Biology subjects

Ma, H.

Publications and source records attributed to Ma, H..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Suppressing cortical glutamatergic neurons produces paradoxical interictal discharges and seizures

IntroductionSeizures are traditionally attributed to excessive excitation or deficient inhibition, yet recent clinical and slice data show they can also paradoxically arise when inhibition outweighs excitation. We chemogenetically suppressed neocortical glutamatergic neurons to test whether such suppression elicits epileptic activity in vivo. MethodsCaMKII-driven Gi-coupled hM4Di or Gq-coupled hM3Dq Designer Receptor Exclusively Activated by Designer Drug (DREADDs) were expressed in cortical glutamatergic neurons of Rasgrf2-jGCaMP8m and wildtype C57BL/6J mice. Widefield calcium imaging and 32-channel transparent electrocorticography were performed before and after systemic clozapine-N-oxide (CNO; 1.25-5 mg kg {superscript 1}). ResultsDREADD activation induced intermittent, large-amplitude, synchronized calcium transients confined to the CaMKII-hM4Di focus, accompanied by focal ECoG spikes that persisted for >3 h and sometimes evolved into seizures. By contrast, CNO activation of excitatory neurons via CaMKII-hM3Dq DREADDs desynchronized activity without epileptiform discharges. The same process duplicated in wild-type animals provoked similar epileptiform discharges. ConclusionSelective suppression of excitation can paradoxically drive cortical networks into hypersynchronous, epileptic states, challenging the simple excess-excitation model of ictogenesis. These findings highlight that seizures may result from relative inhibitory dominance, and that considering this excess inhibition mechanism could inspire new therapeutic approaches.

neuroscience↗

bioRxiv2025

Understanding Fertility Intention Through the Lens of Family Functioning, Fertility Anxiety and Marriage-Fertility Views: A TPB-Based SEM Approach

ABSRTACTO_ST_ABSBackgroundC_ST_ABSGlobal fertility rates are declining, and despite Chinas three-child policy, the number of women of childbearing age continues to shrink. Fertility intention, a key predictor of fertility behavior, is shaped by factors such as socioeconomic stress, family functioning, and psychological traits. ObjectiveGrounded in the Theory of Planned Behavior, this study investigates how family functioning, marriage and fertility values, and fertility anxiety influence the fertility intentions of newlywed, childless young couples. MethodsA cross-sectional survey of 1,292 newlywed, childless couples in Yinchuan, Ningxia (2024) assessed demographics, family functioning (FAD), marriage and fertility values (MFV), and fertility anxiety (FA). Multiple logistic regression and structural equation modeling (SEM) were used. ResultsFamily functioning promoted intentions to have two or more children indirectly via positive communication and mediated by traditional MFV (44.4% of the total effect). Fertility anxiety showed no significant effect. Men preferred more children than women, and fertility intentions increased with age ConclusionsImproving family communication and reinforcing traditional values may help boost fertility intentions. Findings offer insight into the family-psychological mechanisms shaping fertility decisions.

animal behavior and cognition↗

bioRxiv2025

Toxoplasma gondii disrupts vitamin B and K2 biosynthetic pathways in feline gut microbiota: microbial adaptation

Vitamins B and K2 (menaquinone) are critical for microbial and host processes, but their biosynthesis in feline gut microbiota and modulation by Toxoplasma gondii remain unclear. We assembled 1,553 high-quality feline intestinal bacterial genomes from metagenomic and public data to study vitamin B and K2 biosynthesis. We identified 86,829 genes and 159 enzymes, revealing regional differences in gene and species diversity for vitamin production. Among these, 782 genomes supported de novo synthesis of at least one vitamin. T. gondii infection altered synthesis pathways: early infection boosted pyridoxine and riboflavin synthesis in the small intestine, while menadione synthesis declined in both intestines. Actinomycetota and Campylobacterota were key to menaquinone biosynthesis, with T. gondii disrupting canonical pathways and activating alternatives. These findings shed light on the complex interplay between host, parasite, and microbiota in shaping vitamin biosynthesis, offering new perspectives for maintaining feline gut health during parasitic infection.

microbiology↗

bioRxiv2025

Gene-Family Encoding Boosts Domain-Adapted Single-Cell Language Models

Transformer-based single-cell foundation models often rely on ranked-gene (RG) sequences where genes, ranked by expression, are often not functionally related, weakening next-token learning and the structure of learned embeddings. Here, we introduce gene-family (GF) encoding, where expressed genes are grouped into functionally defined families, and ranking performed within each family. Using 100,000 gastric-cancer (GC) cells, we domain-adapted 8-billion-parameter Llama and Qwen backbones with either RG or GF sentences and benchmarked zero-shot performance on embedding-based and generative tasks. GF models outperformed RG models across both tasks and backbones. We scaled GF-Llama to 1.3 million GC cells to obtain GF-Llama-GC and applied it to two applications: resolving fine-grained cellular heterogeneity and discovering cell populations associated with disease progression. GF-Llama-GC revealed immune-cell subclusters not resolved by standard expression-based analyses. Applying in-silico cell removal/transplantation on a chemotherapy responder/non-responder scRNA-seq dataset, GF-Llama-GC highlighted not only epithelial cells but also neutrophils as key cells associated with chemotherapy response.

bioinformatics↗

bioRxiv2025

Regularized Single-cell Imaging Enables Generalizable AI models for Stain-free Cell Viability Screening

Cell viability assays are essential tools in biomedical research and drug development. Artificial intelligence (AI) offers the potential to simplify these assays by predicting cell viability directly from brightfield microscopy images, but current models lack generalizability across diverse cell types and treatments. Here, we introduce a strategy called "regularized imaging", where single cells are isolated in nanowells to generate standardized image patches that simplify segmentation and improve training data quality. We trained our model using example images of live and dead cells from a single cell line exposed to four cytotoxic conditions (ethanol, andrographolide, daunorubicin, and serum starvation). Despite this narrow training dataset, the resulting model accurately identified live and dead cells after treatment by previously unseen compounds, successfully replicating dose-response curves comparable to fluorescence live/dead assays. Importantly, this model effectively generalized across diverse cell types, including both adherent and suspension cells. Additionally, microscopy-based cell viability analysis is non-destructive, enabling repeated measurements to perform kinetic studies to distinguish between fast- and slow-acting compounds. Our findings highlight how regularized single cell imaging enables the training of broadly generalizable AI models to recognize biologically relevant cell features for label-free cell screening workflows. One-sentence SummaryRegularized single-cell imaging in nanowells enables training of generalizable AI models for accurate, stain-free viability screening across previously unseen cell types and contexts.

bioengineering↗

bioRxiv2025

Antibiotic pressures in livestock and meat systems: evidence and interventions for a One Health future

Antibiotic use (ABU) in livestock is a major driver of antimicrobial resistance, yet global levels, determinants, and long-term trajectories remain poorly resolved. We compiled a harmonized dataset across countries for 2020 and a longitudinal series of meat production from 1961 to 2023 to quantify patterns, evaluate socioeconomic and regulatory correlates, and forecast to 2050 using a production linked proxy model. Total ABU correlated strongly with national meat output (Spearman r = 0.906, p < 0.001). ABU intensity in milligrams per kilogram meat was highly heterogeneous and showed no global association with production. Gross domestic product per capita was unrelated to total use or intensity, learning adjusted years of schooling related only weakly to intensity, and legal controls on use or sales alone did not improve efficiency. Projections indicate a near linear rise of about 1,663 tonnes per year, reaching 131,828 tonnes in 2030 and 165,094 tonnes in 2050, with cumulative use in 2020 to 2050 surpassing 1950 to 2020. Reducing intensity by ten to fifty percent by 2050 would avert 16,509 to 82,548 tonnes. Findings motivate an integrated roadmap of source control, farm and market stewardship, and scalable surveillance using production as a proxy within a One Health framework. HighlightsO_LIModern livestock production remains heavily dependent on antibiotics. C_LIO_LIHigher antibiotic use in livestock correlates with lower usage efficiency at the global scale. C_LIO_LICurrent legislative controls on antibiotic use have failed to enhance usage efficiency. C_LIO_LISince the 1950s, global antibiotic use in livestock has followed a steady linear rise, projected to continue through 2050. C_LI

ecology↗

bioRxiv2025

An Objective Detection Method for Tinnitus using Memristors

Approximately 10-20% of the world population experiences tinnitus, which is increased with age and comorbid with frustration, annoyance, anxiety, depression, cognitive dysfunction, insomnia and stress. The underlying mechanisms of tinnitus remain largely unknown and there are no quantifiable biomarkers, making this prevalent disorder a global burden. There are no FDA-approved therapeutics and the current assessment mainly relies on self-reports (e.g., questionnaires), which underscore the need for diagnostic tools for tinnitus. Memristors, nanoscale electronic components mimicking synaptic plasticity, can monitor and control neuronal activity, hold transformative potential for detecting and characterizing tinnitus objectively. Here, we harvested the blood from human and mice with tinnitus, and engineered memristors via magnetron sputtering and made the functional layer with serum. Its core mechanism lies in regulating the reversible formation and rupture of conductive filaments which is formed by utilizing abnormally elevated glutamate concentrations in serum assisted Ag+ ions. This serum-based memristor achieves unprecedented discrimination between tinnitus and non-tinnitus individuals. Furthermore, this platform provides mechanistic insights into tinnitus pathogenesis, with potential implications in other neurological disorders.

pathology↗

bioRxiv2025

A Deep Neural Network Trained on Congruent Audiovisual Speech Reports the McGurk Effect

In the McGurk effect, perception of an auditory syllable changes dramatically when it is paired with an incongruent visual syllable, countering our intuition that speech perception is solely an auditory process. The dominant modeling framework for the study of audiovisual speech perception is that of Bayesian causal inference, but current Bayesian models are unable to predict the wide range of percepts evoked by McGurk syllables. We explored whether a deep neural network (DNN) known as AVHuBERT could provide an alternative modeling framework. AVHuBERT model variants were presented with McGurk syllables consisting of auditory "ba" paired with visual "ga" recorded from 8 different talkers. AVHuBERT identified McGurk syllables as something other than "ba" at a rate of 59%, demonstrating a robust McGurk effect. The rate of the McGurk effect was similar to that observed in humans: 100 participants presented with the same McGurk syllables reported non-"ba" percepts on 56% of trials. AVHubert variants and humans produced a wide variety of responses to McGurk syllables, including the canonical McGurk fusion percept of "da", responses without any initial consonant such as "ah" and responses with other initial consonants such as "fa". The ability to predict percepts experienced by humans but not predicted by current Bayesian models suggest that DNNs and Bayesian models may provide complementary windows into the perceptual mechanisms underlying human audiovisual speech perception.

neuroscience↗

bioRxiv2025

Evaluating large language models in biomedical data science challenges through a classroom experiment

Large language models have shown remarkable capabilities in algorithm design, but their effectiveness in solving data science challenges remains poorly understood. We conducted a classroom experiment in which graduate students used large language models (LLMs) to solve biomedical data science challenges on Kaggle. While their submissions did not top the leaderboards, their prediction scores were often close to those of leading human participants. LLMs frequently recommended gradient boosting methods, which were associated with better performance. Among prompting strategies, self-refinement, where the LLM improves its own initial solution, was the most effective, a result validated using additional LLMs. These findings demonstrate that LLMs can design competitive machine learning solutions, even when used by non-experts.

bioinformatics↗

bioRxiv2025

Integrated metagenome-resolved profiling of the resistome, virulome, and mobilome in the gut microbiota of wild birds

Wild birds, with their extensive geographic distributions and high mobility, are increasingly recognized as important players in the dissemination of antimicrobial resistance. Their gut microbiota, shaped by exposure to diverse environments, may act as both reservoirs and vectors of antibiotic resistance genes (ARGs), virulence factor genes (VFGs), and mobile genetic elements (MGEs). In this study, we reconstructed 2,516 high-quality metagenome-assembled genomes (MAGs) from 718 gut metagenomes of wild birds to comprehensively profile their resistome and virulome. We identified 5,596 ARG-encoding proteins across 389 distinct ARG types, with multidrug resistance emerging as the most dominant category. Escherichia coli was the principal carrier of ARGs, and genes conferring resistance to elfamycin antibiotics via target alteration were notably widespread--indicating persistent antibiotic selection pressures in avian habitats. Co-occurrence analyses revealed extensive genetic linkage between ARGs, VFGs, and MGEs. Critically, we detected 25 ARG-MGE co-localization events within 5-kilobase genomic regions, highlighting a strong potential for horizontal gene transfer and accelerated resistance dissemination within microbial communities. Of particular concern was the detection of the tetX1 gene--conferring resistance to tigecycline, a last-resort antibiotic--in the gut microbiota of Chroicocephalus ridibundus and Cygnus cygnus. This finding strongly implicates anthropogenic pollution in the spread of clinically relevant ARGs into wildlife and emphasizes the risk of environmental transmission to other hosts, including humans. These results underscore the critical ecological role of wild birds in the global antimicrobial resistance network. As both reservoirs and potential vectors of ARGs, they represent a significant but under-monitored interface between environmental and clinical resistance pathways. Enhanced surveillance and mitigation strategies targeting wildlife are urgently needed to curb the environmental propagation of antimicrobial resistance.

microbiology↗

bioRxiv2025

Metagenomic analysis of antimicrobial resistance, virulence, and mobile genetic elements in the gut microbiota of Caprinae species

The gut microbiota of livestock serves as a reservoir for antimicrobial resistance (AMR), yet Caprinae species remain understudied in this context. In this comprehensive metagenomic study, we analyzed 779 gut samples from Caprinae animals and reconstructed 17,023 high-quality metagenome-assembled genomes (MAGs). From these, we identified 4,685 antimicrobial resistance genes (ARGs) and 5,401 virulence factor genes (VFGs). Escherichia coli emerged as a major host carrying high burdens of both ARGs and VFGs. Strong positive correlations between ARGs, VFGs, and mobile genetic elements (MGEs) suggest potential co-selection and genetic linkage. Although MGEs were found in only 1.45% of MAGs, 23 ARGs were physically co-located with MGEs, indicating mobility potential. Additionally, three ARGs were embedded within viral genomes, two of which were associated with Myoviridae phages and one with an unclassified viral source, implicating phages in AMR dissemination. Comparative analyses revealed 292 ARG types shared between Caprinae and the human gut microbiota, including 20 genes representing six clinically critical resistance types: tetX1, tetX4, tmexD3, vanD, vanR, and vanS--conferring resistance to tigecycline, vancomycin, and polymyxins. These findings expand our understanding of the resistome and virulome in Caprinae animals and highlight potential zoonotic transmission pathways, underscoring the need for targeted AMR surveillance and mitigation strategies.

microbiology↗

bioRxiv2025

ZCCHC4 Promotes Translation of Replication-dependent Histone mRNAs by Recruiting Cytoplasmic eIF3 complex

Chromatin instability is a major driving force in tumorigenesis, so the correct chromatin structure is essential for maintaining genome stability during the various stages of the cell cycle and DNA template processes. However, there is limited research on how histones are regulated and whether insufficient histone supply leads to chromatin instability, thereby affecting the process of tumor generation. Our study demonstrates that ZCCHC4 exhibits dual subcellular localization in both the nucleus and cytoplasm. Notably, in the cytoplasm, ZCCHC4 facilitates the translation of replication-dependent (RD) histone mRNAs, potentially through direct interaction with components of the translation initiation machinery. Depletion of ZCCHC4 results in a global reduction in protein translation, particularly affecting the translation of replication-dependent histones. This translational impairment prolongs the S phase of the cell cycle, leading to insufficient histone supply, chromatin relaxation, and genomic instability. Moreover, ZCCHC4 knockout markedly inhibits cell proliferation, colony-forming ability, and the growth of xenograft tumors. In conclusion, this study demonstrates that ZCCHC4 plays a pivotal role in regulating global protein translation by interacting with the eIF3 complex, which is essential for efficient mRNA translation in cancer cells and for sustaining the supply of replication-dependent histones during the S phase.

cancer biology↗

bioRxiv2025

Beach sand beneath our feet: an overlooked reservoir of antibiotic resistance genes and pathogens, revealed by metagenomic evidence from Qingdao's recreational beaches

Coastal beach environments, especially those with heavy tourist activity, represent a dynamic interface between terrestrial and marine microbiomes. However, beach sand is rarely considered in surveillance of antibiotic resistance. In this study, we combined 16S rRNA gene sequencing and shotgun metagenomics to characterize microbial communities and antibiotic resistance genes (ARGs) at four popular recreational beaches in Qingdao, China. We show that beach sands harbor highly diverse bacterial communities with significantly greater richness than adjacent seawater. Beach sand near sewage discharge points had microbial profiles intermediate between raw sewage and open-ocean water, reflecting contributions from both sources. Metagenomic analysis identified a broad "resistome" of over 300 distinct ARGs in these beach and water samples, spanning 33 antibiotic classes and 6 resistance mechanism categories. Notably, the rifampicin resistance gene rpoB2 was the most abundant ARG, and genes conferring resistance to peptide antibiotics were prevalent. Sewage outfalls were found to be major contributors of ARGs, with waste-influenced sand containing a larger and more diverse ARG pool than sand farther from pollution sources. We also detected a high diversity of bacterial virulence factor genes, particularly in sand. Our findings highlight that tourist beaches can serve as reservoirs and mixing zones for antibiotic-resistant and potentially pathogenic bacteria from land-based pollution. This underscores the need to include beach sand in environmental monitoring for antibiotic resistance and to improve wastewater management at recreational coastlines to mitigate public health risks. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/661489v1_ufig1.gif" ALT="Figure 1"> View larger version (84K): org.highwire.dtl.DTLVardef@18705f3org.highwire.dtl.DTLVardef@1979f8forg.highwire.dtl.DTLVardef@16c9029org.highwire.dtl.DTLVardef@6c778d_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

High-throughput Single Cell Motility Analysis using Nanowell-in-Microwells

Cell motility is important to many biological processes including cancer, immune response, and tissue repair. Conventional assays measure bulk cell motility, potentially overlooking important heterogeneity and missing important high motility subpopulations. Here, we introduce a high-throughput single-cell motility assay using nanowell-in-microwell plates to precisely track single cell position and analyze their migratory trajectories. By physically confining individual cells in nanowells, we eliminate cell-cell interactions and simplify cell segmentation and tracking. Using this platform, we characterized the motility of single cells across different culture conditions to identify distinct motility phenotypes. Single-cell trajectory analysis revealed pronounced directional persistence, with cells predominantly maintaining their direction of travel and trajectory along nanowell boundaries. Additionally, our approach facilitates the generation of labeled image datasets suitable for AI models to rapidly identify cell motility phenotypes from single-cell images. Together, our platform provides a robust, scalable method to analyze cell motility phenotypes and migration behavior at single-cell resolution. Significance StatementA novel single-cell motility assay that uses confinement in nanowell-in-microwell to enable high-throughput profiling of single cell motility phenotypes.

bioengineering↗

bioRxiv2025

Application of machine learning in the discovery of antimicrobial peptides: Exploring their potential for ulcerative colitis therapy

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with rising global prevalence, yet existing treatments are not universally effective. Antimicrobial peptides (AMPs), produced by the immune system, have diverse antimicrobial and immune-regulatory functions, making them promising candidates for UC therapy. Using machine learning, we developed a machine learning-based prediction model to identify novel AMPs. The predicted peptides demonstrated significant biological activity in vitro and in vivo. In a dextran sulfate sodium-induced UC mouse model, engineered AMPs notably improved UC-related parameters, such as body weight, disease activity index (DAI), and colon length. These effects were likely mediated by modulation of Akkermansia muciniphila. This study highlights the potential of machine learning-identified AMPs as future therapeutic candidates for UC. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/660148v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@187dc6borg.highwire.dtl.DTLVardef@9800deorg.highwire.dtl.DTLVardef@1611c42org.highwire.dtl.DTLVardef@866406_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2025

AF9/KLF2 gene regulatory circuit links histone lactylation to breast cancer metastasis

Histone lysine L-lactylation (hereafter referred to as histone Kla) is a novel epigenetic mark induced by glycolytic metabolism, serving as a link between metabolic reprogramming and epigenetic regulation. In this study, we uncover an epigenetic-genetic transcriptional regulatory circuit involving AF9 and KLF2 that drives luminal breast cancer progression. AF9, identified as a reader of histone H3 lysine 9 lactylation (H3K9la), promotes KLF2 expression, while KLF2, functioning as a transcription factor for AF9, forms a positive feedback loop that amplifies lactylation-dependent effects. This circuit activates tumor-associated pathways, including TGF{beta}1, glucose and lactate transporters, and metabolic enzymes essential for glycolysis and serine biosynthesis, driving tumorigenesis and metastasis. Spatial and single-cell transcriptomics show AF9-positive tumor cells enriched in regions of active lactylation, correlated with immune evasion through interactions with M2 macrophages. Together, AF9, H3K9la, and KLF2 integrate metabolism, epigenetics, and signaling to promote tumor growth and metastasis, highlighting AF9s central role as a histone lactylation reader and a potential therapeutic target in breast cancer. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/660498v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@56b216org.highwire.dtl.DTLVardef@1c5cbc1org.highwire.dtl.DTLVardef@c42a5corg.highwire.dtl.DTLVardef@b912ec_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2025

High-throughput Single-cell Proteomics Enabled by an Integrated Hyperplexing and Automatic Labelling Approach without Fractionation

Single-cell proteomics (scProteomics) enables comprehensive analysis of protein composition, expression and functions at the single-cell level. While label-free techniques have generated promising results, achieving high-throughput scProteomics remains a substantial challenge. In this study, we present an approach that increases scProteomics throughput by approximately 30-fold through the true integration of isobaric tags (IBT) with tandem mass tags (TMT), a method we term Integral-Hyperplex. Due to remarkable differences in signal response between TMT16 and IBT16 reporter ions, we implemented two normalization strategies to ensure accurate and integrated quantification: (1) the inclusion of a normalization channel in both IBT and TMT groups to serve as internal standards; and (2) the generation of protein-specific conversion factors between IBT16 and TMT16 signals. We validated the quantification accuracy of the Integral-Hyperplex method by labeling HeLa digests at varying ratios. Furthermore, we demonstrated fully automated labeling on the active-matrix digital microfluidics chip, consuming only 12 nL of labeling reagent per single cell and with a reaction volume as low as 20 nL. Our approach was validated through proof-of-principle quantification experiments across three types of single cells. Approximately 2,000 protein groups were quantified per cell, and the three cell types can be well clustered, confirming the reliability of the Integral-Hyperplex approach. Approximately 300 samples can be analyzed per day due to insufficient resolution of timsTOF SCP. Throughput can be further enhanced using TMT32, additional labeling reagents, and more advanced mass spectrometers such as Orbitrap Astral and timsTOF Ultra 2, and our approach is theoretically capable of analyzing up to [~]2,000 single cells per day.

biochemistry↗

bioRxiv2025

Cytoprotective roles of "E3 ubiquitin ligases-NF-κB-autophagy" axis in Pacific oysters Crassostrea gigas exposed to phenanthrene

Phenanthrene (PHE), as one of the most frequently found polycyclic aromatic hydrocarbons can induce immunotoxicity, oxidative stress, and endocrine disruption in marine organisms. However, whether autophagy can be induced by PHE and the regulatory mechanism and cytoprotective roles of autophagy under PHE stress condition have not been unveiled. Our data first unveil a "E3 ubiquitin ligases-NF-{kappa}B-autophagy" axis, which play cytoprotective roles in Pacific oysters Crassostrea gigas exposed to PHE. The results of confocal laser scanning microscope, flow cytometry and transmission electron microscope confirmed that PHE could induce autophagy in the haemocytes of Pacific oysters, and the presence of autophagosomes was also confirmed. The proteomics results showed that the expression of the E3 ubiquitin ligase HUWE1, TRIM36, and autophagy-related protein 7 (ATG7) were significantly upregulated. The expression of genes of the "axis" were significantly upregulated, and the expression of genes of autophagy was downregulated after the inhibition of the NF-{kappa}B, indicating that the expression of the "axis"-related genes can be stimulated by PHE, and thus autophagy is activated. The upregulation of the expression of "axis"-related genes in mouse macrophages, further demonstrating the existence of the "axis" proposed by this study and the "axis" can be activated by PHE. Incorporating with changes of cell number, apoptosis rate, phagocytic capacity, and ROS levels of lymphocytes, we demonstrated that autophagy plays a cytoprotective role in cellular defence against PHE. This study proposed a novel pathway and supplied a comprehensive understanding of the protective role of autophagy in Pacific oysters to cope with pollutants.

cell biology↗