As a novel organophosphate ester widely distributed in airborne particulate matters, tris(2,4-di-tert-butylphenyl) phosphate (AO168=O) would pose a great hazard for the respiratory system. However, the underlying toxic mechanism of AO168=O on the lung organ, especially pulmonary malignant transformation, remained elusive. Hence, our study paid attention to the deleterious impact of AO168=O on malignant transformation of human bronchial epithelial (BEAS-2B) cells, identifying whether inflammation-coupled cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway mediated by TAR DNA-binding protein 43 (TDP-43) was involved in this process. Herein, we have observed that BEAS-2B cells were malignantly transformed upon exposure to AO168=O for 96 h, manifested by the increased mutation frequency at the Hprt locus, the enhanced anchorage-independent growth, the elevated migratory and invasive capabilities. Moreover, transcriptome sequencing, Western blot, quantitative PCR and immunofluorescence assay were adopted to show that the mitochondrial localization of TDP-43 could activate cGAS/STING pathway and inflammatory response upon exposure to 1000 ng/mL AO168=O for 96 h, thereby promoting epithelial-mesenchymal transition (EMT) in BEAS-2B cells deficient in homologous recombination repair. Furthermore, the blockage of inflammation-coupled cGAS/STING pathway reversed EMT and malignant transformation of BEAS-2B cells exposed to 1000 ng/mL AO168=O for 96 h. Collectively, our findings suggested that AO168=O promoted malignant progression of BEAS-2B cells, which was partially linked to the EMT process mediated by the mitochondrial localization of TDP-43. This also provided a valuable insight into the intervention for AO168=O-caused malignant transformation of human bronchial epithelial cells.

Helianthus tuberosus is a perennial herb that belongs to the Asteraceae family and Helianthus genus. It is cultivated in numerous northern and southern China regions, displaying numerous benefits such as its drought and frost resistance, ability to grow on most soils, and low fertilizer requirements. H. tuberosus contains various components, such as inulin, phenolic acids, terpenoids, flavonoids, steroids, phenylpropanoids, and other bioactive compounds with antioxidant, anti-inflammatory, antibacterial, anti-tumor, and immune-modulatory effects. In this paper, based on the new concept of quality marker (Q-marker) proposed by Academician Changxiao Liu, this study analyzed the relationship between plant affinity, chemical composition specificity, traditional medicinal properties, and chemical composition measurability of H. tuberosus, and predicted its Q-markers to provide a reference for the establishment of the quality evaluation system and comprehensive utilization of this herb.

Benzoic acid (BA), a widely recognized low-molecular-weight organic contaminant, is widespread in wastewater and poses significant environmental risks. Consequently, the persistent existence of BA in the ecosystem necessitates the development of effective remediation strategies, particularly bioremediation method utilizing highefficient degradation strains. In this study, a novel BA-degrading bacterium, Pseudomonas sp. BJ-1, was successfully isolated from activated sludge of a paper mill. Based on the central composite design and response surface method (CCD-RSM), the optimal parameters for the biodegradation of BA in an sequencing batch reactor (SBR) were determined as the initial BA concentration of 1037.86 mg center dot L- 1, immobilized bacterial pellets dosage (IBPD) of 213.87 g center dot L- 1, and pH of 7.02, where the maximum degradation efficiency was 99.10 +/- 0.85 % at 24 h. Furthermore, the immobilized bacterial pellets maintained degradation capacity for 5 days, demonstrating a robust activity and structural integrity. Further analysis by whole genome sequencing and liquid chromatography tandem high-resolution mass spectrometry (LC-HRMS) indicated that the removal of BA was dependent on the ortho-cleavage pathway of catechol and eventually entered the TCA cycle. Notably, compared to 77.90 +/- 5.17 % by free bacteria, the degradation efficiency of BA in the actual wastewater was dramatically enhanced to 98.59 +/- 0.04 % by the immobilized bacterial pellets. This study highlights the feasibility of immobilized microbial technology in conjunction with the SBR system in the remediation of BA-containing wastewater, providing valuable insights into the application of bioremediation method in environmental management.

Parkinson’s disease (PD) is a common neurodegenerative disorder with a complicated etiology and pathogenesis. α-Synuclein aggregation, dopaminergic (DA) neuron loss, mitochondrial injury, oxidative stress, and inflammation are involved in the process of PD. Neuroinflammation has been recognized as a key element in the initiation and progression of PD. In this review, we summarize the inflammatory response and pathogenic mechanisms of PD. Additionally, we describe the potential anti-inflammatory therapies, including nod-like receptor pyrin domain containing protein 3 (NLRP3) inflammasome inhibition, nuclear factor κB (NF-κB) inhibition, microglia inhibition, astrocyte inhibition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibition, the peroxisome proliferator-activated receptor γ (PPARγ) agonist, targeting the mitogen-activated protein kinase (MAPK) pathway, targeting the adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway, targeting α-synuclein, targeting miRNA, acupuncture, and exercise. The review focuses on inflammation and will help in designing new prevention strategies for PD.

Herein, a ccRCC targeting nanodrug is designed to enhance chemodynamic therapy (CDT) as well as activate cuproptosis and tumor immunotherapy via ccRCC cell membrane modifying CuO@Gd 2 O 3 yolk-like particles (CGYL) loaded with lactate oxidase (LOx) (mCGYL-LOx). Benefiting from the homologous targeting effect of Renca cell membranes, the mCGYS-LOx can be effectively internalized by Renca cells, open the “gate”, and then release LOx and copper (Cu) ions. LOx can catalyze excessive lactate in Renca cells into H 2 O 2 , following that the produced H 2 O 2 is further converted by Cu ions to the highly toxic ·OH, contributing to tumor CDT. Meanwhile, the excessive Cu ions effectively trigger tumor cuproptosis. These synergistic effects induce the release of damage associated molecular patterns (DAMPs) and activate immunogenic cell death (ICD), leading to DC maturation and infiltration of immune effector cells. Moreover, LOx-mediated lactate consumption downregulates the expression of PD-L1, crippling tumor immune escape. In addition, the mCGYL-LOx improves T 1 -weighted MRI signal, allowing for accurate diagnosis of ccRCC. This study demonstrates that the mCGYL-LOx has great potential for improving therapy of ccRCC via the synergistic actions of CDT and cuproptosis as well as immunotherapy.

Carbon-ion radiation therapy (CIRT) may offer remarkable advantages in cancer treatment with its unique physical and biological characteristics. However, the underlying epigenetic regulatory mechanisms of cancer response to CIRT remain to be identified. In this study, we showed consistent but different degrees of biological effects induced in NSCLC A549 cells by carbon ions of different LET. The genome-wide chromatin accessibility and transcriptional profiles of carbon ion-treated A549 cells were performed using transposase-accessible chromatin sequencing (ATAC-seq) and RNA-seq, respectively, and further gene regulatory network analysis was performed by integrating the two sets of genomic data. Alterations in chromatin accessibility by carbon ions of different LET predominantly occurred in intron, distal intergenic and promoter regions of differential chromatin accessibility regions. The transcriptional changes were mainly regulated by proximal chromatin accessibility. Notably, CCCTC-binding factor (CTCF) was identified as a key transcription factor in the cellular response to carbon ions. The target genes regulated by CTCF in response to carbon ions were found to be closely associated with the LET of carbon ions, particularly in the regulation of gene transcription within the DNA replication- and metabolism-related signaling pathways. This study provides a regulatory profile of genes involved in key signaling pathways and highlighted key regulatory elements in NSCLC A549 cells during CIRT, which expands our understanding of the epigenetic mechanisms of carbon ion-induced biological effects and reveals an important role for LET in the regulation of changes in chromatin accessibility, although further research is needed.

Microcystin-LR (MC-LR) has been recognized as a typical hepatotoxic cyclic peptides produced by cyanobacteria. Nowadays, due to the frequent occurrence of cyanobacterial blooms, the underlying hepatotoxic mechanism of MC-LR has become the focus of attention. In our present work, the mutagenic effect of MC-LR on human normal hepatic (HL-7702) cells regulated by cGAS was mainly studied. Here, we showed that exposure to MC-LR for 1-4 days could activate the cGAS-STING signaling pathway and then trigger immune response in HL-7702 cells. Notably, relative to the treatment with 1 mu M MC-LR for 1-3 days, it was observed that when HL-7702 cells were exposed to 1 mu M MC-LR for 4 days, the mutation frequency at the Hprt locus was remarkably increased. In addition, cGAS in HL-7702 cells was also found to complete the nuclear translocation after 4-day exposure. Moreover, co-immunoprecipitation and homologous recombination (HR)-directed DSB repair assay were applied to show that homologous recombination repair was inhibited after 4-day exposure. However, the intervention of the nuclear translocation of cGAS by transfecting BLK overexpression plasmid restored homologous recombination repair and reduced the mutation frequency at the Hprt locus in HL-7702 cells exposed to MC-LR. Our study unveiled the distinct roles of cGAS in the cytoplasm and nucleus of human hepatocytes as well as potential mutagenic mechanism under the early and late stage of exposure to MC-LR, and provided a novel insight into the prevention and control measures about the hazards of cGAS-targeted MC-LR.

Though telomeres play a crucial role in maintaining genomic stability in cancer cells and have emerged as attractive therapeutic targets in anticancer therapy, the relationship between telomere dysfunction and genomic instability induced by irradiation is still unclear. In this study, we identified that protection of telomeres 1 (POT1), a single-stranded DNA (ssDNA)-binding protein, was upregulated in γ-irradiated HeLa cells and in cancer patients who exhibit radiation tolerance. Knockdown of POT1 delayed the repair of radiation-induced telomeric DNA damage which was associated with enhanced H3K9 trimethylation and enhanced the radiosensitivity of HeLa cells. The depletion of POT1 also resulted in significant genomic instability, by showing a significant increase in end-to-end chromosomal fusions, and the formation of anaphase bridges and micronuclei. Furthermore, knockdown of POT1 disturbed telomerase recruitment to telomere, and POT1 could interact with phosphorylated ATM (p-ATM) and POT1 depletion decreased the levels of p-ATM induced by irradiation, suggesting that POT1 could regulate the telomerase recruitment to telomeres to repair irradiation-induced telomeric DNA damage of HeLa cells through interactions with p-ATM. The enhancement of radiosensitivity in cancer cells can be achieved through the combination of POT1 and telomerase inhibitors, presenting a potential approach for radiotherapy in cancer treatment.

A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding function of the brain. Here, using snRNA-seq and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters with single-cell resolution involving over 6 million cells as well as for 29,655 genes. We have identified new astrocyte clusters, and demonstrated that distinct cell clusters exhibit preference for cortical subregions. In addition, we identified 155 genes exhibiting regional specificity in the brainstem, and 513 long non-coding RNA exhibited regional specificity in the adult brain. Parcellation of brain regions based on spatial transcriptomic information showed large overlap with that by traditional method. Furthermore, we have uncovered 411 transcription factor regulons with spatiotemporal specificity during development. Thus, our study has discovered genes and regulon with spatiotemporal specificity, and provided a high-resolution spatial transcriptomic atlas of the mouse brain.### Competing Interest StatementEmployees of BGI have stock holdings in BGI. All other authors declare no competing interests.

Polybrominated diphenyl ethers (PBDEs) are a group of flame retardants used in plastics, textiles, polyurethane foam, and other materials. They contain two halogenated aromatic rings bonded by an ester bond and are classified according to the number and position of bromine atoms. Due to their widespread use, PBDEs have been detected in soil, air, water, dust, and animal tissues. Besides, PBDEs have been found in various tissues, including liver, kidney, adipose, brain, breast milk and plasma. The continued accumulation of PBDEs has raised concerns about their potential toxicity, including hepatotoxicity, kidney toxicity, gut toxicity, thyroid toxicity, embryotoxicity, reproductive toxicity, neurotoxicity, and immunotoxicity. Previous studies have suggested that there may be various mechanisms contributing to PBDEs toxicity. The present study aimed to outline PBDEs’ toxic effects and mechanisms on different organ systems. Given PBDEs’ bioaccumulation and adverse impacts on human health and other living organisms, we summarize PBDEs’ effects and potential toxicity mechanisms and tend to broaden the horizons to facilitate the design of new prevention strategies for PBDEs-induced toxicity.

Particulate matter 2.5 (PM 2.5 ) is a widely known atmospheric pollutant which could induce the aging-related pulmonary diseases such as acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary �brosis (IPF). In recent years, with the increasing atmospheric pollution, airborne �ne PM 2.5 , which is an integral part of air pollutants, has become a thorny problem. Hence, this study focused on the effect of PM 2.5 on the senescence of pulmonary epithelial (A549) cells, identifying which in�ammatory pathway mediated PM 2.5 -induced cellular senescence and how to play a protective role against this issue. Our data suggested that PM 2.5 induced time- and concentration-dependent increasement in the senescence of pulmonary epithelial cells. Using a inhibitor of cGAS (PF-06928215) and a inhibitor of NF-κB (BAY 11-7082), it was revealed that PM 2.5 -induced senescence was regulated by in�ammatory response, which was closely related to the cGAS/STING/NF-κB pathway activated by DNA damage. Moreover, our study also showed that when A549 cells were exposed to 100 µg/mL PM 2.5 for 48 h, the pretreatment with 20 µM selenomethionine (Se-Met) for 12 h could inhibit in�ammatory response and prevent cellular senescence by hindering cGAS/STING/NF-κB pathway. These �ndings indicated that selenium made a defense capability for PM 2.5 -induced senescence of alveolar epithelial cells, which provided a novel insight for resisting the harm of PM 2.5 to human health. selenium of alveolar epithelial cells by attenuating in�ammatory response mediated by cGAS/STING/NF-κB pathway.

Particulate matter 2.5 (PM2.5) is a widely known atmospheric pollutant which can induce the aging-related pulmonary diseases such as acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF). In recent years, with the increasing atmospheric pollution, airborne fine PM2.5, which is an integral part of air pollutants, has become a thorny problem. Hence, this study focused on the effect of PM2.5 on cellular senescence in the lung, identifying which inflammatory pathway mediated PM2.5-induced cellular senescence and how to play a protective role against this issue. Our data suggested that PM2.5 induced time- and concentration-dependent increasement in the senescence of A549 cells. Using an inhibitor of cGAS (PF-06928215) and an inhibitor of NF-κB (BAY 11–7082), it was revealed that PM2.5-induced senescence was regulated by inflammatory response, which was closely related to the cGAS/STING/NF-κB pathway activated by DNA damage. Moreover, our study also showed that the pretreatment with selenomethionine (Se-Met) could inhibit inflammatory response and prevent cellular senescence by hindering cGAS/STING/NF-κB pathway in A549 cells exposed to PM2.5. Furthermore, in vivo C57BL/6J mice model demonstrated that aging of mouse lung tissue caused by PM2.5 was attenuated by decreasing cGAS expression after Se-Met treatment. Our findings indicated that selenium made a defense capability for PM2.5-induced cellular senescence in the lung, which provided a novel insight for resisting the harm of PM2.5 to human health.

As an important cholesterol oxide, 7-ketocholesterol plays a deleterious role in the occurrence of cancer. Although the fact had been proved that 7-ketocholesterol could induce several biological phenomena, including apoptosis, DNA damage, et al., this issue whether 7-ketocholesterol led to mutagenesis in mammalian cells remains largely unexplored. Here, we investigated the major role of lipid peroxidation in the genotoxic response to 7-ketocholesterol in chinese hamster ovary (CHO) cells. The results showed that 7-ketocholesterol induced gene mutation and DNA double-strand breaks (DSBs) in concentration- and time-dependent manner. After CHO cells were treated with 25 μM 7-ketocholesterol for 48 h, the mutation frequency at hprt gene loci and the level of γ-H2AX protein were both significantly increased. Exposure to 7-ketocholesterol resulted in a concentration-dependent increase in the apoptotic rate and the protein expression of cleaved caspase-3 and -7 in CHO cells. Moreover, a significant increase of superoxide dismutase (SOD) activity and content of malondialdehyde (MDA) was also observed. Using a inhibitor of lipid peroxidation (butylated hydroxytoluene), it was found to remarkably inhibit the genotoxicity and MDA levels caused by 7-ketocholesterol. These findings indicated that lipid peroxidation was involved in the mutagenic process of 7-ketocholesterol in CHO cells.

Toxic pollutant (TP) detection in situ using analytical instruments or whole-cell biosensors is inconvenient. Designing and developing genetically coded biosensors in vitro for real-world TP detection is a promising alternative. However, because the bioactivity and stability of some key biomolecules are weakened in vitro, the response and regulation of reporter protein become difficult. Here, we established a genetically encoded biosensor in vitro with an arsenical resistance operon repressor (ArsR) and GFP reporter gene. Given that the wildtype ArsR did not respond to arsenic and activate GFP expression in vitro, we found, after screening, an evolved ArsR mutant ep3 could respond to arsenic and exhibited an approximately 3.4-fold fluorescence increase. Arsenic induced expression of both wildtype ArsR and ep3 mutant in vitro, however, only ep3 mutant regulated the expression of reporter gene. Furthermore, the effects of cell extracts, temperature, pH, incubation, and equilibrium time were investigated, and the equilibration of reaction mixtures for 30 min at 37 °C was found to be essential for in vitro arsenic detection prior to treatment with arsenic. Based on our data, we established a standard procedure for arsenic detection in vitro. Our results will facilitate the practical application of genetically encoded biosensors in TP monitoring.

Microcystin-LR (MC-LR) is a widely known hepatotoxin which could induce the occurrence and metastasis of hepatocellular carcinoma. In recent years, with the frequent outbreak of cyanobacteria, the harm of MC-LR has gradually attracted more attention. Hence, this study focused on the effect of MC-LR on DNA damage in HepG2 cells, identifying the types and sources of free radicals that make an important function on this issue. Our data suggested that MC-LR induced concentration- and time-dependent increasement of DNA double-strand breaks (DSBs). After exposure to 1 mu M MC-LR for 3 days, the protein expression and immunofluorescence staining of gamma-H2AX was significantly increased. Using a scavenger of mitochondrial O-2(center dot-)(4-hydroxy-tempo), a inhibitor of mitochondrial NOS (7-nitroindazole), and a scavenger of ONOO- (uric acid), it was revealed that ONOO- originated from mitochondria made a significant contribution to the genotoxicity of MC-LR. Moreover, a significant decreasement of mitochondrial membrane potential (MMP) was observed. These findings suggested that peroxynitrite targeting mitochondria plays a vital role in the MC-LR-induced genotoxic response in mammalian cells.

Bisphenol A (BPA) is a toxic environmental pollutant commonly found in wastewater. Using non-toxic materials and eco-friendly technology to remove this pollutant from wastewater presents multiple advantages. Treatment of wastewater with clay minerals has received growing interest because of the environment friendliness of these materials. Bentonite is a 2:1 layered phyllosilicate clay mineral that can support nano-metal catalysts. It can prevent the agglomeration of nano-metal catalysts and improve their activity. In this article, a green catalytic nano zero-valent iron/bentonite composite material (NZVI@bentonite) was synthesized via liquid-phase reduction. The average size of NZVI was approximately 40-50 nm. Good dispersion and low aggregation were observed when NZVI was loaded on the surface or embedded into the nanosheets of bentonite. Degradation of BPA, a harmful contaminant widely found in wastewater at relatively high levels, by NZVI@bentonite was then investigated and compared with that by pristine NZVI through batch Fenton-like reaction experiments. Compared with pristine NZVI and bentonite alone, the NZVI@bentonite showed a higher BPA degradation ratio and offered highly effective BPA degradation up to 450 mg/g in wastewater under optimum operating conditions. Adsorption coupled with the Fenton-like reaction was responsible for BPA degradation by NZVI@bentonite. This work extends the application of NZVI@bentonite as an effective green catalyst for BPA degradation in aqueous environments.

Although it is well acknowledged that the anti-androgenic phthalate diesters can be readily hydrolysed into their monoester counterparts, their metabolites' toxicology remains obscure. Herein, we tested the hypothesis that hydrolysis of one of the two ester bonds can mediate phthalate diesters' potential endocrine effects in MLTC-1 Leydig cells, in line with their ability to disrupt androgen secretion in humans. Five diesters (DMP, DEP, DBP, DBzP and DEHP) and five monoesters (MMP, MEP, MBP, MBzP and MEHP) phthalates as mixtures or individually were applied to cell lines to investigate differences in phthalates' hydrolysis associated with varying side-chain structures and steroidogenic effects. Short-chain diesters DMP, DEP and DBP are more readily hydrolysed compared to the long-chain DEHP, while aromatic alkyl chain DBzP cannot be metabolized completely in vitro. When the hydrolysis processes are interrupted, the diester phthalates' steroidogenic effects can be influenced via regulating related steroidogenic pathway genes. With 10-100 μM treatment exposures, androgenic effects were observed only with DMP or DEP but not for MMP or MEP; while the phthalate diesters DBP, DBzP or DEHP generally exhibited more complex steroidogenic effects than their corresponding monoester counterparts (i.e., biphasic androgen and anti-androgen effects for diesters but monotonic androgen effects for monoesters were observed). DBP elicited hydrolysis-related steroidogenic modulation, in which the anti-androgenic effects of diester DBP reversed into the androgenic effects of monoester MBP at 100 μM. Phthalate metabolites appear to exert different effects at an endocrine level compared to parent compounds, and deeper insights into how the hydrolytic process is related to this alternating toxicity would improve our understanding of a risk assessment for these widespread contaminants in male reproduction.

There is a common sense view for atomic magnetometers that their spin-projection-noises (SPNs) are inversely proportional to root T-2, where T-2 is the transverse relaxation time. We analyze the current atomic magnetometer types and give a counter-example of this common sense, which is the all-optical spin precession modulated three-axis atomic magnetometer proposed by our group in 2015. Unlike the other atomic magnetometers, the SPN of this kind of atomic magnetometers is proportional to root T-2 due to the fact that the scale factor between P-x and B can be unrelated to the transverse relaxation time T-2. We demonstrate this irrelevance experimentally and analyze the SPN theoretically. Using short-pulse ultra-high power laser to fully polarize the atoms, the phenomenon that SPN decreases with T-2 may also be demonstrated experimentally and a new tool for researching SPN in atomic magnetometers may be realized.

To measure the residual magnetic field, which is a kind of static magnetic fields in the magnetic shields, is a tough task in the design of the cylindrical magnetic shields. Here, we demonstrate a method to measure static weak magnetic fields based on low-field nuclear magnetic resonance (NMR), where the static magnetic field's strength can be obtained by measuring nuclear spin precession's frequency. Atomic magnetometers can be adopted to sense the nuclear spin precession, and the nuclear spin can be adopted to measure the static magnetic field through this indirect method to obtain the static magnetic field's strength. With this method, some adverse factors that can make atomic magnetometers yield fluctuations, such as fluctuations in the light intensity and misalignment of the pump and probe beams, can be avoid. We also measure the axial residual magnetic field in the magnetic shields, where the magnetic field's strength is about 235 pT in the direction along the pump beam. By monitoring NMR signals from protons and fluorine nuclei, we realize a nuclear-spin comagnetometer, which can be used to detect static weak magnetic fields. The possibility of using a miniaturized atomic magnetometer sensor (MAMS) for static field measurements is also discussed.

Environmental exposure to arsenic, phthalate esters (PAEs) and perfluorinated compounds (PFCs) has been associated with human semen quality. However, the epidemiological "black-box" of these associations remains poorly uncovered. In this study, based on the association analysis between arsenic, PAE and PFC exposure and semen quality parameters (i.e., semen volume, sperm concentration, sperm count, progressive motility, total motility and normal morphology) in a Chinese male population, we explored the seminal plasma metabolic signatures that may mediate the exposure-outcome relations by using the meet-in-metabolite-analysis (MIMA) approach. As a result, a negative association was found between DMA and sperm concentration, whereas MEHP and PFHxS were positively associated with sperm count and concentration, respectively. Metabolomics analysis revealed that sixteen and twenty-two seminal plasma metabolites were related to sperm concentration and count, respectively, and they are mainly involved in fatty acid, lipid and amino acid metabolism. Moreover, it was further indicated that eicosatetraenoate, carnitines and DHA may impact the inverse association between DMA and sperm concentration, while eicosatetraenoate, carnitines, DHA, PGB2 and tocotrienol are possible mediators of the positive association between PFHxS and sperm concentration. As these metabolic biomarkers are relevant to antioxidation and fatty acid β-oxidation, we suggest that redox balance and energy generation shifts in seminal plasma are involved in the association of human semen quality with environmental DMA and PFHxS exposure.