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To investigate the effect and mechanism of Huogu injection (HG) on steroid-induced osteonecrosis of the femoral head (SONFH), we established a SONFH model in rabbits using horse serum and dexamethasone (DEX) and applied HG locally at the hip joint. We evaluated the therapeutic efficacy at 4 weeks using scanning electron microscopy (SEM), micro-CT, and qualitative histology including H&E, Masson's trichrome, ALP, and TUNEL staining. In vitro, we induced osteogenic differentiation of bone marrow stromal cells (BMSCs) and performed analysis on days 14 and 21 of cell differentiation. The findings, in vivo, including SEM, micro-CT, and H&E staining, showed that HG significantly maintained bone quality and trabecular number. ALP staining indicated that HG promoted the proliferation of bone cells. Moreover, the results of Masson's trichrome staining demonstrated the essential role of HG in collagen synthesis. Additionally, TUNEL staining revealed that HG reduced apoptosis. ALP and ARS staining in vitro confirmed that HG enhanced osteogenic differentiation and mineralization, consistent with the WB and qRT-PCR analysis. Furthermore, Annexin V-FITC/PI staining verified that HG inhibited osteoblast apoptosis, in agreement with the WB and qRT-PCR analyses. Furthermore, combined with the UPLC analysis, we found that naringin enhanced the osteogenic differentiation and accelerated the deposition of calcium phosphate. Salvianolic acid B protected osteoblasts derived from BMSCs against GCs-mediated apoptosis. Thus, this study not only reveals the mechanism of HG in promoting osteogenesis and anti-apoptosis of osteoblasts but also identifies the active-related components in HG, by which we provide the evidence for the application of HG in SONFH.
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Células-Tronco Mesenquimais , Osteogênese , Animais , Coelhos , Diferenciação Celular , Osteoblastos , Apoptose , Células CultivadasRESUMO
A highly enantioselective catalytic reduction of pyrazolo[1,5-a]pyrimidine to zanubrutinib has been realized by the Ir/(R)-t-Bu-FcPhox complex. This chiral product could be obtained in up to >99% ee in the asymmetric transformation without any other additives, providing a new route for the asymmetric synthesis of zanubrutinib.
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The discovery of new genes with novel functions is a major driver of adaptive evolutionary innovation in plants. Especially in woody plants, due to genome expansion, new genes evolve to regulate the processes of growth and development. In this study, we characterized the unique VeA transcription factor family in Populus alba × Populus glandulosa, which is associated with secondary metabolism. Twenty VeA genes were characterized systematically on their phylogeny, genomic distribution, gene structure and conserved motif, promoter binding site, and expression profiling. Furthermore, through ChIP-qPCR, Y1H, and effector-reporter assays, it was demonstrated that PagMYB128 directly regulated PagVeA3 to influence the biosynthesis of secondary metabolites. These results provide a basis for further elucidating the function of VeAs gene in poplar and its genetic regulation mechanism.
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Populus , Fatores de Transcrição , Fatores de Transcrição/genética , Populus/genética , Genômica , Sítios de Ligação , BioensaioRESUMO
The photoperiod is a major environmental factor in flowering control. Water spinach flowering under the inductive short-day condition decreases the yield of vegetative tissues and the eating quality. To obtain an insight into the molecular mechanism of the photoperiod-dependent regulation of the flowering time in water spinach, we performed transcriptome sequencing on water spinach under long- and short-day conditions with eight time points. Our results indicated that there were 6615 circadian-rhythm-related genes under the long-day condition and 8691 under the short-day condition. The three key circadian-rhythm genes, IaCCA1, IaLHY, and IaTOC1, still maintained single copies and similar IaCCA1, IaLHY, and IaTOC1 feedback expression patterns, indicating the conservation of reverse feedback. In the photoperiod pathway, highly conserved GI genes were amplified into two copies (IaGI1 and IaGI2) in water spinach. The significant difference in the expression of the two genes indicates functional diversity. Although the photoperiod core gene FT was duplicated to three copies in water spinach, only IaFT1 was highly expressed and strongly responsive to the photoperiod and circadian rhythms, and the almost complete inhibition of IaFT1 in water spinach may be the reason why water spinach does not bloom, no matter how long it lasts under the long-day condition. Differing from other species (I. nil, I. triloba, I. trifida) of the Ipomoea genus that have three CO members, water spinach lacks one of them, and the other two CO genes (IaCO1 and IaCO2) encode only one CCT domain. In addition, through weighted correlation network analysis (WGCNA), some transcription factors closely related to the photoperiod pathway were obtained. This work provides valuable data for further in-depth analyses of the molecular regulation of the flowering time in water spinach and the Ipomoea genus.
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Ipomoea , Fotoperíodo , Transcriptoma , Ipomoea/genética , Flores/genética , Flores/metabolismo , Ritmo Circadiano/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
The biosynthesis of cellulose, lignin, and hemicelluloses in plant secondary cell walls (SCWs) is regulated by a hierarchical transcriptional regulatory network. This network features orthologous transcription factors shared between poplar and Arabidopsis, highlighting a foundational similarity in their genetic regulation. However, knowledge on the discrepant behavior of the transcriptional-level molecular regulatory mechanisms between poplar and Arabidopsis remains limited. In this study, we investigated the function of PagMYB128 during wood formation and found it had broader impacts on SCW formation compared to its Arabidopsis ortholog, AtMYB103. Transgenic poplar trees overexpressing PagMYB128 exhibited significantly enhanced xylem development, with fiber cells and vessels displaying thicker walls, and an increase in the levels of cellulose, lignin, and hemicelluloses in the wood. In contrast, plants with dominant repression of PagMYB128 demonstrated the opposite phenotypes. RNA sequencing and reverse transcription - quantitative polymerase chain reaction showed that PagMYB128 could activate SCW biosynthetic gene expression, and chromatin immunoprecipitation along with yeast one-hybrid, and effector-reporter assays showed this regulation was direct. Further analysis revealed that PagSND1 (SECONDARY WALL-ASSOCIATED NAC-DOMAIN PROTEIN1) directly regulates PagMYB128 but not cell wall metabolic genes, highlighting the pivotal role of PagMYB128 in the SND1-driven regulatory network for wood development, thereby creating a feedforward loop in SCW biosynthesis.
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Parede Celular , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Populus , Madeira , Populus/genética , Populus/metabolismo , Populus/crescimento & desenvolvimento , Parede Celular/metabolismo , Madeira/crescimento & desenvolvimento , Madeira/genética , Madeira/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Xilema/metabolismo , Xilema/genética , Lignina/biossíntese , Lignina/metabolismo , Plantas Geneticamente Modificadas , Genes de Plantas , Celulose/biossíntese , Celulose/metabolismoRESUMO
BACKGROUND: A common psychological problem among nurses is depression, potentially affecting their well-being and job performance. It is vital to explore how to alleviate nurses' depressive symptoms. AIM: The current research explored the mediating impact of basic psychological needs satisfaction on the link of gratitude with depressive symptoms. METHODS: The nurses in this study were from mainland China. A total of 724 subjects completed an online questionnaire, which included measures of depressive symptoms, basic psychological needs satisfaction and gratitude. RESULTS: Our research found that gratitude was negatively linked to depressive symptoms. Furthermore, basic psychological needs satisfaction had a partial mediation effect on the link of gratitude with depressive symptoms after controlling for five demographic variables. These results suggest that gratitude may influence depressive symptoms via basic psychological needs satisfaction. LINKING EVIDENCE TO ACTION: Our study found that basic psychological need satisfaction partially mediates the gratitude-depression relationship in nurses. The result means that hospital administrators and nurse leaders should design gratitude interventions to alleviate nurses' depressive symptoms. They also help nurses decrease depressive symptoms by creating an environment that meets their basic psychological needs.
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KEY MESSAGE: We identified a dosage-dependent dominant negative form of Sar1c, which confirms the essential role of COPII system in mediating ER export of storage proteins in rice endosperm. Higher plants accumlate large amounts of seed storage proteins (SSPs). However, mechanisms underlying SSP trafficking are largely unknown, especially the ER-Golgi anterograde process. Here, we showed that a rice glutelin precursor accumulation13 (gpa13) mutant exhibited floury endosperm and overaccumulated glutelin precursors, which phenocopied the reported RNAi-Sar1abc line. Molecular cloning revealed that the gpa13 allele encodes a mutated Sar1c (mSar1c) with a deletion of two conserved amino acids Pro134 and Try135. Knockdown or knockout of Sar1c alone caused no obvious phenotype, while overexpression of mSar1c resulted in seedling lethality similar to the gpa13 mutant. Transient expression experiment in tobacco combined with subcellular fractionation experiment in gpa13 demonstrated that the expression of mSar1c affects the subcellular distribution of all Sar1 isoforms and Sec23c. In addition, mSar1c failed to interact with COPII component Sec23. Conversely, mSar1c competed with Sar1a/b/d to interact with guanine nucleotide exchange factor Sec12. Together, we identified a dosage-dependent dominant negative form of Sar1c, which confirms the essential role of COPII system in mediating ER export of storage proteins in rice endosperm.
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Oryza , Proteínas de Armazenamento de Sementes , Proteínas de Armazenamento de Sementes/metabolismo , Oryza/genética , Transporte Proteico/genética , Glutens/genética , Retículo Endoplasmático/metabolismoRESUMO
In this study, we theoretically and experimentally demonstrate that the convolutional neural network (CNN) in combination with the residual blocks and the regression methods can be used to precisely and quickly reconstruct the OAM spectrum of a hybrid OAM mode no matter how the consistent OAM modes have the same or different order indices in both the azimuthal and the radial direction. For cases of the simulation testing, the mean errors of all recognized parameters for hybrid OAM modes in a four-mode fiber (4MF) and a six-mode fiber (6MF) are smaller than 0.003 and 0.008, respectively. To the best of our knowledge, this is the first time that all the OAM modes, probably existing in the core of 4MFs or 6MFs, can be precisely and quickly recognized from intensity distribution of the hybrid OAM mode itself via the deep learning method.
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OBJECTIVES: Takayasu's arteritis (TAK) is a progressive autoimmune vasculitis that mainly affects the aorta and its major branches. While recent studies have identified proinflammatory T cells, including Th1 and Th17 cells, as the dominant infiltrates in the arterial adventitia, mechanisms underpinning the maintenance of such vasculogenic T cells remain obscure. METHODS: 75 patients with TAK and 30 age-matched healthy controls were enrolled in this study. CD4 T cells from TAK patients were activated with anti-CD3/CD28 beads to mimic vasculogenic T cells. The survival of T cells was detected by quantifying Annexin-V+7-AAD+ fractions. Expression and activity of AMP-activated protein kinase (AMPK) were determined using phosflow cytometry and immunoblots. Specific inhibitors and shRNA were applied to block the function of AMPK and Notch1, while erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to reflect the disease activity of TAK patients. RESULTS: T cells from TAK patients undergo spontaneous differentiation into vasculogenic proinflammatory T cells with prolonged survival capacity. Mechanistic explorations uncover AMPK hyperactivity in such T cells from TAK patients, promoting mitochondrial metabolism and their survival. Such AMPK hyperactivity results from the robust Notch1 activity in TAK T cells. Accordingly, T cell-intrinsic phosphor-AMPK reflects the disease activity in clinical TAK patients. CONCLUSIONS: AMPK hyperactivity is essential for maintaining the vasculogenic proinflammatory T cells in TAK patients, serving as a promising therapeutic target for TAK management.
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Arterite de Células Gigantes , Arterite de Takayasu , Humanos , Proteínas Quinases Ativadas por AMP/uso terapêutico , Proteína C-Reativa/metabolismo , Diferenciação Celular , Linfócitos T/imunologiaRESUMO
BACKGROUND: Anthocyanins have distinct biological functions in plant coloring, plant defense against strong light, UV irradiation, and pathogen infection. Aromatic hydroxyl groups and ortho-dihydroxyl groups in anthocyanins are able to inhibit free-radical chain reactions and hydroxyl radicals. Thus, anthocyanins play an antioxidative role by removing various types of ROS. Pepper is one of the solanaceous vegetables with the largest cultivation area in China. The purple-fruited pepper is rich in anthocyanins, which not only increases the ornamental nature of the pepper fruit but also benefits the human body. In this experiment, light-induced regulatory pathways and related specific regulators of anthocyanin biosynthesis were examined through integrative transcriptomic and metabolomic analysis. RESULTS: Results revealed that delphinium 3-O-glucoside significantly accumulated in light exposed surface of pepper fruit after 48 h as compared to shaded surface. Furthermore, through strand-specific sequencing technology, 1341 differentially expressed genes, 172 differentially expressed lncRNAs, 8 differentially expressed circRNAs, and 28 differentially expressed miRNAs were identified significantly different among both surfaces. The flavonoid synthesis pathway was significantly enriched by KEGG analysis including SHT (XM_016684802.1), AT-like (XM_016704776.1), CCoAOMT (XM_016698340.1, XM_016698341.1), CHI (XM_016697794.1, XM_016697793.1), CHS2 (XM_016718139.1), CHS1B (XM_016710598.1), CYP98A2-like (XM_016688489.1), DFR (XM_016705224.1), F3'5'H (XM_016693437.1), F3H (XM_016705025.1), F3'M (XM_016707872.1), LDOX (XM_016712446.1), TCM (XM_016722116.1) and TCM-like (XM_016722117.1). Most of these significantly enriched flavonoid synthesis pathway genes may be also regulated by lncRNA. Some differentially expressed genes encoding transcription factors were also identified including MYB4-like (XM_016725242.1), MYB113-like (XM_016689220.1), MYB308-like (XM_016696983.1, XM_016702244.1), and EGL1 (XM_016711673.1). Three 'lncRNA-miRNA-mRNA' regulatory networks with sly-miR5303, stu-miR5303g, stu-miR7997a, and stu-miR7997c were constructed, including 28 differentially expressed mRNAs and 6 differentially expressed lncRNAs. CONCLUSION: Possible light regulated anthocyanin biosynthesis and transport genes were identified by transcriptome analysis, and confirmed by qRT-PCR. These results provide important data for further understanding of the anthocyanin metabolism in response to light in pepper.
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Antocianinas/biossíntese , Capsicum/genética , Capsicum/metabolismo , MicroRNAs/genética , Antocianinas/análise , Antocianinas/genética , Capsicum/fisiologia , Frutas/fisiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Luz , Pigmentação , Proteínas de Plantas/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genéticaRESUMO
Dense vesicles (DVs) are Golgi-derived plant-specific carriers that mediate post-Golgi transport of seed storage proteins in angiosperms. How this process is regulated remains elusive. Here, we report a rice (Oryza sativa) mutant, named glutelin precursor accumulation8 (gpa8) that abnormally accumulates 57-kDa proglutelins in the mature endosperm. Cytological analyses of the gpa8 mutant revealed that proglutelin-containing DVs were mistargeted to the apoplast forming electron-dense aggregates and paramural bodies in developing endosperm cells. Differing from previously reported gpa mutants with post-Golgi trafficking defects, the gpa8 mutant showed bent Golgi bodies, defective trans-Golgi network (TGN), and enlarged DVs, suggesting a specific role of GPA8 in DV biogenesis. We demonstrated that GPA8 encodes a subunit E isoform 1 of vacuolar H+-ATPase (OsVHA-E1) that mainly localizes to TGN and the tonoplast. Further analysis revealed that the luminal pH of the TGN and vacuole is dramatically increased in the gpa8 mutant. Moreover, the colocalization of GPA1 and GPA3 with TGN marker protein in gpa8 protoplasts was obviously decreased. Our data indicated that OsVHA-E1 is involved in endomembrane luminal pH homeostasis, as well as maintenance of Golgi morphology and TGN required for DV biogenesis and subsequent protein trafficking in rice endosperm cells.
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Glutens/metabolismo , Oryza/genética , Oryza/metabolismo , Isoformas de Proteínas/metabolismo , Transporte Proteico/fisiologia , Sementes/metabolismo , Vacúolos/metabolismo , Proteínas de Transporte Vesicular/metabolismo , China , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Glutens/genética , Mutação , Isoformas de Proteínas/genética , Sementes/genética , Proteínas de Transporte Vesicular/genéticaRESUMO
In this study, a simple and reliable method enabling to well synthesize the complex orbit-angular-momentum (OAM) spectrum of hybrid mode in a few-mode fiber is proposed and numerically demonstrated, which is realized by using the so-called inverse scattering method based on the genetic algorithm (GA), where the main Fourier components of a specially-selected ring in intensity distribution of the hybrid mode is used as the optimization objective. As a proof-of-concept example, power spectrum of a hybrid mode consisted of the first- and second-order OAM modes was successfully reconstructed with an accuracy higher than 0.99. This is the first time, to the best of our knowledge, that the complex OAM spectrum of a fiber hybrid mode consisted of more than two kinds of OAM modes is synthesized directly from the intensity distribution of the hybrid mode itself.
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BACKGROUND: Recent years have seen an increased incidence of social anxiety due to increasing intensive use of social media, especially among young adults. OBJECTIVE: The present study aimed to translate the original English version of Social Anxiety Scale for Social Media Users (SAS-SMU) into Chinese, examine its applicability among Chinese College students via reliability and validity indexes, and investigate the influencing factors contributing to SAS-SMU. METHODS: A cross-sectional study was conducted among a cohort of 1307 Chinese college students, 486 males and 821 females, aged 20.75 ± 3.13 years old. The original version of SAS-SMU was translated into Chinese using the backward and forward translation procedure. An exploratory factor analysis (EFA) and a confirmatory factor (CFA) analysis were used for construction of underlying factor structure. Criterion-related validity was assessed using Interaction anxiousness scale (IAS) and the "extraversion" domain of Eysenck Personality Short Scale (EPQ-R-S). Cronbach's alpha coefficient was computed for evaluation of internal consistency. A multivariate stepwise linear regression analysis was conducted for determining the potential correlates of SMU-related social anxiety. RESULTS: The final Chinese version of SAS-SMU had 21 items. Item analysis, exploratory factor, EFA, and CFA jointly supported a three-factor structure of the translated version, defined as social recognition anxiety, interaction anxiety, and privacy concern anxiety, respectively. The three-factor structure of this scale showed configural, metric, scalar measurement invariance across gender. Cronbach's alpha coefficient of the scale and its three subscales were 0.96, 0.93, 0.94, and 0.91, respectively. The mean SAS-SMU overall score for each college student was 51.63 ± 16.32, with 21.64 ± 7.24 (recognition anxiety), 17.10 ± 6.30 (interaction anxiety), 12.90 ± 4.61 (privacy concern anxiety) for each subscale, respectively. IAS score, mobile phone addiction index (MPAI) score, EPQ-E score, time spent on social media per week, relationship with parents, childhood life status, whether being an only child, and cyber bullying experience can explain 51.1% of the variance of SMU related social anxiety. CONCLUSION: Based on the data, the Chinese version of SAS-SMU has shown to be satisfactory in psychometric properties. Subjects prone to interaction anxiousness, addictive smartphone use, extraversion personality trait, bad relationship with parents, unfortunate childhood life, only-child status, and having cyberbullying experience tend to have a higher level of SMU related social anxiety.
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Mídias Sociais , Adolescente , Adulto , Ansiedade/diagnóstico , Criança , China , Estudos Transversais , Feminino , Humanos , Masculino , Psicometria/métodos , Reprodutibilidade dos Testes , Estudantes , Inquéritos e Questionários , Adulto JovemRESUMO
Light is the key factor affecting the synthesis of anthocyanins in pepper. In this study, pepper fruit under different light days was used as experimental material to explore the synthesis of anthocyanins in purple pepper. A total of 38 flavonoid metabolites were identified in the purple pepper germplasm HNUCA21 by liquid chromatography-tandem mass spectrometry (LC-MS/MS), of which 30 belong to anthocyanins. The detected anthocyanin with the highest content was Delphinidin-3-O-glucoside (17.13 µg/g), which reached the maximum after 168 h of light treatment. Through weighted gene co-expression network analysis (WGCNA), the brown module was identified to be related to the early synthesis of anthocyanins. This module contains many structural genes related to flavonoid synthesis, including chalcone synthase (CHS 107871256, 107864266), chalcone isomerase (CHI 107871144, 107852750), dihydroflavonol 4-reductase (DFR 107860031), flavonoid 3' 5'-hydroxylase (F3'5'H 107848667), flavonoid 3'-monooxygenase (F3M 107862334), leucoanthocyanidin dioxygenase (LDOX 107866341), and trans-cinnamate 4-monooxygenase (TCM 107875406, 107875407). The module also contained some genes related to anthocyanin transport function, such as glutathione S-transferase (GST 107861273), anthocyanidin 3-O-glucosyltransferase (UDPGT 107861697, 107843659), and MATE (107863234, 107844661), as well as some transcription factors, such as EGL1 (107865400), basic helix-loop-helix 104 (bHLH104 107864591), and WRKY44 (107843538, 107843524). The co-expression regulatory network indicated the involvement of CHS, DFR, CHI, and EGL1, as well as two MATE and two WRKY44 genes in anthocyanin synthesis. The identified genes involved in early, middle, and late light response provided a reference for the further analysis of the regulatory mechanism of anthocyanin biosynthesis in pepper.
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Antocianinas , Capsicum , Antocianinas/metabolismo , Capsicum/genética , Capsicum/metabolismo , Cromatografia Líquida , Flavonoides/metabolismo , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Espectrometria de Massas em TandemRESUMO
Fruit color is one of the most critical characteristics of pepper. In this study, pepper (Capsicum baccatum L.) fruits with four trans-coloring periods were used as experimental materials to explore the color conversion mechanism of pepper fruit. By transcriptome and metabolome analysis, we identified a total of 307 flavonoid metabolites, 68 carotenoid metabolites, 29 DEGs associated with flavonoid biosynthesis, and 30 DEGs related to carotenoid biosynthesis. Through WGCNA (weighted gene co-expression network analysis) analysis, positively correlated modules with flavonoids and carotenoids were identified, and hub genes associated with flavonoid and carotenoid synthesis and transport were anticipated. We identified Pinobanksin, Naringenin Chalcone, and Naringenin as key metabolites in the flavonoid biosynthetic pathway catalyzed by the key genes chalcone synthase (CHS CQW23_29123, CQW23_29380, CQW23_12748), cinnamic acid 4-hydroxylase (C4H CQW23_16085, CQW23_16084), cytochrome P450 (CYP450 CQW23_19845, CQW23_24900). In addition, phytoene synthase (PSY CQW23_09483), phytoene dehydrogenase (PDS CQW23_11317), zeta-carotene desaturase (ZDS CQW23_19986), lycopene beta cyclase (LYC CQW23_09027), zeaxanthin epoxidase (ZEP CQW23_05387), 9-cis-epoxycarotenoid dioxygenase (NCED CQW23_17736), capsanthin/capsorubin synthase (CCS CQW23_30321) are key genes in the carotenoid biosynthetic pathway, catalyzing the synthesis of key metabolites such as Phytoene, Lycopene, ß-carotene and ε-carotene. We also found that transcription factor families such as p450 and NBARC could play important roles in the biosynthesis of flavonoids and carotenoids in pepper fruits. These results provide new insights into the interaction mechanisms of genes and metabolites involved in the biosynthesis of flavonoids and carotenoids in pepper fruit leading to color changes in pepper fruit.
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Capsicum , Capsicum/genética , Capsicum/metabolismo , Frutas/metabolismo , Transcriptoma , Licopeno/metabolismo , beta Caroteno/metabolismo , Carotenoides/metabolismo , Metaboloma , Flavonoides/metabolismo , Fatores de Transcrição/metabolismo , Oxigenases de Função Mista/genética , Regulação da Expressão Gênica de PlantasRESUMO
CONTEXT: Jinlida (JLD) as a traditional Chinese medicine formula has been used to treat type 2 diabetes mellitus (T2DM) and studies have shown its anti-obesity effect. OBJECTIVE: To investigate the therapeutic effects of JLD in a mouse model of non-alcoholic fatty liver (NAFL). MATERIALS AND METHODS: C57BL/6J mice were divided into three groups and fed a low-diet diet (LFD), high-fat diet (HFD), or HFD + JLD (3.8 g/kg) for 16 weeks, respectively. The free fatty acids-induced lipotoxicity in HepG2 cells were used to evaluate the anti-pyroptotic effects of JLD. The pharmacological effects of JLD on NAFL were investigated by pathological examination, intraperitoneal glucose and insulin tolerance tests, western blotting, and quantitative real-time PCR. RESULTS: In vivo studies showed that JLD ameliorated HFD-induced liver injury, significantly decreased body weight and enhanced insulin sensitivity and improved glucose tolerance. Furthermore, JLD suppressed both the mRNA expression of caspase-1 (1.58 vs. 2.90), IL-1ß (0.93 vs. 3.44) and IL-18 (1.34 vs. 1.60) and protein expression of NLRP3 (2.04 vs. 5.71), pro-caspase-1 (2.68 vs. 4.92) and IL-1ß (1.61 vs. 2.60). In vitro, JLD inhibited the formation of lipid droplets induced by 2 mM FFA (IC50 = 2.727 mM), reduced the protein expression of NLRP3 (0.74 vs. 2.27), caspase-1 (0.57 vs. 2.68), p20 (1.67 vs. 3.33), and IL-1ß (1.44 vs. 2.41), and lowered the ratio of p-IKB-α/IKB-α (0.47 vs. 2.19). CONCLUSION: JLD has a protective effect against NAFLD, which may be related to its anti-pyroptosis, suggesting that JLD has the potential as a novel agent in the treatment of NAFLD.
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Medicamentos de Ervas Chinesas/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Piroptose/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Glucose/metabolismo , Células Hep G2 , Hepatócitos/patologia , Humanos , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Thioredoxins (TRXs) occur in plant chloroplasts as complex disulphide oxidoreductases. Although many biological processes are regulated by thioredoxins, the regulatory mechanism of chloroplast TRXs are largely unknown. Here we report a rice white panicle2 mutant caused by a mutation in the thioredoxin z gene, an orthologue of AtTRX z in Arabidopsis. white panicle2 (wp2) seedlings exhibited a high-temperature-sensitive albinic phenotype. We found that plastid multiple organellar RNA editing factors (MORFs) were the regulatory targets of thioredoxin z. We showed that OsTRX z protein physically interacts with OsMORFs in a redox-dependent manner and that the redox state of a conserved cysteine in the MORF box is essential for MORF-MORF interactions. wp2 and OsTRX z knockout lines show reduced editing efficiencies in many plastidial-encoded genes especially under high-temperature conditions. An Arabidopsis trx z mutant also exhibited significantly reduced chloroplast RNA editing. Our combined results suggest that thioredoxin z regulates chloroplast RNA editing in plants by controlling the redox state of MORFs.
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Oryza , Proteínas de Plantas , Plastídeos , Edição de RNA , Tiorredoxinas , Cloroplastos/genética , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plastídeos/genética , Tiorredoxinas/genética , Tiorredoxinas/metabolismoRESUMO
In this study, a broadband flat-top second-order orbital angular momentum mode (OAM) converter is proposed and demonstrated using a phase-modulated second-order helical long-period fiber grating (HLPG). The proposed HLPG is designed to be inscribed in a thinned four-mode fiber and operated at wavelengths near the dispersion turning point (DTP). In contrast to most of the HLPG-based OAM mode generators reported to date, where the high-order OAM mode and flat-top broadband have rarely been achieved simultaneously, a second-order OAM(OAM-2) mode converter with a flat-top bandwidth of 113â nm @ -20â dB (ranging from 1530-1643â nm) and a depth fluctuation of less than 3â dB @-26â dB has been successfully demonstrated in this study, such flat-top bandwidth covers the entire C + L bands and represents the best result of the HLPGs reported to date. Tolerance analyses for the fabrication of the designed HLPG were also performed. It is believed that the proposed HLPG may find applications in all-fiber vortex lasers as well as the OAM mode division multiplex (MDM) system.
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Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and photochemistry of Os-arenes, O,O-chelated complexes [Os(η6-p-cymene)(Curc)Cl] (OsCUR-1, Curc = curcumin) and [Os(η6-biphenyl)(Curc)Cl] (OsCUR-2), and N,N-chelated complexes [Os(η6-biphenyl)(dpq)I]PF6 (OsDPQ-2, dpq = pyrazino[2,3-f][1,10]phenanthroline) and [Os(η6-biphenyl)(bpy)I]PF6 (OsBPY-2, bpy = 2,2'-bipyridine), have been investigated. The Os-arene curcumin complexes showed remarkable photocytotoxicity toward a range of cancer cell lines (blue light IC50: 2.6-5.8 µM, photocytotoxicity index PI = 23-34), especially toward cisplatin-resistant cancer cells, but were nontoxic to normal cells. They localized mainly in mitochondria in the dark but translocated to the nucleus upon photoirradiation, generating DNA and mitochondrial damage, which might contribute toward overcoming cisplatin resistance. Mitochondrial damage, apoptosis, ROS generation, DNA damage, angiogenesis inhibition, and colony formation were observed when A549 lung cancer cells were treated with OsCUR-2. The photochemistry of these Os-arene complexes was investigated by a combination of NMR, HPLC-MS, high energy resolution fluorescence detected (HERFD), X-ray adsorption near edge structure (XANES) spectroscopy, total fluorescence yield (TFY) XANES spectra, and theoretical computation. Selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) occurred under blue light or UVA excitation. This new approach to the design of novel Os-arene complexes as phototherapeutic agents suggests that the novel curcumin complex OsCUR-2, in particular, is a potential candidate for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT).
Assuntos
Antineoplásicos/farmacologia , Calixarenos/farmacologia , Complexos de Coordenação/farmacologia , Osmio/farmacologia , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Calixarenos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Dano ao DNA , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Osmio/química , Processos FotoquímicosRESUMO
The specific cytotoxic effects of nanoparticles on tumor cells may be used in future antitumor clinical applications. Gold nanoparticles (AuNPs) have been reported to produce potent cytotoxic effects; however, the precise mechanism is unclear. In this study, AuNPs were synthesized; the average size of the particles was 62.2 ± 6 nm with smooth surface and multiple shapes, which were determined using transmission electron microscopy and field emission scanning electron microscopy. The selected area electron diffraction patterns suggested that the synthesized AuNPs were crystalline. The X-ray photoelectron spectroscopy (XPS) spectrum of the synthesized AuNPs has presented an intense peak at 100 eV, signifying the entire composition of Au in the developed AuNPs. This synthesized AuNPs showed the most potent efficacy in prostate cancer cells, regardless of whether or not they were androgen dependent. Secretome determinations using two-dimensional difference in-gel electrophoresis (2D-DIGE), followed by enzyme-linked immunosorbent assay and quantitative reverse transcriptase-polymerase chain reaction validations, have identified a series of secretory proteins that were dysregulated by AuNP treatment in prostate cancer cells, many of which are highly involved in cytokine-chemokine functions, including CXCL3, interleukin-10, CCL2, and matrix metalloproteinase 9 (MMP9). Further research on molecular mechanism has indicated that AuNPs can trigger the secretion of anticancer factors and myeloid cell-polarizing factors from tumor cells through MMP9 inhibition. These results have clearly signified the cytotoxic potential of AuNPs for treating prostate cancer and may provide a novel direction for prostate cancer therapy in the future.