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In eukaryotic cells, organelle biogenesis is pivotal for cellular function and cell survival. Chloroplasts are unique organelles with a complex internal membrane network. The mechanisms of the migration of imported nuclear-encoded chloroplast proteins across the crowded stroma to thylakoid membranes are less understood. Here, we identified two Arabidopsis ankyrin-repeat proteins, STT1 and STT2, that specifically mediate sorting of chloroplast twin arginine translocation (cpTat) pathway proteins to thylakoid membranes. STT1 and STT2 form a unique hetero-dimer through interaction of their C-terminal ankyrin domains. Binding of cpTat substrate by N-terminal intrinsically disordered regions of STT complex induces liquid-liquid phase separation. The multivalent nature of STT oligomer is critical for phase separation. STT-Hcf106 interactions reverse phase separation and facilitate cargo targeting and translocation across thylakoid membranes. Thus, the formation of phase-separated droplets emerges as a novel mechanism of intra-chloroplast cargo sorting. Our findings highlight a conserved mechanism of phase separation in regulating organelle biogenesis.
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Arabidopsis/metabolismo , Transporte Proteico/fisiologia , Sistema de Translocação de Argininas Geminadas/metabolismo , Proteínas de Cloroplastos/metabolismo , Cloroplastos/metabolismo , Membranas Intracelulares/metabolismo , Proteínas de Membrana/metabolismo , Biogênese de Organelas , Organelas/metabolismo , Transição de Fase , Proteínas de Plantas/metabolismo , Tilacoides/metabolismo , Sistema de Translocação de Argininas Geminadas/fisiologiaRESUMO
Fe-S clusters are ancient, ubiquitous and highly essential prosthetic groups for numerous fundamental processes of life. The biogenesis of Fe-S clusters is a multistep process including iron acquisition, sulfur mobilization, and cluster formation. Extensive studies have provided deep insights into the mechanism of the latter two assembly steps. However, the mechanism of iron utilization during chloroplast Fe-S cluster biogenesis is still unknown. Here we identified two Arabidopsis DnaJ proteins, DJA6 and DJA5, that can bind iron through their conserved cysteine residues and facilitate iron incorporation into Fe-S clusters by interactions with the SUF (sulfur utilization factor) apparatus through their J domain. Loss of these two proteins causes severe defects in the accumulation of chloroplast Fe-S proteins, a dysfunction of photosynthesis, and a significant intracellular iron overload. Evolutionary analyses revealed that DJA6 and DJA5 are highly conserved in photosynthetic organisms ranging from cyanobacteria to higher plants and share a strong evolutionary relationship with SUFE1, SUFC, and SUFD throughout the green lineage. Thus, our work uncovers a conserved mechanism of iron utilization for chloroplast Fe-S cluster biogenesis.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Cloroplastos/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Ferro/metabolismo , Enxofre/metabolismo , Fotossíntese/fisiologiaRESUMO
Genome-scale metabolic models (GEMs) can facilitate metabolism-focused multi-omics integrative analysis. Since Yeast8, the yeast-GEM of Saccharomyces cerevisiae, published in 2019, has been continuously updated by the community. This has increased the quality and scope of the model, culminating now in Yeast9. To evaluate its predictive performance, we generated 163 condition-specific GEMs constrained by single-cell transcriptomics from osmotic pressure or reference conditions. Comparative flux analysis showed that yeast adapting to high osmotic pressure benefits from upregulating fluxes through central carbon metabolism. Furthermore, combining Yeast9 with proteomics revealed metabolic rewiring underlying its preference for nitrogen sources. Lastly, we created strain-specific GEMs (ssGEMs) constrained by transcriptomics for 1229 mutant strains. Well able to predict the strains' growth rates, fluxomics from those large-scale ssGEMs outperformed transcriptomics in predicting functional categories for all studied genes in machine learning models. Based on those findings we anticipate that Yeast9 will continue to empower systems biology studies of yeast metabolism.
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Glycolysis is a major determinant of pulmonary artery smooth muscle cell (PASMC) proliferation in pulmonary hypertension (PH). Circular RNAs (circRNAs) are powerful regulators of glycolysis in multiple diseases; however, the role of circRNAs in glycolysis in PH has been poorly characterized. The aim of this study was to uncover the regulatory mechanism of a new circRNA, circNAP1L4, in human pulmonary artery smooth muscle cell (HPASMC) proliferation through the host protein NAP1L4 to regulate the super-enhancer-driven glycolysis gene hexokinase II (HK II). CircNAP1L4 was downregulated in hypoxic HPASMCs and plasma of PH patients. Functionally, circNAP1L4 overexpression inhibited glycolysis and proliferation in hypoxic HPASMCs. Mechanistically, circNAP1L4 directly bound to its host protein NAP1L4 and affected the ability of NAP1L4 to move into the nucleus to regulate the epigenomic signals of the super-enhancer of HK II. Intriguingly, circNAP1L4 overexpression inhibited the proliferation but not the migration of human pulmonary arterial endothelial cells (HPAECs) cocultured with HPASMCs. Furthermore, pre-mRNA-processing-splicing Factor 8 (PRP8) was found to regulate the production ratio of circNAP1L4 and linear NAP1L4. In vivo, targeting circNAP1L4 alleviates SU5416 combined with hypoxia (SuHx)-induced PH. Overall, these findings reveal a new circRNA that inhibits PASMC proliferation and serves as a therapeutic target for PH.
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Proliferação de Células , Glicólise , Hexoquinase , Hipertensão Pulmonar , Miócitos de Músculo Liso , Artéria Pulmonar , RNA Circular , Humanos , Hexoquinase/metabolismo , Hexoquinase/genética , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/genética , Miócitos de Músculo Liso/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Animais , Camundongos , Masculino , Células Cultivadas , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologiaRESUMO
Phosphorothioate (PT)-modification was discovered in prokaryotes and is involved in many biological functions such as restriction-modification systems. PT-modification can be recognized by the sulfur binding domains (SBDs) of PT-dependent restriction endonucleases, through coordination with the sulfur atom, accompanied by interactions with the DNA backbone and bases. The unique characteristics of PT recognition endow SBDs with the potential to be developed into gene-targeting tools, but previously reported SBDs display sequence-specificity for PT-DNA, which limits their applications. In this work, we identified a novel sequence-promiscuous SBDHga from Hahella ganghwensis. We solved the crystal structure of SBDHga complexed with PT-DNA substrate to 1.8 Å resolution and revealed the recognition mechanism. A shorter L4 loop of SBDHga interacts with the DNA backbone, in contrast with previously reported SBDs, which interact with DNA bases. Furthermore, we explored the feasibility of using SBDHga and a PT-oligonucleotide as targeting tools for site-directed adenosine-to-inosine (A-to-I) RNA editing. A GFP non-sense mutant RNA was repaired at about 60% by harnessing a chimeric SBD-hADAR2DD (deaminase domain of human adenosine deaminase acting on RNA), comparable with currently available RNA editing techniques. This work provides insights into understanding the mechanism of sequence-specificity for SBDs and for developing new tools for gene therapy.
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Edição de RNA , Humanos , Adenosina Desaminase/metabolismo , DNA/química , Edição de Genes , RNA/metabolismo , Enxofre/químicaRESUMO
Lightweight, easily processed, and durable polymeric materials play a crucial role in wearable sensor devices. However, achieving simultaneously high strength and toughness remains a challenge. This study addresses this by utilizing an ion-specific effect to control crystalline domains, enabling the fabrication of a polymeric triboelectric material with tunable mechanical properties. The dense crystal-domain cross-linking enhances energy dissipation, resulting in a material boasting both high tensile strength (58.0 MPa) and toughness (198.8 MJ m-3), alongside a remarkable 416.7% fracture elongation and 545.0 MPa modulus. Leveraging these properties, the material is successfully integrated into wearable self-powered devices, enabling real-time feedback on human joint movement. This work presents a valuable strategy for overcoming the strength-toughness trade-off in polymeric materials, paving the way for their enhanced applicability and broader use in diverse sensing applications.
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Long noncoding RNAs (lncRNAs) are increasingly being recognized as modulators in various biological processes. However, due to their low expression, their systematic characterization is difficult to determine. Here, we performed transcript annotation by a newly developed computational pipeline, termed RNA-seq and small RNA-seq combined strategy (RSCS), in a wide variety of cellular contexts. Thousands of high-confidence potential novel transcripts were identified by the RSCS, and the reliability of the transcriptome was verified by analysis of transcript structure, base composition, and sequence complexity. Evidenced by the length comparison, the frequency of the core promoter and the polyadenylation signal motifs, and the locations of transcription start and end sites, the transcripts appear to be full length. Furthermore, taking advantage of our strategy, we identified a large number of endogenous retrovirus-associated lncRNAs, and a novel endogenous retrovirus-lncRNA that was functionally involved in control of Yap1 expression and essential for early embryogenesis was identified. In summary, the RSCS can generate a more complete and precise transcriptome, and our findings greatly expanded the transcriptome annotation for the mammalian community.
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Anotação de Sequência Molecular , RNA Longo não Codificante , RNA-Seq , Animais , Desenvolvimento Embrionário/genética , Mamíferos/embriologia , Mamíferos/genética , Anotação de Sequência Molecular/métodos , Regiões Promotoras Genéticas/genética , Reprodutibilidade dos Testes , Retroviridae/genética , RNA Longo não Codificante/genética , RNA-Seq/métodos , Sítio de Iniciação de Transcrição , Transcriptoma/genética , Proteínas de Sinalização YAP/genética , Proteínas de Sinalização YAP/metabolismoRESUMO
BACKGROUND: Pseudomonas syringae pv. actinidiae (Psa) is an important bacterial plant pathogen that causes severe damage to the kiwifruit industry worldwide. Three Psa strains were recently obtained from different kiwifruit orchards in Anhui Province, China. The present study mainly focused on the variations in virulence and genome characteristics of these strains based on the pathogenicity assays and comparative genomic analyses. RESULTS: Three strains were identified as biovar 3 (Psa3), along with strain QSY6 showing higher virulence than JZY2 and YXH1 in pathogenicity assays. The whole genome assembly revealed that each of the three strains had a circular chromosome and a complete plasmid. The chromosome sizes ranged from 6.5 to 6.6 Mb with a GC content of approximately 58.39 to 58.46%, and a predicted number of protein-coding sequences ranging from 5,884 to 6,019. The three strains clustered tightly with 8 Psa3 reference strains in terms of average nucleotide identity (ANI), whole-genome-based phylogenetic analysis, and pangenome analysis, while they were evolutionarily distinct from other biovars (Psa1 and Psa5). Variations were observed in the repertoire of effectors of the type III secretion system among all 15 strains. Moreover, synteny analysis of the three sequenced strains revealed eight genomic regions containing 308 genes exclusively present in the highly virulent strain QSY6. Further investigation of these genes showed that 16 virulence-related genes highlight several key factors, such as effector delivery systems (type III secretion systems) and adherence (type IV pilus), which might be crucial for the virulence of QSY6. CONCLUSION: Three Psa strains were identified and showed variant virulence in kiwifruit plant. Complete genome sequences and comparative genomic analyses further provided a theoretical basis for the potential pathogenic factors responsible for kiwifruit bacterial canker.
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Actinidia , Genoma Bacteriano , Genômica , Filogenia , Doenças das Plantas , Pseudomonas syringae , Pseudomonas syringae/genética , Pseudomonas syringae/patogenicidade , China , Actinidia/microbiologia , Virulência/genética , Doenças das Plantas/microbiologiaRESUMO
Covering: up to the end of 2023Type I CRISPR-Cas systems are widely distributed, found in over 40% of bacteria and 80% of archaea. Among genome-sequenced actinomycetes (particularly Streptomyces spp.), 45.54% possess type I CRISPR-Cas systems. In comparison to widely used CRISPR systems like Cas9 or Cas12a, these endogenous CRISPR-Cas systems have significant advantages, including better compatibility, wide distribution, and ease of operation (since no exogenous Cas gene delivery is needed). Furthermore, type I CRISPR-Cas systems can simultaneously edit and regulate genes by adjusting the crRNA spacer length. Meanwhile, most actinomycetes are recalcitrant to genetic manipulation, hindering the discovery and engineering of natural products (NPs). The endogenous type I CRISPR-Cas systems in actinomycetes may offer a promising alternative to overcome these barriers. This review summarizes the challenges and recent advances in CRISPR-based genome engineering technologies for actinomycetes. It also presents and discusses how to establish and develop genome editing tools based on type I CRISPR-Cas systems in actinomycetes, with the aim of their future application in gene editing and the discovery of NPs in actinomycetes.
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Modulating the solvation structure of hydrated zinc ions using organic additives stands as a pragmatic approach to suppress dendrite formation and corrosion on zinc metal anodes (ZMAs), thereby enhancing the rechargeability of aqueous Zn-ion batteries. However, fundamental screening principles for organic additives with diverse molecular structures remain elusive, especially for isomers with the same molecular formula. This study delves into the impact of three isomeric hexagonal alcohols (mannitol, sorbitol, and galactitol) as additives in adjusting Zn2+ solvation structural behaviors within ZnSO4 baseline electrolytes. Electrical measurements and molecular simulations reveal the specific molecular structure of mannitol, which features interweaving electron clouds between adjacent hydroxyl groups, achieving a high local electron cloud density. This phenomenon significantly enhances desolvation abilities, thus establishing a more stable anode/electrolyte interface chemistry. Even at 5 mA cm-2 for 2.5 mAh cm-2 capacity, Zn||Zn symmetric cells with mannitol-regulated electrolyte display an impressive 1170 h lifespan, far exceeding those with other isomer additives and is nearly tenfold longer than that with a pure ZnSO4 electrolyte (120 h). Rather than strictly adhering to focusing on chemical composition, this study with emphasis on optimizing molecular structure offers a promising untapped dimension to screen more efficient additives to enhance the reversibility of ZMAs.
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Engineering Yarrowia lipolytica to produce astaxanthin provides a promising route. Here, Y. lipolytica M2 producing a titer of 181 mg/L astaxanthin was isolated by iterative atmospheric and room-temperature plasma mutagenesis and diphenylamine-mediated screening. Interestingly, a negative correlation was observed between cell biomass and astaxanthin production. To reveal the underlying mechanism, RNA-seq analysis of transcriptional changes was performed in high producer M2 and reference strain M1, and a total of 1379 differentially expressed genes were obtained. Data analysis revealed that carbon flux was elevated through lipid metabolism, acetyl-CoA and mevalonate supply, but restrained through central carbon metabolism in strain M2. Moreover, upregulation of other pathways such as ATP-binding cassette transporter and thiamine pyrophosphate possibly provided more cofactors for carotenoid hydroxylase and relieved cell membrane stress caused by astaxanthin insertion. These results suggest that balancing cell growth and astaxanthin production may be important to promote efficient biosynthesis of astaxanthin in Y. lipolytica.
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Perfilação da Expressão Gênica , Xantofilas , Yarrowia , Yarrowia/genética , Yarrowia/metabolismo , Xantofilas/metabolismo , Engenharia Metabólica , Transcriptoma , Regulação Fúngica da Expressão Gênica , Redes e Vias Metabólicas/genética , Análise do Fluxo Metabólico , Metabolismo dos Lipídeos , BiomassaRESUMO
Streptomyces has an extensive array of bioactive secondary metabolites (SMs). Nevertheless, devising a framework for the heterologous production of these SMs remains challenging. We here reprogrammed a versatile plug-and-play Streptomyces super-chassis and established a universal pipeline for production of diverse SMs via understanding of the inherent pleiotropic effects of ethanol shock on jadomycin production in Streptomyces venezuelae. We initially identified and characterized a set of multiplex targets (afsQ1, bldD, bldA, and miaA) that contribute to SM (jadomycin) production when subjected to ethanol shock. Subsequently, we developed an ethanol-induced orthogonal amplification system (EOAS), enabling dynamic and precise control over targets. Ultimately, we integrated these multiplex targets into functional units governed by the EOAS, generating a universal and plug-and-play Streptomyces super-chassis. In addition to achieving the unprecedented titer and yield of jadomycin B, we also evidenced the potential of this super-chassis for production of diverse heterologous SMs, including antibiotic oxytetracycline, anticancer drug doxorubicins, agricultural herbicide thaxtomin A, and plant growth regulator guvermectin, all with the yields of >10 mg/g glucose in a simple mineral medium. Given that the production of SMs all required complexed medium and the cognate yields were usually much lower, our achievement of using a universal super-chassis and engineering pipeline in a simple mineral medium is promising for convenient heterologous production of SMs.
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Adenosina/análogos & derivados , Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Antibacterianos , Etanol/metabolismo , Minerais/metabolismo , Minerais/farmacologiaRESUMO
The understanding of viral transcription and replication activity in HBeAg-positive chronic hepatitis B (CHB) patients with low-level viraemia (LLV) or previous low-level viraemia (pre-LLV) remains unclear. Our aim was to evaluate and compare circulating hepatitis B virus (HBV) RNA levels in these patient groups with those achieving maintained virological response (MVR). This cross-sectional study included 147 patients: 43 in the LLV group, 25 in the pre-LLV group and 79 in the MVR group. Serum HBV RNA levels were assessed using specific RNA target capture combined with simultaneous amplification and testing method. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Median HBV RNA levels were 6.9 copies/mL in the LLV group, 6.1 copies/mL in the pre-LLV group and 3.8 copies/mL in the MVR group. After PSM, significantly higher HBV RNA levels were observed in the LLV group compared to the MVR group (p < .001), and the pre-LLV group also showed higher HBV RNA levels than the MVR group (p < .001). Both LLV and pre-LLV HBeAg-positive CHB patients exhibited elevated circulating HBV RNA levels compared to those achieving MVR.
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Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , RNA Viral , Carga Viral , Viremia , Humanos , Masculino , Feminino , Estudos Transversais , Adulto , RNA Viral/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Hepatite B Crônica/sangue , Viremia/virologia , Pessoa de Meia-Idade , Resposta Viral Sustentada , DNA Viral/sangueRESUMO
R-loops, three-stranded nucleic acid structures consisting of a DNA: RNA hybrid and displaced single-stranded DNA, play critical roles in gene expression and genome stability. How R-loop homeostasis is integrated into chloroplast gene expression remains largely unknown. We found an unexpected function of FtsHi1, an inner envelope membrane-bound AAA-ATPase in chloroplast R-loop homeostasis of Arabidopsis thaliana. Previously, this protein was shown to function as a component of the import motor complex for nuclear-encoded chloroplast proteins. However, this study provides evidence that FtsHi1 is an ATP-dependent helicase that efficiently unwinds both DNA-DNA and DNA-RNA duplexes, thereby preventing R-loop accumulation. Over-accumulation of R-loops could impair chloroplast transcription but not necessarily genome integrity. The dual function of FtsHi1 in both protein import and chloroplast gene expression may be important to coordinate the biogenesis of nuclear- and chloroplast-encoded subunits of multi-protein photosynthetic complexes. This study suggests a mechanical link between protein import and R-loop homeostasis in chloroplasts of higher plants.
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Proteínas de Arabidopsis , Arabidopsis , Trifosfato de Adenosina/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cloroplastos/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , Transporte Proteico , Estruturas R-Loop , RNA/metabolismo , RNA Helicases/genéticaRESUMO
Soybean (Glycine max) is a typical short-day plant, but has been widely cultivated in high-latitude long-day (LD) regions because of the development of early-maturing genotypes which are photoperiod-insensitive. However, some early-maturing varieties exhibit significant responses to maturity under different daylengths but not for flowering, depicting an evident photoperiodic after-effect, a poorly understood mechanism. In this study, we investigated the postflowering responses of 11 early-maturing soybean varieties to various preflowering photoperiodic treatments. We confirmed that preflowering SD conditions greatly promoted maturity and other postflowering developmental stages. Soybean homologs of FLOWERING LOCUS T (FT), including GmFT2a, GmFT3a, GmFT3b and GmFT5a, were highly accumulated in leaves under preflowering SD treatment. More importantly, they maintained a high expression level after flowering even under LD conditions. E1 RNAi and GmFT2a overexpression lines showed extremely early maturity regardless of preflowering SD and LD treatments due to constitutively high levels of floral-promoting GmFT homolog expression throughout their life cycle. Collectively, our data indicate that high and stable expression of floral-promoting GmFT homologs play key roles in the maintenance of photoperiodic induction to promote postflowering reproductive development, which confers early-maturing varieties with appropriate vegetative growth and shortened reproductive growth periods for adaptation to high latitudes.
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Glycine max , Fotoperíodo , Glycine max/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Flores/fisiologia , Ritmo Circadiano , Regulação da Expressão Gênica de PlantasRESUMO
Developing more effective bioactive ingredients of natural origin is imperative for promoting wound healing. Sea cucumbers have long enjoyed a good reputation as both food delicacies and traditional medicines. In this study, we heterogeneously expressed a Apostichopus japonicus derived novel protein AjPSPLP-3, which exhibits a theoretical molecular weight of 13.034 kDa, through fusion with maltose binding protein (MBP). AjPSPLP-3 contains a strict CXXCXC motif, nine extremely conserved cysteine residues and two highly conserved cysteine residues. The predicted structure of AjPSPLP-3 consists of random coil and nine ß-sheets, Cys30-Cys67, Cys38-Cys58, Cys53-Cys90, Cys56-Cys66, and Cys81-Cys102 participating in the formation of five pairs of disulfide bonds. In vitro experiments conducted on HaCaT cells proved that AjPSPLP-3 and MBP-fused AjPSPLP-3 significantly contribute to HaCaT cells proliferation and migration without exhibiting hemolytic activity on murine erythrocytes. Specifically, treatment with 10 µmol/L MBP-fused AjPSPLP-3 protein increased the viability of HaCaT cells by 12.28% (p < 0.001), while treatment with 10 µmol/L AjPSPLP-3 protein increased viability of HaCaT cells by 6.01% (p < 0.01). Furthermore, wound closure of MBP-fused AjPSPLP-3 and AjPSPLP-3 were 22.51% (p < 0.01) and 7.32% (p < 0.05) higher than that of the control groups in HaCaT cells following 24 h of incubation.
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Clinical trialists often face the challenge of balancing scientific questions with other design features, such as improving efficiency, minimizing exposure to inferior treatments, and simultaneously comparing multiple treatments. While Bayesian response adaptive randomization (RAR) is a popular and effective method for achieving these objectives, it is known to have large variability and a lack of explicit theoretical results, making its use in clinical trials a subject of concern. It is desirable to propose a design that targets the same allocation proportion as Bayesian RAR and achieves the above objectives but addresses the concerns over Bayesian RAR. We propose the frequentist doubly adaptive biased coin designs (DBCD) targeting ethical allocation proportions from the Bayesian framework to satisfy different objectives in clinical trials with time-to-event endpoints. We derive the theoretical properties of the proposed adaptive randomization design and show through comprehensive numerical simulations that it can achieve ethical objectives without sacrificing efficiency. Our combined theoretical and numerical results offer a strong foundation for the practical use of RAR in real clinical trials.
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Projetos de Pesquisa , Humanos , Teorema de Bayes , Distribuição AleatóriaRESUMO
BACKGROUND: Circular RNAs (circRNAs) have been implicated in pulmonary hypertension progression through largely unknown mechanisms. Pulmonary artery endothelial cell (PAEC) dysfunction is a hallmark in the pathogenesis of pulmonary hypertension. However, the specific role of circular RNAs in PAEC injury caused by hypoxia remains unclear. METHODS: In this study, using the Western blotting, RNA pull down, Dual-luciferase reporter assay, immunohistochemistry, and immunofluorescence, we identified a novel circular RNA derived from alternative splicing of the keratin 4 gene (circKrt4). RESULTS: CircKrt4 was upregulated in lung tissues and plasma and specifically in PAECs under hypoxic conditions. In the nucleus, circKrt4 induces endothelial-to-mesenchymal transition by interacting with the Pura (transcriptional activator protein Pur-alpha) to promote N-cadherin gene activation. In the cytoplasm, increased circKrt4 leads to mitochondrial dysfunction by inhibiting cytoplasmic-mitochondrial shuttling of mitochondrial-bound Glpk (glycerol kinase). Intriguingly, circKrt4 was identified as a super enhancer-associated circular RNA that is transcriptionally activated by a transcription factor, CEBPA (CCAAT enhancer binding protein alpha). Furthermore, RBM25 (RNA-binding-motif protein 25) was found to regulate circKrt4 cyclization by increase the back-splicing of Krt4 gene. CONCLUSIONS: These findings demonstrate that a super enhancer-associated circular RNA-circKrt4 modulates PAEC injury to promote pulmonary hypertension by targeting Pura and Glpk.
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Hipertensão Pulmonar , Artéria Pulmonar , Camundongos , Animais , Artéria Pulmonar/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Proliferação de Células , Hipóxia/metabolismo , RNA/genética , Células Endoteliais/metabolismoRESUMO
Herein, Bi3+/Mn4+ doped Ca2LaTaO6 phosphors with a double-perovskite structure were successfully synthesized with solid-state reaction at high temperature. The photoluminescence (PL) performances were investigated in detail. The blue radiation (â¼465 nm) from the Bi3+ ion and the red radiation (â¼686 nm) originating from the Mn4+ ion were obtained under 313 nm excitation. Especially, the pathway of energy transfer (Bi3+ â Mn4+) contributes to enhance the red emission intensity (Mn4+: â¼686 nm) in Ca2LaTaO6:Bi3+/Mn4+ system. The PL mechanism of Ca2LaTaO6:Bi3+/Mn4+ was analyzed through luminescence lifetimes and PL spectra. Moreover, the emitting bands of Ca2LaTaO6:Bi3+/Mn4+ were primarily matched with the absorbing bands of carotenoids and phytochrome PFR on behalf of plant growth, so the phosphors were suitable for the design of a plant growth light under near-ultraviolet to blue excitation. At last, the optical temperature dependent performances of the Ca2LaTaO6:Bi3+/Mn4+ were analyzed with luminescence intensity ratio technology. The sample has presented excellent temperature measuring relative sensitivity (SR = 2.106% K-1). The results illustrated that the Ca2LaTaO6:Bi3+/Mn4+ phosphor also can be used to develop an optical temperature sensor.
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This work demonstrates asymmetric synthesis of the GABA derivative (R)-baclofen and a new herbicidal mode-of-action inhibitor (3S,4S)-tetflupyrolimet featuring low loading (0.5 mol%) organocatalytic addition reactions of dithiomalonates to nitrostyrenes under "on water" conditions. Importantly, we observed that increasing the hydrophobicity of the catalyst does not guarantee improved catalytic performance under "on water" conditions and the trends in the catalytic efficiency of different HBD catalysts under "on water" conditions (with hydrophobic additives) align more closely with those observed in pure hydrophobic organic solvents. These findings propose a valuable tip for screening organocatalysts in developing asymmetric hydrogen-bonding catalysis under "on water" conditions.