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Purpose: Interleukin (IL)-19 was expressed in invasive ductal carcinoma (IDC) of the breast tissue but not in healthy breast tissue. We explored the effects of IL-19 on the pathogenesis of breast cancer and its clinical outcome.Experimental Design: Tumor expression of IL-19 was assessed by immunohistochemistry and/or real-time quantitative PCR between two groups of patients with breast IDC (n = 60 and 143, respectively) with available clinical and survival data. We examined the effects of IL-19 on cytokine and chemokine production as well as proliferation and migration in breast cancer cells. Mice were injected with IL-19–overexpressing or vector control 67NR cells and the tumor growth and lung metastatic micronodules were measured.Results: Of the IDC specimens, high IL-19 expression was associated with advanced tumor stage, high tumor metastasis, and worse survival. In vitro, IL-19 induced transcripts of IL-1β, IL-6, TGF-β, matrix metalloproteinase (MMP)2, MMP9, and CXCR4 in 4T1 breast cancer cells; induced fibronectin expression and assembly; and promoted cancer cell proliferation and migration, which were inhibited by anti-IL-19 monoclonal antibody (mAb). Endogenous fibronectin expression and cancer cell migration were lower in IL-19 knockdown 4T1 cells. In 4T1 cells, hypoxia induced IL-19 and CXCR4 expression, which was inhibited by anti-IL-19 mAb. IL-19 overexpression in noninvasive 67NR cancer cells increased cell proliferation and migration. In vivo, mice injected with IL-19–overexpressing 67NR cell clones showed larger tumors and more metastatic micronodules in the lung.Conclusions: High IL-19 expression in breast cancer tissue is associated with a poor clinical outcome. IL-19 is pivotal in the pathogenesis of breast cancer. Clin Cancer Res; 18(3); 713–25. ©2011 AACR.

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Structural changes known as airway remodeling characterize chronic/severe asthma and contribute to lung dysfunction. We previously reported that neonatal SSEA-1+ pulmonary stem/progenitor cells (PSCs) ameliorated airway inflammation in asthmatic mice. However, the molecular mechanisms by which endogenous SSEA-1+ PSC of adult mice afford beneficial effects in alveolar homeostasis and lung repair after allergen challenge remain incompletely understood. To analyze the expression profile and clarify the biological significance of endogenous adult lung SSEA-1+ cells in asthmatic mice. Lung SSEA-1+ cells and circulating SSEA-1+ cells in peripheral blood were determined by confocal microscopy and cytometric analysis. GFP chimeric mice were used to trace cell lineage in vivo. The roles of circulating SSEA-1+ cells were verified in ovalbumin-induced and house dust mite-induced allergic asthmatic models. In asthmatic mice, endogenous lung SSEA-1+ cells almost disappeared; however, a unique population of circulating SSEA-1+ cells was enriched after the challenge phase. In asthmatic mice, adoptive transfer of circulating SSEA-1+ cells had a specific homing preference for the lung in response to inhaled antigen through upregulating CXCR7–CXCL11 chemokine axis. Circulating SSEA-1+ cells can transdifferentiate in the alveolar space and ameliorate lung inflammation and structural damage through inhibiting the infiltration of inflammatory cells into peribronchovascular and goblet cell hyperplasia areas, reducing the thickened smooth muscle layers and PAS-positive mucus-containing goblet cells. Reinforcing bone marrow-derived circulating SSEA-1+ cells from peripheral blood into lung tissue which create a rescue mechanism in maintaining alveolar homeostasis and tissue repair to mediate lung protection for emergency responses after allergen challenge in asthmatic conditions.

In this paper, an elastic poly(vinylidenefluoride-co-trifluoroethylene) piezoelectric yarn for the application of a muscle patch sensor is presented. The electrospinning method is used to fabricate the piezoelectric yarn, and different parameters were used to control the orientation and structure of piezoelectric fibers. We further develop a post-alignment process to reorganize the orientation of fibers and to reshape fiber microstructures. Two unique microstructures of piezoelectric fibers that have an excellent elastic performance were identified. This piezoelectric yarn is composed of skewed and crimped fibers that align along the elongation direction, and it can be cyclically stretched up to 65% strain with good linearity, durability, and repeatability. Its mechanical behavior is superior to randomly distributed and fully straightened piezoelectric fibers, and it is suitable for long-term use of larger strain sensing. Our study demonstrated that this piezoelectric yarn can be stretched for more than 12 h under a repeated 1 Hz cyclic deformation. Using this elastic piezoelectric yarn, a muscle patch sensor that can be attached to the skin over human muscles for real-time monitoring is developed. The concentric, eccentric, and isometric contractions of biceps and triceps can be measured simultaneously to study their contraction behaviors. To further verify whether this patch sensor can be used under intense exercise conditions, the contraction behavior of a soleus muscle during stationary jumping and running is monitored to demonstrate sensor performance. Finally, this patch sensor is sewed onto a chest band, and it is verified that both breathing movement and heartbeat can be monitored.

Pancreatic ductal adenocarcinoma (PDAC) and cancer-associated cachexia (CAC) are multifactorial and characterized by dysregulated inflammatory networks. Whether the proinflammatory cytokine IL-20 is involved in the complex networks of PDAC and CAC remains unclear. Here, we report that elevated IL-20 levels in tumor tissue correlate with poor overall survival in 72 patients with PDAC. In vivo, we establish a transgenic mouse model (KPC) and an orthotopic PDAC model and examine the therapeutic efficacy of an anti-IL-20 monoclonal antibody (7E). Targeting IL-20 not only prolongs survival and attenuates PD-L1 expression in both murine models but also inhibits tumor growth and mitigates M2-like polarization in the orthotopic PDAC model. Combination treatment with 7E and an anti-PD-1 antibody shows better efficacy in inhibiting tumor growth than either treatment alone in the orthotopic PDAC model. Finally, 7E mitigates cachexic symptoms in CAC models. Together, we conclude IL-20 is a critical mediator in PDAC progression., The pro-inflammatory cytokine IL-20 promotes tumor growth in several cancer types. Here, the authors show that high levels of IL-20 are associated with poor survival in patients with pancreatic ductal adenocarcinoma (PDAC) and that IL-20 blockade reduces tumor growth and alleviates cachexia symptoms in mouse models of PDAC.

In this article, we present a new method to control the direction of traveling waves in either an x-direction or y-direction on a two-dimensional square plate. The core structure was composed of a piezoelectric serial bimorph with four electrodes. Each electrode was spatially designed to activate one of the bending modes and which included the ability to reduce adjacent modes and minimize interference. Our new method differs from other reported methods in that the four electrodes were driven at designated resonant frequencies. In our wave generator, different driving amplitudes and phases were applied to induce the traveling waves to propagate in a specific direction. To design the directional movement and to better understand the pattern of induced traveling waves, an analytical solution was derived to assist in the design of the four driving electrodes. Using our newly developed analytical method, traveling waves can be controlled to travel in either the x-direction or y-direction using two different sets of electrodes, where each electrode can be driven at a specific but different bending mode. We found that both the voltage ratio and phase difference between the two driving electrodes are important factors for optimization.

Background Spinal cord injury (SCI) causes devastating neurological consequences, which can result in partial or total paralysis. Irreversible neurological deficits and glial scar formation are characteristic of SCI. Inflammatory responses are a major component of secondary injury and play a central role in regulating the pathogenesis of SCI. IL-20 is a proinflammatory cytokine involved in renal fibrosis and liver cirrhosis through its role in upregulating TGF-β1 production. However, the role of IL-20 in SCI remains unclear. We hypothesize that IL-20 is upregulated after SCI and is involved in regulating the neuroinflammatory response. Methods The expression of IL-20 and its receptors was examined in SCI rats. The regulatory roles of IL-20 in astrocytes and neuron cells were examined. The therapeutic effects of anti-IL-20 monoclonal antibody (mAb) 7E in SCI rats were evaluated. Results Immunofluorescence staining showed that IL-20 and its receptors were expressed in astrocytes, oligodendrocytes, and microglia in the spinal cord after SCI in rats. In vitro, IL-20 enhanced astrocyte reactivation and cell migration in human astrocyte (HA) cells by upregulating glial fibrillary acidic protein (GFAP), TGF-β1, TNF-α, MCP-1, and IL-6 expression. IL-20 inhibited cell proliferation and nerve growth factor (NGF)-derived neurite outgrowth in PC-12 cells through Sema3A/NRP-1 upregulation. In vivo, treating SCI rats with anti-IL-20 mAb 7E remarkably inhibited the inflammatory responses. 7E treatment not only improved motor and sensory functions but also improved spinal cord tissue preservation and reduced glial scar formation in SCI rats. Conclusions IL-20 might regulate astrocyte reactivation and axonal regeneration and result in the secondary injury in SCI. These findings demonstrated that IL-20 may be a promising target for SCI treatment.

The role of immune mediators, including proinflammatory cytokines in chemotherapy-induced peripheral neuropathy (CIPN), remains unclear. Here, we studied the contribution of interleukin-20 (IL-20) to the development of paclitaxel-induced peripheral neuropathy. Increased serum levels of IL-20 in cancer patients with chemotherapy were accompanied by increased CIPN risk. In mouse models, proinflammatory IL-20 levels in serum and dorsal root ganglia fluctuated with paclitaxel treatment. Blocking IL-20 with the neutralizing antibody or genetic deletion of its receptors prevented CIPN, alleviated peripheral nerve damage, and dampened inflammatory responses, including macrophage infiltration and cytokine release. Mechanistically, paclitaxel upregulated IL-20 through dysregulated Ca homeostasis, which augmented chemotherapy-induced neurotoxicity. Importantly, IL-20 suppression did not alter paclitaxel efficacy on cancer treatment both in vitro and in vivo. Together, targeting IL-20 ameliorates paclitaxel-induced peripheral neuropathy by suppressing neuroinflammation and restoring Ca homeostasis. Therefore, the anti-IL-20 monoclonal antibody is a promising therapeutic for the prevention and treatment of paclitaxel-induced neuropathy.

Structural changes known as airway remodeling characterize chronic/severe asthma and contribute to lung dysfunction. We previously reported that neonatal SSEA-1

Baseflow is among the most important components of streamflow. It is the main source of streamflow from groundwater systems in the dry season and also plays an important role as a water resource in the ecological environment and for human activities. In recent years, because of climate change, the number of dry season days in Taiwan has increased, and the wet season has been delayed, resulting in fewer rainy days and increased precipitation intensity. In addition, the spatial distribution of rainfall is uneven, and rivers are short and fast-flowing. Taiwan has become a country with abundant rainfall but insufficient water resources; therefore, the assessment of baseflow is important. This study selected eight basins with distinct wet and dry seasons in southern Taiwan as the study area. The baseflow characteristics and their relationships with climate features were assessed using time series analysis, baseflow attribution analysis, and wavelet analysis. The results showed that baseflow has an increasing trend; both precipitation and evapotranspiration have a significant positive correlation with baseflow, and the impact of precipitation is greater than that of evaporation. Sensitivity analysis showed that baseflow increases with increasing evaporation and precipitation; this behavior is related to the concentration of precipitation and evaporation in the wet season. Baseflow attribution analysis showed that the contribution of climate change to baseflow (75.0%) was larger than that of human activities (−2.9%), indicating that climate change was the main factor in the increase in baseflow. Wavelet analysis showed that both the El Niño–Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) are correlated with baseflow, where the PDO is more strongly correlated than the ENSO. The main timescales of the ENSO and PDO are a 4–8-year band and an 8-year band, respectively. The ENSO may have a timescale above the 8-year band, and the PDO exhibits periodic correlation changes at a 1-year band.

Producción Científica, The relentless scaling of semiconductor devices pushes the doping level far above the equilibrium solubility, yet the doped material must be sufficiently stable for subsequent device fabrication and operation. For example, in epitaxial silicon doped above the solubility of phosphorus, most phosphorus dopants are compensated by vacancies, and some of the phosphorus-vacancy clusters can become mobile around 700 °C to further cluster with isolated phosphorus ions. For efficient and stable doping, we use microwave annealing to selectively activate metastable phosphorus-vacancy clusters by interacting with their dipole moments, while keeping lattice heating below 700 °C. In a 30-nm-thick Si nanosheet doped with 3 × 1021 cm−3 phosphorus, a microwave power of 12 kW at 2.45 GHz for 6 min resulted in a free-electron concentration of 4 × 1020 cm−3 and a junction more abrupt than 4 decades/nm. The doping profile is stable with less than 4% variation upon thermal annealing around 700 °C for 5 min. Thus, microwave annealing can result in not only efficient activation and abrupt profile in epitaxial silicon but also thermal stability. In comparison, conventional rapid thermal annealing can generate a junction as abrupt as microwave annealing but 25% higher sheet resistance and six times higher instability at 700 °C., Supplemental material: Efficient and stable activation by microwave annealing of nanosheet silicon doped with phosphorus above its solubility limit, Ministry of Science and Technology of Taiwan (Contract MOST 109-2628-M-008-004-MY3)

The mediation of the extracellular matrix is one of the major environmental cues to direct cell migration, such as stiffness-dependent durotaxis and adhesiveness-dependent haptotaxis. In this study, we explore another possible contact guidance: roughness dependent topotaxis. Different from previously reported studies on topotaxis that use standard photolithography to create micron or submicron structures that have identical height and different spatial densities, we develop a new method to programmatically fabricate substrates with different patterns of surface roughness using two-photon polymerization. Surface roughness ranging from 0.29 to 1.11 μm can be created by controlling the voxel distance between adjacently cured ellipsoid voxels. Patterned Ormocomp® masters are transferred to polypropylene films using the nanoimprinting method for cell migration study. Our experimental results suggest that MG63 cells can sense the spatial distribution of their underlying extracellar roughness and modulate their migration velocity and direction. Three characteristic behaviors were identified. First, cells have a higher migration velocity on substrates with higher roughness. Second, cells preferred to migrate from regions of higher roughness to lower roughness, and their migration velocity also decreased with descending roughness. Third, the migration velocity remained unchanged on the lower roughness range on a graded substrate with a steeper roughness. The last cell migration characteristic suggests the steepness of the roughness gradient can be another environmental cue in addition to surface roughness. Finally, the combination of two-photon polymerization and nanoimprint methods could become a new fabrication methodology to create better 3D intricate structures for exploring topotactic cell migrations.

Obesity and its associated complications are global public health concerns. Metabolic disturbances and immune dysregulation cause adipose tissue stress and dysfunction in obese individuals. Immune cell accumulation in the adipose microenvironment is the main cause of insulin resistance and metabolic dysfunction. Infiltrated immune cells, adipocytes, and stromal cells are all involved in the production of proinflammatory cytokines and chemokines in adipose tissues and affect systemic homeostasis. Interferons (IFNs) are a large family of pleiotropic cytokines that play a pivotal role in host antiviral defenses. IFNs are critical immune modulators in response to pathogens, dead cells, and several inflammation-mediated diseases. Several studies have indicated that IFNs are involved in the pathogenesis of obesity. In this review, we discuss the roles of IFN family cytokines in the development of obesity-induced inflammation and insulin resistance.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology that can affect nearly every organ system in the body. Besides genetic and environmental factors, unbalanced pro-inflammatory and anti-inflammatory cytokines contribute to immune dysregulation, trigger an inflammatory response, and induce tissue and organ damage. Inflammatory responses in SLE can be promoted and/or maintained by the availability of cytokines that are overproduced systemically and/or in local tissues. Several key cytokines have been considered potential targets for the reduction of chronic inflammation in SLE. Recent studies indicated that dysregulated production of several cytokines, including those of the IL-1 family and IL-10 family, orchestrate immune activation and self-tolerance, play critical roles in the pathogenesis of SLE. Among IL-1 family cytokines, IL-1, IL-18, IL-33, IL-36, IL-37, and IL-38 had been the most thoroughly investigated in SLE. Additionally, IL-10 family cytokines, IL-10, IL-20, IL-22, IL-26, IL-28, and IL-29 are dysregulated in SLE. Therefore, a better understanding of the initiation and progression of SLE may provide suitable novel targets for therapeutic intervention. In this review, we discuss the involvement of inflammation in the pathogenesis of SLE, with a focus on IL-1 family and IL-10 family cytokines, and highlight pathophysiological approaches and therapeutic potential for treating SLE.

IL-20 is a proinflammatory cytokine of the IL-10 family and involved in several diseases. However, the regulatory role of IL-20 in obesity is not well understood. We explored the function of IL-20 in the pathogenesis of obesity-induced insulin resistance by ELISA, western blotting, and flow cytometry. The therapeutic potential of IL-20 monoclonal antibody 7E for ameliorating diet-induced obesity was analyzed in murine models. Higher serum IL-20 levels were detected in obese patients. It was upregulated in leptin-deficient (ob/ob), leptin-resistant (db/db), and high-fat diet (HFD)-induced murine obesity models. In vitro, IL-20 regulated the adipocyte differentiation and the polarization of bone marrow-derived macrophages into proinflammatory M1 type. It also caused inflammation and macrophage retention in adipose tissues by upregulating TNF-α, monocyte chemotactic protein-1 (MCP-1), netrin-1, and unc5b (netrin receptor) expression in macrophages, and netrin-1, leptin, and MCP-1 in adipocytes. IL-20 promoted insulin resistance by inhibiting glucose uptake in mature adipocytes through the SOCS-3 pathway. In HFD-induced obesity in mice, 7E treatment reduced body weight, and improved glucose tolerance and insulin sensitivity; it also reduced local inflammation and the number of M1-like macrophages in adipose tissues. We have identified a critical role of IL-20 in obesity-induced inflammation and insulin resistance, and we conclude that IL-20 may be a novel target for treating obesity and insulin resistance in patients with metabolic disorders.

In this paper, a cardiac-and-piezoelectric hybrid system is developed for drug screening. The core structure is a polyvinylidene-fluoride piezoelectric membrane that serves as a flexible structure to interact with hiPSC cardiomyocytes and that measures the contraction profile of cardiomyocytes. This design enables the capability of electrically monitoring cardiomyocytes without the aid of an optical system. To guide cardiomyocytes aligning on this circular piezoelectric membrane, concentric rings of polydimethylsiloxane microgrooves are bonded to its surface. Experimental results demonstrate that seeded cardiomyocytes can align and elongate along the circular microgrooves to form a concentric pattern. To promote cardiomyocyte maturation, bipolar stimulation is conducted using a pin and a ring electrode made of a 304 stainless steel sheet. Furthermore, to maintain body temperature and minimize environmental noise, a 304 stainless steel box is constructed to enclose the cardiac-and-piezoelectric hybrid platform. It serves as an incubator and is electrically grounded for electromagnetic interference shielding. Using this system, continuous and repeated contractions of cardiomyocytes can be developed and monitored electrically. The system performance is verified using two commercial drugs: isoproterenol and metoprolol. It is experimentally demonstrated that this system can monitor the dosage effect of both drugs. Our results also show that the measured EC50 and IC50 values of contraction frequency and amplitude are in the same range. These findings suggest that both drugs can influence the beat frequency and contraction force simultaneously. In summary, taking advantage of the electro-mechanical coupling effect of the piezoelectric membrane, this system could be scaled up to perform automatic and parallel screenings for drug discoveries.

Thermoplastic polymers are the primary materials for fabricating commercial microfluidic devices. Despite many excellent properties, the low thermal conductivity is a common limiting factor in speeding up temperature-dependent biological processes, particularly for polymerase chain reactions. There is a need to develop a fabrication process to create thin-film microfluidic devices that can have a small thermal mass and a short microchannel-to-surface distance. This type of device requires the depth of micropatterns to be very close to the film thickness, which can encounter serious fractures during the demolding process. To overcome this challenge, we develop a soft hot embossing process to create micropatterns in a 188 µm thick cyclo-olefin polymeric (COP) film with a high embossing-depth to film-thickness ratio. The advantage of using a soft master is it can easily be peeled off from the molded film without causing a fracture from micropatterns. Polydimethylsiloxane (PDMS) is used as the soft silicone master, and four different 110 µm high micropatterns are studied, including ribs, grooves, and circular columns and cavities. PDMS masters for creating a 110 µm deep microchannel with different arrays of 70 µm deep microwells are also investigated. The heights of these one-layer and two-layer PDMS masters are 58.8% and 95.7% of the film thickness. Experimental findings show that less than 3% height variation can be achieved using a single-layer PDMS master with a low aspect ratio. For the two-layer micropatterns, it was found that a dense array with a smaller gap between microwells can have a better pattern transfer. In summary, this study demonstrates the feasibility of using a soft master to create deep or tall micropatterns in a COP film. The possibility of using a soft hot embossing process to create micropatterns for thin-film microfluidic devices is verified.

In this study, we establish a population-based human induced pluripotent stem cell (hiPSC) drug screening platform for toxicity assessment. After recruiting 1,000 healthy donors and screening for high-frequency human leukocyte antigen (HLA) haplotypes, we identify 13 HLA-homozygous "super donors" to represent the population. These "super donors" are also expected to represent at least 477,611,135 of the global population. By differentiating these representative hiPSCs into cardiomyocytes and neurons we show their utility in a high-throughput toxicity screen. To validate hit compounds, we demonstrate dose-dependent toxicity of the hit compounds and assess functional modulation. We also show reproducible in vivo drug toxicity results using mouse models with select hit compounds. This study shows the feasibility of using a population-based hiPSC drug screening platform to assess cytotoxicity, which can be used as an innovative tool to study inter-population differences in drug toxicity and adverse drug reactions in drug discovery applications.

In this study, we present a new driving method to generate traveling waves in a finite plate for application to piezoelectric motors. Due to resonant modes which dominate the vibration of finite structures, methods to reduce resonant effects such as using an electric sinker or driving at a non-resonant frequency have been reported. To take advantage of natural resonance and to increase driving efficiency, a new method entitled gated two-frequency-two-mode (G-TFTM) was developed. A piezoelectric bimorph of 1.1 g weight with two rectangular actuators was implemented to verify the design concept. One actuator was operated at a first bending mode and the other actuator operated at a second bending mode with a phase difference. The driving signal was gated to generate an intermittent excitation to provide the periodic propulsion. To determine the profile of the induced traveling wave, an analytical solution was derived and a numerical model was used. Using these design tools, we experimentally verified that traveling waves can be generated using a G-TFTM method. A 0.1-g object can be moved at a speed of 3.31 mm/s under the condition of a 70-to-20 voltage ratio and a 137 deg phase difference. The moving direction was found to be reversed by changing the phase to −43 deg. The experimental and numerical data are detailed in this paper to demonstrate the feasibility of this G-TFTM method.

Objectives: Combining domain knowledge and machine learning, we developed a screening tool using the smallest number of bio-features and self-reported symptoms to predict obstructive sleep apnea. Methods: This study analyzed data on 30 self-reported symptoms plus 24 clinical features collected from 3,447 patients who received polysomnography in one regional hospital and one medical center during 2011-2018. We compared the area under the Receiver Operating Characteristic curve among three prediction modules: multivariate logistic regression model, support vector machine, and neural network method. In addition, the odds ratio was also evaluated by gender and age group. Results: We found AUROC consistently increased by 0.01-0.10 after adding the item of self-reported snoring. Besides, the performance of 4-items (gender, age, body mass index, snoring) was similar to those of adding two more items (neck and waist circumference) for the prediction of moderate to severe OSA (Apnea Hypopnea Index ≥15) in all three prediction models, indicating the significance of domain knowledge. The AUROC of the 4-item test set were 0.83, 0.84, and 0.83 for MLR, SVM, and NN, respectively. Further analysis indicated participants with BMI ≥25 and frequent snoring were at higher risk of moderate to severe OSA. Conclusions: The module of OSA developed in this study indicated overweight and frequent snoring as suitable criteria for early detection of OSA by primary care physicians.

Background Interleukin-24 (IL-24) binds to two kinds of receptor complexes, namely IL-20R1/IL-20R2 and IL-20R2/IL-22R1, which are also bound by IL-20. IL-20 plays a detrimental role in liver fibrosis. Due to the sharing of receptor complexes, we aimed to determine whether IL-24 also participates in liver fibrosis. Methods Clinical biopsy specimens from various stages of liver fibrosis were used to analyze IL-24 expression. IL-24 protein was administered to mice with thioacetamide (TAA)-induced liver injury. The direct effects of IL-24 on mouse primary hepatocytes or hepatic stellate cells (HSCs) were analyzed. Wild-type, IL-20R1-, and IL20R2-deficient mice were used to establish a model of acute TAA-induced liver injury. Findings Among patients with more severe liver fibrosis, there was a reduced IL-24/IL-20 ratio. Administration of IL-24 protein protected mice from TAA-induced liver injury and reduction of liver inflammation by antioxidant effects. IL-24 protected hepatocytes from TAA-induced apoptosis and prevented liver fibrosis through the inhibition of the HSCs activation. The protective role of IL-24 acted on liver cells were mainly IL-20R1-independent. IL-20R2-deficient mice exhibited more severe liver injury upon TAA treatment, thus confirming the protective role of IL-24. Interpretation IL-24 plays a key protective role in the progression of liver injury and has therapeutic potential for treating liver injuries. Funding This work was supported by the Ministry of Science and Technology of Taiwan (MOST 106–2320-B-006–024) and Taiwan Liver Disease Prevention & Treatment Research Foundation.