A magnetically reusable Ce-MOF/GO/Fe3O4 composite for effective photocatalytic degradation of chlortetracycline.

Herein, we report a novel 1/GO/Fe3O4 photocatalyst, comprising Ce(BTB)(H2O) (MOF-1, H3BTB = 1,3,5-benzenetrisbenzoic acid), graphene oxide (GO), and iron oxide (Fe3O4) for photocatalytic degradation of chlortetracycline (CTC). This design enables the effective transfer of electrons from the MOF to GO, thereby reducing the photoelectron-hole recombination rate. Therefore, the optimized 1/GO/Fe3O4 photocatalyst with H2O2 shows the highest photocatalytic activity toward CTC. The kinetic constant is 5.4 times that in the system of MOF-1 and hydrogen peroxide, which usually acted as efficient electron acceptors to improve the photocatalytic performance of MOFs. More importantly, light absorption is extended from the ultraviolet to the visible region. Furthermore, 1/GO/Fe3O4 can be quickly recycled under an applied magnetic field and displays outstanding stability and reusability. According to the radical trapping experiments and electron paramagnetic resonance results, hydroxyl radicals, superoxide radicals, and holes all contribute to excellent photocatalytic activity. The possible catalytic mechanism of 1/GO/Fe3O4 is tentatively proposed. This work aims to explore the synergistic effect between metal-organic frameworks (MOFs) and GO, and provide a theoretical basis for MOF-based composites to remove antibiotic contaminants in the environment.

Redox-Controlled Self-Assembly of Vanadium-Seamed Hexameric Pyrogallol[4]Arene Nanocapsules.

Here we report the controlled self-assembly of vanadium-seamed metal-organic nanocapsules with specific metal oxidation state distributions. Three supramolecular assemblies composed of the same numbers of components including 24 metal centers and six pyrogallol[4]arene ligands were constructed: a VIII24L6 capsule, a mixed-valence VIII18VIV6L6 capsule, and a VIV24L6 capsule. Crystallographic studies of the new capsules reveal their remarkable structural complexity and geometries, while marked differences in metal oxidation state distribution greatly affect the photoelectric conversion properties of these assemblies. This work therefore represents a significant step forward in the construction of intricate metal-organic architectures with tailored structure and functionality.

Functional Proliferating Human Hepatocytes: In Vitro Hepatocyte Model for Drug Metabolism, Excretion, and Toxicity.

To develop a functional alternative hepatocyte model for primary human hepatocytes (PHHs) with proliferative property, essential drug metabolic, and transporter functions, proliferating human hepatocytes (ProliHHs) expanded from PHHs were fully characterized in vitro. Herein, ProliHHs generated from multiple PHHs donors could be expanded more than 200-fold within four passages and maintained their metabolic or transporter capacities partially. Furthermore, ProliHHs were able to regain the mature hepatic property after three-dimensional (3D) culture. Particularly, the downregulated mRNA expression and function of three major cytochrome P450 (P450) enzymes (CYP1A2, CYP2B6, and CYP3A4) in the proliferating process (ProliHHs-P) could be recovered by 3D culture. The metabolic variabilities across different PHHs donors could be inherited to their matured ProliHHs (ProliHHs-M). The intrinsic clearances of seven major P450 enzymes in ProliHHs-M correlated well (r = 0.87) with those in PHHs. Also, bile canaliculi structures could be observed in sandwich-cultured ProliHHs (SC-ProliHHs), and the biliary excretion index of four probe compounds [cholyl-lys-fluorescein, 5-(and-6)-carboxy-2', 7'-dichlorofluorescein diacetate (CDF), deuterium-labeled sodium taurocholate acid, and rosuvastatin] in SC-ProliHHs (>10%) were close to sandwich-cultured PHHs. More importantly, both ProliHHs-P and ProliHHs-M could be used to evaluate hepatotoxicity. Therefore, these findings demonstrated that the 3D and sandwich culture system could be used to recover the metabolic and transporter functions in ProliHHs for clearance prediction and cholestasis risk assessment, respectively. Together, ProliHHs could be a promising substitute for PHHs in drug metabolism, transport, and hepatotoxicity screening. SIGNIFICANCE STATEMENT: This report describes the study of drug metabolic capacities, efflux transporter functions, and toxicity assessments of proliferating human hepatocytes (ProliHHs). The metabolic variability in different primary human hepatocyte donors could be inherited by their matured ProliHHs derivatives. Also, ProliHHs could form canalicular networks in sandwich culture and display biliary excretion capacities. More importantly, both the proliferative and maturation statuses of ProliHHs could be used to evaluate hepatotoxicity. Together, ProliHHs were feasible to support drug candidate screening in hepatic metabolism, disposition, and toxicity.

The possible role of SRMS in colorectal cancer by bioinformatics analysis.

BACKGROUND: Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (SRMS) is a non-receptor tyrosine kinase that has been found to be overexpressed in various tumors. However, the role of SRMS in colorectal cancer (CRC) has not been well established. METHODS: We evaluated the expression levels of SRMS in CRC using GEPIA, Oncomine, and HPA datasets. Survival information and gene expression data of CRC were obtained from The Cancer Genome Atlas (TCGA). Then, the association between SRMS and clinicopathological features was analyzed using UALCAN dataset. LinkedOmics was used to determine co-expression and functional networks associated with SRMS. Besides, we used TISIDB to assess the correlation between SRMS and immune signatures, including tumor-infiltrating immune cells and immunomodulators. Lastly, protein-protein interaction network (PPI) was established and the function enrichment analysis of the SRMS-associated immunomodulators and immune cell marker genes were performed using the STRING portal. RESULTS: Compared to normal colorectal tissues, SRMS was found to be overexpressed in CRC tissues, which was correlated with a poor prognosis. In colon adenocarcinoma (COAD), the expression levels of SRMS are significantly correlated with pathological stages and nodal metastasis status. Functional network analysis suggested that SRMS regulates intermediate filament-based processes, protein autophosphorylation, translational initiation, and elongation signaling through pathways involving ribosomes, proteasomes, oxidative phosphorylation, and DNA replication. In addition, SRMS expression was correlated with infiltrating levels of CD4+ T cells, CD56dim, MEM B, Neutrophils, Th2, Th17, and Act DC. The gene ontology (GO) analysis of SRMS-associated immunomodulators and immune cell marker genes showed that they were mainly enriched in the immune microenvironment molecule-related signals. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these genes indicated that they are involved in multiple cancer-related pathways. CONCLUSIONS: SRMS is a promising prognostic biomarker and potential therapeutic target for CRC patients. In particular, SRMS regulates CRC progression by modulating cytokine-cytokine receptor interaction, chemokines, IL-17, and intestinal immune networks for IgA production signaling pathways among others. However, more studies are needed to validate these findings.

Self-Assembly of a Semiconductive and Photoactive Heterobimetallic Metal-Organic Capsule.

We report the synthesis of a novel metal-organic capsule constructed from six pyrogallol[4]arene macrocycles, which are switched together by 16 FeIII and 16 CoII ions. This supramolecular structure is the first instance of a spheroidal heterometallic nanocage assembled through a one-step metal-ligand coordination approach. This new assembly also demonstrates an important proof of concept through the formation of multiple heterometallic metal-metal interactions within the capsule framework. Photophysical and electrochemical studies of self-assembled capsule films indicate their potential as semiconductors. These materials display unexpected photoelectric conversion properties, thus representing an emergent phenomenon in discrete metal-organic supramolecular assemblies.

Biomimetic Self-Assembly of CoII-Seamed Hexameric Metal-Organic Nanocapsules.

A CoII18L6 hexameric metal-organic nanocapsule (MONC) has been prepared and characterized using biomimetic self-assembly as the synthetic methodology. Akin to the biological behavior of zinc-finger proteins' release, uptake, and electrophilic substitution of Zn2+ ions, the assembly of this novel MONC has been accomplished by employing three sequential processes: assembly of the framework, metal ion insertion, and metal exchange, resulting in the formation of the CoII18L6 hexameric MONC. In this work, inspired by the biological behavior of metalloproteins, rational control of multiple complex supramolecular self-assembly has been achieved.

A statistical design for testing apomictic diversification through linkage analysis.

The capacity of apomixis to generate maternal clones through seed reproduction has made it a useful characteristic for the fixation of heterosis in plant breeding. It has been observed that apomixis displays pronounced intra- and interspecific diversification, but the genetic mechanisms underlying this diversification remains elusive, obstructing the exploitation of this phenomenon in practical breeding programs. By capitalizing on molecular information in mapping populations, we describe and assess a statistical design that deploys linkage analysis to estimate and test the pattern and extent of apomictic differences at various levels from genotypes to species. The design is based on two reciprocal crosses between two individuals each chosen from a hermaphrodite or monoecious species. A multinomial distribution likelihood is constructed by combining marker information from two crosses. The EM algorithm is implemented to estimate the rate of apomixis and test its difference between two plant populations or species as the parents. The design is validated by computer simulation. A real data analysis of two reciprocal crosses between hickory (Carya cathayensis) and pecan (C. illinoensis) demonstrates the utilization and usefulness of the design in practice. The design provides a tool to address fundamental and applied questions related to the evolution and breeding of apomixis.

Structural mapping: how to study the genetic architecture of a phenotypic trait through its formation mechanism.

Traditional approaches for genetic mapping are to simply associate the genotypes of a quantitative trait locus (QTL) with the phenotypic variation of a complex trait. A more mechanistic strategy has emerged to dissect the trait phenotype into its structural components and map specific QTLs that control the mechanistic and structural formation of a complex trait. We describe and assess such a strategy, called structural mapping, by integrating the internal structural basis of trait formation into a QTL mapping framework. Electrical impedance spectroscopy (EIS) has been instrumental for describing the structural components of a phenotypic trait and their interactions. By building robust mathematical models on circuit EIS data and embedding these models within a mixture model-based likelihood for QTL mapping, structural mapping implements the EM algorithm to obtain maximum likelihood estimates of QTL genotype-specific EIS parameters. The uniqueness of structural mapping is to make it possible to test a number of hypotheses about the pattern of the genetic control of structural components. We validated structural mapping by analyzing an EIS data collected for QTL mapping of frost hardiness in a controlled cross of jujube trees. The statistical properties of parameter estimates were examined by simulation studies. Structural mapping can be a powerful alternative for genetic mapping of complex traits by taking account into the biological and physical mechanisms underlying their formation.

A dynamic framework for quantifying the genetic architecture of phenotypic plasticity.

Despite its central role in the adaptation and microevolution of traits, the genetic architecture of phenotypic plasticity, i.e. multiple phenotypes produced by a single genotype in changing environments, remains elusive. We know little about the genes that underlie the plastic response of traits to the environment, their number, chromosomal locations and genetic interactions as well as environment impact on their effects. Here we review key statistical approaches for analyzing the genetic variation of phenotypic plasticity due to genotype-environment interactions and describe the implementation of a dynamic model to map specific quantitative trait loci (QTLs) that affect the gradient expression of a quantitative trait across a range of environments. This dynamic model is distinct by incorporating mathematical aspects of phenotypic plasticity into a QTL mapping framework, thereby better unraveling the quantitative attribute of trait response to the environment. By testing the curve parameters that specify environment-dependent trajectories of the trait, the model allows a series of fundamental hypotheses to be tested in a quantitative way about the interplay between gene action/interaction and environmental sensitivity. The model can also make the dynamic prediction of genetic control over phenotypic plasticity within the context of changing environments. We demonstrate the usefulness of the model by reanalyzing a QTL data set for rice, gleaning new insights into the genetic basis for phenotypic plasticity in plant height growth.

A unifying framework for bivalent multilocus linkage analysis of allotetraploids.

An allotetraploid has four paired sets of chromosomes derived from different diploid species, whose meiotic behavior is qualitatively different from the underlying diploids. According to a traditional view, meiotic pairing occurs only between homologous chromosomes, but new evidence indicates that homoeologous chromosomes may also pair to a lesser extent compared with homolog pairing. Here, we describe and assess a unifying analytical framework that incorporates differential chromosomal pairing into a multilocus linkage model. The preferential pairing factor is used to quantify the probability difference of pairing occurring between homologous chromosomes and homoeologous chromosomes. The unifying framework allows simultaneous estimation of the linkage, genetic interference and preferential pairing factor using commonly existing multiplex markers. We compared the unifying approach and traditional approaches assuming random chromosomal pairing by analyzing marker data collected in a full-sib family of tetraploid switchgrass, a bioenergy species whose diploid origins are undefined, but with subgenomes that are genetically well differentiated. The unifying framework provides a better tool for estimating the meiotic linkage and constructing a genetic map for allotetraploids.

A multivalent three-point linkage analysis model of autotetraploids.

Because of its widespread occurrence and role in shaping evolutionary processes in the biological kingdom, especially in plants, polyploidy has been increasingly studied from cytological to molecular levels. By inferring gene order, gene distances and gene homology, linkage mapping with molecular markers has proven powerful for investigating genome structure and organization. Here we review and assess a general statistical model for three-point linkage analysis in autotetraploids by integrating double reduction, a phenomenon that commonly occurs in autopolyploids whose chromosomes are derived from a single ancestral species. This model does not require any assumption on the distribution of the occurrence of double reduction and can handle the complexity of multilocus linkage in terms of crossover interference. Implemented with the expectation-maximization (EM) algorithms, the model can estimate and test the recombination fractions between less informative dominant markers, thus facilitating its practical implications for any autopolyploids in most of which inexpensive dominant markers are still used for their genetic and evolutionary studies. The model was applied to reanalyze a published data in tetraploid switchgrass, validating its practical usefulness and utilization.

2-[(E)-(4-Bromo-phenyl)imino-methyl]-4-chloro-phenol.

In the title compound, C13H9BrClNO, the dihedral angle between the substituted benzene rings is 44.25 (11)°. There are strong intra-molecular O-H⋯N hydrogen bonds, which generate S(6) rings, and also inter-molecular Cl⋯Cl [3.431 (3) Å] and Br⋯ Br [3.846 (1) Å] contacts. The crystal packing a C-H⋯O and C-H⋯π inter-actions.

Physicochemical properties and in vitro digestion behavior of emulsion micro-gels stabilized by κ-carrageenan and whey protein: Effects of sodium alginate addition.

Emulsion micro-gels exhibit significant potential as functional ingredients for modifying food texture, replacing saturated fats, or serving as templates for the controlled release of bioactive compounds. Structural design principles are being applied more frequently to develop innovative emulsion micro-gels. In this paper, whey protein concentrate (WPC), κ-carrageenan and sodium alginate (SA) were utilized for preparing emulsion micro-gels. To reveal the regulation mechanism of the structural and physicochemical properties of emulsion micro-gels on lipid digestion, the influence of SA additions on the structural, physicochemical properties and in vitro digestion behavior of κ-carrageenan/WPC-based emulsion micro-gel were explored. The FTIR results suggest that the emulsion micro-gels are formed through non-covalent interactions. With the increase of SA addition (from 0.7 g/100 mL to 1.0 g/100 mL), the decreased mean droplet size, the increased hardness, elasticity indexes, and water holding capacity, the reduced the related peak times all indicated that the emulsion micro-gels exhibit enhanced rheological, stability, and mechanical properties. It can be concluded from the microstructure, particle size distribution of the emulsion micro-gels during simulated digestion and free fatty acid release that both κ-carrageenan/WPC-based emulsion micro-gel and κ-carrageenan/WPC/SA-based emulsion micro-gel can inhibit lipid digestion due to the ability to maintain structural stability and hindering the penetration of bile salts and lipase through the hydrogel networks. And the ability is regulated by the binding properties the gel matrix and oil droplets, which determine the structure and physicochemical properties of emulsion micro-gels. The research suggested that the structure of emulsion micro-gels can be modified to produce various lipid digestion profiles. It may be significant for certain practical application in the design of low-fat food and controlled release of bioactive agents.

Luminescent lanthanide complexes based on 4,5-di(3,5-dicarboxylphenoxy)phthalic acid as enhanced fluorescence probes for highly selective detection of lead(II) ions in water.

Six novel lanthanide complexes ([Nd2(L)(H2O)6]n·4.58n(H2O) (1), [Ln(H3L)(H2O)]n·0.5n(H2O), Ln = Sm (2), Eu (3), Gd (4), Tb (5), Eu0.18Gd0.62Tb0.20 (6)) have been hydrothermally synthesized based on the ligand 4,5-di(3,5-dicarboxylphenoxy)phthalic acid (H6L). Single crystal X-ray diffraction reveals that complexes 1-6 are 2D structures, where 2-6 are isomorphic. Complexes 3 and 5 exhibit the characteristic fluorescence of Eu(III) and Tb(III) ions respectively, while complex 4 shows blue-green light emission based on the ligand. In particular, the ternary Eu/Gd/Tb complex 6 shows white light emission with a CIE (Commission International del'Eclairage) chromaticity coordinate of (0.330, 0.339) and hence close to pure white light emission. Moreover, complexes 3 and 5 display specific fluorescence-enhanced detection performance for Pb2+ ions: The interaction between Pb2+ ions and the ligand enhances the charge transfer efficiency between the ligand and the Eu(III) and Tb(III) ions and thus leads to fluorescence enhancement of complexes 3 and 5. More importantly, complex 3 exhibits the lowest detection limit of 4.72 nM for Pb2+ ions among the existing complex fluorescent probes. In addition, both complexes 3 and 5 show good performance for recycling and for the detection of Pb2+ in real water samples.

Loss of keratin 23 enhances growth inhibitory effect of melatonin in gastric cancer.

To investigate the effect of keratin 23 (KRT23) on the anticancer activity of melatonin (MLT) against gastric cancer (GC) cells, microarray analysis was applied to screen differentially expressed genes in AGS GC cells following MLT treatment. Western blotting was used to detect the expression of KRT23 in GC cells and normal gastric epithelial cell line GES­1. KRT23 knockout was achieved by CRISPR/Cas9. Assays of cell viability, colony formation, cell cycle, electric cell­substrate impedance sensing and western blotting were conducted to reveal the biological functions of KRT23­knockout cells without or with MLT treatment. Genes downregulated by MLT were enriched in purine metabolism, pyrimidine metabolism, genetic information processing and cell cycle pathway. Expression levels of KRT23 were downregulated by MLT treatment. Expression levels of KRT23 in AGS and SNU­216 GC cell lines were significantly higher compared with normal gastric epithelial cell line GES­1. KRT23 knockout led to reduced phosphorylation of ERK1/2 and p38, arrest of the cell cycle and inhibition of GC cell proliferation. Moreover, KRT23 knockout further enhanced the inhibitory activity of MLT on the tumor cell proliferation by inhibiting the phosphorylation of p38/ERK. KRT23 knockout contributes to the antitumor effects of MLT in GC via suppressing p38/ERK phosphorylation. In the future, KRT23 might be a potential prognostic biomarker and a novel molecular target for GC.

Syntheses and fluorescence properties of lanthanide isostructural complexes derived from aspartic acid.

To protect ecosystem balance and human health, the development of fluorescent sensing materials with high sensitivity and portability has attracted wide attention in several decades. Herein, six lanthanide isostructural complexes {[Ln(µ6-Hcaa)(H2O)]Cl}n (H3caa = N-(4-carboxylbenzyl)-L-aspartic acid, Ln3+ = Ce3+ (1), Pr3+ (2), Nd3+ (3), Sm3+ (4), Eu3+ (5), and Tb3+ (6)) with optical properties based on aspartic acid derivative (H3caa) were synthesized by the solvothermal method and characterized in detail. It is worth noting that complex 6 can not only specifically recognize Cr(VI) with very low detection limits (LODs) of 3.66 nM (Cr2O72-) & 5.35 nM (CrO42-) but also selectively recognize TCs with LODs of 0.24 µM (CTC = chlortetracycline) and 0.25 µM (TC = tetracycline) based on the method of fluorescence detection. In addition, the identification of Cr(VI) and TCs by visual colorimetry may be realized through the combination of a smartphone and portable test strips. This study suggests that complex 6 is a good optical material for detecting heavy metals and antibiotic contaminants in aqueous systems and broadens the development of amino acid derivatives.

Melatonin enhances anti-tumor immunity by targeting macrophages PD-L1 via exosomes derived from gastric cancer cells.

Melatonin (MLT) is a hormone with potential anti-tumor properties, but the molecular mechanisms remain unclear. The present study aimed to explore the effect of MLT on exosomes derived from gastric cancer cells, with the goal of gaining insight into its anti-tumor activity. Results from in vitro experiments showed that MLT was able to enhance the anti-tumor activity of macrophages that had been suppressed by exosomes from gastric cancer cells. This effect was achieved through regulation of the levels of PD-L1 in macrophages via modulation of the associated microRNAs in the cancer-derived exosomes. Furthermore, MLT treatment increased the secretion of TNF-α and CXCL10 by the macrophages. Besides, MLT treatment of gastric cancer cells led to the production of exosomes that promoted the recruitment of CD8+ T cells to the tumor site, resulting in inhibition of tumor growth. Collectively, these results provide evidence for the modulation of the tumor immune microenvironment by MLT through regulation of exosomes derived from gastric cancer cells, suggesting a potential role for MLT in novel anti-tumor immunotherapies.

A hiPSC-derived lineage-specific vascular smooth muscle cell-on-a-chip identifies aortic heterogeneity across segments.

Aortic aneurysm (AA), a potentially lethal condition with the characteristic of aortic dilatation, can only be treated by surgical or endovascular procedures. The underlying mechanisms of AA are unclear and early preventive treatment is still insufficient due to segmental aortic heterogeneity and the limitations of current disease models. Here, we firstly established a comprehensive lineage-specific vascular smooth muscle cell (SMC)-on-a-chip model using human induced pluripotent stem cells to yield cell lineages representing different segments of the aorta and tested the constructed organ-on-a-chip model under various tensile stress conditions. Bulk RNA sequencing, RT-qPCR, immunofluorescence, western blot and FACS analyses were performed to discover the segmental aortic heterogeneity of response for tensile stress and drug testing. The appropriate stretching frequency for all lineages of SMCs was 1.0 Hz, paraxial mesoderm (PM) SMCs were more sensitive to tensile stress than lateral mesoderm (LM) SMCs and neural crest (NC) SMCs. These differences may be related to the different transcriptional profiles of the tension-stressed distinct lineage-specific vascular SMCs, specifically in relation to the PI3K-Akt signaling pathway. Also, the organ-on-a-chip displayed contractile physiology, perfect fluid coordination, and was conducive to drug testing, displaying heterogeneous segmental aortic responses. Compared with LM-SMCs and NC-SMCs, PM-SMCs were more sensitive to ciprofloxacin. The model is evaluated as a novel and suitable supplement to AA animal models for determining differential physiology and drug response in different parts of the aorta. Furthermore, this system could pave the way for disease modeling, drug testing, and the personalized treatment of patients with AA in the future.

A copper-seamed coordination nanocapsule as a semiconductor photocatalyst for molecular oxygen activation.

Here we report that a Cu2+-seamed coordination nanocapsule can serve as an efficient semiconductor photocatalyst for molecular oxygen activation. This capsule was constructed through a redox reaction facilitated self-assembly of cuprous bromide and C-pentyl-pyrogallol[4]arene. Photophysical and electrochemical studies revealed its strong visible-light absorption and photocurrent polarity switching effect. This novel molecular solid material is capable of activating molecular oxygen into reactive oxygen species under simulated sunlight irradiation. The oxygen activation process has been exploited for catalyzing aerobic oxidation reactions. The present work provides new insights into designing nonporous discrete metal-organic supramolecular assemblies for solar-driven molecular oxygen activation.

Human endoderm stem cells reverse inflammation-related acute liver failure through cystatin SN-mediated inhibition of interferon signaling.

Acute liver failure (ALF) is a life-threatening disease that occurs secondary to drug toxicity, infection or a devastating immune response. Orthotopic liver transplantation is an effective treatment but limited by the shortage of donor organs, the requirement for life-long immune suppression and surgical challenges. Stem cell transplantation is a promising alternative therapy for fulminant liver failure owing to the immunomodulatory abilities of stem cells. Here, we report that when transplanted into the liver, human endoderm stem cells (hEnSCs) that are germ layer-specific and nontumorigenic cells derived from pluripotent stem cells are able to effectively ameliorate hepatic injury in multiple rodent and swine drug-induced ALF models. We demonstrate that hEnSCs tune the local immune microenvironment by skewing macrophages/Kupffer cells towards an anti-inflammatory state and by reducing the infiltrating monocytes/macrophages and inflammatory T helper cells. Single-cell transcriptomic analyses of infiltrating and resident monocytes/macrophages isolated from animal livers revealed dramatic changes, including changes in gene expression that correlated with the change of activation states, and dynamic population heterogeneity among these cells after hEnSC transplantation. We further demonstrate that hEnSCs modulate the activation state of macrophages/Kupffer cells via cystatin SN (CST1)-mediated inhibition of interferon signaling and therefore highlight CST1 as a candidate therapeutic agent for diseases that involve over-activation of interferons. We propose that hEnSC transplantation represents a novel and powerful cell therapeutic treatment for ALF.