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1.
Hematology ; 26(1): 295-300, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33648437

RESUMO

OBJECTIVE: To investigate the impact of minimal residual disease (MRD) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of acute leukemia. METHODS: Data from 114 patients who were diagnosed with acute leukemia (AL) and underwent allo-HSCT between Jan 2013 and Dec 2019 were collected and analyzed. The patients were attributed into MRD positive (MRD+) group and MRD negative (MRD-) group. RESULTS: Among the 114 acute leukemia patients, there were 32 MRD+ patients before transplantation, and 82 MRD- patients. No significant difference was found between the MRD+ group and the MRD- group in the incidence of acute graft-versus-host disease (aGvHD) (p = 0.09). Compared with the MRD+ group, the MRD- group had a higher incidence of chronic graft-versus-host disease (cGvHD) (p = 0.008). There is no significance in relapse between the two groups (p = 0.084), while the incidence of relapse was seemingly higher in the MRD+ group: 36.9% Vs 19.7% . We attributed to the lack of sample size and NRM in MRD+ group was remarkably higher. The MRD+ group had significantly worse one-year overall survival (OS) ( , p = 0.003) and one-year progression-free survival (PFS) (, p = 0.009). In the multivariate analysis, MRD+ was an independent prognostic factor for OS (HR = 1.898; 95%CI 1.042-3.457; p = 0.036). CONCLUSION: Pre-transplantation MRD positive status is a risk factor for survival and prognosis after HSCT. Upon this, emphasis should be put on (1) screening more efficient chemo regimen with targeted agents, to help patients reach and keep MRD- status before transplantation; (2) designing better management with different GvHD prophylaxis treatment, timely disease monitoring and preemptive intervention on relapse.

2.
Genetics ; 217(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33724406

RESUMO

Dollo's law posits that evolutionary losses are irreversible, thereby narrowing the potential paths of evolutionary change. While phenotypic reversals to ancestral states have been observed, little is known about their underlying genetic causes. The genomes of budding yeasts have been shaped by extensive reductive evolution, such as reduced genome sizes and the losses of metabolic capabilities. However, the extent and mechanisms of trait reacquisition after gene loss in yeasts have not been thoroughly studied. Here, through phylogenomic analyses, we reconstructed the evolutionary history of the yeast galactose utilization pathway and observed widespread and repeated losses of the ability to utilize galactose, which occurred concurrently with the losses of GALactose (GAL) utilization genes. Unexpectedly, we detected multiple galactose-utilizing lineages that were deeply embedded within clades that underwent ancient losses of galactose utilization. We show that at least two, and possibly three, lineages reacquired the GAL pathway via yeast-to-yeast horizontal gene transfer. Our results show how trait reacquisition can occur tens of millions of years after an initial loss via horizontal gene transfer from distant relatives. These findings demonstrate that the losses of complex traits and even whole pathways are not always evolutionary dead-ends, highlighting how reversals to ancestral states can occur.

3.
Enzyme Microb Technol ; 144: 109741, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33541576

RESUMO

The cholinesterase-based spectrophotometric methods for detection of organophosphate pesticides (OPs) and carbamate pesticides (CPs) have been proposed as a good choice for their high efficiency, simplicity and low cost. The enzyme, as a core reagent, is of great importance for the developed method. In this study, a protein disulfide isomerase (PDI) co-expression strategy in Pichia pastoris was employed to enhance the yield of recombinant Bombyx mori acetylcholinesterase 2 (rBmAChE2). Subsequently, the prepared enzyme reagent was used to detect the pesticides in real samples. The results showed that the co-expression of rBmAChE2 with PDI increased the enzyme activity of the supernatant and the yield of purified rBmAChE2 up to 60 U/mL and 6 mg/L respectively, both almost 5-fold higher than those of original recombinant strain. In addition, 5 g/L gelatin reagent could help to preserve nearly 90% of the rBmAChE2 activity for 90 days in 4°C and the limits of detections (LODs) of the rBmAChE2-based assay for 20 kinds of OPs or CPs ranged from 0.010 to 2.725 mg/kg, which were lower than most of indexes present in current Chinese National Standard (GB/T 5009.199-2003) or the maximum residue limits (GB 2763-2019). Furthermore, the detection results of 23 vegetable samples were verified by the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method, which indicated that the rBmAChE2-based assay in this work is suitable for pesticide residues rapid detection.

4.
Bioinformatics ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560364

RESUMO

MOTIVATION: Diverse disciplines in biology process and analyze multiple sequence alignments (MSAs) and phylogenetic trees to evaluate their information content, infer evolutionary events and processes, and predict gene function. However, automated processing of MSAs and trees remains a challenge due to the lack of a unified toolkit. To fill this gap, we introduce PhyKIT, a toolkit for the UNIX shell environment with 30 functions that process MSAs and trees, including but not limited to estimation of mutation rate, evaluation of sequence composition biases, calculation of the degree of violation of a molecular clock, and collapsing bipartitions (internal branches) with low support. RESULTS: To demonstrate the utility of PhyKIT, we detail three use cases: (1) summarizing information content in MSAs and phylogenetic trees for diagnosing potential biases in sequence or tree data; (2) evaluating gene-gene covariation of evolutionary rates to identify functional relationships, including novel ones, among genes; and (3) identify lack of resolution events or polytomies in phylogenetic trees, which are suggestive of rapid radiation events or lack of data. We anticipate PhyKIT will be useful for processing, examining, and deriving biological meaning from increasingly large phylogenomic datasets. AVAILABILITY: PhyKIT is freely available on GitHub (https://github.com/JLSteenwyk/PhyKIT), PyPi (https://pypi.org/project/phykit/), and the Anaconda Cloud (https://anaconda.org/JLSteenwyk/phykit) under the MIT license with extensive documentation and user tutorials (https://jlsteenwyk.com/PhyKIT). SUPPLEMENTARY INFORMATION: Supplementary data are available on figshare (doi: 10.6084/m9.figshare.13118600) and are available at Bioinformatics online.

5.
Sci Adv ; 7(4)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33523945

RESUMO

Genetic diversity and phylogenetic diversity reflect the evolutionary potential and history of species, respectively. However, the levels and spatial patterns of genetic and phylogenetic diversity of wildlife at the regional scale have largely remained unclear. Here, we performed meta-analyses of genetic diversity in Chinese terrestrial vertebrates based on three genetic markers and investigated their phylogenetic diversity based on a dated phylogenetic tree of 2461 species. We detected strong positive spatial correlations among mitochondrial DNA-based genetic diversity, phylogenetic diversity, and species richness. Moreover, the terrestrial vertebrates harbored higher genetic and phylogenetic diversity in South China and Southwest China than in other regions. Last, climatic factors (precipitation and temperature) had significant positive effects while altitude and human population density had significant negative impacts on levels of mitochondrial DNA-based genetic diversity in most cases. Our findings will help guide national-level genetic diversity conservation plans and a post-2020 biodiversity conservation framework.

6.
Curr Biol ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33607033

RESUMO

Phylogenomic studies using genome-scale amounts of data have greatly improved understanding of the tree of life. Despite the diversity, ecological significance, and biomedical and industrial importance of fungi, evolutionary relationships among several major lineages remain poorly resolved, especially those near the base of the fungal phylogeny. To examine poorly resolved relationships and assess progress toward a genome-scale phylogeny of the fungal kingdom, we compiled a phylogenomic data matrix of 290 genes from the genomes of 1,644 species that includes representatives from most major fungal lineages. We also compiled 11 data matrices by subsampling genes or taxa from the full data matrix based on filtering criteria previously shown to improve phylogenomic inference. Analyses of these 12 data matrices using concatenation- and coalescent-based approaches yielded a robust phylogeny of the fungal kingdom, in which ∼85% of internal branches were congruent across data matrices and approaches used. We found support for several historically poorly resolved relationships as well as evidence for polytomies likely stemming from episodes of ancient diversification. By examining the relative evolutionary divergence of taxonomic groups of equivalent rank, we found that fungal taxonomy is broadly aligned with both genome sequence divergence and divergence time but also identified lineages where current taxonomic circumscription does not reflect their levels of evolutionary divergence. Our results provide a robust phylogenomic framework to explore the tempo and mode of fungal evolution and offer directions for future fungal phylogenetic and taxonomic studies.

7.
J Mater Chem B ; 9(8): 2042-2053, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33587087

RESUMO

The second near-infrared (NIR-II) window (1000-1350 nm) usually offers further improved light penetration, a higher maximum permissible exposure (MPE), and a lower background signal. Development of NIR-II optical diagnosis and phototherapy technologies is of great significance for precise, efficient tumor therapy. In this work, a new type of Ti-based targeting agent (B-TiO2@SiO2-HA) nanotheranostic system with strong NIR-II absorption was designed and fabricated for the first time. Oxygen vacancies were formed in B-TiO2 and its band gap was narrowed, resulting in nanotheranostic systems with full-spectrum responses to stimulation with light. The experimental results showed that B-TiO2@SiO2-HA not only can enable high NIR-II photothermal conversion and provide excellent reactive oxygen species (ROS) production capacity, but also can enable high-resolution photoacoustic imaging (PAI) under NIR-II laser irradiation. Moreover, HA modification gives the nanotheranostic systems the useful ability to target high-CD44-expression tumor cells and tissues. In vitro and in vivo experiments demonstrated that B-TiO2@SiO2-HA exhibited a targeted photothermal/photodynamic (PTT/PDT) effect that produced tumor-cell ablation and apoptosis under the guidance of real-time NIR-II PA imaging. B-TiO2@SiO2-HA exhibits precise nanotheranostic potential for PAI-guided tumor-targeting phototherapy.

8.
Syst Biol ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616672

RESUMO

Topological conflict or incongruence is widespread in phylogenomic data. Concatenation- and coalescent-based approaches often result in incongruent topologies, but the causes of this conflict can be difficult to characterize. We examined incongruence stemming from conflict between likelihood-based signal (quantified by the difference in gene-wise log likelihood score or ΔGLS) and quartet-based topological signal (quantified by the difference in gene-wise quartet score or ΔGQS) for every gene in three phylogenomic studies in animals, fungi, and plants, which were chosen because their concatenation-based IQ-TREE (T1) and quartet-based ASTRAL (T2) phylogenies are known to produce eight conflicting internal branches (bipartitions). By comparing the types of phylogenetic signal for all genes in these three data matrices, we found that 30% - 36% of genes in each data matrix are inconsistent, that is, each of these genes has higher log likelihood score for T1 versus T2 (i.e., ΔGLS >0) whereas its T1 topology has lower quartet score than its T2 topology (i.e., ΔGQS <0) or vice versa. Comparison of inconsistent and consistent genes using a variety of metrics (e.g., evolutionary rate, gene tree topology, distribution of branch lengths, hidden paralogy, and gene tree discordance) showed that inconsistent genes are more likely to recover neither T1 nor T2 and have higher levels of gene tree discordance than consistent genes. Simulation analyses demonstrate that removal of inconsistent genes from datasets with low levels of incomplete lineage sorting (ILS) and low and medium levels of gene tree estimation error (GTEE) reduced incongruence and increased accuracy. In contrast, removal of inconsistent genes from datasets with medium and high ILS levels and high GTEE levels eliminated or extensively reduced incongruence, but the resulting congruent species phylogenies were not always topologically identical to the true species trees.

9.
Respir Med ; 178: 106328, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33588209

RESUMO

BACKGROUND: The outbreak of COVID-19 has caused ever-increasing attention and public panic all over the world. Until now, data are limited about the risk factors to virus shedding in COVID-19 infected patients. METHODS: In this retrospective study, data were collected from 87 patients hospitalized with COVID-19 infection in Suzhou. Using Cox proportional hazards regression and Kaplan-Meier survival analysis, the risk factors to COVID-19 RNA shedding was to be established according to demographic information, clinical characteristics, epidemiological history, antiviral medicine and corticosteroid administration. RESULTS: The median duration of COVID-19 RNA shedding from admission was 13.11 ± 0.76 days. There was no significant difference in viral shedding duration in terms of gender, age, history of Hubei province stay, characteristics of chest CT on admission, lymphocytopenia and clinical severity. By Cox proportional hazards model, excessive 200 mg cumulative corticosteroid (HR, 3.425 [95% CI, 1.339-7.143]), time from illness onset to hospitalization (<5 days) (HR, 2.503 [95% CI, 1.433-4.371]) and arbidol-included therapy (HR, 2.073 [95% CI, 1.185-3.626]) were the independent risk factors to delay COVID-19 RNA shedding. Besides of excessive 200 mg of cumulative corticosteroid (HR, 2.825 [95% CI, 1.201-6.649]), admission within 5 days from illness onset (HR, 2.493 [95% CI, 1.393-4.462]) and arbidol-included therapy (HR, 2.102 [95% CI, 1.073-4.120]), lymphocytopenia (HR, 2.153 [95% CI, 1.097-4.225]) was further identified as another unfavorable factor to 10-day viral shedding. CONCLUSIONS: The potential risk factors could help clinicians to identify patients with delayed viral shedding, thereby providing the rational strategy of treatment and optimal anti-viral interventions.


Assuntos
/complicações , /fisiologia , Eliminação de Partículas Virais , Idoso , China , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
10.
Food Chem Toxicol ; 148: 111971, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33421460

RESUMO

The present study presented the extraction and purification of polysaccharides from artificially cultured Cordyceps cicadae and wild Cordyceps cicadae by pre-soaking ultrasonic water extraction. The effects of different concentrations of polysaccharides on proliferation and cytotoxicity of Hela cells were detected by MTT and LDH methods. The results showed that the proliferation of Hela cells was inhibited by polysaccharides treatment (25 µg/mL-1600 µg/mL). The results of flow cytometry further confirmed that polysaccharides blocked the cell cycle in the S phase and promoted apoptosis. RT-qPCR and Western Blot were used to study the mRNA and protein expression of genes related to cell cycle and apoptosis signaling pathway. The results showed that polysaccharides treatment inhibited the expression of Cyclin E, Cyclin A and CDK2 and up regulated the expression of P53. Further, activation of Caspase cascade reaction, up regulation of death receptor, and the ratio of pro-apoptotic factor/anti-apoptotic factors, thus caused the cell cycle arrest and induced the apoptosis. The above research results lay a foundation for extending the anti-cancer effects of natural plant resources with low toxicity and high efficiency.

11.
Gene ; 777: 145450, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33516793

RESUMO

The Bombyx mori Shadow gene (BmShadow) belongs to the superfamily of cytochrome P450 genes. To elucidate the function of the BmShadow gene and its association with diapause, we employed the CRISPR/Cas9 system to knock out the BmShadow gene in the bivoltine strain Qiufeng. The mutant (BmShadow-/-) was obtained in G2, exhibiting a 42-base deletion corresponded exactly to the amino acids regions from positions 155 to 168. The larvae of BmShadow-/- cannot moult at the pre-moulting stage of the 2nd instar. When the BmShadow-/- larvae were fed with 20E analogue at the late stage of the 2nd instar, they were rescued and developed into the 3rd instar. Rescue experiments indicated that the 20E concentration of BmShadow-/- larvae was significantly lower than that in WT larvae, and the 20E concentration of BmShadow-/- larvae which fed 20E analogue was restored to normal levels. Interestingly, the BmShadow-/- larvae could not moult on the 1st instar when they hatched from eggs after being stored at 5 °C for 40 days or after hibernation, suggesting that the 20E transported from the mother was partially consumed in the diapause maintenance phase. Our study confirmed that BmShadow is involved in 20E synthesis and a 14-amino acids region from position 155 to 168 was essential for its function, also there appears to be no other compensation pathway in vivo, which offered an important potential target locus for the control of silkworm development and the biological control of agricultural and forestry pests.


Assuntos
Bombyx/genética , Sistema Enzimático do Citocromo P-450/genética , Muda/genética , Aminoácidos/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Ecdisterona/genética , Ecdisterona/metabolismo , Proteínas de Insetos/genética , Larva/genética
12.
J Mater Chem B ; 9(4): 1089-1095, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33427258

RESUMO

Near-infrared fluorophores are emerging as promising molecular tools for cancer theranostics because of their inherent biodegradability, low toxicity, and synthetic flexibility. However, they still suffer from several limitations, such as poor photostability and insufficient organelle-targeting stability during photothermal therapy. In this work, we introduce an "aldehyde functionalization" strategy for simultaneously enhancing photostability and mitochondria-immobilization of near-infrared fluorophores for the first time. Based on the proposed strategy, representative near-infrared organic molecules, namely AF-Cy, were rationally designed and synthesized. Upon aldehyde modification, the AF-Cy dyes displayed both remarkable photostability and mitochondrial-targeting stability. The strong absorption in the near-infrared region confers the AF-Cy dyes with outstanding fluorescent/photoacoustic imaging and photothermal therapy capabilities. Finally, in vitro and in vivo studies revealed the enhanced performance in inhibiting the growth of breast tumors under NIR laser radiation, and these results suggested the strong potential of AF-Cy dyes as efficient multimodal imaging-guided photothermal therapy agents, further highlighting the value of this simple strategy in the design high performance near-infrared fluorophores for tumor theranostics.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Corantes Fluorescentes/farmacologia , Mitocôndrias/efeitos dos fármacos , Imagem Multimodal , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Raios Infravermelhos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos , Tamanho da Partícula , Processos Fotoquímicos , Propriedades de Superfície
13.
ChemMedChem ; 16(6): 919-931, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33345434

RESUMO

Phototherapy, a type of photoresponsive regulation of biological activities, together with additional stimuli-responsive features, offers significant potential for enhancing the precision and efficacy of cancer treatments. To achieve tumor-specific therapeutics, numerous studies have focused on the development of smart phototherapeutic nanomaterials (PNMs) that can respond to endogenous pathological characteristics (e. g., mild acidity, the overproduction of glutathione, the overproduction of hydrogen peroxide, the overexpression of specific surface receptors, etc.) present in the tumor and/or exogenous stimuli. Such responsiveness can effectively improve the physicochemical properties, cellular uptake, tumor-targeting performance, and pharmacokinetic profile of PNMs. Herein, we will systematically discuss recent advances in this field. Moreover, potential challenges and future directions in the development of stimuli-responsive PNMs are also presented to support the development of this emerging cutting-edge research area.

14.
Langmuir ; 37(1): 569-577, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33356328

RESUMO

The integration of surface-enhanced Raman spectrum (SERS) and fluorescence-photoacoustic multimodal imaging in near-infrared photothermal therapy is highly desirable for cancer theranostic. However, typically, gold nanotheranostics usually require an additional modification of fluorophores and complex design refinements. In this work, by integrating surface-modified cysteine-hydroxyl merocyanine (CyHMC) molecules onto AuNRs, a novel lysosome-targeted gold-based nanotheranostics AuNRs-CyHMC that combines the specificity of Raman spectrum, the speed of fluorescence imaging, and deep penetration of photoacoustic imaging was successfully fabricated. Interestingly, fluorescence and Raman signals in this AuNRs-CyHMC system do not interfere, but it has pH-sensitive Raman signals and self-fluorescence localization ability under different excitation wavelengths. Fluorescence co-localization experiments further confirmed the lysosome-targeting ability of AuNRs-CyHMC. Typically, the proposed nanotheranostics were capable of SERS monitoring pH changes in both phosphate-buffered saline and living cells. Meanwhile, in vitro and in vivo experiments revealed that AuNRs-CyHMC possessed excellent fluorescence-photoacoustic performance and could be used for multimodal imaging-guided photothermal therapy. Furthermore, our work implied that gold nanotheranostics can provide great potential for cancer diagnosis and treatment.

15.
Food Chem ; 345: 128607, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33310562

RESUMO

Dexamethasone (DEX) is a synthetic long-acting glucocorticoid, which can increase the risk of hypertension and diabetes if it is abused or used improperly. In this study, lateral flow immunoassays (LFIA) based on black and blue latex microspheres (LMs), integrated with a strip reader, was developed for quantitative detection of DEX in milk and pork. The results could be achieved within 15 min. The visible limits of detection (vLODs) were 0.3 ng/mL and 0.7 µg/kg for milk and pork, respectively. The quantitative limits of detection (qLODs) were 0.047 ng/mL and 0.087 µg/kg, respectively. The recoveries ranged from 80.0% to 122.8%. 20 milk and 10 pork samples were analyzed to confirm the performance of the on-site application. The detection results were consistent with the data from LC-MS/MS, indicating the practical reliability of our established assay. The developed LMs-LFIA provides a promising technical support for rapid, sensitive, and on-site detection of DEX.


Assuntos
Cromatografia de Afinidade/métodos , Dexametasona/análise , Contaminação de Alimentos/análise , Látex/química , Microesferas , Leite/química , Carne de Porco/análise , Animais , Cromatografia Líquida , Limite de Detecção , Reprodutibilidade dos Testes , Suínos
16.
PLoS Biol ; 18(12): e3001007, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33264284

RESUMO

Highly divergent sites in multiple sequence alignments (MSAs), which can stem from erroneous inference of homology and saturation of substitutions, are thought to negatively impact phylogenetic inference. Thus, several different trimming strategies have been developed for identifying and removing these sites prior to phylogenetic inference. However, a recent study reported that doing so can worsen inference, underscoring the need for alternative alignment trimming strategies. Here, we introduce ClipKIT, an alignment trimming software that, rather than identifying and removing putatively phylogenetically uninformative sites, instead aims to identify and retain parsimony-informative sites, which are known to be phylogenetically informative. To test the efficacy of ClipKIT, we examined the accuracy and support of phylogenies inferred from 14 different alignment trimming strategies, including those implemented in ClipKIT, across nearly 140,000 alignments from a broad sampling of evolutionary histories. Phylogenies inferred from ClipKIT-trimmed alignments are accurate, robust, and time saving. Furthermore, ClipKIT consistently outperformed other trimming methods across diverse datasets, suggesting that strategies based on identifying and retaining parsimony-informative sites provide a robust framework for alignment trimming.

17.
Nat Commun ; 11(1): 6096, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33257660

RESUMO

Phylogenetic trees are essential for studying biology, but their reproducibility under identical parameter settings remains unexplored. Here, we find that 3515 (18.11%) IQ-TREE-inferred and 1813 (9.34%) RAxML-NG-inferred maximum likelihood (ML) gene trees are topologically irreproducible when executing two replicates (Run1 and Run2) for each of 19,414 gene alignments in 15 animal, plant, and fungal phylogenomic datasets. Notably, coalescent-based ASTRAL species phylogenies inferred from Run1 and Run2 sets of individual gene trees are topologically irreproducible for 9/15 phylogenomic datasets, whereas concatenation-based phylogenies inferred twice from the same supermatrix are reproducible. Our simulations further show that irreproducible phylogenies are more likely to be incorrect than reproducible phylogenies. These results suggest that a considerable fraction of single-gene ML trees may be irreproducible. Increasing reproducibility in ML inference will benefit from providing analyses' log files, which contain typically reported parameters (e.g., program, substitution model, number of tree searches) but also typically unreported ones (e.g., random starting seed number, number of threads, processor type).

18.
BMC Fam Pract ; 21(1): 246, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33250045

RESUMO

BACKGROUND: General practitioners (GPs) are the foundation of any primary healthcare system. Their quality and quantity are directly associated with the effectiveness and quality of the health services of a nation. GPs' shortage and turnover have become an important issue in developed and developing countries. An accurate estimate of turnover intention prevalence among GPs would have important health policy implications, but the overall prevalence is unknown. We aimed to summarize the global prevalence of turnover intention and associated factors among GPs. METHODS: We systematically reviewed the PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) databases from their inception up to May 2020, as well as the reference lists of all included studies. We included observational studies that reported data on turnover intention or their prevalence rate among GPs could be calculated based on the information provided. The prevalence rate of the turnover intentions was estimated using a random-effects meta-analysis. The heterogeneity was evaluated using I2 statistic. Differences by study level characteristics were estimated via subgroup analysis and meta-regression. RESULTS: A total of 25 cross-sectional studies were included (a total of 27,285 participants). The prevalence of turnover intention was 0.47 (95% CI: 0.39-0.55). Those having a lower level of salary (OR = 1.38, 95% CI: 1.13-1.63) and job satisfaction (OR = 1.35, 95% CI: 1.12-1.70) or having lower level of morale (OR = 2.68, 95% CI: 1.56-3.80) had a higher intention. In contrast, GPs with a lower level of professional title had a lower turnover intention (OR = 0.81, 95% CI: 0.65-0.98). CONCLUSIONS: In this systematic review, approximately half of the GPs had the intention to leave their current posts worldwide. The factors associated with turnover intention were higher professional title, lower income level, lower job satisfaction and lower morale.

20.
Biomater Sci ; 8(23): 6515-6525, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33141134

RESUMO

Second near-infrared (NIR-II) window responsive phototheranostic agents have a precise spatiotemporal potential for the diagnosis and treatment of cancer. In this study, a full-spectrum responsive ZrO2-based phototheranostic agent was found to achieve NIR-II photoacoustic (PA) imaging-guided tumour-targeting phototherapy. Initially, the ZrO2-based phototheranostic agent was fabricated through NaBH4 reduction to form boron-doped oxygen-deficient zirconia (ZrO2-x-B), an amino-functionalised SiO2 shell and a further covalent connection with hyaluronic acid (HA), namely, ZrO2-x-B@SiO2-HA. In the ZrO2-x-B@SiO2-HA system, the oxygen vacancy and boron doping resulted in full-spectrum absorption, enabling a high NIR-II photothermal conversion, high-resolution PA imaging ability and a remarkable production of reactive oxygen species (ROS). The surface modification of HA provided ZrO2-x-B@SiO2-HA with water dispersibility and a targeting capability for CD44 overexpressed cancer cells. Furthermore, in vitro and in vivo experiments showed that NIR-II activated ZrO2-x-B@SiO2-HA had a targeted photothermal/photodynamic effect for cancer elimination under the real-time guidance of NIR-II PAs. Hence, ZrO2-x-B@SiO2-HA displays a precise NIR-II radiation-activated phototheranostic potential for PA imaging-guided cancer-targeting photothermal/photodynamic therapy.

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