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1.
Heliyon ; 10(14): e34835, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39148994

RESUMEN

To investigate the alleviating effect and mechanism of the docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced liver injury in mice, the murine liver injury model was established by gavage of BPA (5 mg/kg) or co-administration of BPA and DHA-PS (50 mg/kg or 100 mg/kg) for 6 weeks. The results showed that after administration of 100 mg/kg DHA-PS, the liver index, serum levels of AST, ALT, TC, TG, NEFA, and LDL-C in mice were significantly decreased, while HDL-C was significantly increased. The LPS, IL-6, IL-1ß, TNF-α, and MDA levels in liver tissues were effectively down-regulated, and IL-10, SOD, GSH-Px, and CAT levels were effectively up-regulated. The H&E and Oil Red O staining results showed that liver damage was notably repaired and lipid deposition was notably reduced after DHA-PS administration. Furthermore, metabolomics and immunohistochemical studies revealed that DHA-PS mainly regulates glycerophospholipid metabolism and the SIRT1-AMPK pathway to improve metabolic disorders of the liver caused by BPA. Therefore, DHA-PS could potentially alleviate BPA-induced murine liver injury through suppressing inflammation and oxidative stress, and modulating lipid metabolism disorders.

2.
J Am Chem Soc ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39166377

RESUMEN

Effective design and engineering of catalysts for an optimal performance depend extensively on a profound understanding of the intricate catalytic dynamics under reaction conditions. In this work, we showcase rapid freeze-quench (RFQ) Mössbauer spectroscopy as a powerful technique for quantitatively monitoring the catalytic dynamics of single-Cu-atom-modified SnS2 (Cu1/SnS2) in the electrochemical CO2 reduction reaction (CO2RR). Utilizing the newly established RFQ 119Sn Mössbauer methodology, we clearly identified the dynamic transformation of Cu1/SnS2 to Cu1/SnS and Cu1/Sn during the CO2RR, resulting in an outstanding Faradaic efficiency for formate production (∼90.9%) with a partial current density of 158 mA cm-2. Results from operando Raman spectroscopy, operando attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), quasi in situ electron microscopy, and quasi in situ X-ray photoelectron spectroscopy (XPS) measurements indicate that the anchored single Cu atom in Cu1/SnS2 can accelerate the reduction of SnS with in situ formation of Cu1/Sn under CO2RR conditions, which effectively promote the generation of *CO2-/*OCHO intermediates. Theoretical calculations further support that in situ formed Cu1/Sn works as active sites catalyzing the CO2RR, which reduces the energy barrier for the CO2 activation and formation of the *OCHO intermediate, thereby facilitating the conversion of CO2 to formate. The results of this work provide a thorough understanding of the dynamic evolution of Sn-based catalytic sites in the CO2RR and shed light for engineering single atoms with an optimized catalytic performance. We anticipate that RFQ Mössbauer spectroscopy will emerge as an advanced spectroscopic technique for enabling a genuine visualization of catalytic dynamics across various reaction systems.

3.
Angew Chem Int Ed Engl ; : e202411342, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39078740

RESUMEN

Herein, we firstly develop porous organic cage (POC) as an efficient platform for highly effective radioactive iodine capture under industrial operating conditions (typically ≥ 150 °C, ≤ 150 ppmv of I2). Due to the highly dispersed and readily accessible binding sites as well as sufficient accommodating space, the constructed NKPOC-DT-(I-)Me (NKPOC = Nankai porous organic cage) demonstrates a record-high I2 uptake capacity of 48.35 wt% and extraordinary adsorption capacity of unit ionic site (~1.62) at 150 °C and 150 ppmv of I2. The I2 capacity is 3.5, 1.6, and 1.3 times higher than industrial silver-based adsorbents Ag@MOR and benchmark materials of TGDM and 4F-iCOF-TpBpy-I- under the same conditions. Furthermore, NKPOC-DT-(I-)Me exhibits remarkable adsorption kinetics (k1 = 0.013 min-1), which is 1.2 and 1.6 times higher than TGDM and 4F-iCOF-TpBpy-I- under the identical conditions. NKPOC-DT-(I-)Me thus sets a new benchmark for industrial radioactive I2 adsorbents. This work not only provides a new insight for effectively enhancing the adsorption capacity of unit functional sites, but also advances POC as an efficient platform for radioiodine capture in industry.

4.
Sci China Life Sci ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39060614

RESUMEN

The oxidative pentose phosphate (OPP) pathway provides metabolic intermediates for the shikimate pathway and directs carbon flow to the biosynthesis of aromatic amino acids (AAAs), which serve as basic protein building blocks and precursors of numerous metabolites essential for plant growth. However, genetic evidence linking the two pathways is largely unclear. In this study, we identified 6-phosphogluconate dehydrogenase 2 (PGD2), the rate-limiting enzyme of the cytosolic OPP pathway, through suppressor screening of arogenate dehydrogenase 2 (adh2) in Arabidopsis. Our data indicated that a single amino acid substitution at position 63 (glutamic acid to lysine) of PGD2 enhanced its enzyme activity by facilitating the dissociation of products from the active site of PGD2, thus increasing the accumulation of AAAs and partially restoring the defective phenotype of adh2. Phylogenetic analysis indicated that the point mutation occurred in a well-conserved amino acid residue. Plants with different amino acids at this conserved site of PGDs confer diverse catalytic activities, thus exhibiting distinct AAAs producing capability. These findings uncover the genetic link between the OPP pathway and AAAs biosynthesis through PGD2. The gain-of-function point mutation of PGD2 identified here could be considered as a potential engineering target to alter the metabolic flux for the production of AAAs and downstream compounds.

5.
G3 (Bethesda) ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008417

RESUMEN

Strigolactones(SLs), carotenoid-derived plant hormones, govern the growth and development of both monocotyledonous and dicotyledonous plants. DWARF27 (D27), a plastid-targeted protein located at the initiation site of the core pathway in SL synthesis, plays a crucial role in regulating plant tillering (branching). In rice (Oryza sativa) and wheat (Triticum aestivum), OsD27 and TaD27-B proteins modulate the number of plant tillers by participating in SL biosynthesis. Similarly, AtD27 in Arabidopsis thaliana is required for SL production and has a significant impact on phenotypic changes related to branching. At the same time, TaD27 in wheat has been confirmed as a functional ortholog of AtD27 in Arabidopsis, and both P. juncea and wheat belong to the Triticeae, so we speculate that PjD27 gene may also have the same function as AtD27 in Arabidopsis. In this study, we initially screened the PjD27 gene significantly associated with tillering regulation through transcriptome data analysis and subsequently validated its expression levels using qRT-PCR analysis. Furthermore, we conducted phylogenetic analysis using amino acid sequences from 41 species, including P. juncea, to identify closely related species of P. juncea. Here, we analyze the conservation of D27 protein among P. juncea, rice, wheat, and Arabidopsis and provide preliminary evidence suggesting that PjD27 protein is an ortholog of D27 protein in Arabidopsis. Through reverse genetics, we demonstrate the crucial role of PjD27 in regulating plant branching, establishing it as a functional ortholog of D27 in Arabidopsis. Furthermore, following transient expression in tobacco (Nicotiana tabacum), we demonstrate that the subcellular location of the PjD27 protein is consistent with the cellular location of TaD27-B in wheat. Quantitative analysis of SLs shows that PjD27 is a key gene regulating tillering (branching) by participating in SLs biosynthesis. By elucidating the function of the PjD27 gene, our findings provide valuable genetic resources for new germplasm creation and improving grain yield in P. juncea.

6.
Biochem Biophys Res Commun ; 726: 150259, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-38909535

RESUMEN

Hypoxic-ischemic brain damage (HIBD) in the perinatal period is an important cause of cerebral damage and long-term neurological sequelae, and can place much pressure on families and society. Our previous study demonstrated that miRNA-326 reduces neuronal apoptosis by up-regulating the δ-opioid receptor (DOR) under oxygen-glucose deprivation in vitro. In the present study, we aimed to explore the neuroprotective effects of the miRNA-326/DOR axis by inhibiting apoptosis in HIBD using neonatal miRNA-326 knockout mice. Neonatal C57BL/6 mice, neonatal miRNA-326 knockout mice, and neonatal miRNA-326 knockout mice intraperitoneally injected with the DOR inhibitor naltrindole were treated with hypoxic-ischemia (HI). Neurological deficit scores, magnetic resonance imaging, terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling, and Caspase-3, Bax, and B-cell lymphoma 2 (Bcl-2) expression were evaluated on day 2 after HI. Neurobehavioral analyses were performed on days 2 and 28 after HI. Additionally, the Morris water maze test was conducted on days 28. Compared with HI-treated neonatal C57BL/6 mice, HI-treated neonatal miRNA-326 knockout mice had higher neurological deficit scores, smaller cerebral infarction areas, and improved motor function, reaction ability, and long-term spatial learning and memory. These effects were likely the result of inhibiting apoptosis; the DOR inhibitor reversed these neuroprotective effects. Our findings indicate that miRNA-326 knockout plays a neuroprotective effect in neonatal HIBD by inhibiting apoptosis via the target gene DOR.


Asunto(s)
Animales Recién Nacidos , Apoptosis , Hipoxia-Isquemia Encefálica , Ratones Endogámicos C57BL , Ratones Noqueados , MicroARNs , Receptores Opioides delta , Animales , Masculino , Ratones , Apoptosis/genética , Hipoxia-Isquemia Encefálica/genética , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/patología , MicroARNs/genética , MicroARNs/metabolismo , Fármacos Neuroprotectores/farmacología , Receptores Opioides delta/genética , Receptores Opioides delta/metabolismo
7.
Adv Mater ; 36(35): e2404046, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38842820

RESUMEN

Cobalt carbide (Co2C) possesses high catalytic efficiency Fischer-Tropsch synthesis (FTS), while the products selectivity appears sensitive to crystallography geometry. Since the Anderson-Schulz-Flory (ASF) distribution in FTS is broken through fabricating facetted Co2C nanocrystals, yet the underlying mechanism of Co2C crystallization remains unclarified suffering from sophisticated catalyst composition involving promoter agents. Herein, the synthesis of high-purity single-crystal nanoprisms (Co2C-p) for highly efficient FTS is reported to lower olefins. Through comprehensive microstructure analysis, e.g., high-resolution TEM, in situ TEM and electron diffraction, as well as finite element simulation of gas flow field, for the first time the full roadmap of forming catalytic active cobalt carbides is disclosed, starting from reduction of Co3O4 precursor to CoO intermediate, then carburization into Co2C-s and subsequent ripening growth into Co2C-p. This gas-induced engineering of crystal phase provides a new synthesis strategy, with many new possibilities for precise design of metal-based catalyst for diverse catalytic applications.

8.
Nat Plants ; 10(6): 848-856, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38831044

RESUMEN

The de novo synthesis of genomes has made unprecedented progress and achieved milestones, particularly in bacteria and yeast. However, the process of synthesizing a multicellular plant genome has not progressed at the same pace, due to the complexity of multicellular plant genomes, technical difficulties associated with large genome size and structure, and the intricacies of gene regulation and expression in plants. Here we outline the bottom-up design principles for the de novo synthesis of the Physcomitrium patens (that is, earthmoss) genome. To facilitate international collaboration and accessibility, we have developed and launched a public online design platform called GenoDesigner. This platform offers an intuitive graphical interface enabling users to efficiently manipulate extensive genome sequences, even up to the gigabase level. This tool is poised to greatly expedite the synthesis of the P. patens genome, offering an essential reference and roadmap for the synthesis of plant genomes.


Asunto(s)
Bryopsida , Genoma de Planta , Bryopsida/genética , Biología Sintética/métodos , Programas Informáticos
10.
Nat Plants ; 10(6): 1005-1017, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38773271

RESUMEN

The nuclear pore complex (NPC) is vital for nucleocytoplasmic communication. Recent evidence emphasizes its extensive association with proteins of diverse functions, suggesting roles beyond cargo transport. Yet, our understanding of NPC's composition and functionality at this extended level remains limited. Here, through proximity-labelling proteomics, we uncover both local and global NPC-associated proteome in Arabidopsis, comprising over 500 unique proteins, predominantly associated with NPC's peripheral extension structures. Compositional analysis of these proteins revealed that the NPC concentrates chromatin remodellers, transcriptional regulators and mRNA processing machineries in the nucleoplasmic region while recruiting translation regulatory machinery on the cytoplasmic side, achieving a remarkable orchestration of the genetic information flow by coupling RNA transcription, maturation, transport and translation regulation. Further biochemical and structural modelling analyses reveal that extensive interactions with nucleoporins, along with phase separation mediated by substantial intrinsically disordered proteins, may drive the formation of the unexpectedly large nuclear pore proteome assembly.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Poro Nuclear , Poro Nuclear/metabolismo , Poro Nuclear/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteoma/metabolismo , Proteínas de Complejo Poro Nuclear/metabolismo , Proteínas de Complejo Poro Nuclear/genética , Proteómica
11.
Adv Sci (Weinh) ; 11(20): e2400916, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38520733

RESUMEN

The rigid hull encasing Tartary buckwheat seeds necessitates a laborious dehulling process before flour milling, resulting in considerable nutrient loss. Investigation of lignin composition is pivotal in understanding the structural properties of tartary buckwheat seeds hulls, as lignin is key determinant of rigidity in plant cell walls, thus directly impacting the dehulling process. Here, the lignin composition of seed hulls from 274 Tartary buckwheat accessions is analyzed, unveiling a unique lignin chemotype primarily consisting of G lignin, a common feature in gymnosperms. Furthermore, the hardness of the seed hull showed a strong negative correlation with the S lignin content. Genome-wide detection of selective sweeps uncovered that genes governing the biosynthesis of S lignin, specifically two caffeic acid O-methyltransferases (COMTs) and one ferulate 5-hydroxylases, are selected during domestication. This likely contributed to the increased S lignin content and decreased hardness of seed hulls from more domesticated varieties. Genome-wide association studies identified robust associations between FtCOMT1 and the accumulation of S lignin in seed hull. Transgenic Arabidopsis comt1 plants expressing FtCOMT1 successfully reinstated S lignin content, confirming its conserved function across plant species. These findings provide valuable metabolic and genetic insights for the potential redesign of Tartary buckwheat seed hulls.


Asunto(s)
Fagopyrum , Lignina , Semillas , Lignina/metabolismo , Lignina/genética , Fagopyrum/genética , Fagopyrum/metabolismo , Semillas/genética , Semillas/metabolismo , Metiltransferasas
12.
Curr Med Sci ; 44(1): 212-222, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38393529

RESUMEN

OBJECTIVE: Both sequential embryo transfer (SeET) and double-blastocyst transfer (DBT) can serve as embryo transfer strategies for women with recurrent implantation failure (RIF). This study aims to compare the effects of SeET and DBT on pregnancy outcomes. METHODS: Totally, 261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis. According to different embryo quality and transfer strategies, they were divided into four groups: group A, good-quality SeET (GQ-SeET, n=38 cycles); group B, poor-quality or mixed-quality SeET (PQ/MQ-SeET, n=31 cycles); group C, good-quality DBT (GQ-DBT, n=121 cycles); and group D, poor-quality or mixed-quality DBT (PQ/MQ-DBT, n=71 cycles). The main outcome, clinical pregnancy rate, was compared, and the generalized estimating equation (GEE) model was used to correct potential confounders that might impact pregnancy outcomes. RESULTS: GQ-DBT achieved a significantly higher clinical pregnancy rate (aOR 2.588, 95% CI 1.267-5.284, P=0.009) and live birth rate (aOR 3.082, 95% CI 1.482-6.412, P=0.003) than PQ/MQ-DBT. Similarly, the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET (aOR 4.047, 95% CI 1.218-13.450, P=0.023). The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT, and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT. CONCLUSION: SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups. Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos, no matter whether in SeET or DBT. Embryo quality plays a more important role in pregnancy outcomes for RIF patients.


Asunto(s)
Transferencia de Embrión , Resultado del Embarazo , Femenino , Humanos , Embarazo , Tasa de Natalidad , Transferencia de Embrión/métodos , Índice de Embarazo , Estudios Retrospectivos
13.
Analyst ; 149(5): 1489-1495, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38314794

RESUMEN

A novel cyclooxygenase-2 (COX-2) targeted H2S-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This H2S-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, Caenorhabditis elegans (C. elegans), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous H2S in living cells, demonstrating high sensitivity and specificity and strong anti-interference. COX2-H2S had the ability to not only discern cancer cells from normal cells but also specifically recognize 9L/lacZ cells from other glioblastoma cells (U87-MG and LN229). It could also be successfully applied for the fluorescent live imaging of H2S in both C. elegans and zebrafish.


Asunto(s)
Sulfuro de Hidrógeno , Neoplasias , Animales , Humanos , Caenorhabditis elegans , Ciclooxigenasa 2 , Colorantes Fluorescentes , Sulfuro de Hidrógeno/análisis , Neoplasias/diagnóstico por imagen , Imagen Óptica/métodos , Pez Cebra , Línea Celular Tumoral
14.
Sci China Life Sci ; 67(3): 435-448, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38289421

RESUMEN

Tocopherol is an important lipid-soluble antioxidant beneficial for both human health and plant growth. Here, we fine mapped a major QTL-qVE1 affecting γ-tocopherol content in maize kernel, positionally cloned and confirmed the underlying gene ZmPORB1 (por1), as a protochlorophyllide oxidoreductase. A 13.7 kb insertion reduced the tocopherol and chlorophyll content, and the photosynthetic activity by repressing ZmPORB1 expression in embryos of NIL-K22, but did not affect the levels of the tocopherol precursors HGA (homogentisic acid) and PMP (phytyl monophosphate). Furthermore, ZmPORB1 is inducible by low oxygen and light, thereby involved in the hypoxia response in developing embryos. Concurrent with natural hypoxia in embryos, the redox state has been changed with NO increasing and H2O2 decreasing, which lowered γ-tocopherol content via scavenging reactive nitrogen species. In conclusion, we proposed that the lower light-harvesting chlorophyll content weakened embryo photosynthesis, leading to fewer oxygen supplies and consequently diverse hypoxic responses including an elevated γ-tocopherol consumption. Our findings shed light on the mechanism for fine-tuning endogenous oxygen concentration in the maize embryo through a novel feedback pathway involving the light and low oxygen regulation of ZmPORB1 expression and chlorophyll content.


Asunto(s)
Tocoferoles , Zea mays , Humanos , Tocoferoles/metabolismo , Zea mays/genética , Zea mays/metabolismo , gamma-Tocoferol/metabolismo , Peróxido de Hidrógeno/metabolismo , Fotosíntesis/genética , Clorofila/metabolismo , Hipoxia , Oxígeno/metabolismo
15.
Nat Commun ; 15(1): 686, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263319

RESUMEN

Many types of tumors feature aerobic glycolysis for meeting their increased energetic and biosynthetic demands. However, it remains still unclear how this glycolytic phenomenon is achieved and coordinated with other metabolic pathways in tumor cells in response to growth stimuli. Here we report that activation of AKT1 induces a metabolic switch to glycolysis from the mitochondrial metabolism via phosphorylation of cytoplasmic malic enzyme 2 (ME2), named ME2fl (fl means full length), favoring an enhanced glycolytic phenotype. Mechanistically, in the cytoplasm, AKT1 phosphorylates ME2fl at serine 9 in the mitochondrial localization signal peptide at the N-terminus, preventing its mitochondrial translocation. Unlike mitochondrial ME2, which accounts for adjusting the tricarboxylic acid (TCA) cycle, ME2fl functions as a scaffold that brings together the key glycolytic enzymes phosphofructokinase (PFKL), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pyruvate kinase M2 (PKM2), as well as Lactate dehydrogenase A (LDHA), to promote glycolysis in the cytosol. Thus, through phosphorylation of ME2fl, AKT1 enhances the glycolytic capacity of tumor cells in vitro and in vivo, revealing an unexpected role for subcellular translocation switching of ME2 mediated by AKT1 in the metabolic adaptation of tumor cells to growth stimuli.


Asunto(s)
Carcinogénesis , Transformación Celular Neoplásica , Humanos , Fosforilación , Citosol , Citoplasma , Glucólisis , Proteínas Proto-Oncogénicas c-akt
16.
Sci Adv ; 10(2): eadk0738, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38198548

RESUMEN

The aromatic amino acids (AAAs) phenylalanine, tyrosine, and tryptophan are basic protein units and precursors of diverse specialized metabolites that are essential for plant growth. Despite their significance, the mechanisms that regulate AAA homeostasis remain elusive. Here, we identified a cytosolic aromatic aminotransferase, REVERSAL OF SAV3 PHENOTYPE 1 (VAS1), as a suppressor of arogenate dehydrogenase 2 (adh2) in Arabidopsis (Arabidopsis thaliana). Genetic and biochemical analyses determined that VAS1 uses AAAs as amino donors, leading to the formation of 3-carboxyphenylalanine and 3-carboxytyrosine. These pathways represent distinct routes for AAA metabolism that are unique to specific plant species. Furthermore, we show that VAS1 is responsible for cytosolic AAA biosynthesis, and its enzymatic activity can be inhibited by 3-carboxyphenylalanine. These findings provide valuable insights into the crucial role of VAS1 in producing 3-carboxy AAAs, notably via recycling of AAAs in the cytosol, which maintains AAA homeostasis and allows plants to effectively coordinate the complex metabolic and biosynthetic pathways of AAAs.


Asunto(s)
Arabidopsis , Transaminasas , Aminoácidos , Aminoácidos Aromáticos , Arabidopsis/genética , Citosol , Homeostasis , Transaminasas/genética
17.
Nat Plants ; 10(2): 228-239, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38278952

RESUMEN

Rapid advances in DNA synthesis techniques have enabled the assembly and engineering of viral and microbial genomes, presenting new opportunities for synthetic genomics in multicellular eukaryotic organisms. These organisms, characterized by larger genomes, abundant transposons and extensive epigenetic regulation, pose unique challenges. Here we report the in vivo assembly of chromosomal fragments in the moss Physcomitrium patens, producing phenotypically virtually wild-type lines in which one-third of the coding region of a chromosomal arm is replaced by redesigned, chemically synthesized fragments. By eliminating 55.8% of a 155 kb endogenous chromosomal region, we substantially simplified the genome without discernible phenotypic effects, implying that many transposable elements may minimally impact growth. We also introduced other sequence modifications, such as PCRTag incorporation, gene locus swapping and stop codon substitution. Despite these substantial changes, the complex epigenetic landscape was normally established, albeit with some three-dimensional conformation alterations. The synthesis of a partial multicellular eukaryotic chromosome arm lays the foundation for the synthetic moss genome project (SynMoss) and paves the way for genome synthesis in multicellular organisms.


Asunto(s)
Bryopsida , Epigénesis Genética , Cromosomas , Genómica/métodos , Bryopsida/genética , Elementos Transponibles de ADN
18.
Nat Commun ; 14(1): 7886, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38036514

RESUMEN

The genome of an organism is inherited from its ancestor and continues to evolve over time, however, the extent to which the current version could be altered remains unknown. To probe the genome plasticity of Saccharomyces cerevisiae, here we replace the native left arm of chromosome XII (chrXIIL) with a linear artificial chromosome harboring small sets of reconstructed genes. We find that as few as 12 genes are sufficient for cell viability, whereas 25 genes are required to recover the partial fitness defects observed in the 12-gene strain. Next, we demonstrate that these genes can be reconstructed individually using synthetic regulatory sequences and recoded open-reading frames with a "one-amino-acid-one-codon" strategy to remain functional. Finally, a synthetic neochromsome with the reconstructed genes is assembled which could substitute chrXIIL for viability. Together, our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional eukaryotic chromosomes from entirely artificial sequences.


Asunto(s)
Cromosomas , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Codón , Sistemas de Lectura Abierta , Cromosomas Fúngicos/genética , Genes Fúngicos
19.
Acta Oncol ; 62(12): 1757-1766, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37738252

RESUMEN

BACKGROUND: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear. MATERIALS AND METHODS: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals. RESULTS: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000∼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells. CONCLUSION: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Receptor EphA7 , Factor de Transcripción STAT3 , Humanos , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Transducción de Señal , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Receptor EphA7/metabolismo
20.
Chem Commun (Camb) ; 59(75): 11240-11243, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37656125

RESUMEN

A highly stable thiazole functionalized covalent triazine framework, namely CTF-BT-500, was developed for C2H6/C2H4 separation, which exhibits a record-high ethane uptake (99.7 cm3 g-1) among all reported COFs at 298 K and 1 bar. This work not only presents an excellent C2H6-selective adsorbent, but also provides guidance for the construction of robust adsorbents for value-added gas purification.

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