CXCL16 inhibits epithelial regeneration and promotes fibrosis during the progression of radiation enteritis.

Radiation enteritis (RE) is a prevalent complication of radiotherapy for pelvic malignant tumors, characterized by severe intestinal epithelial destruction and progressive submucosal fibrosis. However, little is known about the pathogenesis of this disease, and so far, there is no specific targeted therapy. Here, we report that CXCL16 is upregulated in the injured intestinal tissues of RE patients and in a mouse model. Genetic deletion of Cxcl16 mitigates fibrosis and promotes intestinal stem cell-mediated epithelial regeneration after radiation injury in mice. Mechanistically, CXCL16 functions on myofibroblasts through its receptor CXCR6 and activates JAK3/STAT3 signaling to promote fibrosis and, at the same time, to transcriptionally modulate the levels of BMP4 and hepatocyte growth factor (HGF) in myofibroblasts. Moreover, we find that CXCL16 and CXCR6 auto- and cross-regulate themselves in positive feedback loops. Treatment with CXCL16 neutralizing monoclonal antibody attenuates fibrosis and improves the epithelial repair in RE mouse model. Our findings emphasize the important role of CXCL16 in the progression of RE and suggest that CXCL16 signaling could be a potential therapeutic target for RE. © 2022 The Pathological Society of Great Britain and Ireland.

The dynamic cellular and molecular features during the development of radiation proctitis revealed by transcriptomic profiling in mice.

BACKGROUND: Radiation proctitis (RP) is the most common complication of radiotherapy for pelvic tumor. Currently there is a lack of effective clinical treatment and its underlying mechanism is poorly understood. In this study, we aimed to dynamically reveal the mechanism of RP progression from the perspective of RNomics using a mouse model, so as to help develop reasonable therapeutic strategies for RP. RESULTS: Mice were delivered a single dose of 25 Gy rectal irradiation, and the rectal tissues were removed at 4 h, 1 day, 3 days, 2 weeks and 8 weeks post-irradiation (PI) for both histopathological assessment and RNA-seq analysis. According to the histopathological characteristics, we divided the development process of our RP animal model into three stages: acute (4 h, 1 day and 3 days PI), subacute (2 weeks PI) and chronic (8 weeks PI), which could recapitulate the features of different stages of human RP. Bioinformatics analysis of the RNA-seq data showed that in the acute injury period after radiation, the altered genes were mainly enriched in DNA damage response, p53 signaling pathway and metabolic changes; while in the subacute and chronic stages of tissue reconstruction, genes involved in the biological processes of vessel development, extracellular matrix organization, inflammatory and immune responses were dysregulated. We further identified the hub genes in the most significant biological process at each time point using protein-protein interaction analysis and verified the differential expression of these genes by quantitative real-time-PCR analysis. CONCLUSIONS: Our study reveals the molecular events sequentially occurred during the course of RP development and might provide molecular basis for designing drugs targeting different stages of RP development.

Ectopic expression of GmRNF1a encoding a soybean E3 ubiquitin ligase affects Arabidopsis silique development and dehiscence.

MAIN CONCLUSION: A soybean E3 ubiquitin ligase, GmRNF1a, may affect pod dehiscence and seed development through MADS family genes. These results would be useful for the study of soybean pod and seed development. Pod dehiscence is one of the critical causes of yield loss in cultivated soybeans, and it is of great significance to understand the molecular mechanisms underlying pod dehiscence in soybeans. In this study, we identified a new RING family member of the E3 ubiquitin ligase, GmRNF1a, which was observed to interact with the MADS-box protein GmAGL1 to regulate siliques dehiscence. Tissue-specific gene expression analysis revealed that GmRNF1a was mainly expressed in flowers and pods in soybean. The subcellular localization assay showed the nuclear and cytoplasmic localization of GmRNF1a. In addition, it was found that GmRNF1a exhibits higher promoter activity in soybean hairy roots as well as in Arabidopsis leaves, flowers, and siliques. Heterologous expression of GmRNF1a in Arabidopsis showed that the transgenic Arabidopsis siliques had a faster maturation rate and cracked earlier than the wild-type plants. The functional and nucleotide diversity analysis suggests that GmRNF1a might play an important role in pod maturation and dehiscence and has been strongly selected for during soybean domestication.

A cation diffusion facilitator, GmCDF1, negatively regulates salt tolerance in soybean.

Salt stress is one of the major abiotic factors that affect the metabolism, growth and development of plants, and soybean [Glycine max (L.) Merr.] germination is sensitive to salt stress. Thus, to ensure the successful establishment and productivity of soybeans in saline soil, the genetic mechanisms of salt tolerance at the soybean germination stage need to be explored. In this study, a population of 184 recombinant inbred lines (RILs) was utilized to map quantitative trait loci (QTLs) related to salt tolerance. A major QTL related to salt tolerance at the soybean germination stage named qST-8 was closely linked with the marker Sat_162 and detected on chromosome 8. Interestingly, a genome-wide association study (GWAS) identified several single nucleotide polymorphisms (SNPs) significantly associated with salt tolerance in the same genetic region on chromosome 8. Resequencing, bioinformatics and gene expression analyses were implemented to identify the candidate gene Glyma.08g102000, which belongs to the cation diffusion facilitator (CDF) family and was named GmCDF1. Overexpression and RNA interference of GmCDF1 in soybean hairy roots resulted in increased sensitivity and tolerance to salt stress, respectively. This report provides the first demonstration that GmCDF1 negatively regulates salt tolerance by maintaining K+-Na+ homeostasis in soybean. In addition, GmCDF1 affected the expression of two ion homeostasis-associated genes, salt overly sensitive 1 (GmSOS1) and Na+/H+ exchanger 1 (GmNHX1), in transgenic hairy roots. Moreover, a haplotype analysis detected ten haplotypes of GmCDF1 in 31 soybean genotypes. A candidate-gene association analysis showed that two SNPs in GmCDF1 were significantly associated with salt tolerance and that Hap1 was more sensitive to salt stress than Hap2. The results demonstrated that the expression level of GmCDF1 was negatively correlated with salt tolerance in the 31 soybean accessions (r = -0.56, P < 0.01). Taken together, these results not only indicate that GmCDF1 plays a negative role in soybean salt tolerance but also help elucidate the molecular mechanisms of salt tolerance and accelerate the breeding of salt-tolerant soybean.

Overexpression of a soybean YABBY gene, GmFILa, causes leaf curling in Arabidopsis thaliana.

BACKGROUND: YABBY genes play important roles in the growth and polar establishment of lateral organs such as leaves and floral organs in angiosperms. However, the functions of YABBY homologous genes are largely unknown in soybean. RESULTS: In this study, we identified GmFILa encoding a YABBY transcription factor belonging to FIL subfamily. In situ mRNA hybridization analysis indicated that GmFILa had specific expression patterns in leaf as well as in flower bud primordia. Ectopic expression of GmFILa in Arabidopsis thaliana altered the partial abaxialization of the adaxial epidermises of leaves. Besides, GmFILa transgenic plants also exhibited longer flowering period and inhibition of shoot apical meristem (SAM) development compared to the wild type plants. Digital expression data and quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that the expression of GmFILa was induced by biotic and abiotic stresses and hormone treatments. Transcriptome analysis suggested that overexpressing GmFILa yielded 82 significant differentially expressed genes (DEGs) in Arabidopsis leaves, which can be classified into transcription factors, transporters, and genes involved in growth and development, metabolism, signal transduction, redox reaction and stress response. CONCLUSIONS: These results not only demonstrate the roles of GmFILa involved in leaf adaxial-abaxial polarity in Arabidopsis, but also help to reveal the molecular regulatory mechanism of GmFILa based on the transcriptomic data.

The α1-adrenergic receptor is involved in hepcidin upregulation induced by adrenaline and norepinephrine via the STAT3 pathway.

Elevated body iron stores are associated with hypertension progression, while hypertension is associated with elevated plasma catecholamine levels in patients. However, there is a gap in our understanding of the connection between catecholamines and iron regulation. Hepcidin is a key iron-regulatory hormone, which maintains body iron balance. In the present study, we investigated the effects of adrenaline (AD) and norepinephrine (NE) on hepatic hepcidin regulation. Mice were treated with AD, NE, phenylephrine (PE, α1-adrenergic receptor agonist), prazosin (PZ, α1-adrenergic receptor antagonist), and/or propranolol (Pro, ß-adrenergic receptor antagonist). The levels of hepcidin, as well as signal transducer and activator of transcription 3 (STAT3), ferroportin 1 (FPN1), and ferritin-light (Ft-L) protein in the liver or spleen, were assessed. Six hours after AD, NE, or PE treatment, hepatic hepcidin mRNA levels increased. Pretreatment with PZ, but not Pro, abolished the effects of AD or NE on STAT3 phosphorylation and hepatic hepcidin expression. When mice were treated with AD or NE continuously for 7 days, an increase in hepatic hepcidin mRNA levels and serum hepcidin concentration was also observed. Meanwhile, the expected downstream effects of elevated hepcidin, namely decreased FPN1 expression and increased Ft-L protein and non-heme iron concentrations in the spleen, were observed after the continuous AD or NE treatments. Taken together, we found that AD or NE increase hepatic hepcidin expression via the α1-adrenergic receptor and STAT3 pathways in mice. The elevated hepatic hepcidin decreased FPN1 levels in the spleen, likely causing the increased iron accumulation in the spleen.

The TGF-ß signalling negative regulator PICK1 represses prostate cancer metastasis to bone.

Backgroud:Constitutive activation of TGF-ß signalling is a well-recognised mechanism in bone metastasis of prostate cancer (PCa). Protein Interacting with PRKCA 1 (PICK1) is a critical negative regulator of the TGF-ß pathway. However, the clinical significance and biological role of PICK1 in PCa bone metastasis remain obscure. METHODS: PICK1 expression is evaluated by immunohistochemistry (IHC) in 198 PCa patients. Statistical analysis is performed to explore correlation between PICK1 expression and clinicopathological features in PCa patients. The biological role of PICK1 is examined in PC-3 and C4-2B cells in vitro and a mouse intracardial model in vivo. RESULTS: PICK1 expression is decreased in PCa tissues with bone metastasis and bone-derived cells and downregulation of PICK1 positively correlates with serum PSA level, Gleason grade and bone metastasis status in PCa patients. Overexpression of PICK1 suppresses PCa cell invasion and migration in vitro and bone metastasis in vivo. Our results further indicate downregulation of PICK1 is caused by miR-210-3p overexpression in PCa tissues with bone metastasis. Clinical negative correlation of PICK1 with miR-210-3p is confirmed in PCa tissues. CONCLUSIONS: Our findings uncover a novel functionally and clinically relevant epigenetic regulatory mechanism for constitutive activation of TGF-ß signalling in bone metastasis of PCa.

Prostate tumour overexpressed-1 promotes tumourigenicity in human breast cancer via activation of Wnt/ß-catenin signalling.

Breast cancer is the most common malignancy in females. The presence of cancer stem cells (CSCs) is the main cause of local and distant tumour recurrence and is associated with poor outcome in breast cancer. However, the molecular mechanisms underlying the maintenance of CSCs remain largely unknown. This study demonstrates that prostate tumour overexpressed-1 (PTOV1) enhances the CSC population and augments the tumourigenicity of breast cancer cells both in vitro and in vivo. Moreover, PTOV1 suppresses transcription of Dickkopf-1 (DKK1) by recruiting histone deacetylases and subsequently reducing DKK1 promoter histone acetylation, followed by activation of Wnt/ß-catenin signalling. Restoration of DKK1 expression in PTOV1-overexpressing cells counteracts the effects of PTOV1 on Wnt/ß-catenin activation and the CSC population. Collectively, these results suggest that PTOV1 positively regulates the Wnt/ß-catenin signalling pathway and enhances tumourigenicity in breast cancer; this novel mechanism may represent a therapeutic target for breast cancer. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The Construction and Characterization of Mitochondrial Ferritin Overexpressing Mice.

Mitochondrial ferritin (FtMt) is a H-ferritin-like protein which localizes to mitochondria. Previous studies have shown that this protein can protect mitochondria from iron-induced oxidative damage, while FtMt overexpression in cultured cells decreases cytosolic iron availability and protects against oxidative damage. To investigate the in vivo role of FtMt, we established FtMt overexpressing mice by pro-nucleus microinjection and examined the characteristics of the animals. We first confirmed that the protein levels of FtMt in the transgenic mice were increased compared to wild-type mice. Interestingly, we found no significant differences in the body weights or organ to body weight ratios between wild type and transgenic mice. To determine the effects of FtMt overexpression on baseline murine iron metabolism and hematological indices, we measured serum, heart, liver, spleen, kidney, testis, and brain iron concentrations, liver hepcidin expression and red blood cell parameters. There were no significant differences between wild type and transgenic mice. In conclusion, our results suggest that FtMt overexpressing mice have no significant defects and the overexpression of FtMt does not affect the regulation of iron metabolism significantly in transgenic mice.

Functional analysis of flower development related gene GsLFY from Glycine soja.

LEAFY/FLORICAULA (LFY/FLO) is a family of plant-specific transcription factors, which plays an important role(s) in the regulation of floral organ formation and development. So far, LFY regulation on floral development in wild soybean has not been reported in the literature. In this study, the LFY gene, GsLFY, has been isolated from Glycine soja, and characterized with molecular and transgenic techniques. The cDNA for GsLFY gene is 1224 bp in length and contains an open reading frame encoding a polypeptide of 407 amino acids. Quantitative RT-PCR analysis shows that GsLFY is prominently expressed in various tissues, including roots, flowers and seeds. Among the four floral organs, GsLFY is expressed highly in sepals and stamens while weakly in the petals and carpels. Yeast two-hybrid experiments show that GsLFY possesses transactivation activity while transient expression analysis with Arabidopsis thaliana protoplasts shows that GsLFY protein is localized in the nucleus, supporting the notion that GsLFY is a transcription factor. The GsLFY transgenic tobacco plants flower about 29 days earlier than the wild-type plants, thereby providing a potential rationale for developing new soybean varieties with altered flowering time.

[Chemical constituents from Polygonum multiflorum].

Six compounds were isolated from the ethyl acetate extract of the tuberous root of Polygonum multiflorum by silical gel, ODS revsered-phase silica gel, Sephadex LH-20, and preparative HPLC. The structures were elucidated as column chromatography over： 2, 3, 5, 4'-tetrahydroxystilbene-2-O-(2″-O-p-hydroxybenzoyl)-ß-D-glucoside(1),2, 3, 5, 4'-tetrahydroxystilbene-2-O-ß-D-glucoside(2),2, 4, 6, 4'-tetrahydroxystilbene-2-O-ß-D-glucoside(3), emodin-8-O-ß-D-glucopyranoside(4), physcion-8-O-ß-D-glucopyranoside(5), and 8-O-methyl-emodin(6) on the basis of spectral analysis. Compound 1 is a new stilbene glycoside.

MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2.

Colorectal cancer (CRC) is the third most common cancer in the USA. MicroRNAs play important roles in the pathogenesis of CRC. In this study, we investigated the role of miR-30b in CRC and found that its expression was significantly lower in CRC tissues than that in normal tissues. We showed that a low expression level of miR-30b was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of miR-30b suppressed CRC cell proliferation in vitro and tumour growth in vivo. Specifically, miR-30b promoted G1 arrest and induced apoptosis. Moreover, KRAS, PIK3CD and BCL2 were identified as direct and functional targets of miR-30b. MiR-30b directly targeted the 3'-untranslated regions of their mRNAs and repressed their expression. This study revealed functional and mechanistic links between miRNA-30b and oncogene KRAS, PIK3CD and BCL2 in the pathogenesis of CRC. MiR-30b not only plays important roles in the regulation of cell proliferation and tumour growth in CRC, but is also a potential prognostic marker or therapeutic target for CRC. Restoration of miR-30b expression may represent a promising therapeutic approach for targeting malignant CRC.

Metastasis-Associated in Colon Cancer-1 Associates With Poor Prognosis and Promotes Cell Invasion and Angiogenesis in Human Cervical Cancer.

OBJECTIVE: The aim of this study is to investigate the clinicopathologic significance and potential role of metastasis-associated in colon cancer-1 (MACC1) in the progression of cervical cancer. METHODS: MACC1 expression was examined in cervical cancer cell lines, 6 matched cervical cancer tissues, and adjacent noncancerous tissues using Western blotting and real-time reverse transcriptase polymerase chain reaction. MACC1 protein expression and localization were determined in 181 paraffin-embedded archived cervical cancer samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance. The effects of MACC1 on cell migration, invasion, and angiogenesis were examined using migration assay, wound healing assay, 3-dimensional morphogenesis assay, and chicken chorioallantoic membrane assay. Western blotting was performed to examine the impact of MACC1 on the Akt and nuclear factor κB signaling pathways. RESULTS: Both protein and messenger RNA levels of MACC1 was up-regulated in cervical cancer cell lines and cervical cancer tissues, as compared with normal tissues. High MACC1 expression was detected in 96 (53%) of 181 of the cervical cancer tissues. In addition, high MACC1 expression correlated significantly with aggressiveness of cervical cancer, including International Federation of Gynecology and Obstetric stage (P = 0.001), pelvic lymph node metastasis (P = 0.004), recurrence (P = 0.037), and poor survival (P = 0.001). Moreover, enforced expression of MACC1 in cervical cancer cell lines significantly enhanced cell migration, invasion, and angiogenesis. Conversely, knockdown of MACC1 caused an inhibition of cell migration, invasion, and angiogenesis. Up-regulation of MACC1 increased, but knockdown of MACC1 decreased the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. Furthermore, enforced expression of MACC1 could enhance, but knockdown of MACC1 could reduce AKT and nuclear factor κB pathway activity. CONCLUSIONS: Our findings suggest that MACC1 protein, as a valuable marker of cervical cancer prognosis, plays an important role in the progression of human cervical cancer cells.

Constituents of Psoralea corylifolia Fruits and Their Effects on Methicillin-Resistant Staphylococcus aureus.

Two new flavonoids, bakuisoflavone (1) and bakuflavanone (2), together with 15 known compounds, were isolated from the fruits of Psoralea corylifolia, and their structures were characterized by spectroscopic data. The effects of the isolated compounds on methicillin-resistant Staphylococcus aureus were also examined. We found that two compounds, isobavachalcone (10) and bakuchiol (12), showed noticeable antibacterial effects on the MRSA strains examined. Quantitation of the major constituents, including anti-MRSA constituents, was then performed. The results showed individual contents of 1.26%-16.49% (w/w) among the examined compounds in the ethyl acetate extract from P. corylifolia fruits.

High expression level and nuclear localization of Sam68 are associated with progression and poor prognosis in colorectal cancer.

BACKGROUND: Src-associated in mitosis (Sam68; 68 kDa) has been implicated in the oncogenesis and progression of several human cancers. The aim of this study was to investigate the clinicopathologic significance of Sam68 expression and its subcellular localization in colorectal cancer (CRC). METHODS: Sam68 expression was examined in CRC cell lines, nine matched CRC tissues and adjacent noncancerous tissues using reverse transcription (RT)-PCR, quantitative RT-PCR and Western blotting. Sam68 protein expression and localization were determined in 224 paraffin-embedded archived CRC samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance. RESULTS: Sam68 was upregulated in CRC cell lines and CRC, as compared with normal tissues; high Sam68 expression was detected in 120/224 (53.6%) of the CRC tissues. High Sam68 expression correlated significantly with poor differentiation (P = 0.033), advanced T stage (P < 0.001), N stage (P = 0.023) and distant metastasis (P = 0.033). Sam68 nuclear localization correlated significantly with poor differentiation (P = 0.002) and T stage (P =0.021). Patients with high Sam68 expression or Sam68 nuclear localization had poorer overall survival than patients with low Sam68 expression or Sam68 cytoplasmic localization. Patients with high Sam68 expression had a higher risk of recurrence than those with low Sam68 expression. CONCLUSIONS: Overexpression of Sam68 correlated highly with cancer progression and poor differentiation in CRC. High Sam68 expression and Sam68 nuclear localization were associated with poorer overall survival.

Occurrence, distribution, and driving factors of current-use pesticides in commonly cultivated crops and their potential risks to non-target organisms: A case study in Hainan, China.

Multiple pesticides are heavily applied in crops grown in China's tropics due to the prevalence of diseases and pests, thus posing potential risks to nontarget organisms (e.g., honeybees, lacewings, ladybugs, and humans). However, there is little information on this topic. This study is the first assessment of the occurrence, driving factors, and ecological/human health risks of 32 current-use pesticides (CUPs) in 10 frequently-planted crops collected from practicing rice-vegetable rotation systems in Hainan, China. Of the 132 whole crop samples, 44 (33.3 %) residues from ≥8 pesticides were detected in 9.09 % of crop samples with concentrations ≥0.5 mg kg-1. Six pesticide residues, namely carbendazim, pyraclostrobin, acetamiprid, thiophanate methyl, phoxim, and imidacloprid, were detected in 72.7 % of samples, with concentrations ranging from 0.0021 to 13.5 (median = 0.032) mg kg-1. Among them, carbendazim, pyraclostrobin, and acetamiprid were the most common, contributions from 10.2 to 25.5 % and a detection frequency ranging from 25.6 to 56.1 %. The order of total concentration of 32 CUPs (∑32 CUP) concentrations during the year was January > May > November > August and vegetables > rice, being highly related with pesticides usage pattern, crop type, plant accumulation/dissipation and plant lipid contents. The ecological risk quotients (RQs) to four beneficial terrestrial organisms showed that 9.6-39.1 % of samples posed a potential medium or high ecological risk, with 13.6-65.9 % of samples at ∑RQ > 1 being highly affected by the residues of neonicotinoids and emamectin benzoate. Emamectin benzoate (8.9 %) and acetamiprid (5.6 %) exceeded the individual Maximum Residue Levels based on Chinese legislation (GB2763-2021). Moreover, cumulative dietary exposure presented a higher risk to humans in 11.0 and 22.0 % of the cases for acute and chronic, mainly originating from the higher concentration contributors of systemic pesticides in edible crops. Therefore, the regulation and monitoring of CUP residues is imperative for rice-vegetable rotation systems in tropical China to avoid negative effects on nontarget organisms.

Analyzing toxicological effects of AsIII and AsV to Chlamys farreri by integrating transcriptomic and metabolomic approaches.

Inorganic arsenic (iAs) is a widespread contaminant in marine environments, which is present in two different oxidation states (arsenate (AsV) and arsenite (AsIII)) that have complex toxic effects on marine organisms. The scallop Chlamys farreri (C. farreri) accumulates high levels of As and is a suitable bioindicator of As. In this report, we integrated transcriptomics and metabolomics to investigate genetic and metabolite changes and functional physiological disturbances in C. farreri exposured to inorganic arsenic. Physiological indicators antioxidant factors and cell apoptosis analysis macroscopically corroborated the toxic effects of inorganic arsenic revealed by omics results. Toxic effects of inorganic arsenic on C. farreri were signaling-mediated, causing interference with a variety of cell growth and small molecule metabolism. The results provide evidence that inorganic arsenic disrupts the physiological functions of bivalves, highlighting the correlations between different metabolic pathways and providing new insights into the toxic effects of environmental pollutants on marine organisms.

Neonicotinoids in draining micro-watersheds dominated by rice-vegetable rotations in tropical China: Multimedia occurrence, influencing factors, transport, and associated ecological risks.

Multimedia contamination by neonicotinoid (NEO) residues has attracted global attention. However, data regarding the multimedia polluted status under certain typical cropping scenarios and the associated risks are scarce. Here, the multimedia occurrence, spatiotemporal distribution, driving factors, transport, and ecological risks of NEOs from tropical rice-vegetable rotation fields were characterized. The heavy NEOs resided in multiple media, and imidacloprid and acetamiprid were the prevailing NEOs, with concentration contributions of 65-80%. The pollution levels of the NEOs, rather than their compositions, exhibited significant spatiotemporal heterogeneity and were highly correlated with the collective (agricultural practices and climate conditions) and differential (e.g., media properties) factors identified using an auto linear regression model. Furthermore, the multimedia transport of NEOs was largely similar but non-negligibly different during the rainy and dry seasons. A new multimedia ecological risk assessment revealed that 50.6% sites were at high risk, and the risk hotspots occurred in the central areas and the winter planting period. The risks were largely contributed by imidacloprid and thiamethoxam, indicating that there were non-ignorable ecological risks. Our results highlight the differential pollution patterns (distribution, transport, and driving factors) of the prevailing NEOs under tropical agricultural scenarios, and the fact that special attention should be paid to the risks posed by NEOs.

Sources, bioaccumulation, and toxicity mechanisms of cadmium in Chlamys farreri.

The Potentially toxic elements (PTEs) cadmium (Cd) is one of the most serious stressors polluting the marine environment. Marine bivalves have specific high enrichment capacity for Cd. Previous studies have investigated the tissue distribution changes and toxic effects of Cd in bivalves, but the sources of Cd enrichment, migration regulation during growth, and toxicity mechanisms in bivalves have not been fully explained. Here, we used stable-isotope labeling to investigate the contributions of Cd from different sources to scallop tissues. We sampled the entire growth cycle of Chlamys farreri, which is widely cultured in northern China, from juveniles to adult scallops. We found tissue variability in the bioconcentration-metabolism pattern of Cd in different bound states, with Cd in the aqueous accounting for a significant contribution. The accumulation pattern of Cd in all tissues during growth was more significant in the viscera and gills. Additionally, we combined a multi-omics approach to reveal a network of oxidative stress-induced toxicity mechanisms of Cd in scallops, identifying differentially expressed genes and proteins involved in metal ion binding, oxidative stress, energy metabolism, and apoptosis. Our findings have important implications for both ecotoxicology and aquaculture. They also provide new insights into marine environmental assessment and mariculture development.