Preliminary Validation of Tumor Cell Attachment Inhibition Assay for Developmental Toxicants With Mouse S180 Cells

This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.

Reversion Mutation in Dark Variants of Luminous Bacteria and Its Application in Gene Toxicant Monitoring

The luminous intensity of dark variant (S1) separated from photobacterium phosph oreum (A2) was 1/10 000 less than that of wild type. Ethidium bromide (EB) (0.6 mg/L), Mytomycin C (MC, 0.05 mg/L), 2 amino fluorene (2 AF, 1.0 mg/L) all cou ld strongly induce reversion mutation for S1 within 24 h and increase reversion ratio significantly. The results of experiments indicated that these revertants had stable genetic characteristic and the mutation may take place at gene levels . The mutagenesis to S1 caused by EB, MC and 2 AF was detected and it may be us ed as a new rapid, simple and sensitive method for gene toxicant monitoring.

Effect of Certain Toxicants on Gonadotropin-Induced Ovarian Non-Esterified Cholesterol Depletion and Steroidogenic Enzyme Stimulation of the Common Carp Cyprinus carpio in vitro

Isolated ovarian tissues from the common carp, Cyprinus carpio were incubated in vitro to obtain a discrete effect of four common toxicants of industrial origin, namely phenol, sulfide, mercuric chloride and cadmium chloride, on gonadotropin-induced alteration of nonesterified and esterified cholesterol and steroidogenic enzymes, △5-3β-HSD and 17β-HSD activity. Stage II ovarian tissue containing 30-40% mature oocytes were shown to be most responsive to gonadotropins in depleting only nonesterified cholesterol moiety and stimulating the activity of both. Safe doses of above mentioned toxicants when added separately to stage II ovarian tissue with oLH (1 μg/incubation) gonadotropin-induced depletion of nonesterified cholesterol and gonadotropin-induced stimulation of the activity of both enzymes was significantly inhibited. Esterified cholesterol remained almost unaltered. Findings clearly indicate the impairment of gonadotropin induced fish ovarian steroidogenesis by the four toxicants separately.

Dynamical Analysis of a Stochastic Predator-Prey System with Lévy Noise and Impulsive Toxicant Input

This paper established a modified Leslie-Gower and Holling-type IV stochastic predator-prey model with Lévy noise and impulsive toxicant input. We study the stability in distribution of solutions by inequality techniques and ergodic method. By comparison method and Itô’s formula, we obtain the sufficient conditions for the survival of each species. Some numerical simulations are introduced to show the theoretical results.

Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem （ES） cells and induced pluripotent stem （iPS） cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem （AFS） ceils as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.

From Environmental Toxicants to Antibacterial Agents:BPA Analogues Selectively Inhibit the Growth of Gram-Positive Bacteria by Disturbing Biosynthesis of the Cell Wall

Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previous studies.However,the toxic effects of the compounds as environmental contaminants on the endocrine system limited their applications in the field of medicine and health.Given the abuse of antibiotics has led to the emergence of multiple super-resistant bacteria,we considered that structural modifications based on the BPA structure will be available for molecular designing of potential antimicrobial agents without drug resistance.In this study,to further improve the antibacterial activity and reduce the biological toxicity,we performed the computational models to evaluate the binding affinities of BPA analogues to the potential target DltA protein in the biosynthesis of cell wall.A series of synthesized achiral analogues ofα,α,α′-tris(4-hydroxyphenyl)-1-ethyl-4-isopropylbenzene(α,α,α′-TEIB)exhibited low minimum inhibitory concentration against Sa25923 and MRSA(2 or 1μg mL−1).Especially,the analogue A4 did not induce the drug-resistant mutants for all tested Gram-positive bacterial strains and exhibited relatively lower cytotoxicity in HepG2 cells.The developed classification model based on the light gradient boosting algorithm showed the superior performances on the internal robustness and generalization ability for the ligand-based virtual screening of bisphenol and polyphenol antimicrobial substances.Collectively,our findings suggest that the molecular structure ofα,α,α′-TEIB is promising as a scaffold,which is expected to achieve a breakthrough in the development of antibiotics which can prevent the invasion of MRSA and other super bacteria.

Food nutrition and toxicology targeting on specific organs in the era of single-cell sequencing

Due to the complex natures of dietary food components,it is difficult to elucidate how the compounds affect host health.Dietary food often selectively presents its mechanism of action on different cell types,and participates in the modulation of targeted cells and their microenvironments within organs.However,the limitations of traditional in vitro assays or in vivo animal experiments cannot comprehensively examine cellular heterogeneity and the tissue-biased influences.Single-cell RNA sequencing(sc RNA-seq)has emerged as an indispensable methodology to decompose tissues into different cell types for the demonstration of transcriptional profiles of individual cells.Sc RNA-seq applications has been summarized on three typical organs(brain,liver,kidney),and two representative immune-and tumor related health problems.The everincreasing role of sc RNA-seq in dietary food research with further improvement can provide sub-cellular information and the coupling between other cellular modalities.In this review,we propose utilizing sc RNAseq to more effectively capture the subtle and complex effects of food chemicals,and how they may lead to health problems at single-cell resolution.This novel technique will be valuable to elucidate the underlying mechanism of both the health benefits of food nutrients and the detrimental consequences food toxicants at the cellular level.

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.

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.

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.

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.

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.

Design of AI-Enhanced and Hardware-Supported Multimodal E-Skin for Environmental Object Recognition and Wireless Toxic Gas Alarm

Post-earthquake rescue missions are full of challenges due to the unstable structure of ruins and successive aftershocks.Most of the current rescue robots lack the ability to interact with environments,leading to low rescue efficiency.The multimodal electronic skin(e-skin)proposed not only reproduces the pressure,temperature,and humidity sensing capabilities of natural skin but also develops sensing functions beyond it—perceiving object proximity and NO2 gas.Its multilayer stacked structure based on Ecoflex and organohydrogel endows the e-skin with mechanical properties similar to natural skin.Rescue robots integrated with multimodal e-skin and artificial intelligence(AI)algorithms show strong environmental perception capabilities and can accurately distinguish objects and identify human limbs through grasping,laying the foundation for automated post-earthquake rescue.Besides,the combination of e-skin and NO2 wireless alarm circuits allows robots to sense toxic gases in the environment in real time,thereby adopting appropriate measures to protect trapped people from the toxic environment.Multimodal e-skin powered by AI algorithms and hardware circuits exhibits powerful environmental perception and information processing capabilities,which,as an interface for interaction with the physical world,dramatically expands intelligent robots’application scenarios.

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.

Rapid detection and risk assessment of soil contamination at lead smelting site based on machine learning

A general prediction model for seven heavy metals was established using the heavy metal contents of 207soil samples measured by a portable X-ray fluorescence spectrometer(XRF)and six environmental factors as model correction coefficients.The eXtreme Gradient Boosting(XGBoost)model was used to fit the relationship between the content of heavy metals and environment characteristics to evaluate the soil ecological risk of the smelting site.The results demonstrated that the generalized prediction model developed for Pb,Cd,and As was highly accurate with fitted coefficients(R^(2))values of 0.911,0.950,and 0.835,respectively.Topsoil presented the highest ecological risk,and there existed high potential ecological risk at some positions with different depths due to high mobility of Cd.Generally,the application of machine learning significantly increased the accuracy of pXRF measurements,and identified key environmental factors.The adapted potential ecological risk assessment emphasized the need to focus on Pb,Cd,and As in future site remediation efforts.