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1.
J Environ Qual ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708516

RESUMO

The emergence of antibiotic resistance genes (ARGs) as contaminants in soil poses a significant threat to public health. Earthworms (Eisenia foetida), which are common inhabitants of soil, have been extensively studied for their influence on ARGs. However, the specific impact of earthworms on penicillin-related ARGs remains unclear. In this study, we investigate the role of earthworms in mitigating ARGs, specifically penicillin-related ARGs, in ampicillin-contaminated soil. Utilizing high-throughput quantitative PCR (HT-qPCR), we quantified a significant reduction in the relative abundance of penicillin-related ARGs in soil treated with earthworms, showing a decrease with a p-value of <0.01. Furthermore, high-throughput 16S rRNA gene sequencing revealed that earthworm intervention markedly alters the microbial community structure, notably enhancing the prevalence of specific bacterial phyla such as Proteobacteria, Firmicutes, Chloroflexi, and Tenericutes. Our findings not only demonstrate the effectiveness of earthworms in reducing the environmental load of penicillin-related ARGs but also provide insight into the alteration of microbial communities as a potential mechanism. This research contributes to our understanding of the role of earthworms in mitigating the spread of antibiotic resistance and provides valuable insights for the development of strategies to combat this global health issue.

2.
Nat Commun ; 15(1): 2359, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504097

RESUMO

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.


Assuntos
Hipertensão , Proteoma , Humanos , Pressão Sanguínea/genética , Proteoma/genética , Proteoma/metabolismo , Transcriptoma/genética , Multiômica , Hipertensão/metabolismo , Rim/metabolismo , Proteínas de Transporte de Sódio-Glucose/genética , Proteínas de Transporte de Sódio-Glucose/metabolismo
3.
World J Microbiol Biotechnol ; 40(5): 136, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38499730

RESUMO

Photosynthetic diazotrophs expressing iron-only (Fe-only) nitrogenase can be developed into a promising biofertilizer, as it is independent on the molybdenum availability in the soil. However, the expression of Fe-only nitrogenase in diazotrophs is repressed by the fixed nitrogen of the soil, limiting the efficiency of nitrogen fixation in farmland with low ammonium concentrations that are inadequate for sustainable crop growth. Here, we succeeded in constitutively expressing the Fe-only nitrogenase even in the presence of ammonium by controlling the transcription of Fe-only nitrogenase gene cluster (anfHDGK) with the transcriptional activator of Mo nitrogenase (NifA*) in several different ways, indicating that the engineered NifA* strains can be used as promising chassis cells for efficient expression of different types of nitrogenases. When applied as a biofertilizer, the engineered Rhodopseudomonas palustris effectively stimulated rice growth, contributing to the reduced use of chemical fertilizer and the development of sustainable agriculture.


Assuntos
Compostos de Amônio , Oryza , Fixação de Nitrogênio , Nitrogenase/genética , Nitrogenase/metabolismo , Nitrogênio/metabolismo , Solo
4.
Heliyon ; 10(4): e26160, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404869

RESUMO

With the continuous improvement of people 's living standards, people have put forward higher requirements for the safety and comfort of housing. Therefore, Inherent Defect Insurance, a financial method to guarantee the quality of construction projects, has also emerged. At present, China 's Inherent Defect Insurance has been gradually promoted, but its claim mechanism has not been analyzed and studied. From the perspective of construction engineering, this paper first makes a bibliometric analysis of the influencing factors of insurance claims that may be caused by construction engineering quality through VOSViewers, and the evaluation index system of inherent defects is constructed. Then, according to the influencing factors, the PSO-LSSVR model is adopted to fit the performance function of the inherent defects. Finally, based on the reliability design principle of engineering structure, the reliability index and failure probability of Inherent Defect Insurance are derived from the performance function of inherent defects. This paper also analyzes its application in insurance practice and determines the relationship between the number of insurance underwriting policies and the initial reserve of insurance at a certain risk level. This paper studies the probability of Inherent Defect Insurance by constructing the reliability model of inherent defect risks in construction quality, and analyzes the anti-risk ability of insurance companies from the perspective of claim, which provides scientific analysis methods and theoretical basis for the scientific decision-making of insurance companies.

5.
J Chemother ; 36(3): 202-207, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37599456

RESUMO

Because of lacking of head-to-head comparison between venetoclax and IDH1/IDH2 inhibitors (ivosidenib/enasidenib) for newly diagnosed unfit patients with acute myeloid leukemia (AML), the optimal option for these patients still remains undefined. We searched relevant published reports. Three RCTs with 180 IDH1 mutant and 165 IDH2 mutant patients were identified. Indirect comparison of OS using fixed effects network meta-analysis (NMA) models indicated venetoclax plus azacitidine (Ven-Aza) significantly improved survival than enasidenib plus azacitidine (Ena-Aza) (HR:0.30, p = 0.005) for those newly diagnosed patients with AML and IDH2 Mutation. And, for those IDH2 mutation patients, Ven-Aza also had the highest probability of 98.3% (OS analysis) and 84.0% (CR/CRi analysis) to be the best intervention among these first-line treatment regimens (Ven-Aza, Ena-Aza and Aza). And, there was a favorable trend towards Ven-Aza in survival analysis (HR:0.69, p = 0.42), when compared to ivosidenib plus azacitidine (Ivo-Aza) for those newly diagnosed patients with AML and IDH1 Mutation. For those IDH1 Mutation, venetoclax plus azacitidine (Ven-Aza) had the highest probability of 65.8% (OS analysis) and 73.0% (CR/CRi analysis) to be the best intervention among these first-line treatment regimens (Ven-Aza, ivosidenib plus azacitidine (Ivo-Aza) and azacitidine (Aza)). In conclusion, venetoclax plus azacitidine could be a good option for unfit newly diagnosed patients with acute myeloid leukemia and IDH1/2 mutation. Considering our limits (only trial data-based network meta-analysis et al.), future trials directly comparing these regimens are warranted.


Assuntos
Aminopiridinas , Compostos Bicíclicos Heterocíclicos com Pontes , Glicina/análogos & derivados , Leucemia Mieloide Aguda , Piridinas , Sulfonamidas , Triazinas , Humanos , Metanálise em Rede , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Azacitidina/uso terapêutico , Mutação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Isocitrato Desidrogenase/genética
6.
Environ Sci Technol ; 57(41): 15693-15702, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37791801

RESUMO

Metals usually served as the active sites of the heterogeneous bifunctional electro-Fenton reaction, which faced the challenge of poor stability under acidic or even neutral conditions. Exploring a metal-free heterogeneous bifunctional electro-Fenton catalyst can effectively solve the above problems. In this work, a stable metal-free heterogeneous bifunctional boron-modified porous carbon catalyst (BTA-1000) was synthesized. For the BTA-1000 catalyst, the yield of H2O2 (294 mg/L) significantly increased. The degradation rate of phenol by BTA-1000 (0.242 min-1) increased by an order of magnitude, compared with the porous carbon catalyst (0.0105 min-1). The BTA catalyst could rapidly degrade industrial dye wastewater, and its specific energy consumption was 5.52 kW h kg-1 COD-1, lower than that in previous reports (6.38-7.4 kW h kg-1 COD-1). DFT and XPS revealed that C═O and -BC2O groups jointly promoted the generation of H2O2, and the -BCO2 group played dominant roles in the generation of •OH because the oxygen atom near the electron-giving groups (-BCO2 group) facilitated the formation of hydrogen bond and H2O2 adsorption. This work gained deep insights into the reaction mechanism of the boron-modified porous carbon catalyst, which helped to guide the development of metal-free heterogeneous bifunctional electro-Fenton catalysts.


Assuntos
Peróxido de Hidrogênio , Poluentes Químicos da Água , Peróxido de Hidrogênio/química , Poluentes Orgânicos Persistentes , Boro , Oxirredução , Poluentes Químicos da Água/análise , Eletrodos , Carbono , Metais , Catálise
7.
Comput Biol Med ; 164: 107339, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37586207

RESUMO

The treatment of breast cancer can potentially impose a burden on the heart, leading to an increased risk of heart failure. Studies have shown that more than half of breast cancer patients die from non-tumor-related causes, with cardiovascular disease (CVD) being the leading cause of death. However, the underlying mechanism linking breast cancer prognosis and heart failure remains unclear. To investigate this, we conducted an analysis where we compared the differentially expressed genes (DEGs) in early and advanced breast cancer with genes associated with heart failure. This analysis revealed 18 genes that overlapped between the two conditions, with 15 of them being related to immune function. This suggests that immune pathways may play a role in the prognosis of breast cancer patients with heart failure. Using gene expression data from 1260 breast cancer patients, we further examined the impact of these 15 genes on survival time. Additionally, through enrichment analysis, we explored the functions and pathways associated with these genes in relation to breast cancer and heart failure. By constructing a transformer model, we discovered that the expression patterns of these 15 genes can accurately predict the occurrence of heart failure. The model achieved an AUC of 0.86 and an AUPR of 0.91. Moreover, through analysis of single-cell sequencing data from breast cancer patients undergoing PD-1 treatment and experiencing heart failure, we identified a significant number of cell-type-specific genes that were shared between both diseases. This suggests that changes in gene expression in immune cells following breast cancer treatment may be associated with the development of heart failure.


Assuntos
Neoplasias da Mama , Doenças Cardiovasculares , Insuficiência Cardíaca , Humanos , Feminino , Neoplasias da Mama/genética , Mama , Insuficiência Cardíaca/genética , Coração , Microambiente Tumoral/genética
8.
Eur J Haematol ; 110(6): 602-607, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36919283

RESUMO

Because of lacking of head-to-head comparison among recently effective novel agents' combination regimens for newly diagnosed patients with mantle-cell lymphoma (MCL) who are ineligible for intensive therapy like autologous stem-cell transplantation, the optimal option for these patients still remains undefined. We searched relevant published reports. Three randomized controlled trials with 1459 subjects were identified. In the network meta-analysis, ibrutinib plus bendamustine and rituximab (Ibru + BR) significantly improved progression-free survival (PFS) when compared to bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP; hazard ratio [HR]: 0.55, p = .03) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; HR: 0.35, p < .001) for newly diagnosed patients with MCL ineligible for intensive therapy. Among these first-line treatment regimens (Ibru + BR, VR-CAP, R-CHOP, and BR), Ibru + BR had the highest probability of 94.9% to be the best intervention in PFS analysis. No significant difference was found in adverse events analysis. Our data indicated that Ibru + BR seemed to prolong the PFS when compared to VR-CAP and R-CHOP for newly diagnosed patients with MCL ineligible for intensive therapy. Considering our limits, prospective clinical trials directly comparing these regimens are warranted.


Assuntos
Linfoma de Célula do Manto , Adulto , Humanos , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Rituximab , Cloridrato de Bendamustina/uso terapêutico , Prednisona/uso terapêutico , Metanálise em Rede , Estudos Prospectivos , Vincristina/efeitos adversos , Doxorrubicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Ann Hematol ; 102(5): 1011-1017, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36947214

RESUMO

Because of lacking of head-to-head comparison among polatuzumab (Pola) vedotin and other novel agents for untreated diffuse large B-cell lymphoma (DLBCL), the optimal option remains undefined. We searched twelve relevant published reports, covering 8376 subjects. Interestingly, the PFS benefit with Pola-R-CHP over other regimens was found prominently in those B-cell-like type (ABC-type) patients. For those ABC-type patients, the PFS advantage with Pola-R-CHP was statistically significant, when compared to R-CHOP+Bort (HR: 0.52, P=0.02), R-CHOP+Ibru (HR: 0.43, P=0.001), R-CHOP+Lena (HR: 0.51, P=0.009), G-CHOP (HR: 0.46, P=0.008), and R-CHOP (HR: 0.40, P<0.001). Meanwhile, for those germinal center B-cell-like (GCB) type patients, no PFS advantage with Pola-R-CHP was found when compared to R-CHOP+Bort (HR: 1.18, P=0.46), R-CHOP+Lena (HR: 1.21, P=0.45), G-CHOP (HR: 1.39, P=0.14), R-CHOP-14 (HR: 0.94, P=0.82), and R-CHOP (HR: 1.00, P=1). The PFS advantage with Pola-R-CHP over other regimens might be confined to those patients of ABC-type DLBCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Humanos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Metanálise em Rede , Prednisona/efeitos adversos , Rituximab/uso terapêutico , Vincristina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Nat Commun ; 14(1): 668, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750564

RESUMO

Systemic lupus erythematosus is a heritable autoimmune disease that predominantly affects young women. To improve our understanding of genetic etiology, we conduct multi-ancestry and multi-trait meta-analysis of genome-wide association studies, encompassing 12 systemic lupus erythematosus cohorts from 3 different ancestries and 10 genetically correlated autoimmune diseases, and identify 16 novel loci. We also perform transcriptome-wide association studies, computational drug repurposing analysis, and cell type enrichment analysis. We discover putative drug classes, including a histone deacetylase inhibitor that could be repurposed to treat lupus. We also identify multiple cell types enriched with putative target genes, such as non-classical monocytes and B cells, which may be targeted for future therapeutics. Using this newly assembled result, we further construct polygenic risk score models and demonstrate that integrating polygenic risk score with clinical lab biomarkers improves the diagnostic accuracy of systemic lupus erythematosus using the Vanderbilt BioVU and Michigan Genomics Initiative biobanks.


Assuntos
Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Fenótipo , Polimorfismo de Nucleotídeo Único
11.
ACS Nano ; 17(3): 2431-2439, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36656264

RESUMO

Antimony (Sb) has been pursued as a promising anode material for sodium-ion batteries (SIBs). However, it suffers from severe volume expansion during the sodiation-desodiation process. Encapsulating Sb into a carbon matrix can effectively buffer the volume change of Sb. However, the sluggish Na+ diffusion kinetics in traditional carbon shells is still a bottleneck for achieving high-rate performance in Sb/C composite materials. Here we design and synthesize a yolk-shell Sb@Void@graphdiyne (GDY) nanobox (Sb@Void@GDY NB) anode for high-rate and long cycle life SIBs. The intrinsic in-plane cavities in GDY shells offer three-dimensional Na+ transporting channels, enabling fast Na+ diffusion through the GDY shells. Electrochemical kinetics analyses show that the Sb@Void@GDY NBs exhibit faster Na+ transport kinetics than traditional Sb@C NBs. In situ transmission electron microscopy analysis reveals that the hollow structure and the void space between Sb and GDY successfully accommodate the volume change of Sb during cycling, and the plastic GDY shell maintains the structural integrity of NBs. Benefiting from the above structural merits, the Sb@Void@GDY NBs exhibit excellent rate capability and extraordinary cycling stability.

12.
Molecules ; 27(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36144545

RESUMO

The World Health Organization predicts that over the next several years, depression will become the most important mental health issue globally. Growing evidence shows that the flower buds of Hemerocallis citrina Baroni (H. citrina) possess antidepressant properties. In the search for new anti-depression drugs, a total of 15 phenylpropanoids and 22 flavonoids were isolated and identified based on spectral data (1D and 2D NMR, HR-ESI-MS, UV) from H. citrina. Among them, compound 8 was a novel compound, while compounds 1-4, 6, 9, 10, 15, 17, 24-26, 28, and 37 were isolated for the first time from Hemerocallis genus. To study the antidepressant activity of phenylpropanoids and flavonoids fractions from H. citrina, macroporous resin was used to enrich them under the guidance of UV characteristics. UHPLC-MS/MS was applied to identify the constituents of the enriched fractions. According to behavioral tests and biochemical analyses, it showed that phenylpropanoid and flavonoid fractions from H. citrina can improve the depressive-like mental state of chronic unpredictable mild stress (CUMS) rats. This might be accomplished by controlling the amounts of the inflammatory proteins IL-6, IL-1ß, and TNF-α in the hippocampus as well as corticosterone in the serum. Thus, the monomer compounds were tested for their anti-neuroinflammatory activity and their structure-activity relationship was discussed in further detail.


Assuntos
Hemerocallis , Animais , Antidepressivos/farmacologia , Corticosterona , Flavonoides/farmacologia , Hemerocallis/química , Interleucina-6 , Ratos , Estresse Psicológico/metabolismo , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa
13.
Sci Rep ; 12(1): 14620, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-36028556

RESUMO

Maize (Zea mays L.) is one of the most widely distributed and important crops in China. Maize ear differentiation plays an important role grain yield formation. However, it is unclear if ear and root morphophysiology status affects yield formation by altering ear differentiation and development under different nitrogen (N) conditions. The aim of this study is to understand how the ear differentiation and development are affected by ear and root morphophysiology traits, as affected by the N rate. The experiment consisted of two N rates: high nitrogen (180 kg ha-1), and low nitrogen (60 kg ha-1). Two N-efficient varieties (NEVs) and two N-inefficient varieties (NIVs) were grown in the field. The results showed higher nitrogen accumulation and grain yield in NEVs than in NIVs, which was mainly attributed to the increased N uptake by the larger root system under both N conditions. Under high N conditions, among ear differentiation-related traits, only FR was significantly positively correlated with grain yield, and NEVs ensure FR through higher N concentration and ZR content in ear at the fertilization stage. Under low N conditions, NEVs obtained higher FP, SR and FR through higher N concentration and IAA in ear at the early stage of ear differentiation, maintained lower AR and BTL by higher RA, R-ZR and E-ZR at the late stage of ear growth. These results suggest that NEVs have a more complex mechanism for obtaining higher grain yield under low N conditions than N sufficiency, and that phytohormones play an important role in this process.


Assuntos
Nitrogênio , Zea mays , Grão Comestível , Reguladores de Crescimento de Plantas , Estruturas Vegetais
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 282: 121637, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-35907313

RESUMO

By dissolving copper chloride in [Bmim]Cl (1-butyl-3-methylimidazolium chloride), chloride ions can coordinate with copper ions and form [CuCl4]2-, thereby inducing the solution being hydrophobic. In the present work, hydrogen bonds between [Bmim]+ and anions are analyzed and discussed by two-dimensional correlation spectroscopy. Time-dependent attenuated total reflection spectroscopy (ATR-FTIR) is introduced to monitor the hygroscopic process of [Bmim]2[CuCl4] and [Bmim]Cl in situ. Hygroscopic capacity and rate of [Bmim]2[CuCl4] shrink compared with [Bmim]Cl. The change of water molecular clusters has been studied by second-derivative spectra in the hygroscopic process. The behaviors of water molecular in the two ionic liquids are also distinctive.


Assuntos
Cloretos , Líquidos Iônicos , Cobre , Interações Hidrofóbicas e Hidrofílicas , Líquidos Iônicos/química , Análise Espectral , Água
15.
Nat Commun ; 13(1): 3258, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672318

RESUMO

Transcriptome-wide association studies (TWAS) are popular approaches to test for association between imputed gene expression levels and traits of interest. Here, we propose an integrative method PUMICE (Prediction Using Models Informed by Chromatin conformations and Epigenomics) to integrate 3D genomic and epigenomic data with expression quantitative trait loci (eQTL) to more accurately predict gene expressions. PUMICE helps define and prioritize regions that harbor cis-regulatory variants, which outperforms competing methods. We further describe an extension to our method PUMICE +, which jointly combines TWAS results from single- and multi-tissue models. Across 79 traits, PUMICE + identifies 22% more independent novel genes and increases median chi-square statistics values at known loci by 35% compared to the second-best method, as well as achieves the narrowest credible interval size. Lastly, we perform computational drug repurposing and confirm that PUMICE + outperforms other TWAS methods.


Assuntos
Estudo de Associação Genômica Ampla , Transcriptoma , Reposicionamento de Medicamentos , Epigenômica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Genômica , Humanos , Polimorfismo de Nucleotídeo Único , Transcriptoma/genética
16.
Stat Med ; 41(1): 180-193, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34672000

RESUMO

Regression is a commonly used statistical model. It is the conditional mean of the response given covariates µ(x)=E(Y|X=x) . However, in some practical problems, the interest is the conditional mean of the response given the covariates belonging to some set A. Notably, in precision medicine and subgroup analysis in clinical trials, the aim is to identify subjects who benefit the most from the treatment, or identify an optimal set in the covariate space which manifests treatment favoritism if a subject's covariates fall in this set and the subject is classified to the favorable treatment subgroup. Existing methods for subgroup analysis achieve this indirectly by using classical regression. This motivates us to develop a new type of regression: set-regression, defined as µ(A)=E(Y|X∈A) which directly addresses the subgroup analysis problem. This extends not only the classical regression model but also improves recursive partitioning and support vector machine approaches, and is particularly suitable for objectives involving optimization of the regression over sets, such as subgroup analysis. We show that the new versatile set-regression identifies the subgroup with increased accuracy. It is easy to use. Simulation studies also show superior performance of the proposed method in finite samples.


Assuntos
Modelos Estatísticos , Projetos de Pesquisa , Ensaios Clínicos como Assunto , Simulação por Computador , Humanos , Análise de Regressão , Máquina de Vetores de Suporte
17.
J Chemother ; 34(2): 87-96, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34139965

RESUMO

Because of lacking of head-to-head comparison among lorlatinib, alectinib and brigatinib for patients with ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced non-small-cell lung cancer (NSCLC), the optimal option for these patients still remains undefined. We searched published reports that described the activity and safety of those novel ALK inhibitors (lorlatinib, alectinib and brigatinib) for ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced NSCLC. Five randomized controlled trials were identified, covering 1111 subjects. In the network meta-analysis, lorlatinib seemed to prolong progression free survival than brigatinib (Hazard Ratio: 0.57, P = 0.03) and alectinib (Hazard ratio: 0.65, P = 0.05) for previously untreated patients with ALK-positive advanced NSCLC as assessed by the independent review committee. Meanwhile, lorlatinib significantly improved significant progression free survival than brigatinib (Hazard ratio: 0.57, P = 0.03) and alectinib (Hazard ratio: 0.59, P = 0.03) for ALK inhibitor-naive patients. Among lorlatinib, alectinib, brigatinib, and crizotinib, lorlatinib had the highest probability to reach the best overall confirmed response rates (probability of 48%) and intracranial confirmed response rates (probability of 44%). No significant difference was found among them in overall survival and adverse events analysis. In terms of progression free survival, our results indicated that lorlatinib was the best treatment choice for patients with ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced NSCLC. The future head-to-head trials assessing the relative efficacy of lorlatinib, alectinib and brigatinib were warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Aminopiridinas , Quinase do Linfoma Anaplásico , Carbazóis , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Lactamas , Neoplasias Pulmonares/tratamento farmacológico , Metanálise em Rede , Compostos Organofosforados , Piperidinas , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis , Pirimidinas
18.
PLoS One ; 16(10): e0259119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34710165

RESUMO

Flowering and fruit set are important traits affecting fruit quality and yield in rabbiteye blueberry (Vaccinium ashei). Intense efforts have been made to elucidate the influence of vernalization and phytohormones on flowering, but the molecular mechanisms of flowering and fruit set remain unclear. To unravel these mechanisms, we performed transcriptome analysis to explore blueberry transcripts from flowering to early fruit stage. We divided flowering and fruit set into flower bud (S2), initial flower (S3), bloom flower (S4), pad fruit (S5), and cup fruit (S6) based on phenotype and identified 1,344, 69, 658, and 189 unique differentially expressed genes (DEGs) in comparisons of S3/S2, S4/S3, S5/S4, and S6/S5, respectively. There were obviously more DEGs in S3/S2 and S5/S4 than in S4/S3, and S6/S5, suggesting that S3/S2 and S5/S4 represent major transitions from buds to fruit in blueberry. GO and KEGG enrichment analysis indicated these DEGs were mostly enriched in phytohormone biosynthesis and signaling, transporter proteins, photosynthesis, anthocyanins biosynthesis, disease resistance protein and transcription factor categories, in addition, transcript levels of phytohormones and transporters changed greatly throughout the flowering and fruit set process. Gibberellic acid and jasmonic acid mainly acted on the early stage of flowering development like expression of the florigen gene FT, while the expression of auxin response factor genes increased almost throughout the process from bud to fruit development. Transporter proteins were mainly associated with minerals during the early flowering development stage and sugars during the early fruit stage. At the early fruit stage, anthocyanins started to accumulate, and the fruit was susceptible to diseases such as fungal infection. Expression of the transcription factor MYB86 was up-regulated during initial fruit development, which may promote anthocyanin accumulation. These results will aid future studies exploring the molecular mechanism underlying flowering and fruit set of rabbiteye blueberry.


Assuntos
Mirtilos Azuis (Planta)/genética , Flores/genética , Frutas/genética , Regulação da Expressão Gênica de Plantas , Transcriptoma , Antocianinas , Mirtilos Azuis (Planta)/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Transdução de Sinais/genética
19.
Water Sci Technol ; 83(10): 2549-2559, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34032630

RESUMO

Electrodeionization (EDI) technology is limited by low regeneration efficiency of ion exchange resins, requirements of high-quality influent water, fouling of the ion exchange membrane and electrode, etc. In this work, a novel bed type called a compound bed in which cation and anion exchange resins were near the cation and anion exchange membrane and placed in layers, was proposed to implement high-efficiency regeneration of ion exchange resins. The influence of different operating conditions on the regeneration efficiency of ion exchange resins was elucidated as well. The regeneration efficiency of ion exchange resins could reach 73.1%, when the device was operated for 5 h under current density of 9 mA/cm2, with a cation and anion exchange resins ratio of 2: 3, influent water conductivity of 1,360 µS/cm and hardness of 400 mg/L. Therefore, the proposed compound bed structure not only widened the inlet water conditions, but also achieved the high-efficiency regeneration of ion exchange resins and anti-fouling of membranes and electrodes.


Assuntos
Resinas de Troca Iônica , Purificação da Água , Resinas de Troca Aniônica , Troca Iônica , Água
20.
Infect Dis Poverty ; 10(1): 46, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789762

RESUMO

BACKGROUND: Brucellosis is an infectious-allergic zoonotic disease caused by bacteria of the genus Brucella. Early diagnosis is the key to preventing, treating, and controlling brucellosis. Fluorescence polarization immunoassay (FPA) is a new immunoassay for relatively rapid and accurate detection of antibodies or antigens based on antigen-antibody interaction. However, there is no report on FPA-based detection of human brucellosis in China. Therefore, this study is to evaluate the value of FPA for the diagnosis of human brucellosis in China. METHODS: We recruited 320 suspected brucellosis cases who had the clinical symptoms and epidemiological risk factors between January and December, 2019. According to China Guideline for Human Brucellosis Diagnosis, the Rose Bengal test (RBT) was used for the screening test, and the serum agglutination test (SAT) was used as the confirmatory test. Brucellosis was confirmed only if the results of both tests were positive. Additionally, FPA and enzyme linked immune sorbent assay (ELISA) were compared with SAT, and their sensitivity, specificity, coincidence rate and consistency coefficient (Kappa value) as diagnostic tests were analyzed individually and in combination. The optimal cut-off value of FPA was also determined using the receiver operator characteristic (ROC) curve. RESULTS: The optimum cut-off value of FPA was determined to be 88.5 millipolarization (mP) units, with a sensitivity of 94.5% and specificity of 100.0%. Additionally, the coincidence rate with the SAT test was 96.6%, and the Kappa value (0.9) showed excellent consistency. The sensitivity and specificity of FPA and ELISA combined were higher at 98.0% and 100.0% respectively. CONCLUSIONS: When the cut-off value of FPA test is set at 88.5 mP, it has high value for the diagnosis of brucellosis. Additionally, when FPA and ELISA are combined, the sensitivity of diagnosis is significantly improved. Thus, FPA may have potential in the future as a diagnostic method for human brucellosis in China.


Assuntos
Brucella , Brucelose , Testes de Aglutinação , Anticorpos Antibacterianos , Brucelose/diagnóstico , Ensaio de Imunoadsorção Enzimática , Imunoensaio de Fluorescência por Polarização , Humanos , Curva ROC , Sensibilidade e Especificidade
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