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1.
Biology (Basel) ; 13(7)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39056731

RESUMO

The changing global climate has significantly impacted the spread of plant pests. The cassava mealybug (Phenacoccus manihoti) is among the most dangerous quarantine pests affecting cassavas worldwide, causing substantial losses in agricultural production and food security across several regions. Although China is currently free of the cassava mealybug, its proximity to affected countries and extensive trade with these regions necessitate a detailed understanding of the pest's distribution pattern and dynamic ecological niche changes. Using the Biomod2 model, we selected two historical climate scenarios and two future climate scenarios (SSP1-2.6 and SSP5-8.5) to investigate the distribution patterns, potential habitats, distribution centers, and dynamic ecological niches of cassava mealybugs in China. Key environmental variables influencing the distribution were identified, including bio4, bio8, bio12, bio18, and bio19. The potential habitat of cassava mealybugs is mainly located in several provinces in southern China. In the future, the suitable habitat is projected to expand slightly under the influence of climate change, maintaining the overall trend, but the distribution center of suitable areas will shift northward. Dynamic ecological niche prediction results indicate the potential for further expansion; however, the ecological niches may be unequal and dissimilar in the invaded areas. The predictions could serve as a valuable reference for early warning systems and management strategies to control the introduction of cassava mealybugs.

2.
Biosens Bioelectron ; 262: 116550, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38976958

RESUMO

Circulating tumor cell (CTC) has been a valuable biomarker for the diagnosis of breast cancer, while folate receptor is a kind of cell surface receptor glycoprotein which is overexpressed in breast cancer. In this work, we have designed and fabricated an electrochemical biosensor for sensitive detection of folate receptor-positive CTCs based on mild reduction assisted CRISPR/Cas system. Specifically, folate functionalized magnetic beads are firstly prepared to capture CTCs owing to the strong affinity between folate and the folate receptors on the surface of cells. Then, the cell membranes are treated by mild reduction so as to expose a large number of free sulfhydryl groups, which can be coupled with maleimide-DNA to introduce the signal amplified CRISPR/Cas12a system. After the trans-cleavage activity of CRISPR/Cas12a is activated, the long chain DNA modified with electroactive molecules methylene blue can be randomly cleaved into short DNA fragments, which are then captured on the graphite electrode through the host-guest recognition with cucurbit [7]uril, generating highly amplified electrochemical signal corresponding to the number of CTCs. The electrochemical biosensor not only demonstrates the sensitivity with a low detection limit of 2 cells/mL, but also highlights its excellent selectivity and stability in complex environment. Therefore, our biosensor may provide an alternative tool for the analysis of CTCs.


Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , Técnicas Eletroquímicas , Limite de Detecção , Células Neoplásicas Circulantes , Humanos , Técnicas Biossensoriais/métodos , Células Neoplásicas Circulantes/patologia , Células Neoplásicas Circulantes/química , Técnicas Eletroquímicas/métodos , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Linhagem Celular Tumoral , Ácido Fólico/química , DNA/química
3.
Brief Bioinform ; 25(Supplement_1)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041913

RESUMO

This study describes the development of a resource module that is part of a learning platform named 'NIGMS Sandbox for Cloud-based Learning' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement. This module is designed to facilitate interactive learning of whole-genome bisulfite sequencing (WGBS) data analysis utilizing cloud-based tools in Google Cloud Platform, such as Cloud Storage, Vertex AI notebooks and Google Batch. WGBS is a powerful technique that can provide comprehensive insights into DNA methylation patterns at single cytosine resolution, essential for understanding epigenetic regulation across the genome. The designed learning module first provides step-by-step tutorials that guide learners through two main stages of WGBS data analysis, preprocessing and the identification of differentially methylated regions. And then, it provides a streamlined workflow and demonstrates how to effectively use it for large datasets given the power of cloud infrastructure. The integration of these interconnected submodules progressively deepens the user's understanding of the WGBS analysis process along with the use of cloud resources. Through this module, we can enhance the accessibility and adoption of cloud computing in epigenomic research, speeding up the advancements in the related field and beyond. This manuscript describes the development of a resource module that is part of a learning platform named ``NIGMS Sandbox for Cloud-based Learning'' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox [1] at the beginning of this Supplement. This module delivers learning materials on the analysis of bulk and single-cell ATAC-seq data in an interactive format that uses appropriate cloud resources for data access and analyses.


Assuntos
Computação em Nuvem , Metilação de DNA , Software , Sequenciamento Completo do Genoma , Sequenciamento Completo do Genoma/métodos , Sulfitos/química , Humanos , Epigênese Genética , Biologia Computacional/métodos
4.
Sci Rep ; 14(1): 13278, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858442

RESUMO

The sandstone is in a state of dry-wet cycle under the repeated action of rainfall, and its mechanical properties are deteriorated to varying degrees, which causes cracks in the sandstone. Therefore, it is of great significance to study the mechanical properties and fracture propagation of sandstone under the action of dry-wet cycles. Currently, there are limited studies using numerical simulation methods to study the fracture extension of rocks under various dry and wet cycling conditions.Therefore, in this paper, the effects of different amounts of dry and wet cycling on the mechanical properties and fracture behavior of sandstone are investigated through uniaxial compression tests and numerical simulations of fracture extension. The findings indicate that the deformation stage of sandstone remains unchanged by the dry-wet cycle. The uniaxial compressive potency and coefficient of restitution gradually diminish as the quantity of cycles rises, while the Poisson's ratio exhibits the opposite trend, and the impact on the mechanical performance of sandstone wanes with cycle increments, and the correlation coefficient surpasses 0.93, signifying a substantial influence of the dry-wet cycle on sandstone's mechanical performances. The discrepancy between the numerical simulation and experimental results is minimal, with a maximum error of only 3.1%, demonstrating the congruence of the simulation and experimental outcomes.The mesoscopic examination of the simulations indicates that the quantity of fractures in the sandstone specimens rises with the escalation of dry-wet cycles, and the steps of analysis linked to crack inception and fracture propagation are accelerated, and the analysis steps from fracture initiation to penetration are also reduced.

5.
Bull Entomol Res ; : 1-12, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38751346

RESUMO

The Argentine ant (Linepithema humile) and the little fire ant (Wasmannia auropunctata) are among the top 100 invasive alien species globally, causing significant ecological and economic harm. Therefore, it is crucial to study their potential geographic distribution worldwide. This study aimed to predict their global distribution under current and future climate conditions. We used distribution data from various sources, including CABI, GBIF, and PIAKey, and key climate variables selected from 19 environmental factors to model their potential geographic distribution using MaxEnt. The AUC values were 0.925 and 0.937 for L. humile and W. auropunctata, respectively, indicating good predictive performance. Suitable areas for L. humile were mainly in southern North America, northern South America, Europe, central Asia, southern Oceania, and parts of Africa, while W. auropunctata suitable areas were mostly in southern North America, most of South America, a small part of Europe, southern Asia, central Africa, and some parts of Oceania. Under climate change scenario, suitable areas for L. humile increased, while highly suitable areas for W. auropunctata decreased. The top four countries with the largest areas of overlapping suitable habitat under current climate were Brazil, China, Australia, and Argentina, while under future SSP585 climate scenario, the top four countries were Brazil, China, Indonesia, and Argentina. Some countries, such as Estonia and Finland, will see an overlapping adaptation area under climate change. In conclusion, this study provides insight into controlling the spread and harm of L. humile and W. auropunctata.

6.
Sci Total Environ ; 927: 172167, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38580118

RESUMO

The improvement of food security and nutrition has attracted wide attention, and microalgae as the most promising food source are being further explored. This paper comprehensively introduces basic and functional nutrients rich in microalgae by elaborated tables incorporating a wide variety of studies and summarizes factors influencing their accumulation effects. Subsequently, multiple comparisons of nutrients were conducted, indicating that microalgae have a high protein content. Moreover, controllable production costs and environmental friendliness prompt microalgae into the list that contains more promising and reliable future food. However, microalgae and -based foods approved and sold are limited strictly, showing that safety is a key factor affecting dietary consideration. Notably, sensory profiles and ingredient clarity play an important role in improving the acceptance of microalgae-based foods. Finally, based on the bottleneck in the microalgae food industry, suggestions for its future development were discussed.


Assuntos
Microalgas , Inocuidade dos Alimentos , Nutrientes/análise , Valor Nutritivo
7.
mSystems ; 8(6): e0102523, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38038441

RESUMO

IMPORTANCE: Amplicon sequencing of targeted genes is the predominant approach to estimate the membership and structure of microbial communities. However, accurate reconstruction of community composition is difficult due to sequencing errors, and other methodological biases and effective approaches to overcome these challenges are essential. Using a mock community of 33 phylogenetically diverse strains, this study evaluated the effect of GC content on sequencing results and tested different approaches to improve overall sequencing accuracy while characterizing the pros and cons of popular amplicon sequence data processing approaches. The sequencing results from this study can serve as a benchmarking data set for future algorithmic improvements. Furthermore, the new insights on sequencing error, chimera formation, and GC bias from this study will help enhance the quality of amplicon sequencing studies and support the development of new data analysis approaches.


Assuntos
Código de Barras de DNA Taxonômico , Microbiota , Composição de Bases , Análise de Sequência de DNA/métodos , Viés
8.
Front Plant Sci ; 14: 1238656, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841613

RESUMO

Introduction: Erigeron philadelphicus and Erigeron annuus are two ecologically destructive invasive plants from the Asteraceae family. Predicting the potential distribution pattern of two invasive alien Erigeron weeds can provide a scientific basis for prevent the further spread of these two weeds in China under climate change. Methods: Based on historical occurrence datasets and environmental variables, we optimized a MaxEnt model to predict the potential suitable habitats of E. philadelphicus and E. annuus. We also analyzed the shifts of distribution centroids and patterns under climate change scenarios. Results: The key variables that affect the potential geographical distribution of E. annuus and E. philadelphicus, respectively, are temperature seasonality and precipitation of the driest month. Moreover, topsoil sodicity and topsoil salinity also influence the distribution of E. philadelphicus. Under climate change, the overall suitable habitats for both invasive alien Erigeron weeds are expected to expand. The potential geographical distribution of E. annuus exhibited the highest expansion under the SSP245 climate scenario (medium forcing scenarios), whereas E. philadelphicus had the highest expansion under the SSP126 climate scenario (lower forcing scenarios) globally. The future centroid of E. annuus is projected to shift to higher latitudes specifically from Hubei to Hebei, whereas E. philadelphicus remains concentrated primarily in Hubei Province. The overlapping suitable areas of the two invasive alien Erigeron plants mainly occur in Jiangsu, Zhejiang, Fujian, Jiangxi, Hunan, Guizhou, and Chongqing, within China. Discussion: Climate change will enable E. annuus to expand into northeastern region and invade Yunnan Province whereas E. philadelphicus was historically the only suitable species. E. annuus demonstrates a greater potential for invasion and expansion under climate change, as it exhibits higher environmental tolerance. The predictive results obtained in this study can serve as a valuable reference for early warning systems and management strategies aimed at controlling the spread of these two invasive plants.

9.
Sensors (Basel) ; 23(20)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37896624

RESUMO

Selecting training samples is crucial in remote sensing image classification. In this paper, we selected three images-Sentinel-2, GF-1, and Landsat 8-and employed three methods for selecting training samples: grouping selection, entropy-based selection, and direct selection. We then used the selected training samples to train three supervised classification models-random forest (RF), support-vector machine (SVM), and k-nearest neighbor (KNN)-and evaluated the classification results of the three images. According to the experimental results, the three classification models performed similarly. Compared with the entropy-based method, the grouping selection method achieved higher classification accuracy using fewer samples. In addition, the grouping selection method outperformed the direct selection method with the same number of samples. Therefore, the grouping selection method performed the best. When using the grouping selection method, the image classification accuracy increased with the increase in the number of samples within a certain sample size range.

10.
Int J Pharm ; 643: 123286, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37532009

RESUMO

Vat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications. To achieve this, instead of employing cross-linking chemistry to fabricate matrices, supramolecular chemistry may be used to impart dynamic interaction between polymer chains. In this study, water-soluble drug-loaded printlets (3D printed tablets) are fabricated via digital light processing (DLP) 3DP for the first time. Six formulations with varying ratios of an electrolyte acrylate monomer, [2-(acryloyloxy)ethyl]trimethylammonium chloride (TMAEA), and a co-monomer, 1-vinyl-2-pyrrolidone (NVP), were prepared to produce paracetamol-loaded printlets. 1H NMR spectroscopy analysis confirmed the integration of TMAEA and NVP in the polymer, and residual TMAEA monomers were found to be present only in trace amounts (0.71 - 1.37 %w/w). The apparent molecular mass of the photopolymerised polymer was found to exceed 300,000 Da with hydrodynamic radii of 15 - 20 nm, estimated based on 1H DOSY NMR measurements The loaded paracetamol was completely released from the printlets between 45 minutes to 5 hours. In vivo single-dose acute toxicity studies in rats suggest that the printlets did not cause any tissue damage. The findings reported in this study represent a significant step towards the adoption of vat photopolymerization-based 3DP to produce personalised medicines.


Assuntos
Acetaminofen , Tecnologia Farmacêutica , Animais , Ratos , Acetaminofen/química , Tecnologia Farmacêutica/métodos , Impressão Tridimensional , Polímeros/química , Liberação Controlada de Fármacos , Comprimidos/química
11.
Chem Commun (Camb) ; 59(26): 3890-3893, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36916831

RESUMO

Identifying the phenotype of aggressive breast cancer (BC) cells is vital for the effectiveness of surgical intervention and standard-of-care therapy. HER-2 is overexpressed in aggressive BC and MMP-2 is a crucial indicator of invasiveness and metastasis of BC, so we have proposed an electrochemical biosensor in this work to identify the phenotype of aggressive BC cells via detection of HER-2 together with MMP-2 by designing a dual-trapping peptide and a metal organic framework (MOF)-based probe. Specifically, the designed peptide contains both a HER-2 recognition sequence and MMP-2-specific substrate, while the MOF-based probe (AuNPs@HRP@ZIF-8), prepared by loading horseradish peroxidase (HRP) and gold nanoparticles (AuNPs) on ZIF-8, can also combine with the peptide. Consequently, sensitive and specific detection of both HER-2 and MMP-2 can be achieved in the wide range from 50 fg mL-1 to 50 ng mL-1 and 10 fg mL-1 to 10 ng mL-1, respectively, and the biosensor can distinguish HER-2+ BC cells and evaluate the invasion capability, which might be extended to provide a method for the accurate identification of tumor features in BC subtypes.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , Neoplasias , Ouro , Metaloproteinase 2 da Matriz , Peroxidase do Rábano Silvestre , Fenótipo , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Limite de Detecção
12.
Biomed Pharmacother ; 160: 114329, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36731343

RESUMO

P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) are clinically relevant efflux transporters implicated in the oral absorption of many food and drug substrates. Here, we hypothesised that food intake could influence protein and mRNA intestinal expression of P-gp/abcb1a, BCRP/abcg2, and MRP2/abcc2 differently in male and female Wistar and Sprague Dawley rats. To test this hypothesis, we used enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) to quantify the protein and mRNA intestinal expression of these transporters, respectively. Our study found food and sex differences in P-gp expression, whereby in the fed state P-gp expression decreased in male Wistar rats, but P-gp expression increased in females. In the fed state, BCRP expression increased in both male and female Wistar rats, compared with the fasted state. In contrast, no sex differences or food effect differences were seen in Sprague Dawley rats for P-gp and BCRP expression. On the other hand, in the fed state, MRP2 expression was higher in male and female Wistar and Sprague Dawley rats when compared with the fasted state. Sex differences were also observed in the fasted state. Overall, significant strain differences were reported for P-gp, BCRP and MRP2 expression. Strong to moderate positive linear correlations were found between ELISA and PCR quantification methods. ELISA may be more useful than PCR as it reports protein expression as opposed to transcript expression. Researchers must consider the influence of sex, strain and feeding status in preclinical studies of P-gp, BCRP and MRP2 drug substrates.


Assuntos
Proteínas de Membrana Transportadoras , Proteínas de Neoplasias , Ratos , Masculino , Feminino , Animais , Ratos Sprague-Dawley , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Ratos Wistar , Proteínas de Neoplasias/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP , Proteína 2 Associada à Farmacorresistência Múltipla , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , RNA Mensageiro/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética
13.
ACS Appl Mater Interfaces ; 15(5): 6411-6419, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36693188

RESUMO

Serum alpha fetoprotein (AFP) is a "gold-standard" biomarker for the diagnosis of hepatocellular carcinoma (HCC). Available pieces of evidence suggest that the ratio of AFP-L3 isoform in the total AFP may provide more accurate prediction for the incidence of HCC. In this work, we design an electrochemical aptasensor for high-accuracy assay of AFP-L3 ratio based on differentiated labeling of AFP isoforms in an orderly fashion. Specifically, total AFP is first captured by an AFP aptamer-functionalized electrode and labeled with quantum dots-functionalized DNA probes via mild reduction. Then, AFP-L3 isoform that strongly binds to Lens culinaris agglutinin is labeled with silver nanoparticles after the exonuclease-catalyzed removal of DNA probes. By tracing the electrochemical responses of quantum dots and silver nanoparticles, respectively, the amounts of total AFP and AFP-L3 isoforms are determined and the AFP-L3 ratio is accordingly calculated to favor the accurate HCC diagnosis. Experimental results prove the high-accuracy assay of AFP-L3 ratio based on the AFP quantitation in a linear range of 0.0008-40 ng mL-1 and AFP-L3 quantitation in a linear range of 0.004-40 ng mL-1. The aptasensor also displays satisfactory specificity and good recoveries even in the complex serum samples. Therefore, the aptasensor may provide a valuable tool for the assay of the AFP-L3 ratio and have a great potential use in early warning of HCC for clinical application.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas Metálicas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas/metabolismo , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais , Prata , Isoformas de Proteínas
14.
J Adv Res ; 53: 61-74, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36574947

RESUMO

INTRODUCTION: The oriental fruit fly Bactrocera dorsalis is one of the most destructive agricultural pests worldwide, with highly debated species delimitation, origin, and global spread routes. OBJECTIVES: Our study intended to (i) resolve the taxonomic uncertainties between B. dorsalis and B. carambolae, (ii) reveal the population structure and global invasion routes of B. dorsalis across Asia, Africa, and Oceania, and (iii) identify genomic regions that are responsible for the thermal adaptation of B. dorsalis. METHODS: Based on a high-quality chromosome-level reference genome assembly, we explored the population relationship using a genome-scale single nucleotide polymorphism dataset generated from the resequencing data of 487 B. dorsalis genomes and 25 B. carambolae genomes. Genome-wide association studies and silencing using RNA interference were used to identify and verify the candidate genes associated with extreme thermal stress. RESULTS: We showed that B. dorsalis originates from the Southern India region with three independent invasion and spread routes worldwide: (i) from Northern India to Northern Southeast Asia, then to Southern Southeast Asia; (ii) from Northern India to Northern Southeast Asian, then to China and Hawaii; and (iii) from Southern India toward the African mainland, then to Madagascar, which is mainly facilitated by human activities including trade and immigration. Twenty-seven genes were identified by a genome-wide association study to be associated with 11 temperature bioclimatic variables. The Cyp6a9 gene may enhance the thermal adaptation of B. dorsalis and thus boost its invasion, which tended to be upregulated at a hardening temperature of 38 °C. Functional verification using RNA interference silencing against Cyp6a9, led to the specific decrease in Cyp6a9 expression, reducing the survival rate of dsRNA-feeding larvae exposed to extreme thermal stress of 45 °C after heat hardening treatments in B. dorsalis. CONCLUSION: This study provides insights into the evolutionary history and genetic basis of temperature adaptation in B. dorsalis.


Assuntos
Tephritidae , Animais , Humanos , Tephritidae/genética , Estudo de Associação Genômica Ampla , Temperatura , Larva
15.
Pest Manag Sci ; 79(4): 1342-1351, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36412239

RESUMO

BACKGROUND: The red imported fire ant, Solenopsis invicta Buren is one of the world's most successful and destructive invasive ant species. In mainland China, fast, monthly and annual pest reports on all pests have been established since 2010. The distribution of S. invicta resulting from climate change in China was predicted using MaxEnt modeling in combination with comprehensive surveillance data and 56 environmental factors. RESULTS: The fast and monthly reports revealed that S. invicta had spread to new territories almost every year in this timeframe. The transportation of seedlings and deployment of turfgrass were the major artificial transmission pathways. Annual reports indicated that control efforts had effectively reduced its occurrence areas and degree of severity of infestations, and retrieved the economic loss caused by S. invicta. The MaxEnt model predicted that S. invicta would expand to 23 provinces in China as a result of climate change. Moisture variables were the key factors affecting the distribution of this pest. CONCLUSION: Based on the theoretical reference framework of this research, China proposed the first-ever integrated tactics against a single pest, jointly involving nine ministries, which include clarifying responsibilities, cutting off transmission pathways, strengthening surveillance, declaring pest distributions and conducting preventive and control campaigns. Practical efforts and measures combating the devastation of S. invicta may shed light on its management and other invasive species worldwide. © 2022 Society of Chemical Industry.


Assuntos
Formigas , Animais , China , Espécies Introduzidas
16.
Biosens Bioelectron ; 222: 115007, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36527832

RESUMO

Fat mass and obesity-associated protein (FTO) regulating the N6-methyladenine (m6A, the most pervasive epigenetic modification) levels within the nucleus has been identified as a potential biomarker for cancer diagnosis and prognosis. However, current methods for FTO detection are complicated or/and not sensitive enough for practical application. Herein, we propose a colorimetric biosensor for detecting FTO based on a delicate design of m6A demethylation-activated DNAzyme. Specifically, an m6A-blocked DNAzyme is constructed as a switch of the biosensor that can be turned on by target FTO. The decreased thermal stability resulting from substrate cleavage leads to a DNAzyme recycling to produce multiple primers. Then the rolling circle amplification (RCA) reactions can be initiated to generate G-quadruplex-DNAzymes catalyzing 2,2-azino-bis-(3-ethylben-zthiazoline-6-sulfonic acid (ABTS) oxidation which can be readily observed by the naked eye. Quantitative detection can also be achieved with a limit of detection (LOD) down to 69.9 fM, exhibiting higher sensitivity than previous reports. Therefore, this biosensor opens a simple and sensitive way to achieve visual assay of FTO via triple signal amplification. In addition, our biosensor has been successfully applied to FTO detection in clinical samples, which shows great potential in clinical molecular diagnostics.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Quadruplex G , Humanos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Técnicas Biossensoriais/métodos , Colorimetria/métodos , Desmetilação , DNA Catalítico/química , Técnicas de Amplificação de Ácido Nucleico/métodos , Obesidade , Tecido Adiposo
17.
Front Med (Lausanne) ; 9: 1019490, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523785

RESUMO

Uncontrolled transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of several variants of concern (VOC). As vaccine-induced neutralizing antibodies against VOC waned over time, breakthrough infections (BTIs) have been reported primarily among healthcare workers or in long-term care facilities. Most BTIs were identified by reverse transcription-polymerase chain reaction (RT-PCR) or antigen test for individuals experiencing symptoms, known as symptomatic BTIs. In this study, we detected seroconversion of anti-nucleocapsid (N) antibody to identify both symptomatic and asymptomatic BTIs in a cohort of COVID-19-naive university employees and students following two or three doses of mRNA vaccines. We reported 4 BTIs among 85 (4.7%) participants caused by the Omicron and Delta VOC during the transition from the Delta to Omicron wave of the pandemic; three were symptomatic and confirmed by RT-PCR test and one asymptomatic. A symptomatic reinfection two and half months after a BTI was found in one participant. Two of three symptomatic BTIs and the reinfection were confirmed by whole genome sequencing. All were supported by a >4-fold increase in neutralizing antibodies against the Delta or Omicron variant. Moreover, we found both symptomatic and asymptomatic BTIs can boost neutralizing antibodies against VOC with variable degrees ranging from 2.5- to 77.4-fold increase in neutralizing antibody titers. As BTIs continue, our findings highlight the application of anti-N antibody test to ongoing studies of immunity induced by spike-based vaccine, and provide new insights into the establishment of herd immunity in the community during the post-vaccination era.

18.
Int J Mol Sci ; 23(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36555339

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious and pathogenic coronavirus that emerged in late 2019 and caused a pandemic of respiratory illness termed as coronavirus disease 2019 (COVID-19). Cancer patients are more susceptible to SARS-CoV-2 infection. The treatment of cancer patients infected with SARS-CoV-2 is more complicated, and the patients are at risk of poor prognosis compared to other populations. Patients infected with SARS-CoV-2 are prone to rapid development of acute respiratory distress syndrome (ARDS) of which pulmonary fibrosis (PF) is considered a sequelae. Both ARDS and PF are factors that contribute to poor prognosis in COVID-19 patients. However, the molecular mechanisms among COVID-19, ARDS and PF in COVID-19 patients with cancer are not well-understood. In this study, the common differentially expressed genes (DEGs) between COVID-19 patients with and without cancer were identified. Based on the common DEGs, a series of analyses were performed, including Gene Ontology (GO) and pathway analysis, protein-protein interaction (PPI) network construction and hub gene extraction, transcription factor (TF)-DEG regulatory network construction, TF-DEG-miRNA coregulatory network construction and drug molecule identification. The candidate drug molecules (e.g., Tamibarotene CTD 00002527) obtained by this study might be helpful for effective therapeutic targets in COVID-19 patients with cancer. In addition, the common DEGs among ARDS, PF and COVID-19 patients with and without cancer are TNFSF10 and IFITM2. These two genes may serve as potential therapeutic targets in the treatment of COVID-19 patients with cancer. Changes in the expression levels of TNFSF10 and IFITM2 in CD14+/CD16+ monocytes may affect the immune response of COVID-19 patients. Specifically, changes in the expression level of TNFSF10 in monocytes can be considered as an immune signature in COVID-19 patients with hematologic cancer. Targeting N6-methyladenosine (m6A) pathways (e.g., METTL3/SERPINA1 axis) to restrict SARS-CoV-2 reproduction has therapeutic potential for COVID-19 patients.


Assuntos
COVID-19 , Neoplasias , Fibrose Pulmonar , Síndrome do Desconforto Respiratório , Humanos , COVID-19/complicações , COVID-19/genética , Pulmão/patologia , Proteínas de Membrana/metabolismo , Metiltransferases/metabolismo , Neoplasias/complicações , Neoplasias/genética , Fibrose Pulmonar/patologia , Fibrose Pulmonar/virologia , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/virologia , RNA-Seq , SARS-CoV-2 , Análise da Expressão Gênica de Célula Única , Fatores de Transcrição/metabolismo
19.
Int J Pharm ; 629: 122365, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36336203

RESUMO

The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40 hydrogenated castor oil), Poloxamer 188 (2-methyloxirane) and Tween 80 (polyoxyethylene (80) sorbitan monooleate) were screened at 0.07 - 5% concentrations for their effect on ranitidine bioavailability in male and female Wistar rats. We show that all excipient concentrations significantly increased ranitidine bioavailability in male, but not female, rats. The effect of these excipients on the intestinal efflux transporters P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and multi-drug resistant protein 2 (MRP2) were also monitored. Measured by ELISA assay, in male rats, peak reductions in intestinal P-gp protein expression occurred in the presence of 1% Cremophor RH 40 and Poloxamer 188 and 0.5% Tween 80. In contrast, no distinct changes were observed in female intestinal P-gp expression. Unlike P-gp, all excipients had a positive effect on MRP2 protein expression - albeit only in males - in a concentration-dependent manner. The excipients did not modulate intestinal BCRP protein expression in either sex. Endogenous hormones and a nuclear receptor (testosterone, oestradiol and pregnane X receptor; PXR) that are purported to regulate intestinal efflux membrane transporter expression were also quantified. In the presence of all excipients, testosterone levels significantly elevated in males, although PXR levels reduced at similar rates in both sexes. No significant effects were identified in oestradiol levels in male and female rats. It is clear that excipients are not inert and their pathway for modulating drug response is multi-dimensional and specific between sexes. This study showed that excipients increased drug bioavailability of a P-gp drug substrate due to its reductive effect on intestinal P-gp expression; we propose that this link may be due to the excipients modulating fundamental testosterone levels. Understanding the implication of excipients on intestinal physiology and hormone levels can therefore improve pharmaceutical design, clinical efficacy and instigate next generation personalised, sex-specific formulations.


Assuntos
Excipientes , Polissorbatos , Masculino , Feminino , Ratos , Animais , Excipientes/farmacologia , Disponibilidade Biológica , Polissorbatos/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Ranitidina , Poloxâmero/metabolismo , Ratos Wistar , Proteínas de Neoplasias/metabolismo , Estradiol , Testosterona
20.
J Control Release ; 349: 354-366, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35817278

RESUMO

First-line treatments for mild to moderate psoriasis are typically topical formulations containing corticosteroids, however, the therapeutic efficacy of these formulations is compromised by limited penetration and skin retention. Even more challenging, off-target corticosteroids are known to adversely affect healthy skin, including induction of epidermal and dermal atrophy. Here, we report a nanoparticle-based topical formulation that cures psoriasis in a single dose, but leaves healthy skin intact. Specifically, we developed tris(hydroxymethyl)aminomethane-modified bioadhesive nanoparticles (Tris-BNPs) that exploit the high permeability characteristic of psoriasis to penetrate only psoriatic skin but not the healthy skin. Furthermore, as Tris-BNPs diffuse and penetrate into the epidermis, the Tris molecules slowly diffuse away, exposing the aldehyde groups of BNPs, which can bind to amine groups present within lesional skin, leading to long local retention of BNPs in lesions of psoriatic skin. The accumulated BNPs within lesions release corticosteroids over a ~ 3 day period to maintain local drug concentration above the therapeutic level. In addition to deeper penetration and longer retention compared with commercial psoriasis treatments, the topical applied Tris-BNPs were not affected by sweating, humidity, or active wiping due to their preferential accumulation between the stratum corneum and the basal cells of the epidermis. Overall, Tris-BNP as a topical formulation hold promise to overcome the limitations of current psoriasis treatment.


Assuntos
Nanopartículas , Psoríase , Aldeídos , Aminas/metabolismo , Humanos , Psoríase/patologia , Pele/metabolismo , Trometamina/metabolismo , Trometamina/uso terapêutico
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