The distribution and abundance of immune cells, particularly T‐cell subsets, play pivotal roles in cancer immunology and therapy. T cells have many subsets with specific function and current methods ...are limited in estimating them, thus, a method for predicting comprehensive T‐cell subsets is urgently needed in cancer immunology research. Here, Immune Cell Abundance Identifier (ImmuCellAI), a gene set signature‐based method, is introduced for precisely estimating the abundance of 24 immune cell types including 18 T‐cell subsets, from gene expression data. Performance evaluation on both the sequencing data with flow cytometry results and public expression data indicate that ImmuCellAI can estimate the abundance of immune cells with superior accuracy to other methods especially on many T‐cell subsets. Application of ImmuCellAI to immunotherapy datasets reveals that the abundance of dendritic cells, cytotoxic T, and gamma delta T cells is significantly higher both in comparisons of on‐treatment versus pre‐treatment and responders versus non‐responders. Meanwhile, an ImmuCellAI result‐based model is built for predicting the immunotherapy response with high accuracy (area under curve 0.80–0.91). These results demonstrate the powerful and unique function of ImmuCellAI in tumor immune infiltration estimation and immunotherapy response prediction.
Immune Cell Abundance Identifier (ImmuCellAI) is a gene set signature‐based method for precisely estimating the abundance of 24 immune cell types including 18 T‐cell subsets. Application of ImmuCellAI to immunotherapy datasets reveals the dynamic change of immune cell abundance. An ImmuCellAI result‐based model for predicting the immunotherapy response achieves high accuracy with area under curve 0.80–0.91.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Spheroid-based three-dimensional (3D) liver culture models, offering a desirable biomimetic microenvironment, are useful for recapitulating liver functions in vitro. However, a user-friendly, robust ...and specially optimized method has not been well developed for a convenient, highly efficient, and safe in situ perfusion culture of spheroid-based 3D liver models. Here, we have developed a biomimetic and reversibly assembled liver-on-a-chip (3D-LOC) platform and presented a proof of concept for long-term perfusion culture of 3D human HepG2/C3A spheroids for building a 3D liver spheroid model. On the basis of a fast and reversible seal of concave microwell-based PDMS-membrane-PDMS sandwich multilayer chips, it enables a high-throughput and parallel perfusion culture of 1080 cell spheroids in a high mass transfer and low fluid shear stress biomimetic microenvironment as well as allowing the convenient collection and analysis of the cell spheroids. In terms of reducing spheroid loss and maintaining cell morphology and viability in long-term perfusion culture, the cell spheroids in the 3D-LOC were more safe and efficient. Notably, the polarisation, liver-specific functions, and metabolic activity of the cell spheroids in 3D-LOC were also remarkably improved and exhibited better long-term maintenance over conventional perfusion methods. Additionally, a robust micromilling method that incorporates secondary PDMS coating techniques (SPCs) for fabricating V-shaped concave microwells was also developed. The V-shaped concave microwell arrays exhibited a higher distribution density and aperture ratio, making it easy to form large-scale and uniform-sized cell spheroids with minimum cell loss. In summary, the proposed 3D-LOC could provide a convenient and robust solution for the long-term safe perfusion culture of hepatic spheroids and be beneficial for a variety of potential applications including development of bio-artificial livers, disease modeling, and drug toxicity screening.
Monoubiquitination of histone H2B on lysine 120 (H2Bub1) is an epigenetic mark generally associated with transcriptional activation, yet the global functions of H2Bub1 remain poorly understood. ...Ferroptosis is a form of non‐apoptotic cell death characterized by the iron‐dependent overproduction of lipid hydroperoxides, which can be inhibited by the antioxidant activity of the solute carrier family member 11 (SLC7A11/xCT), a component of the cystine/glutamate antiporter. Whether nuclear events participate in the regulation of ferroptosis is largely unknown. Here, we show that the levels of H2Bub1 are decreased during erastin‐induced ferroptosis and that loss of H2Bub1 increases the cellular sensitivity to ferroptosis. H2Bub1 epigenetically activates the expression of SLC7A11. Additionally, we show that the tumor suppressor p53 negatively regulates H2Bub1 levels independently of p53's transcription factor activity by promoting the nuclear translocation of the deubiquitinase USP7. Moreover, our studies reveal that p53 decreases H2Bub1 occupancy on the SLC7A11 gene regulatory region and represses the expression of SLC7A11 during erastin treatment. These data not only suggest a noncanonical role of p53 in chromatin regulation but also link p53 to ferroptosis via an H2Bub1‐mediated epigenetic pathway. Overall, our work uncovers a previously unappreciated epigenetic mechanism for the regulation of ferroptosis.
Synopsis
This study uncovers a previously unknown epigenetic regulatory mechanism for the control of ferroptosis by p53‐USP7‐H2Bub1 axis.
H2Bub1 is a novel epigenetic regulator of ferroptosis.
p53 regulates H2Bub1 independent of its transcription factor activity by recruiting the H2Bub1 deubiquitinase USP7 to chromatin.
p53‐USP7 interplay reduces the occupancy of H2Bub1 on the SLC7A11 regulatory region, resulting in transcriptional repression and increased sensitivity to ferroptosis induction.
These results not only suggest a novel role of H2Bub1 in the regulation of ferroptosis but also reveal a relative direct role of p53 in the regulation of chromatin events.
p53 recruits USP7 to the regulatory region of SLC7A11 to reduce H2B monoubiquitination, resulting in transcriptional repression of SCL7A11 and ferroptosis induction. These results uncover an epigenetic regulatory mechanism for the control of ferroptosis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Discrimination of physically similar molecules by porous solids represents an important yet challenging task in industrially relevant chemical separations. Precisely controlled pore dimension and/or ...tailored pore surface functionality are crucial to achieve high‐efficiency separation. Metal‐organic frameworks (MOFs) are promising candidates for these challenging separations in light of their structural diversity as well as highly adjustable pore dimension/functionality. We report here a microporous, ftw‐type Zr‐based MOF structure, HIAM‐410 (HIAM=Hoffmann Institute of Advanced Materials), built on hexanuclear Zr6 cluster and pyrene‐1,3,6,8‐tetracarboxylate (ptc4−). Its crystallographic structure has been determined using continuous rotation electron diffraction (cRED) technique combined with Rietveld refinement against powder X‐ray diffraction data, aided by low‐dose high‐resolution transmission electron microscopy (HRTEM) imaging. The compound features exceptional framework stability that is comparable to the prototype MOF UiO‐66. Interestingly, the linker vacancies in the pristine MOF structure could be partially restored by post‐synthetic linker insertion. Its separation capability of hexane isomers is enhanced substantially upon the linker vacancy engineering. The restored structure exhibits efficient splitting of monobranched and dibranched hexane isomers at both room temperature and industrially relevant temperature.
A highly robust ftw‐type zirconium‐based metal–organic framework has been constructed. Its linker vacancy sites are restored by post‐synthetic linker insertion, which notably enhances its separation performance toward alkane isomers.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A miniaturized multifrequency antenna is proposed. The proposed antenna can generate three separate impedance bandwidths to cover all the 2.4/5.2/5.8-GHz WLAN operating bands and the 2.5/3.5/5.5-GHz ...WiMAX bands. The proposed microstrip-fed antenna mainly consists of a circular ring, a Y-shape-like strip, and a defected ground plane. By adding a Y-shape-like strip in the circular ring, the antenna excites two resonant modes and is with miniaturization structure. Because of the introduction of the cambered ground plane with an isosceles triangle-defect, the third wide band with better impedance matching is obtained. A prototype is experimentally tested, and the measured results show good radiation patterns and enough gains across the operation bands.
It is desirable to extend the surface-enhanced Raman scattering (SERS) from the conventionally used visible range into the infrared region, because the fluorescence background is lower in the ...long-wavelength regime. To do this, it is important to have a SERS substrate suitable for infrared operation. In this work, we report the near infrared SERS operation based on the substrates employing star-shaped gold/silver nanoparticles and hyperbolic metamaterial (HMM) structure. We first fabricate the SERS substrate in which nanoparticles are separated from a silver film by a thin dielectric layer. Performance of the SERS substrate is investigated with a 1064-nm excitation source. Compared with similar silver film-based substrates employing respectively gold and silver spherical nanoparticles, it is found that, Raman intensity scattered by the substrate with star-shaped nanoparticles is 7.4 times stronger than that with gold nanoparticles, and 3.4 times stronger than that with silver nanoparticles. Following this, we fabricate the SERS substrate where the star-shaped nanoparticles are deposited over a HMM structure. The HMM structure comprises three pairs of germanium-silver multilayers. Further experimental result shows that, with the star-shaped nanoparticles, the HMM-based substrate yields 30% higher Raman intensity for near infrared SERS operation than the silver film-based substrate does.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Soybean is one of the most important vegetable oil and protein feed crops. To capture the entire genomic diversity, it is needed to construct a complete high-quality pan-genome from diverse soybean ...accessions. In this study, we performed individual de novo genome assemblies for 26 representative soybeans that were selected from 2,898 deeply sequenced accessions. Using these assembled genomes together with three previously reported genomes, we constructed a graph-based genome and performed pan-genome analysis, which identified numerous genetic variations that cannot be detected by direct mapping of short sequence reads onto a single reference genome. The structural variations from the 2,898 accessions that were genotyped based on the graph-based genome and the RNA sequencing (RNA-seq) data from the representative 26 accessions helped to link genetic variations to candidate genes that are responsible for important traits. This pan-genome resource will promote evolutionary and functional genomics studies in soybean.
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•de novo genome assemblies for 26 representative soybeans•Construction of a graph-based genome•Identification of large structural variations and gene fusion events•Link structural variations to gene expressions and agronomic traits
A high-quality graph-based soybean pan-genome is constructed through de novo genome assemblies of 26 representative wild and cultivated soybean accessions, demonstrating the impact of structural variation on key agronomic traits.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A deep UV light photodetector is assembled by coating multilayer graphene on beta‐gallium oxide (β‐Ga2O3) wafer. Optoelectronic analysis reveals that the heterojunction device is virtually blind to ...light illumination with wavelength longer than 280 nm, but is highly sensitive to 254 nm light with very good stability and reproducibility.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Blood–brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have ...previously reported that lychee seed polyphenols (LSP) exerted anti‐neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO‐1, were examined. In addition, the inhibition of Aβ(25–35)‐induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase‐1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase‐1, IL‐1β, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aβ(25–35)‐induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase‐1, IL‐1β, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aβ(25–35)‐induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1‐mediated autophagy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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