Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 196
Filtrar
1.
Anal Chem ; 96(10): 4259-4265, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38418962

RESUMO

Mass spectrometry (MS) imaging of lipids in tissues with high structure specificity is challenging in the effective fragmentation of position-selective structures and the sensitive detection of multiple lipid isomers. Herein, we develop an MS3 imaging method for the simultaneous analysis of phospholipid C═C and sn-position isomers by on-tissue photochemical derivatization, nanospray desorption electrospray ionization (nano-DESI), and a dual-linear ion trap MS system. A novel laser-based sensing probe is developed for the real-time adjustment of the probe-to-surface distance for nano-DESI. This method is validated in mouse brain and kidney sections, showing its capability of sensitive resolving and imaging of the fatty acyl chain composition, the sn-position, and the C═C location of phospholipids in an MS3 scan. MS3 imaging of phospholipids has shown the capability of differentiation of cancerous, fibrosis, and adjacent normal regions in liver cancer tissues.


Assuntos
Fosfolipídeos , Espectrometria de Massas por Ionização por Electrospray , Camundongos , Animais , Fosfolipídeos/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Isomerismo , Cromatografia Gasosa-Espectrometria de Massas , Diagnóstico por Imagem
2.
J Microsc ; 294(3): 397-410, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38691400

RESUMO

In the dynamic landscape of scientific research, imaging core facilities are vital hubs propelling collaboration and innovation at the technology development and dissemination frontier. Here, we present a collaborative effort led by Global BioImaging (GBI), introducing international recommendations geared towards elevating the careers of Imaging Scientists in core facilities. Despite the critical role of Imaging Scientists in modern research ecosystems, challenges persist in recognising their value, aligning performance metrics and providing avenues for career progression and job security. The challenges encompass a mismatch between classic academic career paths and service-oriented roles, resulting in a lack of understanding regarding the value and impact of Imaging Scientists and core facilities and how to evaluate them properly. They further include challenges around sustainability, dedicated training opportunities and the recruitment and retention of talent. Structured across these interrelated sections, the recommendations within this publication aim to propose globally applicable solutions to navigate these challenges. These recommendations apply equally to colleagues working in other core facilities and research institutions through which access to technologies is facilitated and supported. This publication emphasises the pivotal role of Imaging Scientists in advancing research programs and presents a blueprint for fostering their career progression within institutions all around the world.


Assuntos
Pesquisadores , Humanos , Mobilidade Ocupacional , Pesquisa Biomédica/métodos , Escolha da Profissão
3.
Med Sci Monit ; 30: e944157, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38794788

RESUMO

BACKGROUND Micro-needle knife (MNK) therapy releases the superficial fascia to alleviate pain and improve joint function in patients with acute ankle sprains (AAS). We aimed to evaluate the efficacy and safety of MNK therapy vs that of acupuncture. MATERIAL AND METHODS This blinded assessor, randomized controlled trial allocated 80 patients with AAS to 2 parallel groups in a 1: 1 ratio. The experimental group received MNK therapy; the control group underwent conventional acupuncture treatment at specified acupoints. Clinical efficacy differences between the 2 groups before (time-point 1 [TP1]) and after treatment (TP2) were evaluated using the visual analogue scale (VAS) and Kofoed ankle score. Safety records and evaluations of adverse events were documented. One-month follow-up after treatment (TP3) was conducted to assess the intervention scheme's reliability. RESULTS VAS and Kofoed ankle scores significantly improved in both groups. No patients dropped due to adverse events. At TP1, there were no significant differences between the 2 groups in terms of VAS and Kofoed scores (P>0.05). However, at TP2, efficacy of MNK therapy in releasing the superficial fascia was significantly superior to that of acupuncture treatment (P<0.001). At TP3, no significant differences in scores existed between the groups (P>0.05). CONCLUSIONS This study demonstrates that 6 sessions of MNK therapy to release the superficial fascia safely and effectively alleviated pain and enhanced ankle joint function in patients with AAS, surpassing the efficacy of conventional acupuncture treatment. Future studies should increase the sample size and introduce additional control groups to further validate the superior clinical efficacy of this intervention.


Assuntos
Terapia por Acupuntura , Traumatismos do Tornozelo , Entorses e Distensões , Humanos , Masculino , Feminino , Traumatismos do Tornozelo/terapia , Terapia por Acupuntura/métodos , Adulto , Resultado do Tratamento , Entorses e Distensões/terapia , Pessoa de Meia-Idade , Medição da Dor , Pontos de Acupuntura , Agulhas
4.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33526687

RESUMO

Vertical sleeve gastrectomy (VSG) is one of the most effective and durable therapies for morbid obesity and its related complications. Although bile acids (BAs) have been implicated as downstream mediators of VSG, the specific mechanisms through which BA changes contribute to the metabolic effects of VSG remain poorly understood. Here, we confirm that high fat diet-fed global farnesoid X receptor (Fxr) knockout mice are resistant to the beneficial metabolic effects of VSG. However, the beneficial effects of VSG were retained in high fat diet-fed intestine- or liver-specific Fxr knockouts, and VSG did not result in Fxr activation in the liver or intestine of control mice. Instead, VSG decreased expression of positive hepatic Fxr target genes, including the bile salt export pump (Bsep) that delivers BAs to the biliary pathway. This reduced small intestine BA levels in mice, leading to lower intestinal fat absorption. These findings were verified in sterol 27-hydroxylase (Cyp27a1) knockout mice, which exhibited low intestinal BAs and fat absorption and did not show metabolic improvements following VSG. In addition, restoring small intestinal BA levels by dietary supplementation with taurocholic acid (TCA) partially blocked the beneficial effects of VSG. Altogether, these findings suggest that reductions in intestinal BAs and lipid absorption contribute to the metabolic benefits of VSG.


Assuntos
Colestanotriol 26-Mono-Oxigenase/genética , Gastrectomia/métodos , Obesidade Mórbida/cirurgia , Receptores Citoplasmáticos e Nucleares/genética , Animais , Ácidos e Sais Biliares/biossíntese , Ácidos e Sais Biliares/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Camundongos , Camundongos Knockout , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Redução de Peso/genética
5.
Pain Manag Nurs ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38609804

RESUMO

BACKGROUND: Many studies have focused on the quality of pain management in hospitalized patients with cancer pain, while what happens after discharge remains unclear. AIM: The purpose of this study was to investigate the pain intensity and satisfaction of pain relief among a large sample of Chinese patients with cancer pain after discharge. DESIGN: Cross-sectional, descriptive, correlational research. SETTINGS AND SAMPLE: ABOUT: 1,013 patients were recruited in a tertiary cancer hospital, and their residence addresses were distributed in 6 geographical regions, including 26 provinces, municipalities, and autonomous regions. METHODS: The 1,013 patients with cancer pain were discharged from the wards of a national cancer hospital in China from July 2020 to October 2021. A nurse in the pain clinic followed the patients based on a whole-process information system and collected the data after the cancer pain patients were discharged. The study methods followed the STROBE guidelines. RESULTS: The average age of 1,013 discharged patients was 61.30 (±12.56) years. Moderate and severe background pain (BGP) was reported in 749 patients (73.94%), and more than 3 instances of breakthrough pain (BTP) in the past 24 hours were reported in 541 patients (53.41%). More severe BGP was associated with more frequent BTP (p < .01). In addition, there were 572 patients (56.47%) whose satisfaction with pain relief was lower than 70%. More severe BGP was associated with a lower satisfaction degree (r = -0.796, p < .01). CONCLUSIONS: Pain among discharged Chinese patients with cancer is poorly managed, and there is a low degree of satisfaction with pain relief. Nurses can do more work to assist cancer patients in managing pain more effectively by ensuring they have a plan to report and manage pain after discharge.

6.
J Am Chem Soc ; 145(50): 27680-27689, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38054457

RESUMO

We report a palladium-catalyzed method for 4,3- or 4,1-selective alkenylamination of terminal dienes. Three-component couplings proceed with alkenyl triflates and several amines, giving vicinal carboamination with a Xantphos-supported catalyst and distal difunctionalization with a phosphoramidite ligand. A number of constitutionally different disubstituted dienes also participate in regiodivergent carboaminations. Experimental evidence indicates that selectivity in the Xantphos reactions is largely influenced by the substrate, whereas the phosphoramidite-promoted process is catalyst controlled, orchestrated by a key π-stacking interaction among the ligand, solvent, and substrate.

7.
Anal Chem ; 95(29): 10879-10886, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37427961

RESUMO

Mass spectrometry imaging (MSI) is a powerful methodology that enables the visualization of the spatial distribution of biomolecules, including lipids, peptides, and proteins, from biological tissue sections. While two-dimensional (2D) MSI has been widely reported in various applications, three-dimensional (3D) MSI can enable the mapping of biomolecule distribution in complex biological structures (e.g., organs) with an added dimension. However, traditional 3D MSI techniques are time-consuming since 3D MS images are constructed from 2D MSI analyses of a series of tissue sections. In this study, we propose a 3D MSI workflow, termed DeepS, which uses a 3D sparse sampling network (3D-SSNet) and a sparse sampling strategy to significantly accelerate 3D MSI analyses. Sparsely sampled tissue sections are reconstructed using 3D-SSNet, yielding results comparable to those using full sampling MSI, even at a sampling ratio of 20-30%. The workflow performed well when applied to 3D imaging of a mouse brain with Alzheimer's disease, and combined with transfer learning, it is successfully used for the 3D MSI analyses of more heterogeneous samples, e.g., a mouse brain with glioblastoma and a mouse kidney.


Assuntos
Glioblastoma , Imageamento Tridimensional , Camundongos , Animais , Espectrometria de Massas/métodos , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
8.
Anal Chem ; 95(29): 11099-11105, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37431610

RESUMO

In the past decade, mass spectrometry (MS) has been widely used for a broad range of on-site applications. This is largely attributed to the rapid advancement of technologies, such as ambient ionization and mass spectrometer miniaturization. Here, we report the development of the temperature-tuning desorption ionization (TTDI) method for versatile on-site applications using a miniature MS system. A unique feature of TTDI is its dynamic temperature range applicable from 30 to 800 °C, which enables optimal desorption ionization applied for chemical and biological compounds through tuning the temperature at the sampling spot. The versatility of TTDI has been demonstrated through on-site MS analysis of a variety of samples, such as explosives on surfaces, drugs of abuse in biofluids, and screening biomarkers in tissues.

9.
Anal Chem ; 95(18): 7212-7219, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37078759

RESUMO

Mass spectrometry (MS) has become a powerful tool for metabolome, lipidome, and proteome analyses. The efficient analysis of multi-omics in single cells, however, is still challenging in the manipulation of single cells and lack of in-fly cellular digestion and extraction approaches. Here, we present a streamlined strategy for highly efficient and automatic single-cell multi-omics analysis by MS. We developed a 10-pL-level microwell chip for housing individual single cells, whose proteins were found to be digested in 5 min, which is 144 times shorter than traditional bulk digestion. Besides, an automated picoliter extraction system was developed for sampling of metabolites, phospholipids, and proteins in tandem from the same single cell. Also, 2 min MS2 spectra were obtained from 700 pL solution of a single cell sample. In addition, 1391 proteins, phospholipids, and metabolites were detected from one single cell within 10 min. We further analyzed cells digested from cancer tissue samples, achieving up to 40% increase in cell classification accuracy using multi-omics analysis in comparison with single-omics analysis. This automated single-cell MS strategy is highly efficient in analyzing multi-omics information for investigation of cell heterogeneity and phenotyping for biomedical applications.


Assuntos
Multiômica , Proteoma , Espectrometria de Massas , Proteoma/análise , Fosfolipídeos , Manejo de Espécimes
10.
Radiology ; 309(2): e230681, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37962500

RESUMO

Background Iodinated contrast agents (ICAs), which are widely used in CT angiography (CTA), may cause adverse effects in humans, and their use is time-consuming and costly. Purpose To develop an ICA-free deep learning imaging model for synthesizing CTA-like images and to assess quantitative and qualitative image quality as well as the diagnostic accuracy of synthetic CTA (Syn-CTA) images. Materials and Methods A generative adversarial network (GAN)-based CTA imaging model was trained, validated, and tested on retrospectively collected pairs of noncontrast CT and CTA images of the neck and abdomen from January 2017 to June 2022, and further validated on an external data set. Syn-CTA image quality was evaluated using quantitative metrics. In addition, two senior radiologists scored the visual quality on a three-point scale (3 = good) and determined the vascular diagnosis. The validity of Syn-CTA images was evaluated by comparing the visual quality scores and diagnostic accuracy of aortic and carotid artery disease between Syn-CTA and real CTA scans. Results CT scans from 1749 patients (median age, 60 years [IQR, 50-68 years]; 1057 male patients) were included in the internal data set: 1137 for training, 400 for validation, and 212 for testing. The external validation set comprised CT scans from 42 patients (median age, 67 years [IQR, 59-74 years]; 37 male patients). Syn-CTA images had high similarity to real CTA images (normalized mean absolute error, 0.011 and 0.013 for internal and external test set, respectively; peak signal-to-noise ratio, 32.07 dB and 31.58 dB; structural similarity, 0.919 and 0.906). The visual quality of Syn-CTA and real CTA images was comparable (internal test set, P = .35; external validation set, P > .99). Syn-CTA showed reasonable to good diagnostic accuracy for vascular diseases (internal test set: accuracy = 94%, macro F1 score = 91%; external validation set: accuracy = 86%, macro F1 score = 83%). Conclusion A GAN-based model that synthesizes neck and abdominal CTA-like images without the use of ICAs shows promise in vascular diagnosis compared with real CTA images. Clinical trial registration no. NCT05471869 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zhang and Turkbey in this issue.


Assuntos
Aorta , Angiografia por Tomografia Computadorizada , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Artérias Carótidas
11.
Opt Express ; 31(16): 25829-25839, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710458

RESUMO

In this study, we propose the design of a surface acoustic wave (SAW) near-infrared sensor combined with an MXene quantum dot thin film to improve the infrared absorption efficiency at near-infrared wavelengths. A YZ-cut lithium niobate (LiNbO3) SAW resonator is fabricated as an infrared sensing unit with a resonant frequency shift reflecting the change in infrared radiation. It was observed that the responsivity of the near-infrared sensor (with a base frequency of 460 MHz) increased by approximately 88.89%. Thus, the proposed device exhibits high-performance infrared detection. Owing to the passive wireless capability of the device, it has wide applications.

12.
Phys Rev Lett ; 131(13): 136101, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37832014

RESUMO

Twinning is profuse in bcc transition metals (TMs) except bulk W and Mo. However, W and Mo nanocrystals surprisingly exhibit twinning during room temperature compression, which is completely unexpected as established nucleation mechanisms are not viable in them. Here, we reveal the physical origin of deformation twinning in W and Mo. We employ density functional theory (DFT) and a reduced-constraint slip method to compute the stress-dependent generalized stacking fault enthalpy (GSFH), the thermodynamic quantity to be minimized under constant loading. The simple slipped structures and GSFH lines show that compressive stresses stabilize a two-layer twin embryo, which can grow rapidly via twinning disconnections with negligible energy barriers. Direct atomistic simulations unveil the explicit twinning path in agreement with the DFT GSFH lines. Twinning is thus the preferred deformation mechanism in W and Mo when shear stresses are coupled with high compressive stresses. Furthermore, twinnability can be related to the elastic constants of a stacking fault phase (SFP). The hcp phase may serve as a candidate SFP for the {112}⟨1[over ¯]1[over ¯]1⟩ twinning system in bcc TMs and alloys, which is coincident with the {111}⟨112[over ¯]⟩ twinning in fcc structures.

13.
J Magn Reson Imaging ; 58(3): 732-738, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36594577

RESUMO

BACKGROUND: Glioma genotypes are of importance for clinical decision-making. This data can only be acquired through histopathological analysis based on resection or biopsy. Consequently, there is a need for alternative biomarkers that noninvasively provide reliable information for preoperatively identifying molecular characteristics. PURPOSE: To investigate apparent diffusion coefficient (ADC) as imaging biomarker for preoperatively identifying glioma genotypes based on the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors. STUDY TYPE: Retrospective. SUBJECTS: One hundred and fifty-nine patients (47.6 ± 14.4 years) diagnosed with WHO grade 2-4 glioma including 93 males and 66 females. FIELD STRENGTH/SEQUENCE: A 3 T/spin echo echo planner imaging. ASSESSMENT: The ADC measurements were assessed by two neuroradiologists (both with 6 years of experience). Three different lowest portions inside the tumors without overlap were manually drawn on the ADC maps as regions of interest (ROIs). The mean ADC value of the three ROIs was defined as the minimum ADC value (ADCmin ). An ROI was placed in the contralateral normal appearing white matter (NAWM) to obtain the ADC value (ADCNAWM ). The ADCmin to ADCNAWM ratio (ADCratio ) was calculated. Genetics results were retrospectively recorded from pathologic and genetic test reports. STATISTICAL TESTS: Two-sample independent t-tests, receiver operating characteristic curve analysis, and intraclass correlation coefficient analysis were used. Statistical significance was set at P < 0.05. RESULTS: Isocitrate dehydrogenase (IDH)-mutated glioma showed higher ADCmin and ADCratio than IDH wild-type glioma. Among IDH-mutated glioma, higher ADCmin and ADCratio were found in 1p19q intact glioma than in 1p19q codeletion glioma. ADC parameters enabled differentiation of IDH mutation status with area under the curve (AUC) of 0.84 and 0.86. DATA CONCLUSION: ADC has potential discriminative value for IDH mutation and 1p19q codeletion status. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.


Assuntos
Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Humanos , Glioma/diagnóstico por imagem , Glioma/genética , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Isocitrato Desidrogenase/genética , Mutação , Regiões Promotoras Genéticas , Biomarcadores Tumorais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Imagem de Difusão por Ressonância Magnética , Estudos Retrospectivos , Idoso
14.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674428

RESUMO

Roots are essential for plant growth, and studies on root-related genes, exemplified by WUSCHEL-RELATED HOMEOBOX5 (WOX5), have mainly concentrated on model organisms with less emphasis on the function of these genes in woody plants. Here, we report that overexpression of the WOX5 gene from Liriodendron hybrid (LhWOX5) in Arabidopsis leads to significant morphological changes in both the aerial and subterranean organs. In the Arabidopsis aerial parts, overexpression of LhWOX5 results in the production of ectopic floral meristems and leaves, possibly via the ectopic activation of CLV3 and LFY. In addition, in the Arabidopsis root, overexpression of LhWOX5 alters root apical meristem morphology, leading to a curled and shortened primary root. Importantly, these abnormal phenotypes in the aerial and subterranean organs caused by constitutive ectopic expression of LhWOX5 mimic the observed phenotypes when overexpressing AtWUS and AtWOX5 in Arabidopsis, respectively. Taken together, we propose that the LhWOX5 gene, originating from the Magnoliaceae plant Liriodendron, is a functional homolog of the AtWUS gene from Arabidopsis, while showing the highest degree of sequence similarity with its ortholog, AtWOX5. Our study provides insight into the potential role of LhWOX5 in the development of both the shoot and root.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Meristema/genética , Folhas de Planta/metabolismo , Plantas/metabolismo , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo
15.
Molecules ; 28(6)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36985684

RESUMO

Mass Spectrometry Imaging (MSI) has emerged as a powerful imaging technique for the analysis of biological samples, providing valuable insights into the spatial distribution and structural characterization of lipids. The advancements in high-resolution MSI have made it an indispensable tool for single-cell or subcellular lipidomics. By preserving both intracellular and intercellular information, MSI enables a comprehensive analysis of lipidomics in individual cells and organelles. This enables researchers to delve deeper into the diversity of lipids within cells and to understand the role of lipids in shaping cell behavior. In this review, we aim to provide a comprehensive overview of recent advancements and future prospects of MSI for cellular/subcellular lipidomics. By keeping abreast of the cutting-edge studies in this field, we will continue to push the boundaries of the understanding of lipid metabolism and the impact of lipids on cellular behavior.


Assuntos
Lipidômica , Lipídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Lipídeos/química , Diagnóstico por Imagem , Organelas/química
16.
Angew Chem Int Ed Engl ; 62(52): e202312275, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37946693

RESUMO

Spatial lipidomics based on mass spectrometry imaging (MSI) is a powerful tool for fundamental biology studies and biomarker discovery. But the structure-resolving capability of MSI is limited because of the lack of multiplexed tandem mass spectrometry (MS/MS) method, primarily due to the small sample amount available from each pixel and the poor ion usage in MS/MS analysis. Here, we report a mobility-modulated sequential dissociation (MMSD) strategy for multiplex MS/MS imaging of distinct lipids from biological tissues. With ion mobility-enabled data-independent acquisition and automated spectrum deconvolution, MS/MS spectra of a large number of lipid species from each tissue pixel are acquired, at no expense of imaging speed. MMSD imaging is highlighted by MS/MS imaging of 24 structurally distinct lipids in the mouse brain and the revealing of the correlation of a structurally distinct phosphatidylethanolamine isomer (PE 18 : 1_18 : 1) from a human hepatocellular carcinoma (HCC) tissue. Mapping of structurally distinct lipid isomers is now enabled and spatial lipidomics becomes feasible for MSI.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Espectrometria de Massas em Tandem , Lipidômica/métodos , Lipídeos/química
17.
Angew Chem Int Ed Engl ; 62(9): e202214804, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36575135

RESUMO

Mass spectrometry imaging (MSI) of lipids in biological tissues is useful for correlating molecular distribution with pathological results, which could provide useful information for both biological research and disease diagnosis. It is well understood that the lipidome could not be clearly deciphered without tandem mass spectrometry analysis, but this is challenging to achieve in MSI due to the limitation in sample amount at each image spot. Here we develop a multiplexed MS2 imaging (MS2 I) method that can provide MS2 images for 10 lipid species or more for each sampling spot, providing spatial structural lipidomic information. Coupling with on-tissue photochemical derivatization, imaging of 20 phospholipid C=C location isomers is also realized, showing enhanced molecular images with high definition in structure for mouse brain and human liver cancer tissue sections. Spatially mapped t-distributed stochastic neighbor embedding has also been adopted to visualize the tumor margin with enhancement by structural lipidomic information.


Assuntos
Fosfolipídeos , Espectrometria de Massas em Tandem , Camundongos , Animais , Humanos , Espectrometria de Massas em Tandem/métodos , Diagnóstico por Imagem , Isomerismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
18.
Anal Chem ; 94(40): 13944-13950, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36176011

RESUMO

Disorder of lipid homeostasis is closely associated with a variety of diseases. Although mass spectrometry (MS) approaches have been well developed for the characterization of lipids, it still lacks an integrated and compact MS system that is capable of rapid and detailed lipid structural characterization and can be conveniently transferred into different laboratories. In this work, we describe a novel miniature MS system with the capability of both ozone-induced dissociation (OzID) and collision-induced dissociation (CID) for the assignment of sites of unsaturation and sn-positions in glycerolipids. A miniature ozone generator was developed, which can be operated at a relatively high pressure. By maintaining high-concentration ozone inside the linear ion trap, OzID efficiency was significantly improved for the identification of C═C locations in unsaturated lipids, with reaction times as short as 10 ms. Finally, the miniature OzID MS system was applied to the analysis of C═C locations and sn-positions of lipids from biological samples. Direct sampling and fast detection of changes in phospholipid isomers were demonstrated for the rapid discrimination of breast cancer tissue samples, showing the potential of the miniature OzID MS system for point-of-care analysis of lipid isomer biomarkers in complex samples.


Assuntos
Ozônio , Isomerismo , Espectrometria de Massas , Ozônio/química , Fosfolipídeos , Sistemas Automatizados de Assistência Junto ao Leito
19.
Acc Chem Res ; 54(20): 3873-3882, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34570464

RESUMO

Lipids have pivotal roles in many biological processes, including energy storage, signal transduction, and plasma membrane formation. A disruption of lipid homeostasis is found to be associated with a range of diseases, such as cardiovascular diseases, diabetes, and cancer. Fundamental lipid biology and disease diagnostics can benefit from monitoring lipid changes in cells, tissues, organs, or the whole biological system. Therefore, it is important to develop lipid analysis tools to achieve comprehensive lipid characterization and quantitation. Over the past two decades, mass spectrometry (MS) has become the method of choice for qualitative and quantitative analyses of lipids, owing to its high sensitivity, multiplexed analysis, and soft ionization features. With the rapid development and adoption of ultrahigh-resolution MS, isobaric lipids can now be routinely resolved. By contrast, the structural characterization and quantitation of isomeric lipids remain an analytical challenge. Although some lipid C═C location or sn-isomers can be resolved by chromatography, ion mobility, or selective ionization approaches, a detailed structural characterization on the lipidome-wide level needs to be achieved.Over the past six years, we have successfully combined the Paternò-Büchi (PB) reaction, which is a UV-promoted photocycloaddition reaction specific to the C═C, with tandem MS (MS/MS) to locate the C═C in lipids and quantify lipid C═C location isomers. The PB reactions have analytical advantages such as a simple experimental setup, rapid lipid C═C derivatization, and highly specific C═C cleavage during PB-MS/MS to produce abundant diagnostic ions. More importantly, without a need of isomer separation or a comparison to authentic standards, PB-MS/MS can be directly applied to identify and quantify a mixture of lipid C═C location isomers, often coexisting with molar ratios sensitive to the biological state of the system. The PB-MS/MS method is compatible with conventional shotgun lipidomics employing a nanoelectrospray ionization or a large-sale lipid structural analysis via liquid chromatography (LC) coupled to any mass spectrometer with tandem MS capability. The PB-MS/MS method is highly versatile, as a variety of PB reagents can be tailored to a broad range of applications. Besides UV-promoted PB reactions, visible-light PB reactions have also been developed to offer more flexibility for a lipid analysis. By using selected PB reagents, the sn-positions of fatty acyls can be resolved together with C═C locations in phospholipids. This method has been used in lipidomic analyses of tissue, blood, and plasma from animal models and clinical samples, demonstrating the potential of using lipid C═C or sn-location isomer ratios for phenotyping and disease diagnostics. Lipid isomer-resolving MS imagings of tissues and single-cell lipid analysis have also been demonstrated by a proper implementation of PB-MS/MS.


Assuntos
Lipidômica , Lipídeos/química , Animais , Cromatografia Líquida , Humanos , Processos Fotoquímicos , Espectrometria de Massas em Tandem
20.
Opt Express ; 30(20): 36096-36109, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36258546

RESUMO

For the advantages of the faster computation speed and lower energy consumption, all-optical computation has attracted great attention compared with the traditional electric computation method. Optical switches are the critical elementary units of optical computation devices. However, the traditional optical switches have two shortcomings, expending the outside energy to keep the switch state and the weak multi-level adjustable ability, which greatly restrict the realization of the large-scale photonic integrated circuits and optical spiking neural networks. In this paper, we use a subwavelength grating slot-ridge (SWGSR) waveguides on the silicon platform to design a nonvolatile multi-level adjustable optical switch based on the phase change material Ge2Sb2Te5 (GST). Changing the phase state of GST can modulate the transmission of the optical switch, and the change of the optical transmittance of the optical switch is about 70%, which is much higher than that of previous optical switches. As no static power is required to maintain the phase state, it can find promising applications in optical switch matrices and reconfigurable optical spiking neural networks.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA