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.

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.

EFFECTS OF A TOXICANT ON A SINGLE-SPECIES POPULATION WITH PARTIAL POLLUTION TOLERANCE IN A POLLUTED ENVIRONMENT

We study a model for the long-term behavior of a single-species population with some degree of pollution tolerance in a polluted environment. The model consists of three ordinary differential equations： one for the population density, one for the amount of toxicant inside the living organisms, and one for the amount of toxicant in the environment. We derive sufficient conditions for the persistence and the extinction of the population depending on the exogenous input rate of the toxicant into the environment and the level of pollution tolerance of the organisms. Numerical simulations are carried out to illustrate our main results.

EFFECTS OF TOXICANTS ON CHEMTAT MODELWITH TIME VARIABLE NUTRIENT INPUT ANDWASHOUT

The influence of toxicants on the competition of n populations for time variablenutriellt input rate and time variable washout rate in a chemostat model is investigated.After proving some qualitative properties of the solutions, the threshold between persistence and extinction of the populations has been obtained.

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.

Periodicity in a “Food-limited” Population Model with Toxicants and Time Delays

With the help of a continuation theorem based on Gaines and Mawhin's coincidence degree, we study the global existence of positive periodic solutions of a 'food-limited' population model with toxicants and time delays. Some new results are obtained.

Detection of tris-(2, 3-dibromopropyl) isocyanurate as a neuronal toxicant in environmental samples using neuronal toxicity-directed analysis

Neuronal toxic pollutants in environment possess hazards to human health. It is essential to determine the causative neuronal toxicants in environmental samples. In the present study, viability of primary cultured cerebellar granule neurons (CGNs), combined with sample extraction, chemical fractionation and identification, was applied for screening acid-resistant neuronal toxic substances in environmental samples. River sediments and agricultural soils along the river near a brominated flame retardant (BFR) manufacturing plant in South China were collected to screen the key neuronal toxicants. The results indicated that the manufacturing plant was a source of neuronal toxicity risks. In the sediment and soil near the plant, one of the causative toxicants was identified as tris-(2,3-dibromopropyl) isocyanurate (TBC) using HPLC-MS/MS. In addition, an unknown chemical possibly causing significant neuronal toxicity was isolated from all the soil samples in the region.

Urgently reveal longly hidden toxicant in a familiar fabrication process of biomass-derived environment carbon material

Biomass-derived N-doped carbon(BNC)is an important environmental material and widely used in the fields of water purification and soil remediation.However,the toxicant in the commonly used synthesis process of BNC materials have been largely ignored.Herein,we firstly report the presence of a highly toxic by-product(KCN)in the activation process of BNC materials consequential of the carbothermal reduction reaction.Because this carbothermal reduction reaction also regulates the N-doping and pore development of BNC materials,the KCN content directly relates with the properties of BNC material properties.Accordingly,a high KCN content(-611 mg)can occur in the production process of per g BNC material with high specific surface area(-3600 m^2/g).Because the application performance of BNC material is determined by the surface area and available N doping,therefore,production of a BNC material with high performance entails high risk.Undoubtedly,this study proves a completely new risk recognition on a familiar synthesis process of biomass-based material.And,strict protective device should be taken in fabrication process of biomass-derived carbon material.

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.

信息型常见毒物质谱用户库的建立及其在毒物快速筛选上的应用研究

The spectrum user’s librarys containing 1533 familiar toxicants have been built; A method with high separability and sensitivity has been found,The RT and the detection limit of 210 familiar abuse drugs has been confirmed; the processing methods to analyse spectrum data automatically have been found; It is simple,quick,sensitive and reliable,and can take place of manual operation,It is very useful to screen the familiar toxicants in unkown sample.

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.

Occurrence of microcystins in water,sediment,and aquatic animals in Dau Tieng Reservoir,Vietnam

This study investigates the variations of microcystins(MCs)in water,cyanobacterial blooms,sediment,and aquatic organisms collected from the Dau Tieng Reservoir(DTR).Vietnam.Highperformance liquid chromatography(HPLC)was employed to measure MC concentrations in various target samples.Results indicate that Microcystis spp.dominates as the primary MC producer in the DTR.The average concentrations of analyzed MCs in surface water ranged from 1.10 to 5.54μg/L,temporally and spatially.In sediment,average concentrations varied from 0.15 to 1.13μg/g wet weight(WW)temporally and from 0.41 to 0.72μg/g WW spatially.MCs were detected in different organs of fish species(Oreochromis sp.and Labiobarbus sp.)and in the entire soft tissues of bivalve(Corbicula sp.)and gastropod(Assiminea sp.).The highest observed MC concentration in July was 0.83±0.22μg/g WW in the intestines of fish Oreochromis sp.The presence of MCs in grass shrimp Palaemonetes sp.was observed solely in June,reaching a concentration of 0.28±0.19μg/g WW.This is the first report of MC accumulation in the grass shrimp Palaemonetes sp.during field collection.For the bivalve Corbicula sp.,the presence of analyzed MCs was consistent throughout the study period,except for March and September,with the highest concentrations in July at 0.77±0.1μg/g WW.Pearson correlation analysis revealed significant positive correlations between MCs in water and sediment with MC concentrations in aquatic animals,indicating the potential transfer of MCs across different trophic levels.The estimated daily intake values for analyzed MCs indicate that fish collected from the DTR are considered safe for consumption,as long as only the edible organs,such as the muscle,are consumed.However,bivalves or gastropods collected from the DTR are not safe for human consumption.This study underscored the importance of monitoring MC accumulation in aquatic animals used as food to mitigate adverse effects on human health.

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.