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Global profiling of single-cell proteomes can reveal cellular heterogeneity, thus benefiting precision medicine. However, current mass spectrometry (MS)-based single-cell proteomic sample processing still faces technical challenges associated with processing efficiency and protein recovery. Herein, we present an innovative sample processing platform based on a picoliter single-cell reactor (picoSCR) for single-cell proteome profiling, which involves in situ protein immobilization and sample transfer. PicoSCR helped minimize surface adsorptive losses by downscaling the processing volume to 400 pL with a contact area of less than 0.4 mm2. Besides, picoSCR reached highly efficient cell lysis and digestion within 30 min, benefiting from optimal reagent and high reactant concentrations. Using the picoSCR-nanoLC-MS system, over 1400 proteins were identified from an individual HeLa cell using data-dependent acquisition mode. Proteins with copy number below 1000 were identified, demonstrating this system with a detection limit of 1.7 zmol. Furthermore, we profiled the proteome of circulating tumor cells (CTCs). Data are available via ProteomeXchange with the identifier PXD051468. Proteins associated with epithelial-mesenchymal transition and neutrophil extracellular traps formation (which are both related to tumor metastasis) were observed in all CTCs. The cellular heterogeneity was revealed by differences in signaling pathways within individual cells. These results highlighted the potential of the picoSCR platform to help discover new biomarkers and explore differences in biological processes between cells.
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Proteoma , Proteômica , Análise de Célula Única , Humanos , Análise de Célula Única/métodos , Células HeLa , Proteoma/análise , Proteoma/metabolismo , Proteômica/métodos , Transição Epitelial-Mesenquimal , Reatores BiológicosRESUMO
The scarcity and dynamic nature of phosphotyrosine (pTyr)-modified proteins pose a challenge for researching protein complexes with pTyr modification, which are assembled through multiple protein-protein interactions. We developed an integrated complex-centric platform for large-scale quantitative profiling of pTyr signaling complexes based on cofractionation/mass spectrometry (CoFrac-MS) and a complex-centric algorithm. We initially constructed a trifunctional probe based on pTyr superbinder (SH2-S) for specifically binding and isolation of intact pTyr protein complexes. Then, the CoFrac-MS strategy was employed for the identification of pTyr protein complexes by integrating ion exchange chromatography in conjunction with data independent acquisition mass spectrometry. Furthermore, we developed a novel complex-centric algorithm for quantifying protein complexes based on the protein complex elution curve. Utilizing this algorithm, we effectively quantified 216 putative protein complexes. We further screened 21 regulated pTyr protein complexes related to the epidermal growth factor signal. Our study engenders a comprehensive framework for the intricate examination of pTyr protein complexes and presents, for the foremost occasion, a quantitative landscape delineating the composition of pTyr protein complexes in HeLa cells.
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Algoritmos , Espectrometria de Massas , Fosfotirosina , Transdução de Sinais , Fosfotirosina/metabolismo , Fosfotirosina/análise , Fosfotirosina/química , Humanos , Células HeLa , Cromatografia por Troca Iônica/métodosRESUMO
Exosomes, a growing focus for liquid biopsies, contain diverse molecular cargos. In particular, exosome metabolites with valuable information have exhibited great potential for improving the efficiency of liquid biopsies for addressing complex medical conditions. In this work, we design the directional growth of Ti-metal-organic frameworks on polar-functionalized magnetic particles. This design facilitates the rapid synergistic capture of exosomes with the assistance of an external magnetic field and additionally synergistically enhances the ionization of their metabolites during mass spectrometry detection. Benefiting from this dual synergistic effect, we identified three high-performance exosome metabolites through the differential comparison of a large number of serum samples from individuals with Alzheimer's disease (AD) and normal cognition. Notably, the accuracy of AD identification ranges from 93.18 to 100% using a single exosome metabolite and reaches a flawless 100% with three metabolites. These findings emphasize the transformative potential of this work to enhance the precision and reliability of AD diagnosis, ushering in a new era of improved diagnostic accuracy.
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Doença de Alzheimer , Exossomos , Estruturas Metalorgânicas , Humanos , Doença de Alzheimer/patologia , Estruturas Metalorgânicas/metabolismo , Exossomos/química , Reprodutibilidade dos Testes , Titânio/análiseRESUMO
Nanostructured metal hydrides with unique morphology and improved hydrogen storage properties have attracted intense interests. However, the study of the growth process of highly active borohydrides remains challenging. Herein, for the first time the synthesis of LiBH4 nanorods through a hydrogen-assisted one-pot solvothermal reaction is reported. Reaction of n-butyl lithium with triethylamine borane in n-hexane under 50 bar of H2 at 40-100 °C gives rise to the formation of the [100]-oriented LiBH4 nanorods with 500-800 nm in diameter, whose growth is driven by orientated attachment and ligand adsorption. The unique morphology enables the LiBH4 nanorods to release hydrogen from ≈184 °C, 94 °C lower than the commercial sample (≈278 °C). Hydrogen release amounts to 13 wt% within 40 min at 450 °C with a stable cyclability, remarkably superior to the commercial LiBH4 (≈9.1 wt%). More importantly, up to 180 °C reduction in the onset temperature of hydrogenation is successfully attained by the nanorod sample with respect to the commercial counterpart. The LiBH4 nanorods show no foaming during dehydrogenation, which improves the hydrogen cycling performance. The new approach will shed light on the preparation of nanostructured metal borohydrides as advanced functional materials.
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Anionic redox chemistry enables extraordinary capacity for Li- and Mn-rich layered oxides (LMROs) cathodes. Unfortunately, irreversible surface oxygen evolution evokes the pernicious phase transition, structural deterioration, and severe electrode-electrolyte interface side reaction with element dissolution, resulting in fast capacity and voltage fading of LMROs during cycling and hindering its commercialization. Herein, a redox couple strategy is proposed by utilizing copper phthalocyanine (CuPc) to address the irreversibility of anionic redox. The Cu-N synergistic effect of CuPc could not only inhibit surface oxygen evolution by reducing the peroxide ion O2 2- back to lattice oxygen O2-, but also enhance the reaction activity and reversibility of anionic redox in bulk to achieve a higher capacity and cycling stability. Moreover, the CuPc strategy suppresses the interface side reaction and induces the forming of a uniform and robust LiF-rich cathode electrolyte, interphase (CEI) to significantly eliminate transition metal dissolution. As a result, the CuPc-enhanced LMRO cathode shows superb cycling performance with a capacity retention of 95.0% after 500 long-term cycles. This study sheds light on the great effect of N-based redox couple to regulate anionic redox behavior and promote the development of high energy density and high stability LMROs cathode.
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Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.
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Endométrio , Selectina L , Gravidez , Humanos , Masculino , Feminino , Proteína Beclina-1 , Selectina L/metabolismo , Endométrio/metabolismo , Gonadotropina Coriônica/farmacologia , Gonadotropina Coriônica/metabolismo , Implantação do Embrião/fisiologia , Autofagia , Células Estromais/metabolismo , ApoptoseRESUMO
The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase crucial for cellular differentiation, proliferation, and autophagy. It shows a complex role in the endometrium, influencing both normal and pathogenic conditions. mTOR promotes the growth and maturation of endometrial cells, enhancing endometrial receptivity and decidualization. However, it also contributes to the development of endometriosis (EMs) and endometrial cancer (EC), thus emerging as a therapeutic target for these conditions. In this review, we summarize recent research progress on the mTOR signalling pathway in the endometrium. This provides insights into female endometrial structure and function and guides the prevention and treatment of related diseases.
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Endometriose , Sirolimo , Animais , Feminino , Humanos , Sirolimo/uso terapêutico , Endométrio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais , Proteínas Serina-Treonina Quinases/metabolismo , Mamíferos/metabolismo , Endometriose/metabolismoRESUMO
Uric acid (UA) is an important biomarker, as a high concentration in blood can lead to gout and further renal syndrome. Although several point-of-care testing (POCT) devices have been reported to detect UA, there are some limitations such as the requirement for uricase and the complicated pretreatment of serum/plasma samples, which restricts their use at home or in undeveloped areas. In this work, we developed an approach by applying Zn2+ to precipitate proteins and cells in whole blood to avoid interference with the chromogenic reaction. We used carboxymethylcellulose (CMC) to immobilize tetramethylbenzidine (TMB) on a nitrocellulose membrane for colorimetric detection. Using the oxidization properties of H2O2, which turns TMB into oxidized tetramethylbenzidine (TMBox) in the presence of catalyst gold nanoparticles (AuNPs), we successfully constructed an enzyme-free paper-based POCT device using the reduction reaction of UA and TMBox for simple, speedy, and cheap colorimetric detection of UA, achieving a detection time of 8 min, a linear range of 0-150 µg/mL, and an LOD of 25.79 µg/mL. The UA concentration in whole blood samples was further measured and correlated well with the clinical value (R2 = 0.8212). Thus, the proposed assay has the potential for POCT diagnosis, monitoring, and prognosis of diseases related to UA.
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Nanopartículas Metálicas , Ácido Úrico , Ouro , Colorimetria , Peróxido de Hidrogênio , ZincoRESUMO
Strong metal-support interaction (SMSI) plays a vital role in tuning the geometric and electronic structures of metal species. Generally, a high-temperature treatment (>500 °C) in reducing atmosphere is required for constructing SMSI, which may induce the sintering of metal species. Herein, we use molten salts as the reaction media to trigger the formation of high-intensity SMSI at reduced temperatures. The strong ionic polarization of the molten salt promotes the breakage of Ti-O bonds in the TiO2 support, and hence decreases the energy barrier for the formation of interfacial bonds. Consequently, a high-intensity SMSI state is achieved in TiO2 supported Ir nanoclusters, evidenced by a large number of Ir-Ti bonds at the interface, at a low temperature of 350 °C. Moreover, this method is applicable for triggering SMSI in various supported metal catalysts with different oxide supports including CeO2 and SnO2. This newly developed SMSI construction methodology opens a new avenue and holds significant potential for engineering advanced supported metal catalysts toward a broad range of applications.
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Strong metal-support interaction (SMSI) is crucial to modulating the nature of metal species, yet the SMSI behaviors of sub-nanometer metal clusters remain unknown due to the difficulties in constructing SMSI at cluster scale. Herein, we achieve the successful construction of the SMSI between Pt clusters and amorphous TiO2 nanosheets by vacuum annealing, which requires a relatively low temperature that avoids the aggregation of small clusters. In situ scanning transmission electron microscopy observation is employed to explore the SMSI behaviors, and the results reveal the dynamic rearrangement of Pt atoms upon annealing for the first time. The originally disordered Pt atoms become ordered as the crystallizing of the amorphous TiO2 support, forming an epitaxial interface between Pt and TiO2. Such a SMSI state can remain stable in oxidation environment even at 400 °C. Further investigations prove that the electron transfer from TiO2 to Pt occupies the Pt 5d orbitals, which is responsible for the disappeared CO adsorption ability of Pt/TiO2 after forming SMSI. This work not only opens a new avenue for constructing SMSI at cluster scale but also provides in-depth understanding on the unique SMSI behavior, which would stimulate the development of supported metal clusters for catalysis applications.
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From metabolic waste to biological mediators, exosomes have emerged as the key player in a variety of pathological processes, particularly in oncogenesis. The exosome-mediated communication network involves nearly every step of cancer progression, promoting the proliferation and immune escape of cancer cells. Therefore, the removal of cancer-derived exosomes has profound clinical significance. Current methods for exosome separation and enrichment are either for large-scale samples or require complex pretreatment processes, lacking effective methods for trace-volume exosome capture in situ. Herein, we have developed an in situ exosome capturing and counting device based on the antibody-functionalized capillary. Specific antibodies targeting exosome biomarkers were immobilized to the inner wall of the capillary via biotin-streptavidin interaction for direct cancer exosome capturing. Subsequent exosome staining enabled imaging and enumeration. Acceptable linearity and reproducibility were achieved with our device, with the capturing and detective range between 3.3 × 104 and 3.3 × 108 particles, surpassing the nanoparticle tracking analysis by 2 orders of magnitude while requiring merely 30 µL sample. We demonstrated that MCF-7-derived exosomes induced epithelial-mesenchymal transition of epithelial cells MCF-10A, and our method was able to completely or partially reverse the transition by complete depletion or specific depletion of cancer exosomes without any preprocessing. Moreover, both whole exosomes and cancer-specific exosomes alone from mimic blood samples were successfully captured and counted, without obvious non-specific adsorption. In all, our approach realized the in situ depletion and number-counting of cancer-derived exosomes directly from the complex humoral environment, having the potential to provide a comprehensive tumor therapeutic and prognosis evaluation tool by targeted hemodialysis and counting of tumor-derived exosomes.
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Exossomos , Neoplasias , Humanos , Reprodutibilidade dos Testes , Carcinogênese , Adsorção , AnticorposRESUMO
Pancreatic cancer (PC) has a high mortality, with a fairly low five-year survival rate, because of its delayed diagnosis. Recently, liquid biopsy, especially based on exosomes, has attracted vast attention, thanks to its low invasiveness. Herein, we constructed a protocol for pancreatic cancer related Glypican 1 (GPC1) exosome quantification, based on in situ mass spectrometry signal amplification, by utilizing mass tag molecules on gold nanoparticles (AuNPs). Exosomes were extracted and purified by size-exclusion chromatography (SEC), captured by TiO2 modified magnetic nanoparticles, and then targeted specifically by anti-GPC1 antibody modified on AuNPs. With matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), the signal of PC biomarker, GPC1, was converted to a mass tag signal and amplified. With addition of a certain amount of internal standard molecules modified on AuNPs, the relative intensity ratio of mass tag to internal standard was proportional to the concentration of GPC1(+) exosomes derived from pancreatic cancer cell lines, PANC-1, with good linearity (R2 = 0.9945) in a wide dynamic range from 7.1 × 10 to 7.1 × 106 particles/µL. This method was further applied to plasma samples from healthy control (HC) and pancreatic cancer patients with different tumor load, and exhibited a great potential in discriminating diagnosed PC patients from HC, and has the monitoring potential in PC progression.
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Exossomos , Nanopartículas Metálicas , Neoplasias Pancreáticas , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Glipicanas , Ouro/química , Exossomos/metabolismo , Nanopartículas Metálicas/química , Neoplasias Pancreáticas/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias PancreáticasRESUMO
Circulating tumor cells (CTCs) are crucial in tumor progression and metastasis, but the knowledge of their roles grows slowly at single-cell levels. Characterizing the rarity and fragility of CTCs by nature, highly stable and efficient single-CTC sampling methods are still lacking, which impedes the development of single-CTC analysis. Herein, an improved, capillary-based single-cell sampling (SiCS) method, the so-called bubble-glue single-cell sampling (bubble-glue SiCS), is introduced. Benefiting from the characteristic that the cells tend to adhere to air bubbles in the solution, single cells can be sampled with bubbles as low as 20 pL with a self-designed microbubble-volume-controlled system. Benefiting from the excellent maneuverability, single CTCs are sampled directly from 10 µL volume of real blood samples after fluorescent labeling. Meanwhile, over 90% of the CTCs obtained survived and well proliferated after the bubble-glue SiCS process, which showed considerable superiority for downstream single-CTC profiling. Furthermore, a highly metastatic breast cancer model of the 4T1 cell line in vivo was employed for the real blood sample analysis. Increases in CTC numbers were observed during the tumor progression process, and significant heterogeneities among individual CTCs were discovered. In all, we propose a novel avenue for target SiCS and provide an alternative technique route for CTC separation and analysis.
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Neoplasias da Mama , Células Neoplásicas Circulantes , Humanos , Feminino , Células Neoplásicas Circulantes/patologia , Neoplasias da Mama/patologia , Metástase Neoplásica , Análise de Célula Única/métodos , Biomarcadores TumoraisRESUMO
Traditional lateral flow assay (LFA) is restricted to providing qualitative or semi-quantitative results and often requires special equipment for obtaining quantitative results. Herein, we proposed a naked-eye readout distance quantitative lateral flow assay based on the permeability changes in enzyme-catalyzed hydrogelation, which not only has the advantages of being simple, immediate, of high efficiency and low cost, and accurate in quantification but also avoids the use of special equipment. The developed LFA method includes three principal components of a nitrocellulose (NC) membrane containing a control line (C line) loading goat anti-rabbit (GAR) antibodies and a test line (T line) loading specific antibodies, alginate-tyramine conjugates forming a hydrogel in the presence of hydrogen peroxide (H2O2) and horseradish peroxidase (HRP), and the HRP-AuNPs-Ab probe only labeling targets captured on the T line. Hemoglobin A1c (HbA1c) was chosen as a representative example to demonstrate the feasibility of our method. Under the optimal conditions, the developed LFA method shows excellent performance in standard samples and real human blood samples where the results of real human blood samples show a high linear correlation with the clinical data obtained by ion exchange chromatography (R2 = 0.9929) and the margin of recovery is only 3.8%. All results demonstrated that our developed LFA method not only has enormous potential in the quantitative detection of HbA1c in clinical complex samples but also can serve as a versatile method for highly efficient detection of other target biomolecules due to the fungibility of antibodies.
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Peróxido de Hidrogênio , Nanopartículas Metálicas , Animais , Humanos , Coelhos , Hemoglobinas Glicadas , Peróxido de Hidrogênio/química , Ouro/química , Nanopartículas Metálicas/química , Anticorpos , Permeabilidade , CatáliseRESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which leads to the formation of immune complex deposits in multiple organs and has heterogeneous clinical manifestations. Currently, exosomes for liquid biopsy have been applied in diagnosis and monitoring of diseases, whereas SLE discrimination based on exosomes at the metabolic level is rarely reported. Herein, we constructed a protocol for metabolomic study of urinary exosomes from SLE patients and healthy controls (HCs) with high efficiency and throughput. Exosomes were first obtained by high-performance liquid size-exclusion chromatography (HPL-SEC), and then metabolic fingerprints of urinary exosomes were extracted by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with high throughput and high efficency. With the statistical analysis by orthogonal partial least-squares discriminant analysis (OPLS-DA) model, SLE patients were efficiently distinguished from HCs, the area under the curve (AUC) of the receiver characteristic curve (ROC) was 1.00, and the accuracy of the unsupervised clustering heatmap was 90.32%. In addition, potential biomarkers and related metabolic pathways were analyzed. This method, with the characteristics of high throughput, high efficiency, and high accuracy, will provide the broad prospect of exosome-driven precision medicine and large-scale screening in clinical applications.
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Ultra-low-copy number proteins play a crucial role in exploring cellular heterogeneity and the insight of protein biomarkers in a single cell. However, counting ultra-low-copy number target proteins in a single cell remains a grand challenge. Herein, we developed a so-called single-cell picoliter liquid operating technology for counting target proteins in a single cell. An ingenious volume-controllable sampling technique was employed to capture a single cell for subsequent analysis. Remarkably, 50 pL of sample volume was employed for sample preparation, single-cell capture, in-droplet lysis, and target protein immobilization on a functionalized coverslip in a monolayer. Then, target protein antibodies coupled with quantum dots were added and incubated to label those immobilized proteins. After clean-up, a single-view image under 100× objective was taken, and the 80 × 80 µm2 view image was then applied to count the precise copy number of the target proteins in the single cell. Furthermore, good linearity and repeatability were achieved for ultra-low-copy number proteins, ranging from 1 to 1500. Finally, the expression level of human epidermal growth factor receptor 2 in single cells from both MCF-7 and MDA-MB-231 cell lines was also analyzed. In a word, this work stimulated the development of capillary-based single-cell analysis and updated the connotation of counting ultra-low-copy number proteins.
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Pontos Quânticos , Anticorpos , Humanos , Proteínas/análise , Análise de Célula Única , TecnologiaRESUMO
Efficient isolation and downstream bioinformation analysis of circulating tumor cells (CTCs) in whole blood contribute to the early diagnosis of cancer and investigation of cancer metastasis. However, the separation and release of CTCs remain a great challenge due to the extreme rarity of CTCs and severe interference from other cells in complex clinical samples. Herein, we developed a low-cost and easy-to-fabricate aptamer-functionalized wafer with a three-dimensional (3D) interconnected porous structure by grafting polydopamine (PDA), poly(ethylene glycol) (PEG), and aptamer in sequence (Ni@PDA-PEG-Apt) for the capture and release of CTCs. The Ni@PDA-PEG-Apt wafer integrated the features of Ni foam with a 3D interconnected porous structure offering enough tunnels for cells to flow through and enhancing aptamer-cell contact frequency, the spacer PEG with flexible and high hydrophilic property increasing anti-interference ability and providing the wafer with more binding sites for aptamer, which result in an enhanced capture specificity and efficiency for CTCs. Because of these advantages, the Ni@PDA-PEG-Apt wafer achieved a high capture efficiency of 78.25%. The captured cancer cells were mildly released by endonuclease with up to 61.85% efficiency and good proliferation. Furthermore, tumor cells were injected into mice and experienced circulation in vivo. In blood samples after circulation, 65% of target tumor cells can be efficiently captured by the wafer, followed by released and recultured cells with high viability. Further downstream metabolomics analysis showed that target cancer cells remained with high biological activity and can be well separated from MCF-10A cells based on metabolic profiles by the PCA analysis, indicating the great potential of our strategy for further research on the progression of cancer metastasis. Notably, not only is the wafer cheap with a cost of only 3.58 U.S. dollars and easily prepared by environmental-friendly reagents but also the process of capturing and releasing tumor cells can be completed within an hour, which is beneficial for large-scale clinical use in the future.
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Células Neoplásicas Circulantes , Camundongos , Animais , Células Neoplásicas Circulantes/patologia , Porosidade , Contagem de Células , Polietilenoglicóis/química , Separação Celular/métodos , Linhagem Celular TumoralRESUMO
Plasma exosomes have shown great potential for liquid biopsy in clinical cancer diagnosis. Herein, we present an integrated strategy for isolating and analyzing exosomes from human plasma rapidly and then discriminating different cancers excellently based on deep learning fingerprints of plasma exosomes. Sequential size-exclusion chromatography (SSEC) was developed efficiently for separating exosomes from human plasma. SSEC isolated plasma exosomes, taking as less as 2 h for a single sample with high purity such that the discard rates of high-density lipoproteins and low/very low-density lipoproteins were 93 and 85%, respectively. Benefitting from the rapid and high-purity isolation, the contents encapsulated in exosomes, covered by plasma proteins, were well profiled by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS). We further analyzed 220 clinical samples, including 79 breast cancer patients, 57 pancreatic cancer patients, and 84 healthy controls. After MS data pre-processing and feature selection, the extracted MS feature peaks were utilized as inputs for constructing a multi-classifier artificial neural network (denoted as Exo-ANN) model. The optimized model avoided overfitting and performed well in both training cohorts and test cohorts. For the samples in the independent test cohort, it realized a diagnosed accuracy of 80.0% with an area under the curve of 0.91 for the whole group. These results suggest that our integrated pipeline may become a generic tool for liquid biopsy based on the analysis of plasma exosomes in clinics.
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Aprendizado Profundo , Exossomos , Neoplasias , Exossomos/química , Humanos , Plasma , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
Li-rich Mn-based layered oxides (LMLOs) are promising cathode material candidate for the next-generation Li-ion batteries (LIBs) of high energy density. However, the fast capacity fading and voltage decay as well as low Coulombic efficiency caused by irreversible oxygen release and phase transition during the electrochemical process hinder their practical application. To solve these problems, in the present study, a multifunctional surface construction involving a coating layer, spinel-layered heterostructure, and rich-in oxygen vacancies is successfully conducted by a facile thermal reduction of the LMLO particles with potassium borohydride (KBH4 ) as the reducing agent. The multifunctional surface structure plays synergistic effects on suppressing the interface side reaction, reducing the dissolution of transition metal, increasing electron conductivity and lithium diffusion rate. As a result, electrochemical performances of the LMLO cathode are effectively enhanced. With optimization of the addition of KBH4 , the electrode delivers a reversible capacity of 280 mAh g-1 at 0.1 C, which maintains after 100 cycles. The capacity retention with respect to the initial capacity is as high as 98% at 1 C after 400 cycles. The present work provides insights into designing a highly effective functional surface structure of LMLO cathode materials for high-performance LIBs.
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MgH2 is one of the most promising solid hydrogen storage materials due to its high capacity, excellent reversibility, and low cost. However, its operation temperature needs to be greatly reduced to realize its practical applications, especially in the highly desired fuel cell fields. This work synthesizes a 2D nanoflake-shape bimetallic Ti-Nb oxide of TiNb2 O7 , which has high surface area and shows superior catalytic effect for the hydrogen storage of MgH2 . Incorporated with the TiNb2 O7 nanoflakes as low as 3 wt%, MgH2 shows a low onset dehydrogenation temperature of 178 °C, which is lowered by 100 °C compared with the pristine one. A dehydrogenation capacity as high as 7.0 wt% H2 is achieved upon heating to 300 °C. The capacity retention is as high as 96% after 30 cycles. The mechanism of the improved hydrogen storage properties is analyzed by density functional theory (DFT) calculation and the microstructural evolution during dehydrogenation and hydrogenation. This work provides an MgH2 system with high available capacity and low operation temperature by a unique structural design of the catalyst. The high surface area feature of the TiNb2 O7 nanoflakes and the synthesis method hopefully can develop the application of TiNb2 O7 .