Results from laboratory experiments indicated that the concentrations and toxicities of both water-soluble and 0.1 M HCl-extractable Cu and Cd from soils were in the order of red soil> yellow brown earth> black ...Results from laboratory experiments indicated that the concentrations and toxicities of both water-soluble and 0.1 M HCl-extractable Cu and Cd from soils were in the order of red soil> yellow brown earth> black earth.The toxicity of soil varied with the concentrations of metals.The form,concentration and toxicity of Cu and Cd in soils were determined by cation exchange capacity,content of organic matter and composition of clay minerals in the soil.Addition of CaCO3 could significantly decrease the concentration and toxicity of water-soluble and 0.1 M HCl-extractable Cu or Cd from the red soil,and could notably transform the Cu and Cd from the water-soluble or exchangeable form into the organic,free oxides-occluded or sulfic form.展开更多
Triptolide(TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but ...Triptolide(TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction(LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity.展开更多
[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17...[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.展开更多
Twenty one days old Swiss albino mice that received diphenylhydantoin(25 mg/kg,i.p.,daily for 15 days)progressively developed gait alterations,changes of behavior and cerebellar ataxia.Cerebellar slices were processed...Twenty one days old Swiss albino mice that received diphenylhydantoin(25 mg/kg,i.p.,daily for 15 days)progressively developed gait alterations,changes of behavior and cerebellar ataxia.Cerebellar slices were processed by conventional transmission electron microscopy.The body of Purkinje cells exhibited fragmented limiting plasma membranes,dilated nuclear envelopes,swelling and disassembly of nuclear pores,enlargement of rough and smooth endoplasmic reticulum and a notable detachment of membrane associated ribosomes,to-gether with distorted vacuoles of smooth endoplasmic reticulum,bizarre shaped and swollen mitochondria with dilated cristae,as well as disrupted limiting lysosomal membranes.Degenerated axosomatic synapses apparently corresponding to basket cell axonal endings were recognized.Degenerated Purkinje cell axon initial segments exhibited vacuolar degeneration of myelin sheath,dilated axoplasmic tubular bundles,fragmented axonal mem-branes,swollen mitochondria,and disassembly of cytoskeletal structures.Some edematous and clear secondary and tertiary dendrites exhibited areas of dilated cisterns of smooth endoplasmic reticulum,clear and dark mul-tivesicular bodies,and coated vesicles.Other dendritic ramifications exhibited an electron dense dendroplasm.Degenerated and large climbing fiber endings were observed making axodendritic synapses with edematous Purkinje dendrites.These presynaptic endings appeared depleted or containing few synaptic vesicles.These syn-apses did not exhibit pre-and postsynaptic densities.At the molecular layer,the edematous synaptic varicosities of parallel fibers containing pleomorphic synaptic vesicles and dense extravesicular substance were observed making asymmetric synaptic contacts with swollen Purkinje dendritic spines.These findings are postulated as pathogenic mechanisms of mouse cerebellar ataxia.展开更多
Persistent toxic substances(PTS)represent a paramount environmental issue in the 21st century.Understanding the concentrations and forms of PTS in the environment is crucial for accurately assessing their environmenta...Persistent toxic substances(PTS)represent a paramount environmental issue in the 21st century.Understanding the concentrations and forms of PTS in the environment is crucial for accurately assessing their environmental health impacts.This article presents a concise overview of the components of PTS,pertinent environmental regulations,and conventional detection methodologies.Additionally,we offer an in-depth review of the principles,development,and practical applications of surface-enhanced Raman scattering(SERS)in environmental monitoring,emphasizing the advancements in detecting trace amounts of PTS in complex environmental matrices.Recent progress in enhancing SERS sensitivity,improving selectivity,and practical implementations are detailed,showcasing innovative materials and methods.Integrating SERS with advanced algorithms are highlighted as pivotal areas for future research.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
This study investigates the innovative reuse of sewage sludge with eco-friendly alkaline solutes to improve clayey soil without conventional cementitious binders.The unconfined compressive strength(UCS)was the main cr...This study investigates the innovative reuse of sewage sludge with eco-friendly alkaline solutes to improve clayey soil without conventional cementitious binders.The unconfined compressive strength(UCS)was the main criterion to assess the quality and effectiveness of the proposed solutions,as this test was performed to measure the strength of the stabilized clay by varying binders’dosages and curing times.Moreover,the direct shear test(DST)was used to investigate the Mohr-Coulomb parameters of the treated soil.Microstructure observations of the natural and treated soil were conducted using scanning electron microscope(SEM),energy-dispersive spectroscopy(EDS),and FTIR.Furthermore,toxicity characteristic leaching procedure(TCLP)tests were performed on the treated soil to investigate the leachability of metals.According to the results,using 2.5%of sewage sludge activated by NaOH and Na_(2)SiO_(3)increases the UCS values from 176 kPa to 1.46 MPa after 7 d and 56 d of curing,respectively.The results of the DST indicate that sewage sludge as a precursor increases cohesion and enhances frictional resistance,thereby improving the Mohr-Coulomb parameters of the stabilized soil.The SEM micrographs show that alkali-activated sewage sludge increases the integrity and reduces the cavity volumes in the stabilized soil.Moreover,TCLP tests revealed that the solubility of metals in the treated soil alkaliactivated by sewage sludge significantly decreased.This study suggests that using sewage sludge can replace cement and lime in ground improvement,improve the circular economy,and reduce the carbon footprint of construction projects.展开更多
Owing to their low toxicity and remarkable stability, perovskites based on antimony and bismuth have garnered significant interest in recent years. However, A_(3)B_(2)X_(9) perovskite materials derived from antimony a...Owing to their low toxicity and remarkable stability, perovskites based on antimony and bismuth have garnered significant interest in recent years. However, A_(3)B_(2)X_(9) perovskite materials derived from antimony and bismuth face several challenges, including excessively wide band gaps, elevated defect densities, and suboptimal film quality, all of which hinder advancements in device efficiency. While extensive studies have been undertaken to investigate the effects of modulating the A-site and X-site elements in lead-free A_(3)B_(2)X_(9) perovskites, there remains a notable scarcity of reports addressing the impact of modifications to the B-site element. In this study, we investigated the alloying of antimony and bismuth within the 2D Cs_(3)B_(2)I_(6)Br_(3) perovskite. By systematically varying the ratios of two elements, we found that the incorporation of both antimony and bismuth at the B-site significantly enhances the quality of the perovskite films. Our findings indicate that a 1 : 1 ratio of antimony to bismuth produces the densest films, the highest photoluminescence intensity, and superior photovoltaic performance. Ultimately,the devices fabricated using this optimal ratio achieved an open-circuit voltage(VOC) of 1.01 V and a power conversion efficiency(PCE) of 0.645%.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
Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is...Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.展开更多
Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic ...Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.展开更多
Objective Inflammation and fibrosis are key features of diabetic nephropathy(DN).Triptolide(TP)exhibits anti-inflammatory and anti-fibrotic properties,though its mechanisms of action in DN remain unclear.CREKA(Cys-Arg...Objective Inflammation and fibrosis are key features of diabetic nephropathy(DN).Triptolide(TP)exhibits anti-inflammatory and anti-fibrotic properties,though its mechanisms of action in DN remain unclear.CREKA(Cys-Arg-Glu-Lys-Ala)is a pentapeptide that specifically binds to fibronectin(FN),and the CREKA-modified liposome(CREKA-Lip)represents a novel FN-targeted drug delivery system.This study aimed to investigate the role of TP in diabetic db/db mice and determine whether encapsulation within CREKA-Lip enhances therapeutic efficacy while reducing the multi-organ toxicity of TP.Methods Eight-week-old diabetic db/db mice received tail vein injections twice weekly with vehicle,free TP,or CREKA-Lip/TP for 10 weeks.Urine and serum parameters were measured,and kidney,heart,liver,and testis tissues were collected for pathological evaluation.Protein-protein interaction networks were constructed using Cytoscape and its plug-ins to identify core targets and elucidate the therapeutic mechanism of TP against DN.Inflammatory,fibrotic,apoptotic,and lipid metabolism markers were evaluated in the kidneys of diabetic mice with DN and in high glucose-treated mouse mesangial cells and podocytes using qPCR,Western blot,immunohistochemistry,and immunofluorescence assays.Results TP administration reduced fasting blood glucose levels and glomerular mesangial expansion in diabetic mice.TP significantly suppressed renal inflammation,fibrosis,and apoptosis while enhancing lipid metabolism.Integration of network pharmacology,molecular docking,and transcriptomics revealed that TP ameliorated DN by inhibiting the JAK2-STAT1 signaling pathway.In vitro,TP inhibited high glucose-induced phosphorylation of JAK2 and STAT1,reduced collagen production in mesangial cells,decreased apoptosis,and improved lipid metabolism in podocytes.Moreover,CREKA-Lip/TP exhibited superior efficacy compared with free TP,with a more sustained reduction in urine albumin-to-creatinine ratio and greater inhibition of mesangial expansion.Notably,CREKA-Lip/TP treatment did not induce systemic toxicity.Conclusion TP improves renal inflammation,fibrosis,apoptosis,and lipid homeostasis,thereby ameliorating DN by inhibiting JAK2-STAT1 activation.Targeted delivery of TP via FN-binding CREKA-Lip enhances therapeutic efficacy while minimizing multi-organ 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 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
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
As a new type of pollutant,the harm caused by microplastics(MPs)to organisms has been the research focus.Recently,the proportion of MPs ingested through the digestive tract has gradually increased with the popularity ...As a new type of pollutant,the harm caused by microplastics(MPs)to organisms has been the research focus.Recently,the proportion of MPs ingested through the digestive tract has gradually increased with the popularity of fast-food products,such as takeout.The damage to the digestive system has attracted increasing attention.We reviewed the literature regarding toxicity of MPs and observed that they have different effects on multiple organs of the digestive system.The mechanism may be related to the toxic effects of MPs themselves,interactions with various substances in the biological body,and participation in various signaling pathways to induce adverse reactions as a carrier of toxins to increase the time and amount of body absorption.Based on the toxicity mechanism of MPs,we propose specific suggestions to provide a theoretical reference for the government and relevant departments.展开更多
This study investigated the eco-biocontrol potential of indigenous isolates obtained from agricultural soils in WarboVillage, Papua, Indonesia, targeting the highly destructive fall armyworm (Spodoptera frugiperda) in...This study investigated the eco-biocontrol potential of indigenous isolates obtained from agricultural soils in WarboVillage, Papua, Indonesia, targeting the highly destructive fall armyworm (Spodoptera frugiperda) in corn agroecosystems.A total of 58 bacterial colonies were isolated, of which 18 were morphologically confirmed as Bacillus thuringiensis basedon endospore and parasporal crystal protein characteristics. These isolates were cultured in Tryptose Phosphate Broth andtested for larvicidal activity against second-instar larvae under controlled conditions. Toxicity tests revealed that isolate 18exhibited the highest efficacy, causing 100% larval mortality, followed by isolates 12 and 13 with 93.3%, confirming astrong entomopathogenic potential. The most toxic isolates were further verified by the presence of cry1F and cry2Aagenes through PCR analysis, indicating the molecular basis of their virulence. The innovation of this research lies in thecombination of morphological, toxicological, and molecular characterizations of locally adapted Bacillus thuringiensisstrains, which offers a sustainable, environmentally friendly alternative to chemical pesticides. These findings provide ascientific foundation for developing region-specific bioinsecticides, reducing dependence on synthetic inputs, and supportingsustainable pest management strategies in tropical corn production systems.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
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
Lead(Pb)is a toxic metal found in wastewater,posing significant health risks to both humans and the environment.This study aimed to develop a novel adsorbent for lead removal from aqueous solutions.This adsorbent,a co...Lead(Pb)is a toxic metal found in wastewater,posing significant health risks to both humans and the environment.This study aimed to develop a novel adsorbent for lead removal from aqueous solutions.This adsorbent,a coffee husk extract-capped magnetite with pumice silica nanocomposite(CHE-capped M/PU/Si-NC),was synthesized using a completely green approach.The novelty of this study lies in the green synthesis of silica nanoparticles(SiO_(2)-NPs)throughout the process.Coffee husk extract(CHE)served as both a stabilizing and capping agent for the SiO_(2)-NPs,which were synthesized from sodium silicate(Na_(2)SiO_(3))extracted from bagasse ash(BA).Subsequently,the CHE-capped silica was co-precipitated with phyto-fabricated magnetite and integrated into a pumice matrix to produce the final CHE-capped M/PU/Si-NC adsorbent.The CHE-capped M/PU/Si-NC was characterized using SEM,XRF,FTIR,BET,XRD,TGA,and zeta potential analysis.The surface area of the CHE-capped M/PU/Si-NC was determined to be 313 m^(2)·g^(-1),and TGA results indicated good thermal stability up to 690℃.The zeta potential was measured at-37.7 mV.XRD analysis of CHE-capped M/PU/Si-NC confirmed the formation of magnetite and revealed its crystal structure.The maximum adsorption performance of this material was observed to be 95%at an adsorbent dosage of 2 g·L^(-1) and an initial Pb^(2+)concentration of 100 g·L^(-1).The adsorption kinetics were best described by the pseudo-second-order kinetic model.The Langmuir isotherm provided a good fit with a maximum adsorption capacity of 150 mg·g^(-1)(R^(2)=0.99).Regeneration studies demonstrated that the adsorbent maintained its high Pb^(2+) uptake capacity for up to five cycles.Overall,these findings suggest that this adsorbent is a promising candidate for the removal of Pb^(2+) from water and wastewater.展开更多
文摘Results from laboratory experiments indicated that the concentrations and toxicities of both water-soluble and 0.1 M HCl-extractable Cu and Cd from soils were in the order of red soil> yellow brown earth> black earth.The toxicity of soil varied with the concentrations of metals.The form,concentration and toxicity of Cu and Cd in soils were determined by cation exchange capacity,content of organic matter and composition of clay minerals in the soil.Addition of CaCO3 could significantly decrease the concentration and toxicity of water-soluble and 0.1 M HCl-extractable Cu or Cd from the red soil,and could notably transform the Cu and Cd from the water-soluble or exchangeable form into the organic,free oxides-occluded or sulfic form.
基金supported by the National Natural Science Foundation of China(Grant Nos.81160541and 81373946)the Project of Health Department of Jiangxi Province(Grant No.2011A143)the priority academic program development of Jiangsu higher education institutions(PAPD)
文摘Triptolide(TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction(LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity.
基金Supported by the Incubation Program for Science and Technology Innovative Research Team in Sichuan Province of China(2011-JTD0035)Program of Department of Education in Sichuan Province of China(10ZB050)the Program of Department of Education in Sichuan Province of China(11ZZ022)
文摘[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.
基金a subvention obtained from Biological Research Institute.Faculty of Medicine.Zulia University,the Council for Humanistic and Scientific Devel-opment of Zulia University(CONDES LUZ),and Castejón Foundation.The technical digital help of Lic.Orlando Caste-jón Depablos is deeply appreciated.The author declares no conflicts of interests.
文摘Twenty one days old Swiss albino mice that received diphenylhydantoin(25 mg/kg,i.p.,daily for 15 days)progressively developed gait alterations,changes of behavior and cerebellar ataxia.Cerebellar slices were processed by conventional transmission electron microscopy.The body of Purkinje cells exhibited fragmented limiting plasma membranes,dilated nuclear envelopes,swelling and disassembly of nuclear pores,enlargement of rough and smooth endoplasmic reticulum and a notable detachment of membrane associated ribosomes,to-gether with distorted vacuoles of smooth endoplasmic reticulum,bizarre shaped and swollen mitochondria with dilated cristae,as well as disrupted limiting lysosomal membranes.Degenerated axosomatic synapses apparently corresponding to basket cell axonal endings were recognized.Degenerated Purkinje cell axon initial segments exhibited vacuolar degeneration of myelin sheath,dilated axoplasmic tubular bundles,fragmented axonal mem-branes,swollen mitochondria,and disassembly of cytoskeletal structures.Some edematous and clear secondary and tertiary dendrites exhibited areas of dilated cisterns of smooth endoplasmic reticulum,clear and dark mul-tivesicular bodies,and coated vesicles.Other dendritic ramifications exhibited an electron dense dendroplasm.Degenerated and large climbing fiber endings were observed making axodendritic synapses with edematous Purkinje dendrites.These presynaptic endings appeared depleted or containing few synaptic vesicles.These syn-apses did not exhibit pre-and postsynaptic densities.At the molecular layer,the edematous synaptic varicosities of parallel fibers containing pleomorphic synaptic vesicles and dense extravesicular substance were observed making asymmetric synaptic contacts with swollen Purkinje dendritic spines.These findings are postulated as pathogenic mechanisms of mouse cerebellar ataxia.
基金supported by the National Natural Science Foundation of China(Nos.42077299,and U21A20290)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0750400)the Ordos Key Research and Development Program(No.YF20240037).
文摘Persistent toxic substances(PTS)represent a paramount environmental issue in the 21st century.Understanding the concentrations and forms of PTS in the environment is crucial for accurately assessing their environmental health impacts.This article presents a concise overview of the components of PTS,pertinent environmental regulations,and conventional detection methodologies.Additionally,we offer an in-depth review of the principles,development,and practical applications of surface-enhanced Raman scattering(SERS)in environmental monitoring,emphasizing the advancements in detecting trace amounts of PTS in complex environmental matrices.Recent progress in enhancing SERS sensitivity,improving selectivity,and practical implementations are detailed,showcasing innovative materials and methods.Integrating SERS with advanced algorithms are highlighted as pivotal areas for future research.
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This study investigates the innovative reuse of sewage sludge with eco-friendly alkaline solutes to improve clayey soil without conventional cementitious binders.The unconfined compressive strength(UCS)was the main criterion to assess the quality and effectiveness of the proposed solutions,as this test was performed to measure the strength of the stabilized clay by varying binders’dosages and curing times.Moreover,the direct shear test(DST)was used to investigate the Mohr-Coulomb parameters of the treated soil.Microstructure observations of the natural and treated soil were conducted using scanning electron microscope(SEM),energy-dispersive spectroscopy(EDS),and FTIR.Furthermore,toxicity characteristic leaching procedure(TCLP)tests were performed on the treated soil to investigate the leachability of metals.According to the results,using 2.5%of sewage sludge activated by NaOH and Na_(2)SiO_(3)increases the UCS values from 176 kPa to 1.46 MPa after 7 d and 56 d of curing,respectively.The results of the DST indicate that sewage sludge as a precursor increases cohesion and enhances frictional resistance,thereby improving the Mohr-Coulomb parameters of the stabilized soil.The SEM micrographs show that alkali-activated sewage sludge increases the integrity and reduces the cavity volumes in the stabilized soil.Moreover,TCLP tests revealed that the solubility of metals in the treated soil alkaliactivated by sewage sludge significantly decreased.This study suggests that using sewage sludge can replace cement and lime in ground improvement,improve the circular economy,and reduce the carbon footprint of construction projects.
基金financially supported by the Natural Science Foundation of Zhejiang Province, China (Grant No. LQ22F040001)China Postdoctoral Science Foundation (Grant No. 2022M723281)Science and Technology Planning Project of Shaoxing City (Grant No. 2023B41006)。
文摘Owing to their low toxicity and remarkable stability, perovskites based on antimony and bismuth have garnered significant interest in recent years. However, A_(3)B_(2)X_(9) perovskite materials derived from antimony and bismuth face several challenges, including excessively wide band gaps, elevated defect densities, and suboptimal film quality, all of which hinder advancements in device efficiency. While extensive studies have been undertaken to investigate the effects of modulating the A-site and X-site elements in lead-free A_(3)B_(2)X_(9) perovskites, there remains a notable scarcity of reports addressing the impact of modifications to the B-site element. In this study, we investigated the alloying of antimony and bismuth within the 2D Cs_(3)B_(2)I_(6)Br_(3) perovskite. By systematically varying the ratios of two elements, we found that the incorporation of both antimony and bismuth at the B-site significantly enhances the quality of the perovskite films. Our findings indicate that a 1 : 1 ratio of antimony to bismuth produces the densest films, the highest photoluminescence intensity, and superior photovoltaic performance. Ultimately,the devices fabricated using this optimal ratio achieved an open-circuit voltage(VOC) of 1.01 V and a power conversion efficiency(PCE) of 0.645%.
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 Notional Natural Science Foundation of Chino,No.82160690Colloborotive Innovation Center of Chinese Ministry of Education,No.2020-39Science and Technology Foundation of Guizhou Province,No.ZK[2021]-014(all to FZ)。
文摘Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.
基金supported by the National Natural Science Foundation of China,Nos.82301486(to SL)and 82071325(to FY)Medjaden Academy&Research Foundation for Young Scientists,No.MJR202310040(to SL)+2 种基金Nanjing Medical University Science and Technique Development,No.NMUB20220060(to SL)Medical Scientific Research Project of Jiangsu Commission of Health,No.ZDA2020019(to JZ)Health China Buchang Zhiyuan Public Welfare Project for Heart and Brain Health,No.HIGHER202102(to QD).
文摘Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.
文摘Objective Inflammation and fibrosis are key features of diabetic nephropathy(DN).Triptolide(TP)exhibits anti-inflammatory and anti-fibrotic properties,though its mechanisms of action in DN remain unclear.CREKA(Cys-Arg-Glu-Lys-Ala)is a pentapeptide that specifically binds to fibronectin(FN),and the CREKA-modified liposome(CREKA-Lip)represents a novel FN-targeted drug delivery system.This study aimed to investigate the role of TP in diabetic db/db mice and determine whether encapsulation within CREKA-Lip enhances therapeutic efficacy while reducing the multi-organ toxicity of TP.Methods Eight-week-old diabetic db/db mice received tail vein injections twice weekly with vehicle,free TP,or CREKA-Lip/TP for 10 weeks.Urine and serum parameters were measured,and kidney,heart,liver,and testis tissues were collected for pathological evaluation.Protein-protein interaction networks were constructed using Cytoscape and its plug-ins to identify core targets and elucidate the therapeutic mechanism of TP against DN.Inflammatory,fibrotic,apoptotic,and lipid metabolism markers were evaluated in the kidneys of diabetic mice with DN and in high glucose-treated mouse mesangial cells and podocytes using qPCR,Western blot,immunohistochemistry,and immunofluorescence assays.Results TP administration reduced fasting blood glucose levels and glomerular mesangial expansion in diabetic mice.TP significantly suppressed renal inflammation,fibrosis,and apoptosis while enhancing lipid metabolism.Integration of network pharmacology,molecular docking,and transcriptomics revealed that TP ameliorated DN by inhibiting the JAK2-STAT1 signaling pathway.In vitro,TP inhibited high glucose-induced phosphorylation of JAK2 and STAT1,reduced collagen production in mesangial cells,decreased apoptosis,and improved lipid metabolism in podocytes.Moreover,CREKA-Lip/TP exhibited superior efficacy compared with free TP,with a more sustained reduction in urine albumin-to-creatinine ratio and greater inhibition of mesangial expansion.Notably,CREKA-Lip/TP treatment did not induce systemic toxicity.Conclusion TP improves renal inflammation,fibrosis,apoptosis,and lipid homeostasis,thereby ameliorating DN by inhibiting JAK2-STAT1 activation.Targeted delivery of TP via FN-binding CREKA-Lip enhances therapeutic efficacy while minimizing multi-organ 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.
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)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As a new type of pollutant,the harm caused by microplastics(MPs)to organisms has been the research focus.Recently,the proportion of MPs ingested through the digestive tract has gradually increased with the popularity of fast-food products,such as takeout.The damage to the digestive system has attracted increasing attention.We reviewed the literature regarding toxicity of MPs and observed that they have different effects on multiple organs of the digestive system.The mechanism may be related to the toxic effects of MPs themselves,interactions with various substances in the biological body,and participation in various signaling pathways to induce adverse reactions as a carrier of toxins to increase the time and amount of body absorption.Based on the toxicity mechanism of MPs,we propose specific suggestions to provide a theoretical reference for the government and relevant departments.
基金funded by the Directorate General of Higher Education(DRPM),Ministry of Education,Culture,Research,and Technology of Indonesia,under the auspices of the Research Grant Scheme 2024.
文摘This study investigated the eco-biocontrol potential of indigenous isolates obtained from agricultural soils in WarboVillage, Papua, Indonesia, targeting the highly destructive fall armyworm (Spodoptera frugiperda) in corn agroecosystems.A total of 58 bacterial colonies were isolated, of which 18 were morphologically confirmed as Bacillus thuringiensis basedon endospore and parasporal crystal protein characteristics. These isolates were cultured in Tryptose Phosphate Broth andtested for larvicidal activity against second-instar larvae under controlled conditions. Toxicity tests revealed that isolate 18exhibited the highest efficacy, causing 100% larval mortality, followed by isolates 12 and 13 with 93.3%, confirming astrong entomopathogenic potential. The most toxic isolates were further verified by the presence of cry1F and cry2Aagenes through PCR analysis, indicating the molecular basis of their virulence. The innovation of this research lies in thecombination of morphological, toxicological, and molecular characterizations of locally adapted Bacillus thuringiensisstrains, which offers a sustainable, environmentally friendly alternative to chemical pesticides. These findings provide ascientific foundation for developing region-specific bioinsecticides, reducing dependence on synthetic inputs, and supportingsustainable pest management strategies in tropical corn production systems.
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.
文摘Lead(Pb)is a toxic metal found in wastewater,posing significant health risks to both humans and the environment.This study aimed to develop a novel adsorbent for lead removal from aqueous solutions.This adsorbent,a coffee husk extract-capped magnetite with pumice silica nanocomposite(CHE-capped M/PU/Si-NC),was synthesized using a completely green approach.The novelty of this study lies in the green synthesis of silica nanoparticles(SiO_(2)-NPs)throughout the process.Coffee husk extract(CHE)served as both a stabilizing and capping agent for the SiO_(2)-NPs,which were synthesized from sodium silicate(Na_(2)SiO_(3))extracted from bagasse ash(BA).Subsequently,the CHE-capped silica was co-precipitated with phyto-fabricated magnetite and integrated into a pumice matrix to produce the final CHE-capped M/PU/Si-NC adsorbent.The CHE-capped M/PU/Si-NC was characterized using SEM,XRF,FTIR,BET,XRD,TGA,and zeta potential analysis.The surface area of the CHE-capped M/PU/Si-NC was determined to be 313 m^(2)·g^(-1),and TGA results indicated good thermal stability up to 690℃.The zeta potential was measured at-37.7 mV.XRD analysis of CHE-capped M/PU/Si-NC confirmed the formation of magnetite and revealed its crystal structure.The maximum adsorption performance of this material was observed to be 95%at an adsorbent dosage of 2 g·L^(-1) and an initial Pb^(2+)concentration of 100 g·L^(-1).The adsorption kinetics were best described by the pseudo-second-order kinetic model.The Langmuir isotherm provided a good fit with a maximum adsorption capacity of 150 mg·g^(-1)(R^(2)=0.99).Regeneration studies demonstrated that the adsorbent maintained its high Pb^(2+) uptake capacity for up to five cycles.Overall,these findings suggest that this adsorbent is a promising candidate for the removal of Pb^(2+) from water and wastewater.
