Leveraging Janus Substrates as a Confined "Interfacial Reactor" to Synthesize Ultrapermeable Polyamide Nanofilms.

Porous substrates act as open "interfacial reactors" during the synthesis of polyamide composite membranes via interfacial polymerization. However, achieving a thin and dense polyamide nanofilm with high permeance and selectivity is challenging when using a conventional substrate with uniform wettability. To overcome this limitation, we propose the use of Janus porous substrates as confined interfacial reactors to decouple the local monomer concentration from the total monomer amount during interfacial polymerization. By manipulating the location of the hydrophilic/hydrophobic interface in a Janus porous substrate, we can precisely control the monomer solution confined within the hydrophilic layer without compromising its concentration. The hydrophilic surface ensures the uniform distribution of monomers, preventing the formation of defects. By employing Janus substrates fabricated through single-sided deposition of polydopamine/polyethyleneimine, we significantly reduce the thickness of the polyamide nanofilms from 88.4 to 3.8 nm by decreasing the thickness of the hydrophilic layer. This reduction leads to a remarkable enhancement in water permeance from 7.2 to 52.0 l/m2·h·bar while still maintaining ~96% Na2SO4 rejection. The overall performance of this membrane surpasses that of most reported membranes, including state-of-the-art commercial products. The presented strategy is both simple and effective, bringing ultrapermeable polyamide nanofilms one step closer to practical separation applications.

Comprehensive assessment of mRNA isoform detection methods for long-read sequencing data.

The advancement of Long-Read Sequencing (LRS) techniques has significantly increased the length of sequencing to several kilobases, thereby facilitating the identification of alternative splicing events and isoform expressions. Recently, numerous computational tools for isoform detection using long-read sequencing data have been developed. Nevertheless, there remains a deficiency in comparative studies that systemically evaluate the performance of these tools, which are implemented with different algorithms, under various simulations that encompass potential influencing factors. In this study, we conducted a benchmark analysis of thirteen methods implemented in nine tools capable of identifying isoform structures from long-read RNA-seq data. We evaluated their performances using simulated data, which represented diverse sequencing platforms generated by an in-house simulator, RNA sequins (sequencing spike-ins) data, as well as experimental data. Our findings demonstrate IsoQuant as a highly effective tool for isoform detection with LRS, with Bambu and StringTie2 also exhibiting strong performance. These results offer valuable guidance for future research on alternative splicing analysis and the ongoing improvement of tools for isoform detection using LRS data.

Supergravity-Steered Generic Manufacturing of Nanosheets-Embedded Nanocomposite Hydrogel with Highly Oriented, Heterogeneous Architecture.

Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene-based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force-tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high-efficient movement, pre-orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high-orientation MXene-rich layer (orientation degree, f = 0.83) and a polymer-rich layer. The authors demonstrate that MXene-based nanocomposite hydrogels leverage their high-orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super-low MXene of 0.3 wt%, surpassing most hydrogels-based electromagnetic shielding materials. This versatile supergravity-steered strategy can be further extended to arbitrary nanosheets including MoS2, GO, and C3N4, offering a paradigm in the development of oriented nanocomposites.

Harmonic amide bond density as a game-changer for deciphering the crosslinking puzzle of polyamide.

It is particularly essential to analyze the complex crosslinked networks within polyamide membranes and their correlation with separation efficiency for the insightful tailoring of desalination membranes. However, using the degree of network crosslinking as a descriptor yields abnormal analytical outcomes and limited correlation with desalination performance due to imperfections in segmentation and calculation methods. Herein, we introduce a more rational parameter, denoted as harmonic amide bond density (HABD), to unravel the relationship between the crosslinked networks of polyamide membranes and their desalination performance. HABD quantifies the number of distinct amide bonds per unit mass of polyamide, based on a comprehensive segmentation of polyamide structure and consistent computational protocols derived from X-ray photoelectron spectroscopy data. Compared to its counterpart, HABD overcomes the limitations and offers a more accurate depiction of the crosslinked networks. Empirical data validate that HABD exhibits the expected correlation with the salt rejection and water permeance of reverse osmosis and nanofiltration polyamide membranes. Notably, HABD is applicable for analyzing complex crosslinked polyamide networks formed by highly functional monomers. By offering a powerful toolbox for systematic analysis of crosslinked polyamide networks, HABD facilitates the development of permselective membranes with enhanced performance in desalination applications.

Supported Ionic Liquid Membrane with Highly-permeable Polyamide Armor by In Situ Interfacial Polymerization for Durable CO2 Separation.

Supported ionic liquid membranes (SILMs), owing to their capacities in harnessing physicochemical properties of ionic liquid for exceptional CO2 solubility, have emerged as a promising platform for CO2 extraction. Despite great achievements, existing SILMs suffer from poor structural and performance stability under high-pressure or long-term operations, significantly limiting their applications. Herein, a one-step and in situ interfacial polymerization strategy is proposed to elaborate a thin, mechanically-robust, and highly-permeable polyamide armor on the SILMs to effectively protect ionic liquid within porous supports, allowing for intensifying the overall stability of SILMs without compromising CO2 separation performance. The armored SILMs have a profound increase of breakthrough pressure by 105% compared to conventional counterparts without armor, and display high and stable operating pressure exceeding that of most SILMs previously reported. It is further demonstrated that the armored SILMs exhibit ultrahigh ideal CO2 /N2 selectivity of about 200 and excellent CO2 permeation of 78 barrers upon over 150 h operation, as opposed to the full failure of CO2 separation performance within 36 h using conventional SILMs. The design concept of armor provides a flexible and additional dimension in developing high-performance and durable SILMs, pushing the practical application of ionic liquids in separation processes.

Solid-state, liquid-free ion-conducting elastomers: rising-star platforms for flexible intelligent devices.

Soft ionic conductors have emerged as a powerful toolkit to engineer transparent flexible intelligent devices that go beyond their conventional counterparts. Particularly, due to their superior capacities of eliminating the evaporation, freezing and leakage issues of the liquid phase encountered with hydrogels, organohydrogels and ionogels, the emerging solid-state, liquid-free ion-conducting elastomers have been largely recognized as ideal candidates for intelligent flexible devices. However, despite their extensive development, a comprehensive and timely review in this emerging field is lacking, particularly from the perspective of design principles, advanced manufacturing, and distinctive applications. Herein, we present (1) the design principles and intriguing merits of solid-state, liquid-free ion-conducting elastomers; (2) the methods to manufacture solid-state, liquid-free ion-conducting elastomers with preferential architectures and functions using advanced technologies such as 3D printing; (3) how to leverage solid-state, liquid-free ion-conducting elastomers in exploiting advanced applications, especially in the fields of flexible wearable sensors, bioelectronics and energy harvesting; (4) what are the unsolved scientific and technical challenges and future opportunities in this multidisciplinary field. We envision that this review will provide a paradigm shift to trigger insightful thinking and innovation in the development of intelligent flexible devices and beyond.

Heterogenized Molecular Electrocatalyst Based on a Hydroxo-Bridged Binuclear Copper(II) Phenanthroline Compound for Selective Reduction of CO2 to Ethylene.

Molecular copper catalysts have emerged as promising candidates for the electrochemical reduction of CO2 . Notable features of such systems include the ability of Cu to generate C2+  products and the well-defined active sites that allow for targeted structural tuning. However, the frequently observed in situ formation of Cu nanoclusters has undermined the advantages of the molecular frameworks. It is therefore desirable to develop Cu-based catalysts that retain their molecular structures during electrolysis. In this context, a heterogenized binuclear hydroxo-bridged phenanthroline Cu(II) compound with a short Cu···Cu distance is reported as a simple yet efficient catalyst for electrogeneration of ethylene and other C2 products. In an aqueous electrolyte, the catalyst demonstrates remarkable performance, with excellent Faradaic efficiency for C2 products (62%) and minimal H2 evolution (8%). Furthermore, it exhibits high stability, manifested by no observable degradation during 15 h of continuous electrolysis. The preservation of the atomic distribution of the active sites throughout electrolysis is substantiated through comprehensive characterizations, including X-ray photoelectron and absorption spectroscopy, scanning and transmission electron microscopy, UV-vis spectroscopy, as well as control experiments. These findings establish a solid foundation for further investigations into targeted structural tuning, opening new avenues for enhancing the catalytic performance of Cu-based molecular electrocatalysts.

Selective binding of retrotransposons by ZFP352 facilitates the timely dissolution of totipotency network.

Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been revealed for the totipotency regulatory network around the zygotic genome activation (ZGA) period. However, how the dissolution of the totipotency network is triggered to ensure the timely embryonic development following ZGA is largely unknown. In this study, we identify the unexpected role of a highly expressed 2-cell (2C) embryo specific transcription factor, ZFP352, in facilitating the dissolution of the totipotency network. We find that ZFP352 has selective binding towards two different retrotransposon sub-families. ZFP352 coordinates with DUX to bind the 2C specific MT2_Mm sub-family. On the other hand, without DUX, ZFP352 switches affinity to bind extensively onto SINE_B1/Alu sub-family. This leads to the activation of later developmental programs like ubiquitination pathways, to facilitate the dissolution of the 2C state. Correspondingly, depleting ZFP352 in mouse embryos delays the 2C to morula transition process. Thus, through a shift of binding from MT2_Mm to SINE_B1/Alu, ZFP352 can trigger spontaneous dissolution of the totipotency network. Our study highlights the importance of different retrotransposons sub-families in facilitating the timely and programmed cell fates transition during early embryogenesis.

Multi-channel deep learning model-based myocardial spatial-temporal morphology feature on cardiac MRI cine images diagnoses the cause of LVH.

BACKGROUND: To develop a fully automatic framework for the diagnosis of cause for left ventricular hypertrophy (LVH) via cardiac cine images. METHODS: A total of 302 LVH patients with cine MRI images were recruited as the primary cohort. Another 53 LVH patients prospectively collected or from multi-centers were used as the external test dataset. Different models based on the cardiac regions (Model 1), segmented ventricle (Model 2) and ventricle mask (Model 3) were constructed. The diagnostic performance was accessed by the confusion matrix with respect to overall accuracy. The capability of the predictive models for binary classification of cardiac amyloidosis (CA), hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) were also evaluated. Additionally, the diagnostic performance of best Model was compared with that of 7 radiologists/cardiologists. RESULTS: Model 3 showed the best performance with an overall classification accuracy up to 77.4% in the external test datasets. On the subtasks for identifying CA, HCM or HHD only, Model 3 also achieved the best performance with AUCs yielding 0.895-0.980, 0.879-0.984 and 0.848-0.983 in the validation, internal test and external test datasets, respectively. The deep learning model showed non-inferior diagnostic capability to the cardiovascular imaging expert and outperformed other radiologists/cardiologists. CONCLUSION: The combined model based on the mask of left ventricular segmented from multi-sequences cine MR images shows favorable and robust performance in diagnosing the cause of left ventricular hypertrophy, which could be served as a noninvasive tool and help clinical decision.

Steering carbon dioxide reduction toward C-C coupling using copper electrodes modified with porous molecular films.

Copper offers unique capability as catalyst for multicarbon compounds production in the electrochemical carbon dioxide reduction reaction. In lieu of conventional catalysis alloying with other elements, copper can be modified with organic molecules to regulate product distribution. Here, we systematically study to which extent the carbon dioxide reduction is affected by film thickness and porosity. On a polycrystalline copper electrode, immobilization of porous bipyridine-based films of varying thicknesses is shown to result in almost an order of magnitude enhancement of the intrinsic current density pertaining to ethylene formation while multicarbon products selectivity increases from 9.7 to 61.9%. In contrast, the total current density remains mostly unaffected by the modification once it is normalized with respect to the electrochemical active surface area. Supported by a microkinetic model, we propose that porous and thick films increase both local carbon monoxide partial pressure and the carbon monoxide surface coverage by retaining in situ generated carbon monoxide. This reroutes the reaction pathway toward multicarbon products by enhancing carbon-carbon coupling. Our study highlights the significance of customizing the molecular film structure to improve the selectivity of copper catalysts for carbon dioxide reduction reaction.

GATA2 promotes oxidative stress to aggravate renal ischemia-reperfusion injury by up-regulating Redd1.

Renal ischemia-reperfusion injury (RIRI) is a common pathophysiological process, and it is also an important cause of acute renal failure. Therefore, finding an effective therapeutic target for RIRI is extremely urgent. In our study, we constructed hypoxia-reoxygenation (HR) model in vitro and a renal ischemia-reperfusion (IR) model in vivo. Elevated levels of serum creatinine (Cr), blood urea nitrogen (BUN) tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) along with the decreased levels of superoxide dismutase (SOD) and glutathione (GSH) proved that kidney function was damaged after IR, and pathological changes of renal tissues were observed using HE staining and TUNEL staining. The protein of Redd1 expression level was detected to be upregulated after IR by western blot (WB). However, transfection of short hairpin RNA of Redd1 (sh-Redd1) alleviated the HR injury on LLC-PK1 cells, as evidenced by increased cell viability, proliferation and decreased cell apoptosis; additionally, the accumulation of ROS was inhibited. Sh-Redd1 also alleviated IR injury in the mouse model. Subsequently, GATA2 was proved to be upregulated in IR and HR models and was the transcription factor of Redd1. Knockdown of GATA2 efficiently mitigated the oxidative stress induced damages in vivo and in vitro, while these mitigations were reversed by transfection of Redd1 overexpression plasmid. In conclusion, our study clarified the possible underlying mechanism of protecting RIRI.

The regulation of totipotency transcription: Perspective from in vitro and in vivo totipotency.

Totipotency represents the highest developmental potency. By definition, totipotent stem cells are capable of giving rise to all embryonic and extraembryonic cell types. In mammalian embryos, totipotency occurs around the zygotic genome activation period, which is around the 2-cell stage in mouse embryo or the 4-to 8-cell stage in human embryo. Currently, with the development of in vitro totipotent-like models and the advances in small-scale genomic methods, an in-depth mechanistic understanding of the totipotency state and regulation was enabled. In this review, we explored and summarized the current views about totipotency from various angles, including genetic and epigenetic aspects. This will hopefully formulate a panoramic view of totipotency from the available research works until now. It can also help delineate the scaffold and formulate new hypotheses on totipotency for future research works.

Challenges and Prospects in the Catalytic Conversion of Carbon Dioxide to Formaldehyde.

Formaldehyde (HCHO) is a crucial C1 building block for daily-life commodities in a wide range of industrial processes. Industrial production of HCHO today is based on energy- and cost-intensive gas-phase catalytic oxidation of methanol, which calls for exploring other and more sustainable ways of carrying out this process. Utilization of carbon dioxide (CO2 ) as precursor presents a promising strategy to simultaneously mitigate the carbon footprint and alleviate environmental issues. This Minireview summarizes recent progress in CO2 -to-HCHO conversion using hydrogenation, hydroboration/hydrosilylation as well as photochemical, electrochemical, photoelectrochemical, and enzymatic approaches. The active species, reaction intermediates, and mechanistic pathways are discussed to deepen the understanding of HCHO selectivity issues. Finally, shortcomings and prospects of the various strategies for sustainable reduction of CO2 to HCHO are discussed.

Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency.

Endogenous retroviruses (ERVs) have been reported to participate in pre-implantation development of mammalian embryos. In early human embryogenesis, different ERV sub-families are activated in a highly stage-specific manner. How the specificity of ERV activation is achieved remains largely unknown. Here, we demonstrate the mechanism of how LTR7Ys, the human morula-blastocyst-specific HERVH long terminal repeats, are activated by the naive pluripotency transcription network. We find that KLF5 interacts with and rewires NANOG to bind and regulate LTR7Ys; in contrast, the primed-specific LTR7s are preferentially bound by NANOG in the absence of KLF5. The specific activation of LTR7Ys by KLF5 and NANOG in pluripotent stem cells contributes to human-specific naive pluripotency regulation. KLF5-LTR7Y axis also promotes the expression of trophectoderm genes and contributes to the expanded cell potential toward extra-embryonic lineage. Our study suggests that HERVs are activated by cell-state-specific transcription machinery and promote stage-specific transcription network and cell potency.

ID proteins promote the survival and primed-to-naive transition of human embryonic stem cells through TCF3-mediated transcription.

Inhibition of DNA binding proteins 1 and 3 (ID1 and ID3) are important downstream targets of BMP signalling that are necessary for embryonic development. However, their specific roles in regulating the pluripotency of human embryonic stem cells (hESCs) remain unclear. Here, we examined the roles of ID1 and ID3 in primed and naive-like hESCs and showed that ID1 and ID3 knockout lines (IDs KO) exhibited decreased survival in both primed and naive-like state. IDs KO lines in the primed state also tended to undergo pluripotent dissolution and ectodermal differentiation. IDs KO impeded the primed-to-naive transition (PNT) of hESCs, and overexpression of ID1 in primed hESCs promoted PNT. Furthermore, single-cell RNA sequencing demonstrated that ID1 and ID3 regulated the survival and pluripotency of hESCs through the AKT signalling pathway. Finally, we showed that TCF3 mediated transcriptional inhibition of MCL1 promotes AKT phosphorylation, which was confirmed by TCF3 knockdown in KO lines. Our study suggests that IDs/TCF3 acts through AKT signalling to promote survival and maintain pluripotency of both primed and naive-like hESCs.

DNMT3a negatively regulates PTEN to activate the PI3K/AKT pathway to aggravate renal fibrosis.

BACKGROUND: Renal fibrosis has become one of the major diseases threatening global public health and harming human life and health. PTEN methylation plays an important role in fibrotic diseases of many organs. However, the relationship between PTEN methylation and renal fibrosis is still elusive. METHODS: In the present study, we established a unilateral ureteral obstruction (UUO) mouse model in vivo and a transforming growth factor ß1 (TGF-ß1)-stimulated renal tubular epithelial cell (HK-2) model in vitro. The degree of renal interstitial fibrosis was detected by haematoxylin-eosin (HE) staining and Masson's trichrome staining. Western blot (WB), qRT-PCR, immunohistochemistry (IHC) and methylation-specific PCR (MSP) analyses were used to determine the mechanism by which PTEN methylation regulates renal fibrosis. The α-SMA fibrosis marker was detected by immunofluorescence (IF). Additionally, the relationship of PTEN and DNMT3a in UUO was determined by ChIP-qRT-PCR. RESULTS: Our results showed that the promoter region of PTEN was methylated in UUO. Compared to the sham group, the expression of PTEN was significantly reduced in the UUO group. However, the demethylation reagent significantly inhibited epithelial-mesenchymal transition (EMT), which showed increased expression of E-cadherin and decreased expression of α-SMA and fibronectin. Moreover, treatment of HK-2 cells with 5-aza-dc reversed the activation of the TGF-ß1-induced PI3K/AKT signalling pathway, which inhibited renal fibrosis. WB analysis demonstrated that TGF-ß1 inhibited the PTEN protein expression level and DNMT3a knockdown reversed the inhibitory effect of TGF-ß1 on PTEN expression. Furthermore, ChIP-qRT-PCR showed that DNMT3a interacted with PTEN. Finally, we found that DNMT3a negatively regulated PTEN to activate the PI3K/AKT signalling pathway and aggravate renal fibrosis in vitro and in vivo. CONCLUSION: In summary, these results indicated that renal fibrosis is related to the downregulation of PTEN. Additionally, DNMT3a negatively regulates PTEN to activate the PI3K/AKT signalling pathway and induce EMT in renal tubular epithelial cells, thereby aggravating renal fibrosis.

Molecular Catalysts for the Reductive Homocoupling of CO2 towards C2+ Compounds.

The conversion of CO2 into multicarbon (C2+ ) compounds by reductive homocoupling offers the possibility to transform renewable energy into chemical energy carriers and thereby create "carbon-neutral" fuels or other valuable products. Most available studies have employed heterogeneous metallic catalysts, but the use of molecular catalysts is still underexplored. However, several studies have already demonstrated the great potential of the molecular approach, namely, the possibility to gain a deep mechanistic understanding and a more precise control of the product selectivity. This Minireview summarizes recent progress in both the thermo- and electrochemical reductive homocoupling of CO2 toward C2+ products mediated by molecular catalysts. In addition, reductive CO homocoupling is discussed as a model for the further conversion of intermediates obtained from CO2 reduction, which may serve as a source of inspiration for developing novel molecular catalysts in the future.

The Regulation and Functions of Endogenous Retrovirus in Embryo Development and Stem Cell Differentiation.

Endogenous retroviruses (ERVs) are repetitive sequences in the genome, belonging to the retrotransposon family. During the course of life, ERVs are associated with multiple aspects of chromatin and transcriptional regulation in development and pathological conditions. In mammalian embryos, ERVs are extensively activated in early embryo development, but with a highly restricted spatial-temporal pattern; and they are drastically silenced during differentiation with exceptions in extraembryonic tissue and germlines. The dynamic activation pattern of ERVs raises questions about how ERVs are regulated in the life cycle and whether they are functionally important to cell fate decision during early embryo and somatic cell development. Therefore, in this review, we focus on the pieces of evidence demonstrating regulations and functions of ERVs during stem cell differentiation, which suggests that ERV activation is not a passive result of cell fate transition but the active epigenetic and transcriptional regulation during mammalian development and stem cell differentiation.

Transporting ESCs in FBS at ambient temperature.

We describe a simple, safe, efficient, and environment-friendly method with low cost for transporting cells between laboratories in distant regions. Cell transportation can be carried out at ambient temperature without the consumption of dry ice. It provides researchers across the globe an efficient way to share cell samples in an economical and convenient manner.

Human Pluripotent Stem Cell-Derived Organoids as Models of Liver Disease.

BACKGROUND & AIMS: There are few in vitro models for studying the 3-dimensional interactions among different liver cell types during organogenesis or disease development. We aimed to generate hepatic organoids that comprise different parenchymal liver cell types and have structural features of the liver, using human pluripotent stem cells. METHODS: We cultured H1 human embryonic stem cells (WA-01, passage 27-40) and induced pluripotent stem cells (GM23338) with a series of chemically defined and serum-free media to induce formation of posterior foregut cells, which were differentiated in 3 dimensions into hepatic endoderm spheroids and stepwise into hepatoblast spheroids. Hepatoblast spheroids were reseeded in a high-throughput format and induced to form hepatic organoids; development of functional bile canaliculi was imaged live. Levels of albumin and apolipoprotein B were measured in cell culture supernatants using an enzyme-linked immunosorbent assay. Levels of gamma glutamyl transferase and alkaline phosphatase were measured in cholangiocytes. Organoids were incubated with troglitazone for varying periods and bile transport and accumulation were visualized by live-imaging microscopy. Organoids were incubated with oleic and palmitic acid, and formation of lipid droplets was visualized by staining. We compared gene expression profiles of organoids incubated with free fatty acids or without. We also compared gene expression profiles between liver tissue samples from patients with nonalcoholic steatohepatitis (NASH) versus without. We quantified hepatocyte and cholangiocyte populations in organoids using immunostaining and flow cytometry; cholangiocyte proliferation of cholangiocytes was measured. We compared the bile canaliculi network in the organoids incubated with versus without free fatty acids by live imaging. RESULTS: Cells in organoids differentiated into hepatocytes and cholangiocytes, based on the expression of albumin and cytokeratin 7. Hepatocytes were functional, based on secretion of albumin and apolipoprotein B and cytochrome P450 activity; cholangiocytes were functional, based on gamma glutamyl transferase and alkaline phosphatase activity and proliferative responses to secretin. The organoids organized a functional bile canaliculi system, which was disrupted by cholestasis-inducing drugs such as troglitazone. Organoids incubated with free fatty acids had gene expression signatures similar to those of liver tissues from patients with NASH. Incubation of organoids with free fatty acid-enriched media resulted in structural changes associated with nonalcoholic fatty liver disease, such as decay of bile canaliculi network and ductular reactions. CONCLUSIONS: We developed a hepatic organoid platform with human cells that can be used to model complex liver diseases, including NASH.