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1.
Transl Oncol ; 46: 101998, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38761630

RESUMO

Phyllodes tumors (PTs) has an increased risk of local relapse and distant metastases. Molecular features correlating to histologic grade and aggressive behavior of PTs are poorly characterized. Here, whole exome sequencing (WES) was performed to explore genetic mutations in 61 samples of fibroepithelial breast tumors, including 16 fibroadenomas (FAs), 18 benign PTs, 19 borderline PTs, and 8 malignant PTs. Our work clearly shows that FA, benign PT, borderline PT, and malignant PT are independent entities at the genomic level. They may exist as hidden sub-clones carrying specific genetic alterations. Malignant PT-specific mutations present a multi-gene co-mutational pattern suggesting a synergistic effect of co-mutated genes in processes associated with malignant behavior. Moreover, we made a combined genomic and transcriptomic analysis, which presented a mutated gene-based interaction with expression profiles. We found that EGFR mutations (c.710C > T, c.758A > G, c.1295A > G, and c.2156G > C) serve as a hub of interaction network in borderline PTs, which suggests EGFR tyrosine kinase inhibitors (EGFRi) might be effective for borderline PTs. We found TP53 mutations (c.730G > T, c.844C > T, and c.1019delA) serves as a hub event of molecular changes of malignant PTs. Thus, our study based on the omics platforms of genome and transcriptome provides a better understanding of relapse process and the potential targeted therapy in PTs, which is pivotal in improving molecular-guided patient selection and designing clinically relevant combination strategies.

2.
Water Res ; 253: 121304, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38364463

RESUMO

Efforts in water ecosystem conservation require an understanding of causative factors and removal efficacies associated with mixture toxicity during wastewater treatment. This study conducts a comprehensive investigation into the interplay between wastewater estrogenic activity and 30 estrogen-like endocrine disrupting chemicals (EEDCs) across 12 municipal wastewater treatment plants (WWTPs) spanning four seasons in China. Results reveal substantial estrogenic activity in all WWTPs and potential endocrine-disrupting risks in over 37.5 % of final effluent samples, with heightened effects during colder seasons. While phthalates are the predominant EEDCs (concentrations ranging from 86.39 %) for both estrogenic activity and major EEDCs (phthalates and estrogens), with the secondary and tertiary treatment segments contributing 88.59 ± 8.12 % and 11.41 ± 8.12 %, respectively. Among various secondary treatment processes, the anaerobic/anoxic/oxic-membrane bioreactor (A/A/O-MBR) excels in removing both estrogenic activity and EEDCs. In tertiary treatment, removal efficiencies increase with the inclusion of components involving physical, chemical, and biological removal principles. Furthermore, correlation and multiple liner regression analysis establish a significant (p < 0.05) positive association between solid retention time (SRT) and removal efficiencies of estrogenic activity and EEDCs within WWTPs. This study provides valuable insights from the perspective of prioritizing key pollutants, the necessity of integrating more efficient secondary and tertiary treatment processes, along with adjustments to operational parameters like SRT, to mitigate estrogenic activity in municipal WWTPs. This contribution aids in managing endocrine-disrupting risks in wastewater as part of ecological conservation efforts.


Assuntos
Disruptores Endócrinos , Poluentes Químicos da Água , Purificação da Água , Estrona , Águas Residuárias , Ecossistema , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Estrogênios/análise , Estradiol , Disruptores Endócrinos/análise
3.
Sci Rep ; 13(1): 1803, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36720923

RESUMO

Drug resistance occurs frequently in triple-negative breast cancer (TNBC) and leads to early relapse and short survival. Targeting the DNA damage response (DDR) has become an effective strategy for overcoming TNBC chemoresistance. CENPF (centromere protein) is a key regulator of cell cycle progression, but its role in TNBC chemotherapy resistance remains unclear. Here, we found that CENPF, which is highly expressed in TNBC, is associated with a poor prognosis in patients receiving chemotherapy. In addition, in vitro CENPF knockdown significantly increased adriamycin (ADR)-induced cytotoxicity in MDA-MB-231 cells and ADR-resistant cells (MDA-MB-231/ADR). Then, we demonstrated that CENPF targets Chk1-mediated G2/M phase arrest and binds to Rb to compete with E2F1 in TNBC. Considering the crucial role of E2F1 in the DNA damage response and DNA repair, a novel mechanism by which CENPF regulates the Rb-E2F1 axis will provide new horizons to overcome chemotherapy resistance in TNBC.


Assuntos
Proteínas Cromossômicas não Histona , Resistencia a Medicamentos Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Centrômero , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Fator de Transcrição E2F1/genética , Mitose , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Proteínas Cromossômicas não Histona/genética
4.
BMC Genomics ; 23(1): 799, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463109

RESUMO

BACKGROUND: BMPR1B (Bone morphogenetic protein receptor type-1B) is a receptor in the bone morphogenetic protein (BMP) family and has been identified as a candidate gene for reproductive traits in pigs. Our previous study in Taihu pigs found a specific estrogen response element (ERE) in the first intron of the BMPR1B gene that is associated with the number born alive trait. However, little is known about the mechanism by which the ERE regulates the expression of BMPR1B in the endometrium. RESULTS: Here, a 15-bp InDel (insertion/deletion) (AGCCAGAAAGGAGGA) was identified as a unique variation in Taihu pigs, and was shown to be responsible for the binding of the type I receptor of estrogen (ESR1) to the ERE using dual-luciferase assays. Four BMPR1B transcripts (T1, T2, T3, and T4) were identified by 5' RACE in endometrial tissue. Expression of T3 and T4 in the endometrium of Meishan pigs was significantly higher than in Duroc pigs during pregnancy. Luciferase assays showed that three distinct BMPR1B promoters may drive expression of T1, T3, and T4. Interestingly, ERE-mediated enhancement of T4 promoter activity significantly increased expression of Transcript T4 in the endometrium of Taihu pigs (P < 0.05). In contrast, the ERE inhibited activity of the T3 promoter and decreased expression of the T3 transcript in the Duroc background (P < 0.05). In summary, we identified a 15-bp InDel in the Taihu ERE that can be used as a molecular marker for the number born alive trait, characterized the 5' untranslated regions (UTRs) of BMPR1B transcripts in the endometrium, and determined how the transcripts are processed by alternative splicing events. CONCLUSIONS: Our results provide a foundation for understanding the transcriptional regulation of BMPR1B and its contributions to the unique breeding prolificacy characteristics of Taihu pigs.


Assuntos
Endométrio , Mutação INDEL , Feminino , Gravidez , Suínos/genética , Animais , Íntrons , Regiões 5' não Traduzidas , Estrogênios
5.
Diagn Pathol ; 17(1): 69, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36096860

RESUMO

OBJECTIVES: To investigate lymphoid enhancer factor 1 (LEF-1) protein expression in medulloblastomas (MBs) and its correlation with molecular grouping of MBs. METHODS: Expressions of LEF-1 and ß-catenin were detected by immunohistochemistry, and molecular grouping was performed based on the NanoString and sequencing techniques for 30 MBs. RESULTS: By genetic defining, 3 MBs were WNT-activated, 11 were SHH-activated, 3 were in Group 3 and 13 in Group 4 respectively. Nuclear LEF-1 staining was found in 8 MBs using immunohistochemical method. Three out of 8 showed diffuse and strong nuclear LEF-1 staining which were proved to be WNT-activated genetically, while the other 5 MBs with focal staining were SHH-activated genetically. The expression of LEF-1 protein was significantly correlated with genetically defined WNT-activated MBs (P < 0.0001). We also found focal nuclear ß-catenin expression ( less than 1% of tumor cells) in 5 MBs. LEF-1 positivity was significantly correlated nuclear ß-catenin expression (p < 0.001). CONCLUSIONS: Immunohistochemical staining of LEF-1 can be used as a supplement for ß-catenin to diagnosis WNT-activated Medulloblastomas, when ß-catenin is difficult to recognize for its cytoplasm/membrane staining background. Diffuse nuclear staining of LEF-1 indicates WNT-activated MB.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Biomarcadores , Neoplasias Cerebelares/diagnóstico , Humanos , Meduloblastoma/diagnóstico , Meduloblastoma/genética , Meduloblastoma/metabolismo , Coloração e Rotulagem , Fatores de Transcrição TCF , beta Catenina/metabolismo
6.
Front Cell Dev Biol ; 10: 854640, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493102

RESUMO

Background: Structural variations (SVs) are common genetic alterations in the human genome that could cause different phenotypes and diseases, including cancer. However, the detection of structural variations using the second-generation sequencing was limited by its short read length, which restrained our understanding of structural variations. Methods: In this study, we developed a 28-gene panel for long-read sequencing and employed it to Oxford Nanopore Technologies and Pacific Biosciences platforms. We analyzed structural variations in the 28 breast cancer-related genes through long-read genomic and transcriptomic sequencing of tumor, para-tumor, and blood samples in 19 breast cancer patients. Results: Our results showed that some somatic SVs were recurring among the selected genes, though the majority of them occurred in the non-exonic region. We found evidence supporting the existence of hotspot regions for SVs, which extended our previous understanding that they exist only for single nucleotide variations. Conclusion: In conclusion, we employed long-read genomic and transcriptomic sequencing to identify SVs from breast cancer patients and proved that this approach holds great potential in clinical application.

7.
Front Plant Sci ; 13: 854195, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432390

RESUMO

Based on an analysis of the current situation of nitrogen fertiliser application, it is suggested that improving the nitrogen utilisation efficiency of crops is an important means of promoting the sustainable development of agriculture and realises the zero increase in chemical fertiliser application. Nitrate loss and nitrous oxide (N2O) emissions caused by nitrification and denitrification are the main reasons for the low utilisation rate of nitrogen fertilisers. N2O is a greenhouse gas that has caused a sharp increase in global temperature. Biological nitrification inhibition refers to releasing natural compounds that inhibit nitrification from plant roots. The natural compounds released are called biological nitrification inhibitors (BNIs), which specifically inhibit the activity of microorganisms in soil nitrification. Biological nitrification inhibitors can significantly improve rice (Oryza sativa), corn (Zea mays) and other crops by 5-10%, which can increase the nitrogen utilisation rate of corn by 3.1%, and reduce greenhouse gas N2O emissions. Compared with plants that do not produce BNI, the amount of N2O released can be reduced by up to 90%. The BNI released by Brachialactone (Brachiaria humidicola) accounted for 60-90% of the total inhibition of nitrification. In summary, biological nitrification inhibitors that inhibit nitrification, improve nitrogen utilisation and crop yield, and reduce greenhouse gas emissions play an important role. This paper reviews the plants known to release BNIs, reviews the plants known to inhibit soil nitrification but with unknown BNIs and further discusses the important role of bio nitrification inhibition in agricultural systems.

8.
Genomics Proteomics Bioinformatics ; 20(1): 192-204, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33662625

RESUMO

The importance of structural variants (SVs) for human phenotypes and diseases is now recognized. Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed, few benchmarking procedures are available to confidently assess their performances in biological and clinical research. To facilitate the validation and application of these SV detection approaches, we established an Asian reference material by characterizing the genome of an Epstein-Barr virus (EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls. We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers, including 109× Pacific Biosciences (PacBio) continuous long reads (CLRs), 22× PacBio circular consensus sequencing (CCS) reads, 104× Oxford Nanopore Technologies (ONT) long reads, and 114× Bionano optical mapping platform, and one de novo assembly-based SV caller using CCS reads. A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing, demonstrating the robustness of our SV calls. Combining trio-binning-based haplotype assemblies, we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions (CHCRs), which covered 1.46 gigabase pairs (Gb) and 6882 SVs supported by at least one diploid haplotype assembly. Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology, disease, and clinical research.


Assuntos
Benchmarking , Infecções por Vírus Epstein-Barr , Povo Asiático/genética , Haplótipos , Herpesvirus Humano 4 , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Análise de Sequência de DNA/métodos
9.
Sci Rep ; 11(1): 24217, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930936

RESUMO

The history of plants to be utilized as medicines is thousands of years old. Black cumin is one of the most widely examined plant possessing naturally occurring compounds with antimicrobial potential. Foliar application of growth stimulators is a successful strategy to enhance yield and quality in many crops. A field study was planned to apply growth stimulator like moringa leaf extract on black cumin crop grown under field conditions using RCB design with three replications. All other agronomic inputs and practices were uniform. The treatments were moringa leaf extract concentrations (10%, 20%), growth stages (40 days after sowing, 80 DAS, 120 DAS, 40 + 80 DAS, 40 + 120 DAS, 80 + 120 DAS, 40 + 80 + 120 days after sowing) and two controls unsprayed check (i.e. no moringa leaf extract, no water) and sprayed check (no moringa leaf extract + water). Application of 20% moringa leaf extract at stage-7 (40 + 80 + 120 days after sowing) had significantly increased plant height, branches plant-1, essential oil content, fixed oil content, peroxidase value and iodine value of black cumin oil over unsprayed control. Application of moringa leaf extract showed maximum results and improves growth and yield of black cumin when applied at 40 + 80 + 120 days after sowing. As this study was only conducted using moringa leaf extract, it is advisable to conduct an experiment with various bio stimulants along with fertilizer combinations and growth regulators to check their synergistic effects for more reliable and acceptable recommendations in future.

10.
Front Genet ; 12: 638220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211494

RESUMO

Purpose: Exon deletions make up to 80% of mutations in the DMD gene, which cause Duchenne and Becker muscular dystrophy. Exon 45-55 regions were reported as deletion hotspots and intron 44 harbored more than 25% of deletion start points. We aimed to investigate the fine structures of breakpoints in intron 44 to find potential mechanisms of large deletions in intron 44. Methods: Twenty-two dystrophinopathy patients whose deletion started in intron 44 were sequenced using long-read sequencing of a DMD gene capture panel. Sequence homology, palindromic sequences, and polypyrimidine sequences were searched at the breakpoint junctions. RepeatMasker was used to analyze repetitive elements and Mfold was applied to predict secondary DNA structure. Results: With a designed DMD capture panel, 22 samples achieved 2.25 gigabases and 1.28 million reads on average. Average depth was 308× and 99.98% bases were covered at least 1×. The deletion breakpoints in intron 44 were scattered and no breakpoints clustered in any region less than 500 bp. A total of 72.7% of breakpoints located in distal 100 kb of intron 44 and more repetitive elements were found in this region. Microhomologies of 0-1 bp were found in 36.4% (8/22) of patients, which corresponded with non-homologous end-joining. Microhomologies of 2-20 bp were found in 59.1% (13/22) of patients, which corresponded with microhomology-mediated end-joining. Moreover, a 7 bp insertion was found in one patient, which might be evidence of aberrant replication origin firing. Palindromic sequences, polypyrimidine sequences, and small hairpin loops were found near several breakpoint junctions. No evidence of large hairpin loop formation in deletion root sequences was observed. Conclusion: This study was the first to explore possible mechanisms underlying exon deletions starting from intron 44 of the DMD gene based on long-read sequencing. Diverse mechanisms might be associated with deletions in the DMD gene.

12.
Nat Commun ; 12(1): 60, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397900

RESUMO

Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection.


Assuntos
Nanoporos , Análise de Sequência de DNA , Linhagem Celular , Cromossomos Humanos/genética , Genoma Humano , Humanos , Retinoblastoma/genética , Software
13.
Environ Sci Pollut Res Int ; 28(11): 13697-13711, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33200383

RESUMO

Solar radiation (SR) is essential for yield improvement in lentil, which is a crop of marginal environments. Herein, experiments were conducted over 2 years under a semi-arid environment to study the radiation interception (RI), efficiency, growth, and development of three lentil genotypes (Punjab Masoor-2009 (PM-2009), NIAB Masoor-2006 (NM-2006), and NIAB Masoor-2002 (NM-2002)) in relation to three nitrogen rates (13, 19, and 25 kg ha-1). Seasonal dynamics of intercepted photoactive radiation (IPAR) and cumulated photosynthetic photon flux density were highly associated with seasonal dynamics of leaf area index (LAI), with a high value of R2 (0.93 and 0.89) across all nitrogen rates and genotypes in both years. Nitrogen application promoted growth, and maximum LAI (3.97 and 3.57) and RI (324 and 301 MJ m-2) were attained for the first and second years of study, respectively. Biomass and yield were positively associated with IPAR. Variation in radiation absorption (RA) among genotypes was due to different patterns of LAI development. In both years, yield (23% and 25%) and radiation use efficiency (RUE) for grain yield (0.44 and 0.37 g MJ-1) were respectively higher for PM-2009 than for the other genotypes. Genotype PM-2009 had 15 days shorter crop cycle than others while 14% higher GDDs accumulated in the first year compared with the second due to the higher temperature. High nitrogen (25 kg ha-1) application resulted in higher dry matter (DM), and grain yield (GY), while RUE and PAR were not statistically different under 19 kg N ha-1 application across years. Genotypes PM-2009 and NM-2006 may perform reasonably well under arid to semi-arid regions at farmer field. These findings may assist researchers and crop modelers to optimize the lentil ideotype for efficient light utilization.


Assuntos
Lens (Planta) , Biomassa , Lens (Planta)/genética , Nitrogênio , Fotossíntese , Folhas de Planta
14.
PLoS One ; 15(7): e0235515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692781

RESUMO

BACKGROUND: The skin provides a predominant barrier against chemical, physical and microbial incursion. The intemperate exposure to ultraviolet A (UVA) radiation can cause excessive cellular oxidative stress, leading to skin damage, proteins damage and mitochondrial dysfunction. There is sufficient evidences supporting the proposal that mitochondria is highly implicated in skin photo-damage. METHODS: In the present study, a polysaccharide isolated from Astragalus membranaceus was further purified to be an α-glucan, which was further investigated its beneficial influence on UVA-induced photo-damage in HaCaT cells. RESULTS: Our results showed that the purified Astragalus membranaceus polysaccharide (AP) can protect HaCaT cells from UVA-induced photo-damage through reducing UVA-induced intracellular ROS production and mitochondrial membrane potential, thereby altering ATP content. It was found that the UVA induced damage in HaCaT cells could be effectively restored by co-treatment with AP. CONCLUSIONS: AP exhibited promising potential for advanced application as multifunctional skin care products and drugs.


Assuntos
Astragalus propinquus/química , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Polissacarídeos/farmacologia , Protetores contra Radiação/farmacologia , Raios Ultravioleta/efeitos adversos , Trifosfato de Adenosina/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/química , Protetores contra Radiação/química , Espécies Reativas de Oxigênio/metabolismo
15.
Int J Biol Sci ; 16(8): 1388-1402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210727

RESUMO

Objective: The therapeutic effects of the checkpoint kinase 1 (CHK1)-targeted inhibition in tumor therapy have been confirmed, but how to choose an effective application method in breast cancer with heterogeneous molecular characteristics has remained unclear. Methods: We evaluated the status of CHK1 in breast cancer using the cancer genome atlas database. Chemosensitivity and single-agent antitumor activity of CHK1 inhibition were measured by drug sensitivity assay, cell proliferation assay, cell cycle and apoptosis analysis in breast cancer with different ER/PR status. And based on the conjoint transcriptome atlas analyses, the corresponding mechanism were explored. Results: In ER-/PR-/HER2- breast cancer, CHK1 inhibition enhanced adriamycin (ADR) chemosensitivity which was mediated by the mitotic checkpoint complex (MCC)-anaphase-promoting complex/cyclosome (APC/C)-cyclin B1 axis, Msh homeobox 2 (MSX2) and Bcl-2-like protein 11 (BIM). However, in ER+/PR+/HER2- breast cancer, because of the significant suppression for centromere protein F (CENPF)-mediated transcriptional activation of CHK1 induced by ADR itself, CHK1 inhibition fails to sensitize ADR toxicity. Interestingly, CHK1 inhibition showed the single-agent antitumor activity in ER+/PR+/HER2- breast cancer which was mediated by the cyclin dependent kinase inhibitor 1A (p21), kinesin family member 11 (Eg5) and cell surface death receptor (Fas). Conclusions: CHK1's variable role determines the application of CHK1 inhibition in breast cancer with ER/PR heterogeneity.


Assuntos
Neoplasias da Mama/metabolismo , Quinase 1 do Ponto de Checagem/biossíntese , Receptor alfa de Estrogênio/biossíntese , Receptores de Progesterona/biossíntese , Apoptose , Neoplasias da Mama/genética , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Biologia Computacional , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Feminino , Genoma Humano , Humanos , Estimativa de Kaplan-Meier , Células MCF-7 , Interferência de RNA , Resultado do Tratamento
16.
ACS Appl Bio Mater ; 2(1): 544-554, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31853516

RESUMO

Porphyrin-based nanomaterials can inherently integrate multiple contrast imaging functionalities with phototherapeutic capabilities. We dispersed pheophytin (Pheo) into Pluronic F127 and carried out low-temperature surfactant-stripping to remove the bulk surfactant. Surfactant-stripped Pheo (ss-Pheo) micelles exhibited a similar size, but higher near-infrared fluorescence, compared to two other nanomaterials also with high porphyrin density (surfactant-stripped chlorophyll micelles and porphysomes). Singlet oxygen generation, which was higher for ss-Pheo, enabled photodynamic therapy (PDT). ss-Pheo provided contrast for photoacoustic and fluorescence imaging, and following seamless labeling with 64Cu, was used for positron emission tomography. ss-Pheo had a long blood circulation and favorable accumulation in an orthotopic murine mammary tumor model. Trimodal tumor imaging was demonstrated, and PDT resulted in delayed tumor growth.

17.
Adv Mater ; 31(40): e1902279, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31414515

RESUMO

Surfactant-stripped micelles are formed from a commercially available cyanine fluoroalkylphosphate (CyFaP) salt dye and used for high contrast photoacoustic imaging (PAI) in the second near-infrared window (NIR-II). The co-loading of Coenzyme Q10 into surfactant-stripped CyFaP (ss-CyFaP) micelles improves yield, storage stability, and results in a peak absorption wavelength in the NIR-II window close to the 1064 nm output of Nd-YAG lasers used for PAI. Aqueous ss-CyFaP dispersions exhibit intense NIR-II optical absorption, calculated to be greater than 500 at 1064 nm. ss-CyFaP is detected through 12 cm of chicken breast tissue with PAI. In preclinical animal models, ss-CyFaP is visualized in draining lymph nodes of rats through 3.1 cm of overlaid chicken breast tissue. Following intravenous administration, ss-CyFaP accumulates in neoplastic tissues of mice and rats bearing orthotopic mammary tumors without observation of acute toxic side effects. ss-CyFaP is imaged through whole compressed human breasts in three female volunteers at depths of 2.6-5.1 cm. Taken together, these data show that ss-CyFaP is an accessible contrast agent for deep tissue PAI in the NIR-II window.


Assuntos
Mama/citologia , Mama/diagnóstico por imagem , Raios Infravermelhos , Micelas , Imagem Óptica/métodos , Técnicas Fotoacústicas/métodos , Tensoativos/química , Absorção Fisico-Química , Animais , Humanos , Camundongos , Fosfatos/química , Ratos , Ubiquinona/análogos & derivados , Ubiquinona/química
18.
Nat Genet ; 51(5): 865-876, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31043757

RESUMO

High oil and protein content make tetraploid peanut a leading oil and food legume. Here we report a high-quality peanut genome sequence, comprising 2.54 Gb with 20 pseudomolecules and 83,709 protein-coding gene models. We characterize gene functional groups implicated in seed size evolution, seed oil content, disease resistance and symbiotic nitrogen fixation. The peanut B subgenome has more genes and general expression dominance, temporally associated with long-terminal-repeat expansion in the A subgenome that also raises questions about the A-genome progenitor. The polyploid genome provided insights into the evolution of Arachis hypogaea and other legume chromosomes. Resequencing of 52 accessions suggests that independent domestications formed peanut ecotypes. Whereas 0.42-0.47 million years ago (Ma) polyploidy constrained genetic variation, the peanut genome sequence aids mapping and candidate-gene discovery for traits such as seed size and color, foliar disease resistance and others, also providing a cornerstone for functional genomics and peanut improvement.


Assuntos
Arachis/genética , Arachis/embriologia , Arachis/fisiologia , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Resistência à Doença/genética , Domesticação , Secas , Ecótipo , Evolução Molecular , Genoma de Planta , Cariótipo , Óleo de Amendoim/metabolismo , Melhoramento Vegetal , Doenças das Plantas/prevenção & controle , Proteínas de Vegetais Comestíveis/metabolismo , Poliploidia , Sementes/anatomia & histologia , Sementes/genética
19.
Genomics Proteomics Bioinformatics ; 17(6): 558-575, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-32224189

RESUMO

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Biosciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree genome is 1.12 Gb, with 28,422 predicted genes and over 73% repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites; 17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effects between transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.


Assuntos
Aleurites/genética , Aleurites/metabolismo , Evolução Molecular , Genômica , Óleos de Plantas/metabolismo , Sequência de Bases , Regulação da Expressão Gênica de Plantas , Genoma de Planta/genética
20.
ACS Appl Mater Interfaces ; 10(51): 44231-44239, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30499652

RESUMO

Glutathione is overexpressed in tumor cells and regulates cancer growth, metastasis, and drug resistance. Therefore, detecting glutathione levels may greatly facilitate cancer diagnosis and treatment response monitoring. Photoacoustic (PA) imaging is a noninvasive modality for high-sensitivity, high-resolution, deep-tissue optical imaging. Switchable PA probes that offer signal on/off responses to tumor targets would further improve the detection sensitivity and signal-to-noise ratio of PA imaging. Here, we explore the use of MnO2 nanotubes as a switchable and biodegradable PA probe for dynamic imaging of glutathione in cancer. Glutathione reduces black MnO2 nanotubes into colorless Mn2+ ions, leading to decreased and signal off PA amplitude. In phantoms, we observed a linear response of reduced PA signals of MnO2 nanotubes to increased glutathione concentrations. Using melanoma as the disease model, we demonstrated that MnO2 nanotube-based PA imaging of glutathione successfully distinguished B16F10 melanoma cells from BEAS-2B normal cells and discriminated B16F10 tumors from healthy skin tissues. Our results showed that MnO2 nanotubes are a potent switchable and biodegradable PA probe for glutathione imaging in cancer diagnosis.


Assuntos
Glutationa/metabolismo , Compostos de Manganês , Melanoma , Nanotubos/química , Neoplasias Experimentais , Imagem Óptica/métodos , Óxidos , Técnicas Fotoacústicas/métodos , Neoplasias Cutâneas , Animais , Linhagem Celular Tumoral , Humanos , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Melanoma/diagnóstico por imagem , Melanoma/metabolismo , Camundongos , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo , Óxidos/química , Óxidos/farmacologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/metabolismo
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