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BACKGROUND & AIMS: Nonalcoholic fatty liver disease is highly associated with obesity and progresses to nonalcoholic steatohepatitis when the liver develops overt inflammatory damage. While removing adenosine in the purine salvage pathway, adenosine kinase (ADK) regulates methylation reactions. We aimed to study whether hepatocyte ADK functions as an obesogenic gene/enzyme to promote excessive fat deposition and liver inflammation. METHODS: Liver sections of human subjects were examined for ADK expression using immunohistochemistry. Mice with hepatocyte-specific ADK disruption or overexpression were examined for hepatic fat deposition and inflammation. Liver lipidomics, hepatocyte RNA sequencing (RNA-seq), and single-cell RNA-seq for liver nonparenchymal cells were performed to analyze ADK regulation of hepatocyte metabolic responses and hepatocyte-nonparenchymal cells crosstalk. RESULTS: Whereas patients with nonalcoholic fatty liver disease had increased hepatic ADK levels, mice with hepatocyte-specific ADK disruption displayed decreased hepatic fat deposition on a chow diet and were protected from diet-induced excessive hepatic fat deposition and inflammation. In contrast, mice with hepatocyte-specific ADK overexpression displayed increased body weight and adiposity and elevated degrees of hepatic steatosis and inflammation compared with control mice. RNA-seq and epigenetic analyses indicated that ADK increased hepatic DNA methylation and decreased hepatic Ppara expression and fatty acid oxidation. Lipidomic and single-cell RNA-seq analyses indicated that ADK-driven hepatocyte factors, due to mitochondrial dysfunction, enhanced macrophage proinflammatory activation in manners involving increased expression of stimulator of interferon genes. CONCLUSIONS: Hepatocyte ADK functions to promote excessive fat deposition and liver inflammation through suppressing hepatocyte fatty acid oxidation and producing hepatocyte-derived proinflammatory mediators. Therefore, hepatocyte ADK is a therapeutic target for managing obesity and nonalcoholic fatty liver disease.
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Hepatite , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adenosina Quinase/genética , Adenosina Quinase/metabolismo , Hepatócitos/metabolismo , Hepatite/metabolismo , Fígado/metabolismo , Obesidade/metabolismo , Inflamação/metabolismo , Ácidos Graxos/metabolismo , Camundongos Endogâmicos C57BL , Dieta HiperlipídicaRESUMO
BACKGROUND: As a non-competitive N-methyl d-aspartate receptor antagonist, ketamine exerts rapid-onset and long-lasting antidepressant effects on depression, but some side effects limit its use. To identify a safer compound that may provide similar antidepressant effects, here we investigated whether CP-101,606, a selective NR2B receptor inhibitor, provides similar antidepressant effects and explored its underlying mechanisms. METHODS: To mimic depressive-like behavior, mice were subjected to chronic unpredictable mild stress (CUMS) for 21â¯days. Mice were treated with CP-101,606 at 10, 20, and 40â¯mg/kg doses for 7, 14, and 21â¯days, respectively, followed by a sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). Western blot analysis was performed on several targets (mTOR, p-mTOR, p70S6K, p-p70S6K, PSD-95, and GluA1), along with immunohistochemistry (GluA1) and immunofluorescence (p-mTOR) assays, using hippocampal tissue. RESULTS: CP-101,606 at 20 and 40â¯mg/kg doses for 7 and 14â¯days and fluoxetine 10â¯mg/kg and CP-101606 20â¯mg/kg for 21â¯days ameliorated depression-like behaviors in the SPT, TST, and FST. The effects of CP-101,606 were associated with a reversal of the CUMS-induced decrease in mTOR (Ser2448) and p70S6K (Thr389) phosphorylation and increasing PSD95 and GluA1 synthesis in the hippocampus. CONCLUSIONS: Our results demonstrate that CP-101,606 produces antidepressant effects in CUMS mice, which may be mediated by mTOR signaling cascade upregulation. Our findings suggest the possible utility of CP-101,606 as a treatment for depression.
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Depressão , Proteínas Quinases S6 Ribossômicas 70-kDa , Camundongos , Animais , Depressão/tratamento farmacológico , Depressão/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/farmacologia , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Estresse Psicológico/metabolismo , Hipocampo/metabolismo , Modelos Animais de DoençasRESUMO
High yield has always been an essential target in almost all of the cotton breeding programs. Boll weight (BW) is a key component of cotton yield. Numerous linkage mapping and genome-wide association studies (GWAS) have been performed to understand the genetic mechanism of BW, but information on the markers/genes controlling BW remains limited. In this study, we conducted a GWAS for BW using 51,268 high-quality single-nucleotide polymorphisms (SNPs) and 189 Gossypium hirsutum accessions across five different environments. A total of 55 SNPs significantly associated with BW were detected, of which 29 and 26 were distributed in the A and D subgenomes, respectively. Five SNPs were simultaneously detected in two environments. For TM5655, TM8662, TM36371, and TM50258, the BW grouped by alleles of each SNP was significantly different. The ± 550 kb regions around these four key SNPs contained 262 genes. Of them, Gh_A02G1473, Gh_A10G1765, and Gh_A02G1442 were expressed highly at 0 to 1 days post-anthesis (dpa), - 3 to 0 dpa, and - 3 to 0 dpa in ovule of TM-1, respectively. They were presumed as the candidate genes for fiber cell differentiation, initiation, or elongation based on gene annotation of their homologs. Overall, these results supplemented valuable information for dissecting the genetic architecture of BW and might help to improve cotton yield through molecular marker-assisted selection breeding and molecular design breeding.
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Estudo de Associação Genômica Ampla , Gossypium , Gossypium/genética , Estudo de Associação Genômica Ampla/métodos , Locos de Características Quantitativas , Fenótipo , Genótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo ÚnicoRESUMO
MAIN CONCLUSION: BrSOC1b may promote early flowering of Chinese cabbage by acting on BrAGL9 a, BrAGL9 b, BrAGL2 and BrAGL8 proteins. SOC1 is a flowering signal integrator that acts as a key regulator in controlling plant flowering time. This study focuses on the cloning of the open reading frame of SOC1b (BrSOC1b, Gene ID: Bra000393) gene, and analyzes its structure and phylogenetic relationships. Additionally, various techniques such as vector construction, transgenic technology, virus-induced gene silencing technology, and protein interaction technology were employed to investigate the function of the BrSOC1b gene and its interactions with other proteins. The results indicate that BrSOC1b consists of 642 bp and encodes 213 amino acids. It contains conserved domains such as the MADS domain, K (keratin-like) domain, and SOC1 box. The phylogenetic analysis reveals that BrSOC1b shares the closest homology with BjSOC1 from Brassica juncea. Tissue localization analysis demonstrates that BrSOC1b exhibits the highest expression in the stem during the seedling stage and the highest expression in flowers during the early stage of pod formation. Sub-cellular localization analysis reveals that BrSOC1b is localized in the nucleus and plasma membrane. Furthermore, through genetic transformation of the BrSOC1b gene, it was observed that Arabidopsis thaliana plants expressing BrSOC1b flowered earlier and bolted earlier than wild-type plants. Conversely, Chinese cabbage plants with silenced BrSOC1b exhibited delayed bolting and flowering compared to the control plants. These findings indicate that BrSOC1b promotes early flowering in Chinese cabbage. Yeast two-hybrid and quantitative real-time PCR (qRT-PCR) analyses suggest that BrSOC1b may participate in the regulation of flowering by interacting with BrAGL9a, BrAGL9b, BrAGL2, and BrAGL8 proteins. Overall, this research holds significant implications for the analysis of key genes involved in regulating bolting and flowering in Chinese cabbage, as well as for enhancing germplasm innovation in Chinese cabbage breeding.
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Proteínas de Arabidopsis , Arabidopsis , Filogenia , Melhoramento Vegetal , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Flores/metabolismo , Mostardeira/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Domínio MADS/metabolismoRESUMO
Lint percentage is one of the most essential yield components and an important economic index for cotton planting. Improving lint percentage is an effective way to achieve high-yield in cotton breeding worldwide, especially upland cotton (Gossypium hirsutum L.). However, the genetic basis controlling lint percentage has not yet been systematically understood. Here, we performed a genome-wide association mapping for lint percentage using a natural population consisting of 189 G. hirsutum accessions (188 accessions of G. hirsutum races and one cultivar TM-1). The results showed that 274 single-nucleotide polymorphisms (SNPs) significantly associated with lint percentage were detected, and they were distributed on 24 chromosomes. Forty-five SNPs were detected at least by two models or at least in two environments, and their 5 Mb up- and downstream regions included 584 makers related to lint percentage identified in previous studies. In total, 11 out of 45 SNPs were detected at least in two environments, and their 550 Kb up- and downstream region contained 335 genes. Through RNA sequencing, gene annotation, qRT-PCR, protein-protein interaction analysis, the cis-elements of the promotor region, and related miRNA prediction, Gh_D12G0934 and Gh_A08G0526 were selected as key candidate genes for fiber initiation and elongation, respectively. These excavated SNPs and candidate genes could supplement marker and gene information for deciphering the genetic basis of lint percentage and facilitate high-yield breeding programs of G. hirsutum ultimately.
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Estudo de Associação Genômica Ampla , Gossypium , Gossypium/genética , Fibra de Algodão , Locos de Características Quantitativas , Fenótipo , Melhoramento VegetalRESUMO
Seed-cotton yield (SY) and lint yield (LY) are the most important yield traits of cotton. Thus, it is critical to dissect their genetic architecture. Upland cotton (Gossypium hirsutum) is widely grown worldwide. In this study, a genome-wide association mapping was performed based on the CottonSNP80K array to dissect the genetic architecture of SY and LY in Upland cotton. Twenty-three significant associations were detected within four environments, including 11 associated with SY and 12 associated with LY. Seven single nucleotide polymorphisms (SNPs), TM234, TM237, TM247, TM255, TM256, TM263, and TM264, were co-associated with the two traits, which may indicate pleiotropy or intergenic tight linkages. Five SNPs, TM13332, TM39771, TM57119, TM81653, and TM81660, were coincided with those of previous reports and could be used in marker-assisted selection. Combining functional annotations with expression analyses of the genes identified within 400 kb of the significantly associated SNPs, we hypothesize that the three genes, Gh_D05G1077 and Gh_D13G1571 for SY, and Gh_A11G0775 for LY, may have the potential to increase cotton yield. The results would provide useful information for understanding the genetic basis of yield traits in Upland cotton and for facilitating its high-yield breeding through molecular design.
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Reactive oxygen species (ROS) are important molecules in the plant, which are involved in many biological processes, including fiber development and adaptation to abiotic stress in cotton. We carried out transcription analysis to determine the evolution of the ROS genes and analyzed their expression levels in various tissues of cotton plant under abiotic stress conditions. There were 515, 260, and 261 genes of ROS network that were identified in Gossypium hirsutum (AD1 genome), G. arboreum (A genome), and G. raimondii (D genome), respectively. The ROS network genes were found to be distributed in all the cotton chromosomes, but with a tendency of aggregating on either the lower or upper arms of the chromosomes. Moreover, all the cotton ROS network genes were grouped into 17 families as per the phylogenetic tress analysis. A total of 243 gene pairs were orthologous in G. arboreum and G. raimondii. There were 240 gene pairs that were orthologous in G. arboreum, G. raimondii, and G. hirsutum. The synonymous substitution value (Ks) peaks of orthologous gene pairs between the At subgenome and the A progenitor genome (G. arboreum), D subgenome and D progenitor genome (G. raimondii) were 0.004 and 0.015, respectively. The Ks peaks of ROS network orthologous gene pairs between the two progenitor genomes (A and D genomes) and two subgenomes (At and Dt subgenome) were 0.045. The majority of Ka/Ks value of orthologous gene pairs between the A, D genomes and two subgenomes of TM-1 were lower than 1.0. RNA seq. analysis and RT-qPCR validation, showed that, CSD1,2,3,5,6; FSD1,2; MSD1,2; APX3,11; FRO5.6; and RBOH6 played a major role in fiber development while CSD1, APX1, APX2, MDAR1, GPX4-6-7, FER2, RBOH6, RBOH11, and FRO5 were integral for enhancing salt stress in cotton. ROS network-mediated signal pathway enhances the mechanism of fiber development and regulation of abiotic stress in Gossypium. This study will enhance the understanding of ROS network and form the basic foundation in exploring the mechanism of ROS network-involving the fiber development and regulation of abiotic stress in cotton.
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Gossypium/genética , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Gossypium/fisiologia , FilogeniaRESUMO
BACKGROUND: Fluorescence in situ hybridization (FISH) is an efficient cytogenetic technology to study chromosome structure. Transposable element (TE) is an important component in eukaryotic genomes and can provide insights in the structure and evolution of eukaryotic genomes. RESULTS: A FISH probe derived from bacterial artificial chromosome (BAC) clone 299N22 generated striking signals on all 26 chromosomes of the cotton diploid A genome (AA, 2x=26) but very few on the diploid D genome (DD, 2x=26). All 26 chromosomes of the A sub genome (At) of tetraploid cotton (AADD, 2n=4x=52) also gave positive signals with this FISH probe, whereas very few signals were observed on the D sub genome (Dt). Sequencing and annotation of BAC clone 299N22, revealed a novel Ty3/gypsy transposon family, which was named as 'CICR'. This family is a significant contributor to size expansion in the A (sub) genome but not in the D (sub) genome. Further FISH analysis with the LTR of CICR as a probe revealed that CICR is lineage-specific, since massive repeats were found in A and B genomic groups, but not in C-G genomic groups within the Gossypium genus. Molecular evolutionary analysis of CICR suggested that tetraploid cottons evolved after silence of the transposon family 1-1.5 million years ago (Mya). Furthermore, A genomes are more homologous with B genomes, and the C, E, F, and G genomes likely diverged from a common ancestor prior to 3.5-4 Mya, the time when CICR appeared. The genomic variation caused by the insertion of CICR in the A (sub) genome may have played an important role in the speciation of organisms with A genomes. CONCLUSIONS: The CICR family is highly repetitive in A and B genomes of Gossypium, but not amplified in the C-G genomes. The differential amount of CICR family in At and Dt will aid in partitioning sub genome sequences for chromosome assemblies during tetraploid genome sequencing and will act as a method for assessing the accuracy of tetraploid genomes by looking at the proportion of CICR elements in resulting pseudochromosome sequences. The timeline of the expansion of CICR family provides a new reference for cotton evolutionary analysis, while the impact on gene function caused by the insertion of CICR elements will be a target for further analysis of investigating phenotypic differences between A genome and D genome species.
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Elementos de DNA Transponíveis/genética , Gossypium/genética , Cromossomos Artificiais Bacterianos/genética , Cromossomos de Plantas/genética , Genoma de Planta/genética , Hibridização in Situ Fluorescente , Análise de Sequência de DNA , TetraploidiaRESUMO
INTRODUCTION AND OBJECTIVES: The present study aimed to investigate different peripheral lymphocyte subsets in patients with severe hemophilia A (HA) and factor VIII (FVIII) inhibitor production. For this, age-matched cases of 19 FVIII inhibitor-positive (IP), 21 FVIII inhibitor-negative (IN) and 45 healthy controls were selected for study. METHODS: Flow cytometry was used to analyze the peripheral lymphocyte subsets, including T, B, natural killer (NK) and NKT cells. The T cell subsets included CD3 + CD4-CD8- [double negative T (DNT)], CD3 + CD4 + CD8+ [double-positive T (DPT)], CD3 + CD4 + CD8- and CD3 + CD4-CD8+ T cells. Pairwise comparisons of absolute lymphocyte subset values were conducted among the three groups. The cut-off value for absolute lymphocyte counts was determined using receiver operating characteristic curve analysis. RESULTS: The results demonstrated that the absolute values of DPT cells in the IN and IP groups were significantly lower than those in the healthy control group (P = 0.007). The DNT values were also lower in severe HA patients with or without inhibitor than those in healthy subjects, but these differences were not statistically significant (P = 0.053). In addition, the absolute value of CD4+ Th cells in the IP group was lower than that in the healthy controls (P = 0.013). Although not statistically significant (P = 0.064), the absolute values of NKT cells were higher in the IN group compared with the IP group, and higher in the IP group compared with the healthy control group. There were no statistically significant differences in total T, B, CD8 + and NK cells among the IN, IP and healthy control groups. The cut-off value for absolute CD4+ Th cells in the IN group was < 598/µl. CONCLUSION: The decrease in absolute values of CD4+ Th cells in severe HA patients may contribute to the establishment of infused FVIII immune tolerance. If the CD4+ Th value remains > 598/µl, clinicians should be vigilant for possible FVIII inhibitor production, especially on days prior to FVIII exposure.
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Fator VIII , Hemofilia A , Subpopulações de Linfócitos , Humanos , Hemofilia A/sangue , Hemofilia A/imunologia , Estudos de Casos e Controles , Fator VIII/imunologia , Masculino , Adulto , Adolescente , Adulto Jovem , Feminino , CriançaRESUMO
Exchange bias is extensively studied and widely utilized in spintronic devices, such as spin valves and magnetic tunnel junctions. 2D van der Waals (vdW) magnets, with high-quality interfaces in heterostructures, provide an excellent platform for investigating the exchange bias effect. To date, intrinsic modulation of exchange bias, for instance, via precise manipulation of the magnetic phases of the antiferromagnetic layer, is yet to be fully reached, owing partly to the large exchange fields of traditional bulk antiferromagnets. Herein, motivated by the low-field spin-flop transition of a 2D antiferromagnet, CrPS4, exchange bias is explored by modulating the antiferromagnetic spin-flop phase transition in all-vdW magnetic heterostructures. The results demonstrate that undergoing the spin-flop transition during the field cooling process, the A-type antiferromagnetic ground state of CrPS4 turns into a canted antiferromagnetic one, therefore, it reduces the interfacial magnetic coupling and suppresses the exchange bias. Via conducting different cooling fields, one can select the exchange bias effect switching among the "ON", "depressed", and "OFF" states determined by the spin flop of CrPS4. This work provides an approach to intrinsically modulate the exchange bias in all-vdW heterostructures and paves new avenues to design and manipulate 2D spintronic devices.
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Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases serving as a major threat to human health. While the pathogenesis of NAFLD is multi-factorial, inflammation is considered a critical factor driving the development and progression of NAFLD phenotype, including liver fibrosis. As an essential mediator of innate immunity, stimulator of interferon genes (STING) functions to promote anti-viral immunity. Accumulating evidence also indicates that STING functions to promote the proinflammatory activation of several types of liver cells, especially macrophages/Kupffer cells, in a manner independent of interferon production. Over the past several years, a significant body of literature has validated a detrimental role for STING in regulating the pathogenesis of hepatic steatosis and inflammation. In particular, the STING in macrophages/Kupffer cells has attracted much attention due to its importance in not only enhancing macrophage proinflammatory activation, but also generating macrophage-derived mediators to increase hepatocyte fat deposition and proinflammatory responses, and to activate hepatic stellate cell fibrogenic activation. Both intracellular and extracellular signals are participating in STING activation in macrophages, thereby critically contributing to NAFLD phenotype. This mini review summarizes recent advances on how STING is activated in macrophages in the context of NAFLD pathophysiology.
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Since the genetic transformation of Chinese cabbage (Brassica rapa) has not been well developed, in situ RT-PCR is a valuable option for detecting guard cell-specific genes. We reported an optimized protocol of in situ RT-PCR by using a FAMA homologous gene Bra001929 in Brassica rapa. FAMA in Arabidopsis has been verified to be especially expressed in guard cells. We designed specific RT-PCR primers and optimized the protocol in terms of the (a) reverse transcription time, (b) blocking time, (c) antigen-antibody incubation time, and (d) washing temperature. Our approach provides a sensitive and effective in situ RT-PCR method that can detect low-abundance transcripts in cells by elevating their levels by RT-PCR in the guard cells in Brassica rapa.
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Cotton is one of the most important economic and fiber crops in the world. KNOX is one class of universal transcription factors, which plays important roles in plant growth and development as well as response to different stresses. Although there are many researches on KNOXs in other plant species, there are few reports on cotton. In this study, we systematically and comprehensively identified all KNOX genes in upland cotton and its two ancestral species; we also studied their functions by employing RNA-seq analysis and virus-induced gene silence (VIGS). A total of 89 KNOX genes were identified from three cotton species. Among them, 44 were from upland cotton, 22 and 23 were found in its ancestral species G. raimondii and G. arboreum, respectively. Plant polyploidization and domestication play a selective force driving KNOX gene evolution. Phylogenetic analysis displayed that KNOX genes were evolved into three Classes. The intron length and exon number differed in each Class. Transcriptome data showed that KNOX genes of Class II were widely expressed in multiple tissues, including fiber. The majority of KNOX genes were induced by different abiotic stresses. Additionally, we found multiple cis-elements related to stress in the promoter region of KNOX genes. VIGS silence of GhKNOX4-A and GhKNOX22-D genes showed significant growth and development effect in cotton seedlings under salt and drought treatments. Both GhKNOX4-A and GhKNOX22-D regulated plant tolerance; silencing both genes induced oxidative stresses, evidenced by reduced SOD activity and induced leave cell death, and also enhanced stomatal open and water loss. Thus, GhKNOX4-A and GhKNOX22-D may contribute to drought response by regulating stomata opening and oxidative stresses.
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Secas , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transcriptoma , Estresse Fisiológico/genética , Cloreto de Sódio/metabolismo , Gossypium/genética , Gossypium/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
The Brassicaceae family includes many economically important crop species, as well as cosmopolitan agricultural weed species. In addition, Arabidopsis thaliana, a member of this family, is used as a molecular model plant species. The genus Brassica is mesopolyploid, and the genus comprises comparatively recently originated tetrapolyploid species. With these characteristics, Brassicas have achieved the commonly accepted status of model organisms for genomic studies. This paper reviews the rapid research progress in the Brassicaceae family from diverse omics studies, including genomics, transcriptomics, epigenomics, and three-dimensional (3D) genomics, with a focus on cultivated crops. The morphological plasticity of Brassicaceae crops is largely due to their highly variable genomes. The origin of several important Brassicaceae crops has been established. Genes or loci domesticated or contributing to important traits are summarized. Epigenetic alterations and 3D structures have been found to play roles in subgenome dominance, either in tetraploid Brassica species or their diploid ancestors. Based on this progress, we propose future directions and prospects for the genomic investigation of Brassicaceae crops.
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This study aimed to analyze the most influential publications on vertebral augmentation for treating osteoporotic vertebral compression fracture. The Web of Science database was searched using the key words "percutaneous vertebroplasty," "percutaneous kyphoplasty," "balloon kyphoplasty," "vertebroplasty," "kyphoplasty," and "vertebral augmentation." The top 100 publications were arranged by citations per year and descriptively and visually analyzed. The top 100 publications were cited 25,482 times, with an average of 14.4 citations per paper per year. The corresponding authors of the publications represented 17 nations, with most authors being American (46 authors). Thirty-two journals were involved, with SPINE issuing the most publications (24 papers of the 100). Clinical research (73 of the 100 papers) outnumbered basic studies (14 papers) and systematic reviews (13 papers), and the most publications were published between 2000 and 2004. Co-citation analysis of the key words indicated that the top 5 focus areas were "complication," "balloon kyphoplasty," "vertebral compression fracture," "biomechanics," and "calcium phosphate cement." The top 3 keywords with the strongest citation bursts were "compression fracture," "cement," and "balloon kyphoplasty." The keywords with persistent strong citation bursts are "balloon kyphoplasty" and "augmentation." There are still contrary opinions about vertebral augmentation; new research should be conducted with more deliberate design and longer follow-up.
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Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Cimentos Ósseos/uso terapêutico , Fraturas por Compressão/complicações , Humanos , Cifoplastia/efeitos adversos , Fraturas por Osteoporose/complicações , Fraturas da Coluna Vertebral/etiologia , Resultado do Tratamento , Vertebroplastia/efeitos adversosRESUMO
Drought seriously threats the growth and development of Gossypium hirsutum L. To dissect the genetic basis for drought tolerance in the G. hirsutum L. germplasm, a population, consisting of 188 accessions of G. hirsutum races and a cultivar (TM-1), was genotyped using the Cotton80KSNP biochip, and 51,268 high-quality single-nucleotide polymorphisms (SNPs) were obtained. Based on the phenotypic data of eight drought relative traits from four environments, we carried out association mapping with five models using GAPIT software. In total, thirty-six SNPs were detected significantly associated at least in two environments or two models. Among these SNPs, 8 and 28 (including 24 SNPs in 5 peak regions) were distributed in the A and D subgenome, respectively; eight SNPs were found to be distributed within separate genes. An SNP, TM73079, located on chromosome D10, was simultaneously associated with leaf fresh weight, leaf wilted weight, and leaf dry weight. Another nine SNPs, TM47696, TM33865, TM40383, TM10267, TM59672, TM59675, TM59677, TM72359, and TM72361, on chromosomes A13, A10, A12, A5, D6, and D9, were localized within or near previously reported quantitative trait loci for drought tolerance. Moreover, 520 genes located 200 kb up- and down-stream of 36 SNPs were obtained and analyzed based on gene annotation and transcriptome sequencing. The results showed that three candidate genes, Gh_D08G2462, Gh_A03G0043, and Gh_A12G0369, may play important roles in drought tolerance. The current GWAS represents the first investigation into mapping QTL for drought tolerance in G. hirsutum races and provides important information for improving cotton cultivars.
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Indole is a microbiota metabolite that functions to protect against obesity-associated non-alcoholic fatty liver disease. The present study examined the extent to which indole supplementation alleviates the severity of non-alcoholic steatohepatitis (NASH), which is the advanced form of non-alcoholic fatty liver disease. In C57BL/6J mice, feeding a methionine- and choline-deficient diet (MCD) resulted in significant weight loss, overt hepatic steatosis, and massive aggregations of macrophages in the liver compared with control diet-fed mice. Upon indole supplementation, the severity of MCD-induced hepatic steatosis and inflammation, as well as liver fibrosis, was significantly decreased compared with that of MCD-fed and control-treated mice. In vitro, indole treatment caused significant decreases in lipopolysaccharide-induced proinflammatory responses in hepatocytes incubated with either basal or MCD-mimicking media. However, indole treatment only significantly decreased lipopolysaccharide-induced proinflammatory responses in bone marrow-derived macrophages incubated with basal, but not MCD-mimicking media. These differential effects suggest that, relative to the responses of macrophages to indole, the responses of hepatocytes to indole appeared to make a greater contribution to indole alleviation of NASH, in particular liver inflammation. While indole supplementation decreased liver expression of desmin in MCD-fed mice, treatment of LX2 cells (a line of hepatic stellate cells) with indole also decreased the expression of various markers of hepatic stellate cell fibrogenic activation. Lastly, indole supplementation decreased intestinal inflammation in MCD-fed mice, suggesting that decreased intestinal inflammation also was involved in indole alleviation of NASH. Collectively, these results demonstrate that indole supplementation alleviates MCD-induced NASH, which is attributable to, in large part, indole suppression of hepatocyte proinflammatory responses and hepatic stellate cell fibrogenic activation, as well as intestinal proinflammatory responses.
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Deficiência de Colina , Hepatopatia Gordurosa não Alcoólica , Animais , Colina/metabolismo , Colina/farmacologia , Deficiência de Colina/metabolismo , Dieta , Suplementos Nutricionais , Modelos Animais de Doenças , Indóis/farmacologia , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Metionina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
Chinese cabbage is an important leaf heading vegetable crop. At the heading stage, its leaves across inner to outer show significant morphological differentiation. However, the genetic control of this complex leaf morphological differentiation remains unclear. Here, we reported the transcriptome profiling of Chinese cabbage plant at the heading stage using 24 spatially dissected tissues representing different regions of the inner to outer leaves. Genome-wide transcriptome analysis clearly separated the inner leaf tissues from the outer leaf tissues. In particular, we identified the key transition leaf by the spatial expression analysis of key genes for leaf development and sugar metabolism. We observed that the key transition leaves were the first inwardly curved ones. Surprisingly, most of the heading candidate genes identified by domestication selection analysis obviously showed a corresponding expression transition, supporting that key transition leaves are related to leafy head formation. The key transition leaves were controlled by a complex signal network, including not only internal hormones and protein kinases but also external light and other stimuli. Our findings provide new insights and the rich resource to unravel the genetic control of heading traits.