Toxicity of Cu and Cd in Soils and Detoxication by Additives

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.

Effects of Sub-chronic Intoxication of 1,8-cineole on Blood Biochemical Indexes of Mice

[ 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.

Mouse cerebellar Purkinje cell damage induced by diphenylhydantoin acute intoxication

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.

UPLC/ESI-QTOF-MS-based metabolomics survey on the toxicity of triptolide and detoxication of licorice

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.

Return to work in young and middle-aged colorectal cancer survivors:Factors influencing self-efficacy,fear,resilience,and financial toxicity

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.

Copper homeostasis and neurodegenerative diseases

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.

Non-coding RNAs in acute ischemic stroke:from brain to periphery

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.

Using cemented paste backfill to tackle the phosphogypsum stockpile in China:A down-to-earth technology with new vitalities in pollutant retention and CO_(2) abatement

Phosphogypsum(PG),a hard-to-dissipate by-product of the phosphorus fertilizer production industry,places strain on the biogeochemical cycles and ecosystem functions of storage sites.This pervasive problem is already widespread worldwide and requires careful stewardship.In this study,we review the presence of potentially toxic elements(PTEs)in PG and describe their associations with soil properties,anthropogenic activities,and surrounding organisms.Then,we review different ex-/in-situ solutions for promoting the sustainable management of PG,with an emphasis on in-situ cemented paste backfill,which offers a cost-effective and highly scalable opportunity to advance the value-added recovery of PG.However,concerns related to the PTEs'retention capacity and long-term effectiveness limit the implementation of this strategy.Furthermore,given that the large-scale demand for ordinary Portland cement from this conventional option has resulted in significant CO_(2) emissions,the technology has recently undergone additional scrutiny to meet the climate mitigation ambition of the Paris Agreement and China's Carbon Neutrality Economy.Therefore,we discuss the ways by which we can integrate innovative strategies,including supplementary cementitious materials,alternative binder solutions,CO_(2) mineralization,CO_(2) curing,and optimization of the supply chain for the profitability and sustainability of PG remediation.However,to maximize the co-benefits in environmental,social,and economic,future research must bridge the gap between the feasibility of expanding these advanced pathways and the multidisciplinary needs.

Ordered mesoporous materials for water pollution treatment:Adsorption and catalysis

To meet the growing emission of water contaminants,the development of new materials that enhance the efficiency of the water treatment system is urgent.Ordered mesoporous materials provide opportunities in environmental processing applications due to their exceptionally high surface areas,large pore sizes,and enough pore volumes.These properties might enhance the performance of materials concerning adsorption/catalysis capability,durability,and stability.In this review,we enumerate the ordered mesoporous materials as adsorbents/catalysts and their modifications in water pollution treatment from the past decade,including heavy metals(Hg^(2+),Pb^(2+),Cd^(2+),Cr^(6+),etc.),toxic anions(nitrate,phosphate,fluoride,etc.),and organic contaminants(organic dyes,antibiotics,etc.).These contributions demonstrate a deep understanding of the synergistic effect between the incorporated framework and homogeneous active centers.Besides,the challenges and perspectives of the future developments of ordered mesoporous materials in wastewater treatment are proposed.This work provides a theoretical basis and complete summary for the application of ordered mesoporous materials in the removal of contaminants from aqueous solutions.

The value of toxicological analysis in acute poisoning patients with uncertain exposure histories:a retrospective and descriptive study from an institute of poisoning

BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison exposure.The aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis perspective.METHODS:This was a retrospective and descriptive study from an institute of poisoning.Patient registration information and test reports spanning the period from April 1,2020 to March 31,2022,were obtained.Patients with uncertain exposure histories and who underwent toxicological analysis were included.Clinical manifestations and categories of toxics were analyzed.RESULTS:Among the 195 patients with positive toxicological analysis results,the main causes of uncertain exposure history was disturbance of consciousness(62.6%),unawareness(23.6%)and unwillingness or lack of cooperation(13.8%).The predominant clinical manifestations were disturbed consciousness(62.6%),followed by vomiting and nausea(14.4%)and liver function abnormalities(8.7%).A comparison of clinical manifestations between patients with positive and negative(n=99)toxicological analyses results revealed significantly different proportions of disturbances in consciousness(63%vs.21%),dizziness(1.5%vs.5.1%),multi-organ failure(1.5%vs.7.1%),and local pain(0 vs 4%).The main categories of substances involved were psychiatric medications(23.1%),sedatives(20.5%),insecticides(13.8%),and herbicides(12.8%).CONCLUSION:The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific,and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.

Health risk assessment of heavy metal pollution in groundwater of a karst basin,SW China

To investigate the presence of metal elements and assess their health risk for the populace in the Nandong Underground River Basin(NURB),we conducted an analysis of eleven common heavy metals in the water body.A Health risk assessment(HRA)model was employed to analyze 84 water samples from the NURB.The detection results revealed the following order of heavy metals concentrations:Fe>Al>Mn>Zn>As>Cd>Pb>Cr>Ni>Cu>Hg.Correlation analysis indicated a certain similarity in material source and migration transformation among these eleven metal elements.Our study identified that the health risks for local residents exposed to metal elements in the water of NURB primarily stem from carcinogenic risk(10^(−6)–10^(−4)a^(−1))through the drinking water pathway.Moreover,the health risk of heavy metal exposure for children through drinking water was notably higher than for adults.The maximum health risks of Cr in both underground and surface water exceeded the recommendation standard(5.0×10^(−5)a^(−1))from ICRP,surpassing the values recommended by the Swedish Environmental Protection Agency,the Dutch Ministry of Construction and Environment and the British Royal Society(5.0×10^(−6)a^(−1)).The results of the health risk assessment indicate that Cr in the water of NURB is the primary source of carcinogenic risk for local residents,followed by Cd and As.Consequently,it is imperative to control these three carcinogenic metals when the water was used as drinking water resource.

Transcription factor OsWRKY72 is involved in Cu/Cd toxicity by regulating lignin synthesis in rice

Maintenance of ion homeostasis in plant cells is an essential physiological requirement for sustainable growth,development,and yield of crops.Plants respond to high levels of heavy metals such as copper(Cu)and cadmium(Cd)to avoid irreversible damage at the structural,physiological and molecular levels.Our previous study found that rice germin-like proteins(OsGLPs)are a type of Cu-responsive proteins.The deletion of 10 tandem OsGLP genes on chromosome 8 led to more severe heavy metal toxicity in rice.In this study,we show that rice WRKY transcription factor OsWRKY72 negatively regulates OsGLP8-7transcription.Overexpression of OsWRKY72 weakens the Cu/Cd tolerance of rice when exposed to Cu and Cd.OsWRKY72 suppressed expression of OsGLP8-7 and lignin synthesis genes,resulting in reduced lignin polymerization and consequently lower lignin accumulation in cell walls,thereby increasing the Cu and Cd accumulation.In addition,OsWRKY53 bound to OsWRKY72 to alleviate the transcriptional inhibition of OsGLP8-7.These results revealed that OsWRKY72-OsGLP8-7 is an important module response of rice to heavy metal stress,and that transcription factor OsWRKY72 acts upstream of OsGLP8-7 to regulate Cu/Cd toxicity.

Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Fairy shrimp Branchinella kugenumaensis displays sensitivity to microplastic exposure

The increasing global concern regarding plastic pollution has prompted the research into the consequences of microplastics(MPs)on aquatic ecosystems.Fairy shrimp Branchinella kugenumaensis are freshwater planktonic organisms that have existed for 250 million years.This study aimed to uncover the harmful effects of MPs,with a particular focus on their size variations(0.1,1,and 5μm),on the fairy shrimp.We focused on how MPs could significantly affect the survival and growth of fairy shrimp.Notably,larger MPs,especially those measuring 5μm,caused higher mortality rates and hindered the growth compared to smaller ones.The impact of MPs continued even subsequent to depuration in clean water.The accumulation of MPs within the intestines of fairy shrimp resulted in intestinal blockages,disrupted excretory functions,and harmed intestinal epithelial cells.Examinations at the histological,cellular,and molecular levels showed that exposure to MPs triggered necroptosis in intestinal cells,accompanied by alterations in pathways related to transcription,translation,digestion,energy metabolism,and neurological functions.Furthermore,the effects of MPs on gene expression and pathways varied based on particle size,with larger MPs having a more significant effect and causing a strong response in xenobiotic biodegradation and metabolism pathways.We suggest that the increasing severity of MPs pollution could pose a significant threat to the survival of fairy shrimp.This study provided vital insights into the complex relationship between microplastics and aquatic organisms,and highlighted the urgent need to address the potential devastating impact of plastic pollution on freshwater ecosystems.Additionally,due to their rapid growth,strong reproductive capacity,sensitivity,and ease of cultivation,fairy shrimp hold the potential candidate to serve as a model organism for studying the effects of MPs and other pollutants on freshwater ecosystems.

Assessment of rehabilitation treatment for patients with acute poisoning-induced toxic encephalopathy

BACKGROUND:Poisoned patients often suffer damage to multiple systems,and those experiencing central nervous system disorders present more severe conditions,prolonged hospital stays,and increased mortality rates.We aimed to assess the efficacy of rehabilitation interventions for patients with toxic encephalopathy.METHODS:This retrospective,observational,comparative cohort study was performed at the teaching hospital affiliated of Nanjing Medical University,from October 2020 to December 2022.Patients who met the diagnostic criteria for toxic encephalopathy and exclusion criteria were included,and patients were divided into three subgroups according to Glasgow Coma Scale(GCS).Demographic and clinical characteristics were collected.The effect of the rehabilitation intervention on patients were assessed in the improvement of consciousness status(Glasgow Coma Scale[GCS]score),muscle strength and movement and swallowing function(Fugl-Meyer Assessment[FMA]scale,Water Swallow Test[WST],and Standardized Swallowing Assessment[SSA]).Subgroup analysis was based on different toxic species.RESULTS:Out of the 464 patients with toxic encephalopathy,184 cases received rehabilitation treatments.For the severe toxic encephalopathy patients,patients without rehabilitation intervention have a 2.21 times higher risk of death compared to patients with rehabilitation intervention(Hazard ratio[HR]=2.21).Subgroup analysis revealed that rehabilitation intervention significantly increased the survival rate of patients with pesticide poisoning(P=0.02),while no significant improvement was observed in patients with drug/biological agent poisoning(P=0.44).After rehabilitation intervention,significant improvement in GCS and FMA were observed in severe patients with toxic encephalopathy(P<0.01).CONCLUSION:Active rehabilitation intervention for patients exposed to poisons that can potentially cause toxic encephalopathy may improve the prognosis and reduce the mortality rate in clinical practice.

Preparation and interface state of phosphate tailing-based geopolymers

The long-term storage of phosphate tailings will occupy a large amount of land,pollute soil and groundwater,thus,it is crucial to achieve the harmless disposal of phosphate tailings.In this study,high-performance geopolymers with compressive strength of 38.8 MPa were prepared by using phosphate tailings as the main raw material,fly ash as the active silicon-aluminum material,and water glass as the alkaline activator.The solid content of phosphate tailings and fly ash was 60% and 40%,respectively,and the water-cement ratio was 0.22.The results of XRD,FTIR,SEM-EDS and XPS show that the reactivity of phosphate tailings with alkaline activator is weak,and the silicon-aluminum material can react with alkaline activator to form zeolite and gel,and encapsulate/cover the phosphate tailings to form a dense phosphate tailings-based geopolymer.During the formation of geopolymers,part of the aluminum-oxygen tetrahedron replaced the silicon-oxygen tetrahedron,causing the polycondensation reaction between geopolymers and increasing the strength of geopolymers.The leaching toxicity test results show that the geopolymer has a good solid sealing effect on heavy metal ions.The preparation of geopolymer from phosphate tailings is an important way to alleviate the storage pressure and realize the resource utilization of phosphate tailings.

Environmental concentration of ammonia nitrogen induced marked changes in proteome of clam Ruditapes philippinarum in dose-and time-dependent manner

Previous studies have revealed that ammonia nitrogen has several adverse effects on clam Ruditapes philippinarum.However,knowledge is lacking regarding the related proteins involved in the toxicological responses,which is vital to elucidate the underlying mechanism of ammonia nitrogen.In this study,clams R.philippinarum were exposed to ammonia nitrogen for 21 d at two environmentally relevant concentrations.The tandem mass tags approach(TMT)was applied to assay the differentially expressed proteins(DEPs)in clam gill tissues on the 3 rd and 21 st day.Finally,a total of 7263 proteins were identified.Bioinformatics analyses revealed that clam protein profiles changed in dose-and time dependent manner after ammonia nitrogen exposure.We inferred that the clams may face heavy challenges after ammonia exposure,such as unbalanced gender ratio,lysosomal disease,energy lack,neurological disorders,altered glutamine metabolism,increased lipid synthesis,and impaired immunity.Variation profiles of enzyme activities of glutaminase and glutamine synthase provided direct evidence to verify the related inference from proteome data.Most of the inferred toxic effects merit further study.This study identified important proteins related to ammonia nitrogen toxicity in the clam and indicated the severe stress of marine ammonia pollution on the healthy development of mollusc aquaculture.

Dietary exposure to sulfamethazine,nanoplastics and their binary mixture disrupts the spermatogenesis of marine medaka(Oryzias melastigma)

In the coastal environment,the co-occurrence of antibiotic and nanoplastic pollution is common.Investigating their individual and combined toxicity to marine organisms is of great necessity.In the present study,the reproductive toxicity of sulfamethazine(SMZ)and nanoplastics(polystyrene,PS)via the dietary route on the spermatogenesis of marine medaka(Oryzias melastigma)was examined.After 30 d of dietary exposure,SMZ alone decreased the gonadosomatic index(GSI)value(~35%)and the proportion of undifferentiated type A spermatogonia(A_(und))(~40%),probably by disrupting the testicular sex hormone production,the spermatogenesis-related growth factor network and the balance of apoptosis.Individual exposure to PS did not affect the GSI value or the proportions of germ cells at different developmental stages,but dysregulated the expression of several spermatogenesis-related genes.Interestingly,the presence of PS alleviated the decreased GSI value caused by SMZ.This alleviation effect was achieved by enhancing the spermatogonia differentiation instead of reversing the suppressed self-renewal of A_(und),suggesting that the mixture of PS and SMZ could cause reproductive effects in a different way.These findings expand our knowledge of threats of ubiquitous antibiotic and nanoplastic pollution to fish reproduction and population.

Levisticum officinale extract protects against CCl4-induced hepatotoxicity through anti-inflammatory,anti-fibrotic,and antioxidant properties in rats

Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity.Methods:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then rats received a single dose of CCl4(2.5 mL/kg,50%v/v in liquid paraffin).Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and architecture.Moreover,antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were measured.Results:Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure,improved serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea,total bilirubin,and total protein,enhanced glutathione content and superoxide dismutase and catalase activities in the liver,as well as decreased plasma and hepatic malondialdehyde levels.Immunohistochemical results demonstrated that the extract reduced Ki-67 andα-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale extract.Moreover,Levisticum officinale extract markedly decreased the gene expressions of TNF-α,IL-6,TGF-β1,MCP-1,and COX-2.Conclusions:Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant,anti-inflammatory,and anti-fibrotic activities.