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The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe2+, ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.

Carbon dots (CDs) prepared from biomass usually produce poor quantum yield and reproducibility. A fine separation of raw materials may enhance the fluorescence performance. In this work, embryos of cumin seeds were precisely chosen as the carbon source to prepare (CDs) through hydrothermal method. The obtained product (CDs-E) possessed a higher quantum yield of 10.60 % than those synthesized with testas or whole seeds, which may be due to the relatively smaller particle size and more C-N functional groups. Rutin, as a common natural active component, could quench the fluorescence of CDs-E notably through internal filtering effect. Herein, a highly selective fluorescent sensor based on CDs-E for detecting rutin was proposed with a linearity range of 0.05 ∼ 30 μM and a detection limit of 0.015 μM obtained. Additionally, the developed method was successfully applied for the detection of rutin in Flos Sophorae, rutin tablets and capsules. This work showed the significance of fine classification for natural carbon source in preparation of CDs and provided a feasible method for quality monitoring of rutin-related pharmaceuticals, health care products and traditional Chinese medicinal materials.

Coastal structures are prone to corrosion damage due to prolonged exposure to harsh corrosive environments, resulting in shortened service life and increased maintenance costs. Therefore, state-of-the-art technology is needed for rapid detection of corrosion in steel structures. This paper investigated the impact of training dataset quality on image recognition accuracy based on convolutional neural network technology. Multiple datasets were collected and used for neural network training, with the training results analysed using evaluation metrics. The research outcomes indicated that the quantity of data samples can improve at most by 1.2 times in terms of the average precision, while an excessive number of negative samples could interfere with the model’s ability to recognize positive samples, thereby reducing the precision. Instance segmentation datasets, compared to object detection datasets, were more sensitive to small objects due to their richer annotation information. This paper also proposed methods for improving datasets to enhance model prediction performance. The optimized model, combined with drone photography technology, was applied to practical engineering for bridge corrosion detection, providing technical support for intelligent bridge maintenance.

Diaphragm walls have been widely applied in long-span suspension bridges due to superior mechanical performance and extensive adaptability to various geological conditions. However, limited studies focused on the structural behaviour of rigid joints for diaphragm walls. This paper hence presented the flexural performance of joints through experimental investigation and numerical analysis. Two types of joints were designed to compare the structural response in terms of failure modes and moment resistance. Parametric analysis was carried out to explore critical parameters that influenced the joint performance significantly. A related provision in a current design code was evaluated to check if it was compatible to predict the moment capacity of designed joints. Results suggested that concrete cracks dominated the moment resistance of joints, and numerical analysis was reliable to predict the damage development as well as the moment-deflection relationship. The joint with U-shaped rebar exhibited more excellent performance that the counterpart with C-T lock. The critical parameters that could affect the member behaviour consisted of reinforcement strength, reinforcement diameter and a distance between tensile reinforcement and beam edge. The current design code provided nonconservative estimations of moment capacity, and thus a reduction factor should be proposed to promote satisfactory application.

Flow boiling in the rod bundle channel is an important phenomenon in nuclear reactors. The local inhomogeneous void fraction distribution in the flow channel will affect the flow and heat transfer in two phase flow. A 5 × 5 rod bundle test section is designed and utilized in the experiments and a conductivity probe is utilized to measure the local void fraction of two phase flow. A remote-control stepping driving assembly is designed to drive the void probe. The local void fraction characteristics at the outlet of a 5 × 5 rod bundle channel during subcooled boiling and saturated boiling are experimentally studied when the system pressure is 2∼3 MPa. The outlet subcooling ranges from 0 °C to 18 °C. The mass flux is 2000 kg/m2s and the heat flux ranges from 186.3 kW/m2 to 320.8 kW/m2.The effects of thermal parameters on local phase interfacial parameters in subcooled boiling and saturated boiling are obtained. The research results are important for revealing the two phase flow mechanisms in rod bundle channels.

Previous studies have demonstrated that the underlying mechanisms of myocardial ischemia/reperfusion injury (MIRI) are complex and involve multiple types of regulatory cell death, including ferroptosis, apoptosis, and autophagy. Thus, we aimed to identify the mechanisms underlying MIRI and validate the protective role of epigallocatechin-3-gallate (EGCG) and its related mechanisms in MIRI. An in vivo and in vitro models of MIRI were constructed. The results showed that pretreatment with EGCG could attenuate MIRI, as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) activity and apoptosis, inhibited iron overload, abnormal lipid metabolism, preserved mitochondrial function, decreased infarct size, maintained cardiac function, decreased reactive oxygen species (ROS) level, and reduced TUNEL-positive cells. Additionally, EGCG pretreatment could attenuate ferroptosis, apoptosis, and autophagy induced by MIRI via upregulating 14–3–3η protein levels. Furthermore, the protective effects of EGCG could be abolished with pAd/14–3–3η-shRNA or Compound C11 (a 14–3–3η inhibitor) but not pAd/NC-shRNA. In conclusion, EGCG pretreatment attenuated ferroptosis, apoptosis, and autophagy by mediating 14–3–3η and protected cardiomyocytes against MIRI.

Autosomal dominant neurodevelopmental disorder with or without hyperkinetic movements and seizures (NDHMSD) is a rare neurological disorder characterized by neurodevelopmental disorder and hyperkinetic movement, with or without seizures. Heterozygous mutation in the GRIN1 encoding the subunit 1 of the N-methyl-D-aspartate receptor caused this disorder. We first established an induced pluripotent stem cell (iPSC) line from a male patient with c.389A > G mutation in the GRIN1, via reprogramming with KLF4, SOX2, OCT3/4, and c-MYC. Through identification examination, the iPSCs (GWCMCi006-A) stably expressed pluripotency-associated stem cell markers, maintained a normal karyotype, and showed proliferative potential for three-germ layers differentiation.

Organic and inorganic substances coexist in the livers of marine mammals and may correlate with one another; however, their coexistence mechanisms and relevant key features remain largely unknown. In this study, temporal variations (2011–2021) in the concentrations of nine trace elements and 19 per- and polyfluoroalkyl substances (PFASs) in the livers of Indo-Pacific humpback dolphins (Sousa chinensis) and finless porpoises (Neophocaena phocaenoides) were investigated. Interannual Cd in dolphins increased significantly whereas Pb concentrations decreased over the past decade (p

This study attempted to clarify the carrying-over effect of different nitrogen treatments applied to the main crop on the crop population growth and yield formation of ratoon rice under mechanized cultivation in Southeast China. Based on the constant total nitrogen application amounts (225.00 kg ha−1) in the main crop, an experiment with different ratios of basal and topdressing nitrogen fertilizer (the ratio of basal fertilizer:primary tillering fertilizer:secondary tillering fertilizer:booting fertilizer at 3:1:2:4 (N1), 3:2:1:4 (N2), 3:3:0:4 (N3), and 4:3:0:3 (N4), respectively, and a control without nitrogen treatment (N0)) was set up across two consecutive years in field using hybrid rice variety Yongyou 1540 as the test materials. The results showed that the total tiller number and effective tillering percentage increased in the main crop under the N1 treatment, more nitrogen fertilizer applied in late growth stage of the main crop, and its effective tillering percentage of the main crop was the highest at up to 70.18%, which was 9.15% higher than that of conventional fertilization treatment (N4), more nitrogen fertilizer applied in early growth stage of the main crop. The same tendency was observed in leaf area index (LAI) value of the main crop and its subsequent ratoon rice, which were 16.52 and 29.87% higher, respectively, in the N1 treatment than that in the N4 treatment at the full heading stage. The same was true in the case of the transport rates of stem and sheath dry mater and the canopy light interception rates in both the main and its ratoon crops. The transport rate of stem and sheath in main crop rice under N1 treatment increased by 50.57% compared with N4 treatment. The canopy light interception rate of N1 treatment increased by 5.07% compared with N4 treatment at the full heading stage of the ratoon crop. Therefore, the total actual yield was the highest in the main and its ratoon crops under N1 treatment, averaging 17 351.23 kg ha−1 in two-year trials, which was 23.00% higher than that in the conventional fertilization treatment (N4). The results showed that appropriate nitrogen treatment was able to produce a good crop stand in the main crop, which was essential for producing a good ratoon crop population and high yield especially under mechanized cultivation with low stubble height of the main crop. The study suggested that shifting the proper nitrogen application amounts to the late growth stage of the main crop, such as N1 treatment, not only had a higher productive effect on ensuring the yield of the main crop, but also had a positive effect on the axillary bud sprouts from the stubbles for ratoon rice, resulting in an increased percentage of productive panicles and achieving the goal of one planting with two good harvests under the conditions of our study.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy, which may arise from genetic etiologies. TANC2 mutation may cause the neurodevelopmental disorders and epilepsy such as LGS. By reprogramming with SOX2, KLF4, c-MYC and OCT3/4, we generated an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) collected from a two-year-old Chinese boy individual to be used as a disease model with TANC2 mutation. By fully examination, the resulting iPSCs expressed pluripotency-associated stem cell markers, maintained the normal karyotype and proliferative potential for three-germ layer differentiation.

A new cell line was isolated and characterized from the head kidney of Siganus fuscescens (rabbit fish). The new macrophagic-like cell line was named as rabbit fish macrophage (RFM), and which could be sub-cultured for over 50 cycles since the development. RFM cell line was tested for growth in different temperatures and serum concentrations: the best growing condition was optimized at 20% serum under 28 °C. In cultured RFM cells, sequencing of 18S rRNA, as well as immunostaining of cytokeratin and CD 68, confirmed the identity as macrophagic cell of S. fuscescens. Cultured RFM cells were exposed to challenge of inflammation, as triggered by LPS, showing highly sensitive responses to inflammation, including release of nitric oxide, expression of cytokine, and activation of phagocytosis. The water extract of aerial part of Scutellaria baicalensis, named as SBA, has been shown anti-inflammatory property in S. fuscescens fish. In order to extend the application of SBA in aquaculture, the extract and its effective flavonoids, i.e. baicalin and scutellarin, were applied in LPS-treated RFM cells. Application of SBA extract, baicalin or scutellarin, inhibited the expressions of LPS-induced inflammatory cytokines, i.e. IL-1β, TNF-α, as well as the signaling of transcription factor NF-κB. The results support the established RFM cell line could be an ideal in vitro model in drug screening relating to inflammation. Additionally, the notion of SBA herbal extract in fish aquaculture is supported by its efficacy against inflammation.

Introduction: It has been well established that EGFR Thr790Met is one of the major resistance mechanisms to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). Nevertheless, whether EGFR Thr790Leu (T790L), which shares the mutation site of Thr790 with EGFR Thr790Met, mediates resistance to EGFR TKIs remains elusive. The treatment options for patients harboring this rare mutation have not been reported. Methods: Capture-based targeted ultradeep sequencing was performed on tumor and plasma samples collected at various treatment milestones from three patients with advanced lung adenocarcinoma undergoing targeted therapy. Results: Needle biopsy of lymph node metastasis from patient 1 revealed EGFR T790L at disease progression on first-line treatment of gefitinib. Patient 2 had EGFR T790L identified from needle biopsy of lung tissue at disease progression on icotinib treatment. This patient was subsequently treated with osimertinib and achieved stable disease with a progression-free survival of 9 months. For patient 3, at disease recurrence after surgery, resected lung tumor tissue was retrieved for molecular profiling and revealed EGFR exon 19 deletion and EGFR T790L. The patient subsequently received osimertinib treatment and continued to benefit for 16 months and counting. She has maintained stable disease at the time of submission of this manuscript. Conclusions: We revealed for the first time that EGFR T790L may serve as a potential resistance mechanism to first-generation EGFR TKIs. We also report the first clinical evidence of efficacy generated by osimertinib in patients with lung adenocarcinoma harboring primary or acquired EGFR T790L, shedding light on treatment options for this subset of patients.

Icariin (ICA) and phosphorylated icariin (pICA) have excellent antiviral and antioxidant effects. However, whether ICA and pICA cause anti-LPS-induced intestinal damage remains unclear. In this study, we used Caco-2 cells as a model to investigate the protective effects of ICA and pICA on human colonic epithelial cells and explore their potential mechanisms. Our results indicated that ICA and pICA increased cell viability and decreased lactate dehydrogenase activity in Caco-2 cells. ICA and pICA also attenuated LPS-induced changes in intestinal epithelial cell permeability and reduced the levels of oxidative stress indicators, such as reactive oxygen species, malondialdehyde, and hydrogen peroxide, in Caco-2 cells. Antioxidant indicators, such as superoxide dismutase, glutathione peroxidase, catalase and total antioxidant capacity, were increased, while the levels of IL-1β, IL-6, IL-8 and TNF-α were reduced in the ICA and pICA groups. Furthermore, ICA and pICA decreased the gene abundance and enzyme activities of caspase-3, -8, -9 and -10 in Caco-2 cells. Our data suggest that ICA and pICA effectively attenuated LPS-induced changes in the oxidative stress, inflammation, apoptosis and intestinal permeability of intestinal epithelial cells. These findings provide new insight for treating LPS-induced intestinal injury.

Maize/peanut intercropping system shows the significant yield advantage. Soil microbes play major roles in soil nutrient cycling and were affected by intercropping plants. This experiment was carried out to evaluate the changing of rhizosphere microbial community composition, and the relationship between microbial community and soil enzymatic activities, soil nutrients in maize/peanut intercropping system under the following three treatments: maize (Zea mays L.) and peanut (Arachis hypogaea L.) were intercropped without any separation (NS), by half separation (HS) using a nylon net (50 µm) and complete separation (CS) by using a plastic sheet, respectively. The soil microbial communities were assessed by phospholipid fatty acid (PLFA). We found that soil available nutrients (available nitrogen (Avail N) and available phosphorus (Avail P)) and enzymatic activities (soil urase and phosphomonoesterase) in both crops were improved in NS and HS treatments as compared to CS. Both bacterial and fungal biomasses in both crops were increased in NS followed by HS. Furthermore, Gram-positive bacteria (G+) in maize soils were significant higher in NS and HS than CS, while the Gram-negative (G–) was significant higher in peanut soil. The ratio of normal saturated to monounsaturated PLFAs was significantly higher in rhizosphere of peanut under CS treatment than in any other treatments, which is an indicator of nutrient stress. Redundancy analysis and cluster analysis of PLFA showed rhizospheric microbial community of NS and HS of both plants tended to be consistent. The urase and Avail N were higher in NS and HS of both plants and positively correlated with bacteria, fungi (F) and total PLFAs, while negatively correlated with G+/G– and NS/MS. The findings suggest that belowground interactions in maize/peanut intercropping system play important roles in changing the soil microbial composition and the dominant microbial species, which was closely related with the improving of soil available nutrients (N and P) and enzymatic activities.

Mangrove ecosystems are vital for coastal protection, biodiversity, and pollution interception, yet their interactions with microplastics in rapidly urbanizing regions remain underexplored. This study investigated the microplastic dynamics in the Maozhou River and Dasha River, along with the coastal Xiwan Mangrove Park in the Pearl River Estuary, the second largest estuary in China. Samples were collected from mangrove and surrounding areas, identifying microplastics using Fourier-transform infrared spectroscopy (FTIR) and Laser Direct Infrared (LDIR) techniques. Microplastic concentrations ranged from 245.8 to 1562.4 n/m³ in water and 374.3 to 7475.3 n/kg in sediments. The Maozhou River exhibited consistent microplastic levels across varying hydrological conditions, while the Dasha River and Xiwan Mangrove showed greater sensitivity to water flow changes influenced by urban land use. During high-flow periods, urban river microplastic concentrations decreased due to dilution, whereas mangrove areas experienced elevated levels in water from urban runoff, upstream retention, and sediment resuspension, suggesting a potential for outward release. Weaker water dynamics led to increased microplastic accumulation in mangrove sediments. The distribution of microplastic types was influenced by multiple urban pollution sources, with synthetic rubbers linked to urban transportation comprising over 50 % of some samples, peaking at 79 %. These findings underscore the dual role of mangroves as microplastic sinks and potential sources, highlighting the significant impact of hydrological conditions on their function. This study offers new insights into microplastic pollution in urban mangrove ecosystems and emphasizes the urgent need for improved management strategies in coastal areas facing rapid urbanization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Direct ingestion of micro/nanoplastics (MNPs) results in significant accumulation in gastrointestinal (GI) tract of fish. The breathing process of fish makes MNPs easily retained in their gills. However, the uptake of MNPs in other fish organs remains largely unknown, let alone their kinetic processes. Herein, microplastics (MPs) and nanoplastics (NPs) in vivo imaging and precise quantification in various tissues (GI tract, gill, liver, brain, eye, and skin) of seawater (SW)- and freshwater (FW)- acclimated medaka Oryzias melastigma were achieved at an environmentally relevant concentration. Subsequently, the distribution kinetics of MNPs was investigated over a 96-h uptake and 48-h depuration period. MNPs were quickly and mostly captured in GI tract and gill of O. melastigma, and then transferred to liver and brain likely via blood circulation. Such transport was more efficient for NPs as compared to MPs, as evidenced by the consistently higher bioconcentration factors in both SW and FW conditions. The detection of MNPs in eye and skin of O. melastigma was more of an adsorption process, although the specific mechanisms of adsorption and absorption process can hardly be clearly differentiated. This study presented distribution kinetics of MNPs in O. melastigma and highlighted their possible transportation among tissues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Growing micro- and nano-plastic (MNPs) pollution in the environment poses a threat to marine animals. Due to their excellent filtration capacity, bivalves can easily ingest MNPs, which could be translocated to open circulation system with potential risks. In the present study, the accumulation and elimination of MNPs (200 nm and 1 µm) in the mussel hemolymph serum and hemocytes were firstly quantified, and the differential sensitiveresponses of two subpopulations of hemocytes were then explored by in vivo exposure under environmentally relevant concentration of MNPs (200 µg/L). We demonstrated that MNPs were readily translocated into hemolymph serum, but were immediately followed by efficient internalization by hemocytes. Remarkably, concentrations of MNPs in hemolymph were only 0.63 and 0.39 times lower than the ambient exposure concentration. Granulocytes displayed a much higher potential of accumulating MNPs than the agranulocytes. MPs were more readily internalized by granulocytes, with their estimated maximum bioaccumulation factor (BCF) of 0.29 L/g. Due to the primary function of phagocytic encapsulation of MNPs by granulocytes, lysosome features especially the decline of subsequent lysosome membrane potential could be a potential sensitive biomarker in response to MNPs exposure. Our results provided insights on the bioaccumulation of MNPs at the cellular levels in marine bivalves., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nano- and microplastics (NMPs) pollution is widespread in the oceans, posing potential risks to marine species. This study examined the accumulation capacity and selectivity potentials of NMPs by a marine copepod Parvocalanus crassirostris under different food mixtures by modeling the combined biokinetic and functional response. We investigated two sizes of NMPs (200 nm and 5 µm) across a concentration gradient (0 - 5000 µg/L) and varying diatom abundances (0, 10 4 , 10 5 cells/mL). Fluorescence imaging and quantification revealed that P. crassirostris actively ingested NMPs at low concentration. Accumulation increased with NMPs concentration but eventually saturated due to gut capacity limits, following a Holling type II functional response (i.e., hyperbolic curve). Our novel functional response model estimated the key parameters and demonstrated that the maximum accumulation reached 5.3 % of dry weight with averaged half-saturation constants of 229 µg/L. The size of NMPs did not significantly affect the total accumulation or satiety levels. The presence of diatoms influenced the feeding selectivity and decreased the microplastic accumulation by 73 % at 10 5 cells/mL, while facilitating nanoplastic accumulation by 81 % at 10 4 cells/mL. This study enhanced our understanding of NMPs bioavailability and environmental fate in marine ecosystems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bivalve hemocytes are oyster immune cells composed of several cellular subtypes with different functions. Hemocytes accumulate high concentrations of copper (Cu) and exert critical roles in metal sequestration and detoxification in oysters, however the specific biochemical mechanisms that govern this have yet to be fully uncovered. Herein, we demonstrate that Cu(I) is predominately sequestered in lysosomes via the Cu transporter ATP7A in hemocytes to reduce the toxic effects of intracellular Cu(I). We also found that Cu(I) is translocated along tunneling nanotubes (TNTs) relocating from high Cu(I) cells to low Cu(I) cells, effectively reducing the burden caused by overloaded Cu(I), and that ATP7A facilitates the efflux of intracellular Cu(I) in both TNTs and hemocyte subtypes. We identify that elevated glutathione (GSH) contents and heat-shock protein (Hsp) levels, as well as the activation of the cell cycle were critical in maintaining the cellular homeostasis and function of hemocytes exposed to Cu. Cu exposure also increased the expression of membrane proteins (MYOF, RalA, RalBP1, and cadherins) and lipid transporter activity which can induce TNT formation, and activated the lysosomal signaling pathway, promoting intercellular lysosomal trafficking dependent on increased hydrolase activity and ATP-dependent activity. This study explores the intracellular and intercellular transport and detoxification of Cu in oyster hemocytes, which may help in understanding the potential toxicity and fate of metals in marine animals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Copper (Cu) redox state has been an important issue in biology and toxicology research, but many research gaps remain to be explored due to the limitations in the detecting techniques. Herein, the regulation of Cu homeostasis, including absorption, translocation, utilization, storage, and elimination behavior is discussed. Cuproptosis, a newly identified type of cell death caused by excessive Cu accumulation, which results in the aggregation of DLAT protein or the loss of Fe-S cluster and finally proteotoxic stress, is reviewed. Several longstanding mysteries of diseases such as Wilson disease and toxic effects, may be attributed to cuproptosis. Furthermore, we review the advanced detection methods and application of Cu(I) and Cu(II), especially the in-situ imaging techniques such as XANES, and chemosensors. Most of the existing studies using these detection techniques focus on the bioaccumulation and toxicity of Cu(I) and Cu(II) in cells and aquatic organisms. Finally, it will be important to identify the roles of Cu(I) and Cu(II) in the growth, development, and diseases of organisms, as well as the relationship between bioaccumulation and toxicity of Cu(I) and Cu(II) in cellular and aquatic toxicology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite the growing awareness of potential human and environmental risks associated with sunscreens, identifying the specific constituents responsible for their potential toxicity is challenging. In this study, we applied three different types of sunscreens with contrasting compositions and compared the effects of their particulate and soluble fractions based on 15 cellular biomarkers of HaCaT cells. Multilinear regression analysis revealed that the internalized soluble fractions played a primary role in the overall cytotoxicity of sunscreen mixtures, which was primarily attributed to their biotransformation, generating metabolites with higher toxicity. The presence of plastic microspheres in sunscreens either inhibited the internalization of soluble fractions or led to their redistribution toward lysosomes. Conversely, subcellular toxicity resulting from the sunscreen mixture was predominantly influenced by particulates. Bio-transformable particulates such as ZnO dissolved in the organelles and induced higher subcellular toxicity compared to bioinert particulates such as microplastics. Subcellular biomarkers including lysosomal count, lysosomal size, mitochondrial count and mitochondrial shape emerged as the potential predictors of sunscreen presence. Our study provides important understanding of sunscreen toxicity by elucidating the differential impacts of particulate and soluble fractions in mixture contaminants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SIGNIFICANCE: Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Autosomal dominant neurodevelopmental disorder with or without hyperkinetic movements and seizures (NDHMSD) is a rare neurological disorder characterized by neurodevelopmental disorder and hyperkinetic movement, with or without seizures. Heterozygous mutation in the GRIN1 encoding the subunit 1 of the N-methyl-D-aspartate receptor caused this disorder. We first established an induced pluripotent stem cell (iPSC) line from a male patient with c.389A > G mutation in the GRIN1, via reprogramming with KLF4, SOX2, OCT3/4, and c-MYC. Through identification examination, the iPSCs (GWCMCi006-A) stably expressed pluripotency-associated stem cell markers, maintained a normal karyotype, and showed proliferative potential for three-germ layers differentiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

With the increasing micro(nano)plastics (MNPs) pollution in aquatic environments, fish respiration is encountering a huge threat. Herein, polystyrene (PS) MNPs with three sizes (80 nm, 2 µm, and 20 µm) were exposed to tilapia Oreochromis niloticus at an environmentally relevant concentration of 100 μg/L for 28 days and their impacts on respiratory function were investigated. Based on the results of oxygen consumption and histological analysis, all the three treatments could induce respiratory damages and such impacts were more severe for the 2 µm and 20 µm treatments than for the 80 nm treatment. These results were explained by the more significant upregulation of egln3 and nadk, and the downregulation of isocitrate. Transcriptomics and metabolomics further revealed that TCA cycle played a key role in respiratory dysfunction induced by micro-sized PS particles, and cytokine and chemokine related functions were simultaneously enriched. Although nano-sized PS particles had the potential to penetrate the respiratory epithelium and reached the internal structure of the O. niloticus gills, they were easily expelled through the blood circulation. Our results highlighted the serious threat of MNPs to fish respiration and provided insights into the differential toxicological mechanisms between micro-sized and nano-sized particles, thus assisting in ecological risk assessments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hypoxia is a mounting environmental problem affecting coastal waters globally, posing severe consequences for biodiversity and marine life. Metazoans respond to hypoxia stress via the hypoxia-inducible factor (HIF) pathway, but few studies have addressed the gene diversity of the functionally important HIF-pathway. Understanding whether functional diversity exists in the HIF-pathway is a key first step in identifying genes that may impact hypoxia fitness. Here, we leveraged whole-genome resequencing data and bioinformatics tools to identify the key members of the HIF-pathway (HIFα/β, EGLN, and VHL) and genetic diversity in the threatened Eleutheronema. Phylogenetic analysis revealed that teleost-specific duplicates of epas1 (epas1a/b) were followed by the loss of one of each hif1α and hif1αl in Eleutheronema species. Strong collinearity and similarity of gene characteristics suggested the functional conservation of the HIF-pathway during Eleutheronema evolution. Purifying selection was the major theme in HIF-pathway evolution, leading to a reduction in genetic diversity. Substantially low nucleotide diversity of the HIF-pathway was observed among populations, which might indicate the loss of hypoxia fitness in Eleutheronema. Additionally, the normoxic presence of the HIF-pathway differed among tissues and was species-dependent, indicating their diverse roles during development. Significant regulation of HIF-pathway expression levels was observed across tissues under hypoxic conditions, suggesting critical roles in the hypoxia stress response. Moreover, variant molecular characters suggested different roles in response to hypoxia of the HIF-pathway, which were reflected in the different expression patterns across tissues. Our present study provides novel insights into the interplay between gene diversity within the HIF-pathway and hypoxia fitness in threatened Eleutheronema. We highlighted the importance of HIF-pathway-mediated transcriptional regulation in response to hypoxia stress, which provided valuable information for the genetic mechanisms underlying hypoxia adaptation in fish. The bioinformatic methods developed here have broad applications for other species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Acute toxicity determination is essential in the ecological risk assessment. Traditionally, acute toxicity testing requires substantial numbers of animals and uses death as an apical end point which requires large number of experimental animals and takes days to obtain the results. Application of fish cell lines can provide a possible alternative to traditional acute toxicity test. However, cell-based assay may show several orders of magnitude less sensitive than the animal-based results. Some changes in cellular organelles could have the sensitivity in responding to pollutants. For this reason, a cell-based fluorescent assay was developed using rabbitfish fin cells as model and fluorescent probes to visualize the subcellular responses. The subcellular responses under sewage effluents exposure were captured by confocal microscopy. These cellular responses were quantified and several subcellular indexes represented the toxicity. The optimized assay was then used to determine the toxicity of sewage effluents displaying toxicity to aquatic animals. Through visualization of cellular responses, we further screened several cellular indexes including lysosomal number and mitochondrial size which had a good linear relationship with sewage effluents content. Besides, these cellular indexes had a good agreement between in vivo and in vitro results, demonstrating the accuracy of cellular parameters in representing the acute toxicity of sewage effluents. The developed cell-based testing assay presented here has the characteristics of a faster and cheaper method, which does not require complex facilities and large amount of testing samples. The developed assay may be further applied in predicting the acute toxicity to sewage effluents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fish can regulate their Zn body bioaccumulation, but the mechanisms and physiological responses at the organ level are still largely unknown. In the present study, we exposed the marine seabreams under different Zn levels (deficient, optimum and excess levels) over a period of 4 weeks and examined how fish maintained its regulation of bioaccumulation with associated physiological effects at the fish intestinal organ. Our results indicated that fish intestinal organs constantly controlled the Zip family to "rob" more Zn under Zn-deficiency (with a dietary level of 7.9 mg/kg), whereas restricted the Zn efflux to preserve the intestinal function. Under Zn-excess conditions (193.3 mg/kg), the fish intestine maintained a limited Zn homeostasis (37.8-44.6 μg/mg) by initially inhibiting the influx through the Zip family receptor, but later accelerating both influx and efflux of Zn. Based on the WGCNA method, Zn deficient dietary exposure first resulted in defense response with subsequent switching to antioxidant defense. Instead, excess Zn first triggered the immunological response, but then led to physiological toxicity (abnormal in lipid metabolism). Although Zn had multiple biological functions, it was preferentially involved in lipid metabolism under different dietary Zn doses. This study provided direct evidence for Zn regulation at the organ level and detoxification mechanisms against potential environmental toxicity in fish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Trace transition metal uptake is tightly associated with cellular biological processes. Herein, we demonstrated that copper (Cu) bioaccumulation and uptake were controlled by the cell cycle. A cyclical kinetics of Cu bioaccumulation and surge in S/M phase were observed in the synchronized green algae Chlamydomonas reinhardtii. The labile Cu(I) content also increased in the S/M phase, although the increase was moderate. Based on the comparative analysis of bioaccumulation and transcriptome data, we found the CRR1-mediated Cu uptake pathway, and CTR1 and CTR2 transporters were regulated by the intracellular Cu quota and suppressed during cell division with high Cu content. In contrast, we hypothesized a novel intracellular Cu-quota-independent Cu(I) uptake pathway in which the transporter COPT1 might be responsible for the Cu influx during cell division. Besides, a plunge of ATX1 expression level was also observed during cell division, which indicated an inhibition of the secretory pathway of Cu with the participation of ATX1 in terms of transcriptome level, probably resulting in reduced Cu efflux. Additionally, both fluorometric probe staining and transcriptomic data demonstrated that mitochondria were the dominant destination for the extra Cu content in S/M phase. Finally, some cytotoxic responses were also observed in S/M phase. Pathways related to reactive oxygen species and glutamine metabolic process were enriched in GO term and KEGG enrichment analysis, and glutathione content and cell membrane permeability determined by fluorometric probes also increased during cell division. This study showed a sharp increase of Cu uptake in cell division and revealed the genetic regulation mechanisms for the cell cycle control of Cu uptake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

After the COVID-19 outbreak, masks have become an essential part of people lives. Although several studies have been conducted to determine the release of hazardous substances from masks, how their co-presence poses a potential exposure risk to human health remains unexplored. In this study, we quantitatively compared the leaching of substances from six different common types of masks, including phthalate acid esters (PAEs), metals, and microplastics (MPs), and comprehensively evaluated the potential cytotoxicity of different leachates. MPs smaller than 3 µm were quantified by Py-GC-MS, and reusable masks showed greater releasing potentials up to 1504 µg/g. We also detected the prevalence of PAEs in masks, with the highest release reaching 42 μg/g, with dibutyl phthalate (DBP), diisobutyl phthalate (DiBP) and bis (2-ethylhexyl) phthalate (DEHP) being the predominant types. Moreover, the antimicrobial cloth masks released 173.0 µg of Cu or 4.5 µg of Ag, representing 2.7% and 0.04% of the original masks, respectively. Our cell-based assay results demonstrated for the first time that mask leachate induced nuclear condensation with DNA damage, and simultaneously triggered high levels of glutathione and reactive oxidative stress production, which exacerbated mitochondrial fragmentation, eventually leading to cell death. Combined with substance identification and correlation analysis, PAEs were found to be the contributors to cytotoxicity. Masks containing Cu or Ag led to acidification of lysosomes and alkalinization of cells. These results strongly suggested that the levels of PAEs in the production of regulatory masks should be strictly controlled., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Our current understandings of the effects of microplastics and nanoplastics (MNPs) on aquatic animals are predominantly based on the single types of plastic particles. In the present study, we employed the highly fluorescent MNPs that incorporated aggregation-induced emission fluorogens and investigated the selective ingestion and response of Daphnia exposed to different types of plastics at environmentally relevant concentrations simultaneously. When daphnids were exposed to a single MNP, D. magna ingested them instantly in significant amounts. However, even low concentrations of algae had a significant negative impact on the MNP uptake. Specifically, algae caused the MPs to pass through the gut faster, reduced acidification and esterase activity, and changed the distribution of MPs in the gut. In addition, we also quantified the influences of size and surface charge on the selectivity of D. magna. The daphnids selectively ingested larger and positively charged plastics. MPs effectively reduced the uptake of NP and increased its gut passage time. Aggregation of positively and negatively charged MNPs also influenced the gut distribution and increased the gut passage time. The positively charged MPs accumulated in the middle and posterior gut, while aggregation of MNPs also increased acidification and esterase activity. These findings provided fundamental knowledge on the selectivity of MNPs and the microenvironmental responses of zooplankton guts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Heart failure typically occurs early in the clinical course of sustained cardiac hypertrophy that is accompanied by maladaptive remodeling of the heart. It is critical to discover new mechanisms and effective therapeutic targets to prevent and cure pathological cardiac hypertrophy. The objective of the study was to evaluate the effects of circRNAs on NSD2-induced ventricular remodeling. We screened the dysregulated circRNAs in normal or NSD2 -/- C57BL/6 mice with or without transverse aortic constriction (TAC), and found that circCmss1 significantly increased in normal TAC mice, but decreased in NSD2 -/- TAC mice. Angiotensin II(Ang II)induced neonatal cardiomyocyte hypertrophy in vitro and the pressure overload-induced cardiac hypertrophy in vivo can be reduced by Knocking down circCmss1. We further investigated the downstream signaling of circCmss1 in the progression of NSD2-promoted ventricular remodeling and discovered that circCmss1 could interact with a transcription factor EIF4A3 and induce the expression of transferrin receptor 1 (TfR1), thus activating the ferroptosis in cardiomyocytes. This study highlights the significance of NSD2 activation of circCmss1/EIF4A3/TfR1 as therapeutic targets for treating pathological myocardial hypertrophy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Understanding the adaptive ecological divergence provides important information for revealing biodiversity generation and maintenance. Adaptive ecology divergence in populations occurs in various environments and locations, but its genetic underpinnings remain elusive. We generated a chromosome-level genome of Eleutheronema tetradactylum (~582 Mb) and re-sequenced 50 allopatric E. tetradactylum in two independent environmental axes in China and Thailand Coastal waters as well as 11 cultured relatives. A low level of whole genome-wide diversity explained their decreased adaptive potential in the wild environment. Demographic analysis showed evidence of historically high abundance followed by a continuous distinct decline, plus signs of recent inbreeding and accumulation of deleterious mutations. Extensive signals of selective sweeps with signs of local adaptation to environmental differentiation between China and Thailand at genes related to thermal and salinity adaptation were discovered, which might be the driving factors of the geographical divergence of E. tetradactylum. Many genes and pathways subjected to strong selection under artificial breeding were associated with fatty acids and immunity (ELOVL6L, MAPK, p53/NF-kB), likely contributing to the eventual adaptation of artificial selective breeding. Our comprehensive study provided crucial genetic information for E. tetradactylum, with implications for the further conservation efforts of this threatened and ecologically valuable fish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Zinc ion (Zn) is an essential nutrition element and it is important to understand its regulation and distribution among different cellular organelles. Here, subcellular trafficking of Zn in rabbitfish fin cells was investigated through bioimaging, and the results showed that the toxicity and bioaccumulation of Zn were both dose- and time-dependent. Cytotoxicity of Zn only occurred when the Zn concentration reached 200-250 μM after 3 h of exposure when the cellular quota of Zn:P reached a threshold level around 0.7. Remarkably, the cells were able to maintain homeostasis at a low Zn exposure concentration or within the first 4-h exposure. Zn homeostasis was mainly regulated by the lysosomes which stored Zn within the short exposure period, during which the number and size of lysosomes as well as the lysozyme activity increased in response to incoming Zn. However, with increasing Zn concentration beyond a threshold concentration (> 200 μM) and an exposure time > 3 h, homeostasis was disrupted, leading to an Zn spillover to cytoplasm and other cellular organelles. At the same time, cell viability decreased due to the Zn damage on mitochondria which caused morphological changes (smaller and rounder dots) and over production of reactive oxygen species, indicating the dysfunction of mitochondria. By further purifying the cellular organelles, cell viability was found to be consistent with the mitochondrial Zn amount. This study suggested that the amount of mitochondrial Zn was an excellent predictor of Zn toxicity on fish cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Considering the complexity of coastal and estuarine systems, a great challenge of environmental health assessment is to distinguish between natural and anthropogenically induced stress. Quantification of trace element accumulation in the tissues of sedentary bivalves with subsequent hotspot identification is important to assess the pollution status. The present study conducted a nationwide mapping of bioavailable macro- and trace elements in a widely distributed biomonitoring clam Ruditapes philippinarum from China. Ag, As, Cd, Cr, Cu, and Zn concentrations in the clams showed similar levels as those documented previously in mussels, but were lower than those in oysters at similar sites from China. Notably, the total As concentrations in clams at Xinkai Estuary and Beibu Bay were relatively higher than those at other sites in China. After normalization by tissue biomass, salinity (Na) and nutrient (P), some hotspots were identified with high pollution of trace elements at Liaodong Bay of Bohai Sea, Gold Beach of Qingdao, Dongling Port of Yellow Sea, Hangzhou Bay and adjacent coasts of East China Sea, and Pearl River Estuary and Beibu Bay of South China Sea. This study demonstrated that most trace elements had a path-dependent effect of biomass, except for Cd which showed an indirect pathway of AgNi related accumulation. Results showed significant correlations between Cd, Zn, Ag and Ni, and between Pb/Cr and Ti in clams. After mass normalization, all trace elements displayed significantly positive correlations with Na or P. Simultaneously, the clam biomass played an intermediary role in trace element accumulation in non-linear patterns related to salinity and nutrient. These results are important in evaluating the composite ambiguous information of the historical data of trace element biomonitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Understanding the toxic mechanism of silver nanoparticles (AgNPs) is crucial for it risk assessment in marine environment, but the role of Ag + release in the AgNP toxicity to marine biota is not yet well addressed. This study investigated the toxicity of AgNPs to the veliger larvae of oyster Crassostrea angulata, with a specific focus on the possibility of the involvement of in vivo dissolution of AgNPs in the toxicity via an aggregation-induced emission luminogen (AIEgen)-based imaging technique. AgNO 3 exhibited significantly greater toxicity than AgNPs based on the total Ag, as indicated by lower 50 % growth inhibition concentration (EC 50 ). The average concentration of soluble Ag in seawater at the EC 50 of AgNPs was far lower than the EC 50 of AgNO 3 , indicating that the AgNP toxicity could not be fully explained by the dissolved Ag in the medium. Despite the comparable soluble Ag concentration in seawater for both treatments, more Ag was accumulated in the larvae exposed to AgNPs, suggesting their ability to directly ingest particulate Ag, which was further confirmed by the presence of AgNPs aggregates in the esophagus and stomach. With the application of AIEgen-based imaging technique, in vivo dissolution of AgNPs in oyster larvae was thoroughly verified by an increase in Ag(I) content in the larvae exposed to AgNPs after depuration. The results collectively implied that apart from the Ag released in the medium, the Ag dissolved from the ingested AgNPs may also greatly contribute to the toxicity of AgNPs toward the oyster larvae. The findings of this work shed new light on the bioavailability and toxicity of AgNPs in marine environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)