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1.
Phytopathology ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38170687

RESUMO

After the manuscript was accepted, inconsistencies in the analyses were detected. These inconsistencies affected the general conclusion of the manuscript. This article was retracted on 27 March 2024.Exserohilum turcicum is a devastating fungal pathogen that infects both maize and sorghum, leading to severe leaf diseases of the two crops. According to host specificity, pathogenic isolates of E. turcicum are divided into two formae speciales, namely E. turcicum f. sp. zeae and E. turcicum f. sp. sorghi. To date, the molecular mechanism underlying the host specificity of E. turcicum is marginally known. In this study, the whole genomes of 60 E. turcicum isolates collected from both maize and sorghum were resequenced, which enabled identification of 147,847 high-quality SNPs in total. Based on the SNPs, all isolates were clustered into four genetic groups that had a close relationship with host source. This observation was validated by the result of principal component analysis. The analysis of population structure revealed that there was obvious genetic differentiation between maize and sorghum host populations. Further analysis showed that 5,431 SNPs, including 612 nonsynonymous SNPs, were completely co-segregated with host source. These nonsynonymous SNPs were located in 539 genes in which 18 genes were predicted to encode secretory proteins, including six putative effector genes. The sequence polymorphism analysis of the six effector genes in 60 isolates indicated that these genes were perfectly co-segregated with host source. All SNVs in the coding regions of these genes were non-synonymous substitutions, suggesting that these genes were subject to strong positive selection pressure. These findings provide new insights into the molecular basis of host specificity in E. turcicum.

2.
J Stroke Cerebrovasc Dis ; 33(1): 107491, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37988833

RESUMO

BACKGROUND: The use of stents to treat un-ruptured intracranial aneurysms was first approved in the year 2002 in the United States as a Humanitarian Device Exemption. Antiplatelet therapy is mandatory following stent placement. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been the first line agents for the prevention of thromboembolic events following neuro-endovascular procedures. However, clopidogrel hypo-responsiveness has often been observed. In this analysis, we aimed to systematically compare one year clinical outcome of DAPT with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm. METHODS: Online electronic databases were searched from June 2023 till July 2023 for relevant studies which compared DAPT with ticagrelor or clopidogrel for endovascular intervention in patients with intracranial aneurysm. The endpoints which were analyzed were classified into thromboembolic and hemorrhagic events. A fixed and a random effect statistical model were used during data analysis respectively. Risk ratio (RR) with 95 % confidence interval (CI) was used to represent the data following analysis. RESULTS: Five studies with a total number of 893 participants were included in this analysis. Three hundred and fifty eight (358) participants were assigned to the ticagrelor group whereas 535 participants were assigned to clopidogrel group. Participants' enrollment period ranged from the year 2009 to 2019. Our results showed that during a mean follow-up time period of one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events with RR: 0.33, 95 % CI: 0.16 - 0.68; P = 0.003. In addition, at one year, DAPT with ticagrelor was not associated with any increase in hemorrhagic events (RR: 0.66, 95 % CI: 0.29 - 1.50; P = 0.32) when compared to DAPT with clopidogrel. CONCLUSION: At one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events without any increase in hemorrhagic events when compared to clopidogrel associated DAPT for endovascular intervention of patients with intracranial aneurysm. However, even though ticagrelor-associated DAPT use appeared to be more effective and safe, this hypothesis should only be confirmed in larger upcoming trials.


Assuntos
Aspirina , Aneurisma Intracraniano , Humanos , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Ticagrelor/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Terapia Antiplaquetária Dupla/efeitos adversos , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/tratamento farmacológico , Hemorragia , Resultado do Tratamento
3.
BMC Genomics ; 24(1): 136, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36944913

RESUMO

BACKGROUND: Repetitive DNA sequences accounts for over 80% of maize genome. Although simple sequence repeats (SSRs) account for only 0.03% of the genome, they have been widely used in maize genetic research and breeding as highly informative codominant DNA markers. The genome-wide distribution and polymorphism of SSRs are not well studied due to the lack of high-quality genome DNA sequence data. RESULTS: In this study, using data from high-quality de novo-sequenced maize genomes of five representative maize inbred lines, we revealed that SSRs were more densely present in telomeric region than centromeric region, and were more abundant in genic sequences than intergenic sequences. On genic sequences, tri- and hexanucleotide motifs were more abundant in CDS sequence and some mono- and dinucleotide motifs were more abundant in UTR sequences. Median length and chromosomal density of SSRs were both narrowly range-bound, with median length of 14-18 bp and genome-wide average density of 3355.77 bp/Mbp. LTR-RTs of < 0.4 Mya had higher SSR density (4498-4992 bp/Mbp). The genome-specific and motif-specific SSR polymorphism were studied. Their potential breeding applications were discussed. CONCLUSIONS: We found that the median length of SSR sequences of different SSR motifs was nearly constant. SSR density in genic regions was much higher than intergenic regions. In addition, SSR density at LTR-RTs of different evolutionary ages varied in a narrow range. The SSRs and their LTR-RT carriers evolved at an equal rate. All these observations indicated that SSR length and density were under control of yet unknown evolutionary forces. The chromosome region-specific and motif-specific SSR polymorphisms we observed supported the notion that SSR polymorphism was invaluable genome resource for developing highly informative genome and gene markers in maize genetic research and molecular breeding.


Assuntos
Genoma de Planta , Zea mays , Zea mays/genética , Melhoramento Vegetal , Genômica , Marcadores Genéticos , Repetições de Microssatélites/genética
4.
Small ; 19(47): e2303952, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37485631

RESUMO

Anode-free lithium (Li) batteries are attractive owing to their high energy density. However, Li loss by forming solid-electrolyte interphase (SEI) during cell activation leads to a ≈25% capacity decrease, and the capacity constantly fades upon cycling due to the side reactions on the copper (Cu) current collector. This paper reports high-initial-efficiency, long-cycle-life, and long-calendar-life anode-free Li batteries by using an organic Li salt monolayer bonded on Cu. The functional salt, namely lithium ((4-carbamoylphenyl)sulfonyl)(fluorosulfonyl)imide, electrochemically decomposes and passivates the Cu surface, which reduces Li sacrifice by SEI formation and suppresses galvanic Li corrosion and Li-electrolyte reactions during cycling. This work records a LiF-rich interphase on Cu and guided Li nucleation and growth. A 93.6% initial Li deposition efficiency is realized in a regular carbonate electrolyte, and the galvanic current is decreased to ≈40 nA cm-2 , merely one-tenth of bare Cu. After cell activation, 95.2% capacity is retained for a Cu|LiNi0.8 Mn0.1 Co0.1 pouch cell with a theoretical capacity of 200 mAh, and the cell is operated over 600 cycles. Calendar aging showed no damage to cell performance.

5.
Plant Dis ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037203

RESUMO

Peanut (Arachis hypogaea) is an important economic and oil crop in China. In September 2022, leaf spots were observed on peanut in Luoyang city, Henan province, China (34°49'N, 112°37'E). The disease occurred on about 30% of the peanut leaves in only one 0.5-acre field. Symptoms appeared primarily as brown spots, that varied in shape, and appeared round, oval or irregular. In addition, some disease patches exhibited a concentric ring pattern. Small pieces (5×5 mm) of five diseased leaves were surface disinfected in 3% NaClO for 2 minutes, rinsed three times in sterile distilled water, dried on sterilized filter paper, and cultured on potato dextrose agar (PDA) at 25°C for 3 days. Five isolates with uniform characteristics were obtained and subcultured by transferring hyphal tips to fresh PDA. The colonies of the isolates were circular and the margins were clean. The colonies showed white coloration, and after 5-7 days of incubation on PDA plates, concentric rings with dark green sporodochia appeared on the surface of the colonies. The conidiophores branched repeatedly. The conidiophore stipes unbranched, hyaline, 10.0 to 23.2×1.5 to 3.3 µm (n=50). The conidia were rod-shaped or long oval and single-celled, measuring 4.6 to 8.6×1.4 to 3.1 µm (n=100). Based on these characteristics, the five isolates were identified as Paramyrothecium foliicola (Lombard et al 2016). Genomic DNA was extracted from the representative isolates LH-1-1 and LH-1-2. The internal transcribed spacer (ITS), RNA polymerase II second largest subunit (RPB2), calmodulin (CmdA), and translation elongation factor 1-alpha (tef1) loci were amplified and sequenced using the following primer pairs: ITS1/ITS4 (White et al. 1990), RPB2-5F2/RPB2-7cR (O'Donnell et al. 2007), CAL-228F/CAL-2Rd (Carbone & Kohn 1999), and EF1-728F/EF2 (O'Donnell et al. 1998), respectively. BLASTn analysis revealed that the sequences of ITS (OR352397.1 and OR417392.1), RPB2 (OR413573.1 and OR420678.1), CmdA (OR413572.1 and OR420677.1), and tef1 (OR413574.1 and OR420679.1) had 99 to 100% (553/558 bp, 721/721 bp, 597/598 bp, and 384/389 bp) similarity to P. foliicola (MN593634.1, MN398038.1, OM801785.1, MK335967.1). A phylogenetic tree based on the Maximum Likelihood method also confirmed that the two isolates converge on the same branch as P. foliicola. Pathogenicity tests were performed using leaves of 60-day-old peanut plants (cv. Zhonghua 8). Briefly, uninfected healthy leaves (non-wounded) were inoculated with 30-µl drops containing a spore suspension (5×105 conidia/ml) of LH-1-2, and peanut leaves inoculated with sterile distilled water served as controls. All treatments were incubated in an incubator at 25℃ and high relative humidity with a 12:12 hour light-dark cycle. After 5-7 days, inoculated leaves showed symptoms similar to those observed in the field, while no symptoms were observed on control leaves. The pathogenicity tests were repeated three times. The fungus was reisolated from the infected leaves and identified as P. foliicola based on morphological and molecular characteristics, thus fulfilling Koch's postulates. P. foliicola has previously been reported to cause leaf spot of tomato and mung bean, stem canker of cucumber (Huo et al. 2022; Sun et al.2020; Huo et al. 2021). To our knowledge, this is the first report of P. foliicola causing leaf spot on peanut in the world. Identification of this pathogen will be helpful in monitoring peanut diseases and developing disease control strategies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38105469

RESUMO

BACKGROUND: Medication use in pregnancy is common; however, it is unknown if clinical practice guideline (CPG) prescribing recommendations referred to in Australia at the state, national and international level are consistent. AIMS: This systematic review aimed to: (1) identify sources of CPGs that inform prescribing during pregnancy in Australia; (2) assess CPG quality; and (3) evaluate variation within CPG recommendations for medication use in three common conditions in pregnancy: prophylactic antibiotics following premature rupture of membranes (PROM) at term, antidepressants in pregnancy and metformin in gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A literature search was conducted across PubMed, Scopus and EMBASE databases. Grey literature was identified through publicly available Australian policy statements. Prescribing recommendations for prophylactic antibiotics following PROM at term, antidepressants in pregnancy and metformin in GDM, were compared at the state, national and international levels. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS: We identified 39 CPG sources that inform prescribing during pregnancy in Australia. CPG quality varied between resources. There was minor variation in recommendations for antibiotic prophylaxis in PROM at term. Recommendations regarding metformin use in GDM were also variable, with CPGs either recommending its use as a first-line agent when lifestyle modifications are not effective or when insulin therapy is not practicable. Recommendations for antidepressant use were consistent across CPGs analysed. CONCLUSION: Multiple CPGs exist to inform prescribing during pregnancy in Australia, with variation present within CPG quality and recommendations. These findings offer insight into potential sources of variation in maternal and neonatal health outcomes.

7.
Neurochem Res ; 47(11): 3261-3271, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35904697

RESUMO

Recently, necroptosis has emerged as one of the important mechanisms of ischemia stroke. Necroptosis can be rapidly activated in endothelial cells to cause vascular damage and neuroinflammation. Panax notoginseng saponins (PNS), an ingredient extracted from the root of Panax notoginseng (Burk.) F.H. Chen, was commonly used for ischemic stroke, while its molecular mechanism and targets have not been fully clarified. Our study aimed to clarify the anti-necroptosis effect of PNS by regulating RIP1-RIP3-MLKL signaling pathway in brain microvascular endothelial cells (BMECs) subjected to transient oxygen-glucose deprivation (OGD/resupply [R]). In vitro, the necroptosis model of rat BMECs was established by testing the effect of OGD/R in the presence of the pan-caspase inhibitor z-VAD-FMK. After administration of PNS and Nec-1, cell viability, cell death modality, the expression of RIP1-RIP3-MLKL pathway and mitochondrial membrane potential (Δψm) level were investigated in BMECs upon OGD/R injury. The results showed that PNS significantly enhanced cell viability of BMECs determined by CCK-8 analysis, and protected BMECs from necroptosis by Flow cytometry and TEM. In addition, PNS inhibited the phosphorylation of RIP1, RIP3, MLKL and the downstream expression of PGAM5 and Drp1, while similar results were observed in Nec-1 intervention. We further investigated whether PNS prevented the Δψm depolarization. Our current findings showed that PNS effectively reduced the occurrence of necroptosis in BMECs exposed to OGD/R by inhibition of the RIP1-RIP3-MLK signaling pathway and mitigation of mitochondrial damage. This study provided a novel insight of PNS application in clinics.


Assuntos
Panax notoginseng , Saponinas , Animais , Encéfalo/metabolismo , Caspases/metabolismo , Caspases/farmacologia , Células Endoteliais/metabolismo , Glucose/metabolismo , Necroptose , Oxigênio/metabolismo , Panax notoginseng/química , Proteínas Quinases/metabolismo , Ratos , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Saponinas/farmacologia , Transdução de Sinais
8.
Int J Cancer ; 149(7): 1435-1447, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34019699

RESUMO

Although excess adiposity has been linked with various cancers, association between body composition and some cancers remains unclear, like lung and prostate cancers. We investigated associations of body composition with risk of overall cancer and major site-specific cancers in a prospective cohort of 454 079 cancer-free participants from UK-Biobank. Body composition was measured with bioimpedance analysis. We evaluated hazard ratio (HR) and 95% confidence interval (CI) with multivariate Cox linear and nonlinear models in men and women separately. We identified 27 794 cancers over 7.6 years of follow-up. Multivariable adjusted models including fat-free mass (FFM) and fat mass (FM) showed that FFM was positively associated with overall cancer risk in men and women (HR 1.03, 95% CI 1.01-1.04 and 1.07, 1.04-1.10, respectively); while the association between FM and overall cancer disappeared after adjusting for FFM. FFM was associated with higher risks of obesity-related cancers combined, stomach (women only), malignant melanoma, postmenopausal breast, corpus uteri, prostate, kidney (men only), and blood cancers and lower risk of lung cancer. FM was associated with higher risks of obesity-related cancers combined, esophageal, colon, lung (men only), postmenopausal breast (at the lower end of FM range), and corpus uteri cancers and lower risks of rectal, malignant melanoma (women only), prostate and blood cancers. FFM and FM seemed to have different effects on cancer risk, and the effects varied substantially by cancer type, in both direction and size. Higher FM/FFM ratio was also associated with some cancers risk, and might be a useful predictor of cancer risk.


Assuntos
Adiposidade , Composição Corporal , Índice de Massa Corporal , Neoplasias/classificação , Neoplasias/epidemiologia , Obesidade/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia
9.
J Paediatr Child Health ; 57(7): 1023-1030, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33586839

RESUMO

AIM: Most prescribed medicines during pregnancy are antibiotics, with unknown effects on a fetus and on the infant's acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections. METHODS: Design and participants: The Longitudinal Study of Australian Children birth cohort recruited a nationally-representative sample of 5107 infants in 2004. MEASURES: Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1-6). ANALYSIS: Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. RESULTS: A total of 4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: 'consistently low' (86.2%), 'moderate to low' (5.6%), 'low to moderate' (6.7%) and 'consistently high' (1.4%). Antibiotic use in pregnancy was associated with children following 'consistently high' (adjusted odds ratio 2.04, 95% confidence interval 1.08-3.88, P = 0.03) and 'moderate to low' (adjusted odds ratio 1.78, 95% confidence interval 1.25-2.53, P = 0.001) trajectories. CONCLUSIONS: Antibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for the study of potential mechanisms underlying these associations.


Assuntos
Antibacterianos , Otite , Antibacterianos/efeitos adversos , Austrália/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Gravidez , Fatores de Risco
10.
Heart Surg Forum ; 24(3): E479-E483, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34173751

RESUMO

BACKGROUND: Predictive models can be used to assess the risk of readmission for patients after coronary artery bypass grafting (CABG). However, the majority of the existing prediction models have been developed based on data of western population. Our objective was to develop and validate a risk prediction model for Chinese patients after CABG. METHODS: This study was conducted among 1983 patients who underwent CABG in Wuhan Asian Heart Hospital from January 2017 to October 2019. Pearson's chi-squared and multivariate logistic regression were performed to investigate the risk factors of readmission after CABG. The area under the ROC curve and Hosmer-Lemeshow test were used to validate the discrimination and calibration of the model, respectively. RESULTS: Six risk factors were predictive of readmission: age≥65 years (odds ratio [OR] = 2.19; 95% confidence interval [CI]: 1.11-4.34; P = 0.024),  female (OR = 2.46; 95%CI: 1.26-4.80; P = 0.008), private insurance (OR = 4.23; 95%CI: 1.11-16.11; P = 0.034), diabetes (OR = 2.351; 95%CI: 1.20-4.59; P = 0.012), hypertension (OR = 2.33; 95%CI: 1.16-4.66; P = 0.017), and congenital heart disease (OR = 6.93;95%CI: 2.04-23.52; P = 0.002). The area under the curve c-statistic was 0.876 in the derivation sample and 0.865 in the validation sample. Hosmer-Lemeshow test: P=0.561. CONCLUSION: The risk prediction model in our study can be used to predict the risk of readmission in Chinese patients after CABG.


Assuntos
Ponte de Artéria Coronária , Readmissão do Paciente/tendências , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
11.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6216-6223, 2021 Dec.
Artigo em Zh | MEDLINE | ID: mdl-34951248

RESUMO

This study aims to explore the effect of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Chuanxiong Rhizoma(hereinafter referred to as GNS) on the SIRT1-autophagy pathway of endothelial cell senescence induced by hydrogen peroxide(H_2O_2). To be specific, vascular endothelial cells were classified into the blank control group(control), model group(model), model + DMSO group(DMSO), resveratrol group(RESV), and GNS low-dose(GNS-L), medium-dose(GNS-M), and high-dose(GNS-H) groups. They were treated with H_2O_2 for senescence induction except the control. After intervention of cells in each group with corresponding drugs for 24 h, cell growth status was observed under an inverted microscope, and the formation of autophagosome under the transmission electron microscope. In addition, the changes of microtubule-associated protein 1 light chain 3ß(LC3 B) were detected by immunofluorescence staining. The autophagy flux was tracked with the autophagy double-labeled adenovirus(mRFP-GFP-LC3) fusion protein. Dansylcadaverine(MDC) staining was employed to determine the autophagic vesicles, and Western blot the expression of sirtuin 1(SIRT1), ubiquitin-binding protein p62, and LC3Ⅱ. After H_2O_2 induction, cells demonstrated slow growth, decreased adhesion ability, raised number of SA-ß-gal-stained blue ones, a certain number of autophagosomes with bilayer membrane and secondary lysosomes in the cytoplasm, and slight rise of autophagy flux level. Compared with the model group, GNS groups showed improved morphology, moderate adhesion ability, complete and smooth membrane, decreased SA-ß-gal-stained blue cells, many autophagosomes, autophagic vesicles, and secondary lysosomes in the cytoplasm, increased autophagolysosomes, autophagy flux level, and fluorescence intensity of LC3 B and MDC, up-regulated expression of SIRT1 and LC3Ⅱ, and down-regulated expression of p62, suggesting the improvement of autophagy level. GNS can delay the senescence of vascular endothelial cells. After the intervention, the autophagy flux and related proteins SIRT1, LC3Ⅱand p62 changed significantly, and the autophagy level increased significantly. However, EX527 weakened the effect of Chinese medicine in delaying vascular senescence. GNS may delay the senescence of vascular endothelial cells through the SIRT1 autophagy pathway.


Assuntos
Autofagia , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/efeitos dos fármacos , Panax , Células Cultivadas , Senescência Celular , Peróxido de Hidrogênio , Panax/química , Sirtuína 1/genética
12.
BMC Med Res Methodol ; 20(1): 238, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972373

RESUMO

BACKGROUND: Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities. METHODS: Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years. RESULTS: For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian's agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles. We consider governance, ethical and shared trial oversight, and expectations that trials will adhere to the best practice of the day. CONCLUSIONS: Children and younger adults can access fewer trials than older adults. Integrating trials into mega-cohorts should improve health and well-being by generating faster, larger-scale evidence on a longer and/or broader horizon than previously possible. GenV will explore the limits and details of this approach over the coming years.


Assuntos
Família , Pais , Idoso , Criança , Pré-Escolar , Humanos , Recém-Nascido , Estudos Prospectivos , Estudos Retrospectivos , Vitória
13.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2938-2946, 2020 Jun.
Artigo em Zh | MEDLINE | ID: mdl-32627470

RESUMO

The aim of this paper was to observe the changes of intestinal flora in vascular aging mice, in order to explore the relationship between vascular aging and intestinal flora and the effects of extracts of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma on intestinal flora of vascular aging mice. A model of vascular aging in mice was induced through intrape-ritoneal injection with streptozotocin(STZ) combined with high-fat diet. Biochemical detection was performed on serum cholesterol(CHO), triglyceride(TG), high-density liptein cholesterol(HDL-C), low-density liptein cholesterol(LDL-C) and blood glucose(GLU). HE staining was used to detect mice thoracic aorta morphology, and the expressions of cyclin-dependent kinase inhibitor 2 A(p16) and cyclin-dependent kinase inhibitor 1 A(p21) protein in mice thoracic aorta were detected by Western blot. The 16 S rDNA gene of mice intestinal flora was detected by Illumina MiSeq high-throughput sequencing technology to explore the changes of intestinal flora in each group. The results demonstrated that the GLU level in low-dose and high-dose TCM groups decreased, but with unobvious changes in blood lipid indexes. Metformin could significantly decrease the levels of GLU(P<0.01), CHO and LDL-C in mice(P<0.05). Intravascular injury was not obvious in each drug group, and the expressions of p16 and p21 protein were significantly decreased(P<0.05). The intestinal flora of each group was mainly composed of Firmicutes(F) and Bacteroidetes(B) at the level of the phylum, but the B/F ratio was different from that of the youth group and the blank control group. The B/F ratio of the model group was significantly lower(P<0.01), and compared with the model group, the B/F ratio of the high-dose group and the metformin group was signi-ficantly higher(P<0.05). There were dominant and differential floras in the intestine of each group of mice. The results showed that extracts of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma could improve the intestinal flora structure and create a good intestinal environment by increasing the B/F ratio, which provides a new possible pathway for lowering blood glucose and blood lipids and delaying vascular aging.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Panax , Envelhecimento , Animais , Glucose , Lipídeos , Camundongos
14.
Bull World Health Organ ; 97(7): 486-501B, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31258218

RESUMO

OBJECTIVE: To make a systematic review of risk factors, outcomes and prevalence of extended-spectrum ß-lactamase-associated infection in children and young adults in South-East Asia and the Western Pacific. METHODS: Up to June 2018 we searched online databases for published studies of infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae in individuals aged 0-21 years. We included case-control, cohort, cross-sectional and observational studies reporting patients positive and negative for these organisms. For the meta-analysis we used random-effects modelling of risk factors and outcomes for infection, and meta-regression for analysis of subgroups. We mapped the prevalence of these infections in 20 countries and areas using available surveillance data. FINDINGS: Of 6665 articles scanned, we included 40 studies from 11 countries and areas in the meta-analysis. The pooled studies included 2411 samples testing positive and 2874 negative. A higher risk of infection with extended-spectrum ß-lactamase-producing bacteria was associated with previous hospital care, notably intensive care unit stays (pooled odds ratio, OR: 6.5; 95% confidence interval, CI: 3.04 to 13.73); antibiotic exposure (OR: 4.8; 95% CI: 2.25 to 10.27); and certain co-existing conditions. Empirical antibiotic therapy was protective against infection (OR: 0.29; 95% CI: 0.11 to 0.79). Infected patients had longer hospital stays (26 days; 95% CI: 12.81 to 38.89) and higher risk of death (OR: 3.2; 95% CI: 1.82 to 5.80). The population prevalence of infection was high in these regions and surveillance data for children were scarce. CONCLUSION: Antibiotic stewardship policies to prevent infection and encourage appropriate treatment are needed in South-East Asia and the Western Pacific.


Assuntos
Resistência Microbiana a Medicamentos , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , beta-Lactamases/metabolismo , Sudeste Asiático/epidemiologia , Criança , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/microbiologia , Humanos , Ilhas do Pacífico/epidemiologia , Fatores de Risco
15.
Acta Neurol Scand ; 140(3): 212-218, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31141159

RESUMO

OBJECTIVES: Intravenous glibenclamide (GBC) exerts neuroprotection in both preclinical and preliminary clinical studies. This study explored the safety and potential efficacy of oral GBC in patients with acute hemispheric infarction. MATERIALS & METHODS: During January 2017 and August 2017, adult volunteers were recruited to receive oral GBC treatment, if they presented with an acute anterior ischemic stroke and a National Institute of Health Stroke Score of ≥8. Controls were those who met the above inclusion criteria and had not been on GBC or other sulfonylureas prior to stroke or after hospitalization. Propensity score matching (PSM) was performed to balance baseline characteristics. The primary endpoint was the score on the modified Rankin Scale (mRS) at 6 months. RESULTS: We included 213 patients in the unmatched cohort (20 in the GBC group and 193 in the control group) and 40 patients (20 in each group) in the matched cohort. In both cohorts, GBC treatment did not increase the risks of early death, hypoglycemia, and early neurological deterioration. Although GBC did not substantially improve 6-month functional outcome that measured in shift analysis of mRS, a slight trend toward less severe disability and death (mRS 5-6) was observed. In the matched cohort, GBC treatment was associated with lighter brain edema, when CED score was used for evaluation. CONCLUSIONS: In this study, oral GBC is safe in treating acute hemispheric infarction and might have potential in preventing brain edema and consequential severe disability and death. An adequately powered and randomized trial is warranted.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Glibureto/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Administração Oral , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Glibureto/administração & dosagem , Glibureto/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/efeitos adversos
16.
Ecotoxicol Environ Saf ; 169: 8-17, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30412897

RESUMO

Silicon can increase salt tolerance, but the underlying mechanism has remained unclear. Here, we investigated the effect of silicon on polyamine metabolism and the role of polyamine accumulation in silicon-mediated salt tolerance in cucumber. Seedlings of cucumber 'JinYou 1' were subjected to salt stress (75 mM NaCl) in the presence or absence of added 0.3 mM silicon. Plant growth, polyamine metabolism and effects of exogenous polyamines and polyamine synthesis inhibitor dicyclohexylammonium sulphate on oxidative damage were investigated. The results showed that salt stress inhibited plant growth and decreased leaf chlorophyll levels and the maximum quantum yield of PSII, and added silicon ameliorated these negative effects. Salt stress increased polyamine accumulation in the leaves and roots. Compared with salt stress alone, overall, silicon addition decreased free putrescine concentrations, but increased spermidine and spermine concentrations in both leaves and roots under salt stress. Silicon application resulted in increased polyamine levels under salt stress by promoting the activities of S-adenosylmethionine decarboxylase and arginine decarboxylase while inhibiting the activity of diamine oxidase. Exogenous application of spermidine and spermine alleviated salt-stress-induced oxidative damage, whereas polyamine synthesis inhibitor eliminated the silicon-mediated decrease in oxidative damage. The results suggest that silicon-enhanced polyamine accumulation in cucumber under salt stress may play a role in decreasing oxidative damage and therefore increase the salt tolerance.


Assuntos
Cucumis sativus/efeitos dos fármacos , Poliaminas/metabolismo , Plantas Tolerantes a Sal/efeitos dos fármacos , Silício/farmacologia , Clorofila/metabolismo , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Putrescina/metabolismo , Tolerância ao Sal , Plantas Tolerantes a Sal/crescimento & desenvolvimento , Plantas Tolerantes a Sal/metabolismo , Espermidina/metabolismo , Espermina/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-29277917

RESUMO

Ericerus pela Chavannes (Hemiptera: Coccoidae) is an economically important scale insect because the second instar males secrete a harvestable wax-like substance. In this study, we report the molecular cloning of a fatty acyl-CoA reductase gene (EpFAR) of E. pela. We predicted a 520-aa protein with the FAR family features from the deduced amino acid sequence. The EpFAR mRNA was expressed in five tested tissues, testis, alimentary canal, fat body, Malpighian tubules, and mostly in cuticle. The EpFAR protein was localized by immunofluorescence only in the wax glands and testis. EpFAR expression in High Five insect cells documented the recombinant EpFAR reduced 26-0:(S) CoA and to its corresponding alcohol. The data illuminate the molecular mechanism for fatty alcohol biosynthesis in a beneficial insect, E. pela.


Assuntos
Aldeído Oxirredutases/genética , Hemípteros/genética , Aldeído Oxirredutases/metabolismo , Sequência de Aminoácidos , Animais , Hemípteros/enzimologia , Masculino , Filogenia , Análise de Sequência de DNA
19.
Plant Cell Rep ; 34(9): 1629-46, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26021845

RESUMO

KEY MESSAGE: Silicon enhances root water uptake in salt-stressed cucumber plants through up-regulating aquaporin gene expression. Osmotic adjustment is a genotype-dependent mechanism for silicon-enhanced water uptake in plants. Silicon can alleviate salt stress in plants. However, the mechanism is still not fully understood, and the possible role of silicon in alleviating salt-induced osmotic stress and the underlying mechanism still remain to be investigated. In this study, the effects of silicon (0.3 mM) on Na accumulation, water uptake, and transport were investigated in two cucumber (Cucumis sativus L.) cultivars ('JinYou 1' and 'JinChun 5') under salt stress (75 mM NaCl). Salt stress inhibited the plant growth and photosynthesis and decreased leaf transpiration and water content, while added silicon ameliorated these negative effects. Silicon addition only slightly decreased the shoot Na levels per dry weight in 'JinYou 1' but not in 'JinChun 5' after 10 days of stress. Silicon addition reduced stress-induced decreases in root hydraulic conductivity and/or leaf-specific conductivity. Expressions of main plasma membrane aquaporin genes in roots were increased by added silicon, and the involvement of aquaporins in water uptake was supported by application of aquaporin inhibitor and restorative. Besides, silicon application decreased the root xylem osmotic potential and increased root soluble sugar levels in 'JinYou 1.' Our results suggest that silicon can improve salt tolerance of cucumber plants through enhancing root water uptake, and silicon-mediated up-regulation of aquaporin gene expression may in part contribute to the increase in water uptake. In addition, osmotic adjustment may be a genotype-dependent mechanism for silicon-enhanced water uptake in plants.


Assuntos
Cucumis sativus/fisiologia , Raízes de Plantas/metabolismo , Tolerância ao Sal/efeitos dos fármacos , Silício/farmacologia , Água/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Transporte Biológico , Biomassa , Carboidratos/análise , Cucumis sativus/efeitos dos fármacos , Cucumis sativus/genética , Cucumis sativus/crescimento & desenvolvimento , Ditiotreitol/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Cloreto de Mercúrio/farmacologia , Osmose/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Estômatos de Plantas/efeitos dos fármacos , Estômatos de Plantas/fisiologia , Transpiração Vegetal/efeitos dos fármacos , Característica Quantitativa Herdável , Tolerância ao Sal/genética , Plântula/efeitos dos fármacos , Plântula/fisiologia , Sódio/metabolismo , Solubilidade , Xilema/efeitos dos fármacos , Xilema/fisiologia
20.
AIDS Care ; 26(5): 633-41, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24116389

RESUMO

Effective health care models to scale up combination antiretroviral therapy (ART) are needed in rural southwestern China. We aimed to evaluate the ART treatment outcomes and their associations with patients' demographic characteristics and pre-treatment clinical features in a scaled-up provincial ART program serving eight heavily HIV-affected prefectures in Yunnan Province. We abstracted information from a computerized database for adults initiating ART between July 2007 and September 2008. Survival functions of mortality and treatment failure were calculated by age group, gender, transmission mode, and baseline CD4 count. Multivariable Cox regression analyses were conducted to find independent associations of various demographic and baseline clinical features with outcome variables. Of the 1967 patients in the mortality analysis, there were 110 deaths, of which 16 were coded as accidents or suicides. Adjusted hazard ratios (AHR) associated with mortality were greater for patients with baseline CD4 counts <100 cells/µl vs. patients with CD4 counts ≥200 cells/µl, for male vs. female, for single vs. married, and for those acquired HIV through injection drug use (IDU) vs. other modes of transmission. Successful treatment was 81.3% at six months after treatment started. Immunologic treatment failure was associated with baseline CD4 counts but not with demographic characteristics. Overall loss to follow-up rate was 2.1%. Collaboration between clinics and community networks are distinctive features of Yunnan's model for scaling up ART across a diverse, poor, and rural population. This study finds that the strategy can succeed even if 40% of the patients have a history of IDU.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/mortalidade , Avaliação das Necessidades , Abuso de Substâncias por Via Intravenosa/mortalidade , Adolescente , Adulto , Contagem de Linfócito CD4 , China/epidemiologia , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , População Rural , Abuso de Substâncias por Via Intravenosa/imunologia , Análise de Sobrevida , Falha de Tratamento
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