RESUMO
Biological invasions have become a worldwide problem, and measures to efficiently prevent and control invasions are still in development. Like many other parts of the world, China is undergoing a dramatic increase in plant invasions. Most of the currently 933 established (i.e., naturalized) plant species, of which 214 are categorized as invasive, have been introduced into China for cultivation. It is likely that many of those species are still being traded, particularly online, by plant nurseries. However, studies assessing whether naturalized and invasive species are currently being traded more or less than nonnaturalized aliens are rare. We extracted online-trade information for 13,718 cultivated alien plant taxa on 1688.com, the largest website for domestic B2B in China. We analyzed how the presence in online-nursery catalogs, the number of online nurseries that offerred the species for sale, and the product type (i.e., seeds, live plants and vegetative organs) differed among nonnaturalized, naturalized noninvasive, and invasive species. Compared to nonnaturalized taxa, naturalized noninvasive and invasive taxa were 3.7-5.2 times more likely to be available for purchase. Naturalized noninvasive and invasive taxa were more frequently offered as seeds by online nurseries, whereas nonnaturalized taxa were more frequently offered as live plants. Based on these findings, we propose that, to reduce the further spread of invasive and potentially invasive plants, implementation of plant-trade regulations and a monitoring system of the online horticultural supply chain will be essential.
Assuntos
Espécies Introduzidas , Plantas , Sementes , Comércio , ChinaRESUMO
Anther dehiscence is a crucial event in plant reproduction, tightly regulated and dependent on the lignification of the anther endothecium. In this study, we investigated the rapid lignification process that ensures timely anther dehiscence in Arabidopsis. Our findings reveal that endothecium lignification can be divided into two distinct phases. During Phase I, lignin precursors are synthesized without polymerization, while Phase II involves simultaneous synthesis of lignin precursors and polymerization. The transcription factors MYB26, NST1/2, and ARF17 specifically regulate the pathway responsible for the synthesis and polymerization of lignin monomers in Phase II. MYB26-NST1/2 is the key regulatory pathway responsible for endothecium lignification, while ARF17 facilitates this process by interacting with MYB26. Interestingly, our results demonstrate that the lignification of the endothecium, which occurs within approximately 26 h, is much faster than that of the vascular tissue. These findings provide valuable insights into the regulation mechanism of rapid lignification in the endothecium, which enables timely anther dehiscence and successful pollen release during plant reproduction.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Flores , Regulação da Expressão Gênica de Plantas , Lignina , Lignina/metabolismo , Arabidopsis/metabolismo , Arabidopsis/genética , Flores/metabolismo , Flores/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
PURPOSE: To assess awareness and recognition of vestibular function tests in otorhinolaryngology medical staffs, especially the vestibular evoked myogenic potentials (VEMP) testing in patients with obstructive sleep apnea (OSA). METHODS: A survey was delivered via either email or a social media app. The medical staffs of the Chinese Medical Association of Otolaryngology Head and Neck Surgery from various branches were enrolled. Study data were collected and managed with an online data collection tool. RESULTS: A total of 1781 emails and 623 social media messages were sent to 2404 otorhinolaryngology medical staffs. One hundred and fifty-seven of them participated in the survey, including 24 via emails and 133 via the social media app. Regarding the knowledge of VEMP, only 59 (37.6%) of them agreed that OSA could be related to vertigo/dizziness/imbalance and 28 (17.8%) believed that OSA could result in VEMP abnormalities and would factor this in diagnosing the impairment of the vestibular function of OSA patients. A total of 7.6% of the respondents had never heard of the VEMP tests. Responses regarding the minimum age at which VEMP are possible ranged from younger than 6 months to greater than 18 years of age. Beliefs regarding the utility and reliability of VEMP varied, with 'unsure' being the most frequent response. In addition, only 17.8% of otolaryngologists indicated some access to the VEMP test. CONCLUSIONS: Knowledge and beliefs about the role of VEMP in diagnosing otolithic organ dysfunction caused by OSA in otorhinolaryngology vary widely. It is important for otorhinolaryngology medical staffs to learn the latest literatures and updated knowledge through continuing education.
Assuntos
Otolaringologia , Apneia Obstrutiva do Sono , Potenciais Evocados Miogênicos Vestibulares , Humanos , Lactente , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Reprodutibilidade dos Testes , Inquéritos e Questionários , Apneia Obstrutiva do Sono/diagnósticoRESUMO
The n-octanol-water partition coefficient (logP) is an important physicochemical parameter which describes the behavior of organic compounds. In this work, the apparent n-octanol/water partition coefficients (logD) of basic compounds were determined using ion-suppression reversed-phase liquid chromatography (IS-RPLC) on a silica-based C18 column. The quantitative structure-retention relationship (QSRR) models between logD and logkw (logarithm of retention factor corresponding to 100% aqueous fraction of mobile phase) were established at pH 7.0-10.0. It was found that logD had a poor linear correlation with logkw at pH 7.0 and pH 8.0 when strongly ionized compounds were included in the model compounds. However, the linearity of the QSRR model was significantly improved, especially at pH 7.0, when molecular structure parameters such as electrostatic charge ne and hydrogen bonding parameters A and B were introduced. External validation experiments further confirmed that the multi-parameter models could accurately predict the logD value of basic compounds not only under strong alkaline conditions, but also under weak alkaline and even neutral conditions. The logD values of basic sample compounds were predicted based on the multi-parameter QSRR models. Compared with previous work, the findings of this study extended the pH range for the determination of the logD values of basic compounds, providing an optional mild pH for IS-RPLC experiments.
RESUMO
The deafness-associated m.12201T>C mutation affects the A5-U68 base-pairing within the acceptor stem of mitochondrial tRNAHis The primary defect in this mutation is an alteration in tRNAHis aminoacylation. Here, we further investigate the molecular mechanism of the deafness-associated tRNAHis 12201T>C mutation and test whether the overexpression of the human mitochondrial histidyl-tRNA synthetase gene (HARS2) in cytoplasmic hybrid (cybrid) cells carrying the m.12201T>C mutation reverses mitochondrial dysfunctions. Using molecular dynamics simulations, we demonstrate that the m.12201T>C mutation perturbs the tRNAHis structure and function, supported by decreased melting temperature, conformational changes, and instability of mutated tRNA. We show that the m.12201T>C mutation-induced alteration of aminoacylation tRNAHis causes mitochondrial translational defects and respiratory deficiency. We found that the transfer of HARS2 into the cybrids carrying the m.12201T>C mutation raises the levels of aminoacylated tRNAHis from 56.3 to 75.0% but does not change the aminoacylation of other tRNAs. Strikingly, HARS2 overexpression increased the steady-state levels of tRNAHis and of noncognate tRNAs, including tRNAAla, tRNAGln, tRNAGlu, tRNALeu(UUR), tRNALys, and tRNAMet, in cells bearing the m.12201T>C mutation. This improved tRNA metabolism elevated the efficiency of mitochondrial translation, activities of oxidative phosphorylation complexes, and respiration capacity. Furthermore, HARS2 overexpression markedly increased mitochondrial ATP levels and membrane potential and reduced production of reactive oxygen species in cells carrying the m.12201T>C mutation. These results indicate that HARS2 overexpression corrects the mitochondrial dysfunction caused by the tRNAHis mutation. These findings provide critical insights into the pathophysiology of mitochondrial disease and represent a step toward improved therapeutic interventions for mitochondrial disorders.
Assuntos
Aminoacil-tRNA Sintetases/genética , Surdez/enzimologia , Surdez/genética , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Mutação/genética , RNA de Transferência de Histidina/genética , Trifosfato de Adenosina/metabolismo , Aminoacil-tRNA Sintetases/química , Aminoacil-tRNA Sintetases/metabolismo , Aminoacilação , Linhagem Celular , Respiração Celular , DNA Mitocondrial/metabolismo , Transporte de Elétrons , Humanos , Potencial da Membrana Mitocondrial , Proteínas Mitocondriais/metabolismo , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Desnaturação de Ácido Nucleico , Estabilidade de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , RNA de Transferência de Histidina/química , RNA de Transferência de Histidina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Frações Subcelulares/metabolismoRESUMO
Mitochondrial DNA (mtDNA) mutations have been associated with Leber's hereditary optic neuropathy (LHON) and their pathophysiology remains poorly understood. In this study, we investigated the pathophysiology of a LHON susceptibility allele (m.3394T>C, p.30Y>H) in the Mitochondrial (MT)-ND1 gene. The incidence of m.3394T>C mutation was 2.7% in the cohort of 1741 probands with LHON. Extremely low penetrances of LHON were observed in 26 pedigrees carrying only m.3394T>C mutation, while 21 families bearing m.3394T>C, together with m.11778G>A or m.14484T>C mutation, exhibited higher penetrance of LHON than those in families carrying single mtDNA mutation(s). The m.3394T>C mutation disrupted the specific electrostatic interactions between Y30 of p.MT-ND1 with the sidechain of E4 and backbone carbonyl group of M1 of NDUFA1 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1) of complex I, thereby altering the structure and function of complex I. We demonstrated that these cybrids bearing only m.3394T>C mutation caused mild mitochondrial dysfunctions and those harboring both m.3394T>C and m.11778G>A mutations exhibited greater mitochondrial dysfunctions than cybrids carrying only m.11778G>A mutation. In particular, the m.3394T>C mutation altered the stability of p.MT-ND1 and complex I assembly. Furthermore, the m.3394T>C mutation decreased the activities of mitochondrial complexes I, diminished mitochondrial ATP levels and membrane potential and increased the production of reactive oxygen species in the cybrids. These m.3394T>C mutation-induced alterations aggravated mitochondrial dysfunctions associated with the m.11778G>A mutation. These resultant biochemical defects contributed to higher penetrance of LHON in these families carrying both mtDNA mutations. Our findings provide new insights into the pathophysiology of LHON arising from the synergy between mitochondrial ND1 and ND4 mutations.
Assuntos
Alelos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação , NADH Desidrogenase/genética , Atrofia Óptica Hereditária de Leber/diagnóstico , Atrofia Óptica Hereditária de Leber/genética , Fenótipo , Sequência de Aminoácidos , Animais , Axônios/metabolismo , Linhagem Celular , Genes Mitocondriais , Estudos de Associação Genética , Predisposição Genética para Doença , Camundongos , NADH Desidrogenase/química , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Fosforilação , Transmissão Sináptica , Vesículas Sinápticas/metabolismoRESUMO
To examine the therapeutic effect of Bushen Huoxue recipe (BHR) on women with thin endometrial ovulation disorder and on a rat model of kidney deficiency-related blood stasis. A total of 60 women with thin endometrial ovulation disorder was enrolled. The primary outcome of the study was the pregnancy rate three menstrual cycles after treatment. The study also examined the changes in the type and thickness of uterine artery, uterine artery pulsatility index (PI) and endometrial resistance index (RI). To establish kidney deficiency-related blood stasis in Sprague Dawley (SD) rats, an intragastric administration of hydroxyurea and a tail vein injection of Dextran were given, following with a flashing of the uterine cavity with 95% anhydrous ethanol. A combined regimen of BHR and estradiol valerate significantly increased the rate of pregnancy in women with thin endometrial ovulation disorder. The treatment was accompanied by a significant increase in endometrial thickness and decreases in uterine artery PI and endometrial RI. In rats, kidney deficiency-related blood stasis caused severe loss in endometrial architecture, thickness, and numbers of gland and blood vessel compared to the healthy SD rats. Treatment with BHR could ameliorate the endometrial damages associated with kidney deficiency-related blood stasis.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Endométrio/efeitos dos fármacos , Artéria Uterina/efeitos dos fármacos , Doenças Uterinas/tratamento farmacológico , Adulto , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Nefropatias/complicações , Ovulação , Projetos Piloto , Gravidez , Taxa de Gravidez , Ratos Sprague-Dawley , Doenças Uterinas/etiologiaRESUMO
OBJECTIVES: This study aims to evaluate diagnostic performance of radiomic analysis using computed tomography (CT) to identify lymphovascular invasion (LVI) in patients diagnosed with rectal cancer and assess diagnostic performance of different lesion segmentations. METHODS: The study is applied to 169 pre-treatment CT images and the clinical features of patients with rectal cancer. Radiomic features are extracted from two different volumes of interest (VOIs) namely, gross tumor volume and peri-tumor tissue volume. The maximum relevance and the minimum redundancy, and the least absolute shrinkage selection operator based logistic regression analyses are performed to select the optimal feature subset on the training cohort. Then, Rad and Rad-clinical combined models for LVI prediction are built and compared. Finally, the models are externally validated. RESULTS: Eighty-three patients had positive LVI on pathology, while 86 had negative LVI. An optimal multi-mode radiology nomogram for LVI estimation is established. The area under the receiver operating characteristic curves of the Rad and Rad-clinical combined model in the peri-tumor VOI group are significantly higher than those in the tumor VOI group (Rad: peri-tumor vs. tumor: 0.85 vs. 0.68; Rad-clinical: peri-tumor vs. tumor: 0.90 vs 0.82) in the validation cohort. Decision curve analysis shows that the peri-tumor-based Rad-clinical combined model has the best performance in identifying LVI than other models. CONCLUSIONS: CT radiomics model based on peri-tumor volumes improves prediction performance of LVI in rectal cancer compared with the model based on tumor volumes.
Assuntos
Neoplasias Retais , Humanos , Nomogramas , Prognóstico , Neoplasias Retais/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
Nuclear modifier genes have been proposed to modify the phenotypic expression of mitochondrial DNA mutations. Using a targeted exome-sequencing approach, here we found that the p.191Gly>Val mutation in mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) interacts with the tRNASer(UCN) 7511A>G mutation in causing deafness. Strikingly, members of a Chinese family bearing both the YARS2 p.191Gly>Val and m.7511A>G mutations displayed much higher penetrance of deafness than those pedigrees carrying only the m.7511A>G mutation. The m.7511A>G mutation changed the A4:U69 base-pairing to G4:U69 pairing at the aminoacyl acceptor stem of tRNASer(UCN) and perturbed tRNASer(UCN) structure and function, including an increased melting temperature, altered conformation, instability, and aberrant aminoacylation of mutant tRNA. Using lymphoblastoid cell lines derived from symptomatic and asymptomatic members of these Chinese families and control subjects, we show that cell lines harboring only the m.7511A>G or p.191Gly>Val mutation revealed relatively mild defects in tRNASer(UCN) or tRNATyr metabolism, respectively. However, cell lines harboring both m.7511A>G and p.191Gly>Val mutations displayed more severe defective aminoacylations and lower tRNASer(UCN) and tRNATyr levels, aberrant aminoacylation, and lower levels of other tRNAs, including tRNAThr, tRNALys, tRNALeu(UUR), and tRNASer(AGY), than those in the cell lines carrying only the m.7511A>G or p.191Gly>Val mutation. Furthermore, mutant cell lines harboring both m.7511A>G and p.191Gly>Val mutations exhibited greater decreases in the levels of mitochondrial translation, respiration, and mitochondrial ATP and membrane potentials, along with increased production of reactive oxygen species. Our findings provide molecular-level insights into the pathophysiology of maternally transmitted deafness arising from the synergy between tRNASer(UCN) and mitochondrial YARS mutations.
Assuntos
Mitocôndrias/enzimologia , Mutação , RNA de Transferência de Serina/genética , Tirosina-tRNA Ligase/genética , Povo Asiático , Células Cultivadas , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Tirosina-tRNA Ligase/metabolismoRESUMO
The orthopedic external fixation is always in dynamic mechanical environment with the somatic movement. We used a self-designed mini oscillator to simulate this condition by providing the reciprocating cyclic fluid stress, and observed the behavioral responses of fibroblasts implanted on titanium alloy plane to the stress at different frequencies, including 0.2â¯Hz, 0.6â¯Hz, and 1.0â¯Hz. We found that the cell angle, shape index and expression of vinculin were mostly biphasic-dependent with the increase of frequency, with peaks at 0.6â¯Hz. Whereas the cell area, expression of Col-I and α-SMA were mainly affected by the 1.0â¯Hz stress. Interestingly, 1.0â¯Hz stress also promoted Col-I expression of bone marrow mesenchymal stem cells (BMSCs), although it did not increase α-SMA. These results reveal that 0.6â¯Hz stress improves the alignment, polarity and adherence of fibroblasts on titanium alloy substrates, thus improving the sealing of implants; the 1.0â¯Hz force activates the differentiation of fibroblasts into myofibroblasts and increases collagen produced by stem cells, which probably cause the formation of fibrous capsules around implants.
Assuntos
Ligas/química , Fibroblastos/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Titânio/química , Actinas/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Fibroblastos/efeitos da radiação , Células-Tronco Mesenquimais/metabolismo , Camundongos , Miofibroblastos/efeitos da radiação , Células NIH 3T3 , Desenho de Prótese , Resistência ao Cisalhamento , Estresse Mecânico , Propriedades de Superfície , Vinculina/metabolismoRESUMO
Soil resource heterogeneity can affect plant growth and competitive ability. However, little is known about how soil resource heterogeneity affects competitive interactions between invasive and native plants. We conducted an experiment with an invasive clonal plant Alternanthera philoxeroides and a coexisting native one Alternanthera sessilis. The experiment was a randomized design with three factors, i.e. two species (A. philoxeroides and A. sessilis), two interspecific competition treatments (with and without) and five soil treatments (three homogeneous treatments and two small-scale heterogeneous treatments consisting of two patches of 10 cm × 15 cm and with different initial planting positions). Irrespective of competition, increasing soil resource availability increased the growth of A. philoxeroides. Increasing soil resource availability also increased the growth of A. sessilis without competition, but had no impact with competition. Irrespective of competition, soil resource heterogeneity increased biomass and ramet production of A. philoxeroides, and such effects were independent of initial planting position. For A. sessilis, however, soil resource heterogeneity only increased ramet production when the initial plant was grown in the low-resource patch without competition. Our results suggest that both high soil resource availability and small-scale soil resource heterogeneity can increase the relative competitive ability of the invasive plant A. philoxeroides when grown with its native congener A. sessilis. These findings may partly explain the invasion success of this clonal species in area with high soil resource availability and heterogeneity caused by e.g. nitrogen deposition, fertilization and disturbance.
Assuntos
Amaranthaceae , Solo , Biomassa , Espécies Introduzidas , PlantasRESUMO
OBJECTIVE: To investigate the value of CT-based radiomics signature for preoperatively discriminating mucinous adenocarcinoma (MA) from nomucinous adenocarcinoma (NMA) in rectal cancer and compare with conventional CT values. METHOD: A total of 225 patients with histologically confirmed MA or NMA of rectal cancer were retrospectively enrolled. Radiomics features were computed from the entire tumor volume segmented from the post-contrast phase CT images. The maximum relevance and minimum redundancy (mRMR) and LASSO regression model were performed to select the best preforming features and build the radiomics models using a training cohort of 155 cases. Then, predictive performance of the models was validated using a validation cohort of 70 cases and receiver operating characteristics (ROC) analysis method. Meanwhile, CT values in post- and pre-contrast phase, as well as their difference (D-values) of tumors in two cohorts were measured by two radiologists. ROC curves were also calculated to assess diagnostic efficacies. RESULTS: One hundred and sixty-three patients were confirmed by pathology as NMA and 62 cases were MA. The radiomics signature comprised 19 selected features and showed good discrimination performance in both the training and validation cohorts. The areas under ROC curves (AUC) are 0.93 (95% confidence interval [CI]: 0.89-0.98) in training cohort and 0.93 (95% CI: 0.87-0.99) in validation cohort, respectively. Three sets of CT values of MA in pre- and post-contrast phase, and their difference (D-value) (31±7.0, 51±12.6 and 20±9.3, respectively) were lower than those of NMA (37±5.6, 69±13.3 and 32±11.7, respectively). Comparing to the radiomics signature, using three sets of conventional CT values yielded relatively low diagnostic performance with AUC of 0.84 (95% CI: 0.78-0.88), 0.75 (95% CI: 0.69-0.81) and 0.78 (95% CI: 0.72-0.83), respectively. CONCLUSION: This study demonstrated that CT radiomics features could be utilized as a noninvasive biomarker to identify MA patients from NMA of rectal cancer preoperatively, which is more accurate than using the conventional CT values.
Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Neoplasias Retais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reto/diagnóstico por imagem , Estudos RetrospectivosRESUMO
The 1555AâG mutation in mitochondrial 12S rRNA has been associated with aminoglycoside-induced and non-syndromic deafness in many individuals worldwide. Mitochondrial genetic modifiers are proposed to influence the phenotypic expression of m.1555AâG mutation. Here, we report that a deafness-susceptibility allele (m.4317AâG) in the tRNAIle gene modulates the phenotype expression of m.1555AâG mutation. Strikingly, a large Han Chinese pedigree carrying both m.4317AâG and m.1555AâG mutations exhibited much higher penetrance of deafness than those carrying only the m.1555AâG mutation. The m.4317AâG mutation affected a highly conserved adenine at position 59 in the T-loop of tRNAIle We therefore hypothesized that the m.4317AâG mutation alters both structure and function of tRNAIle Using lymphoblastoid cell lines derived from members of Chinese families (three carrying both m.1555AâG and m.4317AâG mutations, three harboring only m.1555AâG mutation, and three controls lacking these mutations), we found that the cell lines bearing both m.4317AâG and m.1555AâG mutations exhibited more severe mitochondrial dysfunctions than those carrying only the m.1555AâG mutation. We also found that the m.4317AâG mutation perturbed the conformation, stability, and aminoacylation efficiency of tRNAIle These m.4317AâG mutation-induced alterations in tRNAIle structure and function aggravated the defective mitochondrial translation and respiratory phenotypes associated with the m.1555AâG mutation. Furthermore, mutant cell lines bearing both m.4317AâG and m.1555AâG mutations exhibited greater reductions in the mitochondrial ATP levels and membrane potentials and increasing production of reactive oxygen species than those carrying only the m.1555AâG mutation. Our findings provide new insights into the pathophysiology of maternally inherited deafness arising from the synergy between mitochondrial 12S rRNA and tRNA mutations.
Assuntos
Surdez/genética , Mutação , Fenótipo , RNA Mitocondrial/genética , RNA Ribossômico/genética , RNA de Transferência de Isoleucina/genética , Trifosfato de Adenosina/biossíntese , Alelos , Estudos de Casos e Controles , Respiração Celular/genética , Estudos de Coortes , Surdez/metabolismo , Surdez/patologia , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adulto JovemRESUMO
Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c.572G>T, p.191Gly>Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m.11778G>A mutation to cause visual failure. We performed functional assays by using lymphoblastoid cell lines derived from members of Chinese families (asymptomatic individuals carrying m.11778G>A mutation, or both m.11778G>A and heterozygous p.191Gly>Val mutations and symptomatic subjects harboring m.11778G>A and homozygous p.191Gly>Val mutations) and controls lacking these mutations. The 191Gly>Val mutation reduced the YARS2 protein level in the mutant cells. The aminoacylated efficiency and steady-state level of tRNA(Tyr) were markedly decreased in the cell lines derived from patients both carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The failure in tRNA(Tyr) metabolism impaired mitochondrial translation, especially for polypeptides with high content of tyrosine codon such as ND4, ND5, ND6 and COX2 in cells lines carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The YARS2 p.191Gly>Val mutation worsened the respiratory phenotypes associated with m.11778G>A mutation, especially reducing activities of complexes I and IV. The respiratory deficiency altered the efficiency of mitochondrial ATP synthesis and increased the production of reactive oxygen species. Thus, mutated YARS2 aggravates mitochondrial dysfunctions associated with the m.11778G>A mutation, exceeding the threshold for the expression of blindness phenotype. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutation and mutated nuclear-modifier YARS2.
Assuntos
DNA Mitocondrial/genética , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Mutação , Atrofia Óptica Hereditária de Leber/genética , Tirosina-tRNA Ligase/genética , Alelos , Sequência de Bases , Estudos de Casos e Controles , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , DNA Mitocondrial/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Exoma , Regulação da Expressão Gênica , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Neurônios/enzimologia , Neurônios/patologia , Atrofia Óptica Hereditária de Leber/enzimologia , Atrofia Óptica Hereditária de Leber/patologia , Linhagem , Fenótipo , Tirosina-tRNA Ligase/química , Tirosina-tRNA Ligase/metabolismoRESUMO
Cervical ossification of the posterior longitudinal ligament (cOPLL) is one of the major causes of myelopathy. However, the mechanism underlying remains elusive. In the present study, using MILLIPLEX magnetic bead panel, we investigated four serum hormones and six serum cytokines in cOPLL patients and healthy subjects. The results showed that tumor necrosis factore-α (TNF-α) were significantly increased, and DDK-1 was significantly decreased in the serum from male and female cOPLL patients compared with those from healthy controls, respectively. Osteopontin (OPN) and fibroblast growth factor-23 (FGF-23) were significantly increased in male cOPLL patients compared with that in healthy male controls. Further analysis showed that FGF-23 and OPN significantly increased, dickkopf-1 (DKK-1) decreased in the extensive cOPLL group. In addition, a significant positive correlation between the OPN and FGF-23 was observed in male cOPLL patients. The results are useful for understanding the mechanism underlying cOPLL.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Citocinas/sangue , Ossificação do Ligamento Longitudinal Posterior/sangue , Hormônio Paratireóideo/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Exodesoxirribonucleases/sangue , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/etiologia , Osteopontina/sangueRESUMO
The study on nucleic acid retention in ion-pair reversed-phase high-performance liquid chromatography mainly focuses on size-dependence, however, other factors influencing retention behaviors have not been comprehensively clarified up to date. In this present work, the retention behaviors of oligonucleotides and double-stranded DNAs were investigated on silica-based C18 stationary phase by ion-pair reversed-phase high-performance liquid chromatography. It is found that the retention of oligonucleotides was influenced by base composition and base sequence as well as size, and oligonucleotides prone to self-dimerization have weaker retention than those not prone to self-dimerization but with the same base composition. However, homo-oligonucleotides are suitable for the size-dependent separation as a special case of oligonucleotides. For double-stranded DNAs, the retention is also influenced by base composition and base sequence, as well as size. This may be attributed to the interaction of exposed bases in major or minor grooves with the hydrophobic alky chains of stationary phase. In addition, no specific influence of guanine and cytosine content was confirmed on retention of double-stranded DNAs. Notably, the space effect resulted from the stereostructure of nucleic acids also influences the retention behavior in ion-pair reversed-phase high-performance liquid chromatography.
Assuntos
Composição de Bases , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Ácidos Nucleicos/químicaRESUMO
Polydopamine-coated Fe3 O4 magnetic nanoparticles synthesized through a facile solvothermal reaction and the self-polymerization of dopamine have been employed as a magnetic solid-phase extraction sorbent to enrich four phenolic compounds, bisphenol A, tetrabromobisphenol A, (S)-1,1'-bi-2-naphthol and 2,4,6-tribromophenol, from environmental waters followed by high-performance liquid chromatographic detection. Various parameters of the extraction were optimized, including the pH of the sample matrix, the amount of polydopamine-coated Fe3 O4 sorbent, the adsorption time, the enrichment factor of analytes, the elution solvent, and the reusability of the nanoparticles sorbent. The recoveries of these phenols in spiked water samples were 62.0-112.0% with relative standard deviations of 0.8-7.7%, indicating the good reliability of the magnetic solid-phase extraction with high-performance liquid chromatography method. In addition, the extraction characteristics of the magnetic polydopamine-coated Fe3 O4 nanoparticles were elucidated comprehensively. It is found that there are hydrophobic, π-π stacking and hydrogen bonding interactions between phenols and more dispersible polydopamine-coated Fe3 O4 in water, among which hydrophobic interaction dominates the magnetic solid-phase extraction performance.
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Objective To observe the curative effect of Chinese medicine (CM) combined West- ern medicine (WM) in treating rheumatoid arthritis (RA) patients. Methods Totally 351 RA patients were allocated into two groups by their willingness, 52 cases in the control group and 299 cases in the combination group. Treatment of WM mainly included non-steroidal anti-inflammatory drugs, glucocorti- coids, and anti-rheumatic drugs. And treatment based on syndrome differentiation of CM was adopted. Four diagnostic information of CM, joint pain, tenderness, swelling index, laboratory indices, and treat- ment expenses were observed. Disease activity score 28 (DAS28) , quality of life score [health assessment questionnaire (HAQ) ] , and efficacy of disease were assessed. Results After 2-3 months of treatment, the total effective rate was higher in the combination group than in the control group (P < 0. 05). After 6-12 months of treatment, the total effective rate, DAS28, and HAQ score were better in the combination group than in the control group (P <0. 05). There was no statistical difference in use of Western drugs, total expenses of hospitalization, total expenses of outpatient service between the two groups (P >0. 05). Patients who were treated by combined treatment, or having higher DAS obtained better effects after 2-3 months of treatment (P <0. 05). Patients who were treated by combined treatment, or having lower DAS obtained better effects after 6-12 months of treatment (P <0. 05). Conclusions Real world study (RWS) observed that combined CM and WM could get more significant effect. It also could effectively reduce disease activity, improve patients' QOL, with no economic burdens added.
Assuntos
Artrite Reumatoide , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Qualidade de Vida , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Resultado do TratamentoRESUMO
Objective To explore the effect of Wenshen Yangxue Recipe (WYR) on inhibin-ac- tivin-follistatin (INH-ACT-FS) system and gonadal hormone level in anovulatory rats. Methods Anovula- tory rat model was established in 76 rats (9 days old) by subcutaneous injecting testosterone propionate (1. 25 mg/0. 05 mL for each rat) from the nape. Totally 58 successfully modeled rats were divided into 5 groups according to random digit table, i.e., the model group (n =10), the Western medicine (WM) group (n =12), high, middle, and low dose WYR groups (n =12). Besides, another ten 22-day old rats were recruited as a normal group. Distilled water was daily administered to rats in the normal group and the model group by gastrogavage. Clomiphene citrate (0. 58 mg/100 g) was daily administered to rats in the WM group for 5 successive days. WYR at 5. 2, 2. 6, 1. 3 mg/100 g was daily administered to rats in high, middle, and low dose WYR groups for 21 successive days. Levels of follicular stimulating hormone (FSH) , luteinizing hormone (LH) , estradiol (E2) , progesterone (P) , and prolactin (PRL) were detected using radioimmunoassay. Contents of inhibin (INH) , activin (ACT) , and follistatin (FS) were measured using ELISA. Results Compared with the normal group, serum levels of FSH and LH increased, and P level decreased in the model group (P <0. 05) ; INH level decreased and FS level increased in the model group (P<0. 05). Compared with the model group, serum FSH level decreased in the WM group and 3 WYR groups, P level decreased in the WM group (P <0. 05); INH increased and FS levels decreased in the WM group and 3 WYR groups; ACT level increased in the high dose WYR group, with statistical differ- ence (P <0. 05). Conclusion WYR promoted follicular development possibly through regulating INH- ACT-FS system and gonadal hormone level.
Assuntos
Anovulação , Medicamentos de Ervas Chinesas , Folistatina , Inibinas , Ativinas , Animais , Anovulação/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Hormônio Foliculoestimulante , Folistatina/efeitos dos fármacos , Inibinas/efeitos dos fármacos , Hormônio Luteinizante , RatosRESUMO
Systemic adenovirus infection in the immunocompromised host is often fatal and therapeutic options are limited. We report an infant with acute lymphoblastic leukemia who developed disseminated adenovirus infection while lymphopenic during maintenance chemotherapy 6 months following a bout of adenoviral diarrhea. His serum adenoviral load peaked at 35 million copies/mL and was associated with pancytopenia and hepatic injury. Treatment with cidofovir was effective although associated with mild renal injury. The patient recovered fully and completed chemotherapy for infant acute lymphoblastic leukemia.