Resveratrol ameliorates cyprodinil-induced zebrafish cardiac developmental defects as an aryl hydrocarbon receptor antagonist.

Cyprodinil, a globally utilized broad-spectrum pyrimidine amine fungicide, has been observed to elicit cardiac abnormality. Resveratrol (RSV), a naturally occurring polyphenolic compound, showcases remarkable defensive properties in nurturing cardiac development. To investigate whether RSV could protect against cyprodinil-induced cardiac defects, we exposed zebrafish embryos to cyprodinil (500 µg/L) in the presence or absence of RSV (1 µM). Our results showed that RSV significantly mitigated the decrease of survival rate and embryo movement and the hatching delay induced by cyprodinil. In addition, RSV also improved cyprodinil-induced zebrafish cardiac developmental toxicity, including pericardial edema and cardiac function impairment. In mechanism, RSV attenuated the cyprodinil-induced changes in mRNA expression involved in cardiac development, such as myh6, myl7, tbx5, and gata4, and calcium ion channels, such as ncx1h, slc8a4a, and atp2a2b. We further showed that RSV might inhibit the activity of aryl hydrocarbon receptor (AhR) signaling pathways induced by cyprodinil. In summary, our findings establish that the protective effects of RSV against the cardiac developmental toxicity are induced by cyprodinil due to its remarkable ability to inhibit AhR activity. Our findings not only shed light on a new avenue for regulating and ensuring the safe utilization of cyprodinil but also presents a novel concept to promote its responsible use.

Multi-omics integration identifies ferroptosis involved in black phosphorus quantum dots-induced renal injury.

Black phosphorus quantum dots (BPQDs) have recently emerged as a highly promising contender in biomedical applications ranging from drug delivery systems to cancer therapy modalities. Nevertheless, the potential toxicity and its effects on human health need to be thoroughly investigated. In this study, we utilized multi-omics integrated approaches to explore the complex mechanisms of BPQDs-induced kidney injury. First, histological examination showed severe kidney injury in male mice after subacute exposure to 1 mg/kg BPQDs for 28 days. Subsequently, transcriptomic and metabolomic analyses of kidney tissues exposed to BPQDs identified differentially expressed genes and metabolites associated with ferroptosis, an emerging facet of regulated cell death. Our findings highlight the utility of the multi-omics integrated approach in predicting and elucidating potential toxicological outcomes of nanomaterials. Furthermore, our study provides a comprehensive understanding of the mechanisms driving BPQDs-induced kidney injury, underscoring the importance of recognizing ferroptosis as a potential toxic mechanism associated with BPQDs.

Long-term carbaryl exposure leads to behavioral abnormalities and reproductive toxicity in male marine medaka through apoptosis-mediated HPA and HPG axes dysregulation.

Carbaryl is a widely used carbamate pesticide that has been detected in the marine environment, but its effects on marine fish are still unknown. This study was aimed to investigate the effects of long-term exposure of carbaryl on male marine medaka. For this purpose, we set up five exposure concentration groups of 0, 0.1, 1, 10, and 100 µg/L for 180 days. On the one hand, we observed increased aggression and decreased ability to avoid predators in males after exposure, which was affected by the levels of HPA-axis hormones, especially decreased cortisol level. On the other hand, after exposure, HPG axis hormone levels and gene transcription levels were disturbed. Males exhibited a decreased gonadosomatic index and a notable reduction in mature sperm proportion and the F1 generation displayed a significant increase in malformation rate. Additionally, the number of apoptotic cells and the transcription level of apoptosis-related genes in the brains of male marine medaka substantially increased after exposure. Apoptosis of brain cells may be responsible for the disturbance of HPA and HPG axes, consequently leading to behavioral and reproductive abnormalities. These findings provide novel insights into evaluating the toxic effects of carbaryl on male marine medaka and emphasizing the criticality of exploring the potential environmental risks posed by carbaryl in the marine environment, thus providing toxicity value basis for further strengthening marine environmental monitoring and the protection of biological resources.

WWC1 upregulation accelerates hyperuricemia by reduction of renal uric acid excretion through Hippo signaling pathway.

Hyperuricemia (HUA) is a metabolic disorder characterized by elevated serum uric acid (UA), primarily attributed to the hepatic overproduction and renal underexcretion of UA. Despite the elucidation of molecular pathways associated with this underexcretion, the etiology of HUA remains largely unknown. In our study, using by Uox knockout rats, HUA mouse and cell line models, we discovered that the increased WWC1 levels were associated with decreased renal UA excretion. Additionally, using by knockdown and overexpression approaches, we found that WWC1 inhibited UA excretion in renal tubular epithelial cells. Mechanistically, WWC1 activated the Hippo pathway, leading to phosphorylation and subsequent degradation of the downstream transcription factor YAP1, thereby impairing the ABCG2 and OAT3 expression through transcriptional regulation. Consequently, this reduction leaded to a decrease in UA excretion in renal tubular epithelial cells. In conclusion, our study has elucidated the role of upregulated WWC1 in renal tubular epithelial cells inhibiting the excretion of UA in the kidneys and causing HUA.

Letrozole induced a polycystic ovary syndrome model in zebrafish by interfering with the hypothalamic-pituitary-gonadal axis.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women of childbearing age, with an incidence of 5-10%. This study compared the traits of zebrafish with three diagnostic criteria for human PCOS, and the diagnostic criteria for zebrafish PCOS were proposed: decreased fecundity, elevated testosterone (T) or 11-ketotestosterone (11-KT) levels and increased cortical-alveolar oocyte (CO) ratio, enhancing the zebrafish PCOS model's accuracy. According to the mammalian PCOS classification, the type of zebrafsh PCOS is divided into four phenotypes (A, B, C and D), but the four phenotypes of zebrafish PCOS are not fully covered in the existing studies (A and D). In this study, we successfully induced phenotype B zebrafish PCOS model using the aromatase inhibitor, letrozole (LET). That is, wild-type female zebrafish were exposed to 1000 µg/L LET for 30 days. Reproductive tests showed decreased fecundity in female zebrafish exposed to LET (Control: 132.63, 146.00, 173.00; LET: 29.20, 90.00, 82.71). Hormone analysis showed that female zebrafish exposed to LET had significantly lower 17ß-estradiol/testosterone (E2/T) ratios, indicating elevated T levels. Meanwhile, levels of 11-KT in the ovaries exposed to LET were significantly up-regulated (Control: 0.0076 pg/µg; LET: 0.0138 pg/µg). Pathological sections of the ovary showed fewer CO in the LET-exposed group (Control: 16.27%; LET: 8.38%). In summary, the zebrafish PCOS model summarized and studied in this study provide a reliable and economical tool for the screening of therapeutic drugs, as well as for the etiology research and treatment strategies of PCOS.

Long-term exposure to aryl hydrocarbon receptor agonist neburon induces reproductive toxicity in male zebrafish (Danio rerio).

Neburon is a phenylurea herbicide that is widely used worldwide, but its toxicity is poorly studied. In our previous study, we found that neburon has strong aryl hydrocarbon receptor (AhR) agonist activity, but whether it causes reproductive toxicity is not clear. In the present study, zebrafish were conducted as a model organism to evaluate whether environmental concentrations of neburon (0.1, 1 and 10 µg/L) induce reproductive disorder in males. After exposure to neburon for 150 days from embryo to adult, that the average spawning egg number in high concentration group was 106.40, which was significantly lower than 193.00 in control group. This result was mainly due to the abnormal male reproductive behavior caused by abnormal transcription of genes associated with reproductive behavior in the brain, such as secretogranin-2a. The proportions of spermatozoa in the medium and high concentration groups were 82.40% and 83.84%, respectively, which were significantly lower than 89.45% in control group. This result was mainly caused by hormonal disturbances and an increased proportion of apoptotic cells. The hormonal disruption was due to the significant changes in the transcription levels of key genes in the hypothalamus-pituitary-gonadal axis following neburon treatment. Neburon treatment also significantly activated the AhR signaling pathway, causing oxidative stress damage and eventually leading to a significant increase in apoptosis in the exposed group. Together, these data filled the currently more vacant profile of neburon toxicity and might provide information to assess the ecotoxicity of neburon on male reproduction at environmentally relevant concentrations.

Kidney injury contributes to edema of zebrafish larvae caused by quantum dots.

Edema represents a notable outcome in fishes exposed to aquatic pollutants, yet the underlying etiology remains inadequately understood. This investigation delves into the etiological factors of edema formation in 7 days post fertilization (dpf) zebrafish larvae following their exposure to InP/ZnS quantum dots (QDs), which was chosen as a prototypical edema inducer. Given the fundamental role of the kidney in osmoregulation, we used transgenic zebrafish lines featuring fluorescent protein labeling of the glomerulus, renal tubule, and blood vessels, in conjunction with histopathological scrutiny. We identified the pronounced morphological and structural aberrations within the pronephros. By means of tissue mass spectrometry imaging and hyperspectral microscopy, we discerned the accumulation of InP/ZnS QDs in the pronephros. Moreover, InP/ZnS QDs impeded the renal clearance capacity of the pronephros, as substantiated by diminished uptake of FITC-dextran. InP/ZnS QDs also disturbed the expression levels of marker genes associated with kidney development and osmoregulatory function at the earlier time points, which preceded the onset of edema. These results suggest that impaired fluid clearance most likely resulting from pronephros injury contributes to the emergence of zebrafish edema. Briefly, our study provides a perspective: the kidney developmental injury induced by exogenous substances may regulate edema in a zebrafish model.

Icariin induces developmental toxicity via thyroid hormone disruption in zebrafish larvae.

Icariin (ICA) is a natural flavonoid isolated from the traditional Chinese medicinal herb, Epimedium brevicornu Maxim. Although previous studies have reported that ICA exhibits various pharmacological activities, little is known about its toxicology. Herein, zebrafish embryos were exposed to ICA at 0, 2.5, 10, and 40 µM. In developmental analysis, reduced hatching rates, decreased body length, and abnormal swim bladder were found after treatment with 10 and 40 µM ICA. In addition, the ability of locomotor behavior was impaired by ICA. Two important thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), were tested. The exposure resulted in a remarkable alteration of T4 level and a significant decrease of the T3/T4 ratio in the 40 µM, indicating thyroid endocrine disruption. Furthermore, gene transcription analysis showed that genes involved in thyroid development (nkx2.1) and THs synthesis (tg) were up-regulated after ICA exposure. Significant down-regulation of iodothyronine deiodinase (dio1) was also observed in the 10 and 40 µM groups compared to the control. Taken together, our study first demonstrated that ICA caused developmental toxicity possibly through disrupting thyroid development and hormone synthesis. These results show that it is necessary to perform risk assessments of ICA in clinical practice.

Exposure to echimidine impairs the heart development and function of zebrafish larvae.

Pyrrolizidine alkaloids (PAs) are a class of phytotoxins that are widely distributed and can be consumed by humans through their daily diets. Echimidine is one of the most abundant PAs, but its safety, particularly its effects on development, is not fully understood. In this study, we used a zebrafish model to assess the developmental toxicity of echimidine. Zebrafish embryos were exposed to echimidine at concentrations of 0.02, 0.2, and 2 mg/L for 96 h. Our study revealed that embryonic exposure to echimidine led to developmental toxicity, characterized by delayed hatching and reduced body length. Additionally, echimidine exposure had a notable impact on heart development in larvae, causing tachycardia and reducing stroke volume (SV)and cardiac output (CO). Upon exposing the transgenic zebrafish strain Tg(cmlc2:EGFP) to echimidine, we observed atrial dilation and thinning of the atrial wall in developing embryos. Moreover, our findings indicated abnormal expression of genes associated with cardiac development (including gata4, tbx5, nkx2.5 and myh6) and genes involved in calcium signaling pathways (such as cacna1aa, cacna1sa, ryr2a, ryr2b, atp2a2a, atp2a2b, slc8a1, slc8a3 and slc8a4a). In summary, our findings demonstrate that echimidine may impair cardiac development and function in zebrafish larvae by disrupting calcium transport, leading to developmental toxicity. These findings provide insights regarding the safety of products containing PAs in food and medicine.

Topically applied fullerenols protect against radiation dermatitis by scavenging reactive oxygen species.

Adverse skin reactions caused by ionizing radiation are collectively called radiation dermatitis (RD), and the use of nanomedicine is an attractive approach to this condition. Therefore, we designed and large-scale synthesized fullerenols that showed free radical scavenging ability in vitro. Next, we pretreated X-ray-exposed cells with fullerenols. The results showed that pretreatment with fullerenols significantly scavenged intracellular reactive oxygen species (ROS) produced and enhanced the antioxidant capacity, protecting skin cells from X-ray-induced DNA damage and apoptosis. Moreover, we induced RD in mice by applying 30 Gy of X-ray irradiation, followed by treatment with fullerenols. We found that after treatment, the RD scores dropped, and the histological results systematically demonstrated that topically applied fullerenols could reduce radiation-induced skin epidermal thickening, collagen deposition and skin appendage damage and promote hair regeneration after 35 days. Compared with Trolamine cream, a typical RD drug, fullerenols showed superior radiation protection. Overall, the in vitro and in vivo experiments proved that fullerenols agents against RD.

Transgenerational Effects and Mechanisms of Tributyltin Exposure on Neurodevelopment in the Male Offspring of Rats.

This study aimed to investigate the transgenerational effects of tributyltin exposure on rat neurodevelopment in male offspring and the potential mechanisms. Neonatal female rats were exposed to the environmental level of tributyltin and then mated with nonexposed males after sexual maturity to produce the F1 generation. The F1 generation (with primordial germ cell exposure) was mated with nonexposed males to produce nonexposed offspring (the F2 and F3 generations). Neurodevelopmental indicators and behavior were observed for the F1, F2, and F3 generations during postnatal days 1-25 and 35-56, respectively. We found premature eye-opening and delayed visual positioning in newborn F1 rats and anxiety and cognitive deficits in prepubertal F1 male rats. These neurodevelopmental impacts were also observed in F2 and F3 males. Additionally, F1-F3 males exhibited increased serotonin and dopamine levels and a loose arrangement of neurons in the hippocampus. We also observed a reduction in the expression of genes involved in intercellular adhesion and increased DNA methylation of the Dsc3 promoter in F1-F3 males. We concluded that tributyltin exposure led to transgenerational effects on neurodevelopment via epigenetic reprogramming in male offspring. These findings provide insights into the risks of neurodevelopmental disorders in offspring from parents exposed to tributyltin.

Estradiol protects female mice from hyperuricemia induced by PCB138 exposure.

Polychlorinated biphenyls (PCBs) are a type of persistent organic pollutant (POP). Our previous study demonstrated that exposure to 0.5-50 µg/kg bw PCB138 during postnatal days (PND) 3-21 led to elevated serum uric acid (UA) levels and kidney injury in adult male mice. Given that the prevalence of hyperuricemia (HUA) is significantly lower in women than in men, it is worth investigating whether POP-induced HUA and its secondary kidney injury have sexual dimorphism. Herein, we exposed female mice to 0.5-50 µg/kg bw PCB138 during PND 3-21, resulting in elevated serum UA levels, but without causing significant kidney damage. Concurrently, we found a negative correlation between serum 17ß-estradiol (E2) and serum UA levels. We also observed down-regulation of estrogen receptor (ER) protein levels in the kidneys of the PCB138-exposed groups. Furthermore, our study showed that E2 rescued the increased UA level and cytotoxicity caused by HUA in human renal tubular epithelial (HK-2) cells. Collectively, our findings suggest that E2 likely plays a crucial protective role in PCB138-induced HUA and kidney injury in female mice. Our research highlights the existence of sexual dimorphism in kidney injury secondary to HUA induced by POPs, which could provide guidance for individuals of different genders in preventing kidney injury caused by environmental factors.

Chronic diflubenzuron exposure causes reproductive toxic effects in female marine medaka (Oryzias melastigma).

Diflubenzuron, an insecticide commonly used in marine fish farming, has been detected in various marine environments. However, its potential impact on marine fish remains largely unknown. This study investigated the reproductive toxicity of chronic diflubenzuron exposure in female marine medaka (Oryzias melastigma). Marine medaka were exposed continuously to environmentally relevant concentrations of diflubenzuron (0.1, 1, and 10 µg/L) or a solvent control from the fertilized egg to adulthood. In exposed female marine medaka, the gonadosomatic index (GSI) and the number of laid eggs were significantly reduced. Moreover, diflubenzuron-exposed female marine medaka showed altered ovarian histopathology, with an increased relative proportion of immature oocytes and atretic follicles and a decreased relative proportion of mature oocytes. Maternal exposure to diflubenzuron also inhibited the development of the F1 generation, significantly reducing the hatching rate of F1 embryos and significantly increasing the malformation rate of F1 larvae. Furthermore, changes in hormone levels and expression of genes along the hypothalamus-pituitary-gonad-liver (HPGL) axis were observed, which may be the fundamental reason for all the reproductive toxic effects mentioned above. These results provide new insights into the impact of diflubenzuron on the female marine medaka reproductive system and underscore the importance of investigating the potential environmental risks of diflubenzuron in the marine environment.

The hepatoprotective effects of Herbt Tea Essences on phenanthrene-induced liver damage in mice.

Phenanthrene (Phe), one of the most frequently occurring pollutants in nature, can cause substantial damage to the human liver. Herbt Tea Essences (HTE), a kind of black tea extract with strong anti-inflammatory activity, can protect humans against disease. Currently, whether HTE can protect the liver from Phe-induced hepatotoxicity remains unclear. Herein, we explore the protective effects of HTE against Phe-induced hepatotoxicity. Our results showed that Phe exposure could significantly induce liver damage and increase serum hepatic enzyme levels in mice. HTE could prevent liver damage and recover the expression levels of inflammatory factors. Furthermore, we found that HTE suppressed the excessive activation of the nuclear transcription factor kappa-B and transforming growth factor-ß/SMAD signaling pathways to alleviate Phe-induced liver inflammation and fibrosis. Overall, our data showed that HTE treatment could be a new preventive means for Phe-induced liver disease.

Toxicity and ecological risk assessment for two AhR agonistic pesticides mepanipyrim and cyprodinil and their metabolites.

Mepanipyrim and cyprodinil are widely used to control and/or prevent fungal diseases in fruit culture. They are frequently detected in the aquatic environment and some food commodities. Different from TCDD, mepanipyrim and cyprodinil are more easily metabolised in the environments. However, the risk of their metabolites to the ecological environment is unclear and needs to be further confirmed. In this study, we investigated the temporal pattern of mepanipyrim- and cyprodinil-induced CYP1A and AhR2 expression and EROD enzyme activity at different time frames during zebrafish embryonic and larval development. Then, we assessed the ecological risk of mepanipyrim, cyprodinil, and their metabolites to aquatic organisms. Our results showed that mepanipyrim and cyprodinil exposure could increase the expression level of cyp1a and ahr2 genes and EROD activity by a dynamic pattern in different developmental stages of zebrafish. Besides, their several metabolites showed strong AhR agonistic activity. Importantly, these metabolites could cause potential ecological risks to aquatic organisms and should be paid more attention to. Our results would provide an important reference value for environmental pollution control and the use management of mepanipyrim and cyprodinil.

Mepanipyrim induces cardiotoxicity of zebrafish (Danio rerio) larvae via promoting AhR-regulated COX expression pathway.

The wide use of pesticides has seriously threatened human health and the survival of beneficial organisms. The fungicide mepanipyrim is widely used in viticulture practices. Studies of mepanipyrim-induced toxicity in organisms are still scarce, especially studies on cardiotoxicity. In this study, we aimed to investigate mepanipyrim-induced cardiotoxicity in zebrafish (Danio rerio) larvae. We found that mepanipyrim could induce cardiotoxicity by altering the heart rate and cardiomyocyte diameter of larvae. Meanwhile, RNA sequencing and RT-qPCR data indicated that mepanipyrim exposure could dramatically alter the mRNA expression of calcium signaling pathway-, cardiac muscle contraction-, and oxidative respiratory chain-related genes. Interestingly, by the CALUX cell bioassay, we found that most cytochrome c oxidase (COX) family genes exhibited potential AhR-regulated activity, suggesting that mepanipyrim induced cardiotoxicity via a novel AhR-regulated manner in larvae. Additionally, the AhR antagonist CH223191 could effectively prevent mepanipyrim-induced cardiotoxicity in zebrafish larvae. In conclusion, the AhR agonist mepanipyrim could induce cardiotoxicity in a novel unreported AhR-regulated manner, which could specifically affect the expression of COX family genes involved in the mitochondrial oxidative respiratory chain. Our data will help explain the toxic effects of mepanipyrim on organisms and provide new insight into the AhR agonistic activity pesticide-induced cardiotoxicity.

The valence state of iron-based nanomaterials determines the ferroptosis potential in a zebrafish model.

Many nanomaterials containing different valences of iron have been designed for applications in biomedicine, energy, catalyzers, nanoenzymes, and so on. However, the toxic effects of the valence state of iron in iron-based nanomaterials are still unclear. Here, three different-valence iron-based nanomaterials (nFe@Fe3O4, nFe3O4 and nFe2O3) were synthesized and exposed to zebrafish embryos and mammalian cardiomyocytes. All of them induced ferroptosis along with an increase in valence through iron overload and the Fenton reaction. Specifically, we exposed Tg (cmlc2:EGFP) zebrafish to the three iron-based nanomaterials and found that nFe@Fe3O4 treatments led to enlarged ventricles, while nFe3O4 and nFe2O3 increased atrial size, which was consistent with the results from hematoxylin-eosin staining and in situ hybridization. Moreover, we used ferroptosis inhibitors (ferrostatin-1 or deferoxamine) to treat zebrafish along with nanoparticles exposure and found that the cardiac developmental defects caused by nFe3O4 and nFe2O3, but not nFe@Fe3O4, could be completely rescued by ferroptosis inhibitors. We further found that nFe@Fe3O4, rather than nFe3O4 and nFe2O3, reduced the dissolved oxygen in the medium, which resulted in hypoxia and acceleration of heart tube formation and ventricular enlargement, and both were fully rescued by oxygen donors combined with ferroptosis inhibitors. Consistently, these findings were also observed in mammalian cardiomyocytes. In summary, our study demonstrates that the valence state of iron-based nanomaterials determines the ferroptosis potential. Our study also clarifies that high-valence iron-based nanomaterials induce an enlarged atrium via ferroptosis, while low-valence ones increase the ventricular size through both hypoxia and ferroptosis, which is helpful to understand the potential adverse effects of different valences of iron-based nanomaterials on environmental health and assure the responsible and sustainable development of nanotechnology.

Mepanipyrim induces visual developmental toxicity and vision-guided behavioral alteration in zebrafish larvae.

Mepanipyrim, an anilinopyrimidine fungicide, has been extensively used to prevent fungal diseases in fruit culture. Currently, research on mepanipyrim-induced toxicity in organisms is still very scarce, especially visual developmental toxicity. Here, zebrafish larvae were employed to investigate mepanipyrim-induced visual developmental toxicity. Intense light and monochromatic light stimuli-evoked escape experiments were used to investigate vision-guided behaviors. Meanwhile, transcriptomic sequencing and real-time quantitative PCR assays were applied to assess the potential mechanisms of mepanipyrim-induced visual developmental toxicity and vision-guided behavioral alteration. Our results showed that mepanipyrim exposure could induce retinal impairment and vision-guided behavioral alteration in larval zebrafish. In addition, the grk1b gene of the phototransduction signaling pathway was found to be a potential aryl hydrocarbon receptor (AhR)-regulated gene. Mepanipyrim-induced visual developmental toxicity was potentially related to the AhR signaling pathway. Furthermore, mepanipyrim-induced behavioral alteration was guided by the visual function, and the effects of mepanipyrim on long and middle wavelength light-sensitive opsins may be the main cause of vision-guided behavioral alteration. Our results provide insights into understanding the relationship between visual development and vision-guided behaviors induced by mepanipyrim exposure.

Black phosphorus quantum dots cause glucose metabolism disorder and insulin resistance in mice.

Black phosphorus quantum dots (BPQDs) are considered to have wide application prospects due to their excellent properties. However, there is no study on the effect of BPQDs on glucose metabolism. In this study, blood glucose was significantly increased when mice were continuously intragastrically administered 0.1 and 1 mg/kg bw BPQDs. The blood glucose level of the mice was elevated from Day 7 to Day 28. BPQD exposure also decreased the area under the curve (AUC) of the oral glucose tolerance test (OGTT). After exposure, the pancreas somatic index was increased. Moreover, the serum insulin and glucagon levels were elevated and the relative area of islet ß cells was increased in BPQD-exposed mice, while insulin signaling cascades were reduced in muscle tissues. In summary, our study demonstrated for the first time that BPQD exposure induces glucose disorder and insulin resistance in muscle, which is helpful to understand the biosafety of black phosphorus nanomaterials and promote the sustainable development of nanotechnology.