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1.
Plant J ; 118(5): 1372-1387, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38343032

RESUMO

Understanding the genetic basis of population divergence and adaptation is an important goal in population genetics and evolutionary biology. However, the relative roles of demographic history, gene flow, and/or selective regime in driving genomic divergence, climatic adaptation, and speciation in non-model tree species are not yet fully understood. To address this issue, we generated whole-genome resequencing data of Liquidambar formosana and L. acalycina, which are broadly sympatric but altitudinally segregated in the Tertiary relict forests of subtropical China. We integrated genomic and environmental data to investigate the demographic history, genomic divergence, and climatic adaptation of these two sister species. We inferred a scenario of allopatric species divergence during the late Miocene, followed by secondary contact during the Holocene. We identified multiple genomic islands of elevated divergence that mainly evolved through divergence hitchhiking and recombination rate variation, likely fostered by long-term refugial isolation and recent differential introgression in low-recombination genomic regions. We also found some candidate genes with divergent selection signatures potentially involved in climatic adaptation and reproductive isolation. Our results contribute to a better understanding of how late Tertiary/Quaternary climatic change influenced speciation, genomic divergence, climatic adaptation, and introgressive hybridization in East Asia's Tertiary relict flora. In addition, they should facilitate future evolutionary, conservation genomics, and molecular breeding studies in Liquidambar, a genus of important medicinal and ornamental values.


Assuntos
Genoma de Planta , Genoma de Planta/genética , China , Adaptação Fisiológica/genética , Fluxo Gênico , Genética Populacional , Genômica , Isolamento Reprodutivo , Filogenia , Variação Genética , Clima , Especiação Genética
2.
Small ; 20(28): e2311129, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38319033

RESUMO

Constructing concentration differences between anions and cations at the ends of an ionic conductor is an effective strategy in electricity generation for powering wearable devices. Temperature gradient or salinity gradient is the driving force behind such devices. But their corresponding power generation devices are greatly limited in actual application due to their complex structure and harsh application conditions. In this study, a novel ionic concentration gradient electric generator based on the evaporation difference of the electrolyte is proposed. The device can be constructed without the need for semipermeable membranes, and operation does not need to build a temperature difference. As a demonstration, a PVA-Na ionic hydrogel is prepared as an electrolyte for the device and achieved a thermovoltage of more than 200 mV and an energy density of 77.94 J m-2 at 323 K. Besides, the device exhibits the capability to sustain a continuous voltage output for a duration exceeding 1500 min, as well as enabling charging and discharging cycles for 100 iterations. For practical applications, a module comprising 16 sub-cells is constructed and successfully utilized to directly power a light-emitting diode. Wearable devices and their corresponding cell modules are also developed to recycle body heat.

3.
Child Dev ; 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39032033

RESUMO

Reading disability (RD) may be characterized by reduced print-speech convergence, which is the extent to which neurocognitive processes for reading and hearing words overlap. We examined how print-speech convergence changes from children (mean age: 11.07+0.48) to adults (mean age: 21.33+1.80) in 86 readers with or without RD. The participants were recruited in elementary schools and associate degree colleges in China (from 2020 to 2021). Three patterns of abnormalities were revealed: (1) persistent reduction of print-speech convergence in the left inferior parietal cortex in both children and adults with RD, suggesting a neural signature of RD; (2) reduction of print-speech convergence in the left inferior frontal gyrus only evident in children but not adults with RD, suggesting a developmental delay; and (3) increased print-speech convergence in adults with RD than typical adults in the bilateral cerebella/fusiform, suggesting compensations. It provides insights into developmental differences in brain functional abnormalities in RD.

4.
Biomed Chromatogr ; 38(4): e5822, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38237172

RESUMO

Danggui Buxue decoction (DBD) is a traditional Chinese medicine herbal decoction that has a good therapeutic effect on vascular dementia (VaD). However, its pharmacodynamic substances and underlying mechanisms are ambiguous. The work aimed to decipher the pharmacodynamic substances and molecular mechanisms of DBD against VaD rats based on gas chromatography-mass spectrometry metabonomics, network pharmacology, molecular docking, and experimental verification. The results indicated that DBD significantly improved the learning abilities and cognitive impairment in the VaD rat model. Integration analysis of the metabolomics and network pharmacology approach revealed that DBD might primarily affect arachidonic acid (AA) and inositol phosphate metabolic pathways by regulating the platelet activation signaling pathways. Six core targets (TNF [tumor necrosis factor], IL-6 [interleukin 6], PTGS2 [prostaglandin-endoperoxide synthase 2], MAPK1, MAPK3, and TP53) in the platelet activation signaling pathways also had a good affinity to seven main active components (saponins, organic acids, flavonoids, and phthalides) of DBD through the verification of molecular docking. Enzyme-linked immunosorbent assay results (ELISA) showed that the levels of TNF, IL-6, PTGS2, thromboxane B2, and caspase-3 in the platelet activation signaling pathway can be regulated by DBD. Our results indicated that DBD treated VaD mainly by modulating the platelet activation signaling pathway, and AA and inositol phosphate metabolism.


Assuntos
Demência Vascular , Medicamentos de Ervas Chinesas , Animais , Ratos , Ciclo-Oxigenase 2 , Demência Vascular/tratamento farmacológico , Interleucina-6 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Ácido Araquidônico , Fosfatos de Inositol
5.
Theor Appl Genet ; 136(3): 29, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36867248

RESUMO

KEY MESSAGE: Using map-based cloning and transgenic transformation, we revealed that glycogen kinase synthase 3-like kinase, BnaC01.BIN2, modulates plant height and yield in rapeseed. The modification of plant height is one of the most important goals in rapeseed breeding. Although several genes that regulate rapeseed plant height have been identified, the genetics mechanisms underlying rapeseed plant height regulation remain poorly understood, and desirable genetic resources for rapeseed ideotype breeding are scarce. Here, we map-based cloned and functionally verified that the rapeseed semi-dominant gene, BnDF4, greatly affects rapeseed plant height. Specifically, BnDF4 encodes brassinosteroid (BR)-insensitive 2, a glycogen synthase kinase 3 primarily expressed in the lower internodes to modulate rapeseed plant height by blocking basal internode-cell elongation. Transcriptome data showed that several cell expansion-related genes involving auxin and BRs pathways were significantly downregulated in the semi-dwarf mutant. Heterozygosity in the BnDF4 allele results in small stature with no marked differences in other agronomic traits. Using BnDF4 in the heterozygous condition, the hybrid displayed strong yield heterosis through optimum intermediate plant height. Our results provide a desirable genetic resource for breeding semi-dwarf rapeseed phenotypes and support an effective strategy for breeding rapeseed hybrid varieties with strong yield heterosis.


Assuntos
Brassica napus , Brassica rapa , Quinase 3 da Glicogênio Sintase , Melhoramento Vegetal , Agricultura
6.
Int J Mol Sci ; 24(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37958595

RESUMO

Cherries (Prunus Subgenus Cerasus) have economic value and ecological significance, yet their phylogeny, geographic origin, timing, and dispersal patterns remain challenging to understand. To fill this gap, we conducted a comprehensive analysis of the complete chloroplast genomes of 54 subg. Cerasus individuals, along with 36 additional genomes from the NCBI database, resulting in a total of 90 genomes for comparative analysis. The chloroplast genomes of subg. Cerasus exhibited varying sizes and consisted of 129 genes, including protein-coding, transfer RNA, and ribosomIal RNA genes. Genomic variation was investigated through InDels and SNPs, showcasing distribution patterns and impact levels. A comparative analysis of chloroplast genome boundaries highlighted variations in inverted repeat (IR) regions among Cerasus and other Prunus species. Phylogeny based on whole-chloroplast genome sequences supported the division of Prunus into three subgenera, I subg. Padus, II subg. Prunus and III subg. Cerasus. The subg. Cerasus was subdivided into seven lineages (IIIa to IIIg), which matched roughly to taxonomic sections. The subg. Padus first diverged 51.42 Mya, followed by the separation of subg. Cerasus from subg. Prunus 39.27 Mya. The subg. Cerasus started diversification at 15.01 Mya, coinciding with geological and climatic changes, including the uplift of the Qinghai-Tibet Plateau and global cooling. The Himalayans were the refuge of cherries, from which a few species reached Europe through westward migration and another species reached North America through northeastward migration. The mainstage of cherry evolution was on the Qing-Tibet Plateau and later East China and Japan as well. These findings strengthen our understanding of the evolution of cherry and provide valuable insights into the conservation and sustainable utilization of cherry's genetic resources.


Assuntos
Genoma de Cloroplastos , Prunus avium , Prunus , Humanos , Prunus avium/genética , Filogenia , Prunus/genética , Tibet
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(5): 532-537, 2023 May 10.
Artigo em Zh | MEDLINE | ID: mdl-37102284

RESUMO

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness. METHODS: Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13+6 gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ <3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test. RESULTS: The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13+4 weeks (11+5 ~ 13+6 weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS. CONCLUSION: NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.


Assuntos
Medição da Translucência Nucal , Diagnóstico Pré-Natal , Gravidez , Humanos , Feminino , Adulto , Lactente , Medição da Translucência Nucal/métodos , Diagnóstico Pré-Natal/métodos , Aberrações Cromossômicas , Aneuploidia , Feto/diagnóstico por imagem , Ultrassonografia Pré-Natal , Variações do Número de Cópias de DNA , Fatores de Transcrição
8.
Mol Genet Genomics ; 297(3): 699-710, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35286449

RESUMO

Increasing the yield of rapeseed is required to meet the rapidly expanding demand for both edible vegetable oil and biofuel. Branching, an important determinant of yield potential in rapeseed, is controlled by a series of quantitative trait loci (QTLs). To explore the genetic mechanism regulating the natural variation of branching, a BC1F1 population derived from a cross between dense branching 2 (dense branching line) and L72 (normal branching line) was used to map QTL conferring branching in rapeseed. A major QTL, qDB.A03, for branching-related traits was identified by the BeadChip Array assisted bulked segregation analysis method, which was subsequently validated by the classical QTL mapping approach, and fine mapped to the 256 kb region. This interval contains 56 annotated or predicted genes, 8 of which are candidates for controlling the branching trait. Comparative and expression analysis revealed four promising candidate genes for qDB.A03. Fine mapping and identification of the candidate genes for qDB.A03 represents the first step toward unraveling the genetical and molecular mechanisms controlling branching in rapeseed.


Assuntos
Brassica napus , Brassica rapa , Brassica napus/genética , Brassica rapa/genética , Mapeamento Cromossômico/métodos , Fenótipo , Locos de Características Quantitativas/genética , Compostos de Quinolínio
9.
Mol Breed ; 42(7): 41, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37313506

RESUMO

Clubroot disease poses a severe threat to rapeseed (Brassica napus) production worldwide and has recently been spreading across China at an unprecedented pace. Breeding and cultivation of resistant varieties constitute a promising and environment-friendly approach to mitigating this threat. In this study, the clubroot resistance locus PbBa8.1 was successfully transferred into SC4, a shared paternal line of three elite varieties in five generations by marker-assisted backcross breeding. Kompetitive allele specific PCR (KASP) markers of clubroot resistance gene PbBa8.1 and its linked high erucic acid gene (FAE1) were designed and applied for foreground selection, and 1,000 single-nucleotide polymorphisms (SNPs) were selected and used for the background selection. This breeding strategy produced recombinants with the highest recovery ratio of the recurrent parent genome (> 95%) at BC2F2 while breaking the linkage with FAE1 during the selection. An updated version of the paternal line (SC4R) was generated at BC2F3, showing significantly improved clubroot resistance at the seedling stage via artificial inoculation, and was comparable to that of the donor parent. Field trials of the three elite varieties and their updated versions in five environments indicated similar agronomic appearance and final yield. The introduced breeding strategy precisely pyramids the PbBa8.1 and FAE1 loci with the assistance of technical markers in a shorter period and could be applied to other desirable traits for directional improvement in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01305-9.

10.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36362332

RESUMO

Low temperature is a major environmental factor, which limits rapeseed (Brassica napus L.) growth, development, and productivity. So far, the physiological and molecular mechanisms of rapeseed responses to cold stress are not fully understood. Here, we explored the transcriptome and metabolome profiles of two rapeseed genotypes with contrasting cold responses, i.e., XY15 (cold-sensitive) and GX74 (cold-tolerant). The global metabolome profiling detected 545 metabolites in siliques of both genotypes before (CK) and after cold-stress treatment (LW). The contents of several sugar metabolites were affected by cold stress with the most accumulated saccharides being 3-dehydro-L-threonic acid, D-xylonic acid, inositol, D-mannose, D-fructose, D-glucose, and L-glucose. A total of 1943 and 5239 differentially expressed genes were identified from the transcriptome sequencing in XY15CK_vs_XY15LW and GX74CK_vs_GX74LW, respectively. We observed that genes enriched in sugar metabolism and biosynthesis-related pathways, photosynthesis, reactive oxygen species scavenging, phytohormone, and MAPK signaling were highly expressed in GX74LW. In addition, several genes associated with cold-tolerance-related pathways, e.g., the CBF-COR pathway and MAPK signaling, were specifically expressed in GX74LW. Contrarily, genes in the above-mentioned pathways were mostly downregulated in XY15LW. Thus, our results indicate the involvement of these pathways in the differential cold-stress responses in XY15 and GX74.


Assuntos
Brassica napus , Brassica rapa , Brassica napus/genética , Resposta ao Choque Frio/genética , Transcriptoma , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica/métodos , Brassica rapa/genética , Genótipo , Metaboloma , Açúcares
11.
Hum Mutat ; 42(1): 37-49, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33058301

RESUMO

Osteoporotic fractures cause major morbidity and mortality in the aging population. Genome-wide association studies (GWAS) have identified USF3 as the novel susceptibility gene of osteoporosis. However, the functional role in bone metabolism and the target gene of the basic helix-loop-helix transcription factor USF3 are unclear. Here, we show that USF3 enhances osteoblast differentiation and suppresses osteoclastogenesis in cultured human osteoblast-like U-2OS cells. Mechanistic studies revealed that transcription factor USF3 antagonistically interacts with anti-osteogenic TWIST1/TCF12 heterodimer in the WNT16 and RUNX2 promoter, and counteracts CREB1 and JUN/FOS in the RANKL promoter. Importantly, the osteoporosis GWAS variant g.1744A>G (rs2908007A>G) located in the WNT16 promoter confers G-allele-specific transcriptional modulation by USF3, TWIST1/TCF12 and TBX5/TBX15, and USF3 transactivates the osteoclastogenesis suppressor WNT16 promoter activity and antagonizes the repression of WNT16 by TWIST1 and TCF12. The risk G allele of osteoporosis GWAS variant g.3260A>G (rs4531631A>G) in the RANKL promoter facilitates the binding of CREB1 and JUN/FOS and enhances transactivation of the osteoclastogenesis contributor RANKL that is inhibited by USF3. Our findings uncovered the functional mechanisms of osteoporosis novel GWAS-associated gene USF3 and lead single nucleotide polymorphisms rs2908007 and rs4531631 in the regulation of bone formation and resorption.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Estudo de Associação Genômica Ampla , Osteoporose , Idoso , Diferenciação Celular/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Osteoblastos , Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Ligante RANK/genética , Proteínas com Domínio T/genética , Proteínas Wnt/genética , Proteínas Wnt/metabolismo
12.
Exp Physiol ; 106(4): 1061-1071, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33527539

RESUMO

NEW FINDINGS: What is the central question of this study? What is the mechanism of miR-211 in an Alzheimer's disease cell model? What is the main finding and its importance? miR-211 was upregulated in an Alzheimer's disease cell model. It targeted neurogenin 2, reduced the activation of the phosphoinositide 3-kinase-Akt signalling pathway, inhibited the proliferation of the Alzheimer's disease cell model and promoted apoptosis. ABSTRACT: MicroRNAs (miRs) are aberrantly expressed in Alzheimer's disease (AD) patients. This study was intended to investigate the effect of miR-211 on an AD cell model and the involvement of neurogenin 2 (Ngn2). The appropriate dose and time for the effect of Aß1-42 on PC12 cells were determined to establish an AD cell model. An effect of miR-211 expression on cell viability, proliferation and apoptosis was detected after cell transfection. Online prediction and a dual luciferase reporter gene assay were utilized to confirm the binding sequence of miR-211 and Ngn2. qRT-PCR and western blot analysis were applied to measure Ngn2 expression. A gain and loss of function assay of miR-211 and Ngn2 was performed, and activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway was detected. The AD cell model was induced by Aß1-42 treatment. miR-211 expression was significantly enhanced after miR-211 transfection, leading to suppressed proliferation and promotion of apoptosis in Aß1-42 -treated PC12 cells. In addition, miR-211 could downregulate Ngn2 mRNA and protein expression, while overexpression of Ngn2 could reverse the effects of miR-211 on Aß1-42 -treated PC12 cells and significantly enhance the phosphorylated Akt and PI3K protein levels. miR-211 could inhibit growth of PC12 cells by suppressing Ngn2 expression and inactivating the PI3K-Akt signalling pathway.


Assuntos
Doença de Alzheimer , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , MicroRNAs , Proteínas do Tecido Nervoso/metabolismo , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Apoptose , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
13.
Bioorg Chem ; 111: 104849, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33798846

RESUMO

Accumulating researches have contributed much effect to discover novel chemotherapeutic drug for leukemia with expeditious curative effect, of which bromodomain-containing protein 4 (BRD4) inhibitor is considered as a eutherapeutic drug which has presented efficient cell proliferation suppression effect. In this study, we disclosed a series of phenylisoxazole sulfonamide derivatives as potent BRD4 inhibitors. Especially, compound 58 exhibited robust inhibitory potency toward BRD4-BD1 and BRD4-BD2 with IC50 values of 70 and 140 nM, respectively. In addition, compound 58 significantly suppressed cell proliferation of leukemia cell lines HL-60 and MV4-11 with IC50 values of 1.21 and 0.15 µM. In-depth study of the biological mechanism of compound 58 exerted its tumor suppression effect via down-regulating the level of oncogene c-myc. Moreover, in vivo pharmacokinetics (PK) study was conducted and the results demonstrated better pharmacokinetics features versus (+)-JQ1. In summary, our study discovers that compound 58 represents as a novel BRD4 inhibitor for further investigation in development of leukemia inhibitor with potentiality.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Desenho de Fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas/farmacologia , Fatores de Transcrição/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas
14.
Hum Mutat ; 41(3): 709-718, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31883164

RESUMO

Upstream transcription factor family member 3 (USF3) c.3781C>A (rs1026364) in the 3'-untranslated region (3'-UTR) has been firmly associated with bone mineral density (BMD) in genome-wide association study (GWAS). However, the molecular mechanism by which it influences BMD and osteoporosis is unknown. Bioinformatics analyses suggested that the risk c.3781A allele creates a target site for hsa-miR-345-5p binding. Luciferase assay validated that the c.3781A allele displayed significantly lower luciferase activities than the c.3781C allele in the human osteoblast cell line hFOB1.19, osteosarcoma cell lines U-2OS and Saos-2, and embryonic kidney cell line 293T. Furthermore, hsa-miR-345-5p regulated USF3 expression on both messenger RNA and protein levels in hFOB1.19 and U937 cells with heterozygous A/C genotype. Transfection of hsa-miR-345-5p antagomiR in heterozygous hFOB1.19 cells significantly increased the expression of osteogenic marker genes RUNX2, OSTERIX, COL1A1, ALP, OPN, OCN, and alkaline phosphatase activity and matrix mineralization level. Importantly, we found that hsa-miR-345-5p also inhibits osteoblast maturation in cell lines U-2OS with hsa-miR-345-5p nonbinding C/C genotype by targeting RUNX3 and SMAD1. Our findings uncovered a novel pathogenetic mechanism of osteoporosis by GWAS variant c.3781C>A-mediated disruption of hsa-miR-345-5p binding at the 3'-UTR of USF3 and the functional role of hsa-miR-345-5p in osteogenic differentiation.


Assuntos
Alelos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , MicroRNAs/genética , Osteoporose/diagnóstico , Osteoporose/genética , Regiões 3' não Traduzidas , Diferenciação Celular/genética , Linhagem Celular , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Genes Reporter , Humanos , Conformação de Ácido Nucleico , Osteoblastos/citologia , Osteoblastos/metabolismo , Interferência de RNA , RNA Mensageiro/genética , Transcriptoma
15.
Metab Brain Dis ; 35(6): 959-970, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32246322

RESUMO

Paeoniflorin is a natural monoterpene glucoside from Paeoniae Radix with neuroprotective properties. However, it is still unclear whether paeoniflorin has neuroprotective effects on subarachnoid hemorrhage (SAH). This study explores the effect of paeoniflorin on early brain injury (EBI) using rat SAH model. We found that paeoniflorin significantly improves neurological deficits, attenuates brain water content and Evans blue extravasation at 72 h after SAH. Paeoniflorin attenuates the oxidative stress following SAH as evidenced by decrease of reactive oxygen species (ROS), malondialdehyde (MDA), 3-Nitrotyrosine, and 8-Hydroxy-2-deoxy guanosine (8-OHDG) level, increase of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase activity, and up-regulates the nuclear factor erythroid­related factor 2 (Nrf2)/heme oxygenase­1 (HO-1) pathway. Inhibition of microglia activation and neuro-inflammatory response both contributed to paeoniflorin's protective effects. Moreover, paeoniflorin treatment significantly reduces the ratio of Bax/Bcl-2, active caspase-3/ neuronal nuclei (NeuN) and TUNEL/DAPI positive cells at 72 h following SAH. Our results indicate that paeoniflorin may attenuate early brain injury after experimental SAH.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Apoptose/efeitos dos fármacos , Lesões Encefálicas/prevenção & controle , Glucosídeos/administração & dosagem , Monoterpenos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Hemorragia Subaracnóidea/tratamento farmacológico , Animais , Apoptose/fisiologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Células Cultivadas , Injeções Intraperitoneais , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/patologia
16.
Neurol Sci ; 37(6): 995-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26908122

RESUMO

Centronuclear myopathy (CNM) is a congenital myopathy characterized by an abnormally high number of muscle fibers with centrally located nuclei. Autosomal-dominant centronuclear myopathy-1 (CNM1) results from mutations in the dynamin 2 gene (DNM2) and accounts for approximately 50 % of all CNM cases. Up to now, around 35 mutations of DNM2 gene have been identified in CNM; however, the underlying molecular mechanism of DNM2 mutation in the pathology of CNM remains elusive, and the standard clinical characteristics and the genotype-phenotype correlation of DNM2 gene mutation with CNM have not yet been defined. Here, we report the clinical characteristics, molecular diagnosis strategy, and DNM2 gene mutations of four Chinese Han patients with CNM. Congenital myopathy-targeted next-generation sequencing (NGS) was applied to sequence the regions of the genome that contain all the coding regions of all known CNM genes and other congenital myopathy genes. We found potential DNM2 mutations in all four of the patients. Further targeted Sanger DNA sequencing of DNM2 found the 1106G>A (p.R369Q) mutation in patients 1 and 2, the c.1393C>T (p.R465W) mutation in patient 3, and the c.1565G>A (p.R522H) mutation in patient 4, all of which were reported previously to be causative mutations of DNM2-related CNM. Our results suggest that the combination of targeted NGS and Sanger sequencing is an effective, rapid, and reliable strategy for the molecular diagnosis of CNM and other genetically heterogeneous disorders.


Assuntos
Dinamina II/genética , Predisposição Genética para Doença/genética , Mutação/genética , Miopatias Congênitas Estruturais/genética , Adulto , Povo Asiático/etnologia , Povo Asiático/genética , Criança , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Miopatias Congênitas Estruturais/diagnóstico , Miopatias Congênitas Estruturais/etnologia , Índice de Gravidade de Doença , Adulto Jovem
17.
Acta Pharmacol Sin ; 36(3): 323-33, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25619390

RESUMO

AIM: Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. METHODS: Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. RESULTS: DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. CONCLUSION: Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.


Assuntos
Alcaloides/farmacologia , Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quinolizinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/fisiopatologia , Masculino , Fator 88 de Diferenciação Mieloide/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle , Matrinas
18.
Nano Lett ; 14(12): 7188-94, 2014 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-25369350

RESUMO

This paper describes the synthesis, formation mechanism, and mechanical property of multilayered ultrathin Pd nanosheets. An anisotropic, Hanoi Tower-like assembly of Pd nanosheets was identified by transmission electron microscopy and atomic force microscopy (AFM). These nanosheets may contain ultrathin Pd layers, down to single unit cell thickness. Selected area electron diffraction and scanning transmission electron microscopy data show the interconnected atomically thick layers stacking vertically with rotational mismatches, resulting in unique diffractions and Moiré patterns. Density functional theory (DFT) calculation with van der Waals correction (DFT+vdW) shows the adsorption of Pd4(CO)4(OAc)4 on Pd(110) surface (Ead = -5.68 eV) is much stronger than that on Pd(100) (Ead = -4.72 eV) or on Pd(111) (Ead = -3.80 eV). The adsorption strength of this Pd complex is significantly stronger than that of CO on the same Pd surfaces. The DFT+vdW calculation results suggest a new mechanism for the observed anisotropic growth of nanosheets with unusually high aspect ratio, in which the competitive adsorptions between Pd4(CO)4(OAc)4 complex and CO on various surfaces result in a favored growth along the ⟨110⟩ directions and inhibition along ⟨111⟩ directions. The mechanical property of these multilayered Pd nanosheets was studied using AFM and nanoindentation techniques, which indicate multilayered nanosheets show more plastic deformation than the bulk in response to an applied force.

19.
J Environ Sci (China) ; 27: 217-24, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25597680

RESUMO

The emission of N2 is important to remove excess N from lakes, ponds, and wetlands. To investigate the gas emission from water, Gao et al. (2013) developed a new method using a bubble trap device to collect gas samples from waters. However, the determination accuracy of sampling volume and gas component concentration was still debatable. In this study, the method was optimized for in situ sampling, accurate volume measurement and direct injection to a gas chromatograph for the analysis of N2 and other gases. By the optimized new method, the recovery rate for N2 was 100.28% on average; the mean coefficient of determination (R(2)) was 0.9997; the limit of detection was 0.02%. We further assessed the effects of the new method, bottle full of water, vs. vacuum bag and vacuum vial methods, on variations of N2 concentration as influenced by sample storage times of 1, 2, 3, 5, and 7 days at constant temperature of 15°C, using indices of averaged relative peak area (%) in comparison with the averaged relative peak area of each method at 0 day. The indices of the bottle full of water method were the lowest (99.5%-108.5%) compared to the indices of vacuum bag and vacuum vial methods (119%-217%). Meanwhile, the gas chromatograph determination of other gas components (O2, CH4, and N2O) was also accurate. The new method was an alternative way to investigate N2 released from various kinds of aquatic ecosystems.


Assuntos
Cromatografia Gasosa , Monitoramento Ambiental/métodos , Nitrogênio/análise , Poluentes Químicos da Água/análise , Gases/análise
20.
Eur J Obstet Gynecol Reprod Biol ; 294: 206-209, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38295709

RESUMO

Complex twin reduction surgery is a common but challenging procedure that aims to reduce the risks and complications of multiple pregnancies. The search for safer and more effective methods has led to the development of high-intensity focused ultrasound (HIFU) technology in the field of fetal reduction. This technology utilizes high-energy sound waves to focus precisely on specific areas, achieving non-invasive therapeutic effects. This paper discusses the principles and features of HIFU technology, as well as its application in complex twin reduction surgery. The paper aims to elucidate the important role of this technology in improving surgical outcomes and reducing risks, explore the current limitations of the modality, and propose directions for future development. Through these investigations, it is hoped to improve overall understanding of HIFU, and thereby promote the application of this technology in the field of fetal reduction.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Redução de Gravidez Multifetal , Gravidez , Feminino , Humanos
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