The spatial organization of chromatin is pivotal for regulating genome functions. We report an imaging method for tracing chromatin organization with kilobase- and nanometer-scale resolution, ...unveiling chromatin conformation across topologically associating domains (TADs) in thousands of individual cells. Our imaging data revealed TAD-like structures with globular conformation and sharp domain boundaries in single cells. The boundaries varied from cell to cell, occurring with nonzero probabilities at all genomic positions but preferentially at CCCTC-binding factor (CTCF)- and cohesin-binding sites. Notably, cohesin depletion, which abolished TADs at the population-average level, did not diminish TAD-like structures in single cells but eliminated preferential domain boundary positions. Moreover, we observed widespread, cooperative, multiway chromatin interactions, which remained after cohesin depletion. These results provide critical insight into the mechanisms underlying chromatin domain and hub formation.
The 3D organization of chromatin regulates many genome functions. Our understanding of 3D genome organization requires tools to directly visualize chromatin conformation in its native context. Here ...we report an imaging technology for visualizing chromatin organization across multiple scales in single cells with high genomic throughput. First we demonstrate multiplexed imaging of hundreds of genomic loci by sequential hybridization, which allows high-resolution conformation tracing of whole chromosomes. Next we report a multiplexed error-robust fluorescence in situ hybridization (MERFISH)-based method for genome-scale chromatin tracing and demonstrate simultaneous imaging of more than 1,000 genomic loci and nascent transcripts of more than 1,000 genes together with landmark nuclear structures. Using this technology, we characterize chromatin domains, compartments, and trans-chromosomal interactions and their relationship to transcription in single cells. We envision broad application of this high-throughput, multi-scale, and multi-modal imaging technology, which provides an integrated view of chromatin organization in its native structural and functional context.
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•Massively multiplexed FISH enables mapping chromatin structure at genome scale•Multimodal high-throughput imaging places chromatin structure in functional context•Trans-chromosome or long-range interactions occur preferentially among active chromatin•Transcription activity correlates with local enrichment of compartment A chromatin
Su et al. present a high-throughput, multi-modal imaging platform to assay the 3D organization of chromatin at genome scale in its functional context in thousands of cells. This platform enables integrated measurements of more than 1,000 genomic loci together with the transcription activity of more than 1,000 genes in the same cells with landmark nuclear structures, making it possible to directly link gene activity to chromosome folding and to answer interesting biological questions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and ...prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of
genes cause inter-individual variations in metabolism and disease susceptibility. Genetic variants of
,
genes are associated with cardiovascular diseases. Mutations of
,
, and other
genes that generate 20-HETE are a potential risk for cancer.
gene variants are associated with ocular disease, while those of
are linked to skin disease and
is associated with the inflammatory response. The present study comprehensively collected research to provide an updated view of the molecular functionality of
genes and their associations with human diseases. Functional analysis of
genes with clinical implications is necessary to understand inter-individual variations in disease susceptibility and for the development of alternative treatment strategies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The spatial organization of chromatin critically affects genome function. Recent chromosome-conformation-capture studies have revealed topologically associating domains (TADs) as a conserved feature ...of chromatin organization, but how TADs are spatially organized in individual chromosomes remains unknown. Here, we developed an imaging method for mapping the spatial positions of numerous genomic regions along individual chromosomes and traced the positions of TADs in human interphase autosomes and X chromosomes. We observed that chromosome folding deviates from the ideal fractal-globule model at large length scales and that TADs are largely organized into two compartments spatially arranged in a polarized manner in individual chromosomes. Active and inactive X chromosomes adopt different folding and compartmentalization configurations. These results suggest that the spatial organization of chromatin domains can change in response to regulation.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that causes the Coronavirus Disease 2019 (COVID-19), which has been the most challenging pandemic in this ...century. Considering its high mortality and rapid spread, an effective vaccine is urgently needed to control this pandemic. As a result, the academia, industry, and government sectors are working tightly together to develop and test a variety of vaccines at an unprecedented pace. In this review, we outline the essential coronavirus biological characteristics that are important for vaccine design. In addition, we summarize key takeaways from previous vaccination studies of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), highlighting the pros and cons of each immunization strategy. Finally, based on these prior vaccination experiences, we discuss recent progress and potential challenges of COVID-19 vaccine development.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in ...complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.
Electrocatalytic reduction of nitrate (NO3RR) to synthesize ammonia (NH3) provides a competitive manner for carbon neutrality and decentralized NH3 synthesis. Atomically precise nanoclusters, as an ...advantageous platform for investigating the NO3RR mechanisms and actual active sites, remain largely underexplored due to the poor stability. Herein, we report a (NH4)9Ag9(mba)9 nanoclusters (Ag9 NCs) loaded on Ti3C2 MXene (Ag9/MXene) for highly efficient NO3RR performance towards ambient NH3 synthesis with improved stability in neutral medium. The composite structure of MXene and Ag9 NCs enables a tandem catalysis process for nitrate reduction, significantly increasing the selectivity and FE of NH3. Besides, compared with individual Ag9 NCs, Ag9/MXene has better stability with the current density performed no decay after 108 hours of reaction. This work provides a strategy for improving the catalytic activity and stability of atomically precise metal NCs, expanding the mechanism research and application of metal NCs.
Silver nanoclusters loaded on Ti3C2 MXene (Ag9/MXene) displays highly efficient NO3RR performance towards ambient NH3 synthesis in neutral medium. The composite structure of MXene and Ag9 NCs enables a tandem catalysis process for nitrate reduction, significantly increasing the selectivity and FE of NH3.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The ethanol precipitation method has been widely-used for Dendrobium officinale polysaccharides preparation. However, the alcohol-soluble fractions have always been ignored, which causes significant ...wastes of resources and energies. In this study, the extraction, physicochemical properties, and immune regulation activity of an edible D. officinale polysaccharide (DOPs) isolated from the supernatant after 75% ethanol precipitation were systematically investigated. The structural characteristics determination results showed that DOPs was mainly composed of glucose and mannose at a molar ratio of 1.00:5.78 with an average molecular weight of 4.56 × 103 Da, which was made up of α-(1,3)-Glcp as the main skeleton, and the α-(1,4)-Glcp and β-(1,4)-Manp as the branches. Subsequently, the cyclophosphamide (CTX)-induced immunosuppressive mice model was established, and the results demonstrated that DOPs could dose-dependently protect the immune organs against CTX damage, improve the immune cells activities, and promote the immune-related cytokines (IL-2, IFN-γ and TNF-α) secretions. Furthermore, DOPs treatment also effectively enhanced the antioxidant enzymes levels (SOD, GSH-Px) in sera and livers, therefore weakening the oxidative damage of CTX-treated mice. Considering these above data, DOPs presented great potential to be explored as a natural antioxidant and supplement for functional foods.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper proposes a new typology that classifies innovation policy instruments into two dimensions: government-selection versus market-selection, and producer-orientation versus ...consumer-orientation. Such a typology articulates the importance of consumer behavior in the policy design for a transition, and the relevance for the market to select target subjects of policy during the deployment stage of clean technology innovation. We apply this typology to policy instruments of China's new energy vehicle (NEV) industry between 1991 and 2015 in order to explain the industry's rapid growth. The focus of China's policy mix has transited from government-selection to market-selection, and from producer-orientation to consumer-orientation. Other than the new typology, this paper traces the entire history of policy transition within China's NEV industry, and finds the transition to be a result of policy learning, thus contributing to future empirical studies of this industry.
•This paper shows the change of China's innovation policy mix for the new energy vehicle industry.•We design a new typology of innovation policy instruments.•China's policy mix has undergone a transition according to the new typology.•The transition explains why new energy vehicles have recently diffused quickly in China.•Rationale and background of such a transition is provided.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who ...are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients.
We conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled.
Eighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9-20) and 11 (range, 8-19) days, with a cumulative incidence of 97.8 and 97.1% (P = 0.528), respectively. HID recipients had an increased cumulative incidence of grades II-IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%, P < 0.001), grades III-IV aGVHD (10.1 vs. 1.5%, P = 0.026), and chronic GVHD (cGVHD) (30.6 vs. 4.4%, P < 0.001) at 1 year but similar extensive cGVHD (3.4 vs. 0%, P = 0.426). The three-year estimated overall survival (OS) rates were 86.1 and 91.3% (P = 0.358), while the three-year estimated failure-free survival (FFS) rates were 85.0 and 89.8% (P = 0.413) in the HID and MRD cohorts, respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with increased transfusions and poor performance status pre-SCT. We did not observe differences in primary engraftment and survival outcomes by donor type.
Haploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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