Neutrophil and macrophage crosstalk might be a potential target for liver regeneration.

The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single-cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non-parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment.

Liquid crystal monomers (LCMs) in indoor residential dust from Beijing, China: occurrence and human exposure.

Liquid crystal monomers (LCMs) are widely used in electronic devices and emerging as an environmental pollutant, while their occurrence in indoor environments is still less studied. In this study, 32 out of 37 target LCMs were detected in indoor residential dust samples (n = 112) from Beijing, China. Concentrations of Σ32LCMs ranged from 17.8 to 197 ng/g, with a median value of 54.7 ng/g. Fluorinated biphenyls and analogs (FBAs) and cyanobiphenyls and analogs (CBAs), with median concentrations of 22.8 and 15.9 ng/g, respectively, were the main kinds of LCMs. Although 32 LCMs can be detected, four monomers with the highest contamination levels contributed to almost 70% of the total LCMs. Spearman correlation analysis found significant correlations among some monomers, which indicated that they might share similar sources in the residential environment. Estimated daily intakes (EDIs) of LCMs via indoor dust for Beijing residents were calculated, and the results showed that dust ingestion and dermal contact were both main intake pathways to LCMs, and younger people may face higher exposure to LCMs. A comparison to the results of China's total diet study showed that EDIs of LCMs via food consumption might be higher than that via dust intake, while health risks caused by exposure of LCMs for the general population, both through food and dust, were insignificant at present.

An Esterase-Responsive SLC7A11 shRNA Delivery System Induced Ferroptosis and Suppressed Hepatocellular Carcinoma Progression.

Ferroptosis has garnered attention as a potential approach to fight against cancer, which is characterized by the iron-driven buildup of lipid peroxidation. However, the robust defense mechanisms against intracellular ferroptosis pose significant challenges to its effective induction. In this paper, an effective gene delivery vehicle was developed to transport solute carrier family 7 member 11 (SLC7A11) shRNA (shSLC7A11), which downregulates the expression of the channel protein SLC7A11 and glutathione peroxidase 4 (GPX4), evoking a surge in reactive oxygen species production, iron accumulation, and lipid peroxidation in hepatocellular carcinoma (HCC) cells, and subsequently leading to ferroptosis. This delivery system is composed of an HCC-targeting lipid layer and esterase-responsive cationic polymer, a poly{N-[2-(acryloyloxy)ethyl]-N-[p-acetyloxyphenyl]-N} (PQDEA) condensed shSLC7A11 core (G-LPQDEA/shSLC7A11). After intravenous (i.v.) injection, G-LPQDEA/shSLC7A11 quickly accumulated in the tumor, retarding its growth by 77% and improving survival by two times. This study is the first to construct a gene delivery system, G-LPQDEA/shSLC7A11, that effectively inhibits HCC progression by downregulating SLC7A11 expression. This underscores its therapeutic potential as a safe and valuable candidate for clinical treatment.

Decabromodiphenyl ether induces the chromosome association disorders of spermatocytes and deformation failures of spermatids in mice.

The environmental presence of decabromodiphenyl ether (BDE-209), which is toxic to the male reproductive system, is widespread. The current study investigated its mechanism of toxicity in mice. The results showed, that BDE-209 induced DNA damage, decreased the expression of the promoter of meiosis spermatogenesis- and oogenesis-specific basic helix-loop-helix 1 (Sohlh1), meiosis related-factors Lethal (3) malignant brain tumor like 2 (L3MBTL2), PIWI-like protein 2 (MILI), Cyclin-dependent kinase 2 (CDK2), Cyclin A, synaptonemal complex protein 1 (SYCP1) and synaptonemal complex protein 3 (SYCP3), and caused spermatogenic cell apoptosis, resulting in a decrease in sperm quantity and quality. Furthermore, BDE-209 downregulated the levels of anaphase-promoting complex/cyclosome (APC/C), increased the expression of PIWI-like protein 1 (MIWI) in the cytoplasm of elongating spermatids, and decreased the nuclear levels of RING finger protein 8 (RNF8), ubiquitinated (ub)-H2A/ub-H2B, and Protamine 1 (PRM1)/Protamine 2 (PRM2), while increasing H2A/H2B nuclear levels in spermatids. The reproductive toxicity was persistent for 50 days following the withdrawal of BDE-209 exposure. The results suggested that BDE-209 inhibits the initiation of meiosis by decreasing the expression of Sohlh1. Furthermore, the reduced expression of L3MBTL2 inhibited the formation of chromosomal synaptonemal complexes by depressing the expression of meiosis regulators affecting the meiotic progression and also inhibited histone ubiquitination preventing the replacement of histones by protamines, by preventing RNF8 from entering nuclei, which affected the evolution of spermatids into mature sperm.

Efficacy and safety of anlotinib as an adjuvant therapy in hepatocellular carcinoma patients with a high risk of postoperative recurrence.

Objective: Hepatocellular carcinoma (HCC) has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence. This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors. Methods: For this multicenter, retrospective study, we recruited 63 HCC patients who received either anlotinib (n=27) or transcatheter arterial chemoembolization (TACE) (n=36) from six research centers in China between March 2019 and October 2020. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS) and safety. Results: In this study, the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups, respectively. There was no significant difference in the median DFS between the anlotinib [26.8 months, 95% confidence interval (95% CI): 6.8-NE] and TACE groups (20.6 months, 95% CI: 8.4-NE). The 12-month OS rates in the anlotinib and TACE groups were 96.3% and 97.2%, respectively. In the anlotinib group, 19 of 27 patients (70.4%) experienced treatment-emergent adverse events, with the most common events (≥10%) being hypertension (22.2%) and decreased platelet count (22.2%). Conclusions: The results indicate that anlotinib, as a new, orally administered tyrosine kinase inhibitor, has the same efficacy as TACE, and side effects can be well controlled.

Occurrence of legacy and alternative per- and polyfluoroalkyl substances in serum from high exposure population and their disrupting effects on serum lipids and thyroid function.

High exposure of per- and polyfluoroalkyl substances (PFAS) has been reported in main chemical production areas in China, while epidemiological study on exposure risk of PFAS is still limited. In this study, legacy and alternative PFAS were measured in serum samples from 161 adults living in Laizhou Bay, a famous chemical production area located in Shandong province, Northern China. Based on the concentrations of serum PFAS, the disrupting effects of PFAS on serum lipids and thyroid function were further explored. The results showed that the serum perfluorooctanoic acid (PFOA) (geometric mean (GM): 60 ng/mL) in this region was even higher than serum PFOA of residents living in PFOA contaminated water districts in United States and Sweden. 100 % of the serum PFOA was higher than the reference dose for increased total cholesterol (TC). Consistently, higher serum PFOA was marginally correlated with increased TC level (p = 0.062) and low-density lipoprotein (p = 0.065). In addition, higher perfluoroisopropyl perfluorooctanesulfonate and 6:2 chlorinated polyfluoroalkyl ether sulfonates (6,2 Cl-PFESA) were significantly correlated with increased high-density lipoprotein (p = 0.040, 0.022). No significant association was observed between individual PFAS and any thyroid function biomarker. However, using the principal component analysis derived factors to represent the co-exposure patterns, co-exposure of legacy long-chain PFAS showed synergistic effects on the free thyroxine, while the mixture of alternative PFAS showed a synergistic influence on the total and free triiodothyronine.

Legacy and novel brominated flame retardants in animal-derived foods from China Total Diet Study (CTDS): Temporal trends, evidence of substitution, and dietary exposure assessment.

Based on the 6th China Total Diet Study (CTDS) conducted in 2016-2019, the occurrence of both legacy and novel brominated flame retardants (BFRs) was measured in animal-derived foods collected across China. Most BFRs could be frequently detected in food samples, indicating their ubiquity in the environment. Decabromodiphenyl ethane (DBDPE), a typical novel BFR, presented the highest contamination level, whereas legacy BFRs, including decabrominated diphenyl ether (BDE-209), tetrabromobisphenol A (TBBPA), and hexabromocyclododecane (HBCDD), still presented high detection frequencies and relatively abundant proportions in total BFRs. Compared with previous CTDSs conducted from 2007 to 2011, the levels and estimated dietary intakes (EDIs) of most BFRs showed a significant downtrend, which suggested that flame retardant consumption in China has transferred from legacy BFRs to novel BFRs (mainly DBDPE) and from BFRs to other kinds of flame retardants. Based on probabilistic estimation, the median EDIs of mainly used BFRs for the Chinese population ranged from 41.0 to 1.67 × 103 pg/kg bw/day, and meat consumption was the primary source in dietary BFR intake. By conducting the margin of exposure (MOE) approach or comparing with the reference dose (RfD), it can be concluded that daily dietary intakes of BFRs were still unable to cause significant health risks to the general population in China.

BDE-209 induced spermatogenesis disorder by inhibiting SETD8/H4K20me1 related histone methylation in mice.

Past studies have observed that decabromodiphenyl ether (BDE-209) induces reproductive and developmental toxicity, but the specific mechanism remains unclear. Based on our previous work, male mice were orally given BDE-209 at 75 mg/kg/d via continuous exposure for one spermatozoon development period (50 days) and then stopping exposure for another 50 days. The mouse spermatocyte line GC-2spd was used to examine the toxic effects of BDE-209 on histone methylation and spermatogenesis. The findings indicated that BDE-209 damaged testis and epididymis structure, induced spermatogenic cell apoptosis, and decreased sperm quantity and quality after the 50-day exposure. Furthermore, BDE-209 lowered the levels of SETD8/H4K20me1 and activated the upstream signaling of DNA damage response (Mre11/Rad50/NBS1), thereby causing spermatogenic cell cycle arrest and apoptosis. Downregulation of meiotic promoter Stra8 was associated with a decrease in SETD8 after BDE-209 exposure. After stopping the exposure for 50 days, reproductive system damage and meiosis and cell cycle inhibition due to histone methylation did not improve. In vitro experiments revealed that Setd8 overexpression upregulated the histone methylation and Stra8 expression but did not promote the cell cycle in GC-2 cells. Therefore, BDE-209 exposure impaired spermatogenesis by affecting SETD8/H4K20me1-linked histone methylation and inhibiting meiosis initiation and cell cycle progression, thereby resulting in long-term male reproductive toxicity.

DBDPE upregulates NOD-like receptor signaling to induce NLRP3 inflammasome-mediated HAECs pyroptosis.

Decabromodiphenyl ethane (DBDPE), a typical new brominated flame retardant (BFR), is a widespread new pollutant in the environment. Several studies and our previous studies have found that DBDPE can cause aortic endothelial injury and aortic endothelial cell pyroptosis, whereas the molecular mechanism involved has not been elucidated. In this study, we exposed human aortic endothelial cells (HAECs) to 25 µmol/L of DBDPE and analyzed the gene expression profiles by Affymetrix PrimeView™ Human Gene Expression Chip. The results showed that 886 genes were differentially expressed in the DBDPE exposure group. Enrichment analyses revealed that differentially expressed genes were mainly enriched in the inflammatory response and NOD-like receptor signal pathway. Gene-gene functional interaction analyses and crossover genes and pathways analyses found that the NOD-like receptor signal pathway may be involved in regulating NLRP3 and IL-18. We found that NOD2 cannot interact with NLRP3 directly through an immunoprecipitation experiment. Thus, we construct the RIPK2 knockdown HAECs cell line to repress the NOD-like receptor signaling and further study the mechanism of DBDPE-activated NLRP3 inflammasome to induce HAECs pyroptosis. The results showed that RIPK2 knockdown could repress DBDPE-induced NOD-like receptor signaling pathway upregulation, inhibit NLRP3 inflammasome activation, and decrease HAECs pyroptosis. In addition, RIPK2 knockdown decreased the ROS generation in HAECs induced by DBDPE. And NAC pretreated HAECs inhibited DBDPE-induced NLRP3 inflammasome activation and HAECs pyroptosis. These results demonstrated that DBDPE upregulated NOD-like receptor signaling to induce ROS generation and, in turn, activated NLRP3 inflammasome, leading to HAECs pyroptosis.

A global survey of organophosphate esters and their metabolites in milk: Occurrence and dietary intake via milk consumption.

The first global survey of organophosphate esters (OPEs) and their metabolites (mOPEs) in milk was carried out in this study. Concentrations of 21 OPEs and 9 mOPEs were measured in 178 milk samples collected from 30 countries located on 5 continents, and the ubiquity of both OPEs and mOPEs was observed in milk. Concentrations of ∑21OPEs ranged from 53.3 pg/mL to 4270 pg/mL, with a median level of 367 pg/mL. The median level of ∑9mOPEs was 153 pg/mL, with a range of 15-7440 pg/mL. No difference was observed among the levels of both ∑21OPEs and ∑9mOPEs in milk from the five continents. For the relationship between mOPEs and their parent OPEs, some pairs presented significant and positive correlations, which indicated that they shared similar sources. Estimated daily intakes (EDIs) of OPEs/mOPEs via milk consumption were calculated. Asian countries presented relatively low EDIs, and European and American countries, especially Denmark, the Netherlands, Finland and Argentina, presented high EDIs. Current daily OPE intake via milk consumption for global adult populations was far lower than the corresponding reference dose; however, considering that human intake of OPEs occurs via multiple sources, it is too early to conclude that the intake of OPEs were unable to cause health concerns.

Decabromodiphenyl ethane induces male reproductive toxicity by glycolipid metabolism imbalance and meiotic failure.

Decabromodiphenyl ethane (DBDPE) is a typical flame retardant found in various electrical and textile items. DBDPE is abundantly available in the surrounding environment and wild animals based on its persistence and bioaccumulation. DBDPE has been shown to cause apoptosis in rat spermatogenic cells, resulting in reproductive toxicity. However, the toxicity of DBDPE on the male reproductive system and the potential mechanisms are still unclear. This study evaluated the effect of DBDPE on the reproductive system in male SD rats and demonstrated the potential mechanisms of reproductive toxicity. DBDPE (0, 5, 50, and 500 mg/kg/day) was administered via gavage to male SD rats for 28 days. DBDPE caused histopathological changes in the testis, reduced sperm quantity and motility, and raised the malformation rate in rats, according to the findings. Furthermore, it caused DNA damage to rat testicular cells. It inhibited the expressions of spermatogenesis-and oogenesis-specific helix-loop-helix transcription factor 1 (Sohlh1), piwi-like RNA-mediated gene silencing 2 (MILI), cyclin-dependent kinase 2 (CDK2), and CyclinA, resulting in meiotic failure, as well as the expressions of synaptonemal complex proteins 1 and 3 (SYCP1 and SYCP3), leading to chromosomal association disorder in meiosis and spermatocyte cycle arrest. Moreover, DBDPE induced glycolipid metabolism disorder and activated mitochondria-mediated apoptosis pathways in the testes of SD rats. The quantity and quality of sperm might be declining due to these factors. Our findings offer further evidence of the harmful impact of DBDPE on the male reproductive system.

Fat mass and obesity-associated gene (FTO) hypermethylation induced by decabromodiphenyl ethane causing cardiac dysfunction via glucolipid metabolism disorder.

Decabromodiphenyl ethane (DBDPE) is a major alternative to BDE-209 owing to its lower toxicity. However, the mass production and increased consumption of DBDPE in recent years have raised concerns related to its adverse health effects. However, the effect and mechanism of DBDPE on cardiotoxicity have rarely been studied. In the present study, we investigated the impacts of DBDPE on the cardiovascular system in male SD rats and then explored the underlying mechanisms to explain the cardiotoxicity of DBDPE using AC16 cells. Under in vivo conditions, male rats were administered with an oral dosage of DBDPE at 0, 5, 50, and 500 mg/kg/day for 28 days, respectively. Histopathological analysis demonstrated that DBDPE induced cardiomyocyte injury and fibrosis, and ultrastructural observation revealed that DBDPE could induce mitochondria damage and dissolution. DBDPE could thus decrease the level of MYH6 and increase the level of SERCA2, which are the two key proteins involved in the maintenance of homeostasis during myocardial contractile and diastolic processes. Furthermore, DBDPE could increase the serum levels of glucose and low-density lipoprotein but decrease the content of high-density lipoprotein. In addition, DBDPE could activate the PI3K/AKT/GLUT2 and PPARγ/RXRα signaling pathways in AC16 cells. In addition, DBDPE decreased the UCP2 level and ATP synthesis in mitochondria both under in vitro and in vivo conditions, consequently leading to apoptosis via the Cytochrome C/Caspase-9/Caspase-3 pathway. Bisulfite sequencing PCR (BSP) identified the hypermethylation status of fat mass and obesity-associated gene (FTO). 5-aza exerted the opposite effects on the PI3K/AKT/GLUT2, PPARγ/RXRα, and Cytochrome C/Caspase-9/Caspase-3 signaling pathways induced by DBDPE in AC16 cells. In addition, the DBDPE-treated altered levels of UCP2, ATP, and apoptosis were also found to be significantly reversed by 5-aza in AC16 cells. These results suggested that FTO hypermethylation played a regulative role in the pathological process of DBDPE-induced glycolipid metabolism disorder, thereby contributing to the dysfunction of myocardial contraction and relaxation through cardiomyocytes fibrosis and apoptosis via the mitochondrial-mediated apoptotic pathway resulting from mitochondrial dysfunction.

A simple method for simultaneous determination of organophosphate esters and their diester metabolites in dairy products and human milk by using solid-phase extraction coupled to liquid chromatography-tandem mass spectrometry.

Organophosphate esters (OPEs) and their diester metabolites have been frequently found in various environmental matrices and regarded as emerging environmental pollutants, whereas data on their occurrence in foods and human matrices are still limited. In this study, a novel and simple procedure was developed to simultaneously determine 14 OPEs and 6 diester metabolites in dairy products and human milk. After enzymatic hydrolysis by ß-glucuronidase/arylsulfatase, a freeze-dried milk sample was extracted with acetonitrile and purified by solid-phase extraction. Subsequently, all target compounds were determined by HPLC-ESI-MS/MS. Linearity, limits of detection (LODs), recovery, precision, and matrix effects of the proposed methodology were validated, and the parameters of HPLC-ESI-MS/MS were optimized. LODs for OPEs and their diester metabolites were from 0.001 to 0.02 ng/mL, and limits of quantification (LOQs) were 0.01-0.3 ng/mL. Average recoveries at two spiked levels ranged between 67.3 and 121%, with relative standard deviation lower than 20.7%. A test for matrix effects showed that most analytes presented signal suppression, and isotopically labeled ISs were essential for compensating for the matrix effects. Finally, OPEs and their metabolites both showed high detecting frequencies in real samples, which indicated that these emerging pollutants were ubiquitous in foods and the human body, and the impact of the diester metabolites on population exposure must be included in exposure assessment.

Organophosphate esters and their diester metabolites in infant formulas and baby supplementary foods collected in Beijing, China: Occurrence and the implications for infant exposure.

Organophosphate esters (OPEs) have been extensively used as flame retardants and/or plasticizers and they found to be ubiquitous in various environmental matrices along with the gradual phase-out of brominated flame retardants (BFRs). Moreover, their main metabolites, organophosphate di-esters (di-OPEs), were also frequently detected. However, few studies focused on the occurrence of OPEs and di-OPEs in foods. In this study, fourteen OPEs and five di-OPEs were measured in infant formula and baby supplementary food (BSF) collected in Beijing, China. Most OPEs and di-OPEs presented high detection frequencies, which indicated their ubiquity in baby foods. The concentrations of ∑14OPEs in the 75 infant formula samples ranged from 0.79 to 159 ng/g, with a median of 23.2 ng/g, and in which triphenyl phosphate (TPhP) was the most abundant compound. The concentrations of ∑14OPEs in the 32 BSF samples were 4.42-115 ng/g (median: 19.5 ng/g), and tri(3-chloropropyl) phosphate (TCIPP) was predominant. Moreover, no significant difference was observed between OPE levels in infant formula and BSF. The median concentrations of Σ5di-OPEs in infant formula and BSF were 3.39 and 5.43 ng/g, respectively. However, no significantly correlation was observed between concentrations of di-OPEs and their parent compounds, which indicated they have different sources. The median estimated dietary intakes (EDIs) of the ∑14OPEs were from 165 to 383 ng/kg bodyweight (bw)/day for infants via infant formula feeding, and were from 429 to 470 ng/kg bw/day via BSF feeding. A comparison to corresponding reference dose (RfD) suggested that dietary intakes of OPEs to Beijing infants via formula/BSF consumption were still unable to cause significant health concerns. However, EDIs of OPEs for infants were found to be significantly higher than that for Chinese adults, and dietary intake might be the predominant OPE intake pathway for infants. To our knowledge, this is the first study to investigate OPEs and their metabolites in baby foods.

Decabromodiphenyl ether-induced PRKACA hypermethylation contributed to glycolipid metabolism disorder via regulating PKA/AMPK pathway in rat and L-02 cells.

BDE-209 is the most prevalent congener of polybrominated diphenyl ethers and has high bioaccumulation in humans and animals. BDE-209 has been reported to disrupt glycolipid metabolism, but the mechanisms are still unclear. In this study, we found that BDE-209 induced liver tissue injury and hepatotoxicity, increased the glucose and total cholesterol levels in the serum of rats, and increased glucose and triglyceride levels in L-02 cells. BDE-209 exposure changed the PKA, p-PKA, AMPK, p-AMPK, ACC, and FAS expression in rats' liver and L-02 cells. Moreover, BDE-209 induced PRKACA-1 hypermethylation in L-02 cells. AMPK activator (AICAR) inhibited the changes of p-AMPK, ACC, and FAS expression and elevation of glucose and triglyceride levels induced by BDE-209. DNA methylation inhibitor (5-Aza-CdR) reversed BDE-209 induced alters of PKA/AMPK/ACC/FAS signaling pathway. These results demonstrated that BDE-209 could disrupt the glycolipid metabolism by causing PRKACA-1 hypermethylation to regulate the PKA/AMPK signaling pathway in hepatocytes.

Reduced mitochondrial DNA copy number in occupational workers from brominated flame retardants manufacturing plants.

Decabrominated diphenyl ether (BDE-209) and its substitute decabromodiphenyl ethane (DBDPE) are two flame retardants that have similar structure and are widely used in various industrial products. The accumulation and potential toxicity of them to human health have already aroused attention, and some research showed that they may affect mitochondrial function. Therefore, this study focused on the population with high exposure to brominated flame retardants (BFRs) and the related changes in mtDNA copy number (mtDNAcn) in whole blood. 334 blood samples were collected from three groups of people in Shandong Province, including 42 BDE-209 occupational exposure workers from the BDE-209 manufacturing plant, 131 DBDPE occupational exposure workers from the DBDPE manufacturing plant, and 161 non-BFRs occupational exposure residents from the BFRs contaminated area. We measured the levels of BDE-209, DBDPE in serum sample, and the mtDNAcn in whole blood sample and analyzed these data by multiple linear regression. The average concentrations of BDE-209, DBDPE and ∑(BDE-209 + DBDPE) in BDE-209 occupational workers were 3510, 639 and 4600 ng/g lw, respectively; the average concentrations of BDE-209, DBDPE and ∑(BDE-209 + DBDPE) in DBDPE occupational workers were 229, 4040 and 4470 ng/g lw, respectively; the average concentrations of BDE-209, DBDPE and ∑(BDE-209 + DBDPE) in non-BFRs occupational exposure residents were 66.3, 45.7 and 137 ng/g lw, respectively. The relative mtDNAcn was 0.823 in BDE-209 occupational workers, 0.845 in DBDPE occupational workers and 0.989 in non-BFRs occupational exposure residents. A 10-fold increase in BDE-209, DBDPE concentrations was separately associated with a 0.068 and 0.063 decrease in mtDNAcn. Therefore, our study implied that BFRs may affect mitochondrial function. As increasing BFRs exposure has emerged in recent years, the relationship between BFRs exposure and mitochondrial function needs further study.