Dietary salidroside supplementation improves meat quality and antioxidant capacity and regulates lipid metabolism in broilers.

We aimed to explore the effect of salidroside (SAL) on meat quality, antioxidant capacity, and lipid metabolism in broilers. The results demonstrated that SAL significantly reduced the yellowness (b*), shear force, cooking loss, drip loss, MDA, TBARS, and carbonyl content in breast (P < 0.05), while increasing the pH value (P < 0.05), suggesting an improvement in meat quality. SAL lowered the lipid contents in liver and serum (P < 0.05), while increasing the proportion of unsaturated fatty acids in breast (P < 0.05), indicating effective regulation of lipid metabolism by SAL. SAL increased the activity of antioxidant enzymes and the expression of antioxidant genes in both liver and muscle (P < 0.05). Additionally, SAL improved the meat quality and antioxidant capacity of breast subjected to repeated freeze-thaw treatment. SAL may enhance meat quality by improving antioxidative stability and regulating lipid metabolism, potentially serving as a dietary supplement for broilers.

[Role of Virtual Reality in Gastrointestinal Endoscopy Training and Teaching]. / è™šæ‹ŸçŽ°å®žæŠ€æœ¯åœ¨æ¶ˆåŒ–å† é•œåŸ¹è®­ä¸Žæ•™å­¦ä¸­çš„åº”ç”¨è¿›å±•.

Gastrointestinal (GI) endoscope is one of the instruments used extensively in the diagnosis and treatment of digestive tract disorders. China is confronted with a great demand for endoscopists working in grassroots healthcare facilities. Furthermore, endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasonography (EUS), and endoscopic submucosal dissection (ESD) are becoming the prevailing methods of endoscopic treatment of digestive diseases. Therefore, there is a growing demand for senior endoscopists. Currently, an important focus of GI endoscopy training is the acceleration of standardized training for endoscopists working in grassroots health facilities and advanced training for senior endoscopists. Simulation devices based on virtual reality technology exhibit strengths in objectivity, authenticity, and an immersive experience. These devices show advantages in the training method, the number of participants, and assessment over traditional training programs for GI endoscopy. Their application provides a new approach to the training and teaching of GI endoscopy. Herein, we summarized the explorations and practices of using virtual reality technology in the training and teaching of GI endoscopy, analyzed its application status in China, and discussed its prospects for future application.

Facial expression recognition ability and its neuropsychological mechanisms in children with attention deficit and hyperactive disorder. / æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢æ‚£å„¿é¢éƒ¨è¡¨æƒ è¯†åˆ«èƒ½åŠ›åŠå ¶ç¥žç»å¿ƒç†æœºåˆ¶.

Attention deficit and hyperactive disorder (ADHD) is a chronic neurodevelopmental disorder characterized by inattention, hyperactivity-impulsivity, and working memory deficits. Social dysfunction is one of the major challenges faced by children with ADHD. It has been found that children with ADHD can't perform as well as typically developing children on facial expression recognition (FER) tasks. Generally, children with ADHD have some difficulties in FER, while some studies suggest that they have no significant differences in accuracy of specific emotion recognition compared with typically developing children. The neuropsychological mechanisms underlying these difficulties are as follows. First, neuroanatomically. Compared to typically developing children, children with ADHD show smaller gray matter volume and surface area in the amygdala and medial prefrontal cortex regions, as well as reduced density and volume of axons/cells in certain frontal white matter fiber tracts. Second, neurophysiologically. Children with ADHD exhibit increased slow-wave activity in their electroencephalogram, and event-related potential studies reveal abnormalities in emotional regulation and responses to angry faces when facing facial stimuli. Third, psychologically. Psychosocial stressors may influence FER abilities in children with ADHD, and sleep deprivation in ADHD children may significantly increase their recognition threshold for negative expressions such as sadness and anger. This article reviews research progress over the past three years on FER abilities of children with ADHD, analyzing the FER deficit in children with ADHD from three dimensions: neuroanatomy, neurophysiology and psychology, aiming to provide new perspectives for further research and clinical treatment of ADHD.

HIF-1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid-induced osteonecrosis of the femoral head.

With the prevalence of coronavirus disease 2019, the administration of glucocorticoids (GCs) has become more widespread. Treatment with high-dose GCs leads to a variety of problems, of which steroid-induced osteonecrosis of the femoral head (SONFH) is the most concerning. Since hypoxia-inducible factor 1α (HIF-1α) is a key factor in cartilage development and homeostasis, it may play an important role in the development of SONFH. In this study, SONFH models were established using methylprednisolone (MPS) in mouse and its proliferating chondrocytes to investigate the role of HIF-1α in cartilage differentiation, extracellular matrix (ECM) homeostasis, apoptosis and glycolysis in SONFH mice. The results showed that MPS successfully induced SONFH in vivo and vitro, and MPS-treated cartilage and chondrocytes demonstrated disturbed ECM homeostasis, significantly increased chondrocyte apoptosis rate and glycolysis level. However, compared with normal mice, not only the expression of genes related to collagens and glycolysis, but also chondrocyte apoptosis did not demonstrate significant differences in mice co-treated with MPS and HIF-1α inhibitor. And the effects observed in HIF-1α activator-treated chondrocytes were similar to those induced by MPS. And HIF-1α degraded collagens in cartilage by upregulating its downstream target genes matrix metalloproteinases. The results of activator/inhibitor of endoplasmic reticulum stress (ERS) pathway revealed that the high apoptosis rate induced by MPS was related to the ERS pathway, which was also affected by HIF-1α. Furthermore, HIF-1α affected glucose metabolism in cartilage by increasing the expression of glycolysis-related genes. In conclusion, HIF-1α plays a vital role in the pathogenesis of SONFH by regulating ECM homeostasis, chondrocyte apoptosis, and glycolysis.

Multi-omics approaches for drug-response characterization in primary biliary cholangitis and autoimmune hepatitis variant syndrome.

BACKGROUND: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) variant syndrome (VS) exhibit a complex overlap of AIH features with PBC, leading to poorer prognoses than those with PBC or AIH alone. The biomarkers associated with drug response and potential molecular mechanisms in this syndrome have not been fully elucidated. METHODS: Whole-transcriptome sequencing was employed to discern differentially expressed (DE) RNAs within good responders (GR) and poor responders (PR) among patients with PBC/AIH VS. Subsequent gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for the identified DE RNAs. Plasma metabolomics was employed to delineate the metabolic profiles distinguishing PR and GR groups. The quantification of immune cell profiles and associated cytokines was achieved through flow cytometry and immunoassay technology. Uni- and multivariable logistic regression analyses were conducted to construct a predictive model for insufficient biochemical response. The performance of the model was assessed by computing the area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity. FINDINGS: The analysis identified 224 differentially expressed (DE) mRNAs, 189 DE long non-coding RNAs, 39 DE circular RNAs, and 63 DE microRNAs. Functional pathway analysis revealed enrichment in lipid metabolic pathways and immune response. Metabolomics disclosed dysregulated lipid metabolism and identified PC (18:2/18:2) and PC (16:0/20:3) as predictors. CD4+ T helper (Th) cells, including Th2 cells and regulatory T cells (Tregs), were upregulated in the GR group. Pro-inflammatory cytokines (IFN-γ, TNF-α, IL-9, and IL-17) were downregulated in the GR group, while anti-inflammatory cytokines (IL-10, IL-4, IL-5, and IL-22) were elevated. Regulatory networks were constructed, identifying CACNA1H and ACAA1 as target genes. A predictive model based on these indicators demonstrated an AUC of 0.986 in the primary cohort and an AUC of 0.940 in the validation cohort for predicting complete biochemical response. CONCLUSION: A combined model integrating genomic, metabolic, and cytokinomic features demonstrated high accuracy in predicting insufficient biochemical response in patients with PBC/AIH VS. Early recognition of individuals at elevated risk for insufficient response allows for the prompt initiation of additional treatments.

Dissection of a novel major stable QTL on chromosome 7D for grain hardness and its breeding value estimation in bread wheat.

Grain hardness (Gh) is important for wheat processing and end-product quality. Puroindolines polymorphism explains over 60% of Gh variation and the novel genetic factors remain to be exploited. In this study, a total of 153 quantitative trait loci (QTLs), clustered into 12 genomic intervals (C1-C12), for 13 quality-related traits were identified using a recombinant inbred line population derived from the cross of Zhongkemai138 (ZKM138) and Chuanmai44 (CM44). Among them, C7 (harboring eight QTLs for different quality-related traits) and C8 (mainly harboring QGh.cib-5D.1 for Gh) were attributed to the famous genes, Rht-D1 and Pina, respectively, indicating that the correlation of involved traits was supported by the pleotropic or linked genes. Notably, a novel major stable QTL for Gh was detected in the C12, QGh.cib-7D, with ZKM138-derived allele increasing grain hardness, which was simultaneously mapped by the BSE-Seq method. The geographic pattern and transmissibility of this locus revealed that the increasing-Gh allele is highly frequently present in 85.79% of 373 worldwide wheat varieties and presented 99.31% transmissibility in 144 ZKM138-derivatives, indicating the non-negative effect on yield performance and that its indirect passive selection has happened during the actual breeding process. Thus, the contribution of this new Gh-related locus was highlighted in consideration of improving the efficiency and accuracy of the soft/hard material selection in the molecular marker-assisted process. Further, TraesCS7D02G099400, TraesCS7D02G098000, and TraesCS7D02G099500 were initially deduced to be the most potential candidate genes of QGh.cib-7D. Collectively, this study provided valuable information of elucidating the genetic architecture of Gh for wheat quality improvement.

Preparation of Surface Dispersed WO3/BiVO4 Heterojunction Arrays and Their Photoelectrochemical Performance for Water Splitting.

In this work, a surface dispersed heterojunction of BiVO4-nanoparticle@WO3-nanoflake was successfully prepared by hydrothermal combined with solvothermal method. We optimized the morphology of the WO3 nanoflakes and BiVO4 nanoparticles by controlling the synthesis conditions to get the uniform BiVO4 loaded on the surface of WO3 arrays. The phase composition and morphology evolution with different reaction precursors were investigated in detail. When used as photoanodes, the WO3/BiVO4 composite exhibits superior activity with photocurrent at 3.53 mA cm-2 for photoelectrochemical (PEC) water oxidation, which is twice that of pure WO3 photoanode. The superior surface dispersion structure of the BiVO4-nanoparticle@WO3-nanoflake heterojunction ensures a large effective heterojunction area and relieves the interfacial hole accumulation at the same time, which contributes to the improved photocurrents together with the stability of the WO3/BiVO4 photoanodes.

Noninvasive prediction of insufficient biochemical response after ursodeoxycholic acid treatment in patients with primary biliary cholangitis based on pretreatment nonenhanced MRI.

OBJECTIVES: To explore the feasibility of pretreatment nonenhanced magnetic resonance imaging (MRI) in predicting insufficient biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). METHODS: From January 2009 to April 2022, consecutive PBC patients who were treated with UDCA and underwent nonenhanced MRI within 30 days before treatment were retrospectively enrolled. All MR images were independently evaluated by two blinded radiologists. Uni- and multivariable logistic regression analyses were performed to develop a predictive model for 12-month insufficient biochemical response. Model performances were evaluated by computing the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 74 patients (50.6 ± 11.9 years; 62 females) were included. Three pretreatment MRI features, including hepatomegaly (odds ratio [OR]: 4.580; p = 0.011), periportal hyperintensity on T2-weighted imaging (T2WI) (OR: 4.795, p = 0.008), and narrowing of the bile ducts (OR: 3.491; p = 0.027) were associated with 12-month insufficient biochemical response in the multivariable analysis. A predictive model based on the above indicators had an AUC of 0.781, sensitivity of 85.4%, and specificity of 61.5% for predicting insufficient biochemical response. CONCLUSIONS: A noninvasive model based on three pretreatment MRI features could accurately predict 12-month insufficient biochemical response to UDCA in patients with PBC. Early identification of PBC patients at increased risk for insufficient response can facilitate the timely initiation of additional treatment. CLINICAL RELEVANCE STATEMENT: A noninvasive predictive model constructed by incorporating three pretreatment MRI features may help identify patients with primary biliary cholangitis at high risk of insufficient biochemical response to ursodeoxycholic acid and facilitate the timely initiation of additional treatment. KEY POINTS: • Noninvasive imaging features based on nonenhanced pretreatment MRI may predict an insufficient biochemical response to UDCA in PBC patients. • A combined model based on three MRI features (hepatomegaly, periportal hyperintensity on T2-weighted imaging, and narrowing of the bile ducts) further improved the predictive efficacy for an insufficient biochemical response to UDCA in PBC patients, with high sensitivity and specificity. • The nomogram of the combined model showed good calibration and predictive efficacy for an insufficient biochemical response to UDCA in PBC patients. In particular, the calibration curve visualised the clinical applicability of the prediction model.

Emissions reduction strategy in a three-stage agrifood value chain: A dynamic differential game approach.

Agrifood systems account for 31% of global greenhouse gas emissions. Substantial emissions reduction in agrifood systems is critical to achieving the temperature goal set by the Paris Agreement. A key challenge in reducing GHG emissions in the agrifood value chain is the imbalanced allocation of benefits and costs associated with emissions reduction among agrifood value chain participants. However, only a few studies have examined agrifood emissions reduction from a value chain perspective, especially using dynamic methods to investigate participants' long-term emissions reduction strategies. This paper helps fill this gap in the existing literature by examining the impact of collaborations among agrifood value chain participants on correcting those misallocations and reducing emissions in agrifood systems. We develop a dynamic differential game model to examine participants' long-term emissions reduction strategies in a three-stage agrifood value chain. We use the Hamilton-Jacobi-Bellman equation to derive the Nash equilibrium emissions reduction strategies under non-cooperative, cost-sharing, and cooperative mechanisms. We then conduct numerical analysis and sensitivity analysis to validate our model. Our results show that collaboration among value chain participants leads to higher emissions reduction efforts and profits for the entire value chain. Specifically, based on our numerical results, the cooperative mechanism results in the greatest emissions reduction effort by the three participants, which leads to a total that is nearly three times higher than that of the non-cooperative mechanism and close to two times higher than the cost-sharing mechanism. The cooperative mechanism also recorded the highest profits for the entire value chain, surpassing the non-cooperative and cost-sharing mechanisms by around 37% and 16%, respectively. Our results provide valuable insights for policymakers and agrifood industry stakeholders to develop strategies and policies encouraging emissions reduction collaborations in the agrifood value chain and reduce emissions in the agrifood systems.

Incorporation of protein induced by vitamin K absence or antagonist-II into transplant criteria expands beneficiaries of liver transplantation for hepatocellular carcinoma: a multicenter retrospective cohort study in China.

INTRODUCTION: In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver transplantation (LT) is essential. As a crucial diagnostic biomarker for HCC, protein induced by vitamin K absence or antagonist-II (PIVKA-II) has become one of the key indicators for assessing tumor recurrence risk after LT. This study aims to investigate the role of PIVKA-II in recipient selection and prognostic stratification. METHODS: The clinicopathologic data of HCC patients undergoing LT from 2015 to 2020 in six Chinese transplant centers were collected. Univariate and multivariate analyses were performed to determine risk factors for disease free survival (DFS). Based on these risk factors, survival analysis was made by Kaplan-Meier method and their value in prognostic stratification was assessed. RESULTS: A total of 522 eligible HCC patients with pre-LT PIVKA-II records were finally included in this study. Tumor burden>8 cm, α-fetoprotein>400 ng/ml, histopathologic grade III and PIVKA-II>240 mAU/ml were identified as independent risk factors for DFS. DFS of patients with PIVKA-II≤240 mAU/ml ( N =288) were significantly higher than those with PIVKA-II>240 mAU/ml ( N =234) (1-year, 3-year, and 5-year DFS: 83.2, 77.3, and 75.9% vs. 75.1, 58.5, and 50.5%; P <0.001). Compared with Hangzhou criteria ( N =305), incorporating PIVKA-II into Hangzhou criteria (including tumor burden, α-fetoprotein, and histopathologic grade) increased the number of patients with eligibility for LT by 21.6% but achieved comparable DFS and overall survival. CONCLUSIONS: Incorporating PIVKA-II into existing LT criteria could increase the number of eligible HCC patients without compromising post-LT outcomes.

[Response to Primary Biliary Cholangitis Treatment: Influencing Factors and the Role in Prognosis Prediction].

Objective: To examine the influencing factors and prognostic features of poor response to ursodeoxycholic acid (UDCA) treatment in primary biliary cholangitis (PBC) patients with dyslipidemia. Methods: A retrospective study was conducted, covering 512 patients who had a confirmed diagnosis of PBC, and who received treatment at West China Hospital, Sichuan University between January 2009 and March 2022. According to their actual response to UDCA treatment, patients were divided into two groups, UDCA full-response group ( n=305) and UDCA non-responding group ( n=207). The data from the two groups were compared to predict the adverse factors influencing patient response and the area under the curve ( AUC) of the receiver operating characteristic (ROC) curve, identify the cut-off value of total cholesterol (TC), and analyze the differences in baseline laboratory test findings and the rate of responses to treatment. According to the TC cut-off value, patients were divided into a group with TC≥5.415 mmol/L and another group with TC<5.415 mmol/L. In addition, differences in the prognosis of the two groups were assessed by comparing the UK-PBC and GLOBE scores. Results: The baseline data, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), triglycerides (TG), TC, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were significantly increased in the UDCA non-responding group compared to those in the full-response group (all P<0.005), while the albumin level of the UDCA non-responding group was decreased compared to that of the full-response group ( P=0.012). Findings of multi-factor logistic regression analysis suggested that TC (odds ratio [ OR]=1.501, 95% confidence interval [ CI]: 1.275-1.767, P<0.01) and ALP ( OR=1.005, 95% CI: 1.003-1.006, P<0.01) were independent risk factors influencing patient response. The ROC curve analysis suggested worse prognosis for patients with TC≥5.415 mmol/L ( AUC: 0.727, 95% CI: 0.680-0.775, 63.8% sensitivity, 76.4% specificity). In addition, the UK-PBC risk score at 1 year of treatment was higher in the high-TC group (TC≥5.415 mmol/L) than that in the low-TC group (TC<5.415 mmol/L) ( P<0.05). Conclusions: Hypercholesterolemia is an independent risk factor for poor response to UDCA in PBC patients. When the baseline TC is equal to or higher than 5.415 mmol/L, PBC patients have a relatively poor response to UDCA and poor prognosis.

Licochalcone A induces cell cycle arrest and apoptosis via suppressing MAPK signaling pathway and the expression of FBXO5 in lung squamous cell cancer.

Lung squamous cell carcinoma (LSCC) is a highly heterogeneous malignancy with high mortality and few therapeutic options. Licochalcone A (LCA, PubChem ID: 5318998) is a chalcone extracted from licorice and possesses anticancer and anti­inflammatory activities. The present study aimed to elucidate the anticancer effect of LCA on LSCC and explore the conceivable molecular mechanism. MTT assay revealed that LCA significantly inhibited the proliferation of LSCC cells with less cytotoxicity towards human bronchial epithelial cells. 5­ethynyl­2'­deoxyuridine (EdU) assay demonstrated that LCA could reduce the proliferation rate of LSCC cells. The flow cytometric assays indicated that LCA increased the cell number of the G1 phase and induced the apoptosis of LSCC cells. LCA downregulated the protein expression of cyclin D1, cyclin E, CDK2 and CDK4. Meanwhile, LCA increased the expression level of Bax, cleaved poly(ADP­ribose)polymerase­1 (PARP1) and caspase 3, as well as downregulated the level of Bcl­2. Proteomics assay demonstrated that LCA exerted its antitumor effects via inhibiting mitogen­activated protein kinase (MAPK) signaling pathways and the expression of F­box protein 5 (FBXO5). Western blot analysis showed that LCA decreased the expression of p­ERK1/2, p­p38MAPK and FBXO5. In the xenograft tumors of LSCC, LCA significantly inhibited the volumes and weight of tumors in nude mice with little toxicity in vital organs. Therefore, the present study demonstrated that LCA effectively inhibited cell proliferation and induced apoptosis in vitro, and suppressed xenograft tumor growth in vivo. LCA may serve as a future therapeutic candidate of LSCC.

Tunable electrical properties and multiple-phases of ferromagnetic GdS2, GdSe2 and Janus GdSSe monolayers.

With the continuous miniaturization and integration of spintronic devices, the two-dimensional (2D) ferromagnet coupling of ferromagnetic and diverse electrical properties has become increasingly important. Herein, we report three ferromagnetic monolayers: GdS2, GdSe2 and Janus GdSSe. They are bipolar magnetic semiconductors and demonstrate ferroelasticity with a large reversible strain of 73.2%. Three monolayers all hold large magnetic moments of about 8µB f.u.-1 and large spin-flip energy gaps in both the conduction and valence bands, which are highly desirable for applications in bipolar field effect spin filters and spin valves. Our calculations have testified to the feasibility of the experimental achievement of the three monolayers and their stability. Additionally, intrinsic valley polarization occurs in the three monolayers owing to the cooperative interplay between spin-orbit coupling and magnetic exchange interaction. Moreover, we identified square lattices for GdS2 and GdSe2 monolayers. The new and stable square lattices of GdS2 and GdSe2 monolayers show robust ferromagnetism with high Curie temperatures of 648 and 312 K, respectively, and the characteristics of spin-gapless semiconductors. Overall, these findings render GdS2, GdSe2 and Janus GdSSe monolayers promising candidate materials for multifunctional spintronic devices at the nanoscale.

Neutrophil subsets in noncancer liver diseases: Cellular crosstalk and therapeutic targets.

Neutrophils are the most abundant circulating granulocytes, linking innate and adaptive immunity. Neutrophils can regulate inflammatory and immune responses through degranulation, reactive oxygen species generation, the production of cytokines and chemokines, and NETosis. Emerging evidence has indicated that neutrophils contribute to the pathogenesis of various noncancer liver diseases, including nonalcoholic fatty liver disease, alcohol-associated liver disease, hepatic ischemia-reperfusion injury, and liver fibrosis. Cellular interactions among neutrophils, other immune cells, and nonimmune cells constitute a complex network that regulates the immune microenvironment of the liver. This review summarizes novel neutrophil subtypes, including CD177+ neutrophils and low-density neutrophils. Moreover, we provide an overview of the cellular cros stalk of neutrophils in noncancer liver diseases, aiming to shed new light on mechanistic studies of novel neutrophil subtypes. In addition, we discuss the potential of neutrophils as therapeutic targets in noncancer liver diseases, including inhibitors targeting NETosis, granule proteins, and chemokines.

Stretchable, Adhesive, and Bioinspired Visual Electronic Skin with Strain/Temperature/Pressure Multimodal Non-Interference Sensing.

It is highly desirable to construct a single-multimodal sensor that could synchronously perceive multiple stimuli without interference. Here, we propose an adhesive multifunctional chromotropic electronic skin (MCES) that can respond to and distinguish three different stimuli of stain, temperature, and pressure within the two-terminal sensing unit. The mutually discriminating "three-in-one" device converts strain into capacitance and pressure into voltage signals for a tactile stimulus response and produces visual color changes against temperature. In this MCES system, the interdigital capacitor sensor shows high linearity (R2 = 0.998), and temperature sensing is realized via reversible multicolor switching bioinspired by the chameleon, showing attractive potential in visualization interaction. Notably, the energy-harvesting triboelectric nanogenerator in MCES can not only detect pressure incentive but also identify objective material species. Looking forward, these findings promise for multimodal sensor technology with reduced complexity and production costs that are highly anticipated in soft robotics, prosthetics, and human-machine interaction applications.

Hypothermic oxygenated perfusion attenuates DCD liver ischemia-reperfusion injury by activating the JAK2/STAT3/HAX1 pathway to regulate endoplasmic reticulum stress.

BACKGROUND: Hepatic ischemia-reperfusion injury (IRI) in donation after cardiac death (DCD) donors is a major determinant of transplantation success. Endoplasmic reticulum (ER) stress plays a key role in hepatic IRI, with potential involvement of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and the antiapoptotic protein hematopoietic-lineage substrate-1-associated protein X-1 (HAX1). In this study, we aimed to investigate the effects of hypothermic oxygenated perfusion (HOPE), an organ preservation modality, on ER stress and apoptosis during hepatic IRI in a DCD rat model. METHODS: To investigate whether HOPE could improve IRI in DCD livers, levels of different related proteins were examined by western blotting and quantitative real-time polymerase chain reaction. Further expression analyses, immunohistochemical analyses, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and transmission electron microscopy were conducted to analyze the effects of HOPE on ER stress and apoptosis. To clarify the role of the JAK2/STAT3 pathway and HAX1 in this process, AG490 inhibitor, JAX1 plasmid transfection, co-immunoprecipitation (CO-IP), and flow cytometry analyses were conducted. RESULTS: HOPE reduced liver injury and inflammation while alleviating ER stress and apoptosis in the DCD rat model. Mechanistically, HOPE inhibited unfolded protein responses by activating the JAK2/STAT3 pathway, thus reducing ER stress and apoptosis. Moreover, the activated JAK2/STAT3 pathway upregulated HAX1, promoting the interaction between HAX1 and SERCA2b to maintain ER calcium homeostasis. Upregulated HAX1 also modulated ER stress and apoptosis by inhibiting the inositol-requiring enzyme 1 (IRE1) pathway. CONCLUSIONS: JAK2/STAT3-mediated upregulation of HAX1 during HOPE alleviates hepatic ER stress and apoptosis, indicating the JAK2/STAT3/HAX1 pathway as a potential target for IRI management during DCD liver transplantation.

Treatment with imatinib was useful to delay the neointimal hyperplasia of aortocaval fistula in adenine-induced renal failure rats.

PURPOSE: The study was conducted to investigate the effect of the treatment with imatinib, a c-kit specific inhibitor, on the neointimal hyperplasia (NIH) of aortocaval fistula (ACF) in adenine-induced renal failure rats. MATERIALS AND METHODS: All rats were randomly assigned to 4 groups: rats were fed on a normal diet (normal group); rats were fed on a 0.75% adenine-rich diet (renal failure group). The remaining rats underwent ACF after receiving a 0.75% adenine-rich diet and received daily saline gavage (model group) or imatinib gavage (imatinib group) for 7 days after surgery. Immunohistochemical method was used to detect c-kit expression, and Elastomeric Verhoeff-Van Gieson (EVG) staining was used to observe morphological changes of the ACF. The Pearson correlation analysis was used to evaluate the correlations of c-kit expression with intimal thickness and the percentage of stenosis, respectively. RESULTS: The renal failure group showed positive c-kit expression on the intima of the inferior vena cava (IVC), whereas the normal group did not. Compared to the model group, intimal thickness (P = 0.001), the percentage of stenosis (P = 0.006) and c-kit expression (P = 0.04) were decreased in the imatinib group at 8 weeks postoperatively. C-kit expression was positively correlated with both intimal thickness and percentage of stenosis (intimal thickness: R = 0.650, P = 0.003; the percentage of stenosis: R = 0.581, P = 0.011) in both the model and imatinib groups. CONCLUSION: Treatment with imatinib, a c-kit specific inhibitor, was useful to delay the NIH of ACF in adenine-induced renal failure rats.