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
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
Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematic...Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematically examined the potential impacts of M/NPs on ocular health,focusing on exposure pathways,toxicological mechanisms,and resultant damage to the eye.Ocular exposure to M/NPs can occur via direct contact and oral ingestion,with the latter potentially leading to the penetration of particles through ocular biological barriers into ocular tissues.The review highlighted that M/NPs can induce adverse effects on the ocular surface,elevate intraocular pressure,and cause abnormalities in the vitreous and retina.Mechanistically,oxidative stress and inflammation are central to M/NP-induced ocular damage,with smaller particles often exhibiting greater toxicity.Overall,this review underscored the potential risks of M/NPs to ocular health and emphasized the need for further research to elucidate exposure mechanisms,toxicological pathways,and mitigation strategies.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
Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-...Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.展开更多
Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim ...Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.展开更多
Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is uncl...Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.展开更多
Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male W...Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.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
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
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
Soil naturally contains various heavy metals,however,their concentrations have reached toxic levels due to excessive agrochemical use and industrial activities.Heavy metals are persistent and non-biodegradable,causing...Soil naturally contains various heavy metals,however,their concentrations have reached toxic levels due to excessive agrochemical use and industrial activities.Heavy metals are persistent and non-biodegradable,causing environmental disruption and posing significant health hazards.Microbial-mediated remediation is a promising strategy to prevent heavy metal leaching and mobilization,facilitating their extraction and detoxification.Nickel(Ni),being a prevalent heavy metal pollutant,requires specific attention in remediation efforts.Plants have evolved defense mechanisms to cope with environmental stresses,including heavy metal toxicity,but such stress significantly reduces crop productivity.Beneficial microorganisms play a crucial role in enhancing plant yield and mitigating abiotic stress.The impact of heavy metal abiotic stress on plants’growth and productivity requires thorough investigation.Bioremediation using Nickel nanoparticles(Ni NPs)offers an effective approach to mitigating environmental pollution.Microorganisms contribute to nanoparticle bioremediation by immobilizing metals or inducing the synthesis of remediating microbial enzymes.Understanding the interactions between microorganisms,contaminants,and nanoparticles(NPs)is essential for advancing bioremediation strategies.This review focuses on the role of Bacillus subtilis in the bioremediation of nickel nanoparticles to mitigate environmental pollution and associated health risks.Furthermore,sustainable approaches are necessary to minimize metal contamination in seeds.The current review discusses bacterial inoculation in enhancing heavy metal tolerance,plant signal transduction pathways,and the transition from molecular to genomic research in metal stress adaptation.Moreover,the inoculation of advantageous bacteria is crucial for preserving plants under severe mental stress.Different researchers develop a complex,vibrant relationship with plants through a series of events known as plant-microbe interactions.It increases metal stress resistance through the creation of phytohormones.In general,the defensive responses of plants to heavy metal stress,mediated by microbial inoculation require further in-depth research.Further studies should explore the detoxification mechanism of nickel through bioremediation to develop more effective and sustainable remediation strategies.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
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
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 an MCIN RyC Programme MCIN/AEI/10.13039/501100011033the‘European Union Next Generation EU/PRTR’under grant no.RYC2021-032345-I+1 种基金supported by the AEI(grant no.PID2019-107463RJ-I00/AEI/10.13039/501100011033)the Regional Research and Development Programme of the Government of Navarre(call 2019,project NitroHealthy,PC068).
文摘Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrations,are not fully elucidated.This review delves into the physiological and molecular nature of this phenomenon.To date,nitrate-dependent alleviation of ammonium toxicity is the result of cumulative consequences of the role of nitrate as a nutrient and signal in plant performance.The ability to counteract the ammonium-induced acidification through nitrate uptake and metabolism,the enhancement of potassium uptake as an essential nitrate counterion,and the nitratedependent signaling of key factors involved in ammonium assimilation,ROS scavenging,and growth hormone biosynthesis,are the most relevant hallmarks.In addition,evidence suggests that the availability of nitrate and ammonium has driven ecological selection in plants,determining current N preferences,and may have led to the selection of nitrate-dependent and ammonium-sensitive domesticated crops and the inefficient use of N fertilizers in agriculture.As ammonium toxicity limits N fertilization options and reduces agricultural yields,when it could be a more sustainable and cheaper alternative to nitrate,this review provides a better understanding of how plants use nitrate to counteract the problematic aspects of ammonium nutrition.
基金Supported by the Guangdong Provincial Natural Science Foundation(No.2114050001527).
文摘Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematically examined the potential impacts of M/NPs on ocular health,focusing on exposure pathways,toxicological mechanisms,and resultant damage to the eye.Ocular exposure to M/NPs can occur via direct contact and oral ingestion,with the latter potentially leading to the penetration of particles through ocular biological barriers into ocular tissues.The review highlighted that M/NPs can induce adverse effects on the ocular surface,elevate intraocular pressure,and cause abnormalities in the vitreous and retina.Mechanistically,oxidative stress and inflammation are central to M/NP-induced ocular damage,with smaller particles often exhibiting greater toxicity.Overall,this review underscored the potential risks of M/NPs to ocular health and emphasized the need for further research to elucidate exposure mechanisms,toxicological pathways,and mitigation strategies.
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.
文摘Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.
文摘Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.
文摘Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.
基金financially assisted to Timanshi Chansoriya of the fellowship grant of UGC-NFPwD,New Delhi sanctioned vide UGC F.No.01-01/2019-Sch dated 06.11.2020(Serial No.352 ID:NFPWD-2018-20-UTP-6522).
文摘Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.
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 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.
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supported by the project of Sanya Yazhou Bay Science and Technology City,Grant No.SKJC-2023-02-004Education Department of Hainan Province,Grant No.Hnky2024ZD-27Key R&D Project of Hainan Province(Science and Technology Commissioner):405314040001.
文摘Soil naturally contains various heavy metals,however,their concentrations have reached toxic levels due to excessive agrochemical use and industrial activities.Heavy metals are persistent and non-biodegradable,causing environmental disruption and posing significant health hazards.Microbial-mediated remediation is a promising strategy to prevent heavy metal leaching and mobilization,facilitating their extraction and detoxification.Nickel(Ni),being a prevalent heavy metal pollutant,requires specific attention in remediation efforts.Plants have evolved defense mechanisms to cope with environmental stresses,including heavy metal toxicity,but such stress significantly reduces crop productivity.Beneficial microorganisms play a crucial role in enhancing plant yield and mitigating abiotic stress.The impact of heavy metal abiotic stress on plants’growth and productivity requires thorough investigation.Bioremediation using Nickel nanoparticles(Ni NPs)offers an effective approach to mitigating environmental pollution.Microorganisms contribute to nanoparticle bioremediation by immobilizing metals or inducing the synthesis of remediating microbial enzymes.Understanding the interactions between microorganisms,contaminants,and nanoparticles(NPs)is essential for advancing bioremediation strategies.This review focuses on the role of Bacillus subtilis in the bioremediation of nickel nanoparticles to mitigate environmental pollution and associated health risks.Furthermore,sustainable approaches are necessary to minimize metal contamination in seeds.The current review discusses bacterial inoculation in enhancing heavy metal tolerance,plant signal transduction pathways,and the transition from molecular to genomic research in metal stress adaptation.Moreover,the inoculation of advantageous bacteria is crucial for preserving plants under severe mental stress.Different researchers develop a complex,vibrant relationship with plants through a series of events known as plant-microbe interactions.It increases metal stress resistance through the creation of phytohormones.In general,the defensive responses of plants to heavy metal stress,mediated by microbial inoculation require further in-depth research.Further studies should explore the detoxification mechanism of nickel through bioremediation to develop more effective and sustainable remediation strategies.
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%.
