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Seeds are initiated from the carpel margin meristem (CMM) and high seed yield is top one of breeding objectives for many crops. ß-1,3-glucanases play various roles in plant growth and developmental processes; however, whether it participates in CMM development and seed formation remains largely unknown. Here, we identified a ß-1,3-glucanase gene (GLU19) as a determinant of CMM callose deposition and seed yield in cotton. GLU19 was differentially expressed in carpel tissues between Gossypium barbadense (Gb) and Gossypium hirsutum (Gh). Based on resequencing data, one interspecies-specific InDel in the promoter of GLU19 was further detected. The InDel was involved in the binding site of the CRABS CLAW (CRC) transcription factor, a regulator of carpel development. We found that the CRC binding affinity to the GLU19 promoter of G. barbadense was higher than that of G. hirsutum. Since G. barbadense yields fewer seeds than G. hirsutum, we speculated that stronger CRC binding to the GLU19 promoter activated higher expression of GLU19 which in turn suppressed seed production. Consistent with this hypothesis was that the overexpression of GhGLU19 caused reduced seed number, boll weight and less callose formation in CMM. Conversely, GhGLU19-knockdown (GhGLU19-KD) cotton led to the opposite phenotypes. By crossing GhGLU19-KD lines with several G. hirsutum and G. barbadense cotton accessions, all F1 and F2 plants carrying GhGLU19-KD transgenic loci exhibited higher seed yield than control plants without the locus. The increased seed effect was also found in the down-regulation of Arabidopsis orthologs lines, indicating that this engineering strategy may improve the seed yield in other crops.
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Gossypium barbadense, which is one of several species of cotton, is well known for its superior fiber quality. However, the genetic basis of its high-quality fiber remains largely unexplored. Here, we resequenced 269 G. barbadense accessions. Phylogenetic structure analysis showed that the set of accessions was clustered into 3 groups: G1 and G2 mainly included modern cultivars from Xinjiang, China, and G3 was related to widely introduced accessions in different regions worldwide. A genome-wide association study of 5 fiber quality traits across multiple field environments identified a total of 512 qtls (main-effect QTLs) and 94 qtlEs (QTL-by-environment interactions) related to fiber quality, of which 292 qtls and 57 qtlEs colocated with previous studies. We extracted the genes located in these loci and performed expression comparison, local association analysis, and introgression segment identification. The results showed that high expression of hormone-related genes during fiber development, introgressions from Gossypium hirsutum, and the recombination of domesticated elite allelic variation were 3 major contributors to improve the fiber quality of G. barbadense. In total, 839 candidate genes with encoding region variations associated with elite fiber quality were mined. We confirmed that haplotype GB_D03G0092H traced to G. hirsutum introgression, with a 1-bp deletion leading to a frameshift mutation compared with GB_D03G0092B, significantly improved fiber quality. GB_D03G0092H is localized in the plasma membrane, while GB_D03G0092B is in both the nucleus and plasma membrane. Overexpression of GB_D03G0092H in Arabidopsis (Arabidopsis thaliana) significantly improved the elongation of longitudinal cells. Our study systematically reveals the genetic basis of the superior fiber quality of G. barbadense and provides elite segments and gene resources for breeding high-quality cotton cultivars.
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Fibra de Algodão , Perfilação da Expressão Gênica , Genoma de Planta , Estudo de Associação Genômica Ampla , Gossypium , Locos de Características Quantitativas , Gossypium/genética , Fibra de Algodão/análise , Locos de Características Quantitativas/genética , Filogenia , Haplótipos/genética , Regulação da Expressão Gênica de PlantasRESUMO
Plasma membrane represents a critical battleground between plants and attacking microbes. Necrosis-and-ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs), cytolytic toxins produced by some bacterial, fungal and oomycete species, are able to target on lipid membranes by binding eudicot plant-specific sphingolipids (glycosylinositol phosphorylceramide) and form transient small pores, causing membrane leakage and subsequent cell death. NLP-producing phytopathogens are a big threat to agriculture worldwide. However, whether there are R proteins/enzymes that counteract the toxicity of NLPs in plants remains largely unknown. Here we show that cotton produces a peroxisome-localized enzyme lysophospholipase, GhLPL2. Upon Verticillium dahliae attack, GhLPL2 accumulates on the membrane and binds to V. dahliae secreted NLP, VdNLP1, to block its contribution to virulence. A higher level of lysophospholipase in cells is required to neutralize VdNLP1 toxicity and induce immunity-related genes expression, meanwhile maintaining normal growth of cotton plants, revealing the role of GhLPL2 protein in balancing resistance to V. dahliae and growth. Intriguingly, GhLPL2 silencing cotton plants also display high resistance to V. dahliae, but show severe dwarfing phenotype and developmental defects, suggesting GhLPL2 is an essential gene in cotton. GhLPL2 silencing results in lysophosphatidylinositol over-accumulation and decreased glycometabolism, leading to a lack of carbon sources required for plants and pathogens to survive. Furthermore, lysophospholipases from several other crops also interact with VdNLP1, implying that blocking NLP virulence by lysophospholipase may be a common strategy in plants. Our work demonstrates that overexpressing lysophospholipase encoding genes have great potential for breeding crops with high resistance against NLP-producing microbial pathogens.
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Lisofosfolipase , Verticillium , Lisofosfolipase/genética , Gossypium/genética , Peroxissomos , Melhoramento Vegetal , Doenças das Plantas/microbiologia , Resistência à Doença/genética , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Opioid crisis has become a global concern, but whether physical activity (PA) can effectively reduce prescription opioid use remains unclear. The study aimed to examine the relationship of different domains of PA (e.g., occupation-related PA [OPA], transportation-related PA [TPA], leisure-time PA [LTPA]) with prescription opioid use and duration of prescription opioid use. METHODS: This cross-sectional study was conducted on 27,943 participants aged ≥ 18 years from National Health and Nutrition Examination Survey (NHANES, 2007- March 2020). We examined the relationship of different domains of PA with prescription opioid use and duration of prescription opioid use using multivariable logistic regression. Stratified analysis and a series of sensitivity analysis were used to elevate robustness. All analyses were conducted using appropriate sampling weights. RESULTS: Of the 27,943 participants, the mean age was 45.10 years, with 14,018 [weighted, 50.0%] females and 11,045 [weighted, 66.0%] non-Hispanic White. After multivariable adjustment, inverse associations between PA and prescription opioid use were observed for sufficient (≥ 150 min/week) total PA (OR,0.68 95%CI [0.56-0.81]), TPA (OR,0.73 95%CI [0.58-0.92]), and LTPA (OR,0.60 95%CI [0.48-0.75]) compared with insufficient PA(< 150 min/week), but not for sufficient OPA (OR,0.93 95%CI [0.79-1.10]). In addition, the associations were dose-responsive, participants had 22-40%, 27-36%, and 26-47% lower odds of using prescription opioids depending on the duration of total PA, TPA, and LTPA, respectively. Nevertheless, the impact of PA on prescription opioid use varied by duration of opioid use. Sufficient total PA was associated with elevated odds of short-term use of prescription opioids (< 90 days). Comparatively, sufficient total PA, TPA, and LTPA had different beneficial effects on reducing long-term use of prescription opioids (≥ 90 days) depending on the strength of opioids. CONCLUSIONS: This study demonstrated sufficient total PA, TPA, and LTPA were inversely associated with prescription opioid use and varied depending on the duration and strength of prescription opioid use. These findings highlight PA can provide policy guidance to address opioid crisis.
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Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Inquéritos Nutricionais , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Exercício Físico , PrescriçõesRESUMO
Site-specific gene stacking could reduce the number of segregating loci and expedite the introgression of transgenes from experimental lines to field lines. Recombinase-mediated site-specific gene stacking provides a flexible and efficient solution, but this approach requires a recombinase recognition site in the genome. Here, we describe several cotton (Gossypium hirsutum cv. Coker 312) target lines suitable for Mycobacteriophage Bxb1 recombinase-mediated gene stacking. Obtained through the empirical screening of random insertion events, each of these target lines contains a single intact copy of the target construct with precise sequences of RS2, lox, and attP sites that is not inserted within or close to a known gene or near a centromere and shows good expression of the reporter gene gfp. Gene stacking was tested with insertion of different combinations of three candidate genes for resistance to verticillium wilt into three cotton target lines: CTS1, CTS3, and CTS4. Nine site-specific integration events were recovered from 95 independently transformed embryogenic calluses. Southern and DNA sequence analyses of regenerated plants confirmed precise site-specific integration, and resistance to verticillium wilt was observed for plant CTS1i3, which has a single precise copy of site-specifically integrated DNA. These cotton target lines can serve as foundation lines for recombinase-mediated gene stacking to facilitate precise DNA integration and introgression to field cultivars.
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Gossypium , Verticillium , Resistência à Doença/genética , Gossypium/genética , Gossypium/metabolismo , Doenças das Plantas/genética , Plantas Geneticamente Modificadas/metabolismo , Recombinases/genética , Recombinases/metabolismo , TransgenesRESUMO
OBJECTIVE: The study aimed to examine the relationship between secondhand smoke (SHS) exposure and severe headaches or migraine in never-smoking adults verified by serum cotinine. BACKGROUND: Current evidence about the association between self-reported SHS exposure and headaches or migraine is limited and contradictory. An important issue lies in the lack of actual SHS exposure assessment through biomarkers. METHODS: We conducted a cross-sectional study on 4560 never-smoking adults from the National Health and Nutrition Examination Survey (NHANES), 1999-2004. The SHS exposure was evaluated by measuring serum cotinine concentrations. The information regarding severe headaches or migraine was based on self-reporting. RESULTS: The overall prevalence rate of severe headaches or migraine was 20% (919/4560). After adjusting for relevant covariates, we found that heavy SHS exposure (serum cotinine at 1 to 10 ng/mL) was positively associated with severe headaches or migraine (OR: 2.02, 95% CI [1.19, 3.43]); however, no significant association was found between low SHS exposure (serum cotinine at 0.05 to 0.99 ng/mL) and severe headaches or migraine (OR: 1.15, 95% CI [0.91, 1.47]). Restricted cubic spline analysis showed that the natural logarithm of serum cotinine had a linear relationship with severe headaches or migraine (p = 0.335 for nonlinearity). Stratified analysis indicated that individuals with a BMI of <25 (p < 0.001 for interaction) and sedentary activity (p = 0.016 for interaction) modified the relationship between SHS exposure and severe headaches and migraine. Even after altering the definition of SHS exposure, excluding drugs that might affect the metabolism of serum cotinine, and multiple imputation, our sensitivity analysis results remained stable. CONCLUSIONS: The study demonstrated that heavy SHS exposure (serum cotinine at 1 to 10 ng/mL) had a significant positive association with severe headaches or migraine in never-smoking adults. Prospective studies are necessary to verify this relationship in the future.
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Transtornos de Enxaqueca , Poluição por Fumaça de Tabaco , Humanos , Adulto , Inquéritos Nutricionais , Poluição por Fumaça de Tabaco/efeitos adversos , Cotinina/análise , Estudos Transversais , Estudos Prospectivos , Transtornos de Enxaqueca/epidemiologia , Cefaleia/epidemiologia , Cefaleia/etiologia , FumarRESUMO
BACKGROUND: In eudicots, germination begins with water uptake by the quiescent dry seed and is greatly related to the permeability of micropyle enriched callose layers. Once imbibition starts, seeds undergo a cascade of physiological, biochemical, and molecular events to initiate cellular activities. However, the effects of callose on water uptake and following seed metabolic events during germination are largely unknown. Cotton (Gossypium hirsutum) is a eudicot plant with natural fiber and edible oil production for humans. Here, we addressed this question by examining the role of GhGLU19, a gene encoding ß-1,3-glucanase, in cotton seed germination. RESULTS: GhGLU19 belongs to subfamily B and was expressed predominately in imbibed seeds and early seedlings. Compared to wild type, GhGLU19-suppressing and GhGLU19-overexpressing transgenic cotton lines showed the higher and lower seed germination percentage, respectively. Callose was enriched more at inner integument (ii) than that in embryo and seed coat in cotton seeds. In GhGLU19-suppressing lines, callose at ii of cotton seeds was greatly increased and brought about a prolonged water uptake process during imbibition. Both proteomic and transcriptomic analysis revealed that contrary to GhGLU19-overexpressing lines, the glycolysis and pyruvate metabolism was decreased, and abscisic acid (ABA) biosynthesis related genes were downregulated in imbibed seeds of GhGLU19-suppressing lines. Also, endogenous ABA was significantly decreased in GhGLU19-suppressing line while increased in GhGLU19-overexpressing line. CONCLUSIONS: Our results demonstrate that suppression of GhGLU19 improves cotton seed germination via accumulating callose of inner integument, modulating glycolysis and pyruvate metabolism, and decreasing ABA biosynthesis. This study provides a potential way for improving germination percentage in cotton seed production, and other eudicot crops.
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Germinação , Gossypium , Ácido Abscísico/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação/fisiologia , Gossypium/metabolismo , Humanos , Proteômica , Piruvatos/metabolismo , Piruvatos/farmacologia , Sementes/metabolismo , Água/metabolismoRESUMO
BACKGROUND: During the coronavirus disease 2019 (COVID-19) containment, primary health care (PHC) facilities inChina played an important role in providing both healthcare and public care services to community populations. The tasks of COVID-19 containment facilitated by PHC facilities were different among different regions and during different periods of COVID-19 pandemic. We sought to investigate the gaps on task participation, explore existing problems and provide corresponding solutions. METHODS: Semi-structured face-to-face interviews with COVID-19 prevention and control management teams of PHC facilities were conducted. Purposive stratified sampling was used and 32 team members of 22 PHC facilities were selected from Wuhan (as high-risk city), Shanghai (as medium-risk city) and Zunyi (as low-risk city). Framework analysis was employed to analyze the transcribed recordings. RESULTS: The main tasks of PHC facilities during the early period of the pandemic included assisting in contact tracing and epidemiological investigation, screening of populations at high-risk at travel centers/internals, house-by-house, or pre-examination/triage within PHC facilities; at-home/ centralized quarantine management; the work of fever sentinel clinics. Further analyses revealed the existing problems and suggestions for improvement or resolutions. Regular medical supply reserves were recommended because of the medical supply shortage during the pre-outbreak period. Temporarily converted quarantine wards and centralized quarantine centers could be used to deal with pressures on patients' treatment and management of the febrile patients. Only after strict evaluation of nucleic acid testing (NAT) results and housing conditions, decision on quarantine at-home or centralized quarantine centers could be made. Settings of fever sentinel clinics at PHC facilities allowed fever patients with no COVID-19 infection risks for treatment without being transferred to fever clinics of the designed secondary hospitals. Psychological intervention was sometimes in need and really helped in addressing individuals' mental pressures. CONCLUSIONS: During the COVID-19 containment, PHC facilities in China were responsible for different tasks and several problems were encountered in the working process. Accordingly, specific and feasible suggestions were put forward for different problems. Our findings are highly beneficial for healthcare teams and governments in handling similar situations.
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COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Cidades , Humanos , Pandemias/prevenção & controle , Atenção Primária à SaúdeRESUMO
Seedling drought stress is one of the most important constraints affecting soybean yield and quality. To unravel the molecular mechanisms under soybean drought tolerance, we conducted comprehensive comparative transcriptome analyses of drought-tolerant genotype Jindou 21 (JD) and drought-sensitive genotype Tianlong No.1 (N1) seedlings that had been exposed to drought treatment. A total of 6038 and 4112 differentially expressed genes (DEGs) were identified in drought-tolerant JD and drought-sensitive N1, respectively. Subsequent KEGG pathway analyses showed that numerous DEGs in JD are predominately involved in signal transduction pathways, including plant hormone signaling pathway, calcium signaling pathway, and MAPK signaling pathway. Interestingly, JA and BR plant hormone signal transduction pathways were found specifically participating in drought-tolerant JD. Meanwhile, the differentially expressed CPKs, CIPKs, MAPKs, and MAP3Ks of calcium and MAPK signaling pathway were only identified in JD. The number of DEGs involved in transcription factors (TFs) is larger in JD than that of in N1. Moreover, some differently expressed transcriptional factor genes were only identified in drought-tolerant JD, including FAR1, RAV, LSD1, EIL, and HB-PHD. In addition, this study suggested that JD could respond to drought stress by regulating the cell wall remodeling and stress-related protein genes such as EXPs, CALSs, CBPs, BBXs, and RD22s. JD is more drought tolerant than N1 owing to more DEGs being involved in multiple signal transduction pathways (JA, BR, calcium, MAPK signaling pathway), stress-related TFs, and proteins. The above valuable genes and pathways will deepen the understanding of the molecular mechanisms under drought stress in soybean.
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Secas , Plântula , Cálcio/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas/metabolismo , Plântula/metabolismo , Glycine max/genética , Glycine max/metabolismo , Estresse Fisiológico/genética , TranscriptomaRESUMO
BACKGROUND: To study the competency of general practitioners (GPs) in Shanghai, China on prevention and management of type 2 diabetes, also understand factors that may prohibit it. METHODS: A survey questionnaire with 25 questions was designed based on 2013 Chinese Type 2 Diabetes Prevention Guidelines and Chinese Type 2 Diabetes Prevention Guidelines (Grassroots Edition) and conducted among 789 GPs who work at 54 community healthcare centers (CHCs) within 16 districts at Shanghai, China. Excel 2016 and SPSS 24.0 were used for data analysis, and a difference of P < 0.05 was considered to be statistically significant. RESULTS: The GPs did poorly on three aspect of diabetes prevention and treatment: (1) treatment goals in elderly patients, (2) screening methods for high-risk population, and (3) aspirin contraindications. The statistical analysis data showed that GPs who finished standardized training had correct answer on 13.58 ± 3.31 questions out of total 25, with mean accuracy rate of 54.32%. Except the questions for high-risk population screening method and the diagnostic criteria for type 2 diabetes, there was no difference in the accuracy of other questions between GPs with or without standardized training (P < 0.05). However, sex, educational level, and subspecialty experience are affective factors on their competency in type 2 diabetes prevention and treatment knowledge. CONCLUSION: The results indicated that communities should strengthen the training of GPs in diabetes management and bidirectional referral. Frequent continuing education and skills training should be provided among GPs at CHCs to ensure their competency of type 2 diabetes prevention and treatment knowledge after obtaining their GP license disregard of their standardized training. In addition, attention should be paid to GPs who had lower education background or non-clinical subspecialty experience to strengthen their clinical knowledge of type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Clínicos Gerais , Idoso , China , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The WRKY proteins are a superfamily of transcription factors and members play essential roles in the modulation of diverse physiological processes, such as growth, development, senescence and response to biotic and abiotic stresses. However, the biological roles of the majority of the WRKY family members remains poorly understood in soybean relative to the research progress in model plants. RESULTS: In this study, we identified and characterized GmWRKY40, which is a group IIc WRKY gene. Transient expression analysis revealed that the GmWRKY40 protein is located in the nucleus of plant cells. Expression of GmWRKY40 was strongly induced in soybean following infection with Phytophthora sojae, or treatment with methyl jasmonate, ethylene, salicylic acid, and abscisic acid. Furthermore, soybean hairy roots silencing GmWRKY40 enhanced susceptibility to P. sojae infection compared with empty vector transgenic roots. Moreover, suppression of GmWRKY40 decreased the accumulation of reactive oxygen species (ROS) and modified the expression of several oxidation-related genes. Yeast two-hybrid experiment combined with RNA-seq analysis showed that GmWRKY40 interacted with 8 JAZ proteins with or without the WRKY domain or zinc-finger domain of GmWRKY40, suggesting there were different interaction patterns among these interacted proteins. CONCLUSIONS: Collectively, these results suggests that GmWRKY40 functions as a positive regulator in soybean plants response to P. sojae through modulating hydrogen peroxide accumulation and JA signaling pathway.
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Regulação da Expressão Gênica de Plantas , Glycine max/genética , Phytophthora/fisiologia , Doenças das Plantas/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Resistência à Doença/genética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Alinhamento de Sequência , Glycine max/metabolismo , Glycine max/microbiologia , Fatores de Transcrição/química , Fatores de Transcrição/metabolismoRESUMO
Exercise is recognized as an effective method to prevent obesity and alleviate metabolic diseases. Browning of white adipose has the advantage of decreasing insulin resistance. We aim to identify critical differentially expressed genes (DEGs) in white adipose tissue after exercise. We downloaded the gene dataset GSE68161 of C57BL/6 mice from the Gene Expression Omnibus (GEO) database. Then, we analyzed the effect of exercise on up-regulated and down-regulated DEGs by GEO2R and performed protein-protein interaction network analyses. We then identified hub-genes in white adipose tissue and crosstalk genes of a single pathway by the STRING database and Cytoscape. In this study, 72 DEGs were screened out, and they mainly function in glycerol-3-phosphate dehydrogenase activity and in the primary biological process of fatty acid oxidation regulation. The top 5 hub-genes screened out were SLC27A1, COX7A1, PPARGC1A, FABP3, and UCP1. The 3 crosstalk genes found were SLC27A1, SLC27A2, and PPARA. These 3 genes might function as a bridge of the PPAR signaling pathway, adipocytokine signaling pathway and the insulin resistance pathway. SLC27A1 is critical gene for the interactions of signaling pathways in subcutaneous white adipose tissue. Therefore, further relationships between the browning of white adipose and insulin resistance need to be studied.
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Tecido Adiposo Branco/fisiologia , Exercício Físico/fisiologia , Mapas de Interação de Proteínas , Transcriptoma , Adipocinas/metabolismo , Animais , Mineração de Dados , Bases de Dados Genéticas , Regulação para Baixo , Humanos , Resistência à Insulina , Subunidade 1 do Complexo Mediador/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/prevenção & controle , Transdução de Sinais , Regulação para CimaRESUMO
The mediator complex is an essential link between transcription factors and RNA polymerase II, and mainly functions in the transduction of diverse signals to genes involved in different pathways. Limited information is available on the role of soybean mediator subunits in growth and development, and their participation in defense response regulation. Here, we performed genome-wide identification of the 95 soybean mediator subunits, which were unevenly localized on the 20 chromosomes and only segmental duplication events were detected. We focused on GmMED16-1, which is highly expressed in the roots, for further functional analysis. Transcription of GmMED16-1 was induced in response to Phytophthora sojae infection. Agrobacterium rhizogenes mediated soybean hairy root transformation was performed for the silencing of the GmMED16-1 gene. Silencing of GmMED16-1 led to an enhanced susceptibility phenotype and increased accumulation of P. sojae biomass in hairy roots of transformants. The transcript levels of NPR1, PR1a, and PR5 in the salicylic acid defense pathway in roots of GmMED16-1-silenced transformants were lower than those of empty-vector transformants. The results provide evidence that GmMED16-1 may participate in the soybean-P. sojae interaction via a salicylic acid-dependent process.
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Estudo de Associação Genômica Ampla , Glycine max/genética , Glycine max/parasitologia , Interações Hospedeiro-Parasita/genética , Complexo Mediador/metabolismo , Phytophthora/fisiologia , Mapeamento Cromossômico , Cromossomos de Plantas , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Phytophthora/classificação , Doenças das Plantas/genética , Doenças das Plantas/parasitologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Subunidades Proteicas , TranscriptomaRESUMO
BACKGROUND: We aimed to investigate the relationship between quality of life and the factors that may influence it in an elderly community-dwelling population in Shanghai. METHODS: From August to October 2014, elderly individuals were enrolled from three randomly selected communities in Shanghai. Participant information was collected from responses to a general questionnaire and to the Lubben Social Network Scale-6, Cumulative Illness Rating Scale for Geriatrics, Patient Health Questionnaire, and the 12-item Short Form Health Survey. The factors influencing quality of life were explored in a multivariate stepwise linear regression model. RESULTS: Physical and mental component summary scores for the elderly in Shanghai communities were 50.1 ± 10.1 and 47.3 ± 7.9, respectively. Physical component summary scores in the rural area were higher than those in the urban-rural intersection area (a place where urban and rural transitions are taking place) (52.32 ± 9.81 vs 49.63 ± 9.33, P < 0.05) and the urban area (52.32 ± 9.81 vs 47.34 ± 10.18, P < 0.05). Additionally, mental component summary scores in the rural area were higher than those in the urban-rural intersection area (52.63 ± 9.28 vs 48.43 ± 9.42, P < 0.05) and the urban area (52.63 ± 9.28 vs 48.13 ± 10.69, P < 0.05). CONCLUSIONS: Depression, self-care ability, and medical care burden were found to be significantly associated with the quality of life of elderly individuals in Shanghai, China. Therefore, more attention should be paid to the mental health of this elderly population.
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Depressão/epidemiologia , Vida Independente/psicologia , Saúde Mental , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , População Rural/estatística & dados numéricos , Inquéritos e Questionários , População Urbana/estatística & dados numéricosRESUMO
The therapeutic applications of lipid nanoparticle (LNP) formulations of small interfering RNA (siRNA), are hampered by inefficient delivery of encapsulated siRNA to the cytoplasm following endocytosis. Recent work has shown that up to 70% of endocytosed LNP-siRNA particles are recycled to the extracellular medium and thus cannot contribute to gene silencing. Niemann-Pick type C1 (NPC1) is a late endosomal/lysosomal membrane protein required for efficient extracellular recycling of endosomal contents. Here we assess the influence of NP3.47, a putative small molecule inhibitor of NPC1, on the gene silencing potency of LNP-siRNA systems in vitro. Intracellular uptake and colocalization studies revealed that the presence of NP3.47 caused threefold or higher increases in accumulation of LNP-siRNA in late endosomes/lysosomes as compared with controls in a variety of cell lines. The gene silencing potency of LNP siRNA was enhanced up to fourfold in the presence of NP3.47. Mechanisms of action studies are consistent with the proposal that NP3.47 acts to inhibit NPC1. Our findings suggest that the pharmacological inhibition of NPC1 is an attractive strategy to enhance the therapeutic efficacy of LNP-siRNA by trapping LNP-siRNA in late endosomes, thereby increasing opportunities for endosomal escape.
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Proteínas de Transporte/antagonistas & inibidores , Endossomos/química , Lipídeos/química , Glicoproteínas de Membrana/antagonistas & inibidores , Nanopartículas/química , Proteínas/antagonistas & inibidores , RNA Interferente Pequeno/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Linhagem Celular Tumoral , Sinergismo Farmacológico , Inativação Gênica , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Células NIH 3T3 , Proteína C1 de Niemann-Pick , Células RAW 264.7RESUMO
Chronic post-surgical pain (CPSP) is a normal and significant symptom in clinical surgery, such as breast operation, biliary tract operation, cesarean operation, uterectomy and thoracic operation. Severe chronic post-surgical pain could increase post-surgical complications, including myocardial ischemia, respiratory insufficiency, pneumonia and thromboembolism. However, the underlying mechanism is still unknown. Herein, a rat CPSP model was produced via thoracotomy. After surgery, in an initial study, 5 out of 12 rats after surgery showed a significant decrease in mechanical withdrawal threshold and/or increase in the number of acetone-evoked responses, and therefore classified as the CPSP group. The remaining seven animals were classified as non-CPSP. Subsequently, open-chest operation was performed on another 30 rats and divided into CPSP and non-CPSP groups after 21-day observation. Protein expression levels in the dorsal spinal cord tissue were determined by 12.5 % SDS-PAGE. Finally, differently expressed proteins were identified by LC MS/MS and analyzed by MASCOT software, followed by Gene Ontology cluster analysis using PANTHER software. Compared with the non-CPSP group, 24 proteins were only expressed in the CPSP group and another 23 proteins expressed differentially between CPSP and non-CPSP group. Western blot further confirmed that the expression of glutaminase 1 (GLS1) was significantly higher in the CPSP than in the non-CPSP group. This study provided a new strategy to identify the spinal proteins, which may contribute to the development of chronic pain using differential proteomics, and suggested that GLS1 may serve as a potential biomarker for CPSP.
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Dor Crônica/patologia , Glutaminase/metabolismo , Hiperalgesia/patologia , Medula Espinal/patologia , Toracotomia/efeitos adversos , Animais , Biomarcadores/metabolismo , Dor Crônica/diagnóstico , Temperatura Baixa , Eletroforese em Gel de Poliacrilamida , Masculino , Modelos Animais , Proteômica , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Toracotomia/métodosRESUMO
BACKGROUND The purpose of the study was to analyze the risk factors for failed extubation in subjects submitted to infratentorial craniotomy. MATERIAL AND METHODS Patients aged over 18 years who received infratentorial craniotomy for brain tumor resection were consecutively included in this study. Perioperative variables were collected and analyzed. Univariate analyses and multiple logistic regression were used to derive factors related to failed extubation. Patients had follow-up care until either out of hospital or death. RESULTS Throughout the course of the study, 2118 patients were eligible and 94 (4.4%) suffered from extubation failure at some point during their hospital stay. Five factors were recognized as independent risk factors for postoperative failed extubation: craniotomy history, preoperative lower cranial nerve dysfunction, tumor size, tumor position, and maximum change in blood pressure (BP) during the operation. Failed extubation was related to a higher incidence rate of pneumonia, mortality, unfavorable Glasgow Outcome Scale score, longer stay in the neuro-intensive care unit (ICU) and hospitalization, and higher hospitalization costs compared with successful extubation. CONCLUSIONS History of craniotomy, preoperative lower cranial nerve dysfunction, tumor size, tumor position, and maximum change in BP during the operation were independent risk factors related to postoperative failed extubation in patients submitted to infratentorial craniotomy. Extubation failure raises the incidences of postoperative pneumonia, mortality, and higher hospitalization costs, and prolongs neuro-ICU and postoperative length of stay.
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Extubação/métodos , Craniotomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Extubação/mortalidade , Extubação/estatística & dados numéricos , China/epidemiologia , Craniotomia/efeitos adversos , Craniotomia/mortalidade , Craniotomia/estatística & dados numéricos , Feminino , Humanos , Neoplasias Infratentoriais/epidemiologia , Neoplasias Infratentoriais/cirurgia , Unidades de Terapia Intensiva , Intubação Intratraqueal , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Falha de TratamentoRESUMO
BACKGROUND: The 12-item Short-Form Health Survey (SF-12) is the abridged practical version of SF-36. AIMS: This cross-sectional study was aimed to assess the reliability and validity of SF-12 for the health status of Chinese community elderly population. METHODS: The Chinese community elderly people in Xujiahui district of Shanghai were investigated. The internal consistency reliability was assessed using Cronbach's alpha and split-half reliability coefficients. Construct validity was analyzed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Spearman's correlation coefficient (ρ) was used for the evaluation of criterion, convergent, and discriminant validity with Spearman's ρ ≥ 0.4 as satisfactory. Comparisons of the SF-12 summary scores among populations that differed in demographics were performed for discriminant validity. RESULTS: Total 1343 individuals aged ≥60 and <85 years old (response rate: 91.3 %) were analyzed. The Cronbach's α value (0.910) and the split-half reliability coefficient (0.812) reflected satisfactory internal consistency reliability of SF-12. EFA extracted a two-factor model (physical and mental health). About 60.7 % of the total variance was explained by the two factors. CFA showed that the two-factor solution provided a good fit to the data. Good convergent validity and discriminant validity of SF-12 were proved by the correction analyses (Spearman's ρ > 0.4) and the comparisons of the SF-12 summary scores among populations (P < 0.05). SF-12 summary scores were significantly correlated with the SF-36 summary scores (Spearman's ρ > 0.4, P < 0.05). CONCLUSIONS: In conclusion, SF-12 had satisfactory reliability and validity in measuring health status of Chinese community elderly population in Xujiahui district of Shanghai.
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Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/psicologia , Povo Asiático/estatística & dados numéricos , China/epidemiologia , Estudos Transversais , Feminino , Avaliação Geriátrica/métodos , Disparidades nos Níveis de Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Exame Físico , Reprodutibilidade dos TestesRESUMO
PURPOSE: Recent studies have shown that pain sensitivity has a significant relationship with clinical pain and may also predict the intensity of pain and analgesic consumption after surgery. However, the correlation between pre-operative pain sensitivity and stress response during anesthesia has not been investigated. Therefore, we aimed to explore the relationship between pre-operative pain sensitivity and stress responses during intubation and skin incision in this study. METHODS: Fifty women (ASA I-II) aged 20-55 years, undergoing elective abdominal surgery requiring at least a 10-cm-long skin incision were studied. Pain sensitivity, including pain threshold and pain tolerance was measured before surgery. In this study, experimental pain was induced by potassium ion conducted via continuous current. When patients reported feeling pain or acted to stop pain, the intensity of the current was recorded to register pain threshold and pain tolerance. The State-Trait Anxiety Inventory (STAI) was used to examine the pre-operative mental status. General anesthesia was induced with intravenous fentanyl and a target-controlled infusion of propofol. Blood samples for norepinephrine (NE) detection were collected at 10 min after entering the operating theater, immediately before intubation, 2 min after intubation, immediately before skin incision and 2 min after incision. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded at the same time. Pearson's correlation test (SPSS 13.0) was then used to analyze the relationship between pain sensitivity and the changes in MAP, HR and NE level. RESULTS: A total of fifty women were enrolled in the study. Their pre-operative pain threshold and pain tolerance were 0.90 ± 0.40 mA and 2.53 ± 0.77 mA,respectively. Changes in MAP, HR and NE before and after intubation or skin incision were significantly related with pre-operative pain tolerance (P < 0.05); however, pain threshold was not correlated with changes in MAP, HR and NE (P > 0.05). The STAI score did not correlate with the stress response either (P > 0.05). CONCLUSIONS: Pain tolerance had a significant relationship with stress response during intubation and skin incision. We may initially use pain tolerance to direct opioid usage in the future.
Assuntos
Abdome/cirurgia , Anestesia Geral/métodos , Intubação Intratraqueal/efeitos adversos , Limiar da Dor/fisiologia , Adulto , Feminino , Fentanila/administração & dosagem , Frequência Cardíaca/fisiologia , Humanos , Pessoa de Meia-Idade , Norepinefrina/administração & dosagem , Propofol/administração & dosagem , Adulto JovemRESUMO
Glucuronidation reaction of trifluoperazine (TFP) is a typical probe reaction to phenotype the activity of UDP-glucuronosyltransferase 1A4. The present study aims to compare the metabolic behavior of TFP in the liver microsomes from human and cynomolgus monkey, including the kinetic type and parameters. In vitro human liver microsome incubation system was used. The Eadie-Hofstee plot was used to determine the kinetic type. The results showed that the data for human liver microsomes (HLMs) and monkey liver microsomes (MyLMs)-catalyzed glucuronidation were best fit to the substrate inhibition model. For the metabolism of TFP in HLMs, the kinetic parameters were calculated to be 40 ± 5 and 140 ± 20 µM for K m and K si values, respectively. For the MyLM-mediated metabolism of TFP, the K m and K si values were calculated to be 108 ± 10 and 250 ± 30 µM, respectively. The same metabolic kinetic type and different kinetic parameters were demonstrated for the metabolism of TFP between HLMs and MyLMs. All these data were helpful for understanding the metabolism difference of TFP between human and monkey.