Four Generations of Volcano Plots for the Oxygen Evolution Reaction: Beyond Proton-Coupled Electron Transfer Steps?

ConspectusDue to its importance for electrolyzers or metal-air batteries for energy conversion or storage, there is huge interest in the development of high-performance materials for the oxygen evolution reaction (OER). Theoretical investigations have aided the search for active material motifs through the construction of volcano plots for the kinetically sluggish OER, which involves the transfer of four proton-electron pairs to form a single oxygen molecule. The theory-driven volcano approach has gained unprecedented popularity in the catalysis and energy communities, largely due to its simplicity, as adsorption free energies can be used to approximate the electrocatalytic activity by heuristic descriptors.In the last two decades, the binding-energy-based volcano method has witnessed a renaissance with special concepts being developed to incorporate missing factors into the analysis. To this end, this Account summarizes and discusses the different generations of volcano plots for the example of the OER. While first-generation methods relied on the assessment of the thermodynamic information for the OER reaction intermediates by means of scaling relations, the second and third generations developed strategies to include overpotential and kinetic effects into the analysis of activity trends. Finally, the fourth generation of volcano approaches allowed the incorporation of various mechanistic pathways into the volcano methodology, thus paving the path toward data- and mechanistic-driven volcano plots in electrocatalysis.Although the concept of volcano plots has been significantly expanded in recent years, further research activities are discussed by challenging one of the main paradigms of the volcano concept. To date, the evaluation of activity trends relies on the assumption of proton-coupled electron transfer steps (CPET), even though there is experimental evidence of sequential proton-electron transfer (SPET) steps. While the computational assessment of SPET for solid-state electrodes is ambitious, it is strongly suggested to comprehend their importance in energy conversion and storage processes, including the OER. This can be achieved by knowledge transfer from homogeneous to heterogeneous electrocatalysis and by focusing on the material class of single-atom catalysts in which the active center is well defined. The derived concept of how to analyze the importance of SPET for mechanistic pathways in the OER over solid-state electrodes could further shape our understanding of the proton-electron transfer steps at electrified solid/liquid interfaces, which is crucial for further progress toward sustainable energy and climate neutrality.

Bepridil is potent against SARS-CoV-2 in vitro.

Guided by a computational docking analysis, about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). Of these small molecules tested, six displayed a concentration that inhibits response by 50% (IC50) value below 100 µM in inhibiting Mpro, and, importantly, three, that is, pimozide, ebastine, and bepridil, are basic molecules that potentiate dual functions by both raising endosomal pH to interfere with SARS-CoV-2 entry into the human cell host and inhibiting Mpro in infected cells. A live virus-based modified microneutralization assay revealed that bepridil possesses significant anti-SARS-CoV-2 activity in both Vero E6 and A459/ACE2 cells in a dose-dependent manner with low micromolar effective concentration, 50% (EC50) values. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.

Associations between disordered eating, internalizing symptoms, and behavioral and neural correlates of response inhibition in preadolescence.

Response inhibition difficulties are reported in individuals with eating disorders (EDs), anxiety, and depression. Although ED symptoms and internalizing symptoms co-occur in preadolescence, there is limited research examining associations between these symptoms and response inhibition in this age group. This study is the first to investigate the associations between behavioral and neural markers of response inhibition, disordered eating (DE), and internalizing symptoms in a community sample of preadolescents. Forty-eight children (M age = 10.95 years, 56.3% male) completed a Go/NoGo task, whereas electroencephalography was recorded. Self-report measures of DE and internalizing symptoms were collected. Higher levels of anxiety and depression were associated with neural markers of suboptimal response inhibition (attenuated P3NoGo amplitudes) in preadolescence. In contrast, higher levels of depression were associated with greater response inhibition at a behavioral level. These findings suggest internalizing symptoms in preadolescence are associated with P3-indexed difficulties in evaluation and monitoring, but these are not sufficient to disrupt behavioral performance on a response inhibition task. This pattern may reflect engagement of compensatory processes to support task performance. DE was not significantly associated with response inhibition, suggesting that difficulties in response inhibition may only be reliably observed in more chronic and severe DE and ED presentations.

Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal.

In the spinal cord, the central canal forms through a poorly understood process termed dorsal collapse that involves attrition and remodelling of pseudostratified ventricular layer (VL) cells. Here, we use mouse and chick models to show that dorsal ventricular layer (dVL) cells adjacent to dorsal midline Nestin(+) radial glia (dmNes+RG) down-regulate apical polarity proteins, including Crumbs2 (CRB2) and delaminate in a stepwise manner; live imaging shows that as one cell delaminates, the next cell ratchets up, the dmNes+RG endfoot ratchets down, and the process repeats. We show that dmNes+RG secrete a factor that promotes loss of cell polarity and delamination. This activity is mimicked by a secreted variant of Crumbs2 (CRB2S) which is specifically expressed by dmNes+RG. In cultured MDCK cells, CRB2S associates with apical membranes and decreases cell cohesion. Analysis of Crb2F/F/Nestin-Cre+/- mice, and targeted reduction of Crb2/CRB2S in slice cultures reveal essential roles for transmembrane CRB2 (CRB2TM) and CRB2S on VL cells and dmNes+RG, respectively. We propose a model in which a CRB2S-CRB2TM interaction promotes the progressive attrition of the dVL without loss of overall VL integrity. This novel mechanism may operate more widely to promote orderly progenitor delamination.

A doxorubicin-peptide-gold nanoparticle conjugate as a functionalized drug delivery system: exploring the limits.

Efficient transport of pharmaceuticals to malignant cells in the human body often requires the application of drug-delivery systems (DDSs) consisting of several building blocks, each of them bearing a specific function. While nanoparticles are promising as potential carrier moieties, biomolecules may add to the efficient delivery by binding several drug molecules simultaneously. In this contribution, we apply a combination of atomistic molecular dynamics simulations and density functional theory calculations to characterize a multi-component DDS for the transport of the anthracycline antibiotic doxorubicin (DOX), comprising a gold nanoparticle (NP) and a drug-binding peptide (DBP) grafted on the NP surface. We have shown previously that the DDS can stabilize one DOX per DBP. However, by increasing the drug load to a 2 : 1 DOX : DBP ratio the two drug molecules compete for the available adsorption sites, which may cause spontaneous dissociation of one DOX molecule. We identify the chain length of the DBP as a limiting factor for the drug-loading capacity and provide important guidelines for further optimization of multi-component functionalized DDSs.

Cooling Effects Occur in Hepatic Microwave Ablation At Low Vascular Flow Rates and in Close Proximity to Liver Vessels - Ex Vivo.

Background. The impact of vascular cooling effects in hepatic microwave ablation (MWA) is controversially discussed. The objective of this study was a systematic assessment of vascular cooling effects in hepatic MWA ex vivo. Methods. Microwave ablations were performed in fresh porcine liver ex vivo with a temperature-controlled MWA generator (902-928 MHz) and a non-cooled 14-G-antenna. Energy input was set to 9.0 kJ. Hepatic vessels were simulated by glass tubes. Three different vessel diameters (3.0, 5.0, 8.0 mm) and vessel to antenna distances (5, 10, 20 mm) were examined. Vessels were perfused with saline solution at nine different flow rates (0-500 mL/min). Vascular cooling effects were assessed at the largest cross-sectional ablation area. A quantitative and semi-quantitative/morphologic analysis was carried out. Results. 228 ablations were performed. Vascular cooling effects were observed at close (5 mm) and medium (10 mm) antenna to vessel distances (P < .05). Vascular cooling effects occurred around vessels with flow rates ≥1.0 mL/min (P < .05) and a vessel diameter ≥3 mm (P < .05). Higher flow rates did not result in more distinct cooling effects (P > .05). No cooling effects were measured at large (20 mm) antenna to vessel distances (P > .05). Conclusion. Vascular cooling effects occur in hepatic MWA and should be considered in treatment planning. The vascular cooling effect was mainly affected by antenna to vessel distance. Vessel diameter and vascular flow rate played a minor role in vascular cooling effects.

Disordered eating behaviours and basic psychological need satisfaction: the mediating role of anxiety symptoms in preadolescents.

Objective: According to self-determination theory, satisfied basic psychological needs can be a protective factor for psychopathology, including eating disorders and anxiety symptomatology. However, most research has focused on adolescent and adult populations, with less work examining perceived basic psychological need satisfaction from parents in younger samples who report anxiety and disordered eating. This cross-sectional study aimed to investigate whether basic psychological need satisfaction from parents was associated with disordered eating in preadolescents and whether anxiety mediated this relation.Method: A total of 211 preadolescents were recruited from primary schools across south Wales (mean age = 10.27 years, age range = 9-11 years; 49.3% female). Children completed self-report questionnaires on their basic psychological need satisfaction when with parents, as well as disordered eating and anxiety symptoms.Results: It was found that higher needs satisfaction was associated with lower disordered eating and anxiety, with stronger relations found in girls compared with boys. Furthermore, anxiety was found to mediate this relationship.Conclusions: Results suggest that basic psychological needs satisfaction may play an important role in the early emergence of co-occurring disordered eating and anxiety symptoms in boys and girls. The importance of considering anxiety symptoms in future work investigating needs satisfaction in the context of disordered eating and eating disorders is discussed.

Advanced X-ray polarimeter design for nuclear resonant scattering.

This work presents the improvements in the design and testing of polarimeters based on channel-cut crystals for nuclear resonant scattering experiments at the 14.4 keV resonance of 57Fe. By using four asymmetric reflections at asymmetry angles of α1 = -28°, α2 = 28°, α3 = -28° and α4 = 28°, the degree of polarization purity could be improved to 2.2 × 10-9. For users, an advanced polarimeter without beam offset is now available at beamline P01 of the storage ring PETRA III.

Risk factors for upper and lower type prolonged postoperative ileus following surgery for Crohn's disease.

PURPOSE: Prolonged postoperative ileus (PPOI) is common after bowel resections, especially in Crohn's disease (CD). The pathophysiology of PPOI is not fully understood. PPOI could affect only the upper or lower gastrointestinal (GI) tract. The aim of this study was to assess risk factors for diverse types of PPOI, particularly to differentiate PPOI of upper and lower GI tract. METHODS: A retrospective analysis of 163 patients with CD undergoing ileocecal resection from 2015 to 2020 in a single center was performed. PPOI of the upper GI tract was predefined as the presence of vomiting or use of nasogastric tube longer than the third postoperative day. Lower PPOI was predefined as the absence of defecation for more than three days. Independent risk factors were identified by multivariable logistic regression analysis. RESULTS: Overall incidence of PPOI was 42.7%. PPOI of the upper GI tract was observed in 30.7% and lower PPOI in 20.9% of patients. Independent risk factors for upper PPOI included older age, surgery by a resident surgeon, hand-sewn anastomosis, prolonged opioid analgesia, and reoperation, while for lower PPOI included BMI ≤ 25 kg/m2, preoperative anemia, and absence of ileostomy. CONCLUSION: This study identified different risk factors for upper and lower PPOI after ileocecal resection in patients with CD. A differentiated upper/lower type approach should be considered in future research and clinical practice. High-risk patients for each type of PPOI should be closely monitored, and modifiable risk factors, such as preoperative anemia and opioids, should be avoided if possible.

Periportal fields cause stronger cooling effects than veins in hepatic microwave ablation: an in vivo porcine study.

BACKGROUND: Vascular cooling effects are a well-known source for tumor recurrence in thermal in situ ablation techniques for hepatic malignancies. Microwave ablation (MWA) is an ablation technique to be considered in the treatment of malignant liver tumors. The impact of vascular cooling in MWA is still controversial. PURPOSE: To evaluate the influence of different intrahepatic vessel types, vessel sizes, and vessel-to-antenna-distances on MWA geometry in vivo. MATERIAL AND METHODS: Five MWAs (902-928 MHz) were performed with an energy input of 24.0 kJ in three porcine livers in vivo. MWA lesions were cut into 2-mm slices. The minimum and maximum radius of the ablation area was measured for each slice. Distances were measured from ablation center toward all adjacent hepatic vessels with a diameter of ≥1 mm and within a perimeter of 20 mm around the antenna. The respective vascular cooling effect relative to the maximum ablation radius was calculated. RESULTS: In total, 707 vessels (489 veins, 218 portal fields) were detected; 370 (76%) hepatic veins and 185 (85%) portal fields caused a cooling effect. Portal fields resulted in higher cooling effects (37%) than hepatic veins (26%, P < 0.01). No cooling effect could be observed in close proximity of vessels within the central ablation zone. CONCLUSION: Hepatic vessels influenced MWA zones and caused a distinct cooling effect. Portal fields resulted in more pronounced cooling effect than hepatic veins. No cooling effect was observed around vessels situated within the central white zone.

CT-based quantification of short-term tissue shrinkage following hepatic microwave ablation in an in vivo porcine liver model.

BACKGROUND: Microwave ablation (MWA) is a minimally invasive treatment option for solid tumors and belongs to the local ablative therapeutic techniques, based on thermal tissue coagulation. So far there are mainly ex vivo studies that describe tissue shrinkage during MWA. PURPOSE: To characterize short-term volume changes of the ablated zone following hepatic MWA in an in vivo porcine liver model using contrast-enhanced computer tomography (CECT). MATERIAL AND METHODS: We performed multiple hepatic MWA with constant energy parameters in healthy, narcotized and laparotomized domestic pigs. The volumes of the ablated areas were calculated from venous phase CT scans, immediately after the ablation and in short-term courses of up to 2 h after MWA. RESULTS: In total, 19 thermally ablated areas in 10 porcine livers could be analyzed (n = 6 with two volume measurements during the measurement period and n = 13 with three measurements). Both groups showed a statistically significant but heterogeneous volume reduction of up to 12% (median 6%) of the ablated zones in CECT scans during the measurement period (P < 0.001 [n = 13] and P = 0.042 [n = 6]). However, the dimension and dynamics of volume changes were heterogenous both absolutely and relatively. CONCLUSION: We observed a significant short-term volume reduction of ablated liver tissue in vivo. This volume shrinkage must be considered in clinical practice for technically successful tumor treatment by MWA and therefore it should be further investigated in in vivo studies.

Healing of rectal advancement flaps for anal fistulas in patients with and without Crohn's disease: a retrospective cohort analysis.

BACKGROUND: Surgical closure of anal fistulas with rectal advancement flaps is an established standard method, but it has a high degree of healing failure in some cases. The aim of this study was to identify risk factors for anal fistula healing failure after advancement flap placement between patients with cryptoglandular fistulas and patients with Crohn's disease (CD). METHODS: From January 2010 to October 2020, 155 rectal advancement flaps (CD patients = 55, non-CD patients = 100) were performed. Patients were entered into a prospective database, and healing rates were retrospectively analysed. RESULTS: The median follow-up period was 189 days (95% CI: 109-269). The overall complication rate was 5.8%. The total healing rate for all rectal advancement flaps was 56%. CD patients were younger (33 vs. 43 years, p < 0.001), more often female (76% vs. 30%, p < 0.001), were administered more immunosuppressant medication (65% vs. 5%, p < 0.001), and had more rectovaginal fistulas (29% vs. 8%, p = 0.001) and more protective stomas (49% vs. 2%, p < 0.001) than patients without CD. However, no difference in healing rate was noted between patients with or without CD (47% vs. 60%, p = 0.088). CONCLUSIONS: Patients with anal fistulas with and without Crohn's disease exhibit the same healing rate. Although patients with CD display different patient-specific characteristics, no independent factors for the occurrence of anal fistula healing failure could be determined. Trial registration Not applicable due to the retrospective study design.

A 3D Renal Proximal Tubule on Chip Model Phenocopies Lowe Syndrome and Dent II Disease Tubulopathy.

Lowe syndrome and Dent II disease are X-linked monogenetic diseases characterised by a renal reabsorption defect in the proximal tubules and caused by mutations in the OCRL gene, which codes for an inositol-5-phosphatase. The life expectancy of patients suffering from Lowe syndrome is largely reduced because of the development of chronic kidney disease and related complications. There is a need for physiological human in vitro models for Lowe syndrome/Dent II disease to study the underpinning disease mechanisms and to identify and characterise potential drugs and drug targets. Here, we describe a proximal tubule organ on chip model combining a 3D tubule architecture with fluid flow shear stress that phenocopies hallmarks of Lowe syndrome/Dent II disease. We demonstrate the high suitability of our in vitro model for drug target validation. Furthermore, using this model, we demonstrate that proximal tubule cells lacking OCRL expression upregulate markers typical for epithelial-mesenchymal transition (EMT), including the transcription factor SNAI2/Slug, and show increased collagen expression and deposition, which potentially contributes to interstitial fibrosis and disease progression as observed in Lowe syndrome and Dent II disease.

Design criteria for the competing chlorine and oxygen evolution reactions: avoid the OCl adsorbate to enhance chlorine selectivity.

The formation of gaseous chlorine within chlor-alkali electrolysis is accompanied by a selectivity problem, as the evolution of gaseous oxygen constitutes a detrimental side reaction in the same potential range. As such, the development of electrode materials with high selectivity toward the chlorine evolution reaction is of particular importance to the chemical industry. Insight into the elementary reaction steps is ultimately required to comprehend chlorine selectivity on a molecular level. Commonly, linear scaling relationships are analyzed by the construction of a volcano plot, using the binding energy of oxygen, ΔEO, as a descriptor in the analysis. The present article reinvestigates the selectivity problem of the competing chlorine and oxygen evolution reactions by applying a different strategy compared to previous literature studies. On the one hand, a unifying material-screening framework that, besides binding energies, also includes the applied overpotential, kinetics, and the electrochemical-step symmetry index is used to comprehend trends in this selectivity issue for transition-metal oxide-based electrodes. On the other hand, the free-energy difference between the adsorbed oxygen and adsorbed hydroxide, ΔG2, rather than ΔEO is used as a descriptor in the analysis. It is demonstrated that the formation of the OCl adsorbate within the chlorine evolution reaction inherently limits chlorine selectivity, whereas, in the optimum case, the formation of the Cl intermediate can result in significantly higher chlorine selectivity. This finding is used to derive the design criteria for highly selective chlorine evolution electrocatalysts, which can be used in the future to search for potential electrode compositions by material-screening techniques.

Immediate post-interventional contrast-enhanced computed tomography overestimates hepatic microwave ablation - an in vivo animal study.

Objectives: Contrast-enhanced computed tomography (CECT) is used to monitor technical success immediately after hepatic microwave ablation (MWA). However, it remains unclear, if CECT shows the exact extend of the thermal destruction zone, or if tissue changes such as peri-lesionary edema are depicted as well. The objective of this study was to correlate immediate post-interventional CECT with histological and macroscopic findings in hepatic MWA in porcine liver in vivo.Methods: Eleven MWA were performed in porcine liver in vivo with a microwave generator (928 MHz; energy input 24 kJ). CECT was performed post-interventionally. Livers were explanted and ablations were bisected immediately after ablation. Samples were histologically analyzed after vital staining (NADH-diaphorase). Ablation zones were histologically and macroscopically outlined. We correlated histologic findings, macroscopic images and CECT.Results: Three ablation zones were identified in histological and macroscopic findings. Only one ablation zone could be depicted in CECT. Close conformity was observed between histological and macroscopic findings. The ablation zone depicted in CECT overestimated the histological avital central zone and inner red zone (p < = .01). No differences were found between CECT and the histological outer red zone (p > .05).Conclusions: Immediate post-interventional CECT overestimated the clinically relevant zone of complete cell ablation after MWA in porcine liver in vivo. This entails the risk of incomplete tumor ablation and could lead to tumor recurrence.

Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells.

Intestinal organoids have emerged as the new paradigm for modelling the healthy and diseased intestine with patient-relevant properties. In this study, we show directed differentiation of induced pluripotent stem cells towards intestinal-like phenotype within a microfluidic device. iPSCs are cultured against a gel in microfluidic chips of the OrganoPlate, in which they undergo stepwise differentiation. Cells form a tubular structure, lose their stem cell markers and start expressing mature intestinal markers, including markers for Paneth cells, enterocytes and neuroendocrine cells. Tubes develop barrier properties as confirmed by transepithelial electrical resistance (TEER). Lastly, we show that tubules respond to pro-inflammatory cytokine triggers. The whole procedure for differentiation lasts 14 days, making it an efficient process to make patient-specific organoid tubules. We anticipate the usage of the platform for disease modelling and drug candidate screening.

Does a Thermoneutral Electrocatalyst Correspond to the Apex of a Volcano Plot for a Simple Two-Electron Process?

Volcano analyses have been established as a standard tool in the field of electrocatalysis for assessing the performance of electrodes in a class of materials. The apex of the volcano curve, where the most active electrocatalysts are situated, is commonly defined by a hypothetical ideal material that binds its reaction intermediates thermoneutrally at zero overpotential, in accordance with Sabatier's principle. However, recent studies report a right shift of the apex in a volcano curve, in which the most active electrocatalysts bind their reaction intermediates endergonically rather than thermoneutrally at zero overpotential. Focusing on two-electron process, this Viewpoint addresses the question of how the definition of an optimum catalyst needs to be modified with respect to the requirements of Sabatier's principle when kinetic effects and the applied overpotential are included in the analysis.

Influence of Nanopillar Arrays on Fibroblast Motility, Adhesion, and Migration Mechanisms.

Surfaces decorated with high aspect ratio nanostructures are a promising tool to study cellular processes and design novel devices to control cellular behavior. However, little is known about the dynamics of cellular phenomenon such as adhesion, spreading, and migration on such surfaces. In particular, how these are influenced by the surface properties. In this work, fibroblast behavior is investigated on regular arrays of 1 µm high polymer nanopillars with varying pillar to pillar distance. Embryonic mouse fibroblasts (NIH-3T3) spread on all arrays, and on contact with the substrate engulf nanopillars independently of the array pitch. As the cells start to spread, different behavior is observed. On dense arrays which have a pitch equal or below 1 µm, cells are suspended on top of the nanopillars, making only sporadic contact with the glass support. Cells stay attached to the glass support and fully engulf nanopillars during spreading and migration on the sparse arrays which have a pitch of 2 µm and above. These alternate states have a profound effect on cell migration rates. Dynamic F-actin puncta colocalize with nanopillars during cell spreading and migration. Strong membrane association with engulfed nanopillars might explain the reduced migration rates on sparse arrays.

Comparison of different 4D CT-Perfusion algorithms to visualize lesions after microwave ablation in an in vivo porcine model.

Background: Accurate lesion visualization after microwave ablation (MWA) remains a challenge. Computed tomography perfusion (CTP) has been proposed to improve visualization, but it was shown that different perfusion-models delivered different results on the same data set.Purpose: Comparison of different perfusion algorithms and identification of the algorithm enables for the best imaging of lesion after hepatic MWA.Materials and methods: 10 MWA with consecutive CTP were performed in healthy pigs. Parameter-maps were generated using a single-input-dual-compartment-model with Patlak's algorithm (PM), a dual-input-maximum-slope-model (DIMS), a dual-input-one-compartment-model (DIOC), a single-(SIDC) and dual-input-deconvolution-model (DIDC). Parameter-maps for hepatic arterial (AF) and portal venous blood flow (PF), mean transit time, hepatic blood volume (HBV) and capillary permeability were compared regarding the values of the normal liver tissue (NLT), lesion, contrast- and signal-to-noise ratios (SNR, CNR) and inter- and intrarater-reliability using the intraclass correlation coefficient, Bland-Altman plots and linear regression.Results: Perfusion values differed between algorithms with especially large fluctuations for the DIOC. A reliable differentiation of lesion margin appears feasible with parameter-maps of PF and HBV for most algorithms, except for the DIOC due to large fluctuations in PF. All algorithms allowed for a demarcation of the central necrotic zone based on hepatic AF and HBV. The DIDC showed the highest CNR and the best inter- and intrarater reliability.Conclusion: The DIDC appears to be the most feasible model to visualize margins and necrosis zones after microwave ablation, but due to high computational demand, a single input deconvolution algorithm might be preferable in clinical practice.

Development of a Gut-On-A-Chip Model for High Throughput Disease Modeling and Drug Discovery.

A common bottleneck in any drug development process is finding sufficiently accurate models that capture key aspects of disease development and progression. Conventional drug screening models often rely on simple 2D culture systems that fail to recapitulate the complexity of the organ situation. In this study, we show the application of a robust high throughput 3D gut-on-a-chip model for investigating hallmarks of inflammatory bowel disease (IBD). Using the OrganoPlate platform, we subjected enterocyte-like cells to an immune-relevant inflammatory trigger in order to recapitulate key events of IBD and to further investigate the suitability of this model for compound discovery and target validation activities. The induction of inflammatory conditions caused a loss of barrier function of the intestinal epithelium and its activation by increased cytokine production, two events observed in IBD physiopathology. More importantly, anti-inflammatory compound exposure prevented the loss of barrier function and the increased cytokine release. Furthermore, knockdown of key inflammatory regulators RELA and MYD88 through on-chip adenoviral shRNA transduction alleviated IBD phenotype by decreasing cytokine production. In summary, we demonstrate the routine use of a gut-on-a-chip platform for disease-specific aspects modeling. The approach can be used for larger scale disease modeling, target validation and drug discovery purposes.