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1.
JAMA Netw Open ; 7(5): e2411919, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38758552

RESUMO

Importance: Interpatient variabilities in genomic variants may reflect differences in tumor statuses among individuals. Objectives: To delineate interpatient variabilities in RAS variants in thyroid tumors based on the fifth World Health Organization classification of thyroid neoplasms and assess their diagnostic significance in cancer detection among patients with thyroid nodules. Design, Setting, and Participants: This prospective diagnostic study analyzed surgically resected thyroid tumors obtained from February 2016 to April 2022 and residual thyroid fine-needle aspiration (FNA) biopsies obtained from January 2020 to March 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data were analyzed from June 20, 2022, to October 15, 2023. Exposures: Quantitative detection of interpatient disparities of RAS variants (ie, NRAS, HRAS, and KRAS) was performed along with assessment of BRAF V600E and TERT promoter variants (C228T and C250T) by detecting their variant allele fractions (VAFs) using digital polymerase chain reaction assays. Main Outcomes and Measures: Interpatient differences in RAS, BRAF V600E, and TERT promoter variants were analyzed and compared with surgical histopathologic diagnoses. Malignancy rates, sensitivity, specificity, positive predictive values, and negative predictive values were calculated. Results: A total of 438 surgically resected thyroid tumor tissues and 249 thyroid nodule FNA biopsies were obtained from 620 patients (470 [75.8%] female; mean [SD] age, 50.7 [15.9] years). Median (IQR) follow-up for patients who underwent FNA biopsy analysis and subsequent resection was 88 (50-156) days. Of 438 tumors, 89 (20.3%) were identified with the presence of RAS variants, including 51 (11.6%) with NRAS, 29 (6.6%) with HRAS, and 9 (2.1%) with KRAS. The interpatient differences in these variants were discriminated at VAF levels ranging from 0.15% to 51.53%. The mean (SD) VAF of RAS variants exhibited no significant differences among benign nodules (39.2% [11.2%]), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) (25.4% [14.3%]), and malignant neoplasms (33.4% [13.8%]) (P = .28), although their distribution was found in 41.7% of NIFTPs and 50.7% of invasive encapsulated follicular variant papillary thyroid carcinomas (P < .001). RAS variants alone, regardless of a low or high VAF, were significantly associated with neoplasms at low risk of tumor recurrence (60.7% of RAS variants vs 26.9% of samples negative for RAS variants; P < .001). Compared with the sensitivity of 54.2% (95% CI, 48.8%-59.4%) and specificity of 100% (95% CI, 94.8%-100%) for BRAF V600E and TERT promoter variant assays, the inclusion of RAS variants into BRAF and TERT promoter variant assays improved sensitivity to 70.5% (95% CI, 65.4%-75.2%), albeit with a reduction in specificity to 88.8% (95% CI, 79.8%-94.1%) in distinguishing malignant neoplasms from benign and NIFTP tumors. Furthermore, interpatient differences in 5 gene variants (NRAS, HRAS, KRAS, BRAF, and TERT) were discriminated in 54 of 126 indeterminate FNAs (42.9%) and 18 of 76 nondiagnostic FNAs (23.7%), and all tumors with follow-up surgical pathology confirmed malignancy. Conclusions and Relevance: This diagnostic study delineated interpatient differences in RAS variants present in thyroid tumors with a variety of histopathological diagnoses. Discrimination of interpatient variabilities in RAS in combination with BRAF V600E and TERT promoter variants could facilitate cytology examinations in preoperative precision malignancy diagnosis among patients with thyroid nodules.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Telomerase/genética , Idoso , Biópsia por Agulha Fina , Genes ras/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , GTP Fosfo-Hidrolases/genética , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Ontário , Proteínas de Membrana
2.
Front Immunol ; 15: 1363034, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482006

RESUMO

Background: Hay fever, characterized by seasonal allergic reactions, poses a significant health challenge. Existing therapies encompass standard drug regimens, biological agents, and specific immunotherapy. This study aims to assess and compare the effectiveness of anti-IgE (omalizumab), medication therapy, and subcutaneous immunotherapy (SCIT) for hay fever. Methods: Conducted as a retrospective cohort study, this research involved 98 outpatient hay fever patients who underwent routine medication, omalizumab treatment, or SCIT before the onset of the spring pollen season. A follow-up was performed one month after the start of the pollen season. The comprehensive symptoms and drug scores were used to evaluate patients with different intervention methods, facilitating a comparative analysis of therapeutic outcomes. Results: Compared with before treatment, the symptoms of patients treated with the three methods were all significantly relieved, and the medication score were significantly reduced. Patients treated with omalizumab demonstrated higher symptoms and medication scores than SCIT group before treatment, but similar scores after treatment, which were both lower than medicine treatment group. After treatment with omalizumab or SCIT, patients in both groups had significantly lower medication scores than the medication group and were close to no longer using medication for symptom relief. The mountain juniper-sIgE was significantly higher after treatment than before treatment in both medicine treatment group and omalizumab treatment group. Conclusion: Omalizumab and SCIT offer superior effects than medication therapy in hay fever patients.


Assuntos
Anticorpos Anti-Idiotípicos , Omalizumab , Rinite Alérgica Sazonal , Humanos , Omalizumab/uso terapêutico , Rinite Alérgica Sazonal/tratamento farmacológico , Estudos Retrospectivos , Imunossupressores/uso terapêutico , Imunoterapia
3.
ACS Appl Mater Interfaces ; 16(8): 10671-10681, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38359324

RESUMO

The present zwitterionic hydrogel-based wearable sensor exhibits various limitations, such as limited degradation capacity, unavoidable toxicity resulting from initiators, and poor mechanical properties that cannot satisfy practical demands. Herein, we present an initiator and crosslinker-free approach to prepare polyethylene glycol (PEG)@poly[2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl) (PSBMA) interpenetrating polymer network (IPN) hydrogels that are self-polymerized via sunlight-induced and non-covalent crosslinking through electrostatic interaction and hydrogen bonding among polymer chains. The PEG@PSBMA IPN hydrogel possesses tissue-like softness, superior stretchability (∼2344.6% elongation), enhanced fracture strength (∼39.5 kPa), excellent biocompatibility, antibacterial property, reliable adhesion, and ionic conductivity. Furthermore, the sensor based on the IPN hydrogel demonstrates good sensitivity and cyclic stability, enabling effective real-time monitoring of human body activities. Moreover, it is worth noting that the excellent degradability in the saline solution within 8 h makes the prepared hydrogel-based wearable sensor free from the electronic device contamination. We believe that the proposed strategy for preparing physical zwitterionic hydrogels will pave the way for fabricating eco-friendly wearable devices.


Assuntos
Antibacterianos , Materiais Biocompatíveis , Humanos , Contaminação de Medicamentos , Condutividade Elétrica , Hidrogéis , Polímeros
4.
ACS Omega ; 9(1): 509-519, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222531

RESUMO

Adsorption heat conversion systems can provide heating and cooling across time and space in a more environmentally friendly way. Porous materials are potential candidates for water-based adsorption thermal conversion, in which a metal-organic framework (MOF) has a larger specific surface area and porosity than other porous matrices. However, many MOFs with high saturated adsorption capacity have great deficiencies in performance at low water vapor partial pressure, which hinder their application in adsorption thermal conversion. To improve the water vapor adsorption performance of MIL-101 (Cr), different contents of magnesium chloride, lithium chloride, and lanthanum chloride are mixed into MIL-101 (Cr) by an impregnation method. The properties and structures of the materials are characterized by XRD, SEM, nitrogen adsorption tests, water vapor adsorption tests, TG, FTIR, and so on. The results show that the saturated water vapor adsorption capacity of the sample impregnated with salt increases by 1.5-2.3 times, up to 2.24 g/g, compared with that of the unimpregnated sample. When the partial pressure of water vapor is 0.3, the adsorption capacity increases by 5.3-7.5 times and reaches 0.68 g/g at most. The maximum heat storage density of impregnated samples can be increased by 866 J/g. Impregnated MgCl2 can greatly improve the adsorption and thermal conversion performance of MOF, and impregnated MgCl2 and the proper amount of LiCl can further improve the performance of the material system. Our experiments show that the composite impregnation of magnesium chloride and the proper amount of lithium chloride can improve the application performance of the MOF materials in the adsorption thermal conversion process.

5.
Nat Commun ; 14(1): 8395, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110431

RESUMO

The non-classical anodic H2 production from 5-hydroxymethylfurfural (HMF) is very appealing for energy-saving H2 production with value-added chemical conversion due to the low working potential (~0.1 V vs RHE). However, the reaction mechanism is still not clear due to the lack of direct evidence for the critical intermediates. Herein, the detailed mechanisms are explored in-depth using in situ Raman and Infrared spectroscopy, isotope tracking, and density functional theory calculations. The HMF is observed to form two unique inter-convertible gem-diol intermediates in an alkaline medium: 5-(Dihydroxymethyl)furan-2-methanol anion (DHMFM-) and dianion (DHMFM2-). The DHMFM2- is easily oxidized to produce H2 via H- transfer, whereas the DHMFM- is readily oxidized to produce H2O via H+ transfer. The increases in potential considerably facilitate the DHMFM- oxidation rate, shifting the DHMFM- ↔ DHMFM2- equilibrium towards DHMFM- and therefore diminishing anodic H2 production until it terminates. This work captures the critical intermediate DHMFM2- leading to hydrogen production from aldehyde, unraveling a key point for designing higher performing systems.

6.
Sensors (Basel) ; 23(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37687853

RESUMO

To address the challenge of coordinated combat involving multiple UAVs in reconnaissance and search attacks, we propose the Multi-UAV Distributed Self-Organizing Cooperative Intelligence Surveillance and Combat (CISCS) strategy. This strategy employs distributed control to overcome issues associated with centralized control and communication difficulties. Additionally, it introduces a time-constrained formation controller to address the problem of unstable multi-UAV formations and lengthy formation times. Furthermore, a multi-task allocation algorithm is designed to tackle the issue of allocating multiple tasks to individual UAVs, enabling autonomous decision-making at the local level. The distributed self-organized multi-UAV cooperative reconnaissance and combat strategy consists of three main components. Firstly, a multi-UAV finite time formation controller allows for the rapid formation of a mission-specific formation in a finite period. Secondly, a multi-task goal assignment module generates a task sequence for each UAV, utilizing an improved distributed Ant Colony Optimization (ACO) algorithm based on Q-Learning. This module also incorporates a colony disorientation strategy to expand the search range and a search transition strategy to prevent premature convergence of the algorithm. Lastly, a UAV obstacle avoidance module considers internal collisions and provides real-time obstacle avoidance paths for multiple UAVs. In the first part, we propose a formation algorithm in finite time to enable the quick formation of multiple UAVs in a three-dimensional space. In the second part, an improved distributed ACO algorithm based on Q-Learning is introduced for task allocation and generation of task sequences. This module includes a colony disorientation strategy to expand the search range and a search transition strategy to avoid premature convergence. In the third part, a multi-task target assignment module is presented to generate task sequences for each UAV, considering internal collisions. This module provides real-time obstacle avoidance paths for multiple UAVs, preventing premature convergence of the algorithm. Finally, we verify the practicality and reliability of the strategy through simulations.

7.
Dalton Trans ; 52(33): 11671-11678, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37552108

RESUMO

Post-synthetic modification can be used for structural replacement or functional modification of materials after they have been formed or assembled. It can effectively combine various modification methods for metal-organic frameworks (MOFs) such as defect control, replacement of metal sites, or functionalization of ligands. In this work, organic ligands that incorporate N-functionalities or amino groups were introduced into defective UiO-66 through post-synthetic ligand exchange (PSE) to improve its water adsorption performance. Parameters such as water adsorption capacity, half adsorption value (α), and Henry constant KH were used to characterize the water adsorption performance. After PSE, new ligands in different molar ratios entered the skeleton of UiO-66. The N sites or amino groups on the ligands provided new sites for the adsorption of water molecules. The water adsorption capacity and hydrophilicity of all samples were significantly superior to those of LD-UiO-66, which had almost no defects. H-UiO-66-PyDC samples exhibited the highest ligand replacement ratio and a significant enhancement of water adsorption performance. Compared to the unchanged H-UiO-66, the water uptake of H-UiO-66-PyDC increased from 0.08 g g-1 to 0.23 g g-1 at P/P0 = 0.30 and α decreased from 0.36 to 0.28. After 20 water adsorption/desorption tests, the water uptake of all samples did not decrease, showing excellent cycling stability. These results suggest that the combination of defect modulation and PSE is a potential tool to make UiO-66 more appropriate for applications based on reversible adsorption.

8.
JAMA Netw Open ; 6(7): e2323500, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37505499

RESUMO

Importance: Molecular testing of the presence of pathogenic genomic variants in a tumor without quantifying the variant allele fraction (VAF) does not differentiate the variation extent among tumors, often resulting in an inconclusive diagnosis because of interpatient variability. Objective: To examine the association between the quantification of VAFs of BRAF V600E and TERT promoter variants and a definitive cancer diagnosis of thyroid tumors. Design, Setting, and Participants: This diagnostic study analyzed a cohort of 378 surgically resected thyroid tumors with a maximum dimension of 1 cm or larger between March 15, 2016, and March 16, 2020, and a separate cohort of 217 residual thyroid fine-needle aspiration (FNA) biopsy specimens obtained from January 22, 2020, to March 2, 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data analysis was conducted between February 1, 2021, and February 1, 2023. Exposures: Quantitative VAF assays of BRAF V600E and TERT promoter variants (C228T and C250T) were performed by digital polymerase chain reaction molecular assays. Main Outcomes and Measures: The VAFs of BRAF V600E and TERT promoter variants were correlated with tumor histologic diagnoses and histopathologic features to delineate the association of VAF assays with tumor malignancy. The receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, negative predictive value, and logistic regression analysis based on follow-up histopathologic types were used to determine the diagnostic utility of the quantitative molecular assays. Results: A total of 595 specimens, including 378 surgically resected thyroid tumors and 217 thyroid nodule FNA biopsy specimens, were collected from 580 patients (436 [75.2%] female with a mean [SD] age of 50 [16] years and 144 [24.8%] male with a mean [SD] age of 55 [14] years). Sensitive VAF assays of 378 thyroid tumors revealed the presence of the BRAF V600E variant in 162 tumors (42.9%), with 26 (16.0%) at a low VAF of 1% or less and 136 (84.0%) at a high VAF of greater than 1%, and the presence of TERT promoter variants in 49 tumors (13.0%), including 45 C228T variants (91.8%), 15 (33.3%) of which were quantified as having a low VAF (≤1%) and 30 (66.7%) as having a high VAF (>1%), and 4 C250T variants (8.2%) with VAFs between 40.0% and 47.0%. All tumors detected with BRAF V600E and/or TERT promoter variants, whether at low or high VAFs, received a definitive cancer diagnosis. Further analysis delineated a significant association between high VAFs of either variant individually or different VAF levels for both variants in coexistence and aggressive histopathologic features of tumors. Excluding low VAFs assisted in identifying patients at an intermediate-to-high risk of recurrence (odds ratio, 5.3; 95% CI, 1.9-14.6; P = .001). The VAF assays on the residual FNA biopsy specimens showed a high agreement to those on surgical tissues (κ = 0.793, P < .001) and stratified malignancy in 40 of 183 indeterminate FNA cases (21.9%), with a sensitivity of 93.8% (95% CI, 67.7%-99.7%), specificity of 90.0% (95% CI, 75.4%-96.7%), positive predictive value of 78.9% (95% CI, 53.9%-93.0%), and negative predictive value of 97.3% (95% CI, 84.2%-99.9%). Conclusions and Relevance: This diagnostic study suggests that sensitive quantitative VAF assays of BRAF V600E and TERT promoter variants can elucidate the interpatient variability in tumors and facilitate a definitive cancer diagnosis of thyroid nodules by differentiating the variation extent of genomic variants, even at low VAFs.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Telomerase , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Feminino , Humanos , Masculino , Mutação , Ontário , Proteínas Proto-Oncogênicas B-raf/genética , Telomerase/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Adulto , Pessoa de Meia-Idade , Idoso
9.
Plant J ; 115(6): 1528-1543, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37258460

RESUMO

Despite the importance of hybridization in evolution, the evolutionary consequence of homoploid hybridizations in plants remains poorly understood. Specially, homoploid hybridization events have been rarely documented due to a lack of genomic resources and methodological limitations. Actinidia zhejiangensis was suspected to have arisen from hybridization of Actinidia eriantha and Actinidia hemsleyana or Actinidia rufa. However, this species was very rare in nature and exhibited sympatric distribution with its potential parent species, which implied it might be a spontaneous hybrid of ongoing homoploid hybridization. Here, we illustrate the dead-end homoploid hybridization and genomic basis of isolating barriers between A. eriantha and A. hemsleyana through whole genome sequencing and population genomic analyses. Chromosome-scale genome assemblies of A. zhejiangensis and A. hemsleyana were generated. The chromosomes of A. zhejiangensis are confidently assigned to the two haplomes, and one of them originates from A. eriantha and the other originates from A. hemsleyana. Whole genome resequencing data reveal that A. zhejiangensis are mainly F1 hybrids of A. hemsleyana and A. eriantha and gene flow initiated about 0.98 million years ago, implying both strong genetic barriers and ongoing hybridization between these two deeply divergent kiwifruit species. Five inversions containing genes involved in pollen germination and pollen tube growth might account for the fertility breakdown of hybrids between A. hemsleyana and A. eriantha. Despite its distinct morphological traits and long recurrent hybrid origination, A. zhejiangensis does not initiate speciation. Collectively, our study provides new insights into homoploid hybridization in plants and provides genomic resources for evolutionary and functional genomic studies of kiwifruit.


Assuntos
Actinidia , Actinidia/genética , Actinidia/metabolismo , Hibridização Genética , Genoma , Genômica , Plantas/genética , Especiação Genética
10.
Inorg Chem ; 61(45): 17943-17950, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36318203

RESUMO

Adding appropriate modulators can effectively improve the porosity and adsorption performance of UiO-66. Herein, UiO-66 samples were synthesized with p-nitrobenzoic acid (PNBA) and p-hydroxybenzoic acid (PHBA) as modulators. All samples exhibited good crystallinity and thermal stability. The polar functional groups (-NO2 and -OH) and defects were introduced into UiO-66, which significantly improved its water adsorption performance and applications in adsorption heat transformation. With the addition of six equiv PNBA, the saturated water uptake of UiO-66 increased from 0.40 to 0.58 g/g. Also, 4eqPNBA-UiO-66 exhibited the highest water uptake under low relative pressure, which was almost twice that of "low-defect" LD-UiO-66. The addition of PHBA had little effect on the saturated water absorption. However, its highest water uptake at P/P0 = 0.3 is 0.23 g/g, which is equivalent to that of 4eqPNBA-UiO-66. Ten consecutive adsorption/desorption cycles indicated that these samples had good cycle stability.

11.
Nanomicro Lett ; 14(1): 200, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36203066

RESUMO

Electrocatalytic water splitting is a viable technique for generating hydrogen but is precluded from the sluggish kinetics of oxygen evolution reactions (OER). Small molecule oxidation reactions with lower working potentials, such as methanol oxidation reactions, are good alternatives to OER with faster kinetics. However, the typically employed Ni-based electrocatalysts have poor activity and stability. Herein, a novel three-dimensional (3D)-networking Mo-doped Ni(OH)2 with ultralow Ni-Ni coordination is synthesized, which exhibits a high MOR activity of 100 mA cm-2 at 1.39 V, delivering 28 mV dec-1 for the Tafel slope. Meanwhile, hydrogen evolution with value-added formate co-generation is boosted with a current density of more than 500 mA cm-2 at a cell voltage of 2.00 V for 50 h, showing excellent stability in an industrial alkaline concentration (6 M KOH). Mechanistic studies based on density functional theory and X-ray absorption spectroscopy showed that the improved performance is mainly attributed to the ultralow Ni-Ni coordination, 3D-networking structures and Mo dopants, which improve the catalytic activity, increase the active site density and strengthen the Ni(OH)2 3D-networking structures, respectively. This study paves a new way for designing electrocatalysts with enhanced activity and durability for industrial energy-saving hydrogen production.

13.
Nanoscale ; 14(5): 1679-1699, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35048101

RESUMO

The fossil-fuel shortage and severe environmental issues have posed ever-increasing demands on clean and renewable energy sources, for which the exploration of electrocatalysts has been a big challenge toward energy transfer and storage. Some indispensable features of electrocatalysts, such as large surface area, controlled structure, high porosity, and effective functionalization, have been proved to be critical for the improvement of electrocatalytic activities. Recently, the rapid expansion of metal-organic frameworks (MOFs), covalent-organic frameworks (COFs), and porous-organic polymers has provided extensive opportunities for the development of various electrocatalysts. Moreover, combining diverse descriptions of porous-organic frameworks (such as MOFs and COFs) can generate amazing and fantastic properties, affording the formed MOF/COF (including core-shell MOF@MOF and MOF@COF and layer-on-layer MOF-on-MOF or COF-on-MOF) heterostructures wide applications in diverse fields, especially in clean energy and energy transfer. To further boosts electronic conductivity, catalytic performances, and energy storage abilities, these MOF/COF hybrid materials have been widely utilized as versatile precursors for the manufacture of transition metal catalysts embedded within mesoporous carbon nitrides (M@CNx) and porous carbon nitride frameworks (CNx) via a facile pyrolysis process. Given that these M@CNx and CNx hybrids are composed of abundant catalytic centers, rich functionalities, and large specific surface areas, vast applications in energy transfer and energy storage fields can be realized. In this mini-review, we summarize the preparation strategies of MOF/COF-based hybrids, as well as their derivatives, nanostructure formation mechanism of M@CNx and CNx hybrids from MOF/COF-based hybrid materials, and their applications as catalysts for driving diverse reactions and electrode materials for energy storage. Further, current challenges and future prospects of applying these derivatives into energy conversion and storage devices are also discussed.

14.
JAMA Netw Open ; 4(10): e2127243, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613404

RESUMO

Importance: Thyroid cancer, predominantly papillary thyroid carcinoma (PTC), is common, but an estimated 30% of ultrasonography-guided fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate. BRAF variation, associated with poor clinicopathological characteristics, is a useful molecular marker for diagnostics. Objective: To develop a sensitive molecular assay for BRAF V600E detection in remaining tissue of thyroid FNA biopsies to identify patients with cancer carrying a BRAF variation. Design, Setting, and Participants: This diagnostic study used tumor tissue from surgical formalin-fixed, paraffin-embedded (FFPE) specimens and residual tissue from thyroid FNA biopsies for genomic DNA extraction. FFPE specimens served as the validation set, and residual tissue from FNA biopsies served as the test set. A molecular assay was developed for accurate detection of BRAF V600E variation using locked nucleic acid (LNA) probe-based droplet digital polymerase chain reaction (dPCR), and the assay was validated by BRAF V600E immunohistochemical staining (IHC). The study was conducted between February 2019 and May 2021. Results: A total of 271 specimens, including 77 FFPE specimens (with a follow-up of 48 matched surgical specimens) and 146 residual FNA samples, were collected from 223 patients (mean [SD] age, 53.8 [15.3] years; 174 [78.0%] women; 49 [22.0%] men). The molecular assay by dPCR was first established to specifically and accurately detect and quantify wild-type BRAF and variant BRAF in DNA from human follicular thyroid carcinoma-derived FTC-133 and papillary thyroid carcinoma-derived BCPAP cells. The linearity of quantification of BRAF V600E was calculated (y = 0.7339x; R2 = 0.9996) with sensitivity at 0.02 copies/µL and reproducibility in detecting variant DNA at various dilutions(coefficient of variance in 0.3% DNA, 9.63%; coefficient of variance in 1.0% DNA, 7.41%). In validation testing, the dPCR assay and IHC staining exhibited 100% specificity in concordantly identifying BRAF V600E in PTCs (κ = 0.873; P < .001) and sensitivity of 32.0% (95% CI, 19.1% to 44.9%) in dPCR and 26.0% (95% CI, 13.1% to 38.9%) in IHC staining, with an improvement by 23.08% in dPCR compared with the IHC staining. The dPCR assay further detected BRAF V600E in 39 of 146 residual FNA specimens (26.7%). At short-term follow-up, 48 patients, including 14 of 39 patients with BRAF variation and 34 of 107 patients without BRAF variation on residual FNA specimens, underwent resection. The dPCR assay of BRAF status in the matched surgical specimens showed BRAF V600E variations in 12 patients and wild-type BRAF in 36 patients, with a high agreement to that in residual tissue of FNA specimens (κ = 0.789; P < .001). Among 14 patients with BRAF variations on residual FNA, 13 were diagnosed with PTC and 1 was diagnosed with anaplastic thyroid cancer at the thyroidectomy. Conclusions and Relevance: This diagnostic study developed a sensitive molecular assay for detection and quantification of BRAF V600E variation in residual tissue from thyroid FNA biopsies to identify patients with cancer harboring BRAF V600E in a cost-effective manner, highlighting the clinical value of molecular assay of the remaining FNA tissue in the management of thyroid nodules.


Assuntos
Biópsia por Agulha Fina/normas , Proteínas Proto-Oncogênicas B-raf/análise , Nódulo da Glândula Tireoide/patologia , Adulto , Idoso , Biópsia por Agulha Fina/métodos , Biópsia por Agulha Fina/estatística & dados numéricos , Análise Mutacional de DNA/métodos , Técnicas e Procedimentos Diagnósticos/normas , Técnicas e Procedimentos Diagnósticos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/sangue , Reprodutibilidade dos Testes
15.
Cancers (Basel) ; 13(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203725

RESUMO

Background: non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), which is considered as low-risk cancer, should be distinguished from the malignant invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Improved discrimination of NIFTPs from invasive EFVPTCs using a molecular biomarker test could provide useful insights into pre- and post-surgical management of the indeterminate thyroid nodule. Galectin-3 (Gal-3), a ß-galactosyl-binding molecule in the lectin group, is involved in different biological functions in well differentiated thyroid carcinomas. The aim of this study was to determine whether Gal-3 expression as a diagnostic marker could distinguish indolent NIFTP from invasive EFVPTC on tissue specimens from surgical thyroid nodules. Methods: immunohistochemical (IHC) analysis of cytoplasmic and nuclear Gal-3 expression was performed in formalin-fixed paraffin-embedded (FFPE) surgical tissues in four specific diagnostic subgroups- benign nodules, NIFTPs, EFVPTCs and lymphocytic/Hashimoto's thyroiditis (LTs). Results: cytoplasmic Gal-3 expression (mean ± SD) was significantly increased in invasive EFVPTCs (4.80 ± 1.60) compared to NIFTPs (2.75 ± 1.58, p < 0.001) and benign neoplasms (2.09 ± 1.19, p < 0.001) with no significant difference between NIFTPs and benign lesions (p = 0.064). The presence of LT enhanced cytoplasmic Gal-3 expression (3.80 ± 1.32) compared to NIFTPs (p = 0.016) and benign nodules (p < 0.001). Nuclear Gal-3 expression in invasive EFVPTCs (1.84 ± 1.30) was significantly higher than in NIFTPs (1.00 ± 0.72, p = 0.001), but similar to benign nodules (1.44 ± 1.77, p = 0.215), thereby obviating its potential clinical application. Conclusions: our observations have indicated that increased cytoplasmic Gal-3 expression shows diagnostic potential in distinguishing NIFTP among encapsulated follicular variant nodules thereby serving as a possible ancillary test to H&E histopathological diagnostic criteria when LT interference is absent, to assist in the detection of the invasive EFVPTC among such nodules.

16.
Int J Biol Macromol ; 183: 1162-1173, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33971231

RESUMO

With the development of smart devices, higher requirements are put forward for the stimuli-responsive materials. Stimuli-hydrogels as one kind of stimuli-responsive materials with hydrophilicity, demonstrate huge potential in developing intelligent devices for biomedical application. On this basis, we herein report that a sample method was devised to develop a novel composite hydrogel mainly based on oxidized hydroxyethyl cellulose and allyl co-polymer. Subsequently, a series of tests toward this oxidized hydroxyethyl cellulose-based hydrogel due to its structure and performance was applied. Here, the oxidized hydroxyethyl cellulose molecular chains were used as biomacromolecule templates to form Schiff base, borate and hydrogen bonds to obtain unique mechanical properties (fast recovery with almost no-hysteresis and remarkable compressive capacity), while a double bond functionalized spirooxazine (allyl spirooxazine derivative) was applied to endow photo- and pH sensitivity to the oxidized hydroxyethyl cellulose-based transparent hydrogel (T% = 93%) substrate. Furthermore, the oxidized hydroxyethyl cellulose-based hydrogel did exhibit good pH environment adaptability and noncytotoxicity in vitro test. Based on the advanced characteristics, the designed oxidized hydroxyethyl cellulose-based hydrogel has potential applications prospect in the development of safe, fashionable and pH- detectable contact lenses, thereby providing a new strategy for the development of smart, stylish contact lenses.


Assuntos
Celulose/análogos & derivados , Lentes de Contato , Compostos de Espiro/química , Celulose/química , Hidrogéis/síntese química , Hidrogéis/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Processos Fotoquímicos , Bases de Schiff
17.
Int J Mol Sci ; 22(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921262

RESUMO

Hsa-miR-210-3p has been reported to be upregulated in preeclampsia (PE); however, the functions of miR-210-3p in placental development are not fully understood, and, consequently, miR-210-3p's role in the pathogenesis of PE is still under investigation. In this study, we found that overexpression of miR-210-3p reduced trophoblast migration and invasion, extravillous trophoblast (EVT) outgrowth in first trimester explants, expression of endovascular trophoblast (enEVT) markers and the ability of trophoblast to form endothelial-like networks. In addition, miR-210-3p overexpression significantly downregulated the mRNA levels of interleukin-1B and -8, as well as CXC motif ligand 1. These cytokines have been suggested to play a role in EVT invasion and the recruitment of immune cells to the spiral artery remodeling sites. We also showed that caudal-related homeobox transcription factor 2 (CDX2) is targeted by miR-210-3p and that CDX2 downregulation mimicked the observed effects of miR-210-3p upregulation in trophoblasts. These findings suggest that miR-210-3p may play a role in regulating events associated with enEVT functions and its overexpression could impair spiral artery remodeling, thereby contributing to PE.


Assuntos
Fator de Transcrição CDX2/genética , MicroRNAs/genética , Placentação/genética , Artéria Uterina/crescimento & desenvolvimento , Adulto , Movimento Celular/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Placenta/metabolismo , Placenta/patologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Gravidez , Trofoblastos/metabolismo , Trofoblastos/patologia , Artéria Uterina/metabolismo
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 248: 119252, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33316655

RESUMO

A key issue for constructing optical and redox-active receptors is how to conjugate a specific sensing kernel with a multi-signal-responsive system to carry out multi-feature analysis. Mercury is considered to be highly toxic to human health and ecological security. In this work, we present a novel near-infrared optical and redox-active receptor that can sense Hg2+ at ppb level in aqueous media via multi-model monitors with a low detection limit of 8.4 × 10-9 M (1.68 ppb). This receptor features a visible detection, 'off-on' fluorescence response, and efficient electrochemistry assessment, as well as pH-insensitivity to Hg2+ with high sensitivity. In view of its marked near-infrared emission and fluorescence enhancement, we successfully applied this receptor to visualize Hg2+ in live cells. Furthermore, a possible sensing model was established and rationalized with theoretical studies.


Assuntos
Mercúrio , Água , Fluorescência , Corantes Fluorescentes , Humanos , Oxirredução , Rodaminas
19.
Environ Sci Pollut Res Int ; 27(34): 42346-42368, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32862347

RESUMO

The release of toxic organic compounds into the environment in an event of oil spillage is a global menace due to the potential impacts on the ecosystem. Several approaches have been employed for oil spills clean-up, with adsorption technique proven to be more promising for the total reclamation of a polluted site. Of the several adsorbents so far reported, adsorbent-based porous materials have gained attention for the reduction/total removal of different compounds in environmental remediation applications. The superior potential of mesoporous materials based on metal-organic frameworks (MOFs) against conventional adsorbents is due to their intriguing and enhanced properties. Therefore, this review presents recent development in MOF composites; methods of preparation; and their practical applications towards remediating oil spill, organic pollutants, and toxic gases in different environmental media, as well as potential materials in the possible deployment in reclaiming the polluted Niger Delta due to unabated oil spillage and gas flaring.


Assuntos
Poluentes Ambientais , Estruturas Metalorgânicas , Poluição por Petróleo , Ecossistema , Níger
20.
ACS Appl Mater Interfaces ; 12(31): 34999-35010, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32663393

RESUMO

Wastewater pollution has always been one of the most severe worldwide environmental problems. In addition, in light of the frequent oil spills that have occurred in recent years, the treatment of oily wastewater is particularly important. In this work, a novel zeolitic imidazolate framework-8@thiolated graphene (ZIF-8@GSH) composites-based polyimide (PI) nanofibrous membrane was developed via a facile electrospinning and in situ hydrothermal synthesis approaches for effective purification of oily wastewater. The membrane showed superhydrophobicity/superoleophilicity and high separation efficiency (>99.9%) for a wide range of oil/water mixtures and water-in-oil emulsions. Besides, the membrane demonstrated excellent photocatalytic dye degradation, antibacterial, self-cleaning, and mechanochemical durable abilities, showing high potential in oily wastewater treatment and water remediation.


Assuntos
Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Materiais Biomiméticos/farmacologia , Escherichia coli/efeitos dos fármacos , Nanofibras/química , Poluição Química da Água/análise , Antibacterianos/química , Materiais Biomiméticos/química , Testes de Sensibilidade Microbiana , Óleos/química , Tamanho da Partícula , Processos Fotoquímicos , Propriedades de Superfície , Água/química
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