A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Do climate policy uncertainty and investor sentiment drive the dynamic spillovers among green finance markets?

Green finance is an essential instrument for improving the environment and addressing climate change. This study investigates the dynamic spillovers among green finance markets using time-varying parameter vector autoregression (TVP-VAR) spillover indices, and further investigates the impact of climate policy uncertainty and investor sentiment on spillovers based on the generalised autoregressive conditional heteroscedasticity mixed data sampling (GARCH-MIDAS) model. The results indicate that: (i) environmental, social and governance (ESG), clean energy and water markets are information transmitters in the green finance system, whereas green building, green transportation, green bond and carbon markets are mainly information receivers; (ii) green stock markets including clean energy, non-energy and ESG markets transmit and receive greater information in the green finance system, while green bond and carbon markets do less; (iii) the green bond market is more interconnected with other green finance markets after the COVID-19 outbreak; (iv) investor sentiment contributes more to the net total directional spillovers of green resource markets (water and clean energy), while climate policy uncertainty contributes more to total spillovers and the net total directional spillovers of other green finance markets. These findings offer invaluable guidance for both policymakers and environmental investors.

Non-directed Pd-catalysed C-H arylation of [2.2]paracyclophane.

We report herein the palladium-catalysed mono-selective C-H arylation of [2.2]paracyclophane (PCP) with diverse aryl iodides in the absence of any pendant directing groups, providing straightforward and modular access to C4-arylated [2.2]paracyclophanes. Moreover, a new PCP-containing biaryl monophosphine complex could be readily obtained through further derivation of the arylated product.

Integrated miRNA-mRNA analysis reveals the dysregulation of lipid metabolism in mouse liver induced by developmental arsenic exposure.

Developmental arsenic exposure leads to increased susceptibility to liver diseases including nonalcoholic fatty liver diseases, but the mechanism is incompletely understood. In this study, C57BL/6J mice were used to establish a lifetime arsenic exposure model covering developmental stage. We found that arsenic-exposed offspring in later life showed hepatic lipid deposition and increased triglyceride content. Despite no significant hepatic pathological changes in the offspring at weaning, 86 miRNAs and 136 mRNAs were differentially expressed according to miRNA array and mRNA sequencing. The differentially expressed genes (DEGs) were crossed with the target genes predicted by differentially expressed miRNAs (DEMs), and 47 differentially expressed target genes (DETGs) were obtained. Functional annotation suggested that lipid metabolism related pathways were significantly enriched. The pivotal regulator in the four major pathways to maintain liver lipid homeostasis were further determined, with significant alterations found in FABP5, SREBP1, ACOX1 and EHHADH. Of note, miRNA-mRNA integration analysis revealed that miR-7118-5p, miR-7050-5p, miR-27a/b-3p, and miR-103-3p acted as key regulators of fatty acid metabolism genes. Taken together, miRNA-mRNA integration analysis indicates that the lipid metabolism pathway in the liver of weaned mice was dysregulated by developmental arsenic exposure, which may contribute to the development of NAFLD in later life.

Assessing the extreme risk spillovers to carbon markets from energy markets: evidence from China.

Previous studies point to the impact of energy market on carbon market under normal market conditions, but little is known about the impact under extreme market conditions. Motivated by these concerns, we aim to investigate the extreme risk spillovers to carbon markets from traditional fossil energy and new energy markets in China. After using copula model to obtain nonlinear tail dependence structure between carbon and energy markets, we compute conditional Value-at-Risk (CoVaR) to quantify extreme risk spillovers. The results indicate that (i) the risk spillovers from both traditional fossil energy and new energy markets to carbon markets are obviously larger when extreme events cause large shocks to energy markets; (ii) there are risks in the opposite direction in carbon markets when carbon-intensive energy markets are under extreme market conditions, but the direction of risks in carbon markets is uncertain when low-carbon energy markets are under extreme market conditions; (iii) the extreme risk spillovers to carbon markets from energy markets are regionally heterogeneous not only in magnitude but also in direction; (iv) energy markets prefer to transmit extreme risks to more liquid carbon markets. These new findings have valuable implications for both policymakers and participating enterprises in carbon markets.

Blockade of USP14 potentiates type I interferon signaling and radiation-induced antitumor immunity via preventing IRF3 deubiquitination.

PURPOSE: The adaptive immune responses induced by radiotherapy has been demonstrated to largely rely on STING-dependent type I interferons (IFNs) production. However, irradiated tumor cells often fail to induce dendritic cells (DCs) to produce type I IFNs. Hence, we aim to uncover the limitation of STING-mediated innate immune sensing following radiation, and identify efficient reagents capable to rescue the failure of type I IFNs induction for facilitating radiotherapy. METHODS: A targeted cell-based phenotypic screening was performed to search for active molecules that could elevate the production of type I IFNs. USP14 knockout or inhibition was assayed for IFN production and the activation of STING signaling in vitro. The mechanisms of USP14 were investigated by western blot and co-immunoprecipitation in vitro. Additionally, combinational treatments with PT33 and radiation in vivo and in vitro models were performed to evaluate type I IFNs responses to radiation. RESULTS: PT33 was identified as an enhancer of STING agonist elicited type I IFNs production to generate an elevated and durable STING activation profile in vitro. Mechanistically, USP14 inhibition or deletion impairs the deubiquitylation of K63-linked IRF3. Furthermore, blockade of USP14 with PT33 enhances DC sensing of irradiated-tumor cells in vitro, and synergizes with radiation to promote systemic antitumor immunity in vivo. CONCLUSION: Our findings reveal that USP14 is one of the major IFN production suppressors and impairs the activation of IRF3 by removing the K63-linked ubiquitination of IRF3. Therefore, blockage of USP14 results in the gain of STING signaling activation and radiation-induced adaptive immune responses.

Developmental arsenic exposure induces dysbiosis of gut microbiota and disruption of plasma metabolites in mice.

Arsenic is a notorious environmental pollutant. Of note, developmental arsenic exposure has been found to increase the risk of developing a variety of ailments later in life, but the underlying mechanism is not well understood. Many elements of host health have been connected to the gut microbiota. It is still unclear whether and how developmental arsenic exposure affects the gut microbiota. In the present study, we found that developmental arsenic exposure changed intestinal morphology and increased intestinal permeability and inflammation in mouse pups at weaning. These alterations were accompanied by a significant change in gut microbiota, as evidenced by considerably reduced gut microbial richness and diversity. In developmentally arsenic-exposed pups, the relative abundance of Muribaculaceae was significantly decreased, while the relative abundance of Akkermansia and Bacteroides was significantly enhanced at the genus level. Metabolome and pathway enrichment analyses indicated that amino acid and purine metabolism was promoted, while glycerophospholipid metabolism was inhibited. Interestingly, the relative abundance of Muribaculaceae and Akkermansia showed a strong correlation with most plasma metabolites significantly altered by developmental arsenic exposure. These data indicate that gut microbiota dysbiosis may be a critical link between developmental arsenic exposure and metabolic disorders and shed light on the mechanisms underlying increased susceptibility to diseases due to developmental arsenic exposure.

Novel Pyrimidine Derivatives Bearing a 1,3,4-Thiadiazole Skeleton: Design, Synthesis, and Antifungal Activity.

In this study, twenty novel pyrimidine derivatives bearing a 1,3,4-thiadiazole skeleton were designed and synthesized. Then their antifungal activity against Botrytis cinereal (B. cinereal), Botryosphaeria dothidea (B. dothidea), and Phomopsis sp. were determined using the poison plate technique. Biological test results showed that compound 6h revealed lower EC50 values (25.9 and 50.8 µg/ml) on Phompsis sp. than those of pyrimethanil (32.1 and 62.8 µg/ml).

Transcriptome and carotenoid profiling of different varieties of Coffea arabica provides insights into fruit color formation.

The processability and ultimate quality of coffee (C offea arabica) are determined by the composition of the matured fruits. The basis of genetic variation in coffee fruit quality could be explained by studying color formation during fruit maturation. Transcriptome profiling was conducted on matured fruits of four C. arabica varieties (orange colored fruits (ORF); purple colored fruits (PF); red colored fruits (RF) and yellow colored fruits (YF)) to identify key color-regulating genes, biosynthesis pathways and transcription factors implicated in fruit color formation. A total of 39,938 genes were identified in the transcriptomes of the four C. arabica varieties. In all, 2745, 781 and 1224 differentially expressed genes (DEGs) were detected in YF_vs_PF, YF_vs_RF and YF_vs_ORF, respectively, with 1732 DEGs conserved among the three pairwise groups. Functional annotation of the DEGs led to the detection of 28 and 82 key genes involved in the biosynthesis of carotenoids and anthocyanins, respectively. Key transcription factors bHLH, MYB, NAC, MADS, and WRKY implicated in fruit color regulation were detected. The high expression levels of gene-LOC113688784 (PSY), gene-LOC113730013 (ß-CHY), gene-LOC113728842 (CCD7), gene-LOC113689681 (NCED) and gene-LOC113729473 (ABA2) in YF may have accounted for the yellow coloration. The differential expression of several anthocyanin and carotenoid-specific genes in the fruits substantially account for the purple (PF), red (RF), and orange (ORF) colorations. This study provides important insights into fruit color formation and variations in C. arabica and will help to develop coffee varieties with specific color and quality traits.

Nrf2 activation contributes to hepatic tumor-augmenting effects of developmental arsenic exposure.

Developmental arsenic exposure increases cancer risk in later life with the mechanism elusive. Oxidative stress is a dominant determinant in arsenic toxicity. However, the role of Nrf2, a key regulator in antioxidative response, in tumor-augmenting effects by developmental arsenic exposure is unclear. In the present study, wild-type C57BL/6J and Nrf2-konckout (Nrf2-KO) were developmentally exposed to inorganic arsenic via drinking water. For hepatic tumorigenesis analysis, mice were intraperitoneally injected with diethylnitrosamine (DEN) at two weeks of age. Developmental arsenic exposure aggravated tumor multiplicity and burden, and expression of PCNA and AFP in hepatic tumors induced by DEN. Nrf2 activation as indicated by over-expression of Nrf2 and its downstream genes, including Gss, Gsr, p62, Gclc and Gclm, was found in liver tumors, as well as in the livers in developmentally arsenic-exposed pups at weaning. Notably, Nrf2 deficiency attenuated tumor-augmenting effects and over-expression of Nrf2 downstream genes due to developmental arsenic exposure. Furthermore, the levels of urinary DEN metabolite (acetaldehyde) and hepatic DNA damage markers (O6-ethyl-2-deoxyguanosine adducts and γ-histone H2AX) after DEN treatment were elevated by Nrf2 agonist, 2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide. Collectively, our data suggest that augmentation of DEN-induced hepatic tumorigenesis by developmental arsenic exposure is dependent on Nrf2 activation, which may be related to the role of Nrf2 in DEN metabolic activation. Our findings reveal, at least in part, the mechanism underlying increased susceptibility to developing cancer due to developmental arsenic exposure.

Laser-induced crystal growth observed in CsPbBr3 perovskite nanoplatelets.

Benefiting from the easily adjustable optical properties of perovskite, CsPbBr3 nanocrystals (NCs) are considered to show their advantages in the field of display. Here, we report that a selective laser irradiation is used to induce CsPbBr3 nanostructural reshaping and then yielding a morphological change. Under 360 or 405 nm laser irradiation, a hierarchical crystal growth process occurs for the fabricated CsPbBr3 nanoplatelets (NPLs), which are first arranged in a side-by-side manner and reshaped into nanorods (NRs), and then NRs are arranged in the face-to-face manner to reshape into NCs. The entire process is monitored optically and microscopically, which showed that crystal growth relies on seeking a dynamic balance between heat dissipation and accumulation under laser irradiation. The heat on NPLs generated by laser irradiation dissipated with a low dissipation rate and thus led to temperature rising and lattice breaking, which turned out to be the driving force for the crystal growth in CsPbBr3 NPLs. This feasible laser irradiation-assisted method provides for crystal growth a reliable and scalable route toward the preparation of perovskite functional materials.

Assessing market efficiency and liquidity: Evidence from China's emissions trading scheme pilots.

Different from the previous studies that evaluated the degrees of carbon market efficiency as constant, the novelty of this work is to capture degrees of market efficiency that are time-varying over time and its static and dynamic relationship with liquidity in China's five emissions trading system (ETS) pilots (Beijing, Guangdong, Shanghai, Shenzhen and Hubei) from January 2017 to June 2019. For this purpose, this work employs the generalized autoregressive conditional heteroscedasticity in mean (GARCH(1,1)-M) model with state space time-varying parameter (Kalman filter), Modified Amihud illiquidity ratio, fixed effect variable intercept panel regression model and panel impulse response analysis. The empirical results are as follows: (1) Shenzhen pilot is the best performer for the market efficiency, followed by Beijing, Shanghai, Guangdong and Hubei; although the other four except the Shenzhen pilot are inconsistent with weak-form efficiency, the market efficiency of Beijing pilot has improved and the Hubei pilot has the lowest market efficiency; (2) there are the positively long-term equilibrium relationship between market efficiency and market liquidity of pilots; and (3) market liquidity can positively affect the market efficiency of pilots lasting three months. These findings suggest that the market participation ability, linkages between carbon markets, speculation of low market efficiency and carbon derivatives tools can be considered by unified China's national carbon market.

Regulatory Effects of Reward Anticipation and Target on Attention Processing of Emotional Stimulation.

Studies suggest that reward and emotion are interdependent. However, there are discrepancies regarding the interaction between these variables. Some researchers speculate that the inconsistent findings may be due to different targets being used. Although reward and emotion both affect attention, it is not clear whether their impacts are independent. This study examined the impact of reward anticipation on emotion processing for different targets. A cue-target paradigm was used, and behavior and eye-tracking data were recorded in an emotion or sex recognition task under the conditions of reward and non-reward anticipation. The results showed that when the target was related to the emotional attribute of the stimulus, the reward promoted the processing target information, thereby generating reward-oriented attention. When the target was unrelated to the emotional attributes of the stimulus, the reward did not promote the processing target information, and at the same time, individuals had negative emotional biases toward the emotional faces. The results revealed that, in addition to affecting the attention to emotional faces independently, the target regulated the promotion of reward anticipation to emotional attention and attention bias toward negative stimuli.

Nrf2 in keratinocytes protects against skin fibrosis via regulating epidermal lesion and inflammatory response.

Nuclear factor-E2-related factor 2 (Nrf2) is a master transcription factor in antioxidant response, protecting against oxidative damage and various diseases. Previous studies suggest that Nrf2 is suppressed in fibrotic skin and Nrf2 agonists represent a therapeutic strategy, which is mainly attributed to Nrf2 function in fibroblasts. However, constitutive activation of Nrf2 may endow cells with proliferation and survival advantage, facilitating skin tumorigenesis. Non-invasive and mild modulation of Nrf2 via topical application may be helpful. Keratinocytes, which are essential for epidermal formation and function maintenance, have been shown to modulate differentiation of fibroblasts in different stages of fibrosis. In this respect, the role of Nrf2 in keratinocytes in skin fibrosis remains elusive. In the present study, bleomycin (BLM)-induced skin fibrosis model was applied to keratinocyte-specific Nrf2 knockout (Nrf2(K)-KO) mice generated with Keratin 14-Cre/loxp system. BLM treatment significantly suppressed Nrf2 expression in the epidermis. Nrf2 deficiency in keratinocytes exacerbated BLM-induced skin fibrosis according to dermal thickness, and immunostaining of collagen and α-SMA. One-dose BLM treatment led to the emergence of apoptotic cells in the epidermis and an elevated number of macrophages and neutrophils in the dermis, which was aggravated by Nrf2 deficiency, as indicated by TUNEL staining, and expression of F4/80 and Ly6G. In line with in vivo evidence, NRF2 silencing in HaCaT cells significantly decreased cell survival rate in response to BLM due to suppressed expression of antioxidative genes and increased intracellular levels of reactive oxygen species (ROS). The mRNA levels of chemokines and cytokines that are capable of recruiting macrophages and neutrophils, including Mcp-1, Il-6 and Il-8, were increased by Nrf2 deficiency in primary mouse keratinocytes. Moreover, bardoxolone methyl (CDDO-Me), a potent Nrf2 activator, ameliorated BLM-induced skin fibrosis after topical administration. These findings indicate that Nrf2 in keratinocytes protects against skin fibrosis via regulating cell resistance to apoptosis and expression of cytokines and chemokines. The restoration of Nrf2 through topical application might be a potential pharmacologic approach to combat skin fibrosis.

The Role of Reactive Oxygen Species in Arsenic Toxicity.

Arsenic poisoning is a global health problem. Chronic exposure to arsenic has been associated with the development of a wide range of diseases and health problems in humans. Arsenic exposure induces the generation of intracellular reactive oxygen species (ROS), which mediate multiple changes to cell behavior by altering signaling pathways and epigenetic modifications, or cause direct oxidative damage to molecules. Antioxidants with the potential to reduce ROS levels have been shown to ameliorate arsenic-induced lesions. However, emerging evidence suggests that constructive activation of antioxidative pathways and decreased ROS levels contribute to chronic arsenic toxicity in some cases. This review details the pathways involved in arsenic-induced redox imbalance, as well as current studies on prophylaxis and treatment strategies using antioxidants.

Improved thermal stability of photoluminescence in Cs4PbBr6 microcrystals/CsPbBr3 nanocrystals.

Here, Cs4PbBr6 microcrystals (MCs) are synthesized using a two-phase liquid-liquid immiscible method. In order to unravel the bright green photoluminescence (PL) mechanism for in-situ Cs4PbBr6 MCs, the thermal stability of PL spectra for the supernatant and precipitate of reactants is investigated comparatively. Exciton binding energy, exciton-phonon (EP) coefficient and PL lifetime all indicate that the PL of the precipitate has similar temperature dependence as that of the supernatant. It is found that, according to its structural and optical characteristics, the supernatant of the reactants is CsPbBr3 nanocrystals (NCs). We also find that the bright green PL from the precipitate of the reactants is due to CsPbBr3 NCs embedded into Cs4PbBr6 MCs. Experimental results further reveal the size of CsPbBr3 NCs embedded into Cs4PbBr6 MCs is larger than that of CsPbBr3 NCs in the supernatant. The surface passivation of the composites can thus help to suppress the thermal quenching of PL for CsPbBr3 NCs, which opens a new avenue for enhancing the thermal stability of PL for perovskite NCs.

Cs4PbBr6/CsPbBr3 perovskite composites for WLEDs: pure white, high luminous efficiency and tunable color temperature.

Cs4PbBr6/CsPbBr3 perovskite composites are fabricated by room-temperature one-pot mixing synthesis, which is short in time, free from inert gases and delivers a high product yield. Temperature-dependent photoluminescence shows that a larger exciton binding energy of 291.1 meV exhibits better thermal stability compared with that of pure Cs4PbBr6 and CsPbBr3 materials. The CIE chromaticity coordinates (0.1380, 0.7236) of green LEDs designed with Cs4PbBr6/CsPbBr3 perovskite composites show almost no variation under driving current changing from 5 to 30 mA. Furthermore, the ground Cs4PbBr6/CsPbBr3 perovskite composites mixed with red emitting K2SiF6:Mn4+ phosphor are dropped and casted on a blue-emitting InGaN chip. The white light emitting diodes (WLEDs) are presented, which have good luminous efficiency of 65.33 lm W-1 at 20 mA, a correlated color temperature of 5190 K, and the white gamut with chromaticity coordinate of (0.3392, 0.3336). According to the state of art, these excellent characteristics observed are much superior to the reported results of conventional perovskite-based WLEDs, which demonstrate the immense potential and great prospect of Cs4PbBr6/CsPbBr3 perovskite composites to replace conventional phosphors in lighting devices.

Comparative Study on In Vitro Culture of Mouse Bone Marrow Mesenchymal Stem Cells.

In vitro culture of mesenchymal stem cells (MSCs) from mouse bone marrow (BM) has been hampered because of the low yield of MSCs during isolation and the contamination of hematopoietic cells during expansion. The lack of specific mouse BM-MSC markers increases the difficulty. Several techniques have been reported to improve the purity and in vitro growth of mouse BM-MSCs. However, systematic report on comparison of characteristics in primary BM-MSCs between different culture conditions is rare. Here, we studied the effects of oxygen concentrations and initial medium replacement intervals, along with cell passages, on mouse BM-MSCs isolated with differential adhesion method. BM-MSCs exhibited elevated proliferative and clonogenic abilities in 5% oxygen compared with 10% and 21% oxygen, as well as a better expression of the MSC marker Sca-1. Adipogenic and osteogenetic differentiation of BM-MSCs can be observed in both 21% and 5% oxygen. Adipogenic differentiation appeared stronger under normoxia conditions. BM-MSCs showed increased proliferative capacity and adipogenic/osteogenetic differentiation potential when initial medium replacement interval was 4 days compared with 1 day. As passage number increased, cells were more MSC-like in morphology and in expression of surface markers (positive for CD29, CD44, and Sca-1 and negative for CD11b, CD19, and CD45). These data provide new insight into optimizing the culture method and understanding the biological characteristics of mouse BM-MSCs during in vitro expansion.

Strain differences in arsenic-induced oxidative lesion via arsenic biomethylation between C57BL/6J and 129X1/SvJ mice.

Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice. Hepatic antioxidant enzymes were induced by arsenic in transcription in both strains and many were higher in C57BL/6J than 129X1/SvJ mice. Arsenic profiles in the liver, blood and urine and transcription of genes encoding enzymes involved in arsenic biomethylation all indicate a higher arsenic methylation capacity, which contributes to a faster hepatic arsenic excretion, in 129X1/SvJ mice than C57BL/6J mice. Taken together, C57BL/6J mice are more susceptible to oxidative hepatic injury compared with 129X1/SvJ mice after acute arsenic exposure, which is closely associated with arsenic methylation pattern of the two strains.