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OBJECTIVES: To investigate the mechanism by which intestinal epithelial cell (IEC) death induces arthritis. METHODS: IEC death was assessed by staining for necroptosis and apoptosis markers and fluorescence in situ hybridisation at different time points during collagen-induced arthritis (CIA). During the development of CIA, messenger RNA (mRNA) sequencing was performed, followed by Gene Ontology enrichment analysis of differentially expressed genes. Mice deficient for hypoxia-inducible factor 1α (Hif1a) in IECs (Hif1a ∆IEC) were generated and induced for arthritis. mRNA sequencing, chromatin immunoprecipitated (ChIP) DNA sequencing and ChIP-qualitative PCR were performed on IECs from Hif1a ∆IEC mice and littermate controls. Effects of HIF1α stabilisation by inhibition of prolyl hydroxylase domain-containing enzymes and treatment with the inhibitor of receptor-interacting protein kinase-3 (RIPK3) were tested in intestinal organoids and in CIA. RESULTS: IEC underwent apoptotic and necroptotic cell death at the onset of arthritis, leading to impaired gut barrier function. HIF1α was identified as one of the most upregulated genes in IECs during the onset of arthritis. Deletion of Hif1a in IEC enhanced IEC necroptosis, triggered intestinal inflammation and exacerbated arthritis. HIF1α was found to be a key transcriptional repressor for the necroptosis-inducing factor RIPK3. Enhanced RIPK3 expression, indicating necroptosis, was also found in the intestinal epithelium of patients with new-onset rheumatoid arthritis. Therapeutic stabilisation of HIF1α as well as small-molecule-based RIPK3 inhibition rescued intestinal necroptosis in vitro and in vivo and suppressed the development of arthritis. CONCLUSION: Our results identify IEC necroptosis as a critical link between the gut and the development of arthritis.
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Apoptosis , Artritis Experimental , Subunidad alfa del Factor 1 Inducible por Hipoxia , Mucosa Intestinal , Necroptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Animales , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Artritis Experimental/metabolismo , Artritis Experimental/patología , Artritis Experimental/genética , Ratones , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Células Epiteliales/metabolismo , HumanosRESUMEN
This study examined the impact of Semen raphani on the absorption of ginsenosides from Panax ginseng C.A. Meyer (ginseng) using a Caco-2 cell model and Ultra-High-Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS). Six primary ginsenosides (Rg1, Re, Rb1, Rb2, Rc, Rd) were quantified. Results showed that Semen Raphani increased the efflux rate of ginsenosides, particularly at higher concentrations, suggesting it inhibits their absorption. The research elucidates the intestinal absorption process of ginsenosides and the antagonistic mechanism of Semen Raphani against ginseng.
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Ultralong carbon nanotubes (CNTs) are in huge demand in many cutting-edge fields due to their macroscale lengths, perfect structures, and extraordinary properties, while their practical application is limited by the difficulties in their mass production. Herein, we report the synthesis of ultralong CNTs with a dramatically increased yield by a simple but efficient substrate interception and direction strategy (SIDS), which couples the advantages of floating-catalyst chemical vapor deposition with the flying-kite-like growth mechanism of ultralong CNTs. The SIDS-assisted approach prominently improves the catalyst utilization and significantly increases the yield. The areal density of the ultralong CNT arrays with length of over 1 cm reached a record-breaking value of â¼6700 CNTs mm-1, which is 2-3 orders of magnitude higher than the previously reported values obtained by traditional methods. The SIDS provides a solution for synthesizing high-quality ultralong CNTs with high yields, laying the foundation for their mass production.
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A polyvinylpyrrolidone-capped (PVP-capped) strategy is reported to synthesize Ag NPs on silicon wafers via galvanic replacement reaction for SERS detection of adenine, where PVP acts as stabilizing agent in synthesis and efficient enrichment in detection. The morphologies of Ag NPs are optimized with uniform particle size by adjusting synthesis conditions, which hold excellent SERS performances like a high enhancement factor of 1.42 × 106, good uniform, reproducibility, and transferable nature. With the protection of the capped PVP, the Ag NPs keep excellent SERS properties even against harsh conditions of high temperature (100 â) and strong acid and base for 24 h. Utilizing the structural feature of PVP with abundant carbonyl groups, the PVP-capped Ag NPs achieve efficient enrichment of adenine through hydrogen bonding and π-interactions, which is analyzed by density functional theory. Quantitative detection of adenine is performed with a wide linear range from 10-4 to 10-8 M and a low limit of detection of 1 nM. Detection of adenine in human urine samples is achieved with a recovery of 99.1-103.4% and an RSD of less than 5%.
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Transition metal oxides (TMOs) are promising inorganic electrochromic materials (ECMs) that can be widely used in electronic displays and adaptive camouflage. However, there are still huge challenges for TMOs to simultaneously achieve multicolor transformation capability and good cycling stability. Herein, we assemble Au-modified (0.01 wt %) VxO2x+1 (x > 2) nanoflowers (Au@VxO2x+1 NFs) composed of two-dimensional porous nanosheets containing two valences states of vanadium (V4+ and V5+). The Au@VxO2x+1 NFs exhibits outstanding electrochromic performance with five reversible color transformations (orange, yellow, green, gray, and blue) at a voltage less than 1.5 V and excellent cycling stability (2000 cycles without significant decay). To the best of our knowledge, this is the first time that a single vanadium oxide ECM, rather than a device, realizes five color changes. This work provides a feasible way for the efficient preparation of multicolor electrochromic TMOs. The newly developed Au@VxO2x+1 NFs demonstrate the potential application in adaptive camouflage.
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Designing high-performance trifunctional electrocatalysts for ORR/OER/HER with outstanding activity and stability for each reaction is quite significant yet challenging for renewable energy technologies. Herein, a highly efficient and durable trifunctional electrocatalyst RuCoOx is prepared by a unique one-pot glucose-blowing approach. Remarkably, RuCoOx catalyst exhibits a small potential difference (ΔE) of 0.65 V and low HER overpotential of 37 mV (10 mA cm-2), as well as a negligible decay of overpotential after 200â¯000/10â¯000/10â¯000 CV cycles for ORR/OER/HER, all of which show overwhelming superiorities among the advanced trifunctional electrocatalysts. When used in liquid rechargeable Zn-air batteries and water splitting electrolyzer, RuCoOx exhibits high efficiency and outstanding durability even at quite large current density. Such excellent performance can be attributed to the rational combination of targeted ORR/OER/HER active sites into one electrocatalyst based on the double-phase coupling strategy, which induces sufficient electronic structure modulation and synergistic effect for enhanced trifunctional properties.
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Fructokinase (FRK) and fructokinase-like (FLN), belonging to the phosphofructokinase B type subfamily, share substantial sequence similarity, and are crucial in various plant physiological processes. However, there is limited information regarding what functionally differentiates plant FRKs from FLNs. Here, a total of three CsFRKs and two CsFLNs were identified from the cucumber genome. Their significant difference lay in the structure of their G/AXGD motif, which existed as GAGD in CsFRKs, but as G/ASGD in CsFLNs. Comparative phylogenetic analysis classified CsFRKs and CsFLNs into five sub-branches consistent with their quite different exon/intron organizations. Both transcriptome data and RT-qPCR analyses revealed that CsFRK3 was the most active gene, with the highest expression in the majority of tissues tested. Moreover, the expression levels of two putative plastidic genes, CsFRK1 and CsFLN2, were significantly positively associated with chlorophyll accumulation in the chlorophyll-reduced cucumber mutant. Briefly, both CsFRK and CsFLN genes were involved in the development of sink tissues, especially CsFRK3. CsFRK1 and CsFLN2 were recognized as candidates in the chlorophyll biosynthesis pathway of cucumber. These results would greatly assist in further investigation on functional characterization of FRKs and FLNs, especially in the development and chlorophyll biosynthesis of cucumber.
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Cucumis sativus , Cucumis sativus/genética , Cucumis sativus/metabolismo , Filogenia , Fructoquinasas/genética , Fructoquinasas/metabolismo , Intrones , Clorofila/metabolismoRESUMEN
BACKGROUND: A shelf-life that is too short is the main problem with strawberries. Nano-TiO2 can catalyze and oxidize ethylene under ultraviolet (UV) light irradiation to eliminate its ripening effect on fruits and prolong the freshness period. RESULTS: In this work, nano-TiO2 modified by methacryloxy propyl trimethoxyl silane (KH570) was blended with low-density polyethylene (LDPE) to prepare modified atmosphere packaging (MAP), and the influence of TiO2 content on films was analyzed before and after UV treatment. The results show that the modified nano-TiO2 (M-TiO2 ) can be uniformly distributed in LDPE, improving its mechanical strength, hydrophobicity, oxygen barrier and UV shielding properties. A modified atmosphere with low ethylene, low O2 and high CO2 can be created to inhibit the ripening and spoilage of strawberries. The weight loss rate of fruit can be effectively reduced. The tendency of fruit firmness decline and nutrient loss can be slowed and stabilized, contributing to controllable shelf-life. Excellent freshness preservation function can be realized without special UV treatment. CONCLUSION: Since UV treatment is rare in actual storage and transportation, LDPE/M-TiO2 composite film has practical value as MAP for strawberry and similar non-climacteric fruits. © 2022 Society of Chemical Industry.
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Fragaria , Atmósfera , Etilenos/análisis , Fragaria/química , Frutas/química , Oxígeno/análisis , PolietilenoRESUMEN
Fe2O3-based catalysts have promising potential in the selective catalytic reduction (SCR) of NO with NH3 with the advantages of environmental friendliness, excellent medium-high SCR activity, good N2 selectivity, and high SO2 tolerance. However, the NH3-SCR mechanism over Fe2O3-based catalysts remains highly uncertain and controversial due to the complex nature of the SCR reaction. Herein, the NH3-SCR reaction pathways over the α-Fe2O3(012) surface are elucidated at the atomic level by density functional theory calculations and experimental measurements. We demonstrate that, different from the NH3 activation mechanism in numerous SCR catalytic systems, the reaction tends to follow the NO activation mechanism, in which NO activated at Fe sites reacts with NH3 to form a NH2NO intermediate and further decomposes into N2 and H2O, in synchronization with the formation of a surface OH group. Subsequently, the catalyst is regenerated by an O2-assisted surface-dehydrogenation process. The activation of NO as well as the formation of the NH2NO intermediate is the rate-determining step of the complete SCR cycle. This study enhances the atomic-level understanding toward the NH3-SCR reaction and provides insights for the development of Fe2O3-based SCR catalysts.
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Although copper-nitrene has been extensively studied as a versatile active species in various transformations, asymmetric reactions involving copper-nitrene have been limited to the aziridination of olefins. Herein, we report the novel copper-nitrene-catalyzed desymmetric oxaziridination reaction of cyclic diketones with alkyl azides and the subsequent rearrangement of the resulting highly active intermediate, which produces a synthetically challenging chiral bicyclic lactam containing a quaternary carbon center. This procedure not only enriches the copper-nitrene-catalyzed asymmetric reactions, but also provides an alternative strategy to address the inherent challenges of catalytic asymmetric Schmidt reactions. This unique reaction could inspire the investigation of novel copper-nitrene-catalyzed asymmetric transformations and their reaction mechanisms.
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The control of NOx emission from diesel vehicles is of great importance to the environment, and Cu-SAPO-34 is considered to be an effective catalyst for the abatement of NOx from diesel vehicles. Along with catalytic activity, hydrothermal stability is a key property for NOx abatement catalysts. The attack of Cu species and framework atoms by H2O may result in activity loss under both low/high temperature humid conditions, which are inevitable in practical application. Therefore, apart from good catalytic activity, hydrothermal stability under both low/high temperatures for Cu-SAPO-34 is also critical for NOx control in diesel vehicles. Three Cu-SAPO-34 samples were prepared by a one-pot hydrothermal method using propylamine, triethylamine, and morpholine, with Cu-TEPA (tetraethylenepentamine) as the cotemplate. The NH3-SCR activity and the effects of hydrothermal aging at 70 and 800 °C on these Cu-SAPO-34 samples were investigated. The type of cotemplate can affect the Si and Cu species in one-pot-synthesized Cu-SAPO-34 catalysts, so that the catalytic activity as well as the low/high temperature hydrothermal stability is affected by the choice of template. Generally speaking, Cu-SAPO-34 prepared using PA as cotemplate showed superior catalytic activity and hydrothermal stability under low/high temperatures compared with the other two catalysts, which makes PA a more suitable template for one-pot-synthesized Cu-SAPO-34 for use in NOx abatement from diesel vehicle exhaust.
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Emisiones de Vehículos , Zeolitas , Amoníaco , Oxidación-ReducciónRESUMEN
Nanofibers have attracted extensive attention and been applied in various fields due to their high aspect ratio, high specific surface area, flexibility, structural abundance, etc. The electrospinning method is one of the most promising and effective ways to produce nanofibers. The electrospun nanofibers-based films and membranes have already been demonstrated to possess small pore sizes, larges specific surface area, and can be grafted with different functionalities to adapt to various purposes. The environmental applications of nanofibers are one of the essential application fields, and great achievements have been made in this field. To well summarize the development of nanofibers and their environmental applications, we review the nanofiber fabrication methods, advanced fiber structures, and their applications in the field of air filtration, heavy metal removal, and self-cleaning surface. We hope this review and summary can provide readers a comprehensive understanding of the structural design and environmental applications of electrospun nanofibers.
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Pool boiling of ethanol and self-rewetting fluids on bare copper surface and copper surface with polymer nanofibers were studied experimentally. No significant effect of the depths of ethanol layer on the heat removal rate was found. That indicates that only the heat transfer in the liquid microlayer near the heater surface is a dominant factor. As a result, one can expect that self-rewetting fluids can significantly affect boiling performance. Accordingly, several alcohol solutions including the self-rewetting ones were investigated as working fluids in the boiling chamber. It was found that at the 0.1% (v/v) concentration, only the high carbon-alcohol, n-heptanol in aqueous solution, improved boiling heat transfer considerably. Furthermore, the experimental study of the effect of surface nano-texture on boiling characteristics was undertaken. For that aim, polyacrylonitrile (PAN) nanofibers were deposited onto the copper heater surface. Measurements of the boiling curve revealed a detrimental effect of such nano-texture in the case of such working fluids as ethanol and self-rewetting n-heptanol solutions. On the other hand, when polystyrene (PS) nanofibers were deposited onto the copper heater surface instead of PAN nanofibers, a significant improvement in boiling heat transfer was observed. The more hydrophobic nature of PS compared to copper is responsible for this effect, i.e. is the reason of the heat transfer enhancement on such a nano-textured surface compared to the pure copper one. In addition, the critical heat flux in the case of n-heptanol solution was found to be reduced considerably on the PS nano-textured surface compared to the pure copper one. This stems from the increased propensity of the heater surface to be covered by vapor, while the rewetting is insufficiently effective at high heat fluxes in presence of PS nanofibers.
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Bone metastasis is a common complication of certain cancers such as melanoma. The spreading of cancer cells into the bone is supported by changes in the bone marrow environment. The specific role of osteocytes in this process is yet to be defined. By RNA-seq and chemokines screening we show that osteocytes release the chemokine CXCL5 when they are exposed to melanoma cells. Osteocytes-mediated CXCL5 secretion enhanced the migratory and invasive behaviour of melanoma cells. When the expression of the CXCL5 receptor, CXCR2, was down-regulated in melanoma cells in vitro, we observed a significant decrease in melanoma cell migration in response to osteocytes. Furthermore, melanoma cells with down-regulated CXCR2 expression showed less bone metastasis and less bone loss in the bone metastasis model in vivo. Furthermore, when simultaneously down-regulating CXCL5 in osteocytes and CXCR2 in melanoma cells, melanoma progression was abrogated in vivo. In summary, these data suggest a significant role of osteocytes in bone metastasis of melanoma, which is mediated through the CXCL5-CXCR2 pathway.
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Neoplasias Óseas , Movimiento Celular , Quimiocina CXCL5 , Melanoma , Osteocitos , Receptores de Interleucina-8B , Osteocitos/metabolismo , Osteocitos/patología , Neoplasias Óseas/secundario , Neoplasias Óseas/metabolismo , Quimiocina CXCL5/metabolismo , Quimiocina CXCL5/genética , Animales , Melanoma/metabolismo , Melanoma/patología , Melanoma/secundario , Melanoma/genética , Receptores de Interleucina-8B/metabolismo , Receptores de Interleucina-8B/genética , Ratones , Línea Celular Tumoral , Humanos , Transducción de Señal , Melanoma Experimental/patología , Melanoma Experimental/metabolismo , Ratones Endogámicos C57BLRESUMEN
Roots are essential to terrestrial plants, as their growth and morphology are crucial for plant development. The growth of the roots is affected and regulated by several internal and external environmental signals and metabolic pathways. Among them, chromatin modification plays an important regulatory role. In this study, we explore the potential roles of the histone deacetylase AtHD2D in root development and lay the foundation for further research on the biological processes and molecular mechanisms of AtHD2D in the future. Our study indicates that AtHD2D affects the root tip microenvironment homeostasis by affecting the gene transcription levels required to maintain the root tip microenvironment. In addition, we confirmed that AtHD2D is involved in regulating Arabidopsis lateral root development and further explained the possible role of AtHD2D in auxin-mediated lateral root development. AtHD2D can effectively enhance the resistance of Arabidopsis thaliana to abiotic stress. We believe that AtHD2D is involved in coping with abiotic stress by promoting the development of lateral roots. Overexpression of AtHD2D promotes the accumulation of reactive oxygen species (ROS) in roots, indicating that AtHD2D is also involved in developing lateral roots mediated by ROS. Previous studies have shown that the overexpression of AtHD2D can effectively enhance the resistance of Arabidopsis thaliana to abiotic stress. Based on our data, we believe that AtHD2D participates in the response to abiotic stress by promoting the development of lateral roots. AtHD2D-mediated lateral root development provides new ideas for studying the mechanism of HDAC protein in regulating root development.
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Proteínas de Arabidopsis , Arabidopsis , Histona Desacetilasas , Raíces de Plantas , Estrés Fisiológico , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Ácidos Indolacéticos/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Raíces de Plantas/fisiología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Background: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks associated with miR-147, and the regulation of lncRNAs and miRNAs in this setting remains poorly understood. Methods: After establishing a miR-147-/- model mouse, samples of lung tissue were harvested for RNA-sequencing, and differentially expressed lncRNAs, miRNAs, and mRNAs were identified. The miRNA targets of these lncRNAs and the identified miRNAs were first overlapped to facilitate the prediction of target mRNAs, with analyses then examining the overlap between these targets and mRNAs that were differentially expressed. Then, these target mRNAs were subjected to pathway enrichment analyses. These results were ultimately used to establish a miR-147-related ceRNA network. Results: Relative to wild-type mice, the lungs of miR-147-/- mice exhibited 91, 43, and 71 significantly upregulated lncRNAs, miRNAs, and mRNAs, respectively, together with 114, 31, and 156 that were significantly downregulated. The lncRNA-miRNA-mRNA network established based on these results led to the identification of Kcnh6 as a differentially expressed hub gene candidate and enabled the identification of a range of regulatory relationships. KEGG pathway enrichment showed that the mRNA targets of differentially expressed lncRNAs and miRNAs in the mice were associated with tumor-related signaling, endometrial cancer, bladder cancer, and ErbB signaling. Conclusion: These results suggest that the identified ceRNA network in miR-147-/- mice shapes tumor-associated signaling activity, with miR-147 potentially regulating various lncRNAs and miRNAs through Kcnh6, ultimately influencing tumorigenesis. Future studies of the lncRNA, miRNA, and mRNA regulatory targets shown to be associated with miR-147 in the present study may ultimately lead to the identification of novel clinically relevant targets through which miR-147 shapes the pathogenesis of cancer and other diseases.
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Head and neck cancer (HNC) is one of the most common cancers on the planet, with approximately 600,000 new cases diagnosed and 300,000 deaths every year. Research into the biological basis of HNC has advanced slowly over the past decades, which has made it difficult to develop new, more effective treatments. The patient-derived organoids (PDOs) are made from patient tumor cells, resembling the features of their tumors, which are high-fidelity models for studying cancer biology and designing new precision medicine therapies. In recent years, considerable effort has been focused on improving "organoids" technologies and identifying tumor-specific medicine using head and neck samples and a variety of organoids. A review of improved techniques and conclusions reported in publications describing the application of these techniques to HNC organoids is presented here. Additionally, we discuss the potential application of organoids in head and neck cancer research as well as the limitations associated with these models. As a result of the integration of organoid models into future precision medicine research and therapeutic profiling programs, the use of organoids will be extremely significant in the future.
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The main cause of high mortality in cancer patients is tumor metastasis. Exploring the underlying mechanism of tumor metastasis is of great significance for clinical treatments. Here, we identify the transcription factor Apt/FSBP is a suppressor for tumor metastasis. In Drosophila wing disc, knockdown of apt is able to trigger cell migration, whereas overexpression of apt hampers scrib-RNAi-induced tumor cell migration. Further studies show that loss of apt promotes cell migration through activating the JNK pathway. To investigate the role of FSBP, the homolog of Apt in mammals, we construct Fsbp liver-specific knockout mice. Knockout of Fsbp in liver does not cause any detectable physiological defects, but predisposes to tumorigenesis on DEN and CCl4 treatment. In addition, loss of Fsbp accelerates tumor metastasis from liver to diaphragm. Taken together, this study uncovers FSBP is a novel tumor suppressor, and provides it as a considerable drug target for tumor treatment.
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Cultivated strawberry (Fragaria × ananassa), a perennial herb belonging to the family Rosaceae, is a complex octoploid with high heterozygosity at most loci. However, there is no research on the haplotype of the octoploid strawberry genome. Here we aimed to obtain a high-quality genome of the cultivated strawberry cultivar, "Yanli", using single molecule real-time sequencing and high-throughput chromosome conformation capture technology. The "Yanli" genome was 823 Mb in size, with a long terminal repeat assembly index of 14.99. The genome was phased into two haplotypes, Hap1 (825 Mb with contig N50 of 26.70 Mb) and Hap2 (808 Mb with contig N50 of 27.51 Mb). Using the combination of Hap1 and Hap2, we obtained for the first time a haplotype-resolved genome with 56 chromosomes for the cultivated octoploid strawberry. We identified a ~ 10 Mb inversion and translocation on chromosome 2-1. 104 957 and 102 356 protein-coding genes were annotated in Hap1 and Hap2, respectively. Analysis of the genes related to the anthocyanin biosynthesis pathway revealed the structural diversity and complexity in the expression of the alleles in the octoploid F. × ananassa genome. In summary, we obtained a high-quality haplotype-resolved genome assembly of F. × ananassa, which will provide the foundation for investigating gene function and evolution of the genome of cultivated octoploid strawberry.
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Serving as the power plant and signaling hub of a cell, mitochondria contain their own genome which encodes proteins essential for energy metabolism and forms DNA-protein assemblies called nucleoids. Mitochondrial DNA (mtDNA) exists in multiple copies within each cell ranging from hundreds to tens of thousands. Maintaining mtDNA homeostasis is vital for healthy cells, and its dysregulation causes multiple human diseases. However, the players involved in regulating mtDNA maintenance are largely unknown though the core components of its replication machinery have been characterized. Here, we identify C17orf80, a functionally uncharacterized protein, as a critical player in maintaining mtDNA homeostasis. C17orf80 primarily localizes to mitochondrial nucleoid foci and exhibits robust double-stranded DNA binding activity throughout the mitochondrial genome, thus constituting a bona fide new mitochondrial nucleoid protein. It controls mtDNA levels by promoting mtDNA replication and plays important roles in mitochondrial metabolism and cell proliferation. Our findings provide a potential target for therapeutics of human diseases associated with defective mtDNA control.