Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 299
Filtrar
1.
Nat Commun ; 15(1): 5627, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965283

RESUMO

Glycosphingolipids (GSLs) are essential components of cell membranes, particularly enriched in the nervous system. Altered molecular distributions of GSLs are increasingly associated with human diseases, emphasizing the significance of lipidomic profiling. Traditional GSL analysis methods are hampered by matrix effect from phospholipids and the difficulty in distinguishing structural isomers. Herein, we introduce a highly sensitive workflow that harnesses magnetic TiO2 nanoparticle-based selective enrichment, charge-tagging Paternò-Büchi reaction, and liquid chromatography-tandem mass spectrometry. This approach enables mapping over 300 distinct GSLs in brain tissues by defining sugar types, long chain bases, N-acyl chains, and the locations of desaturation and hydroxylation. Relative quantitation of GSLs across multiple structural levels provides evidence of dysregulated gene and protein expressions of FA2H and CerS2 in human glioma tissue. Based on the structural features of GSLs, our method accurately differentiates human glioma with/without isocitrate dehydrogenase genetic mutation, and normal brain tissue.


Assuntos
Encéfalo , Glioma , Glicoesfingolipídeos , Humanos , Glicoesfingolipídeos/metabolismo , Glicoesfingolipídeos/química , Glioma/metabolismo , Glioma/genética , Glioma/patologia , Encéfalo/metabolismo , Lipidômica/métodos , Espectrometria de Massas em Tandem/métodos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Cromatografia Líquida/métodos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Animais , Camundongos
2.
J Biomed Mater Res A ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007419

RESUMO

As the cornerstone of tissue engineering and regeneration medicine research, developing a cost-effective and bionic extracellular matrix (ECM) that can precisely modulate cellular behavior and form functional tissue remains challenging. An artificial ECM combining polysaccharides and fibrillar proteins to mimic the structure and composition of natural ECM provides a promising solution for cardiac tissue regeneration. In this study, we developed a bionic hydrogel scaffold by combining a quaternized ß-chitin derivative (QC) and fibrin-matrigel (FM) in different ratios to mimic a natural ECM. We evaluated the stiffness of those composite hydrogels with different mixing ratios and their effects on the growth of human umbilical vein endothelial cells (HUVECs). The optimal hydrogels, QCFM1 hydrogels were further applied to load HUVECs into nude mice for in vivo angiogenesis. Besides, we encapsulated human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) into QCFM hydrogels and employed 3D bioprinting to achieve batch fabrication of human-engineered heart tissue (hEHT). Finally, the myocardial structure and electrophysiological function of hEHT were evaluated by immunofluorescence and optical mapping. Designed artificial ECM has a tunable modulus (220-1380 Pa), which determines the different cellular behavior of HUVECs when encapsulated in these. QCFM1 composite hydrogels with optimal stiffness (800 Pa) and porous architecture were finally identified, which could adapt for in vitro cell spreading and in vivo angiogenesis of HUVECs. Moreover, QCFM1 hydrogels were applied in 3D bioprinting successfully to achieve batch fabrication of both ring-shaped and patch-shaped hEHT. These QCFM1 hydrogels-based hEHTs possess organized sarcomeres and advanced function characteristics comparable to reported hEHTs. The chitin-derived hydrogels are first used for cardiac tissue engineering and achieve the batch fabrication of functionalized artificial myocardium. Specifically, these novel QCFM1 hydrogels provided a reliable and economical choice serving as ideal ECM for application in tissue engineering and regeneration medicine.

3.
Molecules ; 29(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38930975

RESUMO

As a toxic Volatile Organic Pollutant (TVOC), formaldehyde has a toxic effect on microorganisms, consequently inhibiting the biochemical process of formaldehyde wastewater treatment. Therefore, the selective degradation of formaldehyde is of great significance in achieving high-efficiency and low-cost formaldehyde wastewater treatment. This study constructed a heterogeneous Fe-ZSM-5/H2O2 Fenton system f or the selective degradation of target compounds. By immobilizing Fe3+ onto the surface of a ZSM-5 molecular sieve, Fe-ZSM-5 was prepared successfully. XRD, BET and FT-IR spectral studies showed that Fe-ZSM-5 was mainly composed of micropores. The influences of different variables on formaldehyde-selective heterogeneous Fenton degradation performance were studied. The 93.7% formaldehyde degradation and 98.2% selectivity of formaldehyde compared with glucose were demonstrated in the optimized Fenton system after 360 min. Notably, the resultant selective Fenton oxidation system had a wide range of pH suitability, from 3.0 to 10.0. Also, the Fe-ZSM-5 was used in five consecutive cycles without a significant drop in formaldehyde degradation efficiency. The use of reactive oxygen species scavengers indicated that the hydroxyl radical was the primary active species responsible for degrading formaldehyde. Furthermore, great degradation performance was acquired with high concentrations of formaldehyde for this system, and the degradation efficiency was more than 95.0%.

4.
Sci Rep ; 14(1): 14695, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926501

RESUMO

A facile and environmentally friendly ion exchange-assisted surface passivation (IASP) strategy is presented for synthesizing red emitting Mn4+-activated fluoride phosphors. A substantial, pristine Mn4+-free shell layer, applied as a coating to Mn4+ doped potassium fluorosilicate K2SiF6:Mn4+ (KSFM) phosphors, enhances both water resistance and luminescence efficiency. The stability test of fluoride in water at ambient temperature and boiling water demonstrates that IASP-treated KSFM phosphors are highly water resistant. Furthermore, both the negative thermal temperature (NTQ) fitting results and the photoluminescence (PL) decay confirm that the IASP process effectively passivates surface defects, leading to enhanced luminescence performance. The maximum internal quantum yield (QYi) of the IASP-KSFM phosphor is 94.24%. A white LED realized a high color rendering index (CRI) of 93.09 and luminous efficiency (LE) of 149.48 lm/W. This work presented a novel technique for the development of stable fluoride phosphors and has the potential to increase the use of KSFM phosphors in plant supplementary lighting systems and white light-emitting diodes.

5.
Chembiochem ; : e202400316, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867605

RESUMO

With the increasing use of polyethylene glycol (PEG) based proteins and drug delivery systems, anti-PEG antibodies have commonly been detected among the population, causing the accelerated blood clearance and hypersensitivity reactions, poses potential risks to the clinical efficacy and safety of PEGylated drugs. Therefore, vigilant monitoring of anti-PEG antibodies is crucial for both research and clinical guidance regarding PEGylated drugs. The enzyme-linked immunosorbent assay (ELISA) is a common method for detecting anti-PEG antibodies. However, diverse coating methods, blocking solutions and washing solutions have been employed across different studies, and unsuitable use of Tween 20 as the surfactant even caused biased results. In this study, we established the optimal substrate coating conditions, and investigated the influence of various surfactants and blocking solutions on the detection accuracy. The findings revealed that incorporating 1% bovine serum albumin into the serum dilution in the absence of surfactants will result the credible outcomes of anti-PEG antibody detection.

6.
J Nanobiotechnology ; 22(1): 378, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943185

RESUMO

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.


Assuntos
Valvas Cardíacas , Hidrogéis , Ratos Sprague-Dawley , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Animais , Alicerces Teciduais/química , Anisotropia , Ratos , Hidrogéis/química , Materiais Biocompatíveis/química , Próteses Valvulares Cardíacas , Poliésteres/química , Células Cultivadas , Humanos , Matriz Extracelular/química , Masculino
7.
Exp Cell Res ; 440(2): 114148, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38936760

RESUMO

UBA5, a ubiquitin-like activated enzyme involved in ufmylation and sumoylation, presents a viable target for pancreatic and breast cancer treatments, yet its role in lung adenocarcinoma (LUAD) remains underexplored. This study reveals UBA5's tumor-promoting effect in LUAD, as evidenced by its upregulation in patients and positive correlation with TNM stages. Elevated UBA5 levels predict poor outcomes for these patients. Pharmacological inhibition of UBA5 using DKM 2-93 significantly curtails the growth of A549, H1299, and cisplatin-resistant A549 (A549/DDP) LUAD cells in vitro. Additionally, UBA5 knockdown via shRNA lentivirus suppresses tumor growth both in vitro and in vivo. High UBA5 expression adversely alters the tumor immune microenvironment, affecting immunostimulators, MHC molecules, chemokines, receptors, and immune cell infiltration. Notably, UBA5 expression correlates positively with M2 macrophage infiltration, the predominant immune cells in LUAD. Co-culture experiments further demonstrate that UBA5 knockdown directly inhibits M2 macrophage polarization and lactate production in LUAD. Moreover, in vivo studies show reduced M2 macrophage infiltration following UBA5 knockdown. UBA5 expression is also associated with increased tumor heterogeneity, including tumor mutational burden, microsatellite instability, neoantigen presence, and homologous recombination deficiency. Experiments indicate that UBA5 overexpression promotes cisplatin resistance in vitro, whereas UBA5 inhibition enhances cisplatin sensitivity in both in vitro and in vivo settings. Overall, these findings suggest that targeting UBA5 inhibits LUAD by impeding cancer cell proliferation, M2 macrophage polarization, and cisplatin resistance.


Assuntos
Adenocarcinoma de Pulmão , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Humanos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Feminino , Microambiente Tumoral/efeitos dos fármacos , Camundongos Nus , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Masculino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
8.
Toxicology ; 506: 153850, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38821196

RESUMO

Fine particulate matter (PM2.5)-induced metabolic disorders have attracted increasing attention, however, the underlying molecular mechanism of PM2.5-induced hepatic bile acid disorder remains unclear. In this study, we investigated the effects of PM2.5 components on the disruption of bile acid in hepatocytes through farnesoid X receptor (FXR) pathway. The receptor binding assays showed that PM2.5 extracts bound to FXR directly, with half inhibitory concentration (IC50) value of 21.7 µg/mL. PM2.5 extracts significantly promoted FXR-mediated transcriptional activity at 12.5 µg/mL. In mouse primary hepatocytes, we found PM2.5 extracts (100 µg/mL) significantly decreased the total bile acid levels, inhibited the expression of bile acid synthesis gene (Cholesterol 7 alpha-hydroxylase, Cyp7a1), and increased the expression of bile acid transport genes (Multidrug resistance associated protein 2, Abcc2; and Bile salt export pump, Abcb11). Moreover, these alterations were significantly attenuated by knocking down FXR in hepatocytes. We further divided the organic components and water-soluble components from PM2.5, and found that two components bound to and activated FXR, and decreased the bile acid levels in hepatocytes. In addition, benzo[a]pyrene (B[a]P) and cadmium (Cd) were identified as two bioactive components in PM2.5-induced bile acid disorders through FXR signaling pathway. Overall, we found PM2.5 components could bind to and activate FXR, thereby disrupting bile acid synthesis and transport in hepatocytes. These new findings also provide new insights into PM2.5-induced toxicity through nuclear receptor pathways.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38600661

RESUMO

High-voltage resistant quasi-solid-state polymer electrolytes (QSPEs) are promising for enhancing the energy density of lithium-metal batteries in practice. However, side reactions occurring at the interfaces between the anodes or cathodes and QSPEs considerably reduce the lifespan of high-voltage LMBs. In this study, a copolymer of vinyl ethylene carbonate (VEC) and poly(ethylene glycol) diacrylate (PEGDA) was used as the framework, with a cellulose membrane (CE) as the supporting layer. Based on density functional theory calculations, 1-butyl-1-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide (Pyr14TFSI), an ionic liquid, was screened because of its lowest unoccupied molecular orbital energy level as a modifying agent for the in situ P(VECx-EGy)/Pyrz/LiTFSI@CE QSPEs synthesis. Pyr14+, with a lithiophobic alkyl chain, forms a dense positive ion shielding layer on the protruding tips of deposited lithium, facilitating uniform and smooth lithium deposition. Pyr14TFSI assists in constructing a stable solid electrolyte interphase (SEI) layer on the Li surface enriched with LiF, Li3N, and RCOOLi. The modulation of lithium deposition behavior on the anode by Pyr14TFSI ensures stable Li plating/stripping for >1500 h. A Li-Cu cell exhibits stable cycling for >200 cycles at a current density of 0.05 mA cm-2, with an average Coulombic efficiency of 92.7%. In situ polymerization ensures that P(VECx-EGy)/Pyrz/LiTFSI@CE QSPEs exhibit excellent interface compatibility with the anode and the cathode. The CR2032 button cell Li|P(VEC1-EG0.06)/Pyr0.4/LiTFSI@CE|LiCoO2 demonstrates stable cycling with a negligible capacity decay of 0.083% per cycle for >390 cycles at 25 °C and 0.2 C when using a high-voltage LiCoO2 (4.45 V) cathode. Furthermore, a 7.1 mAh pouch cell achieves stable charge-discharge cycles, confirming the pronounced stability of the as-fabricated QSPE at the interfaces of the high-voltage LiCoO2 cathode and Li anode.

10.
Sensors (Basel) ; 24(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38475188

RESUMO

Hyperspectral anomaly detection is used to recognize unusual patterns or anomalies in hyperspectral data. Currently, many spectral-spatial detection methods have been proposed with a cascaded manner; however, they often neglect the complementary characteristics between the spectral and spatial dimensions, which easily leads to yield high false alarm rate. To alleviate this issue, a spectral-spatial information fusion (SSIF) method is designed for hyperspectral anomaly detection. First, an isolation forest is exploited to obtain spectral anomaly map, in which the object-level feature is constructed with an entropy rate segmentation algorithm. Then, a local spatial saliency detection scheme is proposed to produce the spatial anomaly result. Finally, the spectral and spatial anomaly scores are integrated together followed by a domain transform recursive filtering to generate the final detection result. Experiments on five hyperspectral datasets covering ocean and airport scenes prove that the proposed SSIF produces superior detection results over other state-of-the-art detection techniques.

11.
Cell Regen ; 13(1): 6, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38424219

RESUMO

Calcific Aortic Valve Disease (CAVD) is prevalent among the elderly as the most common valvular heart disease. Currently, no pharmaceutical interventions can effectively reverse or prevent CAVD, making valve replacement the primary therapeutic recourse. Extensive research spanning decades has contributed to the establishment of animal and in vitro cell models, which facilitates a deeper understanding of the pathophysiological progression and underlying mechanisms of CAVD. In this review, we provide a comprehensive summary and analysis of the strengths and limitations associated with commonly employed models for the study of valve calcification. We specifically emphasize the advancements in three-dimensional culture technologies, which replicate the structural complexity of the valve. Furthermore, we delve into prospective recommendations for advancing in vivo and in vitro model studies of CAVD.

12.
Adv Healthc Mater ; 13(13): e2303957, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38339835

RESUMO

Interleukin-37 (IL-37) is a potent anti-inflammatory cytokine belonging to the IL-1 family. This study investigates the regulatory mechanism and reparative effects of IL-37 on HF-related human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) and engineered human heart tissue subjected to hypoxia and H2O2 treatment. The contractile force and Ca2+ conduction capacity of the tissue are assessed using a stretching platform and high-resolution fluorescence imaging system. This investigation reveals that IL-37 treatment significantly enhances cell viability, calcium transient levels, contractile force, and Ca2+ conduction capacity in HF-related hiPSC-CMs and engineered human heart tissue. Notably, IL-37 facilitates the upregulation of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) through enhancing nuclear p-STAT3 levels. This effect is mediated by the binding of p-STAT3 to the SERCA2a promoter, providing a novel insight on the reparative potential of IL-37 in HF. IL-37 demonstrates its ability to enhance systolic function by modulating myocardial calcium handling via the p-STAT3/SERCA2a axis in HF-related engineered human heart tissue (as shown in schematic diagram).


Assuntos
Cálcio , Interleucina-1 , Miócitos Cardíacos , Fator de Transcrição STAT3 , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Engenharia Tecidual , Humanos , Fator de Transcrição STAT3/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Interleucina-1/metabolismo , Interleucina-1/farmacologia , Engenharia Tecidual/métodos , Miócitos Cardíacos/metabolismo , Cálcio/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismo , Sobrevivência Celular/efeitos dos fármacos
13.
Science ; 383(6684): 746-750, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38359138

RESUMO

Chemical reactions are generally assumed to proceed from reactants to products along the minimum energy path (MEP). However, straying from the MEP-roaming-has been recognized as an unconventional reaction mechanism and found to occur in both the ground and first excited states. Its existence in highly excited states is however not yet established. We report a dissociation channel to produce electronically excited fragments, S(1D)+O2(a1Δg), from SO2 photodissociation in highly excited states. The results revealed two dissociation pathways: One proceeds through the MEP to produce vibrationally colder O2(a1Δg) and the other yields vibrationally hotter O2(a1Δg) by means of a roaming pathway involving an intramolecular O abstraction during reorientation motion. Such roaming dynamics may well be the rule rather than the exception for molecular photodissociation through highly excited states.

14.
Cell Death Differ ; 31(2): 239-253, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38182899

RESUMO

Efferocytosis and metabolic reprogramming of macrophages play crucial roles in myocardial infarction (MI) repair. TREM2 has been proven to participate in phagocytosis and metabolism, but how it modulates myocardial infarction remains unclear. In this study, we showed that macrophage-specific TREM2 deficiency worsened cardiac function and impaired post-MI repair. Using RNA-seq, protein and molecular docking, and Targeted Metabolomics (LC-MS), our data demonstrated that macrophages expressing TREM2 exhibited decreased SLC25A53 transcription through the SYK-SMAD4 signaling pathway after efferocytosis, which impaired NAD+ transport into mitochondria, downregulated SLC25A53 thereby causing the breakpoint in the TCA cycle and subsequently increased itaconate production. In vitro experiments confirmed that itaconate secreted by TREM2+ macrophages inhibited cardiomyocyte apoptosis and promoted fibroblast proliferation. Conversely, overexpression of TREM2 in macrophages could improve cardiac function. In summary, our study reveals a novel role for macrophage-specific TREM2 in MI, connecting efferocytosis to immune metabolism during cardiac repair.


Assuntos
Infarto do Miocárdio , Animais , Camundongos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Succinatos/metabolismo , Humanos
15.
Environ Toxicol ; 39(1): 421-434, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37792549

RESUMO

Papillary thyroid cancer (PTC) is a prevalent malignancy worldwide. Spleen tyrosine kinase (SYK) is a crucial enzyme that participates in various biological processes, including cancer progression. This study aims to uncover the biological function of SYK in PTC. SYK expression patterns in PTC were evaluated using quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and western blot. Cell function assays were performed to assess the effects of SYK on PTC. Bioinformatics analysis was conducted to identify intriguing microRNA (miRNA) and circular RNA (circRNA). Dual-Luciferase Reporter or RNA immunoprecipitation assays were used to investigate the correlation among SYK, miR-377-3p, and hsa_circ_0006417. SYK was upregulated in PTC. Overexpression of SYK exhibited a positive correlation with tumor size, lymph node metastasis, and unfavorable disease-free survival. Functional assays revealed that SYK exerted tumorigenic effect on PTC cells through mTOR/4E-BP1 pathway. Mechanistically, hsa_circ_0006417 and miR-377-3p regulated SYK expression, offering modulating its tumor-promoting effects. Collectively, SYK acts as an oncogene in PTC through mTOR/4E-BP1 pathway, which is regulated by the hsa_circ_0006417/miR-377-3p axis, thereby providing a potential alternative for PTC treatment.


Assuntos
MicroRNAs , RNA Circular , Quinase Syk , Neoplasias da Glândula Tireoide , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Quinase Syk/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Serina-Treonina Quinases TOR , RNA Circular/genética
16.
Nano Lett ; 24(1): 51-60, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37823474

RESUMO

The lateral flow immunoassay (LFIA) is a sought-after point-of-care testing platform, yet the insufficient sensitivity of the LFIA limits its application in the detection of tumor biomarkers. Here, a colorimetric signal amplification method, bimetallic nanozyme-mediated in situ-catalyzed reporter deposition (BN-ISCRD), was designed for ultrasensitive cancer diagnosis. The bimetallic nanozyme used, palladium@iridium core-shell nanoparticles (Pd@Ir NPs), had ultrahigh enzyme-like activity, which was further explained by the electron transfer of Pd@Ir NPs and the change in the Gibbs free energy during catalysis through density functional theory calculations. With gastric cancer biomarkers pepsinogen I and pepsinogen II as model targets, this assay could achieve a cutoff value of 10 pg/mL, which was 200-fold lower than that without signal enhancement. The assay was applied to correctly identify 8 positive and 28 negative clinical samples. Overall, this BN-ISCRD-based LFIA showed great merits and potential in the application of ultrasensitive disease diagnosis.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias , Humanos , Imunoensaio/métodos , Biomarcadores Tumorais , Catálise , Neoplasias/diagnóstico , Limite de Detecção , Ouro
17.
Plant Phenomics ; 5: 0123, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38047001

RESUMO

Accurate segmentation and detection of rice seedlings is essential for precision agriculture and high-yield cultivation. However, current methods suffer from high computational complexity and poor robustness to different rice varieties and densities. This article proposes 2 lightweight neural network architectures, LW-Segnet and LW-Unet, for high-precision rice seedling segmentation. The networks adopt an encoder-decoder structure with hybrid lightweight convolutions and spatial pyramid dilated convolutions, achieving accurate segmentation while reducing model parameters. Multispectral imagery acquired by unmanned aerial vehicle (UAV) was used to train and test the models covering 3 rice varieties and different planting densities. Experimental results demonstrate that the proposed LW-Segnet and LW-Unet models achieve higher F1-scores and intersection over union values for seedling detection and row segmentation across varieties, indicating improved segmentation accuracy. Furthermore, the models exhibit stable performance when handling different varieties and densities, showing strong robustness. In terms of efficiency, the networks have lower graphics processing unit memory usage, complexity, and parameters but faster inference speeds, reflecting higher computational efficiency. In particular, the fast speed of LW-Unet indicates potential for real-time applications. The study presents lightweight yet effective neural network architectures for agricultural tasks. By handling multiple rice varieties and densities with high accuracy, efficiency, and robustness, the models show promise for use in edge devices and UAVs to assist precision farming and crop management. The findings provide valuable insights into designing lightweight deep learning models to tackle complex agricultural problems.

18.
Appl Opt ; 62(35): 9291-9298, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38108700

RESUMO

The stability of beam pointing in a laser system depends on the consistency of the optical mirror mount. Typically, a locking mechanism is used to secure the adjustment mechanism after beam alignment, ensuring the mount's stability. However, this process can introduce errors, causing a drift in the optical path. To mitigate this issue, in this study, an interference fit adjustment screw was designed. This development enables the mechanism to self-lock after beam alignment, thereby preventing optical path drift and enhancing overall stability. Specifically, 14 long-term thermal shock stability tests, each lasting 2500 min, were conducted to validate the proposed design. The experimental results showed that the thermal drift of the interference fit adjustment screw was reduced by 47.16%, thermal shift was reduced by 79.59%, and the long-term stability improved by at least 48.67%.

19.
Front Oncol ; 13: 1237308, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37799479

RESUMO

Introduction: The distinction between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) holds clinical significance in staging, therapeutic intervention, and prognosis assessment for multiple lung cancer. Lineage tracing by clinicopathologic features alone remains a clinical challenge; thus, we aimed to develop a multi-omics analysis method delineating spatiotemporal heterogeneity based on tumor genomic profiling. Methods: Between 2012 and 2022, 11 specimens were collected from two patients diagnosed with multiple lung cancer (LU1 and LU2) with synchronous/metachronous tumors. A novel multi-omics analysis method based on whole-exome sequencing, transcriptome sequencing (RNA-Seq), and tumor neoantigen prediction was developed to define the lineage. Traditional clinicopathologic reviews and an imaging-based algorithm were performed to verify the results. Results: Seven tissue biopsies were collected from LU1. The multi-omics analysis method demonstrated that three synchronous tumors observed in 2018 (LU1B/C/D) had strong molecular heterogeneity, various RNA expression and immune microenvironment characteristics, and unique neoantigens. These results suggested that LU1B, LU1C, and LU1D were MPLC, consistent with traditional lineage tracing approaches. The high mutational landscape similarity score (75.1%), similar RNA expression features, and considerable shared neoantigens (n = 241) revealed the IPM relationship between LU1F and LU1G which were two samples detected simultaneously in 2021. Although the multi-omics analysis method aligned with the imaging-based algorithm, pathology and clinicopathologic approaches suggested MPLC owing to different histological types of LU1F/G. Moreover, controversial lineage or misclassification of LU2's synchronous/metachronous samples (LU2B/D and LU2C/E) traced by traditional approaches might be corrected by the multi-omics analysis method. Spatiotemporal heterogeneity profiled by the multi-omics analysis method suggested that LU2D possibly had the same lineage as LU2B (similarity score, 12.9%; shared neoantigens, n = 71); gefitinib treatment and EGFR, TP53, and RB1 mutations suggested the possibility that LU2E might result from histology transformation of LU2C despite the lack of LU2C biopsy and its histology. By contrast, histological interpretation was indeterminate for LU2D, and LU2E was defined as a primary or progression lesion of LU2C by histological, clinicopathologic, or imaging-based approaches. Conclusion: This novel multi-omics analysis method improves the accuracy of lineage tracing by tracking the spatiotemporal heterogeneity of serial samples. Further validation is required for its clinical application in accurate diagnosis, disease management, and improving prognosis.

20.
Cell Mol Life Sci ; 80(11): 330, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37856006

RESUMO

Dramatic alterations in epigenetic landscapes are known to impact genome accessibility and transcription. Extensive evidence demonstrates that senescent cells undergo significant changes in chromatin structure; however, the mechanisms underlying the crosstalk between epigenetic parameters and gene expression profiles have not been fully elucidated. In the present study, we delineate the genome-wide redistribution of accessible chromatin regions that lead to broad transcriptome effects during senescence. We report that distinct senescence-activated accessibility regions (SAAs) are always distributed in H3K27ac-occupied enhancer regions, where they are responsible for elevated flanking senescence-associated secretory phenotype (SASP) expression and aberrant cellular signaling relevant to SASP secretion. Mechanistically, a single transcription factor, TEAD4, moves away from H3K27ac-labled SAAs to allow for prominent chromatin accessibility reconstruction during senescence. The enhanced SAAs signal driven by TEAD4 suppression subsequently induces a robust increase in the expression of adjacent SASP genes and the secretion of downstream factors, which contribute to the progression of senescence. Our findings illustrate a dynamic landscape of chromatin accessibility following senescence entry, and further reveal an insightful function for TEAD4 in regulating the broad chromatin state that modulates the overall transcriptional program of SASP genes.


Assuntos
Senescência Celular , Cromatina , Cromatina/genética , Senescência Celular/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sequências Reguladoras de Ácido Nucleico , Regulação da Expressão Gênica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA