Stroke genetics informs drug discovery and risk prediction across ancestries.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

Genotype imputation accuracy and the quality metrics of the minor ancestry in multi-ancestry reference panels.

Large-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However, whether large-size multi-ancestry or small-size population-specific reference panels are the optimal choices for under-represented populations continues to be debated. We imputed genotypes of East Asian (180k Japanese) subjects using the Trans-Omics for Precision Medicine reference panel and found that the standard imputation quality metric (Rsq) overestimated dosage r2 (squared correlation between imputed dosage and true genotype) particularly in marginal-quality bins. Variance component analysis of Rsq revealed that the increased imputed-genotype certainty (dosages closer to 0, 1 or 2) caused upward bias, indicating some systemic bias in the imputation. Through systematic simulations using different template switching rates (θ value) in the hidden Markov model, we revealed that the lower θ value increased the imputed-genotype certainty and Rsq; however, dosage r2 was insensitive to the θ value, thereby causing a deviation. In simulated reference panels with different sizes and ancestral diversities, the θ value estimates from Minimac decreased with the size of a single ancestry and increased with the ancestral diversity. Thus, Rsq could be deviated from dosage r2 for a subpopulation in the multi-ancestry panel, and the deviation represents different imputed-dosage distributions. Finally, despite the impact of the θ value, distant ancestries in the reference panel contributed only a few additional variants passing a predefined Rsq threshold. We conclude that the θ value substantially impacts the imputed dosage and the imputation quality metric value.

Transition metal single-atoms supported on hexagonal ZnIn2S4 monolayers for the hydrogen evolution reaction.

Herein, we report a series of 5d transition metal (TM) single atoms supported on ZIS as promising catalysts for the hydrogen evolution reaction using first-principles calculations. The binding behaviors of TMs with the ZIS surface in single-atom catalyst formation are analysed using the adsorption energy (Eads), partial density of states (PDOS), charge density difference (CDD), and crystal orbital Hamilton population (COHP). The TM@ZIS (TM = Ta, W, Re, Os, Ir, and Pt) shows excellent hydrogen evolution performance with the Gibbs free energy (ΔGH*) values from -0.120 to 0.128 eV. The Tafel and Heyrovsky reaction mechanisms to drive H2 formation are also identified.

Iodine capture of a two-dimensional layered uranyl-organic framework: a combined DFT and AIMD study.

To develop nuclear energy sustainably, it is important to effectively capture radioiodine in nuclear waste. In this study, we used density functional theory (DFT) and ab initio molecular dynamics (AIMD) calculations to investigate how well the uranyl-organic framework (UOF) could capture radioiodine. We found that the uranyl center and C-N ring sites in both cluster and periodic UOF models are very attractive to the I2 molecule. The adsorption energies of the I2 molecule in the periodic UOF models are as high as -1.10 eV, which is much higher than in the cluster model. The interaction characteristics between the I2 molecule and the UOF were revealed by electronic density topological analyses. Our AIMD simulations at 300 and 600 K have confirmed that the UOF has high adsorption kinetics for I2 molecules and can effectively capture them. The UOF has a high adsorption capacity and good adsorption stability for the I2 molecule, making it a promising option for the environmentally friendly removal of radioiodine.

Periodic Bonding Behaviors of Actinide Atoms (An = Th-Cm) with Negatively Curved Nanographene.

The nanographene with negative curvature has been extensively studied due to its interesting properties and potential applications. In the present work, we have performed all-electron scalar relativistic density functional theory (DFT) calculations to understand the periodic interaction mechanisms of actinide atoms (An = Th, Cm) with the TB8C nanographene. The encapsulated complexes (An@TB8C) were formed due to the octagonal vacancy in the TB8C nanographene. TB8C shows fairly high affinity toward An atoms, especially for Th and Pa. AIMD simulations further confirmed the effective trapping of An atom with TB8C. The partial covalent characters of An-C bonds in An@TB8C were revealed through various bond analysis methods. The 6d electrons of An play an important role in the participation of chemical bonds. The delocalization index (DI) is proposed as a useful descriptor in the study of bond strength involving the actinides. Electronic absorption spectra were simulated for further identification in the experiments. The current work has expanded the potential molecular properties and applications of nanographene.

Adsorption and diffusion of actinyls on the basal gibbsite (001) surface: a theoretical perspective.

Actinides are an important component of nuclear fuel for nuclear power and affect human health, and a key process in the transport of radionuclides in the environment is adsorption on mineral surfaces. In this work, we have used density functional theory (DFT) to investigate the microscopic adsorption and diffusion mechanisms of actinyls, U(V), U(VI), Np(V), Np(VI) Pu(V), and Pu(VI), on the gibbsite (001) surface. Actinyls(VI) are attached to the gibbsite surface through two An-Os bonds, which results in a bidentate inner sphere mode, while actinyls(V) favor a monodentate inner sphere adsorption mode with the gibbsite (001) surface. The solvent effects were considered through an explicit water cluster model. All the actinyls studied can be efficiently adsorbed on the gibbsite (001) surface with binding energies ranging from -113.9 kJ mol-1 to -341.2 kJ mol-1. Electronic structure analyses indicate that the cooperation of the An-Os bonds and hydrogen bonds leads to high adsorption stability of the actinyls with the gibbsite surface. The diffusion barriers of the actinyls on the gibbsite surface were determined, and the high energy barriers indicate that this type of gas-phase diffusion process is not likely to take place.

Role of SESTRIN2/AMPK/ULK1 pathway activation and lysosomes dysfunction in NaAsO2-induced liver injury under oxidative stress.

Arsenic, a serious environmental poison to human health, is widely distributed in nature. As the main organ of arsenic metabolism, liver is easily damaged. In the present study, we found that arsenic exposure can cause liver injury in vivo and in vitro, to date the underlying mechanism of which is yet unclear. Autophagy is a process that depends on lysosomes to degrade damaged proteins and organelles. Here, we reported that oxidative stress can be induced and then activated the SESTRIN2/AMPK/ULK1 pathway, damaged lysosomes, and finally induced necrosis upon arsenic exposure in rats and primary hepatocytes, which was characterized by lipidation of LC3II, the accumulation of P62 and the activation of RIPK1 and RIPK3. Similarly, lysosomes function and autophagy can be damaged under arsenic exposure, which can be alleviated after NAC treatment and aggravated by Leupeptin treatment in primary hepatocytes. Moreover, we also found that the transcription and protein expressions of necrotic-related indicators RIPK1 and RIPK3 in primary hepatocytes were decreased after P62 siRNA. Taken together, the results revealed that arsenic can induce oxidative stress, activate SESTRIN2/AMPK/ULK1 pathway to damage lysosomes and autophagy, and eventually induce necrosis to damage liver.

Mechanism underlying the targeted regulation of the SOD1 3'UTR by the AUF1/Dicer1/miR-155/SOD1 pathway in sodium arsenite-induced liver injury.

Arsenic (As) is a natural hepatotoxicity inducer that is ubiquitous in water, soil, coal, and food. Studies have found that arsenite exposure elicits increased mRNA transcription and decreased protein expression of SOD1 in vivo and in vitro; however, the specific mechanisms remain unclear. Here, we established a model of arsenic-induced chronic liver injury by providing rats with drinking water containing different concentrations of sodium arsenite (NaAsO2) and found that NaAsO2 exposure decreased the mRNA and protein levels of AUF1 and the protein level of SOD1 and elevated the mRNA and protein levels of Dicer1 and miR-155 and the mRNA level of SOD1. Overexpression of AUF1 under NaAsO2 stress in vitro induced Dicer1 mRNA and protein expression and decreased miR-155 levels, which could be reversed by AUF1 siRNA. In addition, miR-155 overexpression downregulated SOD1 mRNA and protein levels, although this change was inhibited after transfection with an miR-155 inhibitor. Taken together, our findings showed that NaAsO2 could upregulate Dicer1 mRNA and protein, thereby increasing miR-155 expression by downregulating AUF1 mRNA and protein expression. A dual-luciferase reporter assay indicated that miR-155 decreased the mRNA and protein levels of SOD1 by targeting the SOD1 3'UTR, resulting in liver injury. This study provides an important research basis for further understanding the factors underlying arsenic-induced liver injury to improve the prevention and control strategies for arsenism.

Development of IL-15/IL-15Rα sushi domain-IgG4 Fc complexes in Pichia pastoris with potent activities and prolonged half-lives.

BACKGROUND: Interleukin-15 (IL-15) is a critical cytokine for the development, proliferation, and function of natural killer (NK) cells, NKT cells, and CD8+ memory T cells and has become one of the most promising protein molecules for the treatment of cancer and viral diseases. However, there are several limitations in applying IL-15 in therapy, such as its low yield in vitro, limited potency, and short half-life in vivo. To date, there are several recombinant IL-15 agonists based on configurational modifications that are being pursued in the treatment of cancer, such as ALT-803, which are mainly produced from mammalian cells. RESULTS: In this study, we designed two different forms of the IL-15 complex, which were formed by the noncovalent assembly of IL-15 with dimeric or monomeric sushi domain of IL-15 receptor α (SuIL-15Rα)-IgG4 Fc fusion protein and designated IL-15/SuIL-15Rα-dFc and IL-15/SuIL-15Rα-mFc, respectively. The two IL-15 complexes were expressed in Pichia pastoris (P. pastoris), and their activities and half-lives were evaluated and compared. Pharmacokinetic analysis showed that IL-15/SuIL-15Rα-dFc had a half-life of 14.26 h while IL-15/SuIL-15Rα-mFc had a half-life of 9.16 h in mice, which were much longer than the 0.7-h half-life of commercial recombinant human IL-15 (rhIL-15). Treatment of mice with intravenous injection of the two IL-15 complexes resulted in significant increases in NK cells, NKT cells, and memory CD8+ T cells, which were not observed after rhIL-15 treatment. Treatment of human peripheral blood mononuclear cells (PBMCs) from healthy donors with the two IL-15 complexes yielded enhanced NK and CD8+ T cell activation and proliferation, which was comparable to the effect of rhIL-15. CONCLUSIONS: These findings indicate that the IL-15/SuIL-15Rα-dFc and IL-15/SuIL-15Rα-mFc produced in P. pastoris exhibit potent activities and prolonged half-lives and may serve as superagonists for immunotherapy in further research and applications.

Incorporation of dumbbell-shaped and Y-shaped cross-linkers in adjustable pullulan/polydopamine hydrogels for selective adsorption of cationic dyes.

Hydrogel adsorbents have attracted considerable attention due to their sludge minimization, good water permeability and renewable performance. Here, a promising strategy for the one-step preparation of pullulan/polydopamine hybird hydrogels (PPGels) was presented. Dumbbell-shaped cross-linker neopentyl glycol diglycidyl ether (NGDE, 2 arms) and Y-shaped cross-linker trimethylolpropane triglycidyl ether (TTE, 3 arms) were selected to study the relationship between cross-linker structure and hydrogel performances. The NGDE possessing less molecular repulsive force and higher reactivity demonstrated more effective cross-linking with the pullulan, which leaded to a decrease in pore size of the hydrogel. Meanwhile, the introduction of polydopamine significantly enhanced the adsorption ability and gave the resulting hybrid gel the specific selectivity toward cationic dyes (96 mg/g for crystal violet, 25.8 mg/g for methylene blue and barely not adsorption for azophloxine). Our data suggested that the electrostatic interaction played a vital role in the dye adsorption process, and the adsorption data could be explained by pseudo-second-order model and Langmuir isotherm model. Furthermore, the obtained PPGel could be easily separated after adsorption. This study describes the relationship between cross-linker structure and properties of pullulan/polydopamine hybrid gels, which provides a new strategy to create polysaccharide-based adsorbents for wastewater remediation.

Elimination of N-glycosylation by site mutation further prolongs the half-life of IFN-α/Fc fusion proteins expressed in Pichia pastoris.

BACKGROUND: Interferon (IFN)-α has been commonly used as an antiviral drug worldwide; however, its short half-life in circulation due to its low molecular weight and sensitivity to proteases impacts its efficacy and patient compliance. RESULTS: In this study, we present an IgG1 Fc fusion strategy to improve the circulation half-life of IFN-α. Three different forms of IgG1 Fc fragments, including the wild type, aglycosylated homodimer and aglycosylated single chain, were each fused with IFN-α and designated as IFN-α/Fc-WT, IFN-α/Fc-MD, and IFN-α/Fc-SC, respectively. The recombinant proteins were expressed in Pichia pastoris and tested using antiviral and pharmacokinetic assays in comparison with the commercial pegylated-IFN-α (PEG-IFN-α). The in vitro study demonstrated that IFN-α/Fc-SC has the highest antiviral activity, while IFN-α/Fc-WT and IFN-α/Fc-MD exhibited antiviral activities comparable to that of PEG-IFN-α. The in vivo pharmacokinetic assay showed that both IFN-α/Fc-WT and IFN-α/Fc-MD have a longer half-life than PEG-IFN-α in SD rats, but IFN-α/Fc-SC has the shortest half-life among them. Importantly, the circulating half-life of 68.3 h for IFN-α/Fc-MD was significantly longer than those of 38.2 h for IFN-α/Fc-WT and 22.2 h for PEG-IFN-α. CONCLUSIONS: The results demonstrate that the elimination of N-glycosylation by mutation of putative N-glycosylation site further prolongs the half-life of the IFN-α/Fc fusion protein and could present an alternative strategy for extending the half-life of low-molecular-weight proteins expressed by P. pastoris for in vivo studies as well as for future clinical applications.

Environmental arsenic pollution induced liver oxidative stress injury by regulating miR-155 through inhibition of AUF1.

Arsenic (As), a common environmental pollutant, has become a hot topic in recent years due to its potentially harmful effects. Liver damage being a central clinical feature of chronic arsenic poisoning. However, the underlying mechanisms remain unclear. We demonstrated that arsenic can lead to oxidative stress in the liver and result in structural and functional liver damage, significantly correlated with the expression of AUF1, Dicer1, and miR-155 in the liver. Interestingly, knockdown AUF1 promoted the up-regulatory effects of arsenic on Dicer1 and miR-155 and the inhibitory effects on SOD1, which exacerbated oxidative damage in rat liver. However, overexpression of AUF1 reversed the up-regulatory effects of arsenic on Dicer1 and miR-155, restored arsenic-induced SOD1 depletion, and attenuated liver oxidative stress injury. Further, we verified the mechanism and targets of miR-155 in regulating SOD1 by knockdown/overexpression of miR-155 and nonsense mutant SOD1 3'UTR experiments. In conclusion, these results powerfully demonstrate that arsenic inhibits AUF1 protein expression, which in turn reduces the inhibitory effect on Dicer1 expression, which promotes miR-155 to act on the SOD1 3'UTR region after high expression, thus inhibiting SOD1 protein expression and enzyme activity, and inducing liver injury. This finding provides a new perspective for the mechanism research and targeted prevention of arsenic poisoning, as well as scientific evidence for formulating strategies to prevent and control environmental arsenic pollution.

Huai Qi Huang ameliorates proteinuria and hematuria in mild IgA nephropathy patients: a prospective randomized controlled study.

BACKGROUND/PURPOSE: Huai Qi Huang (HQH) is a compound Chinese herbal medicine that contains Trametes robiniophila murr, wolfberry fruit, and Polygonatum. In the present study, we investigated the effects of HQH on patients with mild immunoglobulin A nephropathy (IgAN) through a prospective randomized controlled study. METHODS: Forty-five adults diagnosed with IgAN according to renal pathology, who had hematuria or/and proteinuria (≤ 2 g/day), were randomly assigned to receive HQH or no treatment for 12 weeks. Twenty-four hour urinary protein excretion and hematuria were measured at Weeks 0, 4, 8, and 12. The rate of complete remission of proteinuria and hematuria was evaluated. Any adverse events induced by HQH were also observed during the treatment period. RESULTS: Twenty-four hour urinary protein excretion was significantly reduced by HQH treatment compared with that in the control group at Weeks 8 and 12. A much higher rate of complete remission of proteinuria was observed in the HQH group than in control group at Week 12. HQH administration also obviously reduced the extent of hematuria compared with that in the control group at Week 12. HQH treatment dramatically increased the rate of complete remission of hematuria compared with that in control group at Weeks 8 and 12. No obvious adverse events caused by HQH were observed. CONCLUSION: HQH could be a new conservative therapy for IgAN patients who cannot tolerate steroids and immunosuppressive agents. The relapse rate after discontinuing treatment still needs further investigation.

Bone collision detection method for robot assisted fracture reduction based on vibration excitation.

BACKGROUND AND OBJECTIVE: In the process of robotic fracture reduction, there is a risk of unintended collision of broken bones, which is not conducive to ensuring the safety of the reduction system. In order to solve this problem, this paper proposed a vibration-based collision detection method for fracture reduction process. METHODS: Based on the two degree-of-freedom vibration response model, the factors affecting the respond of the vibration, including the excitation voltage, the clamping length at the proximal and distal ends, the mass and tensile force of the soft tissue, were obtained. The effects of these factors on the vibration transfer performance of broken bones and soft tissue were investigated by single factor experiments. RESULTS: The results showed that, in terms of peak value, the increase of excitation voltage would make the vibration amplitude increase linearly, and the increase of soft tissue mass and tension increased the vibration transmission capacity of soft tissue in the frequency range of 500-1000 Hz. In terms of peak frequency, the clamping length at the distal end had the greatest influence, which reached 74 Hz, followed by 45 Hz at the proximal end. While the influence of other factors was little. According to single factor experiments, the excitation frequency in the verification experiments was determined as 677 Hz. Under the vibration interference with the acceleration amplitude of 1.2 G, this method achieved correct detection. CONCLUSION: This research developed a broken bone collision detection method based on vibration excitation. The method can correctly detect the collision of broken bones with strong anti-interference ability. It is of great significance to improve the safety of fracture reduction process.

East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease.

Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer (GU)) or duodenum (duodenal ulcer (DU)). In the present study, we conducted a large-scale, cross-ancestry meta-analysis of PUD combining genome-wide association studies with Japanese and European studies (52,032 cases and 905,344 controls), and discovered 25 new loci highly concordant across ancestries. An examination of GU and DU genetic architecture demonstrated that GUs shared the same risk loci as DUs, although with smaller genetic effect sizes and higher polygenicity than DUs, indicating higher heterogeneity of GUs. Helicobacter pylori (HP)-stratified analysis found an HP-related host genetic locus. Integrative analyses using bulk and single-cell transcriptome profiles highlighted the genetic factors of PUD being enriched in the highly expressed genes in stomach tissues, especially in somatostatin-producing D cells. Our results provide genetic evidence that gastrointestinal cell differentiations and hormone regulations are critical in PUD etiology.

LC/MS/MS-Based Liver Metabolomics to Identify Chronic Liver Injury Biomarkers Following Exposure to Arsenic in Rats.

Arsenic is a widespread natural metalloid element. Long-term chronic exposure to arsenic can lead to different degrees of liver injury. Although the etiology of this disease is well known, to date, the underlying mechanism of arsenic-induced liver injury remains unclear, and no specific treatment exists because of the complexity of arsenic. In the present study, potential biomarkers and metabolic pathways in the livers of Wistar rats treated with arsenic for 24 weeks were investigated using an integrated metabolic approach with an LC-Orbitrap Q Exactive™ HF-X mass spectrometer. Markedly increased liver levels of arsenic, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bile acid (TBA) were detected in the arsenic treatment groups (P < 0.05). Furthermore, histopathological examination of liver tissues showed obviously swollen, loose cytoplasm and increased necrosis in the arsenic treatment groups compared with those in the control group (P < 0.05). Metabonomics results showed that 109 metabolites (variable importance in the projection (VIP) > 1; fold change > 2 or < 0.5; P adjusted < 0.05) changed significantly after exposure to arsenic and included 71 upregulated metabolites and 38 downregulated metabolites. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that 6 metabolic pathways with statistical significance-phenylalanine metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, citrate cycle (TCA cycle), thiamine metabolism, and vitamin B6 metabolism-were selected, and 13 differential metabolites were detected to be involved in regulating these metabolic pathways. The present study could help identify potential biomarkers and their functions, as well as metabolic pathways, likely providing evidence for the early diagnosis, prevention, and mechanistic study of arsenism.

Multi-modal neuroimaging feature fusion for diagnosis of Alzheimer's disease.

BACKGROUND: Compared with single-modal neuroimages classification of AD, multi-modal classification can achieve better performance by fusing different information. Exploring synergy among various multi-modal neuroimages is contributed to identifying the pathological process of neurological disorders. However, it is still problematic to effectively exploit multi-modal information since the lack of an effective fusion method. NEW METHOD: In this paper, we propose a deep multi-modal fusion network based on the attention mechanism, which can selectively extract features from MRI and PET branches and suppress irrelevant information. In the attention model, the fusion ratio of each modality is assigned automatically according to the importance of the data. A hierarchical fusion method is adopted to ensure the effectiveness of Multi-modal Fusion. RESULTS: Evaluating the model on the ADNI dataset, the experimental results show that it outperforms the state-of-the-art methods. In particular, the final classification results of the NC/AD, SMCI/PMCI and Four-Class are 95.21 %, 89.79 %, and 86.15 %, respectively. COMPARISON WITH EXISTING METHODS: Different from the early fusion and the late fusion, the hierarchical fusion method contributes to learning the synergy between the multi-modal data. Compared with some other prominent algorithms, the attention model enables our network to focus on the regions of interest and effectively fuse the multi-modal data. CONCLUSION: Benefit from the hierarchical structure with attention model, the proposed network is capable of exploiting low-level and high-level features extracted from the multi-modal data and improving the accuracy of AD diagnosis. Results show its promising performance.

A coumarin-connected carboxylic indolinium sensor for cyanide detection in absolute aqueous medium and its application in biological cell imaging.

Fluorescent sensor has been noticed in detecting system due to its sensitive, selective, operational simplicity and low cost. We designed a coumarin-connected carboxylic indolium sensor molecule that is water-soluble and cytomembrane-permeable. This infrared (IR) emitter is selectively sensitive towards cyanide detection in aqueous media according to CN- nucleophilic attack on the indole C=N function. Upon the addition of CN- anion, the color of sensor in water varied from blue to colorless by naked eyes and fluorescence quenching was observed by spectroscopic method. This was because the intramolecular charge transfer (ICT) effect occurred when the fluorescent sensor was added with CN-. The minimum detection limit of the sensor's fluorescence response to CN- is 4.44 × 10-7 mol/L. Furthermore, the cytotoxicity test shows the sensor has lower cytotoxicity, and indicates that this sensor can be utilized for practical detection of trace cyanide in wastewater.

The role of PSMB5 in sodium arsenite-induced oxidative stress in L-02 cells.

Endemic arsenism is widely distributed in the world, which can damage multiple organs, especially in skin and liver. The etiology is clear, but the mechanisms involved remain unknown. Ubiquitin-proteasome pathway (UPP) is the main pathway regulating protein degradation of which proteasome subunit beta type-5(PSMB5) plays a dominant role. This paper aims to study the role and mechanism of PSMB5 in sodium arsenite (NaAsO2)-induced oxidative stress liver injury in L-02 cells. Firstly, L-02 cells were exposed to different concentrations of NaAsO2 to establish a liver injury model of oxidative stress, and then mechanisms of oxidative stress were studied with carbobenzoxyl-leucyl-leucl-leucll-line (MG132) and knockdown PSMB5 (PSMB5-siRNA). The oxidative stress indicators, levels of 20S proteasome, the transcription and protein expression levels of PSMB5, Cu-Zn superoxide dismutase (SOD1), and glutathione peroxidase 1 (GPx1) were detected. The results demonstrated that NaAsO2 could induce oxidative stress-induced liver injury and the activity of 20S proteasome and the protein expression of PSMB5, SOD1, and GPx1 decreased. After MG132 or PSMB5-siRNA pretreatment, the gene expression of PSMB decreased. After MG132 or PSMB5-siRNA pretreatment, and then L-02 cells were treated with NaAsO2, the gene expression of PSMB remarkably decreased; however, the protein expression of SOD1 and GPx1 increased. Overall, NaAsO2 exposure could induce oxidative stress liver injury and low expression of PSMB5 in L-02 cells, and PSMB5 might play an important role in the regulation of oxidative stress by regulating the expression of SOD1 and Gpx1.