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1.
Nat Methods ; 20(1): 70-74, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36456785

RESUMEN

Applying rational design, we developed 17 kDa cyanobacteriochrome-based near-infrared (NIR-I) fluorescent protein, miRFP718nano. miRFP718nano efficiently binds endogenous biliverdin chromophore and brightly fluoresces in mammalian cells and tissues. miRFP718nano has maximal emission at 718 nm and an emission tail in the short-wave infrared (SWIR) region, allowing deep-penetrating off-peak fluorescence imaging in vivo. The miRFP718nano structure reveals the molecular basis of its red shift. We demonstrate superiority of miRFP718nano-enabled SWIR imaging over NIR-I imaging of microbes in the mouse digestive tract, mammalian cells injected into the mouse mammary gland and NF-kB activity in a mouse model of liver inflammation.


Asunto(s)
Colorantes Fluorescentes , Imagen Óptica , Ratones , Animales , Colorantes Fluorescentes/química , Mamíferos
2.
BMC Gastroenterol ; 24(1): 153, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702642

RESUMEN

BACKGROUND: Liver diseases were significant source of early readmission burden. This study aimed to evaluate the 30-day unplanned readmission rates, causes of readmissions, readmission costs, and predictors of readmission in patients with acute liver failure (ALF). METHODS: Patients admitted for ALF from 2019 National Readmission Database were enrolled. Weighted multivariable logistic regression models were applied and based on Directed Acyclic Graphs. Incidence, causes, cost, and predictors of 30-day unplanned readmissions were identified. RESULTS: A total of 3,281 patients with ALF were enrolled, of whom 600 (18.3%) were readmitted within 30 days. The mean time from discharge to early readmission was 12.6 days. The average hospital cost and charge of readmission were $19,629 and $86,228, respectively. The readmissions were mainly due to liver-related events (26.6%), followed by infection (20.9%). The predictive factors independently associated with readmissions were age, male sex (OR 1.227, 95% CI 1.023-1.472; P = 0.028), renal failure (OR 1.401, 95% CI 1.139-1.723; P = 0.001), diabetes with chronic complications (OR 1.327, 95% CI 1.053-1.672; P = 0.017), complicated hypertension (OR 1.436, 95% CI 1.111-1.857; P = 0.006), peritoneal drainage (OR 1.600, 95% CI 1.092-2.345; P = 0.016), etc. CONCLUSIONS: Patients with ALF are at relatively high risk of early readmission, which imposes a heavy medical and economic burden on society. We need to increase the emphasis placed on early readmission of patients with ALF and establish clinical strategies for their management.


Asunto(s)
Bases de Datos Factuales , Fallo Hepático Agudo , Readmisión del Paciente , Humanos , Readmisión del Paciente/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Fallo Hepático Agudo/economía , Fallo Hepático Agudo/terapia , Factores de Riesgo , Adulto , Anciano , Costos de Hospital/estadística & datos numéricos , Factores Sexuales , Factores de Tiempo , Modelos Logísticos , Factores de Edad , Incidencia
3.
Lipids Health Dis ; 23(1): 79, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38481325

RESUMEN

OBJECTIVE: Insulin resistance (IR) imposes a significant burden on inflammatory diseases, and the triglyceride-glucose (TyG) index, which is an easily accessible indicator for detecting IR, holds great application potential in predicting the risk of arthritis. The aim of this study is to analyze the association between the TyG index and the risk of new-onset arthritis in the common population aged over 45 using a prospective cohort study design. METHOD: This population-based cohort study involved 4418 participants from the China Health and Retirement Longitudinal Study (from Wave 1 to Wave 4). Multivariate logistic regression models were employed to investigate the association between the TyG index and new-onset arthritis, and RCS analyses were used to investigate potential non-linear relationships. Moreover, decision trees were utilized to identify high-risk populations for incident arthritis. RESULT: Throughout a 7-year follow-up interval, it was found that 396 participants (8.96%) developed arthritis. The last TyG index quartile group (Q4) presented the highest risk of arthritis (OR, 1.39; 95% CI, 1.01, 1.91). No dose-response relationship between the TyG index and new-onset arthritis was identified (Poverall=0.068, Pnon-linear=0.203). In the stratified analysis, we observed BMI ranging from 18.5 to 24 exhibited a heightened susceptibility to the adverse effects of the TyG index on the risk of developing arthritis (P for interaction = 0.035). CONCLUSION: The TyG index can be used as an independent risk indicator for predicting the start of new-onset arthritis within individuals aged 45 and above within the general population. Improving glucose and lipid metabolism, along with insulin resistance, may play a big part in improving the primary prevention of arthritis.


Asunto(s)
Artritis , Resistencia a la Insulina , Humanos , Estudios de Cohortes , Estudios Longitudinales , Estudios Prospectivos , Artritis/diagnóstico , Artritis/epidemiología , Glucosa , Factores de Riesgo , Triglicéridos , Glucemia , Biomarcadores
4.
BMC Public Health ; 24(1): 147, 2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38200420

RESUMEN

BACKGROUND: Low back pain is the leading cause of productivity loss, imposes a significant economic burden on the patients and society. Oxidative stress is considered a critical factor in the complex pathophysiological process and pathogenic mechanism of low back pain. Adjustment dietary pattern can effectively increase antioxidant biomarkers levels within the body to reduce oxidative stress. The composite dietary antioxidant index (CDAI) serves a reliable scoring system for quantifying the potential dietary antioxidant capacity of daily diets. OBJECTIVE: We aim to investigate the potential association between CDAI and low back pain, in order to enhance the management of low back pain through dietary guidance. METHODS: This study included 17,682 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2000, 2001-2002, 2003-2004 and 2009-2010. The weighted logistic regression model was used to investigate the association between CDAI and low back pain, while restricted cubic spline (RCS) was employed to examine non-linear trend and cutoffs. RESULTS: After adjusting for all confounders, the results showed that there was no significant association between CDAI and low back pain. However, individuals in the highest quartile of CDAI exhibited an 11.7% less likelihood of experiencing a low back pain than those in the lowest quartile (OR = 0.883; 95% CI [0.787,0.991], P = 0.034), and the trend test was also significant (P for trend < 0.001). RCS indicated a linear relationship between CDAI and low back pain (P for non-linear = 0.876). Gender subgroup analysis showed that this negative association was significant in the female population (OR = 0.983; 95% CI [0.968, 0.998], P = 0.027), and females in the highest quartile of CDAI were 19.7% less likely to suffer low back pain than those in the lowest quartile (OR = 0.803; 95% CI [0.682,0.945], P = 0.008). Additionally, the changes in zinc (OR = 1.009; 95% CI [1.002, 1.016], P = 0.015) and selenium (OR = 0.379; 95% CI [0.164, 0.875], P = 0.023) per milligram were independently associated with low back pain. CONCLUSION: The fully adjusted model showed no significant association between CDAI and low back pain, but it was significant in quartiles. Meanwhile, subgroup analysis by gender revealed a negative association between CDAI and low back pain in the female population. Additionally, the findings of this study also suggested that the antioxidant diets should be studied in a dietary pattern context.


Asunto(s)
Antioxidantes , Dolor de la Región Lumbar , Adulto , Femenino , Humanos , Estudios Transversales , Encuestas Nutricionales , Dolor de la Región Lumbar/epidemiología , Dieta
5.
Sensors (Basel) ; 24(7)2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38610534

RESUMEN

This study explores the important role of assessing force levels in accurately controlling upper limb movements in human-computer interfaces. It uses a new method that combines entropy to improve the recognition of force levels. This research aims to differentiate between different levels of isometric contraction forces using electroencephalogram (EEG) signal analysis. It integrates eight different entropy measures: power spectrum entropy (PSE), singular spectrum entropy (SSE), logarithmic energy entropy (LEE), approximation entropy (AE), sample entropy (SE), fuzzy entropy (FE), alignment entropy (PE), and envelope entropy (EE). The findings emphasize two important advances: first, including a wide range of entropy features significantly improves classification efficiency; second, the fusion entropy method shows exceptional accuracy in classifying isometric contraction forces. It achieves an accuracy rate of 91.73% in distinguishing between 15% and 60% maximum voluntary contraction (MVC) forces, along with 69.59% accuracy in identifying variations across 15%, 30%, 45%, and 60% MVC. These results illuminate the efficacy of employing fusion entropy in EEG signal analysis for isometric contraction detection, heralding new opportunities for advancing motor control and facilitating fine motor movements through sophisticated human-computer interface technologies.


Asunto(s)
Electroencefalografía , Contracción Isométrica , Humanos , Entropía , Movimiento , Reconocimiento en Psicología
6.
J Stroke Cerebrovasc Dis ; 33(11): 107636, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38346661

RESUMEN

PURPOSE: To explore possible mechanism(s) underlying beneficial effects of acupuncture treatment for alleviating focal cerebral infarction-induced neuronal injury, mitochondrial biogenesis, energy metabolism, oxidative stress and dendrite regeneration were evaluated in rats with experimentally induced cerebral ischemia and dendron reperfusion. MATERIALS AND METHODS: Rats were randomly assigned to three groups (sham-operated, operated group without acupuncture, operated group with acupuncture). RT-PCR and Western blotting were used to assess variations of hippocampal cell mitochondrial DNA (mtDNA) copy number and mRNA and protein expression levels associated with key mitochondrial biogenesis proteins, namely peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiration factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). To evaluate mitochondrial oxidative phosphorylation and respiratory function in ischemic tissues, oxidative phosphorylation protein complex expression levels were assessed via Western blot analysis, mitochondrial membrane potential (MMP) was assessed via confocal microscopy and flow cytometry and adenosine triphosphate (ATP) concentration was assessed using an enzymatic fluorescence-based assay. Immunofluorescence staining was used to evaluate the expression of the neuronal dendron formation marker-Microtubule Associated Protein 2 (MAP2). Additionally, oxidative stress levels were assessed based on superoxide dismutase (SOD) activity, lipid oxidation levels (malondialdehyde, MDA) and glutathione (GSH) levels. Meanwhile, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl staining, transmission electron microscopy observation and neuro behavioral status were used to determine cerebral infarction volume and extent of brain injury. RESULTS: Acupuncture treatment effectively stimulated mRNA-level and protein-level expression associated with PGC-1α, NRF-1 and TFAM and increased levels of electron transport chain complexes I, IV and V, thereby increasing the ATP concentration, maintaining mitochondrial membrane potential, and promoting dendron regeneration levels. Meanwhile, in hippocampal neurons SOD activity and the glutathione/glutathione disulfide (GSH/GSSG) ratio increased and MDA level decreased. CONCLUSION: Acupuncture treatment after ischemic injury promoted mitochondrial biogenesis, as reflected by beneficially increased mitochondrial oxidative phosphorylation complex protein levels and brain tissue energy supply, while preventing oxidative stress injury. These results should guide future explorations to elucidate acupuncture-based mechanisms for alleviating neuronal injury triggered by acute cerebral ischemia.


Asunto(s)
Terapia por Acupuntura , Modelos Animales de Enfermedad , Metabolismo Energético , Infarto de la Arteria Cerebral Media , Factor Nuclear 1 de Respiración , Estrés Oxidativo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Ratas Sprague-Dawley , Transducción de Señal , Factores de Transcripción , Animales , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Masculino , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Factor Nuclear 1 de Respiración/metabolismo , Factor Nuclear 1 de Respiración/genética , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Biogénesis de Organelos , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Potencial de la Membrana Mitocondrial , Hipocampo/metabolismo , Hipocampo/patología , Fosforilación Oxidativa , Ratas
7.
Anesthesiology ; 139(2): 173-185, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37079748

RESUMEN

BACKGROUND: The administration of epinephrine after severe refractory hypotension, shock, or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction. The authors hypothesized that epinephrine induces significant microvascular constriction in the brain, with increased severity after repetitive dosing and in the aged brain, eventually leading to tissue hypoxia. METHODS: The authors investigated the effects of intravenous epinephrine administration in healthy young and aged C57Bl/6 mice on cerebral microvascular blood flow and oxygen delivery using multimodal in vivo imaging, including functional photoacoustic microscopy, brain tissue oxygen sensing, and follow-up histologic assessment. RESULTS: The authors report three main findings. First, after epinephrine administration, microvessels exhibited severe immediate vasoconstriction (57 ± 6% of baseline at 6 min, P < 0.0001, n = 6) that outlasted the concurrent increase in arterial blood pressure, while larger vessels demonstrated an initial increase in flow (108 ± 6% of baseline at 6 min, P = 0.02, n = 6). Second, oxyhemoglobin decreased significantly within cerebral vessels with a more pronounced effect in smaller vessels (microvessels to 69 ± 8% of baseline at 6 min, P < 0.0001, n = 6). Third, oxyhemoglobin desaturation did not indicate brain hypoxia; on the contrary, brain tissue oxygen increased after epinephrine application (from 31 ± 11 mmHg at baseline to 56 ± 12 mmHg, 80% increase, P = 0.01, n = 12). In the aged brains, microvascular constriction was less prominent yet slower to recover compared to young brains, but tissue oxygenation was increased, confirming relative hyperoxia. CONCLUSIONS: Intravenous application of epinephrine induced marked cerebral microvascular constriction, intravascular hemoglobin desaturation, and paradoxically, an increase in brain tissue oxygen levels, likely due to reduced transit time heterogeneity.


Asunto(s)
Microscopía , Oxihemoglobinas , Ratones , Animales , Microcirculación , Oxihemoglobinas/farmacología , Epinefrina/farmacología , Oxígeno , Circulación Cerebrovascular
9.
J Acoust Soc Am ; 149(2): 1258, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33639826

RESUMEN

Shock wave lithotripsy (SWL) has been widely used for non-invasive treatment of kidney stones. Cavitation plays an important role in stone fragmentation, yet it may also contribute to renal injury during SWL. It is therefore crucial to determine the spatiotemporal distributions of cavitation activities to maximize stone fragmentation while minimizing tissue injury. Traditional cavitation detection methods include high-speed optical imaging, active cavitation mapping (ACM), and passive cavitation mapping (PCM). While each of the three methods provides unique information about the dynamics of the bubbles, PCM has most practical applications in biological tissues. To image the dynamics of cavitation bubble collapse, we previously developed a sliding-window PCM (SW-PCM) method to identify each bubble collapse with high temporal and spatial resolution. In this work, to further validate and optimize the SW-PCM method, we have developed tri-modality cavitation imaging that includes three-dimensional high-speed optical imaging, ACM, and PCM seamlessly integrated in a single system. Using the tri-modality system, we imaged and analyzed laser-induced single cavitation bubbles in both free field and constricted space and shock wave-induced cavitation clusters. Collectively, our results have demonstrated the high reliability and spatial-temporal accuracy of the SW-PCM approach, which paves the way for the future in vivo applications on large animals and humans in SWL.


Asunto(s)
Cálculos Renales , Litotricia , Animales , Humanos , Cálculos Renales/terapia , Reproducibilidad de los Resultados
10.
J Stroke Cerebrovasc Dis ; 30(7): 105828, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34010777

RESUMEN

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke which affects the retina. Intravenous thrombolysis is emerging as a compelling therapeutic approach. However, it is not known which patients may benefit from this therapy because there are no imaging modalities that adequately distinguish viable retina from irreversibly infarcted retina. The inner retina receives arterial supply from the central retinal artery and there is robust collateralization between this circulation and the outer retinal circulation, provided by the posterior ciliary circulation. Fundus photography can show canonical changes associated with CRAO including a cherry-red spot, arteriolar boxcarring and retinal pallor. Fluorescein angiography provides 2-dimensional imaging of the retinal circulation and can distinguish a complete from a partial CRAO as well as central versus peripheral retinal non-perfusion. Transorbital ultrasonography may assay flow through the central retinal artery and is useful in the exclusion of other orbital pathology that can mimic CRAO. Optical coherence tomography provides structural information on the different layers of the retina and exploratory work has described its utility in determining the time since onset of ischemia. Two experimental techniques are discussed. 1) Retinal functional imaging permits generation of capillary perfusion maps and can assay retinal oxygenation and blood flow velocity. 2) Photoacoustic imaging combines the principles of optical excitation and ultrasonic detection and - in animal studies - has been used to determine the retinal oxygen metabolic rate. Future techniques to determine retinal viability in clinical practice will require rapid, easily used, and reproducible methods that can be deployed in the emergency setting.


Asunto(s)
Angiografía con Fluoresceína , Imagen de Perfusión , Fotograbar , Oclusión de la Arteria Retiniana/diagnóstico por imagen , Arteria Retiniana/diagnóstico por imagen , Tomografía de Coherencia Óptica , Ultrasonografía , Animales , Velocidad del Flujo Sanguíneo , Toma de Decisiones Clínicas , Circulación Colateral , Humanos , Técnicas Fotoacústicas , Valor Predictivo de las Pruebas , Pronóstico , Flujo Sanguíneo Regional , Arteria Retiniana/fisiopatología , Oclusión de la Arteria Retiniana/fisiopatología , Oclusión de la Arteria Retiniana/terapia
11.
Angew Chem Int Ed Engl ; 60(47): 25020-25027, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34534391

RESUMEN

Adding ferromagnetism into semiconductors attracts much attentions due to its potential usage of magnetic spins in novel devices, such as spin field-effect transistors. However, it remains challenging to stabilize their ferromagnetism above room temperature. Here we introduce an atomic chemical-solution strategy to grow wafer-size NiO thin films with controllable thickness down to sub-nanometer scale (0.92 nm) for the first time. Surface lattice defects break the magnetic symmetry of NiO and produce surface ferromagnetic behaviors. Our sub-nanometric NiO thin film exhibits the highest reported room-temperature ferromagnetic behavior with a saturation magnetization of 157 emu/cc and coercivity of 418 Oe. Attributed to wafer size, the easily-transferred NiO thin film is further verified in a magnetoresistance device. Our work provides a sub-nanometric platform to produce wafer-size ferromagnetic NiO thin films as atomic layer magnetic units in future transparent magnetoelectric devices.

12.
Mol Imaging ; 19: 1536012120981518, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33336621

RESUMEN

Photoacoustic tomography (PAT) has become increasingly popular for molecular imaging due to its unique optical absorption contrast, high spatial resolution, deep imaging depth, and high imaging speed. Yet, the strong optical attenuation of biological tissues has traditionally prevented PAT from penetrating more than a few centimeters and limited its application for studying deeply seated targets. A variety of PAT technologies have been developed to extend the imaging depth, including employing deep-penetrating microwaves and X-ray photons as excitation sources, delivering the light to the inside of the organ, reshaping the light wavefront to better focus into scattering medium, as well as improving the sensitivity of ultrasonic transducers. At the same time, novel optical fluence mapping algorithms and image reconstruction methods have been developed to improve the quantitative accuracy of PAT, which is crucial to recover weak molecular signals at larger depths. The development of highly-absorbing near-infrared PA molecular probes has also flourished to provide high sensitivity and specificity in studying cellular processes. This review aims to introduce the recent developments in deep PA molecular imaging, including novel imaging systems, image processing methods and molecular probes, as well as their representative biomedical applications. Existing challenges and future directions are also discussed.


Asunto(s)
Técnicas Fotoacústicas , Color , Procesamiento de Imagen Asistido por Computador , Imagen Molecular , Tomografía Computarizada por Rayos X
13.
Metab Brain Dis ; 35(3): 463-471, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31728887

RESUMEN

Alzheimer disease (AD) is a growing health problem globally, which causes a progressive decline in learning and memory and multiple disturbances of circadian rhythms. Six Alzheimer's mice and six wild type (WT) mice were involved in this study. Morris Water Maze (MWM) tasks were conducted hourly to evaluate their circadian learning and memory performance. We used a single cosinor-based method to evaluate the circadian learning and memory of Alzheimer's mice and WT mice, respectively. An area sensor was used to record locomotor activity for 2 weeks continuously, including 7 days of 12 h light/12 h dark (LD) conditions and 7 days of 12 h dark/12 h dark (DD) conditions. All WT mice showed circadian rhythm presence in learning and memory, and the peak of escape latency appeared at circadian time (CT) 12. Only one in six Alzheimer's mice showed a circadian rhythm, but the peak of escape latency was postponed to CT20. Alzheimer's mice showed rhythm absence under LD or DD conditions. Under LD conditions, the WT mice activity was higher than that in the Alzheimer's mice during ZT0-5 (p = 0.007) and ZT18-23 (p = 0.353) but lower during ZT6-11 (p < 0.001) and ZT12-17 (p < 0.001). Learning and memory of wild type mice is proved to have a circadian variation throughout a day. In Alzheimer's mice, rhythmic locomotor activity and circadian learning and memory performance were disrupted. Understanding the role of rhythmic disturbances in the process of AD may assist to identify therapeutic targets.


Asunto(s)
Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides , Ritmo Circadiano/fisiología , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Fragmentos de Péptidos , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/fisiopatología , Animales , Modelos Animales de Enfermedad , Ratones , Actividad Motora/fisiología
14.
J Cell Biochem ; 120(5): 8661-8675, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30485531

RESUMEN

Vascular endothelial apoptosis is closely associated with the pathogenesis and progression of diabetic macrovascular diseases. Selenoprotein S (SelS) participates in the protection of vascular endothelial and smooth muscle cells from oxidative and endoplasmic reticulum stress-induced injury. However, whether SelS can protect vascular endothelium from high glucose (HG)-induced apoptosis and the underlying mechanism remains unclear. The present study preliminarily analyzed aortic endothelial apoptosis and SelS expression in diabetic rats in vivo and the effects of HG on human umbilical vein endothelial cell (HUVEC) apoptosis and SelS expression in vitro. Subsequently, SelS expression was up- or downregulated in HUVECs using the pcDNA3.1-SelS recombinant plasmid and SelS-specific small interfering RNAs, and the effects of high/low SelS expression on HG-induced HUVEC apoptosis and a possible molecular mechanism were analyzed. As expected, HG induced vascular endothelial apoptosis and upregulated endothelial SelS expression in vivo and in vitro. SelS overexpression in HUVECs suppressed HG-induced increase in apoptosis and cleaved caspase3 level, accompanied by reduced protein kinase CßII (PKCßII), c-JUN N-terminal kinase (JNK), and B-cell lymphoma/leukemia-2 (Bcl-2) phosphorylation. In contrast, inhibiting SelS expression in HUVECs further aggravated HG-induced increase in apoptosis and cleaved caspase3 level, which was accompanied by increased PKCßII, JNK, and Bcl-2 phosphorylation. Pretreatment with PKC activators blocked the protective effects of SelS and increased the apoptosis and cleaved caspase3 level in HUVECs. In summary, SelS protects vascular endothelium from HG-induced apoptosis, and this was achieved through the inhibition of PKCßII/JNK/Bcl-2 pathway to eventually inhibit caspase3 activation. SelS may be a promising target for the prevention and treatment of diabetic macrovascular complications.

15.
Nat Methods ; 13(8): 627-38, 2016 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-27467726

RESUMEN

The life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs.


Asunto(s)
Técnicas Fotoacústicas/métodos , Tomografía/métodos , Imagen de Cuerpo Entero/métodos , Animales , Fenómenos Fisiológicos Celulares , Humanos
16.
Nat Methods ; 13(1): 67-73, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26550774

RESUMEN

Photoacoustic tomography (PAT) of genetically encoded probes allows for imaging of targeted biological processes deep in tissues with high spatial resolution; however, high background signals from blood can limit the achievable detection sensitivity. Here we describe a reversibly switchable nonfluorescent bacterial phytochrome for use in multiscale photoacoustic imaging, BphP1, with the most red-shifted absorption among genetically encoded probes. BphP1 binds a heme-derived biliverdin chromophore and is reversibly photoconvertible between red and near-infrared light-absorption states. We combined single-wavelength PAT with efficient BphP1 photoswitching, which enabled differential imaging with substantially decreased background signals, enhanced detection sensitivity, increased penetration depth and improved spatial resolution. We monitored tumor growth and metastasis with ∼ 100-µm resolution at depths approaching 10 mm using photoacoustic computed tomography, and we imaged individual cancer cells with a suboptical-diffraction resolution of ∼ 140 nm using photoacoustic microscopy. This technology is promising for biomedical studies at several scales.


Asunto(s)
Acústica , Fitocromo/química , Tomografía/métodos , Animales , Línea Celular Tumoral , Humanos , Ratones
17.
Opt Lett ; 44(15): 3773-3776, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31368965

RESUMEN

Hypoxia, a low tissue oxygenation condition caused by insufficient oxygen supply, leads to potentially irreversible tissue damage, such as brain infarction during stroke. Intravascular oxygenation has long been used by photoacoustic imaging, among other imaging modalities, to study hypoxia. However, intravascular oxygenation describes only the oxygen supply via microcirculation, which does not directly reflect the amount of free oxygen available for metabolism in the interstitial fluid. Therefore, to fully understand hypoxia, it is highly desirable to monitor blood oxygenation as well as tissue oxygenation during the same biological process. In this work, by combining high-resolution photoacoustic microscopy (PAM) and a novel bioreducible N-oxide-based hypoxia-sensitive probe HyP-650, we have demonstrated simultaneous imaging of intravascular oxygenation and tissue hypoxia. We have established detailed chemical, optical, and photoacoustic properties of HyP-650 for hypoxic activation in vitro and in living cells. We have also performed PAM on hindlimb ischemia models and tumor-bearing mice to study the correlation between intravascular oxygenation and tissue oxygenation at various hypoxic levels. We expect that Hyp-650 enhanced photoacoustic imaging will find a variety of applications in brain and cancer research.


Asunto(s)
Vasos Sanguíneos/diagnóstico por imagen , Vasos Sanguíneos/metabolismo , Oxígeno/metabolismo , Técnicas Fotoacústicas/métodos , Animales , Miembro Posterior/irrigación sanguínea , Isquemia/metabolismo , Isquemia/patología , Ratones , Microscopía , Hipoxia Tumoral
18.
Nanotechnology ; 30(35): 355701, 2019 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-31082809

RESUMEN

We report oxygen vacancies (OVs) rich hexagonal ReO3 nanostructured electrocatalysts for efficient hydrogen generation. Through a simple argon plasma exposure, OVs are introduced into the ReO3 nanoparticles (NP) and nanosheets to enhance electrocatalytic activities with decreasing overpotentails from 157 mV and 178 mV to 138 mV and 145 mV at the current density of 10 mA cm-2, respectively. As-processed OVs rich ReO3 NP exhibit a good stability during electrochemical measurements for 20 h in acidic electrolyte. The huge active surface area, abundant OVs and excellent conductivity contribute to the performance according to the experimental data. Further theoretical calculations show that the abundant OVs adsorb H with lower Gibbs free energy facilitating hydrogen evolution.

19.
Biochem Biophys Res Commun ; 503(4): 2866-2871, 2018 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-30146262

RESUMEN

As the most conserved branch of the unfolded protein response (UPR), the inositol-requiring enzyme 1a (IRE1a)/X-box binding protein 1 (XBP1) pathway plays crucial roles in cell survival and cell death by upregulating UPR-associated genes involved in protein entry into the endoplasmic reticulum (ER) and ER-associated degradation (ERAD). Selenoprotein S (SelS) is localized to the ER membrane and involved in ERAD. Although SelS plays an important role in restoring ER stress, the SelS-dependent protective mechanisms against cell death remain unclear. Here, using an inducible SelS knockdown (KD) 3T3-L1 cell model, we showed that SelS KD resulted adipocyte death, which was associated with imbalance of the Bcl-2 family members. Furthermore, SelS KD decreased spliced XBP1 (sXBP1), increased IRE1α and p-JNK, suggesting a role of SelS in the modulation of the IRE1α-sXBP1 pathway. Moreover, adipocyte death induced by SelS suppression can be inhibited by overexpression of sXBP1. Thus, it is proposed that SelS promotes cell survival through the IRE1α-XBP1 signaling pathway.


Asunto(s)
Adipocitos/metabolismo , Muerte Celular/genética , Degradación Asociada con el Retículo Endoplásmico , Endorribonucleasas/genética , Proteínas Serina-Treonina Quinasas/genética , Selenoproteínas/genética , Proteína 1 de Unión a la X-Box/genética , Células 3T3-L1 , Adipocitos/citología , Animales , Diferenciación Celular , Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico/genética , Endorribonucleasas/metabolismo , Regulación de la Expresión Génica , MAP Quinasa Quinasa 4/genética , MAP Quinasa Quinasa 4/metabolismo , Ratones , Proteínas Serina-Treonina Quinasas/metabolismo , Transporte de Proteínas , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Selenoproteínas/antagonistas & inhibidores , Selenoproteínas/metabolismo , Transducción de Señal , Proteína 1 de Unión a la X-Box/metabolismo
20.
Nat Methods ; 12(5): 407-10, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25822799

RESUMEN

We present fast functional photoacoustic microscopy (PAM) for three-dimensional high-resolution, high-speed imaging of the mouse brain, complementary to other imaging modalities. We implemented a single-wavelength pulse-width-based method with a one-dimensional imaging rate of 100 kHz to image blood oxygenation with capillary-level resolution. We applied PAM to image the vascular morphology, blood oxygenation, blood flow and oxygen metabolism in both resting and stimulated states in the mouse brain.


Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/fisiología , Microscopía/métodos , Técnicas Fotoacústicas , Animales , Velocidad del Flujo Sanguíneo , Estimulación Eléctrica , Femenino , Ratones , Reproducibilidad de los Resultados
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