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Bioelectronics is a hot research topic, yet an important tool, as it facilitates the creation of advanced medical devices that interact with biological systems to effectively diagnose, monitor and treat a broad spectrum of health conditions. Electrical stimulation (ES) is a pivotal technique in bioelectronics, offering a precise, non-pharmacological means to modulate and control biological processes across molecular, cellular, tissue, and organ levels. This method holds the potential to restore or enhance physiological functions compromised by diseases or injuries by integrating sophisticated electrical signals, device interfaces, and designs tailored to specific biological mechanisms. This review explains the mechanisms by which ES influences cellular behaviors, introduces the essential stimulation principles, discusses the performance requirements for optimal ES systems, and highlights the representative applications. From this review, we can realize the potential of ES based bioelectronics in therapy, regenerative medicine and rehabilitation engineering technologies, ranging from tissue engineering to neurological technologies, and the modulation of cardiovascular and cognitive functions. This review underscores the versatility of ES in various biomedical contexts and emphasizes the need to adapt to complex biological and clinical landscapes it addresses.
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Estimulación Eléctrica , Humanos , Animales , Ingeniería de Tejidos , Materiales Biocompatibles/química , Medicina RegenerativaRESUMEN
Continuous blood pressure (BP) tracking provides valuable insights into the health condition and functionality of the heart, arteries, and overall circulatory system of humans. The rapid development in flexible and wearable electronics has significantly accelerated the advancement of wearable BP monitoring technologies. However, several persistent challenges, including limited sensing capabilities and stability of flexible sensors, poor interfacial stability between sensors and skin, and low accuracy in BP estimation, have hindered the progress in wearable BP monitoring. To address these challenges, comprehensive innovations in materials design, device development, system optimization, and modeling have been pursued to improve the overall performance of wearable BP monitoring systems. In this review, we highlight the latest advancements in flexible and wearable systems toward continuous noninvasive BP tracking with a primary focus on materials development, device design, system integration, and theoretical algorithms. Existing challenges, potential solutions, and further research directions are also discussed to provide theoretical and technical guidance for the development of future wearable systems in continuous ambulatory BP measurement with enhanced sensing capability, robustness, and long-term accuracy.
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Algoritmos , Dispositivos Electrónicos Vestibles , Humanos , Monitoreo Ambulatorio de la Presión Arterial/instrumentación , Presión Sanguínea , Diseño de EquipoRESUMEN
Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces.
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Algoritmos , Inteligencia Artificial , Odorantes , Olfato , Dispositivos Electrónicos Vestibles , Humanos , Olfato/fisiología , Interfaz Usuario-Computador , Adulto , MasculinoRESUMEN
Methane is a major contributor to anthropogenic greenhouse gas emissions. Identifying large sources of methane, particularly from the oil and gas sectors, will be essential for mitigating climate change. Aircraft-based methane sensing platforms can rapidly detect and quantify methane point-source emissions across large geographic regions, and play an increasingly important role in industrial methane management and greenhouse gas inventory. We independently evaluate the performance of five major methane-sensing aircraft platforms: Carbon Mapper, GHGSat-AV, Insight M, MethaneAIR, and Scientific Aviation. Over a 6 week period, we released metered gas for over 700 single-blind measurements across all five platforms to evaluate their ability to detect and quantify emissions that range from 1 to over 1,500 kg(CH4)/h. Aircraft consistently quantified releases above 10 kg(CH4)/h, and GHGSat-AV and Insight M detected emissions below 5 kg(CH4)/h. Fully blinded quantification estimates for platforms using downward-facing imaging spectrometers have parity slopes ranging from 0.76 to 1.13, with R2 values of 0.61 to 0.93; the platform using continuous air sampling has a parity slope of 0.5 (R2 = 0.93). Results demonstrate that aircraft-based methane sensing has matured since previous studies and is ready for an increasingly important role in environmental policy and regulation.
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Aeronaves , Gases de Efecto Invernadero , Metano , Metano/análisis , Gases de Efecto Invernadero/análisis , Monitoreo del Ambiente/métodos , Cambio Climático , Contaminantes Atmosféricos/análisisRESUMEN
Extensive research has been done in haptic feedback for texture simulation in virtual reality (VR). However, it is challenging to modify the perceived tactile texture of existing physical objects which usually serve as anchors for virtual objects in mixed reality (MR). In this paper, we present ViboPneumo, a finger-worn haptic device that uses vibratory-pneumatic feedback to modulate (i.e., increase and decrease) the perceived roughness of the material surface contacted by the user's fingerpad while supporting the perceived sensation of other haptic properties (e.g., temperature or stickiness) in MR. Our device includes a silicone-based pneumatic actuator that can lift the user's fingerpad on the physical surface to reduce the contact area for roughness decreasing, and an on-finger vibrator for roughness increasing. The results of our perceptual study showed that the participants could perceive changes in roughness, both increasing and decreasing, compared to the original material surface. We also observed the overlapping roughness ratings among certain haptic stimuli (i.e., vibrotactile and pneumatic) and the originally perceived roughness of some materials without any haptic feedback. This suggests the potential to alter the perceived texture of one type of material to another in terms of roughness (e.g., modifying the perceived texture of ceramics as glass). Lastly, a user study of MR experience showed that ViboPneumo could significantly improve the MR user experience, particularly for visual-haptic matching, compared to the condition of a bare finger. We also demonstrated a few application scenarios for ViboPneumo.
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Macrophages, as essential components of the tumor immune microenvironment (TIME), could promote growth and invasion in many cancers. However, the role of macrophages in tumor microenvironment (TME) and immunotherapy in PCa is largely unexplored at present. Here, we investigated the roles of macrophage-related genes in molecular stratification, prognosis, TME, and immunotherapeutic response in PCa. Public databases provided single-cell RNA sequencing (scRNA-seq) and bulk RNAseq data. Using the Seurat R package, scRNA-seq data was processed and macrophage clusters were identified automatically and manually. Using the CellChat R package, intercellular communication analysis revealed that tumor-associated macrophages (TAMs) interact with other cells in the PCa TME primarily through MIF - (CD74+CXCR4) and MIF - (CD74+CD44) ligand-receptor pairs. We constructed coexpression networks of macrophages using the WGCNA to identify macrophage-related genes. Using the R package ConsensusClusterPlus, unsupervised hierarchical clustering analysis identified two distinct macrophage-associated subtypes, which have significantly different pathway activation status, TIME, and immunotherapeutic efficacy. Next, an 8-gene macrophage-related risk signature (MRS) was established through the LASSO Cox regression analysis with 10-fold cross-validation, and the performance of the MRS was validated in eight external PCa cohorts. The high-risk group had more active immune-related functions, more infiltrating immune cells, higher HLA and immune checkpoint gene expression, higher immune scores, and lower TIDE scores. Finally, the NCF4 gene has been identified as the hub gene in MRS using the "mgeneSim" function.
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Antígenos de Histocompatibilidad Clase II , Oxidorreductasas Intramoleculares , Factores Inhibidores de la Migración de Macrófagos , Neoplasias de la Próstata , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Regulación Neoplásica de la Expresión Génica , Pronóstico , Inmunoterapia , Redes Reguladoras de Genes , Antígenos de Diferenciación de Linfocitos B/genética , Antígenos de Diferenciación de Linfocitos B/metabolismoRESUMEN
BACKGROUND: Cardiovascular disease is the main cause of death and disability, with myocardial ischemia being the predominant type that poses a significant threat to humans. Reperfusion, an essential therapeutic approach, promptly reinstates blood circulation to the ischemic myocardium and stands as the most efficacious clinical method for myocardial preservation. Nevertheless, the restoration of blood flow associated with this process can potentially induce myocardial ischemia-reperfusion injury (MIRI), thereby diminishing the effectiveness of reperfusion and impacting patient prognosis. Therefore, it is of great significance to prevent and treat MIRI. PURPOSE: MIRI is an important factor affecting the prognosis of patients, and there is no specific in-clinic treatment plan. In this review, we have endeavored to summarize its pathological mechanisms and therapeutic drugs to provide more powerful evidence for clinical application. METHODS: A comprehensive literature review was conducted using PubMed, Web of Science, Embase, Medline and Google Scholar with a core focus on the pathological mechanisms and potential therapeutic drugs of MIRI. RESULTS: Accumulated evidence revealed that oxidative stress, calcium overload, mitochondrial dysfunction, energy metabolism disorder, ferroptosis, inflammatory reaction, endoplasmic reticulum stress, pyroptosis and autophagy regulation have been shown to participate in the process, and that the occurrence and development of MIRI are related to plenty of signaling pathways. Currently, a range of chemical drugs, natural products, and traditional Chinese medicine (TCM) preparations have demonstrated the ability to mitigate MIRI by targeting various mechanisms. CONCLUSIONS: At present, most of the research focuses on animal and cell experiments, and the regulatory mechanisms of each signaling pathway are still unclear. The translation of experimental findings into clinical practice remains incomplete, necessitating further exploration through large-scale, multi-center randomized controlled trials. Given the absence of a specific drug for MIRI, the identification of therapeutic agents to reduce myocardial ischemia is of utmost significance. For the future, it is imperative to enhance our understanding of the pathological mechanism underlying MIRI, continuously investigate and develop novel pharmaceutical agents, expedite the clinical translation of these drugs, and foster innovative approaches that integrate TCM with Western medicine. These efforts will facilitate the emergence of fresh perspectives for the clinical management of MIRI.
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Daño por Reperfusión Miocárdica , Estrés Oxidativo , Humanos , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Animales , Estrés Oxidativo/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Autofagia/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Piroptosis/efectos de los fármacosRESUMEN
Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.
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Electrónica , Dispositivos Electrónicos Vestibles , Piel , Textiles , ElectrodosRESUMEN
BACKGROUND: Phentolamine is an α-adrenergic receptor blocker that can be used to treat neonatal pneumonia, but its underlying mechanism is unclear. The purpose of this study is to probe the function of phentolamine on lipopolysaccharide (LPS)-induced inflammation and cell death in an in vitro model of neonatal pneumonia. METHODS: Human MRC-5 cells were incubated with varying doses of phentolamine in vitro to evaluate cell viability. Subsequently, LPS was introduced to further investigate the combined effects of phentolamine and LPS on cell viability and apoptosis in MRC-5 cells. The effect of phentolamine/LPS treatment on the Neurotrophic Tyrosine Kinase Receptor A (TrkA)/Protein Kinase B (Akt) signaling pathway and the phosphorylation of pathway proteins in MRC-5 cells was further analyzed via western blot. Additionally, knockout of TrkA and Akt genes in MRC-5 cells was performed to explore the effects of phentolamine/LPS treatment on cell viability, apoptosis levels, and inflammatory factor levels in MRC-5 cells. RESULTS: Preincubation of MRC-5 cells with a low concentration of phentolamine (≤6 µg/mL) protected against LPS-induced cell inflammatory injury. Phentolamine promoted both TrkA and Akt phosphorylation and Akt activation induced by LPS in MRC-5 cells. The protective effect of phentolamine against LPS-induced apoptosis and inflammation was significantly reduced in response to TrkA or Akt gene knockdown in MRC-5 cells. CONCLUSIONS: Phentolamine may protect LPS-induced apoptosis and inflammation by activating the TrkA and Akt signaling pathways.
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Lipopolisacáridos , Neumonía , Recién Nacido , Humanos , Lipopolisacáridos/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/farmacología , Fentolamina/farmacología , Transducción de Señal , Inflamación/metabolismo , ApoptosisRESUMEN
In vitro blood vessel models are significant for disease modeling, drug assays, and therapeutic development. Microfluidic technologies allow to create physiologically relevant culture models reproducing the features of the in vivo vascular microenvironment. However, current microfluidic technologies are limited by impractical rectangular cross-sections and single or nonsynchronous compound mechanical stimuli. This study proposes a new strategy for creating round-shaped deformable soft microfluidic channels to serve as artificial in vitro vasculature for developing in vitro models with vascular physio-mechanical microenvironments. Endothelial cells seeded into vascular models are used to assess the effects of a remodeled in vivo mechanical environment. Furthermore, a 3D stenosis model is constructed to recapitulate the flow disturbances in atherosclerosis. Soft microchannels can also be integrated into traditional microfluidics to realize multifunctional composite systems. This technology provides new insights into applying microfluidic chips and a prospective approach for constructing in vitro blood vessel models.
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Células Endoteliales de la Vena Umbilical Humana , Humanos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Microfluídica/métodos , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Presión , Animales , Dispositivos Laboratorio en un Chip , Células Endoteliales/citología , Células Endoteliales/metabolismo , Vasos Sanguíneos/fisiologíaRESUMEN
Copper (Cu) has been widely used for catalyzing the CO2 reduction reaction (CO2RR), but the plasmonic effect of Cu has rarely been explored for tuning the activity and selectivity of the CO2RR. Herein, we conducted a quantitative analysis on the plasmon-generated photopotential (Ehv) of a Cu nanowire array (NA) photocathode and found that Ehv exclusively reduced the apparent activation energy (Ea) of reducing CO2 to CO without affecting the competitive hydrogen evolution reaction (HER). As a result, the CO production rate was enhanced by 52.6% under plasmon excitation when compared with that under dark conditions. On further incorporation with a polycrystalline Si photovoltaic device, the Cu NA photocathode exhibits good stability in terms of photocurrent and syngas production (CO : H2 = 2 : 1) within 10 h. This work validates the crucial role of the plasmonic effect of Cu on modulating the activity and selectivity of the CO2RR.
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Sorting single cells from a population was of critical importance in areas such as cell line development and cell therapy. Image-based sorting is becoming a promising technique for the nonlabeling isolation of cells due to the capability of providing the details of cell morphology. This study reported the focusing of cells using microwell arrays and the following automatic size sorting based on the real-time recognition of cells. The simulation first demonstrated the converged streamlines to the symmetrical plane contributed to the focusing effect. Then, the influence of connecting microchannel, flowing length, particle size, and the sample flow rate on the focusing effect was experimentally analyzed. Both microspheres and cells could be aligned in a straight line at the Reynolds number (Re) of 0.027-0.187 and 0.027-0.08, respectively. The connecting channel was proved to drastically improve the focusing performance. Afterward, a tapered microwell array was utilized to focus sphere/cell spreading in a wide channel to a straight line. Finally, a custom algorithm was employed to identify and sort the size of microspheres/K562 cells with a throughput of 1 event/s and an accuracy of 97.8/97.1%. The proposed technique aligned cells to a straight line at low Reynolds numbers and greatly facilitated the image-activated sorting without the need for a high-speed camera or flow control components with high frequency. Therefore, it is of enormous application potential in the field of nonlabeled separation of single cells.
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Tamaño de la Partícula , Humanos , Microesferas , Células K562 , Simulación por ComputadorRESUMEN
Objective: To comprehensively analyze characteristics of thyroid dysfunction associated with iodine contrast media (ICM) based on data from the FDA adverse event reporting system (FAERS). Methods: Disproportionate analysis was employed to identify signals of thyroid dysfunction caused by ICM, and descriptive analysis was performed to examine the clinical characteristics of reported cases involving ICM-related thyroid dysfunctions. Results: A total of 83 adverse event reports were identified, documenting thyroid dysfunctions associated with ICM agents. Treatment with ICM was significantly associated with higher reporting of hypothyroidism ([ROR] = 2.21, 95 % CI: 1.59-3.08; IC025 = 0.58) and hyperthyroidism (ROR = 3.49, 95 % CI: 2.37-5.13; IC025 = 1.14). Among the six ICM agents investigated, iodixanol demonstrated the highest signal strength in both hypothyroidism (ROR = 9.47) and hyperthyroidism (ROR = 5.44). Hypothyroidism and hyperthyroidism almost occurred in the first 30 days after ICM administration (76.9 % and 70 % of patients, respectively). Furthermore, the proportion of severe outcomes in hyperthyroidism was significantly higher than that in hypothyroidism (12/26 vs. 2/35, P = 0.009). Conclusion: The present study highlights the varying risks of thyroid dysfunction associated with different ICM agents, with iodixanol exhibiting the highest signal intensity. Hypothyroidism and hyperthyroidism associated with ICM generally manifest within the first month following administration. Consequently, monitoring of thyroid function during this period is strongly recommended for ICM agents presenting higher risk profiles.
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The rapid diagnosis of respiratory virus infection through breath and blow remains challenging. Here we develop a wireless, battery-free, multifunctional pathogenic infection diagnosis system (PIDS) for diagnosing SARS-CoV-2 infection and symptom severity by blow and breath within 110 s and 350 s, respectively. The accuracies reach to 100% and 92% for evaluating the infection and symptom severity of 42 participants, respectively. PIDS realizes simultaneous gaseous sample collection, biomarker identification, abnormal physical signs recording and machine learning analysis. We transform PIDS into other miniaturized wearable or portable electronic platforms that may widen the diagnostic modes at home, outdoors and public places. Collectively, we demonstrate a general-purpose technology for rapidly diagnosing respiratory pathogenic infection by breath and blow, alleviating the technical bottleneck of saliva and nasopharyngeal secretions. PIDS may serve as a complementary diagnostic tool for other point-of-care techniques and guide the symptomatic treatment of viral infections.
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Líquidos Corporales , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Manejo de Especímenes , SalivaRESUMEN
Extended anterior transpetrosal approach (ATPA) includes drilling the petrous bone to achieve maximal exposure of the petroclival region. Injuring of surrounding neurovascular structures, such as the internal carotid artery (ICA), during the procedure may result in severe complications. In this study, we aimed to use computer topographic images to provide comprehensive anatomic information on the petrous bone and surrounding structures to help surgeons during the extended ATPA. Computer topographic angiography images of 110 individuals were reviewed, and measurements were performed on coronal, sagittal, and axial planes following multiplanar reformation. The petrous apex and sagittal midline were used to locate the anterior, middle, and posterior parts of the petrous bone and petrosal segment of the ICA during the ATPA. The thicknesses of the petrous bone were 3.28±0.71, 3.53±0.88, and 7.02±1.11 mm at the petrous apex, trigeminal impression, and internal opening of internal auditory canal (IAC) positions, respectively. The distances between the petrous apex to the trigeminal impression, internal opening of the IAC, auris interna, and labyrinth were 7.39±1.62, 15.95±2.48, 17.39±2.39, and 29.00±3.18 mm, respectively. Furthermore, the petrosal segment of the ICA was located at the above landmarks on the petrous bone. Our findings provide anatomic information on the petrous bone and surrounding structures during the extended ATPA procedure based on fixed anatomic landmarks so as to achieve maximal exposure and reduce the number of complications.
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Oído Interno , Hueso Petroso , Humanos , Hueso Petroso/diagnóstico por imagen , Hueso Petroso/cirugía , AngiografíaRESUMEN
When it comes to mass spectrometry data analysis for identification of peptide pairs linked by N-hydroxysuccinimide (NHS) ester cross-linkers, search engines bifurcate in their setting of cross-linkable sites. Some restrict NHS ester cross-linkable sites to lysine (K) and protein N-terminus, referred to as K only for short, whereas others additionally include serine (S), threonine (T), and tyrosine (Y) by default. Here, by setting amino acids with chemically inert side chains such as glycine (G), valine (V), and leucine (L) as cross-linkable sites, which serves as a negative control, we show that software-identified STY-cross-links are only as reliable as GVL-cross-links. This is true across different NHS ester cross-linkers including DSS, DSSO, and DSBU, and across different search engines including MeroX, xiSearch, and pLink. Using a published data set originated from synthetic peptides, we demonstrate that STY-cross-links indeed have a high false discovery rate. Further analysis revealed that depending on the data and the search engine used to analyze the data, up to 65% of the STY-cross-links identified are actually K-K cross-links of the same peptide pairs, up to 61% are actually K-mono-links, and the rest tend to contain short peptides at high risk of false identification.
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Ésteres , Proteínas , Reactivos de Enlaces Cruzados/química , Espectrometría de Masas/métodos , Péptidos/química , Proteínas/metabolismoRESUMEN
Cuproptosis is a novel form of cell death in tumours. However, the clinical impact and mechanism of cuproptosis in bladder cancer (BC) remain unclear. This study aimed to explore the functions of long noncoding RNAs (lncRNAs) related to cuproptosis in BC and develop a prognostic predictive model. RNA sequencing and clinicopathological data were derived from The Cancer Genome Atlas and randomly divided into training and validation groups. Cuproptosis-related lncRNAs were identified by Cox regression analysis and least absolute shrinkage and selection operator, and the patients were divided into high- and low-risk groups according to the median value of the signature-based risk score. We established a signature of 17 cuproptosis-associated lncRNAs in the training set. In both sets, patients with higher signature-based risk scores had a notably higher probability of death (P ≤ 0.001) and a shorter survival duration. Cox regression analyses confirmed the risk score as an independent predictor of BC prognosis in the entire set. The area under the curve (AUC) values for 1-, 3-, and 5-year survival were 0.767, 0.734, and 0.764, respectively, confirming that the signature could determine the prognosis of BC. A signature-based nomogram was developed, and its prediction accuracy was validated using calibration curves. Several drugs, including Gemcitabine, Oxaliplatin, Mitoxantrone, Camptothecin, Cytarabine and Irinotecan may benefit low-risk BC patients more. Finally, in vitro experiments confirmed that the cuproptosis-related lncRNAs are highly expressed in bladder cancer cells after cuproptosis induced by exogenous copper ions. In conclusion, a cuproptosis-related lncRNA signature independently predicted prognosis in BC, indicating a possible mechanism and clinical treatment approach.
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Apoptosis , ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Humanos , Nomogramas , Oxaliplatino , Pronóstico , Neoplasias de la Vejiga Urinaria/genética , CobreRESUMEN
Pectolinarin and linarin are two major flavone O-glycosides of Cirsium japonicum, which has been used for thousands of years in traditional Chinese medicine. Pharmacological research on pectolinarin and linarin is meaningful and necessary. Here, a process for the purification of pectolinarin and linarin from C. japonicum was established using macroporous resin enrichment followed by prep-HPLC separation. The results show the purity of pectolinarin and linarin reached 97.39% and 96.65%, respectively. The in vitro bioactivities result shows the ORAC values of pectolinarin and linarin are 4543 and 1441 µmol TE/g, respectively, meanwhile their inhibition rate of BSA-MGO-derived AGEs is 63.58% and 19.31% at 2 mg/mL, which is 56.03% and 30.73% in the BSA-fructose system, respectively. The COX-2 inhibition rate at 50 µg/mL of linarin and pectolinarin reached 55.35% and 40.40%, respectively. Furthermore, the in vivo bioassay combining of histopathologic evaluation and biochemical analysis of liver glutamic oxaloacetic transaminase, serum creatinine and TNF-α show pectolinarin can alleviate lipopolysaccharide (LPS)-induced acute liver and kidney injury in mice. Metabolomics analysis shows that pectolinarin attenuates LPS-challenged liver and kidney stress through regulating the arachidonic acid metabolism and glutathione synthesis pathways. Collectively, our work presents a solid process for pectolinarin and linarin purification and has discovered a promising natural therapeutic agent-pectolinarin.
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Cirsium , Ratones , Animales , Lipopolisacáridos , Glicósidos/farmacologíaRESUMEN
Separation and clonal culture and growth kinetics analysis of target cells in a mixed population is critical for pathological research, disease diagnosis, and cell therapy. However, long-term culture with time-lapse imaging of the isolated cells for clonal analysis is still challenging. This paper reports a microfluidic device with four-level filtration channels and a pneumatic microvalve for size sorting and in situ clonal culture of single cells. The valve was on top of the filtration channels and used to direct fluid flow by membrane deformation during separation and long-term culture to avoid shear-induced cell deformation. Numerical simulations were performed to evaluate the influence of device parameters affecting the pressure drop across the filtration channels. Then, a droplet model was employed to evaluate the impact of cell viscosity, cell size, and channel width on the pressure drop inducing cell deformation. Experiments showed that filtration channels with a width of 7, 10, 13, or 17 µm successfully sorted K562 cells into four different size ranges at low driving pressure. The maximum efficiency of separating K562 cells from media and whole blood was 98.6% and 89.7%, respectively. Finally, the trapped single cells were cultured in situ for 4-7 days with time-lapse imaging to obtain the lineage trees and growth curves. Then, the time to the first division, variation of cell size before and after division, and cell fusion were investigated. This proved that cells at the G1 and G2 phases were of significantly distinct sizes. The microfluidic device for size sorting and clonal expansion will be of tremendous application potential in single-cell studies.
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Técnicas Analíticas Microfluídicas , Microfluídica , Microfluídica/métodos , Filtración , Dispositivos Laboratorio en un Chip , CinéticaRESUMEN
In recent years, the role of intrinsic biophysical features, especially cellular stiffness, in diverse cellular and disease processes is being increasingly recognized. New high throughput techniques for the quantification of cellular stiffness facilitate the study of their roles in health and diseases. In this review, we summarized recent discovery about how cellular stiffness is involved in cell stemness, tumorigenesis, and blood diseases. In addition, we review the molecular mechanisms underlying the gene regulation of cellular stiffness in health and disease progression. Finally, we discussed the current understanding on how the cytoskeleton structure and the regulation of these genes contribute to cellular stiffness, highlighting where the field of cellular stiffness is headed.