects of chemotherapy are urgently needed.Recently,the nutritional value of ...Chemotherapy-induced toxicity(CIT)remains a major concern in cancer patients undergoing chemotherapy.New approaches to ameliorate the side effects of chemotherapy are urgently needed.Recently,the nutritional value of citrus fruits has attracted wide attention.Hesperidin and its aglycone hesperetin are the main active components in citrus fruits.Hesperidin and hesperetin have a wide range of pharmacological activities,including antioxidant and anti-inflammatory properties.This review aims to provide insights into the potential application of citrus flavonoids in CIT and summarize the underlying mechanisms of hesperidin and hesperetin in alleviating CIT.We have collected and collated relevant scientific articles on hesperidin and hesperetin and their treatment of CIT from different scientific databases.Hesperidin and its glycosides can reduce the toxicity of chemotherapeutic drugs,and their therapeutic effects are mainly through anti-inflammatory and antioxidant effects.At present,modern medical treatment is the main treatment method for CIT,but hesperidin,as an extract of food and medicinal materials,can greatly alleviate CIT.While killing tumor cells,chemotherapeutic drugs also damage normal cells leading to toxic effect on various organs.The pathological mechanism of CIT has not been fully elucidated,but current evidences indicate that cellular stress plays a key role.The citrus flavonoids hesperidin and hesperetin have the protective effect against CIT,highlighting its potential as an adjuvant in chemotherapy regimens.Hesperidin may also have synergistic anti-tumor activity with chemotherapeutic agents.We believe that more functional foods and anti-CIT drugs based on natural foods will be developed.展开更多
Phytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century.Traditional methods,such as fungicides,have drawbacks including high cost,r...Phytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century.Traditional methods,such as fungicides,have drawbacks including high cost,restrictions on organic farming,potential risks to the environment and human health,and the development of resistant strains.In this study,we employed cutting-edge computer-based techniques,including Quantitative Structure-Activity Relationship(QSAR)modeling and molecular docking simulations,to uncover new fungicidal compounds and gain insights into their specific mechanisms of action against P.infestans.QSAR modeling on the number of compounds tested as P.infestans inhibitors was performed using an interactive OCHEM web platform.The predictive ability of the developed classification models had a balanced accuracy(BA)of 77–85%for the training set and BA?89–93%for the validation external test set.During the in vitro testing against P.infestans,thirteen synthesized 2-oxoimidazolidine-4-sulfonamides demonstrated inhibition rates,ranging from 23.6%to 87.4%.The fungicidal potential of six of these fungicides ranged from 79.3%to 87.4%,which is comparable to the activity of known fungicides.Acute toxicity results using the well-known aquatic marker Daphnia magna showed that the most active sulfonamides 3d,3f,3h,3j,3k,and 3l,with LC_(50) values ranging from 13.7 to 52.9 mg/L,are low-toxicity compounds.The molecular docking results demonstrated a potential mechanism of the antifungal action of the studied 2-oxoimidazolidin-4-sulfonamide derivatives via the inhibition of fungal CYP51,a sterol biosynthesis enzyme.展开更多
Mycotoxins are the most widely existing pollutants in both dietary provisions and livestock feed,and they pose a series of hazards for humans and animals.Deoxynivalenol(DON)is a prevalent mycotoxin that is primarily p...Mycotoxins are the most widely existing pollutants in both dietary provisions and livestock feed,and they pose a series of hazards for humans and animals.Deoxynivalenol(DON)is a prevalent mycotoxin that is primarily produced by Fusarium spp.and commonly found in various cereal products.Feeding swine diets contaminated with trichothecene DON can lead to major adverse effects,including reduced feed intake,diminished weight gains,and compromised immune function.Among all animal species,swine are the most sensitive to DON.Here we explore the disruption of gut health by DON,considering aspects such as intestinal histomorphology,epithelial barrier functions,immune system,microflora,and short-chain fatty acid production in the intestines.Numerous additives have been documented for their potential in the detoxification of DON.These additives can alleviate the toxic effects of DON on pigs by modulating the Nrf2-Keap1,mitogen-activated protein kinases(MAPKs)and Nuclear factor kappa-B(NF-κB)signaling pathways.Additionally,there are additives capable of mitigating the toxicity of DON through adsorption or biotransformation.This update has novel potential for advancing our comprehension of the mechanisms linked to DON intestinal toxicity and facilitating the formulation of innovative strategies to mitigate the impact of DON.展开更多
This paper reviewed the toxicity,maximum residue limits(MRLs)and current residue status of commonly used plant growth regulators in vegetables,including 2,4-dichlorophenoxyacetic acid(2,4-D),naphthaleneacetic acid(NAA...This paper reviewed the toxicity,maximum residue limits(MRLs)and current residue status of commonly used plant growth regulators in vegetables,including 2,4-dichlorophenoxyacetic acid(2,4-D),naphthaleneacetic acid(NAA),ethephon,gibberellin,and paclobutrazol.Methods for reducing residues of plant growth regulators in vegetables were discussed,and recommendations and strategies for their application were proposed.展开更多
The potential toxicity of ionic liquids(ILs)affects their applications;how to control the toxicity is one of the key issues in their applications.To understand its toxicity structure relationship and promote its green...The potential toxicity of ionic liquids(ILs)affects their applications;how to control the toxicity is one of the key issues in their applications.To understand its toxicity structure relationship and promote its greener application,six different machine learning algorithms,including Bagging,Adaptive Boosting(AdaBoost),Gradient Boosting(GBoost),Stacking,Voting and Categorical Boosting(CatBoost),are established to model the toxicity of ILs on four distinct datasets including Leukemia rat cell line IPC-81(IPC-81),Acetylcholinesterase(AChE),Escherichia coli(E.coli)and Vibrio fischeri.Molecular descriptors obtained from the simplified molecular input line entry system(SMILES)are used to characterize ILs.All models are assessed by the mean square error(MSE),root mean square error(RMSE),mean absolute error(MAE)and correlation coefficient(R^(2)).Additionally,an interpretation model based on SHapley Additive exPlanations(SHAP)is built to determine the positive and negative effects of each molecular feature on toxicity.With additional parameters and complexity,the Catboost model outperforms the other models,making it a more reliable model for ILs'toxicity prediction.The results of the model's interpretation indicate that the most significant positive features,SMR_VSA5,PEOE_VSA8,Kappa2,PEOE_VSA6,SMR_VSA5,PEOE_VSA6 and EState_VSA1,can increase the toxicity of ILs as their levels rise,while the most significant negative features,VSA_EState7,EState_VSA8,PEOE_VSA9 and FpDensityMorgan1,can decrease the toxicity as their levels rise.Also,an IL's toxicity will grow as its average molecular weight and number of pyridine rings increase,whereas its toxicity will decrease as its hydrogen bond acceptors increase.This finding offers a theoretical foundation for rapid screening and synthesis of environmentally-benign ILs.展开更多
[Objectives]This study was conducted to investigate the joint toxicity of fungicides on aquatic ecosystems.[Methods]Using zebrafish as a model organism,an LC-MS/MS simultaneous detection method was established for flu...[Objectives]This study was conducted to investigate the joint toxicity of fungicides on aquatic ecosystems.[Methods]Using zebrafish as a model organism,an LC-MS/MS simultaneous detection method was established for fluxapyroxad and pyraclostrobin(with detection limits at ng/L level),and their acute toxicity,joint toxicity and toxic mechanisms were systematically evaluated.[Results]The toxicity of pyraclostrobin(96 h-LC 50=0.052 mg/L)to zebrafish was approximately 25.8 times higher than that of fluxapyroxad(96 h-LC 50=1.34 mg/L).Joint toxicity evaluation using the fixed-ratio ray design revealed that six of the seven mixture ratios exhibited additive effects(AI=0.62-1.47),while the 8:1 ratio showed antagonism(AI=2.14).The analysis of toxicity mechanisms indicated that both fungicides induced oxidative stress,lipid peroxidation,and cellular damage through inhibition of mitochondrial complex III and II,respectively,with pyraclostrobin inducing more pronounced hepatic MDA elevation(2.56-fold)and antioxidant enzyme inhibition.Ecological risk assessment demonstrated that fluxapyroxad posed moderate risk(RQ=0.16-0.90),while pyraclostrobin posed moderate to high risk(RQ=0.56-3.56),and crustaceans faced the highest risk.[Conclusions]This study elucidated the mechanism underlying toxicity differences due to distinct mitochondrial targets,providing a scientific basis for fungicide management.展开更多
Zearalenone(ZEN)is a non-steroidal estrogenic mycotoxin biosynthesized by the polyketide reaction,which has estrogenic effects and triggers toxic effects,such as reproductive toxicity,hepatotoxicity,genotoxicity,and i...Zearalenone(ZEN)is a non-steroidal estrogenic mycotoxin biosynthesized by the polyketide reaction,which has estrogenic effects and triggers toxic effects,such as reproductive toxicity,hepatotoxicity,genotoxicity,and immunotoxicity in organism.Due to its impact on human and animal health and the economic losses engendered by ZEN,detoxification strategies for contaminated foods and feeds to reduce or eliminate the toxic effects of ZEN by chemical,physical and biological methods are crucial.Detoxification by microbial means has broad application prospects,with the advantages of high efficiency,high specificity,mild conditions of action,no harmful metabolites,and safety.It may help to improve the function of intestinal barriers so that the intestinal epithelial barrier is more resistant to mycotoxins,and other pathogenic microorganisms.This article provided an overview of the metabolic pathways and animal toxicity of ZEN in organism,and summarized the effects of the current research status,detoxification mechanisms and in vivo applications of ZEN biodetoxification,in order to provide a reference for the prevention and control of ZEN.展开更多
This review is to elucidate the retinal toxicity following intraocular injections of cefuroxime,including possible risk factors,clinical manifestations,visual prognosis and treatment.Refereed publications were retriev...This review is to elucidate the retinal toxicity following intraocular injections of cefuroxime,including possible risk factors,clinical manifestations,visual prognosis and treatment.Refereed publications were retrieved from PubMed,the Cochrane Library,and EMBASE databases,using the search terms cefuroxime,retina,macular edema,serous retinal detachment,toxic,cataract surgery.The screening was not limited by publication date,country or study type.We screened out 51 articles out of which 32 met the inclusion criteria for this systematic review.Data regarding sample size calculation reporting and trial characteristics were extracted for each trial.Retinal toxicity can be caused by both high and standard doses of cefuroxime injections in different ethnic groups,with risk factors including overdose,blood-retinal barrier disruption,anterior and posterior chamber connection.The typical clinical manifestations of retinal toxicity are cystoid macular edema and extensive serous retinal detachment,mainly involving the outer nuclear and outer plexiform layers,with a good prognosis for visual acuity in most cases,but in a small number of cases,the prognosis is not satisfactory.In conclusion,though the current use of intracameral injection antibiotics in cataract surgery is gradually increasing,the potential risks should not be ignored.Unexplained poor vision on the first day after cataract surgery can be supplemented with macular optical coherence tomography to rule out cefuroxime-related retinal toxicity.展开更多
基金supported by an MCIN RyC Programme MCIN/AEI/10.13039/501100011033the‘European Union Next Generation EU/PRTR’under grant no.RYC2021-032345-I+1 种基金supported by the AEI(grant no.PID2019-107463RJ-I00/AEI/10.13039/501100011033)the Regional Research and Development Programme of the Government of Navarre(call 2019,project NitroHealthy,PC068).
文摘Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrations,are not fully elucidated.This review delves into the physiological and molecular nature of this phenomenon.To date,nitrate-dependent alleviation of ammonium toxicity is the result of cumulative consequences of the role of nitrate as a nutrient and signal in plant performance.The ability to counteract the ammonium-induced acidification through nitrate uptake and metabolism,the enhancement of potassium uptake as an essential nitrate counterion,and the nitratedependent signaling of key factors involved in ammonium assimilation,ROS scavenging,and growth hormone biosynthesis,are the most relevant hallmarks.In addition,evidence suggests that the availability of nitrate and ammonium has driven ecological selection in plants,determining current N preferences,and may have led to the selection of nitrate-dependent and ammonium-sensitive domesticated crops and the inefficient use of N fertilizers in agriculture.As ammonium toxicity limits N fertilization options and reduces agricultural yields,when it could be a more sustainable and cheaper alternative to nitrate,this review provides a better understanding of how plants use nitrate to counteract the problematic aspects of ammonium nutrition.
文摘Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.
基金supported by the Guangdong Provincial Key Area Research and Development Program[grant number 2022B0202090002]China Postdoctoral Science Foundation[grant number 2024M760977].
文摘Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.
基金Supported by the Chongqing Medical University Program for Youth Innovation in Future Medicine,No.W0019Chongqing Municipal Education Commission’s 14th Five-Year Key Discipline Support Project,No.20240101 and No.20240102。
文摘BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.
文摘The herbal drink “Attoté” has been widely used in the Abidjan district to treat a number of illnesses, notably erectile dysfunction. Despite the popularity of its therapeutic effects, very few studies have been carried out on its effects on the health of users. The aim of this study was to identify the constituents contained in the phytomedicinal product and to assess their potential adverse effects in vivo. Phytochemical screening was conducted to identify the bioactive molecules in “Attoté” and to evaluate its hepatic effects in vivo. Forty (40) Wistar rats, randomly divided into 4 groups, with 10 animals per group (5 males and 5 females) were used to study potential hepatotoxic effects. Group 1 animals (control group) received distilled water. Batches I, II and III received by gavage a volume of Attoté extract corresponding to 1 ml/100 g body weight at 200 mg/kg, 400 mg/kg and 800 mg/kg, respectively. Attoté extract was administered daily at the same time for 28 days, and serum was collected every two weeks to assess hepatic biochemical markers by spectrophotometry using a Cobas C311® HITACHI biochemistry system. After one month of study, the rats were euthanized by ether overdose and the livers were harvested for morphological and histopathological analysis. Phytochemical screening revealed the presence of alkaloids, polyphenols, leucoanthocyanes, anthraquinones and quinones. Hepatic biochemical and hematological parameters such as red globular, hemoglobin, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALPs) and gamma glutamyl transferase (GGT) showed no significant change (p > 0.05) in the treated rat group compared with controls. However, these variations were moderate and transient, with values remaining almost within their standard limits. Microscopic observations of liver tissue sections from treated rats showed no liver damage or dysfunction. This study merits further investigation, with a view to gaining a better understanding of the cytotoxic mechanisms of herbal medicinal beverages, with a view to their reformulation as improved traditional medicines (ITMs).
文摘Developmental and reproductive toxicity(DART)endpoint entails a toxicological assessment of all developmental stages and reproductive cycles of an organism.In silico tools to predict DART will provide a method to assess this complex toxicity endpoint and will be valuable for screening emerging pollutants as well as for m anaging new chemicals in China.Currently,there are few published DART prediction models in China,but many related research and development projects are in progress.In 2013,WU et al.published an expert rule-based DART decision tree(DT).This DT relies on known chemical structures linked to DART to forecast DART potential of a given chemical.Within this procedure,an accurate DART data interpretation is the foundation of building and expanding the DT.This paper excerpted case studies demonstrating DART data curation and interpretation of four chemicals(including 8-hydroxyquinoline,3,5,6-trichloro-2-pyridinol,thiacloprid,and imidacloprid)to expand the existing DART DT.Chemicals were first selected from the database of Solid Waste and Chemicals Management Center,Ministry of Ecology and Environment(MEESCC)in China.The structures of these 4 chemicals were analyzed and preliminarily grouped by chemists based on core structural features,functional groups,receptor binding property,metabolism,and possible mode of actions.Then,the DART conclusion was derived by collecting chemical information,searching,integrating,and interpreting DART data by the toxicologists.Finally,these chemicals were classified into either an existing category or a new category via integrating their chemical features,DART conclusions,and biological properties.The results showed that 8-hydroxyquinoline impacted estrous cyclicity,s exual organ weights,and embryonal development,and 3,5,6-trichloro-2-pyridinol caused central nervous system(CNS)malformations,which were added to an existing subcategory 8e(aromatic compounds with multi-halogen and nitro groups)of the DT.Thiacloprid caused dystocia and fetal skeletal malformation,and imidacloprid disrupted the endocrine system and male fertility.They both contain 2-chloro-5-methylpyridine substituted imidazolidine c yclic ring,which were expected to create a new category of neonicotinoids.The current work delineates a t ransparent process of curating toxicological data for the purpose of DART data interpretation.In the presence of sufficient related structures and DART data,the DT can be expanded by iteratively adding chemicals within the a pplicable domain of each category or subcategory.This DT can potentially serve as a tool for screening emerging pollutants and assessing new chemicals in China.
基金Supported by The Central Public-Interest Scientific Institution Basal Research Fund,CAFS(2025XT0902)Earmarked Fund for China Agriculture Research System(CARS-46).
文摘The extensive co-occurrence of pyrethroid insecticides such as lambda-cyhalothrin(LCT)and cypermethrin(CPM)in aquatic systems poses a potential risk,yet a significant research gap exists regarding their combined toxicological effects.In this study,the single and joint acute toxicity effects of lambda-cyhalothrin(LCT)and cypermethrin(CPM)on Nile tilapia fingerlings were investigated using 96-h bioassays.Results showed both were highly toxic,with LCT(96-h LC 50=66.53μg/L)being four-fold more potent than CPM(259.41μg/L).Regression analysis confirmed positive correlation(P<0.01)between pesticide concentration and observed mortality.The binary mixture exhibited synergistic effect with Additive Index(AI)>0,indicating combined effects exceeded the sum of their individual actions.This synergism likely stems from mutual inhibition of metabolic detoxification pathways,leading to increased internal concentrations and amplified neurotoxicity.Generally,this study confirmed that single-compound risk assessments dangerously underestimate pyrethroid mixture hazards,necessitating their inclusion in regulatory frameworks for accurate aquatic biodiversity protection.
基金Supported by The Central Public-Interest Scientific Institution Basal Research Fund,CAFS(2025XT0902)Earmarked Fund for China Agriculture Research System(CARS-46).
文摘In this study,the single and jiont acute toxicity effects of pendimethalin(herbicide)and fenitrothion(organophosphate insecticide)were investigated on juvenile zebrafish(Danio rerio)under semi-static conditions.Mortality was assessed at 24,48,72,and 96 h.The study revealed that pendimethalin exhibited higher toxicity than fenitrothion.The 96-h LC 50 values were 0.477 mg/L for pendimethalin and 2.634 mg/L for fenitrothion.Joint exposure produced enhanced toxicity,with 96-h LC 50 values of 0.204 mg/L(pendimethalin equivalent)and 1.139 mg/L(fenitrothion equivalent).Regression analysis showed a significant positive correlation(p<0.05)between pesticide concentration and mortality,while toxicity indices confirmed synergistic interactions.These findings underscore the ecological risks posed by pesticide mixtures and highlight the importance of regulating pesticide use to safeguard aquatic organisms and maintain environmental sustainability.
基金This work was supported by the Focused Research Effort on Chemicals in the Working Environment(FFIKA)from the Danish Government.
文摘Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration technique,where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea.Instillation requires minimal test material,delivers an exact dose deep into the lung,and is less labor-intensive than inhalation exposures.However,one shortcoming is that the pro-cedure may induce short-term inflammation.To minimize this,we tested different modifications of the technique to identify the potential for refinement.Methods:First,we tested whether previous findings of increased inflammation could be confirmed.Next,we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle(Disposable-syringe/steel-needle)induced less inflammation than the use of our standard set-up,a 250μL reusable glass syringe with a disposable plastic catheter(Glass-syringe/plastic-catheter).Finally,we tested if access to pelleted and liquid feed prior to instillation affected inflammation.We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.Results:Vehicle-instilled mice showed a small increase in neutrophil numbers com-pared to untreated mice.Neutrophil numbers were slightly elevated in the groups in-stilled with Disposable-syringe/steel-needle;an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pel-lets compared to liquid feed.We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.Conclusion:The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation,confirming this as a preferred instillation procedure.
基金Supported by the Central Public-interest Scientific Institution Basal Research Fund,CAFS(2025XT0902)the earmarked fund for China Agriculture Research System(CARS-46).
文摘This study attempted to assess the lethal concentration(96-h LC_(50))effects of imidacloprid(neonicotinoid pesticide),thiamethoxam(neonicotinoid pesticide),and their combination on juvenile Zebrafish(Danio rerio).Each set of trials contained a control(de-chlorinated tap water),and the experiments were repeated three times.The fish(n=10)were randomly measured with an average length of(3.4±0.34)cm and weight of(1±0.1)g.The temperature was kept at 24℃.Experiments 1 and 2 were designed to investigate at the acute toxicity of imidacloprid and thiamethoxam on juvenile zebrafish(Danio rerio)respectively,whereas experiment 3 was aimed at the combined toxicity of IMI and THM on zebrafish.The tests followed the same study design,and each experiment used seven different logarithmic concentrations of imidacloprid insecticides(310.00,317.08,324.33,331.74,339.32,347.07,355.00 mg/L)and thiamethoxam(175.00,185.52,200.93,215.30,230.70,247.20,264.88 mg/L).The results show that THM is more toxic than IMI,with LC_(50)values of 190.34 mg/L for THM and 310.92 mg/L for IMI.Both individual toxicities showed a substantial positive connection(P<0.05)with confidence limits of 321.50-300.68 mg/L for IMI and 199.91-181.21 mg/L for THM.The joint toxicity test was carried out using the 96-h LC_(50)values of imidacloprid and thiamethoxam obtained in the individual acute toxicity trials at a 1:1 ratio.The Additive Index(AI)demonstrated that imidacloprid and thiamethoxam acted synergistically on D.rerio.As a matter of fact,more research is needed to better understand the impact of IMI and THM on other aquatic organisms and also create strategies to mitigate its harmful effects on aquatic life.
基金approved by the Institutional Review Board of Università Cattolica del Sacro Cuore-Policlinico Gemelli IRCCS(number DIPUSVSP-21-03-252).
文摘Background:Adult medulloblastoma(MB)represents less than 1%of central nervous system malignancies,lacking standardized therapeutic approaches due to its rarity.This retrospective single-center analysis aimed to assess survival outcomes and treatment-associated toxicities in adult MB patients managed with pediatric-derived protocols.Methods:Eighteen patients(≥18 years)with MB treated at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)(January 1997–January 2024)were analyzed.All received craniospinal radiotherapy with posterior fossa boost,followed by adjuvant chemotherapy utilizing pediatric regimens(PNET3,PNET4,PNET5,or high-risk protocols incorporating high-dose chemotherapy with autologous stem cell rescue).Primary outcomes included overall survival(OS)and progression-free survival(PFS).Secondary analyses focused on comprehensive toxicity assessment.Results:The cohort included 11 males and 7 females(median age:23 years).Metastatic disease was present in 6 patients(33%)at diagnosis.Histopathological distribution showed classic MB(55.5%),desmoplastic/nodular(39%),and large cell/anaplastic variants(5.5%).Molecular subgrouping(available in 6 patients)identified SHH subgroup in four cases and WNT subgroup in two.Three-year and fiveyear overall survival rates reached 94.5%and 88.8%,respectively.Treatment-related adverse events included grade 3–4 hematologic toxicities,clinically significant weight loss,and grade≥3 neurological and ototoxic complications.These toxicities necessitated treatment modifications including dose adjustments,cycle delays,and occasional early discontinuation.Conclusions:Adult MB patients treated with pediatric-adapted protocols demonstrated excellent long-termsurvival outcomes,comparable to or surpassing historical data.Despite frequent toxicity requiring treatment modifications,these regimens proved feasible with acceptable risk-benefit profiles.These results support implementing modified pediatric protocols for adult MB management.Future multicenter investigations with larger cohorts are essential for refining risk stratification,optimizing treatment intensity,and evaluating long-term outcomes in this rare malignancy.
文摘To evaluate the subchronic and chronic toxicity of Fuyanxiao capsules,Sprague-Dawley(SD)rats were used in toxicity studies.In the subchronic toxicity study,50 female rats were randomly divided into a high-dose group(5.4g/kg/day)and a control group,with 15 rats in each,and medium(2.7g/kg/day)and low(1.35g/kg/day)dose groups,with 10 rats in each.The test substance was administered orally(mixed with feed,twice daily)for 90 consecutive days.In the chronic toxicity study,40 female rats were randomly divided into high,medium,and low dose groups and a control group,with 10 rats in each.The test substance was administered orally in the same manner for 180 consecutive days.Clinical signs,body weight,and food consumption were observed and recorded daily.At the end of the terminal phase(the first 10 rats from each group,1 day after the last dose)and the recovery phase(the last 5 rats from the control group and the high-dose group,observed for an additional 28 days after the last dose),blood and urine samples,as well as organs,were collected.Organ coefficients were calculated,and various hematological and urinary indicators were detected,followed by pathological analysis.The results showed that there were no significant differences in body weight,food consumption,or organ coefficients between any of the dose groups and the control group in both subchronic and chronic toxicity studies(P>0.05).Histopathological examination revealed no lesions,suggesting no tissue or organ damage in any of the dose groups.The rats exhibited good mental status,and hematological and urinary physiological indicators were within normal ranges,indicating stable liver and kidney function,hematopoietic system of the bone marrow,and internal environment in all dose groups.Therefore,Fuyanxiao capsule has no obvious subchronic or chronic toxicity in SD rats,and it is safe and reliable to use at reasonable dosage in clinical practice.
基金Innovative Team Project of Ordinary Universities in Guangdong Province(No.2022KCXTD016).
文摘Chemotherapy-induced toxicity(CIT)remains a major concern in cancer patients undergoing chemotherapy.New approaches to ameliorate the side effects of chemotherapy are urgently needed.Recently,the nutritional value of citrus fruits has attracted wide attention.Hesperidin and its aglycone hesperetin are the main active components in citrus fruits.Hesperidin and hesperetin have a wide range of pharmacological activities,including antioxidant and anti-inflammatory properties.This review aims to provide insights into the potential application of citrus flavonoids in CIT and summarize the underlying mechanisms of hesperidin and hesperetin in alleviating CIT.We have collected and collated relevant scientific articles on hesperidin and hesperetin and their treatment of CIT from different scientific databases.Hesperidin and its glycosides can reduce the toxicity of chemotherapeutic drugs,and their therapeutic effects are mainly through anti-inflammatory and antioxidant effects.At present,modern medical treatment is the main treatment method for CIT,but hesperidin,as an extract of food and medicinal materials,can greatly alleviate CIT.While killing tumor cells,chemotherapeutic drugs also damage normal cells leading to toxic effect on various organs.The pathological mechanism of CIT has not been fully elucidated,but current evidences indicate that cellular stress plays a key role.The citrus flavonoids hesperidin and hesperetin have the protective effect against CIT,highlighting its potential as an adjuvant in chemotherapy regimens.Hesperidin may also have synergistic anti-tumor activity with chemotherapeutic agents.We believe that more functional foods and anti-CIT drugs based on natural foods will be developed.
基金supported by the BASF Open Innovative Platform(Project OI39).
文摘Phytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century.Traditional methods,such as fungicides,have drawbacks including high cost,restrictions on organic farming,potential risks to the environment and human health,and the development of resistant strains.In this study,we employed cutting-edge computer-based techniques,including Quantitative Structure-Activity Relationship(QSAR)modeling and molecular docking simulations,to uncover new fungicidal compounds and gain insights into their specific mechanisms of action against P.infestans.QSAR modeling on the number of compounds tested as P.infestans inhibitors was performed using an interactive OCHEM web platform.The predictive ability of the developed classification models had a balanced accuracy(BA)of 77–85%for the training set and BA?89–93%for the validation external test set.During the in vitro testing against P.infestans,thirteen synthesized 2-oxoimidazolidine-4-sulfonamides demonstrated inhibition rates,ranging from 23.6%to 87.4%.The fungicidal potential of six of these fungicides ranged from 79.3%to 87.4%,which is comparable to the activity of known fungicides.Acute toxicity results using the well-known aquatic marker Daphnia magna showed that the most active sulfonamides 3d,3f,3h,3j,3k,and 3l,with LC_(50) values ranging from 13.7 to 52.9 mg/L,are low-toxicity compounds.The molecular docking results demonstrated a potential mechanism of the antifungal action of the studied 2-oxoimidazolidin-4-sulfonamide derivatives via the inhibition of fungal CYP51,a sterol biosynthesis enzyme.
基金supported by the National Key Research and Development Program of China(2021YFD1301003)the Beijing University of Agriculture Science and Technology Innovation“Spark Action”Support Program,China(BUA-HHXD2022011)the key research and development Program of Shaanxi Province,China(2022NY-095)。
文摘Mycotoxins are the most widely existing pollutants in both dietary provisions and livestock feed,and they pose a series of hazards for humans and animals.Deoxynivalenol(DON)is a prevalent mycotoxin that is primarily produced by Fusarium spp.and commonly found in various cereal products.Feeding swine diets contaminated with trichothecene DON can lead to major adverse effects,including reduced feed intake,diminished weight gains,and compromised immune function.Among all animal species,swine are the most sensitive to DON.Here we explore the disruption of gut health by DON,considering aspects such as intestinal histomorphology,epithelial barrier functions,immune system,microflora,and short-chain fatty acid production in the intestines.Numerous additives have been documented for their potential in the detoxification of DON.These additives can alleviate the toxic effects of DON on pigs by modulating the Nrf2-Keap1,mitogen-activated protein kinases(MAPKs)and Nuclear factor kappa-B(NF-κB)signaling pathways.Additionally,there are additives capable of mitigating the toxicity of DON through adsorption or biotransformation.This update has novel potential for advancing our comprehension of the mechanisms linked to DON intestinal toxicity and facilitating the formulation of innovative strategies to mitigate the impact of DON.
文摘This paper reviewed the toxicity,maximum residue limits(MRLs)and current residue status of commonly used plant growth regulators in vegetables,including 2,4-dichlorophenoxyacetic acid(2,4-D),naphthaleneacetic acid(NAA),ethephon,gibberellin,and paclobutrazol.Methods for reducing residues of plant growth regulators in vegetables were discussed,and recommendations and strategies for their application were proposed.
基金funded by Research Platforms and Projects for Higher Education Institutions of Department of Education of Guangdong Province in 2024(2024KTSCX256)2023 Guangdong Province Higher Vocational Education Teaching Quality and Teaching Reform Project(2023JG080).
文摘The potential toxicity of ionic liquids(ILs)affects their applications;how to control the toxicity is one of the key issues in their applications.To understand its toxicity structure relationship and promote its greener application,six different machine learning algorithms,including Bagging,Adaptive Boosting(AdaBoost),Gradient Boosting(GBoost),Stacking,Voting and Categorical Boosting(CatBoost),are established to model the toxicity of ILs on four distinct datasets including Leukemia rat cell line IPC-81(IPC-81),Acetylcholinesterase(AChE),Escherichia coli(E.coli)and Vibrio fischeri.Molecular descriptors obtained from the simplified molecular input line entry system(SMILES)are used to characterize ILs.All models are assessed by the mean square error(MSE),root mean square error(RMSE),mean absolute error(MAE)and correlation coefficient(R^(2)).Additionally,an interpretation model based on SHapley Additive exPlanations(SHAP)is built to determine the positive and negative effects of each molecular feature on toxicity.With additional parameters and complexity,the Catboost model outperforms the other models,making it a more reliable model for ILs'toxicity prediction.The results of the model's interpretation indicate that the most significant positive features,SMR_VSA5,PEOE_VSA8,Kappa2,PEOE_VSA6,SMR_VSA5,PEOE_VSA6 and EState_VSA1,can increase the toxicity of ILs as their levels rise,while the most significant negative features,VSA_EState7,EState_VSA8,PEOE_VSA9 and FpDensityMorgan1,can decrease the toxicity as their levels rise.Also,an IL's toxicity will grow as its average molecular weight and number of pyridine rings increase,whereas its toxicity will decrease as its hydrogen bond acceptors increase.This finding offers a theoretical foundation for rapid screening and synthesis of environmentally-benign ILs.
基金Supported by New Project of Postgraduate Scientific Research Innovation in 2024(ZSCX2024Y21).
文摘[Objectives]This study was conducted to investigate the joint toxicity of fungicides on aquatic ecosystems.[Methods]Using zebrafish as a model organism,an LC-MS/MS simultaneous detection method was established for fluxapyroxad and pyraclostrobin(with detection limits at ng/L level),and their acute toxicity,joint toxicity and toxic mechanisms were systematically evaluated.[Results]The toxicity of pyraclostrobin(96 h-LC 50=0.052 mg/L)to zebrafish was approximately 25.8 times higher than that of fluxapyroxad(96 h-LC 50=1.34 mg/L).Joint toxicity evaluation using the fixed-ratio ray design revealed that six of the seven mixture ratios exhibited additive effects(AI=0.62-1.47),while the 8:1 ratio showed antagonism(AI=2.14).The analysis of toxicity mechanisms indicated that both fungicides induced oxidative stress,lipid peroxidation,and cellular damage through inhibition of mitochondrial complex III and II,respectively,with pyraclostrobin inducing more pronounced hepatic MDA elevation(2.56-fold)and antioxidant enzyme inhibition.Ecological risk assessment demonstrated that fluxapyroxad posed moderate risk(RQ=0.16-0.90),while pyraclostrobin posed moderate to high risk(RQ=0.56-3.56),and crustaceans faced the highest risk.[Conclusions]This study elucidated the mechanism underlying toxicity differences due to distinct mitochondrial targets,providing a scientific basis for fungicide management.
基金Supported by China Agriculture Research System(CARS-35)the Natural Science Foundation of Heilongjiang Province of China(LH2021C038)。
文摘Zearalenone(ZEN)is a non-steroidal estrogenic mycotoxin biosynthesized by the polyketide reaction,which has estrogenic effects and triggers toxic effects,such as reproductive toxicity,hepatotoxicity,genotoxicity,and immunotoxicity in organism.Due to its impact on human and animal health and the economic losses engendered by ZEN,detoxification strategies for contaminated foods and feeds to reduce or eliminate the toxic effects of ZEN by chemical,physical and biological methods are crucial.Detoxification by microbial means has broad application prospects,with the advantages of high efficiency,high specificity,mild conditions of action,no harmful metabolites,and safety.It may help to improve the function of intestinal barriers so that the intestinal epithelial barrier is more resistant to mycotoxins,and other pathogenic microorganisms.This article provided an overview of the metabolic pathways and animal toxicity of ZEN in organism,and summarized the effects of the current research status,detoxification mechanisms and in vivo applications of ZEN biodetoxification,in order to provide a reference for the prevention and control of ZEN.
基金Supported by Shanghai Engineering Research Center of Precise Diagnosis and Treatment of Eye Diseases,Shanghai,China(No.19DZ2250100)Shanghai First People’s Hospital Featured Research Projects(No.CCTR-2022C08).
文摘This review is to elucidate the retinal toxicity following intraocular injections of cefuroxime,including possible risk factors,clinical manifestations,visual prognosis and treatment.Refereed publications were retrieved from PubMed,the Cochrane Library,and EMBASE databases,using the search terms cefuroxime,retina,macular edema,serous retinal detachment,toxic,cataract surgery.The screening was not limited by publication date,country or study type.We screened out 51 articles out of which 32 met the inclusion criteria for this systematic review.Data regarding sample size calculation reporting and trial characteristics were extracted for each trial.Retinal toxicity can be caused by both high and standard doses of cefuroxime injections in different ethnic groups,with risk factors including overdose,blood-retinal barrier disruption,anterior and posterior chamber connection.The typical clinical manifestations of retinal toxicity are cystoid macular edema and extensive serous retinal detachment,mainly involving the outer nuclear and outer plexiform layers,with a good prognosis for visual acuity in most cases,but in a small number of cases,the prognosis is not satisfactory.In conclusion,though the current use of intracameral injection antibiotics in cataract surgery is gradually increasing,the potential risks should not be ignored.Unexplained poor vision on the first day after cataract surgery can be supplemented with macular optical coherence tomography to rule out cefuroxime-related retinal toxicity.
