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Inflammation is a complex physiological response involving various cellular and molecular events. Sulfur dioxide (SO2), recognized as both an endogenous signaling molecule and anti-inflammatory agent, plays a crucial role in modulating inflammation and maintaining cellular homeostasis. To gain deeper insights into the dynamics of inflammation-related processes, real-time monitoring of SO2 concentrations within cellular organelles is imperative. Here, we developed a near-infrared fluorescent probe, R2, equipped with lysosomal targeting features. R2 effectively monitors dynamic SO2 concentration changes during inflammation. The fluorescence intensity at 703 nm of R2 shows a strong linear correlation with the concentration of SO2, displaying a rapid response time to SO2 within 10 s and maintaining excellent photostability. The successful application of R2 in elucidating dynamic SO2 concentration changes in lysosomal during cellular and rat inflammatory processes underscores its significant potential as a tool for understanding the pathogenesis of inflammation-related diseases.
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Colorantes Fluorescentes , Inflamación , Lisosomas , Dióxido de Azufre , Lisosomas/metabolismo , Lisosomas/química , Dióxido de Azufre/análisis , Animales , Inflamación/metabolismo , Colorantes Fluorescentes/química , Humanos , Ratas , Ratones , Espectrometría de Fluorescencia , MasculinoRESUMEN
Gesture recognition has emerged as a significant research domain in computer vision and human-computer interaction. One of the key challenges in gesture recognition is how to select the most useful channels that can effectively represent gesture movements. In this study, we have developed a channel selection algorithm that determines the number and placement of sensors that are critical to gesture classification. To validate this algorithm, we constructed a Force Myography (FMG)-based signal acquisition system. The algorithm considers each sensor as a distinct channel, with the most effective channel combinations and recognition accuracy determined through assessing the correlation between each channel and the target gesture, as well as the redundant correlation between different channels. The database was created by collecting experimental data from 10 healthy individuals who wore 16 sensors to perform 13 unique hand gestures. The results indicate that the average number of channels across the 10 participants was 3, corresponding to an 75% decrease in the initial channel count, with an average recognition accuracy of 94.46%. This outperforms four widely adopted feature selection algorithms, including Relief-F, mRMR, CFS, and ILFS. Moreover, we have established a universal model for the position of gesture measurement points and verified it with an additional five participants, resulting in an average recognition accuracy of 96.3%. This study provides a sound basis for identifying the optimal and minimum number and location of channels on the forearm and designing specialized arm rings with unique shapes.
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Algoritmos , Gestos , Reconocimiento de Normas Patrones Automatizadas , Humanos , Masculino , Femenino , Adulto , Reconocimiento de Normas Patrones Automatizadas/métodos , Adulto Joven , Miografía/métodos , Mano/fisiología , Voluntarios Sanos , Reproducibilidad de los ResultadosRESUMEN
Pressure-sensitive paints (PSP) enable non-intrusive visualization of surface pressure distribution on model surface which is important for aerodynamic studies. However, conventional PSP materials suffer from photobleaching and inadequate sensitivity. In this work, we rationally designed and synthesized novel dendritic oxygen probes (PT1 and PT2) by covalently grafting fluorinated dendrons onto platinum tetrakis(pentafluorophenyl)porphyrin (PT0) (a common oxygen probe). Subsequently, PT2 loaded nanofibers membranes from polycaprolactone (PCL) were fabricated by electrospinning. Fabricated membranes showed high oxygen sensitivity (I0/I100 = 35.3) with excellent flexibility, good reversibility, and outstanding photostability (merely 2.0% intensity loss after prolonged irradiation). The pressure sensitivity was found around 0.73 % per kilopascal. Furthermore, significant variation in emission intensity with respect to the variation in air pressure (1.3-101.32 kPa), facilitates the naked eye visualization of the pressure distribution on the membrane surface. Such excellent oxygen and pressure sensitivity and photostability might be due to high fluorine contents of complex dendritic structure of PT2. This flexible fluorine-functionalized dendritic oxygen probe puts forward a facile and effective strategy to develop advanced PSP materials enabling accurate pressure mapping for aerodynamic studies.
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ABSTRACT: Conventional "1-variable-at-a-time" analyses to identify treatment effect modifiers are often underpowered and prone to false-positive results. This study used a "risk-modeling" approach guided by the Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement framework: (1) developing and validating a multivariable model to estimate predicted future back-related functional limitations as measured by the Roland-Morris Disability Questionnaire (RMDQ) and (2) stratifying patients from a randomized controlled trial (RCT) of lumbar epidural steroid injections (LESIs) for the treatment of lumbar spinal stenosis into subgroups with different individualized treatment effects on RMDQ scores at the 3-week follow-up. Model development and validation were conducted in a cohort (n = 3259) randomly split into training and testing sets in a 4:1 ratio. The model was developed in the testing set using linear regression with least absolute shrinkage and selection regularization and 5-fold cross-validation. The model was then applied in the testing set and subsequently in patients receiving the control treatment in the RCT of LESI. R2 values in the training set, testing set, and RCT were 0.38, 0.32, and 0.34, respectively. There was statistically significant modification ( P = 0.03) of the LESI treatment effect according to predicted risk quartile, with clinically relevant LESI treatment effect point estimates in the 2 quartiles with greatest predicted risk (-3.7 and -3.3 RMDQ points) and no effect in the lowest 2 quartiles. A multivariable risk-modeling approach identified subgroups of patients with lumbar spinal stenosis with a clinically relevant treatment effect of LESI on back-related functional limitations.
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Estenosis Espinal , Humanos , Estenosis Espinal/tratamiento farmacológico , Inyecciones Epidurales/efectos adversos , Inyecciones Epidurales/métodos , Proyectos de Investigación , Terapia Conductista , Esteroides/uso terapéutico , Esteroides/efectos adversos , Vértebras Lumbares , Resultado del TratamientoRESUMEN
BACKGROUND: Tuberculosis (TB) is a serious chronic infectious disease caused by Mycobacterium tuberculosis complex (MTBC). Hence, the development of a novel, simple, rapid and sensitive method to detect MTBC is of great significance for the prevention and treatment of TB. RESULTS: In this study, multiple cross displacement amplification (MCDA) combined with a nanoparticle-based lateral flow biosensor (LFB) was developed to simultaneously detect two target genes (IS6110 and mpb64) of MTBC (MCDA-LFB). One suite of specific MCDA primers designed for the IS6110 and mpb64 genes was validated using genomic DNA extracted from the reference strain H37Rv. The MCDA amplicons were analyzed using a real-time turbidimeter, colorimetric indicator (malachite green, MG) and LFBs. The optimal amplification temperature and time were confirmed, and the MCDA-LFB method established in the current report was evaluated by detecting various pathogens (i.e., reference strains, isolates and clinical sputum samples). The results showed that the two sets of MCDA primers targeting the IS6110 and mpb64 genes could effectively detect MTBC strains. The optimal reaction conditions for the MCDA assay were determined to be 67 °C for 35 min. The MCDA assay limit of detection (LoD) was 100 fg per reaction for pure genomic DNA. The specificity of the MCDA-LFB assay was 100%, and there were no cross-reactions for non-MTBC strains. For sputum samples and MTBC strain detection, the positive rate of MCDA-LFB for the detection of MTBC strains was consistent with seminested automatic real-time PCR (Xpert MTB/RIF) and higher than acid-fast staining (AFS) and culture assays when used for sputum samples. The MCDA-LFB assay was a rapid tool, and the whole procedure for MCDA-LFB, including DNA template preparation, MCDA reaction and amplification product analysis, was completed within 70 min. CONCLUSION: The MCDA-LFB assay targeting the IS6110 and mpb64 genes is a simple, rapid, sensitive and reliable detection method, and it has potential significance for the prevention and treatment of TB.
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Técnicas Biosensibles , Mycobacterium tuberculosis/genética , Técnicas de Amplificación de Ácido Nucleico/normas , Tuberculosis/microbiología , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Genes Bacterianos/genética , Humanos , Sensibilidad y Especificidad , TiempoRESUMEN
Tuberculosis (TB) is a chronic infectious disease mainly caused by Mycobacterium tuberculosis (MTB), but other members of the Mycobacterium tuberculosis complex (MTBC), especially Mycobacterium bovis (pyrazinamide-resistant organisms), may also be involved. Thus, the ability to rapidly detect and identify MTB from other MTBC members (e.g., M. bovis, Mycobacterium microti, Mycobacterium africanum) is essential for the prevention and treatment of TB. A novel diagnostic method for the rapid detection and differentiation of MTB, which employs multiplex loop-mediated isothermal amplification (mLAMP) combined with a nanoparticle-based lateral flow biosensor (LFB), was established (mLAMP-LFB). Two sets of specific primers that target the IS6110 and mtp40 genes were designed according to the principle of LAMP. Various pathogens were used to optimize and evaluate the mLAMP-LFB assay. The optimal conditions for mLAMP-LFB were determined to be 66°C and 40 min, and the amplicons were directly verified by observing the test lines on the biosensor. The LAMP assay limit of detection (LoD) was 125 fg per vessel for the pure genomic DNA of MTB and 4.8 × 103 CFU/ml for the sputum samples, and the analytical specificity was 100%. In addition, the whole process, including the clinical specimen processing (35 min), isothermal amplification (40 min), and result confirmation (1-2 min), could be completed in approximately 80 min. Thus, mLAMP-LFB is a rapid, reliable, and sensitive method that is able to detect representative members of MTBC and simultaneously differentiate MTB from other MTBC members, and it can be used as a potential screening tool for TB in clinical, field, and basic laboratory settings.
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Tuberculosis (TB) is the deadliest infectious caused by Mycobacterium tuberculosis complex (MTBC). Because most TB cases occur within low-income populations, developing a specific, sensitive, cost-saving, and rapid point-of-care test for the early diagnosis of TB is important for achieving the WHO's End Tuberculosis Strategy. In the current study, a novel nucleic acid detection strategy that includes multiplex loop-mediated isothermal amplification combined with a nanoparticle-based lateral flow biosensor (mLAMP-LFB) was used to detect MTBC. The two sets of LAMP primers specific to the IS6110 and gyrB genes of MTBC were successfully designed and validated for the detection of MTBC. The preferred reaction conditions for this assay were confirmed to be 65 °C for 40 min, and the amplification products could be visually identified through LFB within 2 min. The full assay process, including genomic DNA template extraction, LAMP reaction, and product detection, could be completed in 80 min. The limit detection of the assay was 100 fg of DNA in pure culture. The specificity of the assay was 100%, and it had no cross-reactions to other strains. Thus, the m-LAMP-LFB technology established in the present study was an objective, rapid, simple, and sensitive assay for MTBC identification, which could be applied in a clinical setting, especially in resource-constrained regions of the world.
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Técnicas Biosensibles , Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis , Técnicas de Amplificación de Ácido Nucleico , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Nanopartículas , Sensibilidad y Especificidad , Tuberculosis/diagnósticoRESUMEN
Cancer proteomics has become a powerful technique for characterizing the protein markers driving transformation of malignancy, tracing proteome variation triggered by therapeutics, and discovering the novel targets and drugs for the treatment of oncologic diseases. To facilitate cancer diagnosis/prognosis and accelerate drug target discovery, a variety of methods for tumor marker identification and sample classification have been developed and successfully applied to cancer proteomic studies. This review article describes the most recent advances in those various approaches together with their current applications in cancer-related studies. Firstly, a number of popular feature selection methods are overviewed with objective evaluation on their advantages and disadvantages. Secondly, these methods are grouped into three major classes based on their underlying algorithms. Finally, a variety of sample separation algorithms are discussed. This review provides a comprehensive overview of the advances on tumor maker identification and patients/samples/tissues separations, which could be guidance to the researches in cancer proteomics.
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Dysregulation of dopamine neurotransmission has been linked to the development of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). To investigate the mechanisms underlying this phenomenon, this study used an inducible HIV-1 transactivator of transcription (Tat) transgenic (iTat-tg) mouse model, which demonstrates brain-specific Tat expression induced by administration of doxycycline. We found that induction of Tat expression in the iTat-tg mice for either 7 or 14 days resulted in a decrease (â¼30%) in the V max of [3H]dopamine uptake via both the dopamine transporter (DAT) and norepinephrine transporter (NET) in the prefrontal cortex (PFC), which was comparable to the magnitude (â¼35%) of the decrease in B max for [3H]WIN 35,428 and [3H]nisoxetine binding to DAT and NET, respectively. The decreased V max was not accompanied by a reduction of total or plasma membrane expression of DAT and NET. Consistent with the decreased V max for DAT and NET in the PFC, the current study also found an increase in the tissue content of DA and dihydroxyphenylacetic acid in the PFC of iTat-tg mice after 7 days' administration of doxycycline. Electrophysiological recordings in layer V pyramidal neurons of the prelimbic cortex from iTat-tg mice found a significant reduction in action potential firing, which was not sensitive to selective inhibitors for DAT and NET, respectively. These findings provide a molecular basis for using the iTat-tg mouse model in the studies of NeuroHIV. Determining the mechanistic basis underlying the interaction between Tat and DAT/NET may reveal novel therapeutic possibilities for preventing the increase in comorbid conditions as well as HAND. SIGNIFICANCE STATEMENT: Human immunodeficiency virus (HIV)-1 infection disrupts dopaminergic neurotransmission, leading to HIV-associated neurocognitive disorders (HANDs). Based on our in vitro and in vivo studies, dopamine uptake via both dopamine and norepinephrine transporters is decreased in the prefrontal cortex of HIV-1 Tat transgenic mice, which is consistent with the increased dopamine and dihydroxyphenylacetic acid contents in this brain region. Thus, these plasma membrane transporters are an important potential target for therapeutic intervention for patients with HAND.
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Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Dopamina/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Corteza Prefrontal/metabolismo , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética , Animales , Transporte Biológico , Expresión Génica , Masculino , Ratones , Ratones Transgénicos , Neuronas/metabolismo , Corteza Prefrontal/citologíaRESUMEN
BACKGROUND: Enterococcus faecalis, an opportunistic bacterial pathogen, is one of the most frequently isolated bacterial species and cause of serious nosocomial infections in recent decades. A reliable and rapid assay for E. faecalis detection is significant for the diagnosis and follow-up treatment. METHODS: A novel assay method, named multiple cross displacement amplification linked with nanoparticle-based lateral flow biosensor (MCDA-LFB), was applied for detecting E. faecalis strains. A set of special 10 primers was designed according to E. faecalis-specific gene Ef0027. The MCDA amplification conditions, including the target DNA concentration, reaction temperature and time, were optimized. The sensitivity and specificity of MCDA method were tested in the current study, and then, the MCDA-LFB technology was applied to detect the E. faecalis strain from clinical samples. RESULTS: The E. faecalis specific primers were valid for the establishment of MCDA-LFB technology forthe detection of E. faecalis based on the Ef0027 gene. The MCDA amplification condition was optimized at 62°C for 35 min. The MCDA products were directly sensed and displayed with a biosensor. The full process, comprising genomic DNA template preparation (approximately 30 mins), amplification of MCDA (35 mins), and the product identification (approximately 2 mins), could be achieved in 70 mins. The MCDA technique could detect as little as 10 fg per reaction system of pure E. faecalis genomic DNA. The specificity of E. faecalis-MCDA-LFB method is 100%, with no cross-reactions to non-E. faecalis strains. CONCLUSION: The MCDA-LFB technique established in the present study is a reliable, simple, rapid, sensitive and specific method to assay E. faecalis and can be applied for the detection of clinical samples.
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Nanoscience becomes one of the most cutting-edge research directions in recent years since it is gradually matured from basic to applied science. Nanoparticles (NPs) and nanomaterials (NMs) play important roles in various aspects of biomedicine science, and their influences on the environment have caused a whole range of uncertainties which require extensive attention. Due to the quantitative and dynamic information provided for human proteome, mass spectrometry (MS)-based quantitative proteomic technique has been a powerful tool for nanomedicine study. In this article, recent trends of progress and development in the nanomedicine of proteomics were discussed from quantification techniques and publicly available resources or tools. First, a variety of popular protein quantification techniques including labeling and label-free strategies applied to nanomedicine studies are overviewed and systematically discussed. Then, numerous protein profiling tools for data processing and postbiological statistical analysis and publicly available data repositories for providing enrichment MS raw data information sources are also discussed.
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Espectrometría de Masas/tendencias , Nanomedicina , Proteómica , Humanos , ProteomaRESUMEN
Mitophagy protects against ischemic neuronal injury by eliminating damaged mitochondria, but it is unclear how mitochondria in distal axons are cleared. We find that oxygen and glucose deprivation-reperfusion reduces mitochondrial content in both cell bodies and axons. Axonal mitochondria elimination was not abolished in Atg7 fl/fl ;nes-Cre neurons, suggesting the absence of direct mitophagy in axons. Instead, axonal mitochondria were enwrapped by autophagosomes in soma and axon-derived mitochondria prioritized for elimination by autophagy. Intriguingly, axonal mitochondria showed prompt loss of anterograde motility but increased retrograde movement upon reperfusion. Anchoring of axonal mitochondria by syntaphilin blocked neuronal mitophagy and aggravated injury. Conversely, induced binding of mitochondria to dynein reinforced retrograde transport and enhanced mitophagy to prevent mitochondrial dysfunction and attenuate neuronal injury. Therefore, we reveal somatic autophagy of axonal mitochondria in ischemic neurons and establish a direct link of retrograde mitochondrial movement with mitophagy. Our findings may provide a new concept for reducing ischemic neuronal injury by correcting mitochondrial motility.
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Axones/patología , Isquemia Encefálica/patología , Corteza Cerebral/patología , Mitocondrias/patología , Mitofagia , Neuronas/patología , Animales , Proteína 7 Relacionada con la Autofagia/fisiología , Axones/metabolismo , Isquemia Encefálica/metabolismo , Corteza Cerebral/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Noqueados , Mitocondrias/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Ubiquitina-Proteína Ligasas/fisiologíaRESUMEN
One of the most challenging puzzles in drug discovery is the identification and characterization of candidate drug of well-balanced profile between efficacy and safety. So far, extensive efforts have been made to evaluate this balance by estimating the quantitative structure-therapeutic relationship and exploring target profile of adverse drug reaction. Particularly, the therapeutic index (TI) has emerged as a key indicator illustrating this delicate balance, and a clinically successful agent requires a sufficient TI suitable for it corresponding indication. However, the TI information are largely unknown for most drugs, and the mechanism underlying the drugs with narrow TI (NTI drugs) is still elusive. In this study, the collective effects of human protein-protein interaction (PPI) network and biological system profile on the drugs' efficacy-safety balance were systematically evaluated. First, a comprehensive literature review of the FDA approved drugs confirmed their NTI status. Second, a popular feature selection algorithm based on artificial intelligence (AI) was adopted to identify key factors differencing the target mechanism between NTI and non-NTI drugs. Finally, this work revealed that the targets of NTI drugs were highly centralized and connected in human PPI network, and the number of similarity proteins and affiliated signaling pathways of the corresponding targets was much higher than those of non-NTI drugs. These findings together with the newly discovered features or feature groups clarified the key factors indicating drug's narrow TI, and could thus provide a novel direction for determining the delicate drug efficacy-safety balance.