From genetic associations to genes: methods, applications, and challenges.

Genome-wide association studies (GWASs) have identified numerous genetic loci associated with human traits and diseases. However, pinpointing the causal genes remains a challenge, which impedes the translation of GWAS findings into biological insights and medical applications. In this review, we provide an in-depth overview of the methods and technologies used for prioritizing genes from GWAS loci, including gene-based association tests, integrative analysis of GWAS and molecular quantitative trait loci (xQTL) data, linking GWAS variants to target genes through enhancer-gene connection maps, and network-based prioritization. We also outline strategies for generating context-dependent xQTL data and their applications in gene prioritization. We further highlight the potential of gene prioritization in drug repurposing. Lastly, we discuss future challenges and opportunities in this field.

Development and global validation of a 1-week-old piglet head finite element model for impact simulations.

PURPOSE: Child head injury under impact scenarios (e.g. falls, vehicle crashes, etc.) is an important topic in the field of injury biomechanics. The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties. However, up to date, piglet head models with accurate geometry and material properties, which have been validated by impact experiments, are seldom. We aim to develop such a model for future research. METHODS: In this study, first, the detailed anatomical structures of the piglet head, including the skull, suture, brain, pia mater, dura mater, cerebrospinal fluid, scalp and soft tissue, were constructed based on CT scans. Then, a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models. Finally, the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model. RESULTS: Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature. The average peak force and duration of the guide drop tower test were similar to that of the simulation, with an error below 10%. The inaccuracy was below 20%. The average peak force and duration reported in the literature were comparable to those of the simulation, with the exception of the duration for an impact energy of 11 J. The results showed that the model was capable to capture the response of the pig head. CONCLUSION: This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.

Angiopoietin-like protein 4 promotes very-low-density lipoprotein assembly and secretion in bovine hepatocytes in vitro.

In dairy cows, fatty liver is one of the most common metabolic diseases that occurs during the periparturient period. Angiopoietin-like protein 4 (ANGPTL4) is a well-known downstream target of peroxisome proliferator-activated receptors (PPARs), which regulate the glucose and fatty acid metabolisms. The inhibition of lipoprotein lipase (LPL) activity interferes with the storage of triglycerides (TG) in adipocytes, which plays an essential role in lipid metabolism in rodents. However, it remains unclear whether ANGPTL4 is involved in the pathological process of fatty liver in dairy cows as a result of the regulation of the hepatocellular lipid transport system. This study intended to investigate the effect of ANGPTL4 on the very-low-density lipoprotein (VLDL) assembly and secretion in bovine hepatocytes. Bovine hepatocytes were isolated using a modified two-step perfusion and collagenase digestion process, and treated with different concentrations of ANGPTL4 (0, 4, 12, and 24 ng/ml) for 24 hr. The results showed that a high concentration of ANGPTL4 could significantly increase the extracellular concentration of VLDL while reducing the intracellular content of TG. Thus, it was confirmed that ANGPTL4 could promote the transport of TG in the form of VLDL by partially regulating the expression of related proteins in hepatocytes, thereby contributing to the partial adaptive regulation of lipid transport in dairy cows.

Temperature Rise Associated with Adiabatic Shear Band: Causality Clarified.

One of the most important issues related to adiabatic shear failure is the correlation among temperature elevation, adiabatic shear band (ASB) formation and the loss of load capacity of the material. Our experimental results show direct evidence that ASB forms several microseconds after stress collapse and temperature rise reaches its maximum about 30 µs after ASB formation. This observation indicates that temperature rise cannot be the cause of ASB. Rather, it might be the result of adiabatic shear localization. As such, the traditional well-accepted thermal-softening mechanism of ASB needs to be reconsidered.

Serum hepatokines in dairy cows: periparturient variation and changes in energy-related metabolic disorders.

BACKGROUND: During peripartum period, dairy cows are highly susceptible to energy metabolism disorders such as fatty liver and ketosis. Angiopoietin-like protein 4 (ANGPTL4) and fibroblast growth factor 21 (FGF21), known as hepatokines, play important roles in lipid metabolism. The purposes of our study were to evaluate variations of serum ANGPTL4 and FGF21 concentrations in periparturient dairy cows and changes in these serum analyte concentrations of energy-related metabolic disorders in early lactation dairy cows. This study was divided into two experiments. Experiment I: Blood parameters were measured in healthy periparturient Holstein cows from 4 wk antepartum to 4 wk postpartum (n = 219). In this experiment, weekly blood samples were obtained from 4 wk before the expected calving date through 4 wk after calving. Experiment II: Blood parameters were measured in healthy cows (n = 30) and cows with clinical ketosis (n = 29) and fatty liver (n = 25) within the first 4 wk of lactation. In the present study, all blood samples were collected from the coccygeal vein in the early morning before feeding. RESULTS: Serum ANGPTL4 and FGF21 concentrations peaked at parturition, and declined rapidly over the following 2 wk Serum ANGPTL4 and FGF21 concentrations were positively correlated with serum non-esterified fatty acids (NEFA) concentration (r = 0.856, P = 003; r = 0.848, P = 0.004, respectively). Cows with clinical ketosis and fatty liver had significantly higher serum ANGPTL4 and FGF21 concentrations than healthy cows (P < 0.01). CONCLUSION: Serum ANGPTL4 and FGF21 concentrations were elevated during peripartum period, suggesting that energy balance changes that were associated with parturition contributed significantly to these effects. Although FGF21 and ANGPTL4 could play important roles in the adaptation of energy metabolism, they may be involved in the pathological processes of energy metabolism disorders of dairy cows in the peripartum period.

Extraction, Purification, Structural Characterization, and Antitumor Effects of Water-Soluble Intracellular Polysaccharide (IPSW-1) from Phellinus igniarius Mycelia.

Phellinus igniarius is a commonly used Chinese medicine fungus, and its polysaccharide is a valuable bioactive with antioxidant, antiaging, antitumor activities, etc. However, their bioactivities are influenced by their structural and physicochemical properties. Hence, this research isolated and purified homogeneous water-soluble intracellular polysaccharide (IPSW-1) from P. igniarius mycelia. A coherent study of its structural characteristics, conformation, and antitumor mechanisms was evaluated. The results showed IPSW-1 has no triple helical conformation according to the Congo red test. Based on FT-IR, periodate oxidation, Smith degradation, methylation analysis, 1H and 13C NMR spectroscopy data, and IPSW-1 consisted of α-d-glucopyranose (Glcp). The backbone of IPSW-1 consisted primarily of repeating three (1 → 6)-linked α-d-Glcp and one (1 → 3,4)-linked α-d-Glcp, with one terminal α-d-Glcp as side chains of 3-O-connected to the main chain for every four residues. The IPSW-1 had an inhibitory influence on HepG2 cell proliferation and inhibited the migration and invasion ability by down-regulating the expression levels of MMP-7 and RhoA. Moreover, IPSW-1 could inhibit the lysis of autophagosomes to inhibit autophagy and regulate mitochondrial membrane potential and pro-apoptotic protein Bax, which causes the caspase cascade to promote apoptosis, thereby inhibiting the role of tumor cells. These findings show IPSW-1 holds potential as an innovative functional food.

S100A9, as a potential predictor of prognosis and immunotherapy response for GBM, promotes the malignant progression of GBM cells and migration of M2 macrophages.

In the past decades, the therapeutic effect of glioblastoma (GBM) has not been significantly improved. Generous evidence indicates that S100A9 has a wide range of functions in tumors, but its exploration in GBM is less. The purpose of this study is to conduct a comprehensive bioinformatics analysis and cytological experiment on S100A9 in GBM. The expression data and clinical data of GBM samples were downloaded from the public database, and comprehensive bioinformatics analysis was performed on S100A9 in GBM using R software. Wound healing assay and transwell assay were used to detect the migration activity of cells, and colony formation assay, EdU staining, and CCK-8 assay were used to detect the proliferation activity of cells. The effect of S100A9 on the migration activity of M2 macrophages was verified by the cell co-culture method. The protein expression was detected by western blotting and immunohistochemical staining. S100A9 is an independent prognostic factor in GBM patients and is related to poor prognosis. It can be used as an effective tool to predict the response of GBM patients to immune checkpoint inhibitors (ICIs). In addition, S100A9 can promote the malignant progression of GBM and the migration of M2 macrophages. On the whole, our study highlights the potential value of S100A9 in predicting prognosis and immunotherapeutic response in GBM patients. More importantly, S100A9 may promote the malignant progress of GBM by involving in some carcinogenic pathways and remodeling the tumor microenvironment (TME).

WTAP regulates the production of reactive oxygen species, promotes malignant progression, and is closely related to the tumor microenvironment in glioblastoma.

RNA modifications have been substantiated to regulate the majority of physiological activities in the organism, including the metabolism of reactive oxygen species (ROS), which plays an important role in cells. As for the effect of RNA modification genes on ROS metabolism in glioblastoma (GBM), it has not been studied yet. Therefore, this study aims to screen the RNA modification genes that are most related to ROS metabolism and explore their effects on the biological behavior of GBM in vitro. Here, an association between WTAP and ROS metabolism was identified by bioinformatics analysis, and WTAP was highly expressed in GBM tissue compared with normal brain tissue, which was confirmed by western blotting and immunohistochemical staining. When using a ROS inducer to stimulate GBM cells in the WTAP overexpression group, the ROS level increased more significantly and the expression levels of superoxide dismutase 1 (SOD1) and catalase (CAT) also increased. Next, colony formation assay, wound healing assay, and transwell assay were performed to investigate the proliferation, migration, and invasion of GBM cells. The results showed that WTAP, as an oncogene, promoted the malignant progression of GBM cells. Functional enrichment analysis predicted that WTAP was involved in the regulation of tumor/immune-related functional pathways. Western blotting was used to identify that WTAP had a regulatory effect on the phosphorylation of PI3K/Akt signaling. Finally, based on functional enrichment analysis, we further performed immune-related analysis on WTAP. In conclusion, this study analyzed WTAP from three aspects, which provided new ideas for the treatment of GBM.

Joint analysis of proteome, transcriptome, and multi-trait analysis to identify novel Parkinson's disease risk genes.

Genome-wide association studies (GWAS) have identified multiple risk variants for Parkinson's disease (PD). Nevertheless, how the risk variants confer the risk of PD remains largely unknown. We conducted a proteome-wide association study (PWAS) and summary-data-based mendelian randomization (SMR) analysis by integrating PD GWAS with proteome and protein quantitative trait loci (pQTL) data from human brain, plasma and CSF. We also performed a large transcriptome-wide association study (TWAS) and Fine-mapping of causal gene sets (FOCUS), leveraging joint-tissue imputation (JTI) prediction models of 22 tissues to identify and prioritize putatively causal genes. We further conducted PWAS, SMR, TWAS, and FOCUS using a multi-trait analysis of GWAS (MTAG) to identify additional PD risk genes to boost statistical power. In this large-scale study, we identified 16 genes whose genetically regulated protein abundance levels were associated with Parkinson's disease risk. We undertook a large-scale analysis of PD and correlated traits, through TWAS and FOCUS studies, and discovered 26 casual genes related to PD that had not been reported in previous TWAS. 5 genes (CD38, GPNMB, RAB29, TMEM175, TTC19) showed significant associations with PD at both the proteome-wide and transcriptome-wide levels. Our study provides new insights into the etiology and underlying genetic architecture of PD.

Comment on "Cryoforged nanotwinned titanium with ultrahigh strength and ductility".

We analyze the results of Zhao et al. (Reports, 17 September 2021, p. 1363) with a focus on the mechanical properties and microstructural evolution. We conclude that their results, together with the explanations and interpretations, are confusing, misleading, or even wrong.

Quantification and statistical analysis on the cranial vault morphology for Chinese children 3-10 years old.

BACKGROUND AND OBJECTIVE: Head injury is the leading cause of fatalities and disabilities in children. Characterizing the variation in cranial size/shape and thickness during growth is important for developing finite element models of child heads and evaluating head injury risk at different ages. However, the quantitative morphological features of the cranial vault (size/shape and non-uniform thickness distribution) have not been accounted for in children aged between 3 and 10 years old (YO). METHODS: Geometrically equivalent discrete points were identified on 42 head CT scans of 3-10 YO children by separation, curve dividing, and point fitting. Based on discrete points, the principal component analysis and regression (PCA&R) method was used to develop a statistical model of the cranial vault as a function of age and head circumference. RESULTS: The ontogeny of three-dimensional cranial morphology and non-uniform thickness from 3 to 10 years of age was quantified and cranial vault morphologies for 3-10 YO children were generated in 1 year intervals. CONCLUSIONS: The automatic method, the procedure of identifying discrete points from CT scans, and the developed quantitative cranial vault model are reliable and accurate.

MiR-182-5p Mediated by Exosomes Derived From Bone Marrow Mesenchymal Stem Cell Attenuates Inflammatory Responses by Targeting TLR4 in a Mouse Model of Myocardial Infraction.

Exosomes derived from mesenchymal stem cells (MSCs) could protect against myocardial infarction (MI). TLR4 is reported to play an important role in MI, while microRNA-182-5p (miR-182-5p) negatively regulates TLR4 expression. Therefore, we hypothesize that MSCs-derived exosomes overexpressing miR-182-5p may have beneficial effects on MI. We generated bone marrow mesenchymal stem cells (BM-MSCs) and overexpressed miR-182-5p in these cells for exosome isolation. H2O2-stimulated neonatal mouse ventricle myocytes (NMVMs) and MI mouse model were employed, which were subjected to exosome treatment. The expression of inflammatory factors, heart function, and TLR4 signaling pathway activation were monitored. It was found that miR-182-5p decreased TLR4 expression in BM-MSCs and NMVMs. Administration of exosomes overexpressing miR-182-5p to H2O2-stimulated NMVMs enhanced cell viability and suppressed the expression of inflammatory cytokines. In addition, they promoted heart function, suppressed inflammatory responses, and de-activated TLR4/NF-κB signaling pathway in MI mice. In conclusion, miR-182-5p transferred by the exosomes derived from BM-MSCs protected against MI-induced impairments by targeting TLR4.

FGF21 Reduces Lipid Accumulation in Bovine Hepatocytes by Enhancing Lipid Oxidation and Reducing Lipogenesis via AMPK Signaling.

During the periparturient period, dairy cows suffer drastic metabolic stress because of plasma increased non-esterified fatty acids (NEFAs) that stem from a negative energy balance. Fibroblast growth factor 21 (FGF21) is a hepatokine that activates the AMP-activated protein kinase (AMPK) signaling pathway to maintain intracellular energy balance and tissue integrity via the promotion of catabolism and the inhibition of anabolic regulation. FGF21 treatment caused a 50% reduction in triglyceride (TG) content in liver in dairy cows. However, it is not clear whether FGF21 regulates lipid metabolism in bovine liver. The purpose of this study was to evaluate the influence of FGF21 on lipid metabolism via AMPK signaling in bovine hepatocytes. The hepatocytes isolated from calves were treated with different concentrations of FGF21 or co-treated with AMPK inhibitor (BML-275). Herein, the study showed that FGF21 significantly reduced TG content in a dose-response manner and promoted very-low-density lipoprotein (VLDL) secretion via an up-regulation of the proteins (ApoB 100, ApoE and MTTP) involved in VLDL secretion. Otherwise, the genes associated with lipid transport (LDLR and CD36) and lipid oxidation (PPARGC1A, ACOX1 and CPT1A), were up-regulated following FGF21 treatment. Moreover, FGF21 treatment inhibited lipogenesis via SREBF1, ACACA, FASN and ACLY inhibition. After being co-treated with the AMPK inhibitor, FGF21-induced changes were reversed in some genes. In conclusion, these results indicate that FGF21 adaptively regulates energy metabolism for a negative impact on lipogenesis, strengthens lipid oxidation, and inhibited lipid transportation via AMPK signaling in bovine hepatocytes. The present data suggest the possibility that FGF21 has potential value in alleviating perinatal metabolic diseases in dairy cows, and specific research in vivo should be studied in more detail.

Plasticity and Deformation Mechanisms of Ultrafine-Grained Ti in Necking Region Revealed by Digital Image Correlation Technique.

The conventional engineering stress-strain curve could not accurately describe the true stress-strain and local deformability of the necking part of tensile specimens, as it calculates the strain by using the whole gauge length, assuming the tensile specimen was deformed uniformly. In this study, we employed 3D optical measuring digital image correlation (DIC) to systematically measure the full strain field and local strain during the whole tensile process, and calculate the real-time strain and actual flow stress in the necking region of ultrafine-grained (UFG) Ti. The post-necking elongation and strain hardening exponent of the UFG Ti necking part were then measured as 36% and 0.101, slightly smaller than those of the coarse grained Ti (52% and 0.167), suggesting the high plastic deformability in the necking part of the UFG Ti. Finite elemental modeling (FEM) indicates that when necking occurs, strain is concentrated in the necking region. The stress state of the necking part was transformed from uniaxial in the uniform elongation stage to a triaxial stress state. A scanning electron microscopic (SEM) study revealed the shear and ductile fracture, as well as numerous micro shear bands in the UFG Ti, which are controlled by cooperative grain boundary sliding. Our work revealed the large plastic deformability of UFG metals in the necking region under a complex stress state.

Swainsonine promotes apoptosis by impairing lysosomal function and inhibiting autophagic degradation in rat primary renal tubular epithelial cells.

Swainsonine (SW), an indolizidine alkaloid, is the primary toxin in locoweeds that causes toxicity syndrome in livestock. Current research shows that SW can induce both apoptosis and autophagy. However, the relationship between, and regulatory mechanism of, autophagy and apoptosis in SW-mediated cytotoxicity remain unclear. In this study, we investigated the role of autophagy and apoptosis in SW-induced cytotoxicity in rat primary renal tubular epithelial cells (RTECs). We examined the effect of SW on lysosomal function using western blotting, transmission electron microscopy, fluorescent microscopy, and flow cytometry. The results showed that SW induced both autophagy and apoptosis, and autophagy protected RTECs from cellular damage. Activating autophagy using rapamycin (Rapa) inhibited apoptosis, while suppressing autophagy using bafilomycin A1 (Baf A1) greatly enhanced SW-induced apoptosis. SW treatment suppressed the expression of lysosomal-related proteins, and co-incubation with SW and aloxistatin (E64d) further promoted apoptosis and LC3-II accumulation in RTECs. These results suggest that SW causes toxicity by disrupting lysosomal dysfunction, inhibiting autophagic degradation, and promoting apoptosis.

Swainsonine Triggers Paraptosis via ER Stress and MAPK Signaling Pathway in Rat Primary Renal Tubular Epithelial Cells.

Swainsonine (SW), an indolizidine alkaloid extracted from locoweeds, was shown toxic effects in multiple studies, but the underlying action mechanism remains unclear. SW is known to cause autophagy and apoptosis, but there has been no report on paraptosis mediated cell death. Here, we showed that SW induced rat primary renal tubular epithelial cells (RTECs) death accompanied by vacuolation in vitro. The fluorescence with the endoplasmic reticulum (ER)-Tracker Red and transmission electron microscopy (TEM) results indicated that the vacuoles were of ER origin, typical of paraptosis. The level of ER stress markers, such as polyubiquitinated proteins, Bip, CHOP and cytoplasmic concentration of Ca2+ have drastically increased. Interestingly, autophagy inhibitor could not interrupt but enhanced the induction of cytoplasmic vacuolization. Furthermore, MAPK pathways were activated by SW and inhibitors of ERK and JNK pathways could prevent the formation of cytoplasmic vacuolization. In this study, we confirmed that SW induced cell paraptosis through ER stress and MAPK signaling pathway, thus further laying a theoretical foundation for the study of SW toxicity mechanism.

Estimation of a statistical geometric model for the cervical vertebrae of children aged 10-18 years.

Child neck injuries in motor vehicle crashes (MVCs) result in high morbidity and mortality rates. Estimating a statistical cervical vertebrae geometric model and quantifying the variations of the size and shape with age are very important for investigating the dynamic response and injury risk to a child's cervical spine, as well as for providing a geometric basis for developing child anthropomorphic test devices (ATDs) and finite element models (FEMs) of different ages. In this study, spatial geometric points were automatically extracted from the cervical vertebrae computed tomography (CT) scans of 30 children aged 10 to 18 years old (YO), and a statistical geometric model was estimated for the cervical vertebrae as a function of age and neck circumference/neck length according to the method of principal component analysis and regression (PCA&R). Based on this statistical model, geometric point sets representing cervical vertebrae geometries at different ages and percentiles were generated and formed to envelope surfaces. Meanwhile, the size changes of the cervical vertebrae with child growth from 10 to 18 YO were quantified. In general, the anteroposterior length (APL), transverse process width (TPW), vertebral body height (VBH), and vertebral body depth (VBD) of the cervical vertebrae increase with age; the VBH and VBD increase faster than the APL and TPW. Compared with other vertebrae, the APL of C7 is larger, and the rate of increase of C1 with age is evidently slower. The TPWs of C1 and C7 are greater than those of C2 to C6. C7 has higher average values for the VBH and VBD than C3 to C6.

CHOP Regulates Endoplasmic Reticulum Stress-Mediated Hepatoxicity Induced by Monocrotaline.

Monocrotaline (MCT), a pyrrolizidine alkaloid, is the major toxin in Crotalaria, which causes cell apoptosis in humans and animals. It has been reported that the liver is a vulnerable target of MCT. However, the exact molecular mechanism of the interaction between endoplasmic reticulum (ER) stress and liver injury induced by MCT is still unclear. In this study, the cytotoxicity of MCT on primary rat hepatocytes was analyzed by a CCK-8 assay and Annexin V-FITC/PI assay. Protein expression was detected by western blotting and immunofluorescence staining. As a result, MCT significantly decreased the cell viability and mediated the apoptosis of primary rat hepatocytes. Meanwhile, MCT could also induce ER stress in hepatocytes, indicated by the expression of ER stress-related proteins, including GRP78, p-IRE1α, ATF6, p-eIF2α, ATF4, and CHOP. Pretreatment with 4-PBA, an inhibitor of ER stress, or knockdown of CHOP by siRNA could partly enhance cell viability and relieve the apoptosis. Our findings indicate that ER stress is involved in the hepatotoxicity induced by MCT, and CHOP plays an important role in this process.

Electromagnetic Hopkinson bar: A powerful scientific instrument to study mechanical behavior of materials at high strain rates.

The split Hopkinson bar (SHB) has been widely used for testing the dynamic mechanical behavior of materials. However, it is hard to involve complex stress conditions in traditional SHB due to its intrinsic characteristics. The Electromagnetic Hopkinson bar (E-Hopkinson bar) has been recently proposed as a solution. Different from the traditional SHB, the stress pulse of the E-Hopkinson bar is generated directly by the electromagnetic force. Therefore, the stress pulse that loads the specimen can be accurately controlled. With this advantage, some experiments that cannot be done with traditional SHB can be conducted by the E-Hopkinson bar technique. In this review, we introduced briefly the basic principles of the E-Hopkinson bar. Some lasted tests, such as symmetrically dynamic compression/tension of materials, interlaminar fracture of composites, dynamic Bauschinger effect of metals, intermediate strain rate tests, and dynamic multi-axial tests were also introduced. This new technique will be helpful for those researchers in the field of solid mechanics, especially when the strain rate and complex stress condition are involved.

The PERK/eIF2α/ATF4/CHOP pathway plays a role in regulating monocrotaline-induced endoplasmic reticulum stress in rat liver.

Monocrotaline (MCT) belongs to the category of Pyrrolizdine Alkaloids (PAs), which is one of important hepatotoxic alkaloid in Crotalaria Lin. Apoptosis is one mechanism of toxic responses induced by MCT. However, the underlying mechanism of liver apoptosis caused by MCT through Endoplasmic reticulum (ER) stress continues to be incompletely understood. In this study, we describe the role of ER stress in MCT induced hepatotoxicity in rats. 24 male rats were randomly divided into 3 groups: normal saline group, 45 mg/kg MCT group and 90 mg/kg MCT group. After 48 h of saline/MCT administration, the livers were collected for analysis of ER stress-related proteins by Western blotting. The expression of GRP78, p-IRE1α, ATF6 and caspase-12 showed a dose-dependent increase. PERK/eIF2α/ATF4/CHOP pathway is one of the major ER stress pathways which is required for cell survival. Therefore, through analyzing the effects of MCT on this pathway, we found the protein levels of p-PERK, p-eIF2α, ATF4 and CHOP were increase obviously. All these results indicate that MCT induces ER stress in rat liver. The PERK/eIF2α/ATF4/CHOP pathway is involved in the regulation of MCT-induced ER stress in the liver of rat.