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Peptide amphiphiles (PAs) are highly tunable molecules that were recently found to exhibit aggregation-induced emission (AIE) when they self-assemble into nanofibers. Here, we leverage decades of molecular design and self-assembly study of PAs to strategically tune their molecular motion within nanofibers to enhance AIE, making them a highly useful platform for applications such as sensing, bioimaging, or materials property characterization. Since AIE increases when aggregated molecules are rigidly and closely packed, we altered the four most closely packed amino acids nearest to the hydrophobic core by varying the order and composition of glycine, alanine, and valine pairs. Of the six PA designs studied, C16VVAAK2 had the highest quantum yield at 0.17, which is a more than 10-fold increase from other PA designs including the very similar C16AAVVK2, highlighting the importance of precise amino acid placement to anchor rigidity closest to the core. We also altered temperature to increase AIE. C16VVAAK2 exhibited an additional 4-fold increase in maximum fluorescence intensity when the temperature was raised from 5 to 65 °C. As the temperature increased, the secondary structure transitioned from ß-sheet to random coil, indicating that further packing an already aligned molecular system makes it even more readily able to transfer energy between the electron-rich amides. This work both unveils a highly fluorescent AIE PA system design and sheds insights into the molecular orientation and packing design traits that can significantly enhance AIE in self-assembling systems.
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Nanofibras , Nanofibras/química , Fluorescência , Peptídeos/química , Estrutura Secundária de Proteína , AmidasRESUMO
BACKGROUND: Understanding the genetic diversity in endangered species that occur inforest remnants is necessary to establish efficient strategies for the species conservation, restoration and management. Panax vietnamensis Ha et Grushv. is medicinally important, endemic and endangered species of Vietnam. However, genetic diversity and structure of population are unknown due to lack of efficient molecular markers. RESULTS: In this study, we employed Illumina HiSeq™ 4000 sequencing to analyze the transcriptomes of P. vietnamensis (roots, leaves and stems). Raw reads total of 23,741,783 was obtained and then assembled, from which the generated unigenes were 89,271 (average length = 598.3191 nt). The 31,686 unigenes were annotated in different databases i.e. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Nucleotide Collection (NR/NT) and Swiss-Prot for functional annotation. Further, 11,343 EST-SSRs were detected. From 7774 primer pairs, 101 were selected for polymorphism validation, in which; 20 primer pairs were successfully amplified to DNA fragments and significant amounts of polymorphism was observed within population. The nine polymorphic microsatellite loci were used for population structure and diversity analyses. The obtained results revealed high levels of genetic diversity in populations, the average observed and expected heterozygosity were HO = 0.422 and HE = 0.479, respectively. During the Bottleneck analysis using TPM and SMM models (p < 0.01) shows that targeted population is significantly heterozygote deficient. This suggests sign of the bottleneck in all populations. Genetic differentiation between populations was moderate (FST = 0.133) and indicating slightly high level of gene flow (Nm = 1.63). Analysis of molecular variance (AMOVA) showed 63.17% of variation within individuals and 12.45% among populations. Our results shows two genetic clusters related to geographical distances. CONCLUSION: Our study will assist conservators in future conservation management, breeding, production and habitats restoration of the species.
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Etiquetas de Sequências Expressas , Variação Genética , Repetições de Microssatélites , Panax/genética , Espécies em Perigo de Extinção , Perfilação da Expressão Gênica , Fluxo Gênico , Marcadores Genéticos , Genética Populacional , Sequenciamento de Nucleotídeos em Larga Escala , Anotação de Sequência Molecular , VietnãRESUMO
Dengue is the most prevalent arboviral disease of humans. The host and virus variables associated with dengue virus (DENV) transmission from symptomatic dengue cases (n = 208) to Aedes aegypti mosquitoes during 407 independent exposure events was defined. The 50% mosquito infectious dose for each of DENV-1-4 ranged from 6.29 to 7.52 log10 RNA copies/mL of plasma. Increasing day of illness, declining viremia, and rising antibody titers were independently associated with reduced risk of DENV transmission. High early DENV plasma viremia levels in patients were a marker of the duration of human infectiousness, and blood meals containing high concentrations of DENV were positively associated with the prevalence of infectious mosquitoes 14 d after blood feeding. Ambulatory dengue cases had lower viremia levels compared with hospitalized dengue cases but nonetheless at levels predicted to be infectious to mosquitoes. These data define serotype-specific viremia levels that vaccines or drugs must inhibit to prevent DENV transmission.
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Aedes/virologia , Vírus da Dengue/genética , Dengue/epidemiologia , Dengue/transmissão , Dengue/virologia , Insetos Vetores/virologia , Animais , Sequência de Bases , Estudos de Coortes , Vírus da Dengue/classificação , Ensaio de Imunoadsorção Enzimática , Interações Hospedeiro-Patógeno , Humanos , Funções Verossimilhança , Modelos Genéticos , Dados de Sequência Molecular , Filogenia , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Sorotipagem , Vietnã/epidemiologia , Viremia/epidemiologiaRESUMO
BACKGROUND: Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo. METHODS: We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever. RESULTS: The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment. CONCLUSIONS: Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. CLINICAL TRIALS REGISTRATION: NCT01096576.
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Antivirais/administração & dosagem , Dengue/tratamento farmacológico , Nucleosídeos/administração & dosagem , Administração Oral , Adulto , Antígenos Virais/sangue , Antivirais/efeitos adversos , Dengue/patologia , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Método Duplo-Cego , Febre/tratamento farmacológico , Humanos , Masculino , Nucleosídeos/efeitos adversos , Placebos/administração & dosagem , Resultado do Tratamento , Carga Viral , Viremia/tratamento farmacológico , Adulto JovemRESUMO
Cinnamomumparthenoxylon (Jack) Meisn. is a tree in genus Cinnamomum that has been facing global threats due to forest degradation and habitat fragmentation. Many recent studies aim to describe habitats and assess population and species genetic diversity for species conservation by expanding afforestation models for this species. Understanding their current and future potential distribution plays a major role in guiding conservation efforts. Using five modern machine-learning algorithms available on Google Earth Engine helped us evaluate suitable habitats for the species. The results revealed that Random Forest (RF) had the highest accuracy for model comparison, outperforming Support Vector Machine (SVM), Classification and Regression Trees (CART), Gradient Boosting Decision Tree (GBDT) and Maximum Entropy (MaxEnt). The results also showed that the extremely suitable ecological areas for the species are mostly distributed in northern Vietnam, followed by the North Central Coast and the Central Highlands. Elevation, Temperature Annual Range and Mean Diurnal Range were the three most important parameters affecting the potential distribution of C.parthenoxylon. Evaluation of the impact of climate on its distribution under different climate scenarios in the past (Last Glacial Maximum and Mid-Holocene), in the present (Worldclim) and in the future (using four climate change scenarios: ACCESS, MIROC6, EC-Earth3-Veg and MRI-ESM2-0) revealed that of C.parthenoxylon would likely expand to the northeast, while a large area of central Vietnam will gradually lose its adaptive capacity by 2100.
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Cinnamomumparthenoxylon is an endemic and endangered species with significant economic and ecological value in Vietnam. A better understanding of the genetic architecture of the species will be useful when planning management and conservation. We aimed to characterize the transcriptome of C.parthenoxylon, develop novel molecular markers, and assess the genetic variability of the species. First, transcriptome sequencing of five trees (C.parthenoxylon) based on root, leaf, and stem tissues was performed for functional annotation analysis and development of novel molecular markers. The transcriptomes of C.parthenoxylon were analyzed via an Illumina HiSeqTM 4000 sequencing system. A total of 27,363,199 bases were generated for C.parthenoxylon. De novo assembly indicated that a total of 160,435 unigenes were generated (average length = 548.954 bp). The 51,691 unigenes were compared against different databases, i.e. COG, GO, KEGG, KOG, Pfam, Swiss-Prot, and NR for functional annotation. Furthermore, a total of 12,849 EST-SSRs were identified. Of the 134 primer pairs, 54 were randomly selected for testing, with 15 successfully amplified across nine populations of C.parthenoxylon. We uncovered medium levels of genetic diversity (PIC = 0.52, Na = 3.29, Ne = 2.18, P = 94.07%, Ho = 0.56 and He = 0.47) within the studied populations. The molecular variance was 10% among populations and low genetic differentiation (Fst = 0.06) indicated low gene flow (Nm = 2.16). A reduction in the population size of C.parthenoxylon was detected using BOTTLENECK (VP population). The structure analysis suggested two optimal genetic clusters related to gene flow among the populations. Analysis of molecular variance (AMOVA) revealed higher genetic variation within populations (90%) than among populations (10%). The UPGMA approach and DAPC divided the nine populations into three main clusters. Our findings revealed a significant fraction of the transcriptome sequences and these newlydeveloped novel EST-SSR markers are a very efficient tool for germplasm evaluation, genetic diversity and molecular marker-assisted selection in C.parthenoxylon. This study provides comprehensive genetic resources for the breeding and conservation of different varieties of C.parthenoxylon.
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INTRODUCTION: Vietnam aims for 95% of commune health stations (CHSs) to have functional hypertension management programs by 2025. However, limited resources may impede the Central Highland region health system from achieving this goal. We assessed the availability and readiness of hypertension management services at CHSs in the Central Highland region and identified challenges to facilitate evidence-based planning. METHODS: We used a mixed-methods cross-sectional design to assess hypertension management services using WHO's service availability and readiness assessment (SARA) tools in all 579 CHSs in the region, combined with twenty in-depth interviews of hypertension program focal points at communal, district, and provincial levels in all four provinces. We descriptively analyzed quantitative data and thematically analyzed qualitative data. RESULTS: Hypertension management services were available at 65% of CHSs, and the readiness of the services was 62%. The urban areas had higher availability and readiness indices in most domains (basic amenities, basic equipment, and essential medicines) compared to rural areas, except for staff and training. The qualitative results showed a lack of trained staff and ambiguity in national hypertension treatment guidelines, insufficient essential medicines supply mechanism, and low priority and funding limitations for the hypertension program. CONCLUSION: The overall availability and readiness for hypertension diagnosis and management service at CHSs in the Central Highland region were low, reflecting inadequate capacity of the primary healthcare facilities. Some measures to strengthen hypertension programs in the region might include increased financial support, ensuring a sufficient supply of basic medicines, and providing more specific treatment guidelines.
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Medicamentos Essenciais , Hipertensão , Humanos , Vietnã/epidemiologia , Estudos Transversais , Confiabilidade dos Dados , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/terapia , Atenção Primária à SaúdeRESUMO
Cinnamomum balansae Lecomte (Lauraceae), an economically important forest tree, is distributed in the tropical forests of central and northern Vietnam, which has been threatened in recent decades due to the destruction of its habitat and over-exploitation. The genetic diversity and population structure of the species have not been fully evaluated. We used a set of 15 microsatellites to analyze 161 adult trees from 9 different populations, representing the geographical distribution of C. balansae. Ninety-two different alleles were identified. Here our results showed a low genetic diversity level with an average H o = 0.246 and H e = 0.262, and a high level of genetic differentiation (F ST = 0.601). The bottleneck tests indicated evidence of a reduction in the population size of the two populations (TC and CP). Additionally, all three clustering methods (Bayesian analysis, principal coordinate analysis, and Neighbor-joining tree) were identified in the two genetic groups. The Mantel test showed a significant positive correlation between genetic distance and geographic distance (R 2 = 0.7331). This study will provide a platform for the conservation of C. balansae both in ex-situ and in-situ plans.