Loss Of Regeneration Research Articles

The evolutionary loss of cardiac regeneration – Is endothermy the interfering factor?

The evolutionary loss of cardiac regeneration – Is endothermy the interfering factor?

Four-Objective Optimization of an Irreversible Stirling Heat Engine with Linear Phenomenological Heat-Transfer Law.

This paper combines the mechanical efficiency theory and finite time thermodynamic theory to perform optimization on an irreversible Stirling heat-engine cycle, in which heat transfer between working fluid and heat reservoir obeys linear phenomenological heat-transfer law. There are mechanical losses, as well as heat leakage, thermal resistance, and regeneration loss. We treated temperature ratio of working fluid and volume compression ratio as optimization variables, and used the NSGA-II algorithm to carry out multi-objective optimization on four optimization objectives, namely, dimensionless shaft power output , braking thermal efficiency , dimensionless efficient power and dimensionless power density . The optimal solutions of four-, three-, two-, and single-objective optimizations are reached by selecting the minimum deviation indexes with the three decision-making strategies, namely, TOPSIS, LINMAP, and Shannon Entropy. The optimization results show that the reached by TOPSIS and LINMAP strategies are both 0.1683 and better than the Shannon Entropy strategy for four-objective optimization, while the s reached for single-objective optimizations at maximum , , , and conditions are 0.1978, 0.8624, 0.3319, and 0.3032, which are all bigger than 0.1683. This indicates that multi-objective optimization results are better when choosing appropriate decision-making strategies.

Macrophage-mediated PDGF Activation Correlates With Regenerative Outcomes Following Musculoskeletal Trauma.

Our objective was to identify macrophage subpopulations and gene signatures associated with regenerative or fibrotic healing across different musculoskeletal injury types. Subpopulations of macrophages are hypothesized to fine tune the immune response after damage, promoting either normal regenerative, or aberrant fibrotic healing. Mouse single-cell RNA sequencing data before and after injury were assembled from models of musculoskeletal injury, including regenerative and fibrotic mouse volumetric muscle loss (VML), regenerative digit tip amputation, and fibrotic heterotopic ossification. R packages Harmony , MacSpectrum , and Seurat were used for data integration, analysis, and visualizations. There was a substantial overlap between macrophages from the regenerative VML (2mm injury) and regenerative bone models, as well as a separate overlap between the fibrotic VML (3mm injury) and fibrotic bone (heterotopic ossification) models. We identified 2 fibrotic-like (FL 1 and FL 2) along with 3 regenerative-like (RL 1, RL 2, and RL 3) subpopulations of macrophages, each of which was transcriptionally distinct. We found that regenerative and fibrotic conditions had similar compositions of proinflammatory and anti-inflammatory macrophages, suggesting that macrophage polarization state did not correlate with healing outcomes. Receptor/ligand analysis of macrophage-to-mesenchymal progenitor cell crosstalk showed enhanced transforming growth factor β in fibrotic conditions and enhanced platelet-derived growth factor signaling in regenerative conditions. Characterization of macrophage subtypes could be used to predict fibrotic responses following injury and provide a therapeutic target to tune the healing microenvironment towards more regenerative conditions.

Experiment and characterization of dynamic thermal storage characteristics of porous media thermal storage system

The aim is to understand the thermal storage characteristics of porous media thermal storage materials under thermal dynamic conditions, and obtain the dynamic thermal storage characteristics parameters of thermal storage materials. In the 120 kW thermal dynamic thermal storage system of porous media, we studied the dynamic thermal storage characteristics of honeycomb porous ceramic thermal storage materials with different pore diameters (2.9, 4, 5.5 mm) and lengths (100–400 mm) under different hot flue gas conditions include thermal storage rate, thermal storage efficiency and storage. The results show that the relationship between the heat storage rate and time is parabolic, and the heat storage efficiency gradually decreases with the heat storage time. At the same time, the regenerative rate and unit regenerative resistance loss increase with the increase of specific surface area or the decrease of pore diameter of regenerator, and the regenerative efficiency increases with the increase of regenerator length. According to the experimental research and analysis, the dynamic heat storage characteristics of porous regenerator can be characterized by heat storage rate, heat storage efficiency and unit heat storage resistance loss.

Cellular senescence: a key therapeutic target in aging and diseases.

Cellular senescence is a hallmark of aging defined by stable exit from the cell cycle in response to cellular damage and stress. Senescent cells (SnCs) can develop a characteristic pathogenic senescence-associated secretory phenotype (SASP) that drives secondary senescence and disrupts tissue homeostasis, resulting in loss of tissue repair and regeneration. The use of transgenic mouse models in which SnCs can be genetically ablated has established a key role for SnCs in driving aging and age-related disease. Importantly, senotherapeutics have been developed to pharmacologically eliminate SnCs, termed senolytics, or suppress the SASP and other markers of senescence, termed senomorphics. Based on extensive preclinical studies as well as small clinical trials demonstrating the benefits of senotherapeutics, multiple clinical trials are under way. This Review discusses the role of SnCs in aging and age-related diseases, strategies to target SnCs, approaches to discover and develop senotherapeutics, and preclinical and clinical advances of senolytics.

Multi-objective optimization of Stirling heat engine with various heat and mechanical losses

The finite time thermodynamics is used to perform the thermodynamic analysis of the Stirling heat engine in this paper, and the multi-objective optimization of the heat engine cycle is carried out by Non-dominated Sorting Genetic Algorithm II (NSGA-II). In addition to various heat transfer losses (thermal resistance, regeneration loss and heat leakage), there are also mechanical losses in the cycle. The temperature ratio (x) and volume compression ratio (λ) are taken as the optimization variables, the multi-objective optimization is carried out for four objectives of cycle dimensionless shaft power, braking thermal efficiency, dimensionless efficient power and dimensionless ecological function, and effects of the two variables on the characteristics of the four optimization objectives are analyzed. Three decision-making methods, Linear Programming Techniques for Multidimensional Analysis of Preference (LINMAP), Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) and Shannon Entropy, are used to compare and analyze the optimization results of different combinations of optimization objective. The results show that the deviation indexes of quadru-objective optimization are smaller than those of single-objective optimization results, and it means that comparing with the single-objective optimization, multi-objective optimization can make better balance the four objective functions.

99. Aging Associated Loss of Vegfa Impairs Muscle Regeneration

Purpose: Global populations, particularly in developed countries, have continued to age. Notably, aging is intimately correlated with frailty, a parameter that has been previously demonstrated to correlate significantly with mortality and concomitantly correlate with loss of muscle mass. The molecular mechanisms behind aging associated impaired skeletal muscle regeneration remain incompletely understood. Our group previously demonstrated aging-associated loss of hypoxia signaling impairs skeletal muscle myogenic potential. Given these findings, we hypothesized vascular endothelial growth factor (VEGFA), a potent downstream signal well characterized in nascent vascular ingrowth and muscle progenitor differentiation, to critically regulate regeneration in young and aged skeletal muscle. Methods: Young C57BL/6 mice (12-14 weeks old) and old C57BL/6 mice (24-25 months old) were subjected to a previously validated model of muscle cryoinjury (n=5-6/group) to induce regeneration. The tibialis anterior muscle was injured using direct contact with a metal probe cooled in dry ice. Quantifications of cross sectional area (CSA) of myofibers were performed across 10 photos/sample by blinded reviewer via ImageJ. Western blots were performed from whole TA muscle lysates for quantification of VEGFA with GAPDH for normalization. To evaluate the role of VEGF in muscle regeneration, we performed a similar and separate series of experiments using VEGFlo (Jackson Labs Stock No. 027315) mice, which exhibit a systemic, 75% decrease in VEGFA activity, and littermate controls. In addition, ML228, a hypoxia signaling activator known to increase VEGFA levels, was injected into both young and old mice, as well as VEGFlo and littermate controls, to determine whether VEGFA augmentation promotes muscle regeneration in aging. Results: Old mice demonstrated markedly impaired ability of regenerating myofiber CSA on days post injury (DPI) 5 in comparison to young mice (Young vs. Old: 526 vs. 373µm2, p<.001) and DPI 10 (Y v. O: 1250 vs. 833µm2, p<.001). VEGFA protein levels were markedly reduced in the gastrocnemius of old mice in comparison to young. Similarly, VEGFlo mice exhibited significantly smaller CSA of regenerating fibers as compared to littermate controls (WT vs. lo: 541 vs. 238µm2, p=.0011). Pharmacologic augmentation of VEGFA, using ML228, improved skeletal muscle regeneration in both old mice and VEGFlo mice. (WT vs. lo: CSA 757 vs. 662µm2, p=.387). Conclusions: Muscle regeneration declines with with aging, in a fashion correlated to loss of VEGFA levels within skeletal muscle. Systemic loss of VEGFA is further correlated with poor muscle regeneration in genetically modified mice. Furthermore, exogenous activation of hypoxic signaling/VEGFA reverses this reduced capacity for muscle regeneration in old and VEGFlo mice. Supplementation of VEGFA could represent a therapeutic target in aging patients with skeletal muscle loss.

Twist2-driven chromatin remodeling governs the postnatal maturation of dermal fibroblasts.

Dermal fibroblasts lose stem cell potency after birth, which prevents regenerative healing. However, the underlying intracellular mechanisms are largely unknown. We uncover the postnatal maturation of papillary fibroblasts (PFs) driven by the extensive Twist2-mediated remodeling of chromatin accessibility. A loss of the regenerative ability of postnatal PFs occurs with decreased H3K27ac levels. Single-cell transcriptomics, assay for transposase-accessible chromatin sequencing (ATAC-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) reveal the postnatal maturation trajectory associated with the loss of the regenerative trajectory in PFs, which is characterized by a marked decrease in chromatin accessibility and H3K27ac modifications. Histone deacetylase inhibition delays spontaneous chromatin remodeling, thus maintaining the regenerative ability of postnatal PFs. Genomic analysis identifies Twist2 as a major regulator within chromatin regions with decreased accessibility during the postnatal period. When Twist2 is genetically deleted in dermal fibroblasts, the intracellular cascade of postnatal maturation is significantly delayed. Our findings reveal the comprehensive intracellular mechanisms underlying intrinsic postnatal changes in dermal fibroblasts.

A thermal-coupled/gas-coupled hybrid high-frequency pulse tube cryocooler attaining the liquid-helium temperature

High-frequency pulse tube cryocooler (HPTC) has become an attractive method for space cooling in the liquid-helium temperature range, due to its advantages of potential high efficiency, no moving parts at the cold end, small size, and light weight. However, key problems such as large regenerator losses and insufficient phase-shifting ability challenge it to obtain the liquid-helium temperature. A thermal-coupled/gas-coupled hybrid refrigeration process of HPTC has been designed to obtain the liquid-helium temperature. One HPTC working in the liquid-nitrogen temperature range is used as a pre-cooling stage, and another two-stage gas-coupled structure is employed to obtain liquid-helium temperature. The simulation results show that the lowest no-load temperature is 3.6 K and a cooling power of 84 mW can be provided at 6 K with a total input PV power of 128 W and 10.9 W/77 K pre-cooling power when Helium-4 is chosen as the working gas. An experimental prototype was designed, built, and tested. The simulation and experiment results will be introduced in detail in this paper.

Thermodynamic analysis and optimization of a novel hybrid system using thermoacoustic cycle to harvest waste heat of high temperature PEMFC

The high temperature proton exchange membrane fuel cell (HTPEMFC) shows multiple advantages over the traditional PEMFC. To achieve the waste heat effective utilization of the fuel cell, a novel hybrid system mainly including a HTPEMFC and a thermo-acoustic cycle (TAC) is proposed. By considering the major irreversible losses, such as ohmic, concentration and activation losses, regenerative loss, heat transfer loss between the HTPEMFC and the TAC, and heat leak loss from the HTPEMFC to the environment, the expressions for the output power and energy efficiency of the proposed system are obtained. Based on typical conditions, the maximum power density for the proposed system increases by 33.3% compared with a single HTPEMFC system, and the corresponding energy efficiency also improves by 34.5%. The sensitive analysis is represented, and coupling a TAC unite to recover the HTPEMFC waste heat shows significant advantages by comparing with other available HTPEMFC-based hybrid systems. Finally, the proposed system is optimized using ideal point method based on the multi-objective optimization. The optimal power density is 6147.8 W m−2, and the optimal efficiency is 53.9%. This work proves the feasibility of the HTPEMFC-TAC system, and hints the broad prospect of low-grade heat collections through a TAC.

An Up-To-Date Overview of Dental Tissue Regeneration Using Dental Origin Mesenchymal Stem Cells: Challenges and Road Ahead.

Stem cells (SCs) research has experienced exponential growth in recent years. SC-based treatments can enhance the lives of people suffering from cardiac ischemia, Alzheimer’s disease, and regenerative drug conditions, like bone or loss of teeth. Numerous kinds of progenitor/SCs have been hypothesized to depend on their potential to regain and/or heal wounded tissue and partly recover organ function. Growing data suggest that SCs (SCs) are concentrated in functions and that particular tissues have more SCs. Dental tissues, in particular, are considered a significant cause of mesenchymal stem cells (MSCs) cells appropriate for tissue regeneration uses. Tissue regeneration and SCs biology have particular attention in dentistry because they may give a novel method for creating clinical material and/or tissue redevelopment. Dental pulp, dental papilla, periodontal ligament, and dental follicle contain mesenchymal SCs. Such SCs, which must be identified and cultivated in specific tissue culture environments, may be used in tissue engineering applications such as tooth tissue, nerve regeneration, and bone redevelopment. A new cause of SCs, induced pluripotent SCs, was successfully made from human somatic cells, enabling the generation of the patient and disease-specific SCs. The dental SC’s (DSCs) multipotency, rapid proliferation rate, and accessibility make it an ideal basis of MSC for tissue redevelopment. This article discusses current advances in tooth SC investigation and its possible application in tissue redevelopment.

Immunohistochemistry indicates that persistent inflammation determines failure of tail, limb and finger regeneration in the Lizard Podarcis muralis

BackgroundThe presence of white blood inflammatory cells in injured tissues and their effect on the process of organ regeneration in lizards has been assessed on tail, limb and digits. MethodsThe present immunohistochemical survey analyzes the occurrence of CD68-labeled cells in lizard organs uncapable of regenerating tissues that exhibit strong inflammatory activity. ResultsThis marker mainly identifies macrophages and mast cells present in large number within tissues of injured limbs and digits. Also a high inflammation is associated with amputated tails that do not regenerate, derived from cauterization or infection of tissues of the tail stump. In the healing limbs and fingers at 12–20 days post-amputation, numerous CD68-labeled cells, most likely macrophages, are seen among superficial connective tissues and injured muscles and bones. These cells likely stimulate and give rise to scarring tissues and no regeneration of limb and fingers occurs. In the cauterized or in the infected tail stump a strong accumulation of CD68-positive mast cells and macrophages is observed, where they likely evoke epidermal coagulation, formation of scarring connective tissue, and loss of regeneration. ConclusionsThe present observations provide further cytological evidence that support the notion that a strong and lasting inflammatory condition impedes organ regeneration in specifically lizards and, more generally other vertebrates as well.

In vivo overexpression of frataxin causes toxicity mediated by iron-sulfur cluster deficiency

Friedreich's ataxia is a rare disorder resulting from deficiency of frataxin, a mitochondrial protein implicated in the synthesis of iron-sulfur clusters. Preclinical studies in mice have shown that gene therapy is a promising approach to treat individuals with Friedreich's ataxia. However, a recent report provided evidence that AAVrh10-mediated overexpression of frataxin could lead to cardiotoxicity associated with mitochondrial dysfunction. While evaluating an AAV9-based frataxin gene therapy using a chicken β-actin promoter, we showed that toxic overexpression of frataxin could be reached in mouse liver and heart with doses between 1 × 1013 and 1 × 1014 vg/kg. In a mouse model of cardiac disease, these doses only corrected cardiac dysfunction partially and transiently and led to adverse findings associated with iron-sulfur cluster deficiency in liver. We demonstrated that toxicity required frataxin's primary function by using a frataxin construct bearing the N146K mutation, which impairs binding to the iron-sulfur cluster core complex. At the lowest tested dose, we observed moderate liver toxicity that was accompanied by progressive loss of transgene expression and liver regeneration. Together, our data provide insights into the toxicity of frataxin overexpression that should be considered in the development of a gene therapy approach for Friedreich's ataxia.

Why Has the Ability to Regenerate Following CNS Injury Been Repeatedly Lost Over the Course of Evolution?

While many vertebrates can regenerate both damaged neurons and severed axons in the central nervous system (CNS) following injury, others, including all birds and mammals, have lost this ability for reasons that are still unclear. The repeated evolutionary loss of regenerative competence seems counterintuitive, and any explanation must account for the fact that regenerative competence is lost in both cold-blooded and all warm-blooded clades, that both injury-induced neurogenesis and axonal regeneration tend to be lost in tandem, and that mammals have evolved dedicated gene regulatory networks to inhibit injury-induced glia-to-neuron reprogramming. Here, different hypotheses that have been proposed to account for evolutionary loss of regenerative competence are discussed in the light of new insights obtained into molecular mechanisms that control regeneration in the central nervous system. These include pleiotropic effects of continuous growth, enhanced thyroid hormone signaling, prevention of neoplasia, and improved memory consolidation. Recent evidence suggests that the most compelling hypothesis, however, may be selection for greater resistance to the spread of intra-CNS infections, which has led to both enhanced reactive gliosis and a loss of injury-induced neurogenesis and axonal regeneration. Means of testing these hypotheses, and additional data that are urgently needed to better understand the evolutionary pressures and mechanisms driving loss of regenerative competence, are also discussed.

Hydrodynamic and Heat Transfer Characteristics of Miniature Stirling Cryocooler Regenerators — A Review

Miniature Stirling coolers are preferred to provide cryogenic cooling for infra-red (IR) sensors used for communication, military, and space applications. They provide 0.25–1.5[Formula: see text]W of cooling effect at 60–80[Formula: see text]K. Miniature Stirling coolers used for space applications are time tested, reliable, and have the maximum COP compared to other types of coolers. Helium is used as the working fluid because of its low boiling point, high thermal conductivity, high ratio of specific heat, and inert gas properties. A regenerator is the primary heat exchanger in the system, which periodically exchanges heat with the cold and hot gases passing through the regenerator material. The effectiveness of the regenerator is the most important parameter influencing the cooling effect produced by the system. For the optimum performance of the cryocooler, the regenerator should have maximum heat transfer area, minimum void volume, minimum pressure drop, large heat capacity ratio between the matrix material and gas, and minimum longitudinal conduction. Since some of these requirements are conflicting in nature, the design of the regenerator becomes a challenge in the overall design of the cooler. A state-of-the-art review of regenerator materials, designs, and operation is presented in this study. The different sources of regenerator losses and the issues related to regenerator design and optimization are discussed in detail. Results of various experimental and numerical investigations conducted on a Stirling regenerator are discussed and the recent developments in material selection and design are highlighted.

Fluorescent spectroscopic assessment before and after radiation treatment in oral cavity cancer and its clinical correlation.

Biochemical changes in irradiated malignant tissue lead to altered autofluorophores status which should be different for cancerous tissue (residual/recurrence) and irradiated normal tissue. If this irradiated tissue is examined through fluorescent spectroscopy, we can find the spectroscopic changes occurring after the completion of treatment which can be helpful in evaluating treatment response. Punch biopsy sample was examined through fluorescent spectroscopy in oral cavity cancer patients before and after definitive radiation treatment. The change in spectroscopic pattern before and after radiation treatment was recorded and assessed. Final analysis was done in 36 samples. In irradiated tissue, it has been observed that there was increase in the intensity of collagen fluorescence. It was found that the Half width half maximum (HWHM) is more in case of preirradiated sample. The decrease in the HWHM in case of irradiated sample shows the decrease in the number of cells (cell density as compared to that in preirradiated sample). These spectral findings are well-explained pathophysiologically and clinically as amount of collagen are increased in irradiated tissues due to loss of cancerous cells and regeneration of collagen cross-links (fibrosis) and reproduction of normal tissue as a response to radiation treatment. After thorough study in a large number of samples, we may be able in the future to grade the alteration in fluorescence of collagen obtained after radiation treatment in terms of complete, partial, or no response.

Yap Promotes Noncanonical Wnt Signals From Cardiomyocytes for Heart Regeneration.

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Establishment of a murine model of acute-on-chronic liver failure with multi-organ dysfunction

Acute-on-chronic liver failure (ACLF) is a distinct clinical entity with high probability of organ failure and mortality. Since patients generally present late, experimental models are needed to understand the pathophysiology and natural course of the disease. To reproduce the syndrome of ACLF, chronic liver disease was induced in C57BL6 mice (6-8weeks; approximately 20-24g weight) by intraperitoneal administration of carbon tetrachloride (CCl4) for 10weeks followed by an acute injury with acetaminophen (APAP) and lipopolysaccharide (LPS). Blood, ascitic fluid, and organs were collected to study cell death, regeneration, and fibrosis. At 24h post-APAP/LPS infusion, the liver tissue showed increased hepatocyte ballooning and endothelial cell TUNEL positivity. This was followed by progressive hepatocyte necrosis from perivascular region at day 7 to lobular region by day 11. ACLF (day 7 and day 11) animals showed increase in bilirubin (p < 0.05), prothrombin time (p < 0.0001), blood ammonia (p < 0.001), and portal pressure post-acute hepatocellular injury similar to human ACLF. Ascites was noticed by day 11 with median serum-ascites albumin gradient of 1.2 (1.1-1.3)g/dL. In comparison to cirrhosis, ACLF group (day 7 and day 11) showed significant decrease in Sirius red (p ≤ 0.0001), collagen1 (p < 0.0001), and a-SMA proportionate area (p < 0.0001) with loss of hepatocytes regeneration (p < 0.005). At day 11, ACLF animals also showed significant increase in serum creatinine (p < 0.05) and acute tubular necrosis suggestive of organ failure, compared to cirrhotic animals. The CCL4/APAP/LPS (CALPS) model of ACLF mimics the clinical, biochemical, and histological features of ACLF with demonstrable progressive hepatocellular necrosis, liver failure, impaired regeneration, development of portal hypertension, and organ dysfunction in an animal with chronic liver disease.

Robotic living donor hepatectomy: Is it the future?

Donor liver hepatectomy has always been associated with significant risks and complications affect up to 1/3 of patients. The vast majority are related to large incisions, severe postoperative pain, lung atelectasis, extensive intrabdominal adhesions as well as intraoperative blood loss and biliary injuries. The advent of robotic surgery can improve outcomes through minimally invasive approaches and use of superb technological instruments, but its use for donor hepatectomy is still in infancy. This review summarises its current state and challenges. Review of published literature. Robotic liver surgery offers significant advantages: small access wounds, stable magnified 3-D intraabdominal views, multidimensional instrument articulation. For liver donor resection this allows close individual biliary and vascular dissection, improved haemostasis by ligating vascular pedicles precisely, parenchymal transection facilitated by better views and reduced blood loss. Even in the challenging right donor hepatectomy, a fourth robotic arm allows for identification of accessory veins and venous reconstruction if necessary. Published studies show longer operative time for the robotic population but comparable intraoperative blood loss and similar incidence of early allograft dysfunction, vascular complications (hepatic artery thrombosis, portal vein thrombosis or stenosis), and 1-year liver regeneration and liver function tests. Robotic hepatectomy has the potential to revolutionize living donor liver surgery and to minimize major complications and their associated morbidity. However it is still limited to few highly expert centers and requires extensive operative experience in robotic and liver resections. As exposure to minimally invasive techniques grows, it could become the mainstay of practice in the next decade.

Loss of hepatocyte identity following aberrant YAP activation: A key mechanism in alcoholic hepatitis

Alcoholic hepatitis (AH) is a life-threatening disease with limited therapeutic options, as the molecular mechanisms leading to death are not well understood. This study evaluates the Hippo/Yes-associated protein (YAP) pathway which has been shown to play a role in liver regeneration. The Hippo/YAP pathway was dissected in explants of patients transplanted for AH or alcohol-related cirrhosis and in control livers, using RNA-seq, real-time PCR, western blot, immunohistochemistry and transcriptome analysis after laser microdissection. We transfected primary human hepatocytes with constitutively active YAP (YAPS127A) and treated HepaRG cells and primary hepatocytes isolated from AH livers with a YAP inhibitor. We also used mouse models of ethanol exposure (Lieber de Carli) and liver regeneration (carbon tetrachloride) after hepatocyte transduction of YAPS127A. In AH samples, RNA-seq analysis and immunohistochemistry of total liver and microdissected hepatocytes revealed marked downregulation of the Hippo pathway, demonstrated by lower levels of active MST1 kinase and abnormal activation of YAP in hepatocytes. Overactivation of YAP in hepatocytes invitro and invivo led to biliary differentiation and loss of key biological functions such as regeneration capacity. Conversely, a YAP inhibitor restored the mature hepatocyte phenotype in abnormal hepatocytes taken from patients with AH. In ethanol-fed mice, YAP activation using YAPS127A resulted in a loss of hepatocyte differentiation. Hepatocyte proliferation was hampered by YAPS127A after carbon tetrachloride intoxication. Aberrant activation of YAP plays an important role in hepatocyte transdifferentiation in AH, through a loss of hepatocyte identity and impaired regeneration. Thus, targeting YAP is a promising strategy for the treatment of patients with AH. Alcoholic hepatitis is characterized by inflammation and a life-threatening alteration of liver regeneration, although the mechanisms behind this have not been identified. Herein, we show that liver samples from patients with alcoholic hepatitis are characterized by profound deregulation of the Hippo/YAP pathway with uncontrolled activation of YAP in hepatocytes. We used human cell and mouse models to show that inhibition of YAP reverts this hepatocyte defect and could be a novel therapeutic strategy for alcoholic hepatitis.