Metallothionein 1E Alleviates Cadmium-induced Renal Cytotoxicity through Promoting Mitochondrial Functional Recovery

The pervasive utilization of industrial substances has escalated human exposure to cadmium(Cd),a metal associated with long-term negative health outcomes such as renal dysfunction,neurological disorders,and various cancers^([1]).Once ingested by humans,Cd interacts with cysteine-rich metallothioneins(MTs)which have metal-binding and antioxidant properties and is subsequently transported to the kidney^([2]).

Protective effect of resveratrol against cadmium-induced toxicity on ovine oocyte in vitro maturation and fertilization

Background:Heavy metal cadmium(Cd)is a widespread environmental contaminant with a potential toxicity that might negatively affect female reproduction and fertility.It has been reported that Cd exposure impaired the quality of oocytes and led to a defective maturation and fertilization,through oxidative stress induction.Resveratrol(Res)is a natural polyphenol with strong antioxidant properties that exhibited protective role in preventing oocyte redox homeostasis disruption and quality decline.Here,we explored whether the addition of Res to in vitro maturation(IVM)medium might act as a protection against Cd-induced toxicity on ovine oocyte maturation and fertilization.Firstly,we evaluated the effect of supplementing IVM medium with two different Res concentrations(1and 2μmol/L)on nuclear maturation and fertilization of oocytes matured under CdCl2(2μmol/L)exposure.Therefore,the concentration of 1μmol/L Res was selected to analyse the effects of this compound on intracellular ROS levels,mitochondrial(mt)distribution and activity,chromatin configuration,cytoskeleton morphology,cortical granules(CGs)distribution and mRNA expression of genes associated with cellular response to oxidative stress(i.e.SIRT1,SOD 1,GPX1,GSR,CAT)in Cd-exposed in vitro matured oocytes.Results:We found that 1μmol/L Res restored the reduced oocyte meiotic competence induced by Cd exposure as well as,Res sustained oocyte ability to be normally fertilized and decreased polyspermic fertilization at both tested concentrations.Moreover,we demonstrated that 1μmol/L Res mitigated Cd-induced alterations of oocyte cytoplasmic maturation by reducing reactive oxygen species(ROS)accumulation,preventing mt dysfunction,maintaining the correct meiotic spindle and cortical F-actin assembly and the normal cortical granule distribution as well as up-regulating SIRT1,SOD1 and GPX1 genes.Conclusions:Taken together,our findings highlighted the beneficial influence exerted by Res in preventing Cdinduced disturbance of nuclear and cytoplasmic maturation and subsequent fertilization in ovine oocytes.Res treatment may help to establish defence strategies counteracting Cd-induced toxicity on the female gamete.

TOX介导T细胞耗竭的机制及其逆转研究

胸腺细胞选择相关的高迁移率族蛋白(TOX)是一种与DNA结合的转录因子,参与免疫细胞的发育过程。TOX是促进T细胞耗竭的关键转录因子,并与肿瘤的发生发展密切相关,提示TOX可能是潜在的免疫生物标志物和恶性肿瘤免疫治疗的靶点。本文就TOX介导T细胞耗竭的分子机制及其逆转研究的最新进展做一综述,为设计基于TOX更为精准的肿瘤免疫治疗策略提供依据。

Putrescine Modulates Cadmium Fixation Ability of Cell Wall to Decrease Cadmium Accumulation in Rice,a Process Might Depend on Nitric Oxide

Although putrescine(PUT)has been linked to plants'responses to cadmium(Cd)stress,the exact mechanism is still elusive.In the current investigation,the endogenous PUT concentration in rice roots was enhanced by Cd stress.Exogenous PUT increased root cell wall hemicellulose levels,which in turn increased its Cd binding capacity,concurrently decreasing the transcription level of genes such as OsNRAMP1 and OsCd1 that are responsible for root Cd absorption.As a result。

Combined Effect of Temperature and Cadmium on Molecular Responses of Hsp70 and P-gp Genes in Crassostrea gigas

To evaluate the combined effect of temperature and cadmium on the molecular responses of heat shock protein 70(hsp70)and P-glycoprotein(P-gp)in mantle,digestive gland and gills of Crassostrea gigas,oysters were exposed to combinations of five temperature levels(10,15,20,25,and 30℃)and 10μg L^(-1)cadmium for 21 days.Oysters were sampled for mRNA quantification by qPCR,and the results showed that the P-gp gene expression changed significantly after treatment at different temperatures and different treatment times.The P-gp gene expression was the highest in the digestive gland.Compared with the control group,the P-gp gene expression in cadmium treatment groups at all the different temperatures were significantly higher than the control group.The control oysters(kept at 10℃during the whole experiment without cadmium)expressed low levels of hsp70,but the groups treated with cadmium displayed somewhat higher levels.The present study demonstrated hsp70 and P-gp played an important role in the detoxification of Cd in C.gigas,and confirmed temperature should be considered for the assessment of Cd-induced toxicity in oysters.

Appropriate Supply of Ammonium Nitrogen and Ammonium Nitrate Reduces Cadmium Content in Rice Seedlings by Inhibiting Cadmium Uptake and Transport

Reasonable nitrogen(N) application is a promising strategy for reducing crop cadmium(Cd) toxicity. However, the specific form of N and the required amount that affect Cd tolerance and accumulation in rice remain unclear. This study explored the influence of different N-fertilizer forms(NH_(4)NO_(3), NH_4Cl, and KNO_(3)) and dosages on Cd tolerance and uptake in Cd-stressed N-sensitive and N-insensitive indica rice accessions. The results indicated that the Cd tolerance of N-sensitive indica accessions is more robust than that of N-insensitive ones. Furthermore, the shoot Cd content and Cd translocation rate in both N-sensitive and N-insensitive indica accessions decreased with an appropriate supply of NH_(4)NO_(3) and NH_4Cl, whereas they were comparable or slightly increased with increased KNO_(3). Unfortunately, we did not find significant and regular differences in Cd accumulation or translocation between N-sensitive and N-insensitive rice accessions. Consistent with the reduction of shoot Cd content, the addition of NH_(4)NO_(3) and NH_4Cl also inhibited the instantaneous root Cd^(2+) uptake. The expression changes of Cd transport-related genes under different N forms and dosages suggested that the decreased shoot Cd content, caused by the increased supply of NH_(4)NO_(3) and NH_4Cl, is likely achieved by reducing the transcription of OsNRAMP1 and OsIRT1. In summary, our findings reveal that an appropriate supply of NH_(4)NO_(3) and NH_4Cl could reduce Cd uptake and transport in rice seedlings, suggesting that rational N management could reduce the Cd risk in rice production.

Tissue distribution of cadmium and its effect on reproduction in Spodoptera exigua

Vegetable fields are often contaminated by heavy metals,and Spodoptera exigua is a major vegetable pest which is stressed by heavy metals mainly by feeding.In this study,cadmium accumulation in the tissues of S.exigua exposed to cadmium and its effects on the growth and development of the parents and the offspring were investigated.Under the stress of different concentrations of cadmium(0.2,3.2,and 51.2 mg kg^(-1)),the cadmium content in each tissue of S.exigua increased in a dose-dependent manner.At the larval stage,the highest cadmium accumulation was found in midgut in all three cadmium treatments,but at the adult stage,the highest cadmium content was found in fat body.In addition,the cadmium content in ovaries was much higher than in testes.When F1S.exigua was stressed by cadmium and the F_(2)generation was not fed a cadmium-containing diet,the larval survival,pupation rate,emergence rate and fecundity of the F_(2)generation were significantly reduced in the 51.2 mg kg^(-1)treatment compared to the corresponding F1generation.Even in the F_(2)generation of the 3.2 mg kg^(-1)treatment,the fecundity was significantly lower than in the parental generation.The fecundity of the only-female stressed treatment was significantly lower than that of the only-male stressed treatment at the 3.2 and 51.2 mg kg^(-1)cadmium exposure levels.When only mothers were stressed at the larval stage,the fecundity of the F_(2)generation was significantly lower than that of the F1generation in the 51.2 mg kg^(-1)treatment,and it was also significantly lower than in the 3.2 and 0.2 mg kg^(-1)treatments.The results of our study can provide useful information for forecasting the population increase trends under different heavy metal stress conditions and for the reliable environmental risk assessment of heavy metal pollution.

Detoxification strategy of Microcystis aeruginosa to the toxicity of Cd(Ⅱ):role of EPS in alleviating toxicity

Although many studies have found that cadmium(Cd)can be toxic to microalgae,only a few reports focused on the role of extracellular polymeric substances(EPS)in Cd(Ⅱ)detoxification.The biochemical and physiological endpoints of Microcystis aeruginosa,including the composition and functional groups of soluble EPS(SL-EPS),loosely bound EPS(LB-EPS),and tightly bound EPS(TB-EPS),were detected to elucidate the toxicity and detoxification mechanisms of Cd(Ⅱ)for cyanobacteria.Toxicological and physiological assays on M.aeruginosa showed that the 0.25-mg/L Cd(Ⅱ)resulted in a larger inhibition on growth and F_(v)/F_(m).Nevertheless,Cd(Ⅱ)significantly induced much higher contents of superoxide dismutase(SOD),intracellular microcystin LR(MC-LR),extracellular MC-LR,and EPS.Scanning electron microscopy with energy dispersive X-ray spectroscopy confirmed that Cd(Ⅱ)was absorbed into the EPS layer.Fourier transform infrared spectrum analysis revealed that the functional groups bound with Cd(Ⅱ)of algae biomass,SL-EPS,LB-EPS,and TB-EPS were somewhat different.The C=O/C=N groups ofδ-lactam or protein were their prominent functional groups,suggesting that amide or proteins in the EPS played a key role in the adsorption in Cd(Ⅱ).The concentration of 0.25 mg/L of Cd(Ⅱ)may change the chemical structure of EPS by altering the production of protein-like substances containing tryptophan.This study indicated that M.aeruginosa could detoxify Cd(Ⅱ)stress via induction of antioxidant capacity(higher SOD activity and MC synthesis),EPS production,and modification in chemical structure of EPS.

Advances in Understanding Cadmium Stress and Breeding of Cadmium-Tolerant Crops

Cadmium(Cd) pollution has emerged as a critical global environmental concern, due to its significant toxicity, environmental persistence, and the pervasiveness of contamination. Significantly, the bioaccumulation of Cd in agricultural crops constitutes a primary vector for its entry into the human diet. This issue warrants urgent attention from both the scientific community and policymakers to develop and implement effective mitigation strategies. This review delves into the physiological impacts of Cd stress on plants, including the suppression of photosynthetic activity, amplification of oxidative stress, and disruptions in mineral nutrient homeostasis. Additionally, the resistance mechanisms deployed by plants in response to Cd stress have been explored, and the prospective contributions of molecular breeding strategies in augmenting crop tolerance to Cd and minimizing its bioaccumulation have been assessed. By integrating and analyzing these findings, we seek to inform future research trajectories and proffer strategic approaches to enhance agricultural sustainability, safeguard human health, and protect environmental integrity.

Optimized silicon fertilization regime weakens cadmium translocation and increases its biotransformation in rice tissues

In acidic paddy fields of South China,rice(Oryza sativa L.)faces the dual challenges of cadmium(Cd)toxicity and silicon(Si)deficiency.Although previous studies have highlighted the functions of Si application timing and strategies in mitigating Cd-stressed rice,the precise mechanisms underlying the health restoration of Cd-toxic rice and the assurance of grain safety remain elusive.This study explored Cd translocation and detoxification in the shoots of rice regulated by various Si fertilization regimes:Si(T)(all Si added before transplanting),Si(J)(all Si added at jointing),and Si(TJ)(half Si added both before transplanting and at jointing).The findings revealed that the regime of Si(TJ)was more beneficial to rice health and grain safety than Si(T)and Si(J).The osmotic regulators such as proline,soluble sugars,and soluble proteins were significantly boosted by Si(TJ)compared to other Si treatments,and which enhanced membrane integrity,balanced intracellular pH,and increased Cd tolerance of rice.Furthermore,Si(TJ)was more effective than Si(T)and Si(J)on the Cd sequestration in the cell wall,Cd bio-passivation,and the down-regulated expression of the Cd transport genes.The concentrations of Cd in the xylem and phloem treated with Si(TJ)were reduced significantly.Additionally,Si(TJ)facilitated much more Cd bound with the outer layer proteins of grains,and promoted Cd chelation and complexation by phytic acid,phenolics,and flavonoids.Overall,Si(TJ)outperformed Si(T)and Si(J)in harmonizing the phycological processes,inhibiting Cd translocation,and enhancing Cd detoxification in rice plant.Thereby the split Si application strategy offers potential for reducing Cd toxicity in rice grain.

Effects of In-Situ Cadmium Exposure on Morphometric Indices of Anabas testudineus

Anthropogenic activities have greatly affected water resources on a global scale where the world is experiencing water quality and resources issues. Heavy metal is a crucial group of pollutants that is toxic to the environment even at low concentrations due to its bioaccumulation and biomagnification capabilities in living organisms. The detrimental effects of heavy metals on living organisms are due to their bioaccumulation in the aquatic ecosystem. Cadmium may result in adverse health effects due to its high toxicity. The study is conducted to determine the cadmium exposure effects on the morphometric indices of Anabas testudineus which are the Scaling Coefficient (SC) and Condition Factor (K) of such species. Anabas testudineus is exposed to four different cadmium treatment groups namely the control group, cadmium treatment group of 0.005 mg/L, 0.010 mg/L, and 0.015 mg/L for 16 weeks. The findings of the study have reported inconsistent trends in the values of SC and a decrease in the value of K with increasing cadmium concentration. The trend for the average SC has shown an overall decrease in value while the pattern of the K value is inconsistent in each treatment group with exposure time. Collectively, no significant differences for SC and K of A. testudineus in different treatment groups as well as comparison between treatment groups with time exposure.

Causal Analysis Between Rice Growth and Cadmium Accumulation and Transfer under Arbuscular Mycorrhizal Inoculation

Cadmium(Cd)contamination in rice has been a serious threat to human health.To investigate the effects of arbuscular mycorrhizal fungi(AMF)on the Cd translocation in rice,a controlled pot experiment was conducted.The results indicated that AMF significantly increased rice biomass,with an increase of up to 40.0%,particularly in root biomass by up to 68.4%.Notably,the number of prominent rice individuals also increased,and their plasticity was enhanced following AMF inoculation.AMF led to an increase in the net photosynthetic rate and antioxidant enzyme activity of rice.In the AMF treatment group,the Cd concentration in the rice roots was significantly higher(19.1%‒68.0%)compared with that in the control group.Conversely,the Cd concentration in the rice seeds was lower in the AMF treatment group,indicating that AMF facilitated the sequestration of Cd in rice roots and reduced Cd accumulation in the seeds.Path coefficients varied across different treatments,suggesting that AMF inoculation reduced the direct impact of soil Cd concentration on the total Cd accumulation in seeds.The translocation of Cd was consistently associated with simultaneous growth dilution and compensatory accumulation as a result of mycorrhizal effects.Our study quantitatively analyzed this process through path analysis and clarified the causal relationship between rice growth and Cd transfer under the influence of AMF.

A monolithic integrated medium wave Mercury Cadmium Telluride polarimetric focal plane array

A medium wave(MW)640×512(25μm)Mercury Cadmium Telluride(HgCdTe)polarimetric focal plane array(FPA)was demonstrated.The micro-polarizer array(MPA)has been carefully designed in terms of line grating structure optimization and crosstalk suppression.A monolithic fabrication process with low damage was explored,which was verified to be compatible well with HgCdTe devices.After monolithic integration of MPA,NETD<9.5 mK was still maintained.Furthermore,to figure out the underlying mechanism that dominat⁃ed the extinction ratio(ER),specialized MPA layouts were designed,and the crosstalk was experimentally vali⁃dated as the major source that impacted ER.By expanding opaque regions at pixel edges to 4μm,crosstalk rates from adjacent pixels could be effectively reduced to approximately 2%,and promising ERs ranging from 17.32 to 27.41 were implemented.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Phytotoxicity of cadmium on protein, proline and antioxidant enzyme activities in growing Arachis hypogaea L. seedlings

Phytotoxicity of cadmium on growing Arachis hypogaea L. seedlings was studied. Seeds were exposed to 25, 50, and 100 μmol/L CdCl2 concentrations, for a period of 10, 15, 20 and 25 d. The extent of damage to chlorophyll, protein, proline, nitrate and nitrite reductase, antioxidant enzyme activity in leaves and roots were evaluated after 10 d of cadmium stress. The higher concentration of cadmium （100 μmol/L） resulted （leaves and roots） total chlorophyll 91.01%, protein 79.51%, 83.61%, nitrate reductase 79.39%, 80.72% and nitrite reductase 77.07%, 75.88% activity decreased with increase in cadmium concentrations and exposure periods. Cadmium caused significant changes in the activity of antioxidative enzymes. Contrastingly Cd treated plant tissues showed an increase in proline 159.87%, 239.6%, gluthion reductase （GR） 337.72%, 306.14%, superoxide disumutase （SOD） 688.56%, 381.72%, ascorbate peroxidase （APX） 226.47%, 252.14%, peroxidase （POD） 72.19%, 60.29% and catalase （CAT） 228.96%, 214.74% as compared to control. Cadmium stress caused a significant increase in the rate of SOD activity in leaves and roots of plant species. Results show the crop A. hypogaea is highly sensitive even at very low cadmium concentrations.

Variation of Cd concentration in various rice cultivars and derivation of cadmium toxicity thresholds for paddy soil by species-sensitivity distribution

It is imperative to derive an appropriate cadmium (Cd) health risk toxicity threshold for paddy soils to ensure the Cd con-centration of rice grains meet the food safety standard. In this study, 20 rice cultivars from the main rice producing areas in China were selected, and a pot-experiment was conducted to investigate transformation of Cd in paddy soil-rice system with 0 (CK), 0.3 mg kg–1 (T1) and 0.6 mg kg–1 (T2) Cd treatments in greenhouse. The results showed that Cd concentrations of rice grains existed signiifcant difference (P<0.05) in 20 rice cultivars under the same Cd level in soil. The Cd concentrations of rice grains of the CK, T1 and T2 treatments were in the range of 0.143–0.202, 0.128–0.458 and 0.332–0.806 mg kg–1, respectively. Marked differences of the ratios of Cd concentration for soil to rice grain (BCFs) and transfer factors (TFs, root to grain and straw to grain) among the tested cultivars were observed in this study. The bioconcentration factors (BCFgrain) and TFs of the 20 rice cultivars were 0.300–1.112 and 0.342–0.817, respectively. The TFs of Cd from straw to grain ranged from 0.366 to 1.71, with signiifcant differences among these 20 rice cultivars. The bioconcentration factors (BCFgrain) and TFs among the 20 rice cultivars ranged from 0.300–1.112 and 0.342–0.817, respectively. The species-sensitivity distribu-tion (SSD) of Cd sensitivity of the rice species could be iftted wel with Burr-III (R2=0.987) based on the data of BCFs. The toxicity threshold of Cd derived from SSD for the paddy soil was 0.507 mg kg–1 in the present study.

Ecological toxicity of reactive X-3B red dye and cadmium acting on wheat (Triticum aestivum)

Ecological toxicity of reactive X\|3B red dye and cadmium in both their single form and their combined form on wheat was studied using the experimental method of seed and root exposure. The single factor exposure indicated that the inhibitory rate of wheat root elongation was significantly increased with the increase in the concentration of the dye in the cultural solution, although seed germination of wheat was not sensitive to the dye. The toxicity of cadmium was greatly higher than that of the dye, but low concentration cadmium (<40 mg/L) could promote the germination of wheat seed. Interactive effects of the dye and cadmium on wheat were complicated. There was no significant correlation between the inhibitory rate of seed germination and the concentrations of the dye and cadmium. Low concentration cadmium could strengthen the toxicity of the dye acting on root elongation. On the contrary, high concentration cadmium could weaken the toxicity of the dye acting on root elongation.

Interactions of cadmium and aluminum toxicity in their effect on growth and physiological parameters in soybean

The effect of Al and Cd on the growth, photosynthesis, and accumulation of Al, Cd and plant nutrients in two soybean genotypes were determined using hydroponic culture. There were six treatments: pH 6.5; pH 4.0; pH 6.5+1.0 μmol/L Cd; pH 4.0+1.0 μmol/L Cd; pH 4.0+150 μmol/L Al; pH 4.0+1.0 μmol/L Cd+150 μmol/L Al. The low pH (4.0) and Al treatments caused marked reduction in root length, shoot height, dry weight, chlorophyll content (SPAD value) and photosynthetic rate. Al-sensitive cv. Zhechun 2 accumulated comparatively more Al and Cd in plants than Al-tolerant cv. Liao 1. Compared with pH 6.5, pH 4.0 resulted in significant increase in Cd and Al concentration in plants. Combined application of Cd and Al enhanced their accu-mulation in roots, but caused a reduction in shoots. The concentrations of all 10 nutrients (P, K, Ca, Mg, Fe, Mn, Cu, Zn and B), except Mo were also increased when plants were exposed to pH lower than pH 6.5. Al addition caused a reduction in the con-centration of most nutrients in plant roots and shoots; but K, Mn and Zn in roots were increased. Treatments with Cd alone or together with Al reduced the concentrations of all the plant nutrients in plants. Al-sensitive genotype Zhechun 2 has lower nutrient concentration than Al-tolerant genotype Liao 1. The current findings imply that Al and Cd are synergistic in their effect on plant growth, physiological traits and nutrient uptake.

Cadmium Toxicity in Plants and Role of Mineral Nutrients in Its Alleviation

Cadmium (Cd) is a toxic heavy metal that enters the environment through various anthropogenic sources, and inhibits plant growth and development. Cadmium toxicity may result from disturbance in plant metabolism as a consequence of disturbance in the uptake and translocation of mineral nutrients. Plant nutrients and Cd compete for the same transporters and, therefore, presence of Cd results in mineral nutrients deficiency. The optimization of mineral nutrients under Cd stress could reduce Cd toxicity by greater availability at the transport site resulting in reduced accumulation of Cd, and could also alleviate Cd-induced toxic effects by enhancing biochemical reactions and physiological processes in plants. In the present review the role of plant macro, micro and beneficial elements in alleviating Cd stress in crop plants is discussed.

Toxicity of cadmium and lead on tropical midge larvae,Chironomus kiiensis Tokunaga and Chironomus javanus Kieffer(Diptera:Chironomidae)

Objective:To investigate the acute toxicity of cadmium and lead on larvae of two tropical Chironomid species,Chironomus kiiensis(C.kiiensis) Tokunaga and Chironomus javanus(C. javanus) Kieffer.Methods:Different larval instars(first-fourth) were exposed using a sialic non-replacement testing procedures to various concentrations of cadmium and lead.Results: In general,younger larvae(first and second instars) of both species were more sensitive to both metals than older larvae(third and forth instars).The toxic effects of the metals on C.kiiensis and C. javanus were influenced by the age of the larvae(first to fourth instars),types of metals(cadmium or lead) and duration of larval exposure(24,48,72 and 96 h) to the metals.Conclusions:Cadmium was more toxic to the chironomids than lead and C.javanus was significantly more sensitive to both metals than C.kiiensis(P<0.05).