The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ ...The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ mixture on zebrafish(Danio rerio).Acute tests determined 96-h LC_(50) values of 123.41 mg/L for GIS and 103.95 mg/L for ATZ.In the joint toxicity test,these values decreased to 60.96 and 50.88 mg/L,respectively.The Additive Index(AI)analysis revealed a consistent synergistic interaction between the herbicides at all exposure intervals.These findings underscore the enhanced ecological threat of herbicide mixtures and highlight the necessity of considering joint effects in environmental risk assessments.展开更多
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
AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided...AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.展开更多
Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of ...Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.展开更多
Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed...Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.展开更多
Albumin,owing to its high abundance and excellent biocompatibility,is widely used as a drug carrier to enhance delivery efficiency and reduce systemic toxicity.The Michael addition between albumin thiols and maleimide...Albumin,owing to its high abundance and excellent biocompatibility,is widely used as a drug carrier to enhance delivery efficiency and reduce systemic toxicity.The Michael addition between albumin thiols and maleimide-functionalized prodrugs is a common in situ macromolecular prodrug strategy.However,the resulting reversible adducts are susceptible to retro-Michael reactions in vivo,leading to premature drug release and off-target effects.To address this limitation,a gemcitabine prodrug(GAB)bearing a chloroacetamide group was designed to form irreversible covalent bonds with albumin via nucleophilic substitution.A maleimide-based prodrug(GAM)was synthesized as a control.Compared to GAM,GAB showed faster and stronger albumin binding in plasma,enhanced blood circulation time,improved tumor accumulation,and superior in vivo antitumor efficacy.Moreover,GAB exhibited a better safety profile,with reduced cytotoxicity in normal tissues and no observable systemic toxicity.These advantages are attributed to the stable albumin-drug conjugate formed by GAB,which improves drug retention and targeted delivery.This study presents an effective and generalizable albumin-hitchhiking strategy for constructing irreversible prodrugs,offering a promising approach to enhance the therapeutic index of chemotherapeutic agents.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
Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which...Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which urgently needs to be addressed in clinical application.Liposomes have been considered ideal vehicles for reducing CDDP toxicity due to their high biocompatibility,low toxicity and passive targeting ability.Nevertheless,CDDP's poor water/lipid solubility usually results in a low liposome druglipid ratio,limiting tumor delivery ability.Herein,a CDDP-polyphenol complex liposome was designed to increase the drug loading capacity of CDDP to realize the reduction of toxicity and effective antitumor effect simultaneously.The complex was prepared via complexation reaction of different stoichiometric ratios of CDDP and polyphenolic substances(gallic acid,epigallocatechin gallate and tannic acid),followed by encapsulation of complex in liposomes to improve tumor targeting.Notably,the molecular interaction forces between CDDP and polyphenolic substances were intensively investigated through a binding force disruption assay.In vitro studies demonstrated that the optimal formulation of CDDP-epigallocatechin gallate complex liposome(CDDP-EGCG Lips) showed the highest CDDP encapsulation efficiency,favorable stability,pH-sensitive release,enhanced cellular uptake and apoptosis effect.In vivo studies revealed that CDDP-EGCG Lips retarded the elimination of CDDP to prolong their circulation time,inhibited the growth of tumors,and significantly reduced the toxic side effects compared to CDDP monotherapy.This delivery strategy holds great promise for improving the clinical use of platinum-based drugs.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
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
Drug toxicity is closely related to both clinical drug safety and new drug development.Therefore,it is vital to understand the mechanisms of drug toxicity fully and to use appropriate research models with advanced tec...Drug toxicity is closely related to both clinical drug safety and new drug development.Therefore,it is vital to understand the mechanisms of drug toxicity fully and to use appropriate research models with advanced technologies.Zebrafish has become an important vertebrate animal model for highthroughput drug screening and toxicity assessment.At the same time,zebrafish has an intact biological complexity,reflecting the whole organism's toxicity,which gives it an advantage over other highthroughput models in toxicity studies.Despite the gradual increase in toxicity studies utilizing zebrafish,a comprehensive and systematic review of the underlying mechanisms and new techniques is still lacking.This review aims to analyze common toxicity mechanisms in zebrafish models,such as oxidative stress,endoplasmic reticulum stress,inflammation,and apoptosis,and macroscopic changes in biological processes like lipid metabolism disorders and neurotransmitter expression abnormalities.It also introduces new technologies applied in toxicity assessment,such as gene editing,novel fluorescence imaging technology,3D imaging technology,and novel automated technology for high-throughput screening,such as fish capsules.In addition,it also summarizes the advantages and disadvantages of the model.By doing so,it will provide new suggestions for the development and improvement of the model,make it better serve the toxicity study of clinical drugs and provide a more comprehensive perspective for drug toxicity study,thus promoting the development of the field of drug toxicity study.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
This study reviews the hepatotoxic chemicals,mechanisms of toxicity,and detoxification methods of Toosendan Fructus(TF).Limonin-type triterpenoids,as primary hepatotoxic components,mediate toxicity though inflammation...This study reviews the hepatotoxic chemicals,mechanisms of toxicity,and detoxification methods of Toosendan Fructus(TF).Limonin-type triterpenoids,as primary hepatotoxic components,mediate toxicity though inflammation,oxidative stress,mitochondrial dysfunction,ferroptosis,and apoptosis.Hepatotoxicity can be mitigated by controlling dosage,using processed forms of the herbs,and through rational herbal compatibility.The review provides insights for enhancing the safety and clinical application of TF.展开更多
but its application is constrained by hepatotoxicity.This study aimed to investigate the feasibility of reducing AAEO’s toxicity through storage and to evaluate changes in chemical composition,toxicity,and bioactivit...but its application is constrained by hepatotoxicity.This study aimed to investigate the feasibility of reducing AAEO’s toxicity through storage and to evaluate changes in chemical composition,toxicity,and bioactivity.Methods:Gas chromatography-mass spectrometry was used to analyze compositional changes during storage.Zebrafish acute toxicity tests and the liver-specific transgenic zebrafish model Tg(fabp10:EGFP)were used to assess toxicity.Antimicrobial,analgesic,and antioxidant assays evaluated variations in bioactivity.Results:Over the 150-day storage period,gas chromatography-mass spectrometry analysis identified 39 components.Zebrafish acute toxicity tests showed that the LD50 of AAEO stored for 0,30,60,90,120,and 150 days were 0.10μL·mL^(-1),0.10μL·mL^(-1),0.10μL·mL^(-1),0.11μL·mL^(-1),0.13μL·mL^(-1),and 0.14μL·mL^(-1),respectively,demonstrating a 40%reduction in acute toxicity after 150 days of storage.Using the liver-specific green fluorescent transgenic Tg(fabp10:EGFP)zebrafish model,the inhibition rates of AAEO on hepatic fluorescence intensity were measured at 68.5%,43.5%,42.6%,37.8%,34.6%,and 31.9% at different time points,confirming reduced hepatotoxicity after storage.Additionally,the antioxidant and analgesic activities of AAEO were significantly enhanced(p<0.05)after storage,while the antibacterial activity decreased(p<0.05).Conclusions:After storage,AAEO significantly reduces hepatotoxicity,with a 40% decrease in acute toxicity after 150 days.Meanwhile,the antioxidant and analgesic activities of AAEO increase,while its antibacterial activity decreases after storage.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
Peptide-based therapeutics hold great promise for the treatment of various diseases;however,their clinical application is often hindered by toxicity challenges.The accurate prediction of peptide toxicity is crucial fo...Peptide-based therapeutics hold great promise for the treatment of various diseases;however,their clinical application is often hindered by toxicity challenges.The accurate prediction of peptide toxicity is crucial for designing safe peptide-based therapeutics.While traditional experimental approaches are time-consuming and expensive,computational methods have emerged as viable alternatives,including similarity-based and machine learning(ML)-/deep learning(DL)-based methods.However,existing methods often struggle with robustness and generalizability.To address these challenges,we propose HyPepTox-Fuse,a novel framework that fuses protein language model(PLM)-based embeddings with conventional descriptors.HyPepTox-Fuse integrates ensemble PLM-based embeddings to achieve richer peptide representations by leveraging a cross-modal multi-head attention mechanism and Transformer architecture.A robust feature ranking and selection pipeline further refines conventional descriptors,thus enhancing prediction performance.Our framework outperforms state-of-the-art methods in cross-validation and independent evaluations,offering a scalable and reliable tool for peptide toxicity prediction.Moreover,we conducted a case study to validate the robustness and generalizability of HyPepTox-Fuse,highlighting its effectiveness in enhancing model performance.Furthermore,the HyPepTox-Fuse server is freely accessible at https://balalab-skku.org/HyPepTox-Fuse/and the source code is publicly available at https://github.com/cbbl-skku-org/HyPepTox-Fuse/.The study thus presents an intuitive platform for predicting peptide toxicity and supports reproducibility through openly available datasets.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
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
To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic r...To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic risk. To test the acute toxicity of hyperoside, we determined the median lethal dose （LD 50 ） in mice. Forty healthy BALB/c mice （20 per sex） were administered a single oral dose of 5000 mg/kg hyperoside via the intragastrical route. The number of animals poisoned and died was noted daily for 14 consecutive days. All animals survived and appeared active and normal, indicating that the LD 50 of hyperoside was more than 5000 mg/kg. Potential genotoxicity of hyperoside was investigated using a bacterial reverse mutation assay （Ames test）, a chromosome aberration test in Chinese hamster lung （CHL） fibroblasts, and an in vivo micronucleus test in rat bone marrow cells. In the bacterial reverse mutation assay, we observed no increases in the number of revertant colonies at any concentrations of hyperoside regardless of metabolic activation （S9） in all tester strains （TA97, TA98, TA100 and TA102） compared to the vehicle control （P0.05）. Hyperoside did not cause significant structural aberration in CHL cells in the presence or absence of S9 （P0.05）. The micronuclei rates of mice bone marrow cell in all groups showed no significant difference when compared with the negative control （P0.05）. In summary, hyperoside showed no genotoxicity in our experimental conditions.展开更多
基金Supported by The Central Public-Interest Scientific Institution Basal Research Fund,CAFS(2025XT0902)Earmarked for China Agriculture Research System(CARS-46).
文摘The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ mixture on zebrafish(Danio rerio).Acute tests determined 96-h LC_(50) values of 123.41 mg/L for GIS and 103.95 mg/L for ATZ.In the joint toxicity test,these values decreased to 60.96 and 50.88 mg/L,respectively.The Additive Index(AI)analysis revealed a consistent synergistic interaction between the herbicides at all exposure intervals.These findings underscore the enhanced ecological threat of herbicide mixtures and highlight the necessity of considering joint effects in environmental risk assessments.
基金funding from Deutsche Forschungsgemeinschaft (DFG)supported by an MCIN Ry C Programme MCIN/ AEI/10.13039/501100011033+2 种基金by the ‘European Union Next Generation EU/PRTR’ under grant no. RYC2021-032345-Isupported 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 Nitro Healthy, 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AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.
文摘Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.
基金funded by The Tunisian Ministry of Research and Higher Education.
文摘Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.
基金supported by the National Natural Science Foundation of China(Nos.82372115,52073139 and 82404553)the Postdoctoral Fellowship Program of Chinese Postdoctoral Science Foundation(No.GZC20231085).
文摘Albumin,owing to its high abundance and excellent biocompatibility,is widely used as a drug carrier to enhance delivery efficiency and reduce systemic toxicity.The Michael addition between albumin thiols and maleimide-functionalized prodrugs is a common in situ macromolecular prodrug strategy.However,the resulting reversible adducts are susceptible to retro-Michael reactions in vivo,leading to premature drug release and off-target effects.To address this limitation,a gemcitabine prodrug(GAB)bearing a chloroacetamide group was designed to form irreversible covalent bonds with albumin via nucleophilic substitution.A maleimide-based prodrug(GAM)was synthesized as a control.Compared to GAM,GAB showed faster and stronger albumin binding in plasma,enhanced blood circulation time,improved tumor accumulation,and superior in vivo antitumor efficacy.Moreover,GAB exhibited a better safety profile,with reduced cytotoxicity in normal tissues and no observable systemic toxicity.These advantages are attributed to the stable albumin-drug conjugate formed by GAB,which improves drug retention and targeted delivery.This study presents an effective and generalizable albumin-hitchhiking strategy for constructing irreversible prodrugs,offering a promising approach to enhance the therapeutic index of chemotherapeutic agents.
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 National Natural Science Foundation of China (Nos.81872823,82073782,and 82241002)the Key R&D Plan of Ganjiang New District of Jiangxi (No.2023010)。
文摘Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which urgently needs to be addressed in clinical application.Liposomes have been considered ideal vehicles for reducing CDDP toxicity due to their high biocompatibility,low toxicity and passive targeting ability.Nevertheless,CDDP's poor water/lipid solubility usually results in a low liposome druglipid ratio,limiting tumor delivery ability.Herein,a CDDP-polyphenol complex liposome was designed to increase the drug loading capacity of CDDP to realize the reduction of toxicity and effective antitumor effect simultaneously.The complex was prepared via complexation reaction of different stoichiometric ratios of CDDP and polyphenolic substances(gallic acid,epigallocatechin gallate and tannic acid),followed by encapsulation of complex in liposomes to improve tumor targeting.Notably,the molecular interaction forces between CDDP and polyphenolic substances were intensively investigated through a binding force disruption assay.In vitro studies demonstrated that the optimal formulation of CDDP-epigallocatechin gallate complex liposome(CDDP-EGCG Lips) showed the highest CDDP encapsulation efficiency,favorable stability,pH-sensitive release,enhanced cellular uptake and apoptosis effect.In vivo studies revealed that CDDP-EGCG Lips retarded the elimination of CDDP to prolong their circulation time,inhibited the growth of tumors,and significantly reduced the toxic side effects compared to CDDP monotherapy.This delivery strategy holds great promise for improving the clinical use of platinum-based drugs.
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supported by the Jiangsu Province University Basic Science(natural science)Research Major Project(Grant No.:24KJA360007,China)Nanjing University of Chinese Medicine TCM First-classDiscipline“Leading Plan”Scientific Research Project(Grant No.:ZYXYL2024-001,China)+4 种基金National Natural Science Foundation of China(Grant Nos.:U21A20408,81873189,China)Jiangsu Provincial TCM Science and Technology Development Program Project(Grant No.:MS2021004,China)High-Level Key Discipline Construction Project of the National Administration of Traditional Chinese Medicine-Resource Chemistry of Chinese Medicinal Materials(Grant No.:ZYYZDXK-2023083,China)National Administration of Traditional Chinese Medicine Chinese Medicine Innovation Team and Talent Support Program Project(Grant No.:ZYYCXTD-D-202005,China)Innovation and Entrepreneurship Training Program for College Students(Grant No.:202410315138Y,China).
文摘Drug toxicity is closely related to both clinical drug safety and new drug development.Therefore,it is vital to understand the mechanisms of drug toxicity fully and to use appropriate research models with advanced technologies.Zebrafish has become an important vertebrate animal model for highthroughput drug screening and toxicity assessment.At the same time,zebrafish has an intact biological complexity,reflecting the whole organism's toxicity,which gives it an advantage over other highthroughput models in toxicity studies.Despite the gradual increase in toxicity studies utilizing zebrafish,a comprehensive and systematic review of the underlying mechanisms and new techniques is still lacking.This review aims to analyze common toxicity mechanisms in zebrafish models,such as oxidative stress,endoplasmic reticulum stress,inflammation,and apoptosis,and macroscopic changes in biological processes like lipid metabolism disorders and neurotransmitter expression abnormalities.It also introduces new technologies applied in toxicity assessment,such as gene editing,novel fluorescence imaging technology,3D imaging technology,and novel automated technology for high-throughput screening,such as fish capsules.In addition,it also summarizes the advantages and disadvantages of the model.By doing so,it will provide new suggestions for the development and improvement of the model,make it better serve the toxicity study of clinical drugs and provide a more comprehensive perspective for drug toxicity study,thus promoting the development of the field of drug toxicity study.
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.
文摘This study reviews the hepatotoxic chemicals,mechanisms of toxicity,and detoxification methods of Toosendan Fructus(TF).Limonin-type triterpenoids,as primary hepatotoxic components,mediate toxicity though inflammation,oxidative stress,mitochondrial dysfunction,ferroptosis,and apoptosis.Hepatotoxicity can be mitigated by controlling dosage,using processed forms of the herbs,and through rational herbal compatibility.The review provides insights for enhancing the safety and clinical application of TF.
基金supported by grants from the National Natural Science Foundation of China(82074026)the National Interdisciplinary Innovation Team of Traditional Chinese Medicine(ZYYCXTD-D-202209).
文摘but its application is constrained by hepatotoxicity.This study aimed to investigate the feasibility of reducing AAEO’s toxicity through storage and to evaluate changes in chemical composition,toxicity,and bioactivity.Methods:Gas chromatography-mass spectrometry was used to analyze compositional changes during storage.Zebrafish acute toxicity tests and the liver-specific transgenic zebrafish model Tg(fabp10:EGFP)were used to assess toxicity.Antimicrobial,analgesic,and antioxidant assays evaluated variations in bioactivity.Results:Over the 150-day storage period,gas chromatography-mass spectrometry analysis identified 39 components.Zebrafish acute toxicity tests showed that the LD50 of AAEO stored for 0,30,60,90,120,and 150 days were 0.10μL·mL^(-1),0.10μL·mL^(-1),0.10μL·mL^(-1),0.11μL·mL^(-1),0.13μL·mL^(-1),and 0.14μL·mL^(-1),respectively,demonstrating a 40%reduction in acute toxicity after 150 days of storage.Using the liver-specific green fluorescent transgenic Tg(fabp10:EGFP)zebrafish model,the inhibition rates of AAEO on hepatic fluorescence intensity were measured at 68.5%,43.5%,42.6%,37.8%,34.6%,and 31.9% at different time points,confirming reduced hepatotoxicity after storage.Additionally,the antioxidant and analgesic activities of AAEO were significantly enhanced(p<0.05)after storage,while the antibacterial activity decreased(p<0.05).Conclusions:After storage,AAEO significantly reduces hepatotoxicity,with a 40% decrease in acute toxicity after 150 days.Meanwhile,the antioxidant and analgesic activities of AAEO increase,while its antibacterial activity decreases after storage.
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.
基金supported by the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT,Republic of Korea(Grant No.:RS-2024-00344752)supported by the Department of Integrative Biotechnology,Sungkyunkwan University(SKKU)and the BK21 FOUR Project,Republic of Korea.
文摘Peptide-based therapeutics hold great promise for the treatment of various diseases;however,their clinical application is often hindered by toxicity challenges.The accurate prediction of peptide toxicity is crucial for designing safe peptide-based therapeutics.While traditional experimental approaches are time-consuming and expensive,computational methods have emerged as viable alternatives,including similarity-based and machine learning(ML)-/deep learning(DL)-based methods.However,existing methods often struggle with robustness and generalizability.To address these challenges,we propose HyPepTox-Fuse,a novel framework that fuses protein language model(PLM)-based embeddings with conventional descriptors.HyPepTox-Fuse integrates ensemble PLM-based embeddings to achieve richer peptide representations by leveraging a cross-modal multi-head attention mechanism and Transformer architecture.A robust feature ranking and selection pipeline further refines conventional descriptors,thus enhancing prediction performance.Our framework outperforms state-of-the-art methods in cross-validation and independent evaluations,offering a scalable and reliable tool for peptide toxicity prediction.Moreover,we conducted a case study to validate the robustness and generalizability of HyPepTox-Fuse,highlighting its effectiveness in enhancing model performance.Furthermore,the HyPepTox-Fuse server is freely accessible at https://balalab-skku.org/HyPepTox-Fuse/and the source code is publicly available at https://github.com/cbbl-skku-org/HyPepTox-Fuse/.The study thus presents an intuitive platform for predicting peptide toxicity and supports reproducibility through openly available datasets.
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.
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National Nature Science Foundation of China (Grant No.30572350)New Drug Foundation of State Administration of Traditional Chinese Medicine (Grant No.DIX005A)
文摘To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic risk. To test the acute toxicity of hyperoside, we determined the median lethal dose （LD 50 ） in mice. Forty healthy BALB/c mice （20 per sex） were administered a single oral dose of 5000 mg/kg hyperoside via the intragastrical route. The number of animals poisoned and died was noted daily for 14 consecutive days. All animals survived and appeared active and normal, indicating that the LD 50 of hyperoside was more than 5000 mg/kg. Potential genotoxicity of hyperoside was investigated using a bacterial reverse mutation assay （Ames test）, a chromosome aberration test in Chinese hamster lung （CHL） fibroblasts, and an in vivo micronucleus test in rat bone marrow cells. In the bacterial reverse mutation assay, we observed no increases in the number of revertant colonies at any concentrations of hyperoside regardless of metabolic activation （S9） in all tester strains （TA97, TA98, TA100 and TA102） compared to the vehicle control （P0.05）. Hyperoside did not cause significant structural aberration in CHL cells in the presence or absence of S9 （P0.05）. The micronuclei rates of mice bone marrow cell in all groups showed no significant difference when compared with the negative control （P0.05）. In summary, hyperoside showed no genotoxicity in our experimental conditions.
