ABSTRACT
Advanced glycation end products (AGEs) are formed by the Maillard reaction, a nonenzymatic process that occurs widely in cooking, food processing, and within the human body. Primarily, AGEs are formed by the glycation of reducing sugars with amino groups, and this process is heat-dependent. With changes in lifestyle, there has been an increase in the diversity of dietary habits, including those patterns associated with Western diets, which include the consumption of processed foods that are rich in AGEs. Excessive intake and exposure to AGEs are known to cause abnormalities in body function such as obesity, diabetes, and fatty liver, and the beneficial effects of AGEs in food processing in improving food flavor and quality. To obtain meaningful data regarding AGEs in a variety of food and human samples, it is necessary to more precisely characterize and analyze the AGEs extracted from samples to obtain accurate results. This review explores the recent analytical research and characterization of AGEs in foods, including casein, ß-lactoglobulin, soy protein, and meat protein, and in human samples, such as glycated-albumin, hemoglobin, and plasma. Additionally, it explores the metabolic fate of AGEs in the body and the mechanisms of disease associated with metabolic abnormalities that may be caused by the consumption of foods containing AGEs. This review aims to provide an overview of the perspectives of relevant recent and future research on metabolic abnormalities caused by foods containing AGEs or by AGEs produced in the body.
Subject(s)
Glycation End Products, Advanced , Metabolic Diseases , Glycation End Products, Advanced/adverse effects , Glycation End Products, Advanced/metabolism , Glycation End Products, Advanced/chemistry , Humans , Metabolic Diseases/etiology , Food Analysis , Maillard Reaction , Animals , Food Handling/methodsABSTRACT
Ablation cancer therapy using percutaneous intra-tumoral injection of ethanol is a promising method for targeted and effective locoregional cancer therapy. Magnetic gelatin microsphere (MGM) colloidal ethanol solution is developed as a potential injectable tumor ablation agent. The MGM was fabricated by electrostatic interactions among gelatin, acrylic acid, and acrylic acid-coated iron oxide nanoparticles. The fabricated MGM was dispersed in ethanol solution to form injectable MGM colloidal ethanol solution. The MGM colloidal ethanol solution can be easily infused and undergo in situ gelation via solvent exchange from ethanol to water in an artificial tissue. Furthermore, the MGM colloidal ethanol solution allowed doxorubicin (Dox) chemo-agent loading and its sustained release upon the formation of a drug depot by in situ gelation in artificial tissues. Our in vitro study demonstrated that locally delivered ethanol and Dox with MGM colloidal ethanol solution promoted the anti-cancer therapeutic efficacy with a significantly suppressed cancer cell recovery rate. Overall, our developed injectable MGM colloidal ethanol solution that can be transformed to a hydrogel drug depot at the injection site holds clinical potential for a new class of chemo-ablation agents.
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is a major issue because it is closely associated with metabolic diseases. Advanced glycation end products (AGEs) are implicated as risk factors for steatosis during NAFLD progression. AGEs influence NAFLD progression through a receptor-independent pathway involving AGE cross-link formation and a receptor-dependent pathway that binds to receptors like receptors for advanced glycation end products (RAGE). The objectives of this study are to examine the effect of Lindera obtusiloba Blume (LO) on NAFLD promoted by Nε-(carboxymethyl)lysine (CML), one of the most common dietary AGEs. The anti-glycation effects of LO were evaluated by inhibiting the AGEs formation and AGEs-collagen cross-links breaking. The efficacy of LO against NAFLD promoted by CML was assessed using both in vitro and in vivo models. NAFLD was induced in mice by feeding a high-fat diet and orally administering CML over a period of 12 weeks, and the effects of LO on lipid metabolism and its regulatory mechanisms were investigated. LO showed the effect of inhibited AGEs formation and breakage, and collagen cross-linking. Fed a high-fat diet with administered CML by gavage, LO administration resulted in a reduction in body weight, fat mass, serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. LO reduced hepatic CML accumulation and RAGE expression in mice fed a high-fat diet and orally administered CML. LO alleviated hepatic steatosis accompanied by lipid accumulation and histological damage by suppressing the expression of sterol regulatory element-binding protein 1c, carbohydrate response element binding protein, fatty acid synthase, stearoyl-CoA desaturase1, tumor necrosis factor-α, and interleukin-1ß. LO alleviated the MAPK/NF-κB expression by attenuating CML and RAGE expression. Taken together, our results demonstrate that LO alleviates the progression of NAFLD by lowering the levels of AGEs by downregulating CML/RAGE expression.
Subject(s)
Glycation End Products, Advanced , Lindera , Lysine , Non-alcoholic Fatty Liver Disease , Receptor for Advanced Glycation End Products , Non-alcoholic Fatty Liver Disease/drug therapy , Animals , Lysine/analogs & derivatives , Glycation End Products, Advanced/metabolism , Male , Mice , Receptor for Advanced Glycation End Products/metabolism , Lindera/chemistry , Plant Extracts/pharmacology , Mice, Inbred C57BL , Humans , Diet, High-Fat/adverse effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Lipid Metabolism/drug effects , Disease Models, AnimalABSTRACT
BACKGROUND AND OBJECTIVES: Assessment of thoracolumbar spine flexibility is crucial for determining which osteotomy to perform (posterior column osteotomy or 3-column osteotomy) to restore sagittal balance. Although preoperative bolster supine X-rays have been used to evaluate spine flexibility, their correlation with postoperative spinopelvic parameters has not been reported. We aimed to evaluate the predictive value of bolster X-ray for correcting sagittal deformities after thoracolumbar fusion surgery. METHODS: We retrospectively evaluated patients who underwent bolster supine radiography before posterior thoracolumbar fusion. Demographic data, operative records, and radiographic parameters were also recorded. The segmental Cobb angle, defined as the angle between the upper endplate of the uppermost and lower endplates of the lowest instrumented vertebrae, was compared between bolster and postoperative X-ray to evaluate the correlation between them. The predictive value of bolster X-ray for postoperative deformity correction was measured using intraclass correlation coefficients (ICC). RESULTS: Forty-two patients were included. The preoperative segmental Cobb angle (-1.4 ± 22.4) was significantly lower than the bolster segmental Cobb angle (23.2 ± 18.7, P < .001) and postoperative segmental Cobb angle (27.9 ± 22.3, P < .001); however, no significant difference was observed between the bolster and postoperative segmental Cobb angles (P = .746). Bolster X-ray showed a very strong correlation with postoperative X-ray (r = 0.950, P < .001) for segmental Cobb angle. Bolster supine X-ray had good-to-excellent reliability for postoperative X-ray with an ICC of 0.913 (95% CI, 0.760-0.962, P < .001) for the segmental Cobb angle. CONCLUSION: Bolster supine X-rays demonstrate good-to-excellent reliability with postoperative X-rays for segmental Cobb angles. These findings offer valuable insights into the selection of appropriate osteotomy techniques for clinical practice.
ABSTRACT
As an anti-myogenic factor, the myostatin (MSTN) gene was mainly considered as a genetic marker to improve meat production. Moreover, an additional effect of the MSTN mutation on reducing fat deposition in various farm animals suggested a potential application of the MSTN gene on regulating fat deposition in poultry species. Although increase in muscle mass resulted from muscle hyperplasia in the MSTN mutant quail, cellular mechanism behind the decrease in fat deposition was not investigated in the quail model. In the current study, to investigate sexual dimorphic association between fat deposition and Mstn mutation in quail, leg and abdominal fat pads from 4-month-old male and female quail were histologically analyzed. Interestingly, abdominal and leg fat pad weights were significantly decreased by the MSTN mutation only in female quail, but not in male quail, showing sexual dimorphism in regulating fat deposition by the MSTN mutation in quail. Histological analysis also revealed that fat cell sizes of leg and abdominal fats were significantly reduced only in female groups aligning with the decreased fat pad weights. Sexual dimorphic effect of the MSTN mutation on fat cell hypotrophy and reduced fat pad weights in quail provided an important scientific finding to be considered on the usage of the MSTN gene as a genetic marker to reduce fat deposition in poultry species.
Subject(s)
Adipose Tissue , Coturnix , Mutation , Myostatin , Animals , Myostatin/genetics , Myostatin/metabolism , Female , Male , Coturnix/genetics , Coturnix/physiology , Adipose Tissue/metabolism , Sex Characteristics , Avian Proteins/genetics , Avian Proteins/metabolismABSTRACT
The myostatin (MSTN) gene is considered a potential genetic marker to improve economically important traits in livestock, since the discovery of its function using the MSTN knockout mice. The anti-myogenic function of the MSTN gene was further demonstrated in farm animal species with natural or induced mutations. In poultry species, myogenesis in cell culture was regulated by modulation of the MSTN gene. Also, different expression levels of the MSTN gene in poultry models with different muscle mass have been reported, indicating the conserved myogenic function of the MSTN gene between mammalian and avian species. Recent advances of CRISPR/Cas9-mediated genome editing techniques have led to development of genome-edited poultry species targeting the MSTN gene to clearly demonstrate its anti-myogenic function and further investigate other potential functions in poultry species. This review summarizes research conducted to understand the function of the MSTN gene in various poultry models from cells to whole organisms. Furthermore, the genome-edited poultry models targeting the MSTN gene are reviewed to integrate diverse effects of the MSTN gene on different traits of poultry species.
ABSTRACT
Although advanced robots can adeptly mimic human movement and aesthetics, they are still unable to adapt or evolve in response to external experiences. To address this limitation, we propose an innovative approach that uses parallel-processable retention-engineered synaptic devices in the control system. This approach aims to simulate a human-like learning system without necessitating complex computational systems. The retention properties of the synaptic devices were modulated by adjusting the amount of Ag/AgCl ink sprayed. This changed the voltage drop across the interface between the gate electrode and the electrolyte. Furthermore, the unrestricted movement of ions in the electrolyte enhanced the signal multiplexing capability of the ion gel, enabling device-level parallel processing. By integrating the unique characteristics of the synaptic devices with actuators, we successfully emulated a human-like workout process that includes feedback between acute and chronic responses. The proposed control system offers an innovative approach to reducing system complexity and achieving a human-like learning system in the field of biomimicry.
Subject(s)
Robotics , Humans , Robotics/methods , Synapses/physiology , Biomimetics/methodsABSTRACT
Left ventricular twist is influenced by the unique oriented structure of myocardial fibers. Replicating this intricate structural-functional relationship in an in vitro heart model remains challenging, mainly due to the difficulties in achieving a complex structure with synchrony between layers. This study introduces a novel approach through the utilization of bioprinting-assisted tissue assembly (BATA)-a synergistic integration of bioprinting and tissue assembly strategies. By flexibly manufacturing tissue modules and assembly platforms, BATA can create structures that traditional methods find difficult to achieve. This approach integrates engineered heart tissue (EHT) modules, each with intrinsic functional and structural characteristics, into a layered, multi-oriented tissue in a controlled manner. EHTs assembled in different orientations exhibit various contractile forces and electrical signal patterns. The BATA is capable of constructing complex myocardial fiber orientations within a chamber-like structure (MoCha). MoCha replicates the native cardiac architecture by exhibiting three layers and three alignment directions, and it reproduces the left ventricular twist by exhibiting synchronized contraction between layers and mimicking the native cardiac architecture. The potential of BATA extends to engineering tissues capable of constructing and functioning as complete organs on a large scale. This advancement holds the promise of realizing future organ-on-demand technology.
ABSTRACT
Peroxisome proliferator-activated receptor alpha (PPARA) is a ligand-activated transcription factor that is a key mediator of lipid metabolism and metabolic stress in the liver. Accumulating evidence shows that PPARA regulates the expression of various protein coding and non-coding genes that modulate metabolic stress in the liver. CBFA2/RUNX1 partner transcriptional co-repressor 3 (CBFA2T3) is a DNA-binding transcription factor that belongs to the myeloid translocation gene family. Many studies have shown that CBFA2T3 is associated with acute myeloid leukemia. Especially, CBFA2T3-GLIS2 fusion is a chimeric oncogene associated with a poor survival rate in pediatric acute megakaryocytic leukemia. A previous study identified that PPARA activation promoted Cbfa2t3 induction in liver and that Cbfa2t3 may have a modulatory role in metabolic stress. However, the effect of CBFA2T3 gene expression on metabolic stress is not understood. In this study, the PPARA ligand WY14643 activated Cbfa2t3 expression in mouse liver. Glucose tolerance test and insulin tolerance test data showed that insulin resistance is increased in Cbfa2t3-/- mice compared to Cbfa2t3+/+ mice. Hepatic CBFA2T3 modulates heat shock protein family A member 1b and carbonic anhydrase 5a expression. Histology analysis revealed lipid droplet and lipid accumulation in the liver of fasting Cbfa2t3-/- mice but not Cbfa2t3+/+ mice. The expression of lipid accumulation-related genes, such as Cd36, Cidea, and Fabp1, was increased in the liver of fasting Cbfa2t3-/- mice. Especially, basal expression levels of Cidea mRNA were elevated in the liver of Cbfa2t3-/- mice compared to Cbfa2t3+/+ mice. Much higher induction of Cidea mRNA was seen in the liver of Cbfa2t3-/- mice after WY14643 administration. These results indicate that hepatic CBFA2T3 is a PPARA-sensitive gene that may modulate metabolic stress in mouse liver.
Subject(s)
Fasting , Lipid Metabolism , Liver , PPAR alpha , Animals , Lipid Metabolism/genetics , Liver/metabolism , Mice , PPAR alpha/metabolism , PPAR alpha/genetics , Male , Mice, Inbred C57BL , Insulin Resistance , Mice, Knockout , Pyrimidines/pharmacologyABSTRACT
In this study, we propose a generative data augmentation technique to overcome the challenges of severely limited data when designing a deep learning-based automated strabismus diagnosis system. We implement a generative model based on the StyleGAN2-ADA model for system design and assess strabismus classification performance using two classifiers. We evaluate the capability of our proposed method against traditional data augmentation techniques and confirm a substantial enhancement in performance. Furthermore, we conduct experiments to explore the relationship between the diagnosis agreement among ophthalmologists and the generation performance of the generative model. Beyond FID, we validate the generative samples on the classifier to establish their practicality. Through these experiments, we demonstrate that the generative model-based data augmentation improves overall quantitative performance in scenarios of extreme data scarcity and effectively mitigates overfitting issues during deep learning model training.
Subject(s)
Deep Learning , Strabismus , Humans , Strabismus/diagnosis , Strabismus/classification , AlgorithmsABSTRACT
Glucosinolates (GSLs) are defensive secondary metabolites produced by Brassicaceae species in response to abiotic and biotic stresses. The biosynthesis of GSL compounds and the expression of GSL-related genes are highly modulated by endogenous signals (i.e., circadian clocks) and environmental cues, such as temperature, light, and pathogens. However, the detailed mechanism by which light signaling influences GSL metabolism remains poorly understood. In this study, we found that a light-signaling factor, ELONGATED HYPOCOTYL 5 (HY5), was involved in the regulation of GSL content under light conditions in Arabidopsis (Arabidopsis thaliana). In hy5-215 mutants, the transcript levels of GSL pathway genes were substantially upregulated compared with those in wild-type plants. The content of GSL compounds was also substantially increased in hy5-215 mutants, whereas 35S::HY5-GFP/hy5-215 transgenic lines exhibited comparable levels of GSL-related transcripts and GSL content to those in WT plants. HY5 physically interacts with HISTONE DEACETYLASE9 (HDA9) and binds to the proximal promoter region of MYB29 and IMD1 to suppress aliphatic GSL biosynthetic processes. These results demonstrate that HY5 suppresses GSL accumulation during the daytime, thus properly modulating GSL content daily in Arabidopsis plants.
ABSTRACT
Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), often have concomitant mental disorders such as depression and anxiety. Therefore, a bidirectional approach involving the gut and brain axes is necessary for the prevention and treatment thereof. In this study, we explored the potential of Poncirus trifoliata extract (PT), traditionally known for its neuroprotective effects against gastrointestinal diseases, as a natural treatment agent for IBD in a dextran sulfate sodium (DSS)-induced colitis model. Oral administration of PT ameliorated weight loss and inflammatory responses in mice with DSS-induced colitis. Furthermore, PT treatment effectively restored the colon length and ameliorated enterocyte death by inhibiting DSS-induced reactive oxygen species (ROS)-mediated necroptosis. The main bioactive components of PT, poncirin and naringin, confirmed using ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-qTOF), can be utilized to regulate necroptosis. The antidepressant-like effects of PT were confirmed using open field test (OFT) and tail suspension test (TST). PT treatment also restored vascular endothelial cell integrity in the hippocampus. In the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) regions of the hippocampus, PT controlled the neuroinflammatory responses of proliferated microglia. In conclusion, PT, which contains high levels of poncirin and naringin, has potential as a bidirectional therapeutic agent that can simultaneously improve IBD-associated intestinal and mental disorders.
Subject(s)
Colitis , Depression , Dextran Sulfate , Flavanones , Mice, Inbred C57BL , Plant Extracts , Poncirus , Animals , Poncirus/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , Male , Mice , Depression/drug therapy , Flavanones/pharmacology , Flavanones/isolation & purification , Colitis/drug therapy , Colitis/chemically induced , Colitis/pathology , Behavior, Animal/drug effects , Disease Models, Animal , Antidepressive Agents/pharmacology , Antidepressive Agents/isolation & purification , Flavonoids/pharmacology , Flavonoids/isolation & purification , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Reactive Oxygen Species/metabolismABSTRACT
Limited studies using animal models with a few natural mutations in melanophilin (Mlph) provided partial functions of Mlph in melanosome trafficking. To investigate cellular functions of Mlph, especially ZnF motif of Mlph, we analyzed all three Mlph knockout (KO) quail lines, one and two base pair (bp) deletions as models for total KO, and three bp deletion causing deletion of one Cysteine (C84del) in the ZnF motif. All quail lines had diluted feather pigmentation with impaired dendritogenesis and melanosome transport in melanocytes. In vitro studies revealed capability of binding of the ZnF motif to PIP3, and impairment of PI3P binding and mislocalization of MLPH proteins with ZnF motif mutations. The shortened melanocyte dendrites by the C84del mutation were rescued by introducing WT Mlph in vitro. These results revealed the diluted feather pigmentation by Mlph mutations resulted from congregation of melanosomes in the cell bodies with impairment of the dendritogenesis and the transport of melanosomes to the cell periphery.
Subject(s)
Feathers , Melanocytes , Melanosomes , Pigmentation , Animals , Feathers/metabolism , Melanocytes/metabolism , Pigmentation/genetics , Melanosomes/metabolism , Quail , Mutation , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolismABSTRACT
This study proposes a titanium silicide (TiSi2) recombination layer for perovskite/tunnel oxide passivated contact (TOPCon) 2-T tandem solar cells as an alternative to conventional transparent conductive oxide (TCO)-based recombination layers. TiSi2 was formed while TiO2 was made by oxidizing a Ti film deposited on the p+-Si layer. The reaction formation mechanism was proposed based on the diffusion theory supported by experimental results. The optical and electrical properties of the TiSi2 layer were optimized by controlling the initial Ti thicknesses (5-100 nm). With the initial Ti of 50 nm, the lowest reflectance and highly ohmic contact between the TiO2 and p+-Si layers with a contact resistivity of 161.48 mΩ·cm2 were obtained. In contrast, the TCO interlayer shows Schottky behavior with much higher contact resistivities. As the recombination layer of TiSi2 and the electron transport layer of TiO2 are formed simultaneously, the process steps become simpler. Finally, the MAPbI3/TOPCon tandem device yielded an efficiency of 16.23%, marking the first reported efficiency for a device including a silicide-based interlayer.
ABSTRACT
PURPOSE: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. MATERIALS AND METHODS: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. RESULTS: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. CONCLUSIONS: Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.
ABSTRACT
Background/Purpose: In vat photopolymerization, post-polymerization of the three-dimensional (3D) printing resin is necessary to ensure the optimum physical properties of the printed objects. This study aimed to evaluate the potential use of a handheld polywave light-emitting diode (LED) dental light-curing unit (LCU) for post-polymerizing 3D printed resins by measuring the microhardness and biaxial flexural strength of the post-polymerized resin. Material and methods: 3D printed 1- and 2-mm-thick disks were irradiated with a dental LCU at 3200 mW/cm2. Post-polymerization was repeated either on one side from the top surface: two cycles (T2), four cycles (T4), and eight cycles (T8), or on both sides from the top and bottom surfaces: one cycle (T1B1), two cycles (T2B2), and four cycles (T4B4) for each side. The microhardness and biaxial strength of the disks were compared to those post-polymerized by a conventional desktop polymerizing unit (PC) and those without post-polymerization (NC). Results: Microhardness of the disks varied between the top and bottom surfaces of the 1-mm and 2-mm-thick disks, depending on the post-polymerization methods. T8 and T4B4 produced comparable microhardness on the top surface to PC for both thicknesses. In contrast, PC, T2B2, and T4B4 exhibited the highest microhardness on the bottom surface. Except for NC, the 1-mm-thick disks had a higher biaxial flexural strength than the 2-mm-thick disks. T4B4 resulted in the highest biaxial flexural strength for both thicknesses, which was comparable to that of the desktop polymerizing unit. Conclusion: The microhardness and biaxial flexural strengths of the post-polymerized 3D-printed disks increase with polymerization time. With sufficient polymerization from both sides, the polywave LCU has the potential to be a viable alternative to desktop polymerization units.
ABSTRACT
Electrostatic capacitors are foundational components of advanced electronics and high-power electrical systems owing to their ultrafast charging-discharging capability. Ferroelectric materials offer high maximum polarization, but high remnant polarization has hindered their effective deployment in energy storage applications. Previous methodologies have encountered problems because of the deteriorated crystallinity of the ferroelectric materials. We introduce an approach to control the relaxation time using two-dimensional (2D) materials while minimizing energy loss by using 2D/3D/2D heterostructures and preserving the crystallinity of ferroelectric 3D materials. Using this approach, we were able to achieve an energy density of 191.7 joules per cubic centimeter with an efficiency greater than 90%. This precise control over relaxation time holds promise for a wide array of applications and has the potential to accelerate the development of highly efficient energy storage systems.
ABSTRACT
[This corrects the article DOI: 10.1021/acsomega.9b04199.].
ABSTRACT
Advanced heterogeneous integration technologies are pivotal for next-generation electronics. Single-crystalline materials are one of the key building blocks for heterogeneous integration, although it is challenging to produce and integrate these materials. Remote epitaxy is recently introduced as a solution for growing single-crystalline thin films that can be exfoliated from host wafers and then transferred onto foreign platforms. This technology has quickly gained attention, as it can be applied to a wide variety of materials and can realize new functionalities and novel application platforms. Nevertheless, remote epitaxy is a delicate process, and thus, successful execution of remote epitaxy is often challenging. Here, we elucidate the mechanisms of remote epitaxy, summarize recent breakthroughs, and discuss the challenges and solutions in the remote epitaxy of various material systems. We also provide a vision for the future of remote epitaxy for studying fundamental materials science, as well as for functional applications.
ABSTRACT
Hepatocyte nuclear factor 4A (HNF4A/NR2a1), a transcriptional regulator of hepatocyte identity, controls genes that are crucial for liver functions, primarily through binding to enhancers. In mammalian cells, active and primed enhancers are marked by monomethylation of histone 3 (H3) at lysine 4 (K4) (H3K4me1) in a cell type-specific manner. How this modification is established and maintained at enhancers in connection with transcription factors (TFs) remains unknown. Using analysis of genome-wide histone modifications, TF binding, chromatin accessibility and gene expression, we show that HNF4A is essential for an active chromatin state. Using HNF4A loss and gain of function experiments in vivo and in cell lines in vitro, we show that HNF4A affects H3K4me1, H3K27ac and chromatin accessibility, highlighting its contribution to the establishment and maintenance of a transcriptionally permissive epigenetic state. Mechanistically, HNF4A interacts with the mixed-lineage leukaemia 4 (MLL4) complex facilitating recruitment to HNF4A-bound regions. Our findings indicate that HNF4A enriches H3K4me1, H3K27ac and establishes chromatin opening at transcriptional regulatory regions.