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The sweetness of apple fruit is a key factor in the improvement of apple varieties, with fructose being the sweetest of the soluble sugars, playing a crucial role in determining the overall sweetness of the apple. Therefore, uncovering the key genes controlling fructose accumulation and deciphering the regulatory mechanisms of fructose are vitally important for the improvement of apple varieties. In this study, through BSA-seq and transcriptome analysis of the 'Changfu 2' × 'Golden Delicious' F1 hybrid population, MdNAC5 was identified as a key regulatory gene for fructose content. MdNAC5 was shown to significantly influence fructose accumulation in both apples and tomatoes. Furthermore, we conducted a detailed identification of sugar transporters and metabolic enzymes in apples, discovering that MdNAC5 can enhance fructose accumulation in vacuoles and the conversion of sucrose to fructose by binding to and activating the promoters of the vacuolar sugar transporter MdTST2 and the neutral invertase MdNINV6. Additionally, MdNAC5 regulated the MdEIN3.4-MdSWEET15a module, strengthening the unloading of sucrose in the phloem of the fruit. Our results reveal a new mechanism by which MdNAC5 regulates fructose accumulation in apples and provide theoretical foundations for improving apple sweetness through genetic modification.
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A novel mangrove soil-derived actinomycete, strain S2-29T, was found to be most closely related to Saccharopolyspora karakumensis 5K548T based on 16 S rRNA sequence (99.24% similarity) and genomic phylogenetic analyses. However, significant divergence in digital DNA-DNA hybridization, average nucleotide identity, and unique biosynthetic gene cluster possession distinguished S2-29T as a distinct Saccharopolyspora species. Pan genome evaluation revealed exceptional genomic flexibility in genus Saccharopolyspora, with > 95% accessory genome content. Strain S2-29T harbored 718 unique genes, largely implicated in energetic metabolisms, indicating different metabolic capacities from its close relatives. Several uncharacterized biosynthetic gene clusters in strain S2-29T highlighted the strain's untapped capacity to produce novel functional compounds with potential biotechnological applications. Designation as novel species Saccharopolyspora mangrovi sp. nov. (type strain S2-29T = JCM 34,548T = CGMCC 4.7716T) was warranted, expanding the known Saccharopolyspora diversity and ecology. The discovery of this mangrove-adapted strain advances understanding of the genus while highlighting an untapped source of chemical diversity.
Assuntos
DNA Bacteriano , Genoma Bacteriano , Filogenia , RNA Ribossômico 16S , Saccharopolyspora , Microbiologia do Solo , Saccharopolyspora/genética , Saccharopolyspora/metabolismo , Saccharopolyspora/classificação , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Família Multigênica , Genômica , Análise de Sequência de DNA , Áreas Alagadas , Hibridização de Ácido Nucleico , Técnicas de Tipagem BacterianaRESUMO
Rocaglaol, embedding a cyclopenta[b]benzofuran scaffold, was isolated mainly from the plants of Aglaia and exhibited nanomolar level antitumor activity. However, the drug-like properties of these compounds are poor. To improve the physicochemical properties of rocaglaol, 36 nitrogen-containing phenyl-substituted rocaglaol derivatives were designed and synthesized. These derivatives were tested for the inhibitory effects on three tumor cell lines, HEL, MDA-231, and SW480, using the MTT assay. Among them, 22 derivatives exhibited good cytotoxic activities with IC50 values between 0.11 ± 0.07 and 0.88 ± 0.02 µM. Fourteen derivatives exhibited stronger cytotoxicity than the positive control, adriamycin. In particular, a water-soluble derivative revealed selective cytotoxic effects on HEL cells (IC50 = 0.19 ± 0.01 µM). This compound could induce G1 cell cycle arrest and apoptosis in HEL cells. Western blot assays suggested that the water-soluble derivative could downregulate the expression of the marker proteins of apoptosis, PARP, caspase-3, and caspase-9, thus inducing apoptosis. Further CETSA and Western blot studies implied that this water-soluble derivative might be an inhibitor of friend leukemia integration 1 (Fli-1). This water-soluble derivative may serve as a potential antileukemia agent by suppressing the expression of Fli-1.
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Antineoplásicos , Benzofuranos , Antineoplásicos/farmacologia , Apoptose , Doxorrubicina , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The Osiris gene family is believed to play important roles in insect biology. Previous studies mainly focused on the roles of Osiris in Drorophila, how Osiris operates during the development of other species remains largely unknown. Here, we investigated the role of LmOsi17 in development of the hemimetabolous insect Locusta migratoria. LmOsi17 was highly expressed in the intestinal tract of nymphs. Knockdown of LmOsi17 by RNA interference (RNAi) in nymphs resulted in growth defects. The dsLmOsi17-injected nymphs did not increase in body weight or size and eventually died. Immunohistochemical analysis showed that LmOsi17 was localized to the epithelial cells of the foregut and the gastric caecum. Histological observation and hematoxylin-eosin staining indicate that the foregut and gastric caecum are deformed in dsLmOsi17 treated nymphs, suggesting that LmOsi17 is involved in morphogenesis of foregut and gastric caecum. In addition, we observed a significant reduction in the thickness of the new cuticle in dsLmOsi17-injected nymphs compared to control nymphs. Taken together, these results suggest that LmOsi17 contributes to morphogenesis of intestinal tract that affects growth and development of nymphs in locusts.
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Proteínas de Insetos , Locusta migratoria , Morfogênese , Ninfa , Animais , Locusta migratoria/crescimento & desenvolvimento , Locusta migratoria/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Ninfa/crescimento & desenvolvimento , Interferência de RNA , IntestinosRESUMO
Developing economical, efficient, and durable oxygen evolution catalysts is crucial for achieving sustainable energy conversion and storage. Ruddlesden-Popper-type perovskite oxides are at the forefront of oxygen evolution reaction (OER) research. However, their activity and stability are far from satisfactory. Therefore, we emphasize the paradigm shift in designing efficient perovskite-type OER catalysts through anion defect engineering. The Cl anion-doped A2BO4-type perovskite oxides, SrLaCoO4-xClx (SLCOClx), were employed as highly efficient OER catalysts, wherein Cl could tune the electronic structure of SrLaCoO4 (SLCO) to enhance the OER activity effectively. Especially, SLCOCl0.15 demonstrates significantly enhanced OER activity, and the overpotential is only 370 mV at 10 mA·cm-2, which is significantly better than that of SLCO (510 mV). As confirmed by experience results and density functional theory (DFT) calculation, due to the doping of Cl, obviously increasing the ratio of Co2+/Co3+, more abundant oxygen vacancies (O22-/O-) are generated, and the electrical conductivity is increased, which together promote the improvement of OER activity.
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The abnormal modification of histone is an important factor restricting development of porcine cloned embryos. Overexpression of histone H3K9me3 demethylase KDM4 family can effectively improve the developmental efficiency of cloned embryos. In order to explore the effects of overexpression of H3K9me3 demethylase on the development of porcine cloned embryos, KDM4A mRNA and KDM4D mRNA were injected respectively into porcine cloned embryos at the 1-cell stage and 2-cell stage to detect the blastocyst rate; 2-cell stage cloned embryos injected with KDM4A mRNA and embryo injection water (the control group) at the 1-cell stage were collected to detect the expression level of H3K9me3, and 4-cell stage cloned embryos were collected for single cell transcriptome sequencing, then the sequencing data was analyzed with KEGG and GO. The results showed that the blastocyst rate of porcine cloned embryos injected with KDM4A mRNA at 1-cell stage was significantly higher than that of the control group (25.32 ± 0.74% vs 14.78 ± 0.87%), while cloned embryos injected with KDM4D mRNA had a similar blastocyst rate with cloned embryos in control group (16.27 ± 0.77% vs 14.78 ± 0.87%). Porcine cloned embryos injected with KDM4A mRNA and KDM4D mRNA at 2-cell stage had a similar blastocyst rate with cloned embryos in control group (32.18 ± 1.67%, 30.04 ± 0.91% vs 31.22 ± 1.40%). The expression level of H3K9me3 in cloned embryos injected with KDM4A mRNA at 1-cell stage was lower than that in control group. There were 133 differentially expressed genes detected by transcriptome sequencing, including 52 up-regulated genes and 81 down-regulated genes. Pathways enriched by GO analyses were mainly related to protein localization. Pathways enriched by KEGG analyses were related to cellular senescence and acute myeloid leukemia. These results suggest that overexpression of histone H3K9me3 demethylase KDM4A can significantly improve the developmental efficiency of porcine cloned embryos.
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Histona Desmetilases , Histonas , Suínos/genética , Animais , Histona Desmetilases/metabolismo , Histona Desmetilases/farmacologia , Histonas/genética , Histonas/metabolismo , Técnicas de Transferência Nuclear , Desenvolvimento Embrionário/genética , Blastocisto/metabolismo , RNA Mensageiro/metabolismo , Clonagem de OrganismosRESUMO
The anterior cingulate cortex (ACC) is located in the frontal part of the cingulate cortex, and plays important roles in pain perception and emotion. The thalamocortical pathway is the major sensory input to the ACC. Previous studies have show that several different thalamic nuclei receive projection fibers from spinothalamic tract, that in turn send efferents to the ACC by using neural tracers and optical imaging methods. Most of these studies were performed in monkeys, cats, and rats, few studies were reported systematically in adult mice. Adult mice, especially genetically modified mice, have provided molecular and synaptic mechanisms for cortical plasticity and modulation in the ACC. In the present study, we utilized rabies virus-based retrograde tracing system to map thalamic-anterior cingulate monosynaptic inputs in adult mice. We also combined with a new high-throughput VISoR imaging technique to generate a three-dimensional whole-brain reconstruction, especially the thalamus. We found that cortical neurons in the ACC received direct projections from different sub-nuclei in the thalamus, including the anterior, ventral, medial, lateral, midline, and intralaminar thalamic nuclei. These findings provide key anatomic evidences for the connection between the thalamus and ACC.
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Giro do Cíngulo , Tálamo , Animais , Giro do Cíngulo/metabolismo , Camundongos , Vias Neurais , Neurônios , Ratos , Núcleos Talâmicos/fisiologiaRESUMO
A modulated structure with symmetrical characteristic higher than three-dimensional is a fascinating crystallographic type, and it is randomly encountered by researchers. Herein, we prepared 0.1 mm level single crystals of Na3La(VO4)2 and determined its structure to be a (3 + 1)-dimensional modulated structure using the X-ray diffraction analysis method for single crystals. Its super space group was determined to be Pca21(0ß0)000. On the other hand, we introduced Tb3+ into the Na3La(VO4)2 host lattice to fabricate phosphors Na3La1-x(VO4)2:xTb3+ and studied their photoluminescence properties. Interestingly, for the strong absorption of the Na3La(VO4)2 host lattice in the range of 200-400 nm, the traditional 330-385 nm light is unable to efficiently excite Tb3+ ions in the Na3La(VO4)2 host to generate luminescence of Tb3+. Instead, Na3La1-x(VO4)2:xTb3+ is suitable to be excited by 487 nm to generate emitting light at 543, 584, and 622 nm, due to Tb3+ characteristic 4f â 4f transitions of 5D4 â 7FJ (J = 5, 4, 3). Hence, the Tb3+-doped Na3La(VO4)2 phosphors have potential applications for white-light-emitting diodes.
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Ostreid herpesvirus 1 (OsHV-1) infection caused mortalities with relevant economic losses in bivalve aquaculture industry worldwide. Initially described as an oyster pathogen, OsHV-1 can infect other bivalve species, like the blood clam Scapharca broughtonii. However, at present, little is known about the molecular interactions during OsHV-1 infection in the blood clam. We produced paired miRNA and total RNA-seq data to investigate the blood clam transcriptional changes from 0 to 72 h after experimental infection with OsHV-1. High-throughput miRNA sequencing of 24 libraries revealed 580 conserved and 270 new blood clam miRNAs, whereas no genuine miRNA was identified for OsHV-1. Total 88-203 differently expressed miRNAs were identified per time point, mostly up-regulated and mainly targeting metabolic pathways. Most of the blood clam mRNAs, in contrast, were down-regulated up to 60 h post-injection, with the trend analysis revealing the activation of immune genes only when comparing the early and latest stage of infection. Taken together, paired short and long RNA data suggested a miRNA-mediated down-regulation of host metabolic and energetic processes as a possible antiviral strategy during early infection stages, whereas antiviral pathways appeared upregulated only at late infection.
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Crassostrea , Herpesviridae , MicroRNAs , Scapharca , Animais , Crassostrea/genética , Vírus de DNA/fisiologia , Mecanismos de Defesa , Herpesviridae/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Scapharca/genética , Análise de Sequência de RNARESUMO
Hyperpatone A (1), a highly oxidated polycyclic polyprenylated acylphloroglucinol (PPAP), along with a biosynthesized related PPAP (2) was isolated from Hypericum patulum under the guidance of LC-MS investigation. Architecturally, compound 1 represents the first PPAP with an unprecedented 8/6/5/6/5 pentacyclic skeleton and an intramolecular peroxy bridge, which might be derived from the [3.3.1]-type bicyclic polyprenylated acylphloroglucinol via the critical Baeyer-Villiger oxidation, decarboxylation, and intramolecular cyclization. The structures were established by extensive spectroscopic analysis, ACD software calculation, and quantum chemical computations. A plausible biogenetic pathway of 1 and 2 was also proposed. Importantly, both compounds exhibited moderate cytotoxic activities against the HEL cell line with the IC50 values ranging from 10.2 to 19.2 µM. Moreover, compound 1 showed an inhibitory effect on NO production in lipopolysaccharide-stimulated RAW264.7 cells at a lower concentration of 5 or 1 µM.
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Hypericum , Estrutura Molecular , Hypericum/química , Floroglucinol/química , EsqueletoRESUMO
BACKGROUND: The present study was designed to identify and understand the potential effectiveness of therapeutic target in intervertebral disc degeneration (IVDD) and its regulation mechanism. METHODS: The role and mechanism of interleukin-18 (IL-18) in the disease were investigated. The IVDD degenerative nucleus pulposus (NP) tissues from the human and mouse models were used.A total of three groups of Male BALB/c mice were randomly made i.e control, IVDD, and IVDD+Ad-shIL-18 groups. After Ad-shIL-18 transfection, the expression of ECM synthesis related protein Aggrecan (ACAN) and Collagen II, apoptotic effector Caspases (Caspase-3, 8, 9, 12 and Cleaved-Caspase 3, 8, 9, 12), pro-apoptotic gene Bax and anti-apoptotic factors Bcl-2 in NP cells of the human were evaluated. RESULTS: The results of our study revealed that the mRNA and protein expression levels of IL-18 were notably increased in the NP tissues of IVDD patients and mice models. In the IVDD mice model, Ad-sh-IL-18 treatment reversed the IVDD progression. The levels of Aggrecan and Collagen II, contributing to ECM degradation in NP cells, were also significantly increased. Additionally, Ad-sh-IL-18 could inhibit the NP cell's apoptosis via regulating the caspase-3/9 pathway. CONCLUSION: The IL-18 knockdown via the caspase-3/9 pathway, might reduce the NP cell's death as well as the imbalance between catabolism and anabolism of ECM in IVDD.
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Degeneração do Disco Intervertebral , Agrecanas/genética , Animais , Apoptose , Caspase 3/genética , Colágeno/uso terapêutico , Humanos , Interleucina-18 , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , Masculino , CamundongosRESUMO
Atypical chemokine receptor 3 (ACKR3) has emerged as a key player in various biological processes. Its atypical "intercepting receptor" properties have established ACKR3 as the major regulator in the pathophysiological processes in many diseases. In this study, we investigated the role of ACKR3 activation in promoting colorectal tumorigenesis. We showed that ACKR3 expression levels were significantly increased in human colon cancer tissues, and high levels of ACKR3 predicted the increased severity of cancer. In Villin-ACKR3 transgenic mice with a high expression level of CKR3 in their intestinal epithelial cells, administration of AOM/DSS induced more severe colorectal tumorigenesis than their WT littermates. Cancer cells of Villin-ACKR3 transgenic mice were characterised by the nuclear ß-arrestin-1 (ß-arr1)-activated perturbation of rRNA biogenesis. In HCT116 cells, cotreatment with CXCL12 and AMD3100 selectively activated ACKR3 and induced nuclear translocation of ß-arr1, leading to an interaction of ß-arr1 with nucleolar and coiled-body phosphoprotein 1 (NOLC1). NOLC1, as the phosphorylated protein, further interacted with fibrillarin, a conserved nucleolar methyltransferase responsible for ribosomal RNA methylation in the nucleolus, thereby increasing the methylation in histone H2A and promoting rRNA transcription in ribosome biogenesis. In conclusion, ACKR3 promotes colorectal tumorigenesis through the perturbation of rRNA biogenesis by the ß-arr1-induced interaction of NOLC1 with fibrillarin.
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Transformação Celular Neoplásica , Neoplasias Colorretais , Receptores CXCR , Animais , Humanos , Camundongos , beta-Arrestina 1/genética , beta-Arrestina 1/metabolismo , beta-Arrestinas/metabolismo , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Quimiocina CXCL12 , Neoplasias Colorretais/genética , Camundongos Transgênicos , Proteínas Nucleares/genética , Fosfoproteínas/metabolismo , Receptores CXCR/metabolismoRESUMO
OBJECTIVE: This study aimed to investigate the effect of continuing nursing care team mode on postoperative outpatient chemotherapy patients with pancreatic cancer. METHODS: One-hundred patients receiving postoperative outpatient chemotherapy for pancreatic cancer between September 2019 and December 2020 were enrolled in this study and divided into two groups, an intervention group and a control group (n = 50 each), by random number table method or coin tossing method. The patients in the intervention group were followed up using continuing nursing care team mode, while those in the control group were followed up using the traditional telephone follow-up mode. The effects of the two modes on patients' self-care ability, quality of life, anxiety, hospital waiting time, and the nurses' communication ability and self-efficacy were compared and analyzed. RESULTS: The self-care ability and quality of life of the patients in the intervention group were better than those of the control group (p < 0.05), the anxiety score and hospital waiting times were lower than those in the control group (p < 0.05), and the communication ability and general self-efficacy of the nurses were also significantly stronger than those in the control group (p < 0.05). CONCLUSION: The application of the continuing nursing care team mode for follow-up can improve the self-care ability and quality of life of patients, effectively reduce the anxiety and hospital waiting time of outpatient chemotherapy patients, and improve the nurses' communication ability and general self-efficacy. Therefore, this practice is worthy of clinical popularization.
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Neoplasias Pancreáticas , Qualidade de Vida , Humanos , Autoeficácia , Ansiedade/etiologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Equipe de Assistência ao PacienteRESUMO
Two new maytansinoids, N-methyltreflorine (1: ) and methyltrewiasine (2: ), were isolated from the dried fruits of Trewia nudiflora, together with three known congeners (3: â-â5: ). Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1: and 2: was determined by X-ray crystallographic analysis. Compounds 1: â-â5: exhibited strong cytotoxicity against human tumor cell lines, including HeLa, MV-4â-â11, and MCF-7, with IC50 values ranging from 0.12 to 11 nM. Compounds 1: and 4: also showed inhibitory activity against the MCF-7/ADR cell line with IC50 values of 13 and 28 nM, respectively. Compounds 1: and 2: significantly inhibited tubulin polymerization in vitro with IC50 values of 3.6 and 3.2 µM, respectively.
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Antineoplásicos , Tubulina (Proteína) , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Células HeLa , Humanos , Células MCF-7 , Estrutura Molecular , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismoRESUMO
Three new aglain derivatives (1-3), one known aglain derivative (4), two known rocaglamide derivatives (5 and 6), four known triterpenoids (7-10), and three steroids (11-13) were isolated from Aglaia odorata Lour. Their structures were established through the analysis of detailed spectroscopic data and electronic circular dichroism calculations. Five compounds (1 and 4-7) exhibited cytotoxic activities on human leukemia cells (HEL) and human breast cancer cells with IC50 values in the range of 0.03-8.40â µM. In particular, the cytotoxicity of compound 5 was six times stronger than that of the positive control (adriamycin) in HEL cell lines.
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Aglaia , Antineoplásicos Fitogênicos , Antineoplásicos , Triterpenos , Aglaia/química , Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Dicroísmo Circular , Humanos , Estrutura Molecular , Extratos Vegetais/química , Triterpenos/químicaRESUMO
Naringenin (5,7,4'-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic samples, the identification and efficient characterization of drug metabolites are difficult. Here, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry was used to obtain mass spectral information of plasma (processed by three methods), urine, feces, liver tissue, and liver microsome samples. Moreover, a novel analytical strategy named "ion induction and deduction" was proposed to systematically screen and identify naringenin metabolites in vivo and in vitro. The analysis strategy was accomplished by the establishment of multiple "net-hubs" and the induction and deduction of fragmentation behavior. Finally, 78 naringenin metabolites were detected and identified from samples of rat plasma, urine, feces, liver tissue, and liver microsomes, of which 67 were detected in vivo and 13 were detected in vitro. Naringenin primarily underwent glucuronidation, sulfation, oxidation, methylation, ring fission, and conversion into phenolic acid and their composite reactions. The current study provides significant help in extracting target information from complex samples and sets the foundation for other pharmacology and toxicology research.
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Flavanonas , Ratos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas , Microssomos HepáticosRESUMO
This study aims to identify and analyze the metabolites of imperatorin in rats by UHPLC-Q-Exactive Orbitrap MS. Specifically, after rats were treated(ig) with imperatorin, the plasma, urine, and feces were collected, and the samples were processed by solid phase extraction. Then, UHPLC-Q-Exactive Orbitrap MS was performed. In MS, 0.1% formic acid water(A)-acetonitrile(B) was applied as mobile phase for gradient elution and the data of MS in both positive and negative ion modes were collected. The metabolites of imperatorin in blood, urine, and feces of rats were analyzed to explore the metabolic pathways of imperatorin in rats. According to accurate molecular weight, multistage MS data, MS fragmentation rule of the standard substance, and previous reports, a total of 51 metabolites were identified, with 35, 40, and 16 from plasma, urine, and feces, separately. The main metabolic pathways were oxidization, glucuronidation, isopentenyl removal, sulphation, carboxylation, among others. The conclusion in this study is expected to serve as a reference for the further development and the further pharmacodynamics study of imperatorin.
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Plasma , Extração em Fase Sólida , Animais , Cromatografia Líquida de Alta Pressão , Fezes , Furocumarinas , RatosRESUMO
Myomesin-1 (encoded by MYOM1 gene) is expressed in almost all cross-striated muscles, whose family (together with myomesin-2 and myomesin-3) helps to cross-link adjacent myosin to form the M-line in myofibrils. However, little is known about its biological function, causal relationship and mechanisms underlying the MYOM1-related myopathies (especially in the heart). Regrettably, there is no MYMO1 knockout model for its study so far. A better and further understanding of MYOM1 biology is urgently needed. Here, we used CRISPR/Cas9 gene-editing technology to establish an MYOM1 knockout human embryonic stem cell line (MYOM1-/- hESC), which was then differentiated into myomesin-1 deficient cardiomyocytes (MYOM1-/- hESC-CMs) in vitro. We found that myomesin-1 plays an important role in sarcomere assembly, contractility regulation and cardiomyocytes development. Moreover, myomesin-1-deficient hESC-CMs can recapitulate myocardial atrophy phenotype in vitro. Based on this model, not only the biological function of MYOM1, but also the aetiology, pathogenesis, and potential treatments of myocardial atrophy caused by myomesin-1 deficiency can be studied.
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Cálcio/metabolismo , Conectina/deficiência , Suscetibilidade a Doenças , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Miócitos Cardíacos/metabolismo , Alelos , Diferenciação Celular/genética , Linhagem Celular , Células-Tronco Embrionárias/metabolismo , Edição de Genes , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Predisposição Genética para Doença , Humanos , Imagem Molecular , Atrofia Muscular/patologia , Miócitos Cardíacos/patologia , Miócitos Cardíacos/ultraestrutura , Fenótipo , Sarcômeros/metabolismo , Sarcômeros/ultraestruturaRESUMO
Diabetic retinopathy (DR) is one of the common complications in diabetic patients. Nowadays, VEGF pathway is subject to extensive research. However, about 27% of the patients have a poor visual outcome, with 50% still having edema after two years' treatment of diabetic macular edema (DME) with ranibizumab. Docosahexaenoic acid (DHA), the primary ω-3 long-chain polyunsaturated fatty acid (LC-PUFA), reduces abnormal neovascularization and alleviates neovascular eye diseases. A study reported that fish oil reduced the incidence of retinopathy of prematurity (ROP) by about 27.5% in preterm infants. Although ω-3 LC-PUFAs protects against pathological retinal neovascularization, the treatment effectiveness is low. It is interesting to investigate why DHA therapy fails in some patients. In human vitreous humor samples, we found that the ratio of DHA and DHA-derived metabolites to total fatty acids was higher in vitreous humor from DR patients than that from macular hole patients; however, the ratio of DHA metabolites to DHA and DHA-derived metabolites was lower in the diabetic vitreous humor. The expression of Mfsd2a, the LPC-DHA transporter, was reduced in the oxygen-induced retinopathy (OIR) model and streptozotocin (STZ) model. In vitro, Mfsd2a overexpression inhibited endothelial cell proliferation, migration and vesicular transcytosis. Moreover, Mfsd2a overexpression in combination with the DHA diet obviously reduced abnormal retinal neovascularization and vascular leakage, which is more effective than Mfsd2a overexpression alone. These results suggest that DHA therapy failure in some DR patients is linked to low expression of Mfsd2a, and the combination of Mfsd2a overexpression and DHA therapy may be an effective treatment.
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Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Retinopatia Diabética/metabolismo , Edema Macular/metabolismo , Simportadores/metabolismo , Animais , Linhagem Celular , Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Tipo 1/dietoterapia , Retinopatia Diabética/dietoterapia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Retina/metabolismo , Simportadores/genética , Corpo Vítreo/metabolismo , CicatrizaçãoRESUMO
A Gram-negative bacterium, designated S1-65T, was isolated from soil samples collected from a cotton field located in the Xinjiang region of PR China. Results of 16S rRNA gene sequence analysis revealed that strain S1-65T was affiliated to the genus Steroidobacter with its closest phylogenetic relatives being 'Steroidobacter cummioxidans' 35Y (98.4â%), 'Steroidobacter agaridevorans' SA29-B (98.3â%) and Steroidobacter agariperforans KA5-BT (98.3â%). 16S rRNA-directed phylogenetic analysis showed that strain S1-65T formed a unique phylogenetic subclade next to 'S. agaridevorans' SA29-B and S. agariperforans KA5-BT, suggesting that strain S1-65T should be identified as a member of the genus Steroidobacter. Further, substantial differences between the genotypic properties of strain S1-65T and the members of the genus Steroidobacter, including average nucleotide identity and digital DNA-DNA hybridization, resolved the taxonomic position of strain S1-65T and suggested its positioning as representing a novel species of the genus Steroidobacter. The DNA G+C content of strain S1-65T was 62.5 mol%, based on its draft genome sequence. The predominant respiratory quinone was ubiquinone-8. The main fatty acids were identified as summed feature 3 (C16:1ω6c/C16:1ω7c), C16â:â0 and iso-C15â:â0. In addition, its polar lipid profile was composed of aminophospholipid, diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Here, we propose a novel species of the genus Steroidobacter: Steroidobacter gossypii sp. nov. with the type strain S1-65T (=JCM 34287T=CGMCC 1.18736T).