RESUMO
Chemical molecular structures are a direct and convenient means of expressing chemical knowledge, playing a vital role in academic communication. In chemistry, hand drawing is a common task for students and researchers. If we can convert hand-drawn chemical molecular structures into machine-readable formats, like SMILES encoding, computers can efficiently process and analyze these structures, significantly enhancing the efficiency of chemical research. Furthermore, with the progress of educational technology, automated grading is gaining popularity. When machines automatically recognize chemical molecular structures and assess the correctness of the drawings, it offers great convenience to teachers. We created ChemReco, a tool designed to identify chemical molecular structures involving three atoms: C, H, and O, providing convenience for chemical researchers. Currently, there are limited studies on hand-drawn chemical molecular structures. Therefore, the primary focus of this paper is constructing datasets. We propose a synthetic image method to rapidly generate images resembling hand-drawn chemical molecular structures, enhancing dataset acquisition efficiency. Regarding model selection, the hand-drawn chemical molecule structural recognition model developed in this article achieves a final recognition accuracy of 96.90%. This model employs the encoder-decoder architecture of EfficientNet + Transformer, demonstrating superior performance compared to other encoder-decoder combinations.
RESUMO
Flexible strain sensors have been widely researched in fields such as smart wearables, human health monitoring, and biomedical applications. However, achieving a wide sensing range and high sensitivity of flexible strain sensors simultaneously remains a challenge, limiting their further applications. To address these issues, a cross-scale combinatorial bionic hierarchical design featuring microscale morphology combined with a macroscale base to balance the sensing range and sensitivity is presented. Inspired by the combination of serpentine and butterfly wing structures, this study employs three-dimensional printing, prestretching, and mold transfer processes to construct a combinatorial bionic hierarchical flexible strain sensor (CBH-sensor) with serpentine-shaped inverted-V-groove/wrinkling-cracking structures. The CBH-sensor has a high wide sensing range of 150% and high sensitivity with a gauge factor of up to 2416.67. In addition, it demonstrates the application of the CBH-sensor array in sign language gesture recognition, successfully identifying nine different sign language gestures with an impressive accuracy of 100% with the assistance of machine learning. The CBH-sensor exhibits considerable promise for use in enabling unobstructed communication between individuals who use sign language and those who do not. Furthermore, it has wide-ranging possibilities for use in the field of gesture-driven interactions in human-computer interfaces.
Assuntos
Aprendizado de Máquina , Língua de Sinais , Humanos , Biônica , Dispositivos Eletrônicos Vestíveis , Gestos , Impressão TridimensionalRESUMO
Flexible strain sensors have been continuously optimized and widely used in various fields such as health monitoring, motion detection, and human-machine interfaces. There is a higher demand for sensors that can sensitively identify both the strain amplitude and direction in real-time to adapt to complex human movements. This study proposes a flexible strain sensor construction strategy based on V-groove/wrinkle hierarchical structures via a facile and scalable prestretching approach. A gold film is sputtered on a V-groove structure soft substrate under a vertical biaxial prestrain. When the strain is released, a variety of wondrous V-groove/wrinkle hierarchical structures are formed. The microstructure and the properties of the resulting sensor can be controlled by adjusting the prestrain, which has obvious anisotropic response characteristics and exhibits high sensitivity (maximum gauge factor up to 20,727.46) and a wide sensing range (up to 51%). In addition, the resulting multidirectional sensor based on double-sided microstructures has an exceptional directional selectivity of 67.39, at an advanced level among all stretchable multidirectional strain sensors reported so far. The sensor can detect human motion signals and distinguish motion patterns, proving its great potential in the field of human motion detection and laying a foundation for high-performance wearable devices.
RESUMO
Pneumoconiosis is one of the most serious occupational diseases worldwide. Silicosis due to prolonged inhalation of free silica dust during occupational activities is one of the main types. Cuproptosis is a newly discovered mode of programmed cell death characterized by the accumulation of free copper in the cell, which ultimately leads to cell death. Increased copper in the serum of silicosis patients, suggests that the development of silicosis is accompanied by changes in copper metabolism, but whether cuproptosis is involved in the progression of silicosis is actually to be determined. To test this hypothesis, we screened the genetic changes in patients with idiopathic fibrosis by bioinformatics methods and predicted and functionally annotated the cuproptosis-related genes among them. Subsequently, we established a mouse silicosis model and detected the concentration of copper ions and the activity of ceruloplasmin (CP) in serum, as well as changes of the concentration of copper and cuproptosis related genes in mouse lung tissues. We identified 9 cuproptosis-related genes among the differential genes in patients with IPF at different times and the tissue-specific expression levels of ferredoxin 1 (FDX1) and Lipoyl synthase (LIAS) proteins. Furthermore, serum CP activity and copper ion levels in silicosis mice were elevated on days 7th and 56th after silica exposure. The expression of CP in mouse lung tissue elevated at all stages after silica exposure. The mRNA level of FDX1 decreased on days 7th and 56th, and the protein level remained in accordance with the mRNA level on day 56th. LIAS and Dihydrolipoamide dehydrogenase (DLD) levels were downregulated at all times after silica exposure. In addition, Heatshockprotein70 (HSP70) expression was increased on day 56. In brief, our results demonstrate that there may be cellular cuproptosis during the development of experimental silicosis in mice and show synchronization with enhanced copper loading in mice.
Assuntos
Cobre , Silicose , Humanos , Animais , Camundongos , Cobre/toxicidade , Silicose/genética , Apoptose , Biologia Computacional , Modelos Animais de Doenças , RNA Mensageiro , Dióxido de Silício/toxicidadeRESUMO
Silicosis is one of the most common and severe types of pneumoconiosis and is characterized by lung dysfunction, persistent lung inflammation, pulmonary nodule formation, and irreversible pulmonary fibrosis. The transdifferentiation of fibroblasts into myofibroblasts is one of the main reasons for the exacerbation of silicosis. However, the underlying mechanism of transcription factors regulating silicosis fibrosis has not been clarified. The aim of this study was to investigate the potential mechanism of transcription factor FOXF1 in fibroblast transdifferentiation in silica-induced pulmonary fibrosis. Therefore, a silicosis mouse model was established, and we found that FOXF1 expression level was significantly down-regulated in the silicosis group, and after overexpression of FOXF1 by adeno-associated virus (AAV), FOXF1 expression level was up-regulated, and silicosis fibrosis was alleviated. In order to further explore the specific regulatory mechanism of FOXF1 in silicosis, we established a fibroblasts transdifferentiation model induced by TGF-ß in vitro. In the model, the expression levels of SMAD2/3 and P-SMAD2/3 were up-regulated, but the expression levels of SMAD2/3 and P-SMAD2/3 were down-regulated, inhibiting transdifferentiation and accumulation of extracellular matrix after the overexpressed FOXF1 plasmid was constructed. However, after silencing FOXF1, the expression levels of SMAD2/3 and P-SMAD2/3 were further up-regulated, aggravating transdifferentiation and accumulation of extracellular matrix. These results indicate that the activation of FOXF1 in fibroblasts can slow down the progression of silicosis fibrosis by inhibiting TGF-ß/SMAD2/3 classical pathway, which provides a new idea for further exploration of silicosis treatment.
Assuntos
Transdiferenciação Celular , Fibroblastos , Fibrose Pulmonar , Transdução de Sinais , Silicose , Fator de Crescimento Transformador beta , Animais , Humanos , Masculino , Camundongos , Transdiferenciação Celular/genética , Células Cultivadas , Modelos Animais de Doenças , Fibroblastos/citologia , Fibroblastos/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Pulmão/patologia , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Dióxido de Silício , Silicose/complicações , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Proteína Smad3/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Base editors, developed from the CRISPR/Cas system, consist of components such as deaminase and Cas variants. Since their emergence in 2016, the precision, efficiency, and safety of base editors have been gradually optimized. The feasibility of using base editors in gene therapy has been demonstrated in several disease models. Compared with the CRISPR/Cas system, base editors have shown great potential in hematopoietic stem cells (HSCs) and HSC-based gene therapy, because they do not generate double-stranded breaks (DSBs) while achieving the precise realization of single-base substitutions. This precise editing mechanism allows for the permanent correction of genetic defects directly at their source within HSCs, thus promising a lasting therapeutic effect. Recent advances in base editors are expected to significantly increase the number of clinical trials for HSC-based gene therapies. In this review, we summarize the development and recent progress of DNA base editors, discuss their applications in HSC gene therapy, and highlight the prospects and challenges of future clinical stem cell therapies.
Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Terapia Genética , Doenças Hematológicas , Células-Tronco Hematopoéticas , Humanos , Terapia Genética/métodos , Edição de Genes/métodos , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Doenças Hematológicas/terapia , Doenças Hematológicas/genética , Sistemas CRISPR-Cas/genética , Animais , Transplante de Células-Tronco HematopoéticasRESUMO
We have previously found that a mixture exposure of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and cadmium (Cd) causes kidney damage; however, the mechanism was not fully understood. The aryl hydrocarbon receptor (AhR) is a ligand-receptor transcription factor that plays an important role in the adaptive response or metabolic detoxification of environmental toxins. Thus, this study aimed to examine the role of AhR in kidney toxicity. BDE-47 (50 µM) or Cd (5 µM) exposure reduced cell viability in renal tubular epithelial cells (HKC), with a larger effect observed in co-treatment. The cell morphology presented pyroptotic changes, including swollen cells, large bubbles, and plasma membrane pore formation. The gene expressions of AhR, heat shock protein 90 (Hsp90), AhR nuclear translocator (ARNT), and cytochrome P450 1B1 (CYP1B1) were increased, while CYP1A1 was decreased. Reactive oxygen species (ROS) were generated, which was reduced by the AhR antagonist CH223191. The apoptosis, necrosis, and intracellular lactated hydrogenase (LDH) release was elevated, and this was attenuated by N-acetylcysteine (NAC). Furthermore, the pyroptosis pathway was activated with increased protein levels of cleaved-caspase-3 and gasdermin E N-terminal (GSDME-NT), while caspase-8, caspase-3, and GSDME were decreased. These effects were alleviated by NAC and CH223191. Our data demonstrate a combined effect of BDE-47 and Cd on nephrotoxicity by activating AhR to induce ROS contributing to GSDME-dependent pyroptosis, and retardation of the AhR pathway could reduce this toxicity.
Assuntos
Cádmio , Receptores de Hidrocarboneto Arílico , Receptores de Hidrocarboneto Arílico/metabolismo , Cádmio/toxicidade , Caspase 3/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Piroptose , Éter , Células Epiteliais/metabolismoRESUMO
Polymer modification using silicone rubber represents a promising avenue for enhancing physico-mechanical properties. However, achieving optimal performance through direct blending is hindered by the poor interface compatibility between silicone rubber and the matrix. In this study, we prepared super-tough thermoplastic vulcanizates (TPVs) of polylactic acid/silicone rubber through dynamic vulcanization with PLA, methyl vinyl silicone rubber (MVQ), glycidyl methacrylate grafted MVQ (MVQ-g-GMA), and fumed silica nanoparticles (SiO2). The impact of the SiO2 addition in MVQ on the morphology, mechanical properties, crystallization, and thermal properties of the TPVs was investigated. The results showed that MVQ-g-GMA and SiO2 exhibited a synergistic compatibilization effect significantly improving the interfacial adhesion between PLA and MVQ. Therefore, the impact and tensile strength of the TPVs increased from 8.0 kJ/m2 and 22.2 MPa to 62.6 kJ/m2 and 36.7 MPa, respectively. Moreover, the TPVs also presented good low-temperature toughness with a maximum impact strength of 40.4 kJ/m2 at -20 °C. Additionally, improvements in thermal stability and crystallization rate were also observed. Overall, combining organic and inorganic synergistic compatibilization is a feasible and effective method to fabricate outstanding low-temperature toughness to PLA.
Assuntos
Dióxido de Silício , Elastômeros de Silicone , Poliésteres , PolímerosRESUMO
Until now, the specific pathogenesis of silicosis is not clear. Exosomal miRNAs, as a newly discovered intercellular communication medium, play an important role in many diseases. Our previous research found that serum exosomal miR125a-5p was increased in silicosis patients by miRNAs high-throughput sequencing. TRAF6, is a target gene of miR125a-5p, which is involved in T-cell differentiation. Furthermore, results from animal study indicate that knockdown of miR-125a-5p can regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6. However, the level of serum exosomal miR125a-5p in silicosis patients has not been reported, the role of macrophages-secreted exosomal miR-125a-5p in regulating T cell differentiation to promote fibroblast transdifferentiation (FMT) remains unknown. In this study, the levels of serum exosomal miR125a-5p and serum TGF-ß1, IL-17A, IL-4 cytokines in silicosis patients were elevated, with the progression of silicosis, the level of serum exosomal miR125a-5p and serum IL-4 were increased; thus, the serum level of IFN-γ was negatively correlated with the progression of silicosis. In vitro, the levels of miR125a-5p in macrophages, exosomes, and T cells stimulated by silica were significantly increased. When the mimic was transfected into T cells, which directly suppressed TRAF6 and caused the imbalance of T cells differentiation, induced FMT. To sum up, these results indicate that exosomal miR-125a-5p may by targeting TRAF6 of T cells, induces the activation and apoptosis of T cells and the remodeling of Th1/Th2 and Th17/Tregs distribution, ultimately promotes FMT. Suggesting that exosomal miR-125a-5p may be a potential therapeutic target for silicosis.
Assuntos
MicroRNAs , Silicose , Animais , Humanos , Linfócitos T Reguladores , Dióxido de Silício/toxicidade , Transdiferenciação Celular , Interleucina-4 , Fator 6 Associado a Receptor de TNF , Células Th17 , Silicose/genética , MicroRNAs/genética , FibroblastosRESUMO
Regulating the chemical/thermal stability and catalytic activity of coordination polymers (CPs) to achieve high catalytic performance is topical and challenging. The CPs are competent in promoting oxidative cross-coupling, yet they have not received substantial attention. Here, the ligand effect of the secondary ligand of CPs for oxidative cross-coupling reactions was investigated. Specifically, four new isostructural CPs [Co(Fbtx)1.5(4-R-1,2-BDC)]n (denoted as Co-CP-R, Fbtx = 1,4-bis(1,2,4-triazole-1-ylmethyl)-2,3,5,6-tetrafluorobenzene, 4-R-1,2-BDC = 4-R-1,2-benzenedicarboxylate, R = F, Cl, Br, CF3) were prepared. It was found that in the reactions of oxidative amination of benzoxazoles with secondary amines and the oxidative coupling of styrenes with benzaldehydes, both the chemical and thermal stabilities of the four Co-CPs with the R group followed the trend of -CF3 > -Br > -Cl > -F. Density functional theory (DFT) calculations suggested that the difference in reactivity may be ascribed to the effect of substituent groups on the electron transition energy of the cobalt(II) center of these Co-CPs. These findings highlight the secondary ligand effect in regulating the stability and catalytic performance of coordination networks.
RESUMO
Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising candidates for cell-free therapy in various diseases, including chronic cutaneous wounds. However, the lack of standardized protocols for EVs' preparation and identification poses a significant challenge to their clinical application. Thus, the objective was to develop a safe and efficient method for the large-scale production of hUCMSC-derived EVs while establishing a comprehensive identification protocol encompassing morphology, particle size distribution, protein expression, and purity. This study observed that most of the EVs acquired through the protocol exhibited either a cup-shaped or round-shaped structure, with a median diameter of ~73.25 nm. The proportions of EVs positive for CD9, CD63, and CD81 were 37.5%, 38.6%, and 19.8%, respectively. To enhance their therapeutic potential in wound treatment, EVs were incorporated into chitosan hydrogel, forming chitosan hydrogel-EVs (CS-EVs). Furthermore, it was demonstrated that CS-EVs exhibited continuous release of EVs into the surrounding environment and, importantly, that the released EVs were internalized by human umbilical vein endothelial cells (HUVECs), resulting in significant enhancement of cell migration and angiogenesis. Additionally, in a rat model of diabetic foot ulcers, CS-EVs demonstrated a robust therapeutic effect in promoting wound healing. Following a 15-day treatment period, the group treated with CS-EVs demonstrated an impressive 93.3% wound closure ability, accompanied by a high degree of re-epithelialization. In contrast, the control group exhibited only a 71.5% reduction in wound size. In summary, this study offers solutions for the purification, characterization, and application of EVs in clinical wound treatment. These results not only offer fresh perspectives on the involvement of hUCMSC-derived EVs in wound healing but also introduce a non-invasive approach for applying EVs that holds practical significance in skin repair.
Assuntos
Quitosana , Diabetes Mellitus , Pé Diabético , Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Animais , Ratos , Pé Diabético/terapia , Hidrogéis , Células Endoteliais da Veia Umbilical HumanaRESUMO
Gastric cancer (GC) is one of the main causes of cancer-related death. Lysine acetyltransferases 2 A (KAT2A) is a succinyltransferase that plays an essential role in cancer development. The pyruvate kinase M2 (PKM2) is a glycolysis rate-limiting enzyme that mediates the glycolysis of cancers. This study aimed to explore the effects and mechanism of KAT2A in GC progression. The effects of biological behaviors of GC cells were evaluated by MTT, colony formation and seahorse assays. The succinylation modification was assessed by immunoprecipitation (IP). The interaction between proteins were detected by Co-IP and immunofluorescence. A pyruvate kinase activity detection kit was used to evaluate the activity of PKM2. Western blot was performed to detect the expression and oligomerization of protein. Herein, we confirmed that KAT2A was highly expressed in GC tissues and was associated with a poor prognosis. Function studies showed that knockdown of KAT2A inhibited cell proliferation and glycolytic metabolism of GC. Mechanistically, KAT2A could directly interacted with PKM2 and KAT2A silencing inhibited the succinylation of PKM2 at K475 site. In addition, the succinylation of PKM2 altered its activity rather than its protein levels. Rescue experiments showed that KAT2A promoted GC cell growth, glycolysis, and tumor growth by promoting PKM2 K475 succinylation. Taken together, KAT2A promotes the succinylation of PKM2 at K475 to inhibit PKM2 activity, thus promotes the progression of GC. Therefore, targeting KATA2 and PKM2 may provide novel strategies for the treatment of GC.
RESUMO
Society and consumers are increasingly concerned about food safety and the sustainability of food production systems. A significant amount of by-products and discards are generated during the processing of aquatic animals, which still needs to be fully utilized by the food industry. The management and sustainable use of these resources are essential to avoiding environmental pollution and resource waste. These by-products are rich in biologically active proteins, which can be converted into peptides by enzymatic hydrolysis or fermentation treatment. Therefore, exploring the extraction of collagen peptides from these by-products using an enzymatic hydrolysis technology has attracted a wide range of attention from numerous researchers. Collagen peptides have been found to possess multiple biological activities, including antioxidant, anticancer, antitumor, hypotensive, hypoglycemic, and anti-inflammatory properties. These properties can enhance the physiological functions of organisms and make collagen peptides useful as ingredients in food, pharmaceuticals, or cosmetics. This paper reviews the general methods for extracting collagen peptides from various processing by-products of aquatic animals, including fish skin, scales, bones, and offal. It also summarizes the functional activities of collagen peptides as well as their applications.
RESUMO
ABSTRACT: Blast lung injuries (BLIs) are frequent because of industrial accidents and terrorist groups. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs (BMSCs-Exo) have become a hot topic in modern biology because of their significance in damage healing, immune regulation, and gene therapy. The aim of this study is to investigate the effect of BMSCs and BMSCs-Exo on BLI in rats caused by gas explosion. Here, BMSCs and BMSCs-Exo were transplanted into BLI rats via tail vein and then evaluated pathological alterations, oxidative stress, apoptosis, autophagy, and pyroptosis in the lung tissue. Through histopathology and changes in malondialdehyde (MDA) and superoxide dismutase (SOD) contents, we discovered that oxidative stress and inflammatory infiltration in the lungs were significantly reduced by BMSCs and BMSCs-Exo. After treatment with BMSCs and BMSCs-Exo, apoptosis-related proteins, such as cleaved caspase-3 and Bax, were significantly decreased, and the ratio of Bcl-2/Bax was significantly increased; the level of pyroptosis-associated proteins, including NLRP3, GSDMD-N, cleaved caspase-1, IL-1ß, and IL-18, were decreased; autophagy-related proteins, beclin-1 and LC3, were downregulated while P62 was upregulated; the number of autophagosomes was decreased. In summary, BMSCs and BMSCs-Exo attenuate BLI caused by gas explosion, which may be associated with apoptosis, aberrant autophagy, and pyroptosis.
Assuntos
Exossomos , Lesão Pulmonar , Células-Tronco Mesenquimais , Humanos , Lesão Pulmonar/metabolismo , Proteína X Associada a bcl-2/metabolismo , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , ApoptoseRESUMO
BACKGROUND: We performed a bioinformatics analysis to screen for cell cycle-related differentially expressed genes (DEGs) and constructed a model for the prognostic prediction of patients with early-stage lung squamous cell carcinoma (LSCC). METHODS: From a gene expression omnibus (GEO) database, the GSE157011 dataset was randomly divided into an internal training group and an internal testing group at a 1:1 ratio, and the GSE30219, GSE37745, GSE42127, and GSE73403 datasets were merged as the external validation group. We performed single-sample gene set enrichment analysis (ssGSEA), univariate Cox analysis, and difference analysis, and identified 372 cell cycle-related genes. Additionally, we combined LASSO/Cox regression analysis to construct a prognostic model. Then, patients were divided into high-risk and low-risk groups according to risk scores. The internal testing group, discovery set, and external verification set were used to assess model reliability. We used a nomogram to predict patient prognoses based on clinical features and risk values. Clinical relevance analysis and the Human Protein Atlas (HPA) database were used to verify signature gene expression. RESULTS: Ten cell cycle-related DEGs (EIF2B1, FSD1L, FSTL3, ORC3, HMMR, SETD6, PRELP, PIGW, HSD17B6, and GNG7) were identified and a model based on the internal training group constructed. From this, patients in the low-risk group had a higher survival rate when compared with the high-risk group. Time-dependent receiver operating characteristic (tROC) and Cox regression analyses showed the model was efficient and accurate. Clinical relevance analysis and the HPA database showed that DEGs were significantly dysregulated in LSCC tissue. CONCLUSION: Our model predicted the prognosis of early-stage LSCC patients and demonstrated potential applications for clinical decision-making and individualized therapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Proteínas Relacionadas à Folistatina , Neoplasias Pulmonares , Humanos , Prognóstico , Reprodutibilidade dos Testes , Carcinoma de Células Escamosas/genética , Ciclo Celular , Neoplasias Pulmonares/genética , Pulmão , Proteínas MetiltransferasesRESUMO
Silicosis caused by long-term inhalation of crystalline silica during occupational activities seriously threatens the health of occupational populations. Imbalances in T helper 1(Th1), Th2, Th17, and regulatory T cells (Tregs) promote the development of pulmonary silicosis. Exosomes and their contents, especially microRNAs (miRNAs), represent a new type of intercellular signal transmission mediator related to various diseases including pulmonary fibrosis. However, whether exosomal miRNAs can affect the progression of silicosis by regulating T cell differentiation remains to be determined. To test this hypothesis, we established a miR-125a-5p antagomir mouse model and examined changes in miR-125a-5p levels and T cell subtypes. We found that miR-125a-5p levels were increased in lung tissues and serum exosomes in the silica group at 7 days and 28 days. Downregulation of miR-125a-5p attenuated α-smooth muscle actin (α-SMA), collagen I, fibronectin, p-p65, and p-inhibitor of nuclear factor kappa B (NF-κB) kinase (IKK) protein expression, while tumor necrosis factor receptor-associated factor 6 (TRAF6) and p-inhibitor of κBα (IKBα) expression were increased. MiR-125a-5p anta-miR treatment contributes to the maintenance of Th1/Th2 balance during the progression of pulmonary fibrosis. Our findings indicated that knockdown miR-125a-5p could regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6.
Assuntos
Exossomos , MicroRNAs , Fibrose Pulmonar , Dióxido de Silício , Silicose , Animais , Camundongos , Proliferação de Células , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Dióxido de Silício/toxicidade , Silicose/genética , Silicose/patologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Exossomos/genética , Exossomos/metabolismoRESUMO
Flexible strain sensors occupying a large part of human body detection and wearable electronics, which have a wide sensing range and high sensitivity, are crucial in fully monitoring human motion signals. This study proposed a strategy to construct flexible strain sensors based on the V-groove/wrinkles hierarchical array. The V-groove array was prepared on a polydimethylsiloxane (PDMS) substrate through mold transfer printing. The gold film was sputtered on the prestretching PDMS substrate, and the V-groove/wrinkles hierarchical array was formed after strain release. Compared with the sensors based on single-scale wrinkle structures and a V-groove array, the fabricated strain sensor with the hierarchical array showed high sensitivity (maximum gauge factor up to 2,557.71) and a wide sensing range (up to 45%). In addition, the dynamic characteristics of the sensor were investigated in detail, indicating that the sensor had a fast response (less than 130 ms), a low detection limit (0.1% strain), and good stability (almost no performance loss after 10,000 cycles). In practical applications, the sensor was used to detect sizable physical motion and weak physiological signals, demonstrating great potential application value in human motion detection. This study could provide new ideas for preparing high-performance flexible strain sensors.
RESUMO
Exosomes have emerged as potential biomarkers for pancreatic cancer (PaC). However, it is still challenging to get quantitative detection of exosomes with the specific surface receptors. In this study, a highly sensitive detection system is first constructed for the direct quantitation of specific exosomes in real samples using hierarchical surface-enhanced Raman scattering substrate (H-SERS substrate) and rapid enrichment strategy magnetic beads @ exosomes @ SERS detection probes (MEDP). It is found that the detection system (MEDP @ H-SERS substrate) could provide a 3.5 times higher SERS intensity compared with MEDP sandwich immunocomplex only. Moreover, LRG1-positive exosomes (LRG1-Exos) and GPC1-positive exosomes (GPC1-Exos) are chosen to distinguish PaC through exosome proteomics and database screening. The lower limit of detection (LOD) is 15 particles µL-1 using the MEDP @ H-SERS substrate. Significantly, the detection in clinical samples shows that the innovative combination of LRG1-Exos and GPC1-Exos could improve the diagnostic efficiency of PaC, with an area under the operating characteristic curve (AUC) of 0.95. Even for the early-stage PaC, the diagnostic accuracy is still high (AUC = 0.95). Collectively, the findings indicate that the MEDP @ H-SERS substrate has great potential for the early diagnosis of PaC.
Assuntos
Exossomos , Neoplasias Pancreáticas , Detecção Precoce de Câncer , Humanos , Imunoensaio , Neoplasias Pancreáticas/diagnóstico , Análise Espectral Raman , Neoplasias PancreáticasRESUMO
As nanoscale extracellular vesicles, exosomes are secreted by various cell types, and they are widely distributed in multiple biological fluids. Studies have shown that tumor-derived exosomes can carry a variety of primary tumor-specific molecules, which may represent a novel tool for the early detection of cancer. However, the clinical translation of exosomes remains a challenge due to the requirement of large quantities of samples when enriching the cancer-related exosomes in biological fluids, the insufficiency of traditional techniques for exosome subpopulations, and the complex exosome isolation of the current commercially available exosome phenotype profiling approaches. The evolving surface-enhanced Raman scattering (SERS) technology, with properties of unique optoelectronics, easy functionalization, and the particular interaction between light and nanoscale metallic materials, can achieve sensitive detection of exosomes without large quantities of samples and multiplexed phenotype profiling, providing a new mode of real-time and noninvasive analysis for cancer patients. In the present review, we mainly discussed exosome detection based on SERS, especially SERS immunoassay. The basic structure and function of exosomes were firstly introduced. Then, recent studies using the SERS technique for cancer detection were critically reviewed, which mainly included various SERS substrates, biological modification of SERS substrates, SERS-based exosome detection, and the combination of SERS and other technologies for cancer diagnosis. This review systematically discussed the essential aspects, limitations, and considerations of applying SERS technology in the detection and analysis of cancer-derived exosomes, which could provide a valuable reference for the early diagnosis of cancer through SERS technology. STATEMENT OF SIGNIFICANCE: Surface-enhanced Raman scattering (SERS) has been applied to exosomes detection to obtain better diagnostic results. In past three years, several reviews have been published in exosome detection, which were narrowly focus on methods of exosome detection. Selection and surface functionalization of the substrate and the combination detection with different methods based on SERS will provide new strategies for the detection of exosomes. This review will focus on the above aspects. This emerging detection method is constantly evolving and contributing to the early discovery of diseases in the future.
Assuntos
Exossomos , Neoplasias , Exossomos/metabolismo , Humanos , Neoplasias/diagnóstico , Neoplasias/metabolismo , Análise Espectral Raman/métodosRESUMO
AIM OF THE STUDY: The aim of the study was to fabricate collagen-based composite dressings, evaluate the efficiency for wound healing and reveal the mechanism of promoting wound healing. MATERIALS AND METHODS: An innovative bi-layered composite wound dressing was developed using two marine biomacromolecules (collagen and chitosan). Full-thickness skin defect model was performed to evaluate the wound healing activity in vivo. The levels of inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL-1, IL-6, IL-8) and growth factors like transforming growth factor beta (TGF-ß), vascular epidermal growth factor (VEGF) and basic fibroblast growth factor (bFGF) were quantified by ELISA assays. The total amount of collagen was quantified by hydroxyproline content. The proliferation and viability of fibroblast cells cultured on collagen sponges were determined by CCK-8 assay. RESULTS: The results of wound closure and histopathological analysis indicated that non-crosslinked collagen-based bi-layered composite dressing stimulated wound healing, accelerated re-epithelialization and accomplished wound healing within a time span of 28 days. The results of levels of inflammatory cytokines and growth factors showed that collagen-based composite dressings could reduce the inflammatory response and upregulate growth factors levels to accelerate the wound healing. The results of hydroxyproline content and CCK-8 assay indicated that collagen-based composite dressings could also promote collagen synthesis and fibroblasts viability and proliferation. CONCLUSION: The non-crosslinked collagen-based bi-layered composite dressing could be applied for an efficient and ideal wound dressing. Therefore, the findings provided the essential theoretical basis for the potential of collagen-based composite dressing applied in wound healing fields.