A DNA demethylase reduces seed size by decreasing the DNA methylation of AT-rich transposable elements in soybean.

Understanding how to increase soybean yield is crucial for global food security. The genetic and epigenetic factors influencing seed size, a major crop yield determinant, are not fully understood. We explore the role of DNA demethylase GmDMEa in soybean seed size. Our research indicates that GmDMEa negatively correlates with soybean seed size. Using CRISPR-Cas9, we edited GmDMEa in the Dongnong soybean cultivar, known for small seeds. Modified plants had larger seeds and greater yields without altering plant architecture or seed nutrition. GmDMEa preferentially demethylates AT-rich transposable elements, thus activating genes and transcription factors associated with the abscisic acid pathway, which typically decreases seed size. Chromosomal substitution lines confirm that these modifications are inheritable, suggesting a stable epigenetic method to boost seed size in future breeding. Our findings provide insights into epigenetic seed size control and suggest a strategy for improving crop yields through the epigenetic regulation of crucial genes. This work implies that targeted epigenetic modification has practical agricultural applications, potentially enhancing food production without compromising crop quality.

Transformation of 6:6 PFPiA in the gut of Xenopus laevis: Synergistic effects of CYP450 enzymes and gut microflora.

As a frequently detected per- and polyfluoroalkyl substance in the environment, 6:6 perfluoroalkylhypophosphinic acid (6:6 PFPiA) is vulnerable to transformation in the liver of organisms, but the transformation in gut is still unclear. This study investigates the molecular mechanisms of 6:6 PFPiA transformation in the gut of Xenopus laevis upon a 28-day exposure in water. Before Day 16, a notable correlation (p = 0.03) was observed between the transformation product (PFHxPA) and cytochrome P450 (CYP450) enzyme concentration in gut. This suggests that CYP450 enzymes played an important role in the transformation of 6:6 PFPiA in the gut, which was verified by an in vitro incubation with gut tissues, and supported by the molecular docking results of 6:6 PFPiA binding with CYP450 enzymes. From the day 16, the CYP450 concentration in gut decreased by 31.3 % due to the damage caused by 6:6 PFPiA, leading to a decrease in the transformation capacity in gut, but the transformation rate was stronger than in liver. This was in contrast with the in vitro experiment, where transformation was stronger in liver. In the mean time, the abundance of Bacteroidota in gut increased, which released hydrolytic enzyme and then could participate in the transformation as well. This study reveals the potential of the gut in metabolizing environmental pollutants, and provides profound insights into the potential health risks caused by 6:6 PFPiA in organisms.

Microeukaryotic plankton community dynamics under ecological water replenishment: Insights from eDNA metabarcoding.

Ecological water replenishment (EWR) is an important strategy for river restoration globally, but timely evaluation of its ecological effects at a large spatiotemporal scale to further adjust the EWR schemes is of great challenge. Here, we examine the impact of EWR on microeukaryotic plankton communities in three distinct river ecosystems through environmental DNA (eDNA) metabarcoding. The three ecosystems include a long-term cut-off river, a short-term connected river after EWR, and long-term connected rivers. We analyzed community stability by investigating species composition, stochastic and deterministic dynamics interplay, and ecological network robustness. We found that EWR markedly reduced the diversity and complexity of microeukaryotic plankton, altered their community dynamics, and lessened the variation within the community. Moreover, EWR disrupted the deterministic patterns of community organization, favoring dispersal constraints, and aligning with trends observed in naturally connected rivers. The shift from an isolated to a temporarily connected river appeared to transition community structuring mechanisms from deterministic to stochastic dominance, whereas, in permanently connected rivers, both forces concurrently influenced community assembly. The ecological network in temporarily connected rivers post-EWR demonstrated significantly greater stability and intricacy compared to other river systems. This shift markedly bolstered the resilience of the ecological network. The eDNA metabarcoding insights offer a novel understanding of ecosystem resilience under EWR interventions, which could be critical in assessing the effects of river restoration projects throughout their life cycle.

Climate-related naturally occurring epimutation and their roles in plant adaptation in A. thaliana.

DNA methylation has been proposed to be an important mechanism that allows plants to respond to their environments sometimes entirely uncoupled from genetic variation. To understand the genetic basis, biological functions and climatic relationships of DNA methylation at a population scale in Arabidopsis thaliana, we performed a genome-wide association analysis with high-quality single nucleotide polymorphisms (SNPs), and found that ~56% on average, especially in the CHH sequence context (71%), of the differentially methylated regions (DMRs) are not tagged by SNPs. Among them, a total of 3235 DMRs are significantly associated with gene expressions and potentially heritable. 655 of the 3235 DMRs are associated with climatic variables, and we experimentally verified one of them, HEI10 (HUMAN ENHANCER OF CELL INVASION NO.10). Such epigenetic loci could be subjected to natural selection thereby affecting plant adaptation, and would be expected to be an indicator of accessions at risk. We therefore incorporated these climate-related DMRs into a gradient forest model, and found that the natural A. thaliana accessions in Southern Europe that may be most at risk under future climate change. Our findings highlight the importance of integrating DNA methylation that is independent of genetic variations, and climatic data to predict plants' vulnerability to future climate change.

Tactile corpuscle-inspired piezoresistive sensors based on (3-aminopropyl) triethoxysilane-enhanced CNPs/carboxylated MWCNTs/cellulosic fiber composites for textile electronics.

Recently, wearable electronic products and gadgets have developed quickly with the aim of catching up to or perhaps surpassing the ability of human skin to perceive information from the external world, such as pressure and strain. In this study, by first treating the cellulosic fiber (modal textile) substrate with (3-aminopropyl) triethoxysilane (APTES) and then covering it with conductive nanocomposites, a bionic corpuscle layer is produced. The sandwich structure of tactile corpuscle-inspired bionic (TCB) piezoresistive sensors created with the layer-by-layer (LBL) technology consists of a pressure-sensitive module (a bionic corpuscle), interdigital electrodes (a bionic sensory nerve), and a PU membrane (a bionic epidermis). The synergistic mechanism of hydrogen bond and coupling agent helps to improve the adhesive properties of conductive materials, and thus improve the pressure sensitive properties. The TCB sensor possesses favorable sensitivity (1.0005 kPa-1), a wide linear sensing range (1700 kPa), and a rapid response time (40 ms). The sensor is expected to be applied in a wide range of possible applications including human movement tracking, wearable detection system, and textile electronics.

BDE-209-induced genotoxicity, intestinal damage and intestinal microbiota dysbiosis in zebrafish (Danio Rerio).

The environmental presence of polybrominated diphenyl ethers (PBDEs) is ubiquitous due to their wide use as brominated flame retardants in industrial products. As a common congener of PBDEs, decabromodiphenyl ether (BDE-209) can pose a health risk to animals as well as humans. However, to date, few studies have explored BDE-209's toxic effects on the intestinal tract, and its relevant mechanism of toxicity has not been elucidated. In this study, adult male zebrafish were exposed to BDE-209 at 6 µg/L, 60 µg/L and 600 µg/L for 28 days, and intestinal tissue and microbial samples were collected for analysis to reveal the underlying toxic mechanisms. Transcriptome sequencing results demonstrated a dose-dependent pattern of substantial gene differential expression in the group exposed to BDE-209, and the differentially expressed genes were mainly concentrated in pathways related to protein synthesis and processing, redox reaction, and steroid and lipid metabolism. In addition, BDE-209 exposure caused damage to intestinal structure and barrier function, and promoted intestinal oxidative stress, inflammatory response, apoptosis and steroid and lipid metabolism disorders. Mechanistically, BDE-209 induced intestinal inflammation by increasing the levels of TNF-α and IL-1ß and activating the NFκB signaling pathway, and might induce apoptosis through the p53-Bax/Bcl2-Caspase3 pathway. BDE-209 also significantly inhibited the gene expression of rate-limiting enzymes such as Sqle and 3ßhsd (p < 0.05) to inhibit cholesterol synthesis. In addition, BDE-209 induced lipid metabolism disorders through the mTOR/PPARγ/RXRα pathway. 16S rRNA sequencing results showed that BDE-209 stress reduced the richness and diversity of intestinal microbiota, and reduced the abundance of probiotics (e.g., Bifidobacterium and Faecalibacterium). Overall, the results of this study help to clarify the intestinal response mechanism of BDE-209 exposure, and provide a basis for evaluating the health risks of BDE-209 in animals.

Flexible Capacitive Pressure Sensor with High Sensitivity and Wide Range Based on a Cheetah Leg Structure via 3D Printing.

Flexible pressure sensors can be used in human-computer interaction and wearable electronic devices, but one main challenge is to fabricate capacitive sensors with a wide pressure range and high sensitivity. Here, we designed a capacitive pressure sensor based on a bionic cheetah leg microstructure, validated the benefits of the bionic microstructure design, and optimized the structural feature parameters using 3D printing technology. The pressure sensor inspired by the cheetah leg shape has a high sensitivity (0.75 kPa-1), a wide linear sensing range (0-280 kPa), a fast response time of roughly 80 ms, and outstanding durability (24,000 cycles). Furthermore, the sensor can recognize a finger-operated mouse, monitor human motion, and transmit Morse code information. This work demonstrates that bionic capacitive pressure sensors hold considerable promise for use in wearable devices.

Bioinspired Engineering of Fillable Gradient Structure into Flexible Capacitive Pressure Sensor Toward Ultra-High Sensitivity and Wide Working Range.

Tactile sensing is required for electronic skin and intelligent robots to function properly. However, the dielectric layer's poor structural compressibility in conventional pressure sensors results in a limited pressure sensing range and low sensitivity. To solve this issue, a flexible pressure sensor with a crocodile-inspired fillable gradient structure is provided. The fillable gradient structure and grooves in the pressure sensor accommodate the deformed microstructure that permits the enhancement of the media layer compressibility via COMSOL finite element simulation and optimization. The pressure sensor exhibits a high sensitivity of up to 0.97 k Pa-1 (0-4 kPa), a wide pressure detection range (7 Pa-380 kPa), and outstanding repeatability. The sensor can detect Morse code, robotic grabbing, and human motion monitoring. As a result, flexible sensors with a bionic fillable gradient structure pave the way for wearable devices and offer a novel method for achieving highly precise tactile perception.

Adaptive anisotropic pixel-by-pixel correction method for a space-variant degraded image.

Large field-of-view optical imaging systems often face challenges in the presence of space-variant degradation. The existence of degradation leads to target detection and recognition being difficult or even unsuccessful. To address this issue, this paper proposes an adaptive anisotropic pixel-by-pixel space-variant correction method. First, we estimated region acquisition of local space-variant point spread functions (PSFs) based on Haar wavelet degradation degree distribution, and obtained initial PSF matrix estimation with inverse distance weighted spatial interpolation. Then, we established a pixel-by-pixel space-variant correction model based on the PSF matrix. Third, we imposed adaptive sparse regularization terms of the Haar wavelet based on the adaptive anisotropic iterative reweight strategy and non-negative regularization terms as the constraint in the pixel-by-pixel space-variant correction model. Finally, as the correction process is refined to each pixel, the split-Bregman multivariate separation solution algorithm was employed for the pixel-by-pixel spare-variant correction model to estimate the final PSF matrix and the gray value of each pixel. Through this algorithm, the "whole image correction" and "block correction" is avoided, the "pixel-by-pixel correction" is realized, and the final corrected images are obtained. Experimental results show that compared with the current advanced correction methods, the proposed approach in the space-variant wide field correction of a degraded image shows better performance in preserving the image details and texture information.

Underlying Mechanisms for the Sex- and Chemical-Specific Hepatotoxicity of Perfluoroalkyl Phosphinic Acids in Common Carp (Cyprinus carpio).

The hepatotoxicities of perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively investigated, while little is known about the sex-specific differences. In this study, common carp were exposed to the emerging perfluoroalkyl phosphinic acids (6:6 and 8:8 PFPiAs) for 14 days to disclose sex-specific hepatotoxicity. Apparent hepatotoxicity, including cell necrosis, apoptosis, and steatosis, was observed in both male and female carp liver. The observed hepatocyte steatosis was predominantly attributed to the dysregulation of hepatic lipid metabolism but was based on sex-specific mechanisms. It was manifested as inhibited oxidative decomposition of fatty acids (FAs) in the female liver, whereas it enhanced the uptake of FAs into the male liver, both of which led to excessive lipid accumulation. Untargeted lipidomics validated that the metabolism pathways of FA, sphingolipid, glycerolipid, and glycerophospholipid were disrupted by both compounds, leading to the generation of reactive oxygen species and oxidative stress. The oxidative stress further evolved into inflammation, manifested as promoted expression of proinflammatory cytokines and repressed expression of anti-inflammatory cytokines. Consistently, all of the changes were more noticeable in male carp, suggesting that male fish were more susceptible to PFPiA disruption. 8:8 PFPiA was less accumulated but caused stronger hepatotoxicity than 6:6 PFPiA, possibly because of the stronger binding capacity of 8:8 PFPiA to nuclear transcription factors mediating lipid metabolism and inflammation. The findings of this study highlight the significance of sex- and chemical-dependent bioaccumulation and the toxicity of PFASs in organisms.

Tetrahedral Framework Nucleic Acids Based Small Interfering RNA Targeting Receptor for Advanced Glycation End Products for Diabetic Complications Treatment.

Complications arising from diabetes can threaten multiple organs. Advanced glycation end products (AGEs) play a significant role in inducing these complications. Highly processed diets and hyperglycemia facilitate the accumulation of AGEs in the body. Interaction between AGEs and their main receptor (RAGE) initiates the transmission of intracellular inflammatory and cell death signals, which ultimately lead to complications. To counter AGEs-induced damage, we developed an siRNA-binding tetrahedral framework nucleic acids (TDN) system, termed Tsi, which combines the potent cell membrane penetrability and serum stability of TDN with the gene-targeting specificity of siRNA-RAGE. Tsi effectively and persistently downregulates the expression of RAGE, thereby suppressing inflammation by blocking the NF-κB pathway as well as exhibiting antioxidant functions. Furthermore, Tsi regulates the pyroptosis state of macrophages via the NLRP3/caspase-1 axis, which inhibits the spread of cell death signals and maintains homeostasis. This is of great significance for the synergistic treatment strategy for systemic complications in patients with refractory hyperglycemia. In summary, this study describes a nanomedicine that targets the RAGE and suppresses AGE-induced inflammation. This nucleic acid drug holds long-lasting efficacy and is independent of lowering hyperglycemia, which provides a strategy for the treatment of diabetic complications and age-related diseases.

A review of the toxic effects of ammonia on invertebrates in aquatic environments.

Aquatic invertebrates are the organisms most susceptible to ammonia toxicity. However, the toxic effects of ammonia on invertebrates are still poorly understood. This study reviews the research progress in ammonia toxicology for the period from 1986 to 2023, focusing on the effects on invertebrates. Through examining the toxic effects of ammonia at different levels of organization (community, individual, tissue and physiology, and molecular) as well as the results from omics studies, we determined that the most significant effects were on the reproductive capacity of invertebrates and the growth of offspring, although different populations show variation in their tolerance to ammonia, and tissues have varied potential to respond to ammonia stress. A multicomponent analysis is an in-depth technique employed in toxicological studies, as it can be used to explore the enrichment pathways and functional genes expressed under ammonia stress. This study comprehensively discusses ammonia toxicity from multiple aspects in order to provide new insights into the toxic effects of ammonia on aquatic invertebrates.

Novel Insights on 6:6 Perfluoroalkyl Phosphonic Acid-Induced Melanin Synthesis Disorders Leading to Pigmentation in Tadpoles.

As alternatives to traditional per- and polyfluoroalkyl substances, perfluoroalkyl phosphonic acids (PFPiAs) are widely present in aquatic environments and can potentially harm aquatic organisms. Pigmentation affects the probability of aquatic organisms being preyed on and serves as an important toxic endpoint of development, but little is known about the impacts of PFPiAs on the development of aquatic organisms. In this study, Xenopus laevis embryos were exposed to 6:6 PFPiA (1, 10, and 100 nM) for 14 days. The developed tadpoles exhibited evident pigmentation with increased melanin particle size and density on the skin. Pathological and behavioral experiments revealed that the retinal layers became thinner, reducing the photosensitivity and disturbing the circadian rhythm of the tadpoles. Compared to the control group, the exposed tadpoles showed higher levels but less changes of melanin throughout the light/dark cycle, as well as distinct oxidative damage. Consequently, the expression level of microphthalmia-associated transcription factor (MITF), a key factor inducing melanin synthesis, increased significantly. Molecular docking analysis suggested that 6:6 PFPiA forms strong interactions in the binding pocket of MITF, implying that it could activate MITF directly. The activation of MITF ultimately promotes melanin synthesis, resulting in pigmentation on tadpoles.

Effects of Puerarin-Loaded Tetrahedral Framework Nucleic Acids on Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is recognized as a common refractory orthopedic disease that causes severe pain and poor quality of life in patients. Puerarin (Pue), a natural isoflavone glycoside, can promote osteogenesis and inhibit apoptosis of bone mesenchymal stem cells (BMSCs), demonstrating its great potential in the treatment of osteonecrosis. However, its low aqueous solubility, fast degradation in vivo, and inadequate bioavailability, limit its clinical application and therapeutic efficacy. Tetrahedral framework nucleic acids (tFNAs) are promising novel DNA nanomaterials in drug delivery. In this study, tFNAs as Pue carriers is used and synthesized a tFNA/Pue complex (TPC) that exhibited better stability, biocompatibility, and tissue utilization than free Pue. A dexamethasone (DEX)-treated BMSC model in vitro and a methylprednisolone (MPS)-induced ONFH model in vivo is also established, to explore the regulatory effects of TPC on osteogenesis and apoptosis of BMSCs. This findings showed that TPC can restore osteogenesis dysfunction and attenuated BMSC apoptosis induced by high-dose glucocorticoids (GCs) through the hedgehog and Akt/Bcl-2 pathways, contributing to the prevention of GC-induced ONFH in rats. Thus, TPC is a promising drug for the treatment of ONFH and other osteogenesis-related diseases.

Mechanisms for the structural dependent transformation of 6:2 and 8:2 polyfluoroalkyl phosphate diesters in wheat (Triticum aestivum L.).

Polyfluoroalkyl phosphate esters (PAPs) are widely used and detected in various environmental media and organisms, but little is known about their behaviors in plants. In this study, the uptake, translocation and transformation of 6:2 and 8:2 diPAP in wheat using hydroponic experiments were investigated. 6:2 diPAP was more easily taken up by roots and translocated to shoots than 8:2 diPAP. Their phase I metabolites were fluorotelomer saturated carboxylates (FTCAs), fluorotelomer unsaturated carboxylates (FTUCAs) and perfluoroalkyl carboxylic acids (PFCAs). PFCAs with even-numbered chain length were the primary phase I terminal metabolites suggesting that they were mainly generated through ß-oxidation. Cysteine and sulfate conjugates were the primary phase II transformation metabolites. The higher levels and ratios of phase II metabolites in the 6:2 diPAP exposure group indicated that the phase I metabolites of 6:2 diPAP were more susceptible to phase II transformation than that of 8:2 diPAP, which was confirmed by density functional theory calculation. Enzyme activity analyses and in vitro experiments demonstrated that cytochrome P450 and alcohol dehydrogenase actively participated in the phase Ⅰ transformation of diPAPs. Gene expression analyses showed that glutathione S-transferase (GST) was involved in the phase Ⅱ transformation, and the subfamily GSTU2 played a dominant role.

Examining Concentration-Reliant Zn Deposition/Stripping Behavior in Organic Alcohol/Sulfones-Modified Aqueous Electrolytes.

The practical application of Zn metal anodes in electronic devices is hindered by dendrite growth and parasitic reactions. Electrolyte optimization, particularly the introduction of organic co-solvents, is widely used to circumvent these challenges. Various organic solvents in a wide range of concentrations have been reported; however, their influences and corresponding working mechanisms at different concentrations are largely unexplored in the same organic species. Herein, economical, low-flammable ethylene glycol (EG) is used as a model co-solvent in aqueous electrolytes to examine the relationship between its concentration, anode-stabilizing effect, and mechanism. Two maximal values are observed for the lifetime of Zn/Zn symmetric batteries under EG concentrations from 0.05 vol% to 48 vol%. Zn metal anodes can stably run for over 1700 h at a low EG content (0.25 vol%) and high EG content (40 vol%). Based on the complementary experimental and theoretical calculations, the enhancements in low- and high-content EG are ascribed to the specific surface adsorption for suppressed dendrite growth and the regulated solvation structure for inhibited side reactions, respectively. Intriguingly, a similar concentration-reliant bimodal phenomenon is observed in other low-flammable organic solvents (e.g., glycerol and dimethyl sulfoxide), thereby suggesting universality of this study and providing insight into electrolyte optimization.

Nano shield: a new tetrahedral framework nucleic acids-based solution to radiation-induced mucositis.

Radiation-induced oral mucositis (RIOM) is considered to be one of the most important public health problems today, affecting the overall well-being of millions of patients who have received radiotherapy. Nevertheless, the field of preventing and treating RIOM is still widely unexplored. Curcumin (Cur) with its promising anti-inflammatory and antioxidant properties is accompanied with obstacles in application, including poor dissolubility, instability and low bioavailability. In this study, a tetrahedral framework nucleic acid drug delivery system (TFNAS) was synthesized and established using a novel method to carry Cur (Cur-TFNAS) for efficient drug delivery. The results showed that Cur-TFNAS enhanced the antioxidant capacity of human oral mucosal keratin-forming cells (HOKs) compared to free Cur and TFNAS. Meanwhile, Cur-TFNAS reduced DNA damage and shielded the cells from inflammatory factors. A similar result was also well documented in vivo. Herein, we consider that Cur-TFNAS acts as a nano-shield for preventing radiation oral mucositis and shows important clinical value in the future.

Intrinsic mechanisms for the inhibition effect of graphene oxide on the catalysis activity of alpha amylase.

Comprehending the interactions between graphene oxide (GO) and enzymes is critical for understanding the toxicities of GO. In this study, the inherent interactions of GO with α-amylase as a typical enzyme, and the impacts of GO on the conformation and biological activities of α-amylase were systematically investigated. The results reveal that GO formed ground-state complex with α-amylase primarily via hydrogen bonding and van der Waals interactions, thus quenching the intrinsic fluorescence of the protein statically. Particularly, the strong interactions altered the microenvironment of tyrosine and tryptophan residues, caused rearrangement of polypeptide structure, and reduced the contents of α-helices and ß-sheets, thus changing the conformational structure of α-amylase. According to molecular docking results, GO binds with the amino acid residues (i.e., His299, Asp300, and His305) of α-amylase mainly through hydrogen bonding, which is in accordance with in vitro incubation experiments. As a consequence, the ability of α-amylase to catalyze starch hydrolysis into glucose was depressed by GO, suggesting that GO might cause dysfunction of α-amylase. This study discloses the intrinsic binding mechanisms of GO with α-amylase and provides novel insights into the adverse effects of GO as it enters organisms.

Tetrahedral framework nucleic acid nanomaterials reduce the inflammatory damage in sepsis by inhibiting pyroptosis.

Sepsis is a highly lethal condition and is caused by the dysregulation of the body's immune response to infection. Indeed, sepsis remains the leading cause of death in severely ill patients, and currently, no effective treatment is available. Pyroptosis, which is mainly activated by cytoplasmic danger signals and eventually promote the release of the pro-inflammatory factors, is a newly discovered programmed cell death procedure that clears infected cells while simultaneously triggering an inflammatory response. Increasing evidence indicates that pyroptosis participates in the development of sepsis. As a novel DNA nanomaterial, tetrahedral framework nucleic acids (tFNAs) characterized by its unique spatial structure, possess an excellent biosafety profile and can quickly enter the cell to impart anti-inflammatory and anti-oxidation effects. In this study, the roles of tFNAs in the in vitro model of macrophage cell pyroptosis and in the in vivo model of septic mice were examined, and it was found that tFNAs could mitigate organ inflammatory damage in septic mice, wherein they reduced inflammatory factor levels by inhibiting pyroptosis. These results provide possible new strategies for the future treatment of sepsis.

Novel Insight into the Mechanisms of Neurotoxicity Induced by 6:6 PFPiA through Disturbing the Gut-Brain Axis.

As alternatives to traditional per- and polyfluoroalkyl substances, perfluoroalkyl phosphonic acids (PFPiAs) are frequently detected in aquatic environments, but the neurotoxic effects and underlying mechanisms remain unclear. In this study, male zebrafish were exposed to 6:6 PFPiA (1 and 10 nM) for 28 days, which exhibited anxiety-like symptoms. Gut microbiome results indicated that 6:6 PFPiA significantly increased the abundance of Gram-negative bacteria, leading to enhanced levels of lipopolysaccharide (LPS) and inflammation in the gut. The LPS was delivered to the brain through the gut-brain axis (GBA), damaged the blood-brain barrier (BBB), stimulated neuroinflammation, and caused apoptosis as well as neural injury in the brain. This mechanism was verified by the fact that antibiotics reduced the LPS levels in the gut and brain, accompanied by reduced inflammatory responses and anxiety-like behavior. The BBB damage also resulted in the enhanced accumulation of 6:6 PFPiA in the brain, where it might bind strongly with and activate aryl hydrocarbon receptor (AhR) to induce brain inflammation directly. Additionally, as the fish received treatment with an inhibitor of AhR, the inflammation response and anxiety-like behavior decreased distinctly. This study sheds light on the new mechanisms of neurotoxicity-induced 6:6 PFPiA due to the interruption on GBA.