Association between Single Nucleotide Polymorphisms of PRKD1 and KCNQ3 Gene and Milk Quality Traits in Gannan Yak (Bos grunniens).

Protein kinase D1 (PRKD1) functions primarily in normal mammary cells, and the potassium voltage-gated channel subfamily Q member 3 (KCNQ3) gene plays an important role in controlling membrane potential and neuronal excitability, it has been found that this particular gene is linked to the percentage of milk fat in dairy cows. The purpose of this study was to investigate the relationship between nucleotide polymorphisms (SNPs) of PRKD1 and KCNQ3 genes and the milk quality of Gannan yak and to find molecular marker sites that may be used for milk quality breeding of Gannan yak. Three new SNPs were detected in the PRKD1 (g.283,619T>C, g.283,659C>A) and KCNQ3 gene (g.133,741T>C) of 172 Gannan lactating female yaks by Illumina yak cGPS 7K liquid-phase microarray technology. Milk composition was analyzed using a MilkoScanTM milk composition analyzer. We found that the mutations of these three loci significantly improved the lactose, milk fat, casein, protein, non-fat milk solid (SNF) content and acidity of Gannan yaks. The lactose content of the TC heterozygous genotype population at g.283,619T>C locus was significantly higher than that of the TT wild-type population (p < 0.05); the milk fat content of the CA heterozygous genotype population at g.283,659C>A locus was significantly higher than that of the CC wild-type and AA mutant populations (p < 0.05); the casein, protein and acidity of the CC mutant and TC heterozygous groups at the g.133,741T>C locus were significantly higher than those of the wild type (p < 0.05), and the SNF of the TC heterozygous group was significantly higher than that of the mutant group (p < 0.05). The results showed that PRKD1 and KCNQ3 genes could be used as candidate genes affecting the milk traits of Gannan yak.

Proteomic Analysis Reveals the Effects of Different Dietary Protein Levels on Growth and Development of Jersey-Yak.

Jersey-yak is a hybrid offspring of Jersey cattle and yak (Bos grunniens). Changing the feeding system of Jersey-yak can significantly improve its growth performance. In this study, tandem mass tag (TMT) proteomics technology was used to determine the differentially expressed proteins (DEPs) of the longissimus lumborum (LL) muscle of Jersey-yak fed different protein levels of diet. The results showed that compared with the traditional grazing feeding, the growth performance of Jersey-yaks was significantly improved by crude protein supplementation after grazing. A total of 3368 proteins were detected in these muscle samples, of which 3365 were quantified. A total of 434 DEPs were identified. Through analyses, it was found that some pathways related to muscle growth and development were significantly enriched, such as Rap1 signaling pathway, mTOR signaling pathway, and TGF-beta signaling pathway. A number of DEPs enriched in these pathways are related to muscle cell development, differentiation, and muscle development, including integrin subunit alpha 7 (ITGA7), myosin heavy chain 8 (MYH8), and collagen type XII alpha 1 chain (COL12A1). In conclusion, the results of this study provide insights into the proteomics of different feeding patterns of Jersey-yak, providing a stronger basis for further understanding the biological mechanism of hybrid varieties.

Role of HIF-1α in hypercoagulable state of COPD in rats.

OBJECTIVE: To explore the role of HIF-1α in hypercoagulable state of COPD induced by lipopolysaccharide plus smoking in rats. It also has to explore the regulatory mechanism of HIF-1α-EPO/EDN-1/VEGF pathway by using its activator and inhibitor. METHODS: 60 Sprague-Dawley rats (SD rats) were randomly divided into healthy control group, COPD hypercoagulable control group, activator group, and inhibitor group with 15 rats in each group. The healthy control group was fed freely. The other groups were given smoke and lipopolysaccharide by tracheal instillation to establish the experimental animal model of COPD hypercoagulability. After successful modeling, each experimental group was given 0.9 % sodium chloride solution and corresponding drugs by intraperitoneal injection for 7 days. Lung function was detected after drug administration. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. Enzyme-linked immunosorbent assay was used to detect serum D-D,F (1 + 2),IL-6,TNF-α. The mRNA expressions of HIF-1α, EPO, EDN-1, and VEGF were detected by RT-PCR. Western-Blot and IHC were used to detect the expression of HIF-1α, EPO, EDN-1, and VEGF in lung tissue of rats. RESULTS: Compared with the healthy control group, rats in COPD hypercoagulable control group had COPD symptoms/signs, decreased lung function, increased the expression of serum D-D and F (1 + 2), increased the expression of inflammatory factors IL-6,TNF-α, and increased the expression of proteins HIF-1α, EPO, EDN-1 and VEGF. Compared with COPD hypercoagulable control group, lung function in activator group and inhibitor group had no obvious changes. The expressions of serum D-D,F (1 + 2),IL-6,TNF-α in activator group have increased noticeably. The expressions of proteins HIF-1α, EPO, EDN-1, and VEGF have further increased. Compared with COPD hypercoagulable control group, the expression of serum D-D, F (1 + 2), HIF-1α, EPO, EDN-1, and VEGF in the inhibitor group decreased. CONCLUSION: HIF-1α-EPO/EDN-1/VEGF pathway plays an important role in the hypercoagulable state of COPD. HIF-1α inhibitor can improve airway inflammation and reduce hypercoagulability in COPD model rats.

A comprehensive study on the ecotoxicity of ivermectin to earthworms (Eisenia fetida).

Ivermectin (IVM) is a dewormer commonly utilized in animal farming. Nevertheless, there is a deficiency of research on the bioecotoxicity of IVM in soil. In this study, earthworms were utilized as test animals to investigate the ecotoxicological impacts of IVM. The experiment lasted 28 days and involved adding varied doses of IVM to a culture substrate of soil mixed with cow dung and feeding it to earthworms. The experiment entailed recording earthworm weight, number of earthworm cocoons, histological damage, oxidative stress indicators, and gene expression levels. The analysis results showed that earthworm growth and reproduction were hampered by IVM. Moreover, pathological damage to the earthworms increased with increasing IVM concentration, which caused increased oxidative damage to the earthworms. These findings offer a summary of the impact of IVM on earthworms and a reference point for future research examining the ecological implications of IVM.

Biomechanical effects of transverse connectors on total en bloc spondylectomy of the lumbar spine: a finite element analysis.

BACKGROUND: The influence of total en bloc spondylectomy (TES) on spinal stability is substantial, necessitating strong fixation to restore spinal stability. The transverse connector (TC) serves as a posterior spinal instrumentation that connects the left and right sides of the pedicle screw-rod system. Several studies have highlighted the potential of a TC in enhancing the stability of the fixed segments. However, contradictory results have suggested that a TC not only fails to improve the stability of the fixed segments but also might promote stress associated with internal fixation. To date, there is a lack of previous research investigating the biomechanical effects of a TC on TES. This study aimed to investigate the biomechanical effects of a TC on internal fixation during TES of the lumbar (L) spine. METHODS: A single-segment (L3 segment) TES was simulated using a comprehensive L spine finite element model. Five models were constructed based on the various positions of the TC, namely the intact model (L1-sacrum), the TES model without a TC, the TES model with a TC at L1-2, the TES model with a TC at L2-4, and the TES model with a TC at L4-5. Mechanical analysis of these distinct models was conducted using the Abaqus software to assess the variations in the biomechanics of the pedicle screw-rod system, titanium cage, and adjacent endplates. RESULTS: The stability of the surgical segments was found to be satisfactory across all models. Compared with the complete model, the internal fixation device exhibited the greatest constraint on overextension (95.2-95.6%), while showing the least limitation on left/right rotation (53.62-55.64%). The application of the TC had minimal effect on the stability of the fixed segments, resulting in a maximum reduction in segment mobility of 0.11° and a variation range of 3.29%. Regardless of the use of a TC, no significant changes in stress were observed for the titanium cage. In the model without the TC, the maximum von Mises stress (VMS) for the pedicle screw-rod system reached 136.9 MPa during anterior flexion. Upon the addition of a TC, the maximum VMS of the pedicle screw-rod system increased to varying degrees. The highest recorded VMS was 459.3 MPa, indicating a stress increase of 335.5%. Following the TC implantation, the stress on the adjacent endplate exhibited a partial reduction, with the maximum stress reduced by 27.6%. CONCLUSION: The use of a TC in TES does not improve the stability of the fixed segments and instead might result in increased stress concentration within the internal fixation devices. Based on these findings, the routine utilisation of TC in TES is deemed unnecessary.

Comparative Study on Nutritional Characteristics and Volatile Flavor Substances of Yak Milk in Different Regions of Gannan.

This study aimed to investigate the nutritional properties of yak milk in various areas of Gannan. The milk composition analyzer, automatic amino acid analyzer, and flavor analyzer were used to detect the conventional nutrients, amino acids, and volatile flavor substances of 249 yak milks in Meiren grassland, Xiahe grassland, and Maqu grassland (hereinafter referred to as Meiren yak, Xiahe yak, and Maqu yak) in the Gannan area. The results showed that the fat content of Meiren yak milk was significantly higher than that of Maqu yak and Xiahe yak (p < 0.05). The protein content of Meiren yak milk was significantly higher than that of Xiahe yak (p < 0.05), but not significantly different from that of Maqu yak (p > 0.05). The casein content in the milk of Maqu yak was significantly higher than that of Meiren yak and Xiahe yak (p < 0.05). There was no significant difference in the lactose content of yak milk in the three regions (p > 0.05). The content of glutamic acid in the milk of Meiren yak, Xiahe yak, and Maqu yak was noticeably high, which was 1.03 g/100 g, 1.07 g/100 g, and 1.10 g/100 g, respectively. The total amino acid (TAA) content was 4.78 g/100 g, 4.87 g/100 g, and 5.0 g/100 g, respectively. The ratios of essential amino acids (EAA) and total amino acids (TAA) in the milk of Meiren yak, Xiahe yak, and Maqu yak were 42.26%, 41.27%, and 41.39%, respectively, and the ratios of essential amino acids (EAA) and nonessential amino acids (NEAA) were 73.19%, 70.28%, and 70.61%, respectively. In the yak milk samples collected from three different regions, a total of 34 volatile flavor compounds were detected, including 10 aldehydes, five esters, six ketones, four alcohols, two acids, and seven others. The main flavor substances qualitatively obtained from Meiren yak milk were ethyl acetate, n-valeraldehyde, acetic acid, heptanal, and n-hexanal. Xiahe yak milk mainly contains ethyl acetate, isoamyl alcohol, n-valeraldehyde, heptanal, and ethyl butyrate. Maqu yak milk mainly contains ethyl acetate, n-valeraldehyde, isoamyl alcohol, heptanal, ethyl butyrate, and n-hexanal. Principal component analysis showed that the flavor difference between Xiahe yak and Maqu yak was small, while the flavor difference between Xiahe yak, Maqu yak, and Meiren yak was large. The findings of this research can serve as a foundation for the future advancement and application of yak milk.

Effects of dietary crude protein levels in the concentrate supplement after grazing on rumen microbiota and metabolites by using metagenomics and metabolomics in Jersey-yak.

Introduction: The crude protein level in the diet will affect the fermentation parameters, microflora, and metabolites in the rumen of ruminants. It is of great significance to study the effect of crude protein levels in supplementary diet on microbial community and metabolites for improving animal growth performance. At present, the effects of crude protein level in supplementary diet on rumen fermentation parameters, microbial community, and metabolites of Jersey-Yak (JY) are still unclear. Methods: The purpose of this experiment was to study the appropriate crude protein level in the diet of JY. The rumen fermentation indexes (volatile fatty acids and pH) were determined by supplementary diets with crude protein levels of 15.16 and 17.90%, respectively, and the microbial community and metabolites of JYs were analyzed by non-target metabonomics and metagenome sequencing technology, and the changes of rumen fermentation parameters, microbial flora, and metabolites in the three groups and their interactions were studied. Results and Discussion: The crude protein level in the supplementary diet had significant effects on pH, valeric acid, and the ratio of acetic acid to propionic acid (p < 0.05). The protein level had no significant effect on the dominant microflora at the phylum level (p > 0.05), and all three groups were Bacteroides and Firmicutes. The results of metabolite analysis showed that the crude protein level of supplementary diet significantly affected the metabolic pathways such as Bile secretion and styrene degradation (p < 0.05), and there were different metabolites between the LP group and HP group, and these different metabolites were related to the dominant microbial to some extent. To sum up, in this experiment, the effects of crude protein level in supplementary diet on rumen microorganisms and metabolites of JY and their relationship were studied, which provided the theoretical basis for formulating a more scientific and reasonable supplementary diet in the future.

Mn- and Yb-Doped BaTiO3-(Na0.5Bi0.5)TiO3 Ferroelectric Relaxor with Low Dielectric Loss.

In this work, a Mn-and Yb-doped BaTiO3-(Na0.5Bi0.5)TiO3 ferroelectric relaxor was designed and prepared. The effects of Mn on the microstructures, dielectric and electrical properties of the ceramics were investigated. The X-ray structural analysis shows a perovskite structure. The SEM images show the homogeneous microstructure of ceramics with an average grain size of about 1 µm. The temperature-dependent permittivity shows relaxor characteristics as Mn-doped. Mn at a low level (x ≤ 0.005) is beneficial for low dielectric loss and high resistivity. The maximum resistivity of ≥3 × 1012 Ω cm and minimum dielectric loss of ≤0.06 can be achieved at x ≤ 0.005. The resistivity of the ceramics follows the Arrhenius law with activation energy decreasing from ~1.31 to 1.01 eV as x increases. With lower Mn dopant, oxygen vacancies and charge carrier concentration partially decrease with Mn doping, which is helpful to improve the insulation resistance and decrease the dielectric loss.

Evaluating the clinical role of fibrinogen, D-dimer, mean platelet volume in patients with acute exacerbation of COPD.

BACKGROUND: There is limited research on clinical indicators for clinicians to judge the hypercoagulability of COPD patients. OBJECTIVE: The aim in this study was to evaluate the level changes of fibrinogen (FIB), d-dimer (D-D), and mean platelet volume (MPV) in plasma during the stable phase of chronic obstructive pulmonary disease (COPD), as compared with acute exacerbation of COPD (AECOPD). METHODS: A total of 240 patients admitted with COPD in our hospital and 60 healthy people were enrolled in this prospective study using data from August 2016 to August 2017. Patients were allocated to AECOPD or stable COPD group. The levels of white blood cell (WBC) count, absolute neutrophil counts (NEU%), activated partial thromboplastin time (APTT), prothrombin time (PT), and hypoxia inducible factor-1(HIF-1) were detected. The MPV, D-D, and the FIB level were also determined and compared between groups. RESULTS: The WBC count, NEU%, FIB, and D-D were significantly higher in the AECOPD group than in the stable COPD group and the healthy group (P < 0.05), while the MPV, APTT and PT was significantly lower in the AECOPD group than in the stable COPD group and the healthy group (P < 0.05). Additionally, MPV was significantly negatively correlated with WBC count (r=-0.798) and NEU% (r=-0.749) in the AECOPD group (P < 0.05); and the percentage of forced expiratory volume in one second (FEV1) in the predicted value was significantly negatively correlated with D-D (r=-0.891) and FIB (r=-0.656) (P <0.05). CONCLUSION: We demonstrated that, for patients hospitalized for exacerbation of COPD, MPV may indeed be a valid indicator of inflammation and a marker of thrombosis.

Polymorphisms of CCSER1 Gene and Their Correlation with Milk Quality Traits in Gannan Yak (Bos grunniens).

Coiled-coil serine-rich protein 1 (CCSER 1) gene is a regulatory protein gene. This gene has been reported to be associated with various economic traits in large mammals in recent years. The aim of this study was to investigate the association between CCSER1 gene single nucleotide polymorphisms (SNPs) and Gannan yaks and to identify potential molecular marker loci for breeding milk quality in Gannan yaks. We genotyped 172 Gannan yaks using Illumina Yak cGPS 7K liquid microarrays and analyzed the correlation between the three SNPs loci of the CCSER1 gene and the milk qualities of Gannan yaks, including milk fat, protein and casein. It was found that mutations at the g.183,843A>G, g.222,717C>G and g.388,723G>T loci all affected the fat, protein, casein and lactose traits of Gannan yak milk to varying extents, and that the milk quality of individuals with mutant phenotypes was significantly improved. Among them, the milk fat content of AG heterozygous genotype population at g.183,843A>G locus was significantly higher than that of AA and GG genotype populations (p < 0.05); the casein and protein content of mutant GG and CG genotype populations at g.222,717C>G locus was significantly higher than that of wild-type CC genotype population (p < 0.05); and the g.388,723G>T locus of the casein and protein contents of the mutant TT genotype population were significantly higher (p < 0.05) than those of the wild-type GG genotype population. These results provide potential molecular marker sites for Gannan yak breeding.

Multi-omics revealed the effects of dietary energy levels on the rumen microbiota and metabolites in yaks under house-feeding conditions.

Yak (Bos grunniens) is a unique large ruminant species in the Qinghai-Tibetan Plateau (QTP). Changing the energy levels of their rations can significantly improve their growth performance. Therefore, studying the effects of dietary energy levels on the rumen microflora and metabolites of yak is crucial for enhancing the development of the yak industry. Currently, there is a lack of understanding regarding the impact of feeding energy diets on rumen fermentation parameters, microbial functions, and metabolites. This study was designed to determine the appropriate energy level for feeding yak. Three test diets with metabolizable energy levels of 7.57 MJ/kg, 9.44 MJ/kg, and 11.9 MJ/kg were used and the concentration of volatile fatty acids (VFA) in rumen fluid was measured. The microbial communities, functions, and metabolites in yaks were studied by 16S rRNA sequencing, metagenome, and LC-MS non-targeted metabolomics to investigate the relationships among rumen fermentation parameters, microbial diversity, and metabolites. Ration energy levels significantly affect total VFA, acetate, propionate, butyrate, iso-valerate, valerate, and acetate/propionate (p < 0.05). At the phylum level, the dominant phyla in all three treatment groups were Bacteroidota, Firmicutes, and Actinobacteriota. At the genus level, the abundance of the unclassified_o__Bacteroidales, norank_f_Muribaculaceae, Lachnospiraceae_NK4A136_group, and Family _XIII_AD3011_group showed significant differences (p < 0.05) and were significantly correlated with differential metabolites screened for phosphatidylcholine [PC(16:0/0:0), PC(18:3/0:0)], uridine 3'-monophosphate, and adenosine monophosphate, etc. CAZymes family analysis showed that GHs and CEs differed significantly among the three groups. In addition, differential metabolites were mainly enriched in the pathways of lipid metabolism, nucleotide metabolism, and biosynthesis of other secondary metabolites, and the concentrations of differential metabolites were correlated with microbial abundance. In summary, this study analyzed the effects of ration energy levels on rumen microorganisms and metabolites of yaks and their relationships. The results provided a scientific basis for the selection of dietary energy for yaks in the house feeding period in the future.

Distinguished representation of identical mentions in bio-entity coreference resolution.

BACKGROUND: Bio-entity Coreference Resolution (CR) is a vital task in biomedical text mining. An important issue in CR is the differential representation of identical mentions as their similar representations may make the coreference more puzzling. However, when extracting features, existing neural network-based models may bring additional noise to the distinction of identical mentions since they tend to get similar or even identical feature representations. METHODS: We propose a context-aware feature attention model to distinguish similar or identical text units effectively for better resolving coreference. The new model can represent the identical mentions based on different contexts by adaptively exploiting features, which enables the model reduce the text noise and capture the semantic information effectively. RESULTS: The experimental results show that the proposed model brings significant improvements on most of the baseline for coreference resolution and mention detection on the BioNLP dataset and CRAFT-CR dataset. The empirical studies further demonstrate its superior performance on the differential representation and coreferential link of identical mentions. CONCLUSIONS: Identical mentions impose difficulties on the current methods of Bio-entity coreference resolution. Thus, we propose the context-aware feature attention model to better distinguish identical mentions and achieve superior performance on both coreference resolution and mention detection, which will further improve the performance of the downstream tasks.

Association of dyslipidaemia with osteoporosis in postmenopausal women.

OBJECTIVE: To assess the association of dyslipidaemia with osteoporosis in postmenopausal women. METHODS: Data from 160 postmenopausal women with newly diagnosed osteoporosis (osteoporosis group) and 156 healthy controls (control group) were retrospectively reviewed from 2016 to 2020. The primary outcomes were laboratory values assessed by a multivariate binary logistic regression model. RESULTS: Factors that greatly increased the risk of being in the osteoporosis group included high low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) levels. The osteoporosis group had lower HDL and higher LDL levels than the control group. A multivariate binary logistic regression model showed that lower HDL and higher LDL levels were the only variables that were significantly associated with osteoporosis (odds ratio 1.86, 95% confidence interval: 3.66-4.25 and odds ratio 1.47, 95% confidence interval: 1.25-2.74, respectively). CONCLUSION: Low HDL and high LDL levels may be associated with the occurrence of osteoporosis in postmenopausal women.

Knowledge enhanced LSTM for coreference resolution on biomedical texts.

MOTIVATION: Bio-entity Coreference Resolution focuses on identifying the coreferential links in biomedical texts, which is crucial to complete bio-events' attributes and interconnect events into bio-networks. Previously, as one of the most powerful tools, deep neural network-based general domain systems are applied to the biomedical domain with domain-specific information integration. However, such methods may raise much noise due to its insufficiency of combining context and complex domain-specific information. RESULTS: In this article, we explore how to leverage the external knowledge base in a fine-grained way to better resolve coreference by introducing a knowledge-enhanced Long Short Term Memory network (LSTM), which is more flexible to encode the knowledge information inside the LSTM. Moreover, we further propose a knowledge attention module to extract informative knowledge effectively based on contexts. The experimental results on the BioNLP and CRAFT datasets achieve state-of-the-art performance, with a gain of 7.5 F1 on BioNLP and 10.6 F1 on CRAFT. Additional experiments also demonstrate superior performance on the cross-sentence coreferences. AVAILABILITY AND IMPLEMENTATION: The source code will be made available at https://github.com/zxy951005/KB-CR upon publication. Data is avaliable at http://2011.bionlp-st.org/ and https://github.com/UCDenver-ccp/CRAFT/releases/tag/v3.1.3. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Bio-semantic relation extraction with attention-based external knowledge reinforcement.

BACKGROUND: Semantic resources such as knowledge bases contains high-quality-structured knowledge and therefore require significant effort from domain experts. Using the resources to reinforce the information retrieval from the unstructured text may further exploit the potentials of such unstructured text resources and their curated knowledge. RESULTS: The paper proposes a novel method that uses a deep neural network model adopting the prior knowledge to improve performance in the automated extraction of biological semantic relations from the scientific literature. The model is based on a recurrent neural network combining the attention mechanism with the semantic resources, i.e., UniProt and BioModels. Our method is evaluated on the BioNLP and BioCreative corpus, a set of manually annotated biological text. The experiments demonstrate that the method outperforms the current state-of-the-art models, and the structured semantic information could improve the result of bio-text-mining. CONCLUSION: The experiment results show that our approach can effectively make use of the external prior knowledge information and improve the performance in the protein-protein interaction extraction task. The method should be able to be generalized for other types of data, although it is validated on biomedical texts.

Neurotoxicity of Mn3O4 nanoparticles: Apoptosis and dopaminergic neurons damage pathway.

Mn3O4 nanoparticles (NPs) are used increasingly in various fields due to their excellent physiochemical properties. Previous studies have documented that Mn-based nanomaterials resulted in excess reactive oxygen species (ROS) generation and dopamine (DA) reduction both in vivo and in vitro experiments. However, little is known about the mechanism of ROS production and DA decrease induced by Mn-based nanomaterials. The present study was carried out to elucidate the mechanism of the co-incubation model of dopaminergic neuron PC12 cells and the synthesized Mn3O4 NPs. The results demonstrated that exposure to Mn3O4 NPs reduced cell viability, increased level of lactate dehydrogenase (LDH), triggered oxidative stress and induced apoptosis. Notably, the level of ROS was remarkably increased (>10-fold) with Mn3O4 NPs exposure. We also found that mitochondrial calcium Ca2+ uniporter (MCU) was up-regulated and the mitochondrial Ca2+ concentration ([Ca2+]mito) increased induced by Mn3O4 NPs in PC12 cells. Furthermore, the MCU inhibitor RuR significantly attenuated Mn3O4 NPs-induced [Ca2+]mito, ROS production and apoptosis. In PC12 cells, the decrease of DA content was mainly due to the downregulation of DOPA decarboxylase (DDC) expression caused by Mn3O4 NPs treatment. The expression of proteins related to DA storage system was not significantly affected by treatment.

Chemosensitization effect of cerium oxide nanosheets by suppressing drug detoxification and efflux.

Cerium oxide (CeO2) nanomaterials (NMs) have wide applications in biomedicine and are also detected with increasing bioaccumulation in various biological and environmental media. Thus, a system was developed to evaluate the chemosensitization effect of CeO2 NMs. Herein, we discovered that low doses of CeO2 NMs could trigger reactive oxygen species (ROS) production and decrease mitochondrial membrane potential (MMP) without causing severe toxicity to cancer cells, while pretreatment of the cells with CeO2 NMs enhanced the toxicity of the chemotherapeutic agent doxorubicin (DOX). The reduced efflux of DOX was mainly attributed to adenosine triphosphate (ATP) depletion, followed by attenuation of exocytosis and enhancement of DOX retention. Further investigations revealed that CeO2 NM-induced ROS production caused depletion of intracellular glutathione (GSH) and consequent impairment of DOX detoxification. Moreover, CeO2 NMs were found to enhance the chemosensitization of cancer cells rather than normal cells. Thus, this study uncovered the underlying application potential of CeO2 NMs in cancer therapy by enhancing the efficacy of chemotherapeutic agent, which is associated with disruption of mitochondrial function and impairment of drug detoxification.