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1.
Bioorg Med Chem ; 107: 117750, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38776567

RESUMEN

Analgesia and blood sugar control are considered as two main unmet clinical needs for diabetes related neuropathic pain patients. Transient receptor potential vanilloid type-1 (TRPV1) channel is a highly validated target for pain perception, while no TRPV1 antagonists have been approved due to hyperthermia side effects. Herein, two series of new TRPV1 antagonists with flavonoid skeleton were designed by the structure-based drug design (SBDD) strategy. After comprehensive evaluation, compound CX-3 was identified as a promising TRPV1 antagonist. CX-3 exhibited equivalent TRPV1 antagonistic activity with classical TRPV1 antagonist BCTC in vitro, and exerted better analgesic activity in vivo than that of BCTC in the formalin induced inflammatory pain model without hyperthermia risk. Moreover, CX-3 exhibited robust glucose-lowering effects and showed high selectivity over other ion channels. Overall, these findings identified a first-in-class highly selective TRPV1 antagonist CX-3, which is a promising candidate to target the pathogenesis of diabetes related neuropathic pain.


Asunto(s)
Analgésicos , Hipoglucemiantes , Canales Catiónicos TRPV , Animales , Humanos , Masculino , Ratones , Ratas , Analgésicos/farmacología , Analgésicos/química , Analgésicos/síntesis química , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/síntesis química , Estructura Molecular , Ratas Sprague-Dawley , Relación Estructura-Actividad , Canales Catiónicos TRPV/antagonistas & inhibidores , Canales Catiónicos TRPV/metabolismo
2.
IEEE Sens J ; 24(4): 4380-4386, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38505656

RESUMEN

Photoacoustic (PA) imaging provides deep tissue molecular imaging of chromophores with optical absorption contrast and ultrasonic resolution. Present PA imaging techniques are predominantly limited to one 2D plane per acquisition. 2D ultrasound transducers, required for real-time 3D PA imaging, are high-cost, complex to fabricate and have limited scalability in design. We present novel PCB-based 2D matrix ultrasound transducer arrays that are capable of being bulk manufactured at low-cost without using laborious ultrasound fabrication tools. The 2D ultrasound array specifications are easily scalable with respect to widely available PCB design and fabrication tools at low cost. To demonstrate scalability, we fabricated low (11 MHz) frequency 8x8 matrix array and high (40 MHz) frequency 4x4 matrix array by directly bonding an undiced polyvinylidene fluoride (PVDF) piezoelectric material of desired thickness to the custom designed PCB substrate. Characterization results demonstrate wideband PA receive sensitivity for both low (87%) and high (188%) frequency arrays. Volumetric PA imaging results of light absorbing targets inside optical scattering medium demonstrate improved spatial resolution and field of view with increase in aperture size.

3.
BMC Nurs ; 23(1): 20, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38183055

RESUMEN

BACKGROUND: Persistent pain is the most reported symptom in patients with rheumatoid arthritis (RA); however, effective and brief assessment tools are lacking. We validated the Chinese version of the Global Pain Scale (C-GPS) in Chinese patients with RA and proposed a short version of the C-GPS (s-C-GPS). METHOD: The study was conducted using a face-to-face questionnaire survey with a multicenter cross-sectional design from March to December 2019. Patients aged > 18 years who met the RA diagnostic criteria were included. Based on the classical test theory (CTT) and the item response theory (IRT), we assessed the validity and reliability of the C-GPS and the adaptability of each item. An s-C-GPS was developed using IRT-based computerized adaptive testing (CAT) analytics. RESULTS: In total, 580 patients with RA (mean age, 51.04 ± 24.65 years; mean BMI, 22.36 ± 4.07 kg/m2), including 513 (88.4%) women, were included. Most participants lived in a suburb (49.3%), were employed (72.2%) and married (91.2%), reported 9-12 years of education (66.9%), and had partial medical insurance (57.8%). Approximately 88.1% smoked and 84.5% drank alcohol. Analysis of the CTT demonstrated that all items in the C-GPS were positively correlated with the total scale score, and the factor loadings of all these items were > 0.870. A significant positive relationship was found between the Visual Analog Scale (VAS) and the C-GPS. IRT analysis showed that discrimination of the C-GPS was between 2.271 and 3.312, and items 6, 8, 13, 14, and 16 provided a large amount of information. Based on the CAT and clinical practice, six items covering four dimensions were included to form the s-C-GPS, all of which had very high discrimination. The s-C-GPS positively correlated with the VAS. CONCLUSION: The C-GPS has good reliability and validity and can be used to evaluate pain in RA patients from a Chinese cultural background. The s-C-GPS, which contains six items, has good criterion validity and may be suitable for pain assessment in busy clinical practice. TRIAL REGISTRATION: This cross-sectional study was registered in the Chinese Clinical Trial Registry (ChiCTR1800020343), granted on December 25, 2018.

4.
Methods ; 207: 103-109, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36155250

RESUMEN

The task of predicting drug-target affinity (DTA) plays an increasingly important role in the early stage of in silico drug discovery and development. Currently, a variety of machine learning-based methods have been presented for DTA prediction and achieved outstanding performance, which is beneficial for speeding up the development of new drugs. However, most convolutional neural networks (CNNs) based methods ignore the significance of information from CNN layers with different scales for DTA prediction. In addition, each feature provides different contributions to the final task. Therefore, in this study, we propose a novel end-to-end deep learning-based framework, MultiscaleDTA, to predict drug-target binding affinity. MultiscaleDTA incorporates multi-scale CNNs and a self-attention mechanism to capture multi-scale and comprehensive features for characterizing the intrinsic properties of drugs and targets. Extensive experimental results on both regression and binary classification tasks demonstrate that MultiscaleDTA achieves competitive performance compared to state-of-the-art methods.


Asunto(s)
Aprendizaje Automático , Redes Neurales de la Computación , Desarrollo de Medicamentos , Descubrimiento de Drogas
5.
Angew Chem Int Ed Engl ; 62(31): e202306583, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37277318

RESUMEN

Cell encapsulation has been studied for various applications ranging from cell transplantation to biological production. However, current encapsulation technologies focus on cell protection rather than cell regulation that is essential to most if not all cell-based applications. Here we report a method for cell nanoencapsulation and regulation using an ultrathin biomimetic extracellular matrix as a cell nanocapsule to carry nanoparticles (CN2 ). This method allows high-capacity nanoparticle retention at the vicinity of cell surfaces. The encapsulated cells maintain high viability and normal metabolism. When gold nanoparticles (AuNPs) are used as a model to decorate the nanocapsule, light irradiation transiently increases the temperature, leading to the activation of the heat shock protein 70 (HSP70) promoter and the regulation of reporter gene expression. As the biomimetic nanocapsule can be decorated with any or multiple NPs, CN2 is a promising platform for advancing cell-based applications.


Asunto(s)
Nanopartículas del Metal , Nanocápsulas , Nanopartículas , Oro , Biomimética/métodos , Matriz Extracelular
6.
Microcirculation ; 29(6-7): e12776, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35793421

RESUMEN

Microcirculation facilitates the blood-tissue exchange of nutrients and regulates blood perfusion. It is, therefore, essential in maintaining tissue health. Aberrations in microcirculation are potentially indicative of underlying cardiovascular and metabolic pathologies. Thus, quantitative information about it is of great clinical relevance. Photoacoustic imaging (PAI) is a capable technique that relies on the generation of imaging contrast via the absorption of light and can image at micron-scale resolution. PAI is especially desirable to map microvasculature as hemoglobin strongly absorbs light and can generate a photoacoustic signal. This paper reviews the current state of the art for imaging microvascular networks using photoacoustic imaging. We further describe how quantitative information about blood dynamics such as the total hemoglobin concentration, oxygen saturation, and blood flow rate is obtained using PAI. We also discuss its importance in understanding key pathophysiological processes in neurovascular, cardiovascular, ophthalmic, and cancer research fields. We then discuss the current challenges and limitations of PAI and the approaches that can help overcome these limitations. Finally, we provide the reader with an overview of future trends in the field of PAI for imaging microcirculation.


Asunto(s)
Técnicas Fotoacústicas , Microcirculación , Técnicas Fotoacústicas/métodos , Diagnóstico por Imagen , Microvasos/fisiología , Hemoglobinas/metabolismo
7.
Opt Lett ; 47(5): 1121-1124, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35230306

RESUMEN

Optical resolution photoacoustic microscopy (OR-PAM) can map the cerebral vasculature at capillary-level resolution. However, the OR-PAM setup's bulky imaging head makes awake mouse brain imaging challenging and inhibits its integration with other optical neuroimaging modalities. Moreover, the glass cranial windows used for optical microscopy are unsuitable for OR-PAM due to the acoustic impedance mismatch between the glass plate and the tissue. To overcome these challenges, we propose a lithium niobate based transparent ultrasound transducer (TUT) as a cranial window on a thinned mouse skull. The TUT cranial window simplifies the imaging head considerably due to its dual functionality as an optical window and ultrasound transducer. The window remains stable for six weeks, with no noticeable inflammation and minimal bone regrowth. The TUT window's potential is demonstrated by imaging the awake mouse cerebral vasculature using OR-PAM, intrinsic optical signal imaging, and two-photon microscopy. The TUT cranial window can potentially also be used for ultrasound stimulation and simultaneous multimodal imaging of the awake mouse brain.


Asunto(s)
Técnicas Fotoacústicas , Vigilia , Animales , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Ratones , Neuroimagen/métodos , Imagen Óptica , Técnicas Fotoacústicas/métodos , Cráneo/diagnóstico por imagen
8.
BMC Musculoskelet Disord ; 23(1): 1050, 2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36460993

RESUMEN

BACKGROUND: Chronic low back pain is a common musculoskeletal disease. With the increasing number of patients, it has become a huge economic and social burden. It is urgent to relieve the burden of patients. There are many common rehabilitation methods, and aquatic physical therapy is one of them. The purpose of this systematic review and meta-analysis is to summarize the existing literature and analyze the impact of aquatic physical therapy on pain intensity, quality of life and disability of patients with chronic low back pain. METHODS: Through 8 databases, we searched randomized controlled trials on the effect of aquatic physical therapy on patients with chronic low back pain. These trials published results on pain intensity, quality of life, and disability. This review is guided by Cochrane Handbook for systematic reviews of interventions version 5.1.0. The level of evidence was assessed through GRADE. RESULTS: A total of 13 articles involving 597 patients were included. The results showed that compared with the control group, aquatic physical therapy alleviated the pain intensity (Visual Analogue Scale: SMD = -0.68, 95%CI:-0.91 to -0.46, Z = 5.92, P < 0.00001) and improved quality of life (physical components of 36-Item Short Form Health Survey or Short-Form 12: SMD = 0.63, 95%CI:0.36 to 0.90, Ζ = 4.57, P < 0.00001; mental components of 36-Item Short Form Health Survey or Short-Form 12: SMD = 0.59, 95%CI:0.10 to 1.08, Ζ = 2.35, P = 0.02), and reduced disability (Roland Morris Disability Questionnaire: SMD = -0.42, 95%CI:-0.66 to -0.17, Ζ = 3.34, P = 0.0008; Oswestry Disability Index or Oswestry Low Back Pain Disability Questionnaire: SMD = -0.54, 95%CI:-1.07 to -0.01, Ζ = 1.99, P = 0.05). However, aquatic physical therapy did not improve patients' pain at rest (Visual Analogue Scale at rest: SMD = -0.60, 95%CI:-1.42 to 0.23, Ζ = 1.41, P = 0.16). We found very low or low evidence of effects of aquatic physical therapy on pain intensity, quality of life, and disability in patients with chronic low back pain compared with no aquatic physical therapy. CONCLUSIONS: Our systematic review showed that aquatic physical therapy could benefit patients with chronic low back pain. However, because the articles included in this systematic review have high bias risk or are unclear, more high-quality randomized controlled trials are needed to verify.


Asunto(s)
Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/terapia , Calidad de Vida , Modalidades de Fisioterapia , Examen Físico , Dimensión del Dolor
9.
Sensors (Basel) ; 22(15)2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-35957175

RESUMEN

The receive sensitivity of lead zirconate titanate (PZT) piezoelectric micromachined ultrasound transducers (PMUTs) was improved by applying a DC bias during operation. The PMUT receive sensitivity is governed by the voltage piezoelectric coefficient, h31,f. With applied DC biases (up to 15 V) on a 2 µm PbZr0.52Ti0.48O3 film, e31,f increased 1.6 times, permittivity decreased by a factor of 0.6, and the voltage coefficient increased by ~2.5 times. For released PMUT devices, the ultrasound receive sensitivity improved by 2.5 times and the photoacoustic signal improved 1.9 times with 15 V applied DC bias. B-mode photoacoustic imaging experiments showed that with DC bias, the PMUT received clearer photoacoustic signals from pencil leads at 4.3 cm, compared to 3.7 cm without DC bias.


Asunto(s)
Diagnóstico por Imagen , Transductores , Sesgo , Diseño de Equipo , Ultrasonografía/métodos
10.
Psychol Health Med ; 25(10): 1179-1191, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32129673

RESUMEN

This study aimed to assess the effects of cognitive behavioral therapy on the psychological and physiological health of rheumatoid arthritis patients. An extensive literature search was conducted, using the PubMed, Web of Science, Cochrane Library, Embase, CNKI Scholar, WanFang, and VIP databases, from inception to December2018. The quality of the studies was evaluated by 2 independent authors, according to the basic criteria provided by the Cochrane Handbook for evaluating randomized trials. Meta-analysis was performed with Review Manager 5.3. Six randomized controlled trials met the inclusion criteria of the current study. Using standard mean differences (SMD) and 95% confidence intervals (CI), our results showed that cognitive behavioral therapy could significantly reduce levels of anxiety (SMD = -0.30, 95% CI [-0.52, -0.09], P= 0.005) and depression (SMD = -0.48, 95% CI [-0.70, -0.27], P< 0.00001), and relieve fatigue symptoms (SMD = -0.35, 95% CI [-0.60, -0.10], P= 0.006) in rheumatoid arthritis patients.This is the first known assessment of the efficacy of cognitive behavioral therapy on rheumatoid arthritis patients using meta-analysis. Large-scale randomized controlled trials need to be implemented to further explore this issue.


Asunto(s)
Ansiedad/rehabilitación , Artritis Reumatoide/psicología , Artritis Reumatoide/rehabilitación , Terapia Cognitivo-Conductual , Fatiga/rehabilitación , Humanos
11.
J Clin Rheumatol ; 26(3): 94-98, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30601165

RESUMEN

OBJECTIVE: Medication adherence plays an important role in improving symptoms and ameliorating the progression of systemic lupus erythematosus (SLE). The purpose of this study was to examine the medication adherence rate and explore the related factors for nonadherence in Chinese SLE patients. METHODS: A cross-sectional study from The Second Affiliated Hospital of Nantong University between January 2017 and February 2018 was conducted. Patients with SLE completed the Compliance Questionnaire on Rheumatology to evaluate adherence, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) for disease activity, and the Hospital Anxiety and Depression Scale to assess anxiety and depression. χ Analyses, independent samples t tests, and logistic regression models were used to analyze data. RESULTS: This study included 144 SLE patients, and we found that 43.1% (n = 62) of the patients were nonadherence. Education, SLEDAI, anxiety, and depression were correlated with adherence in SLE patients. Moreover, logistic regression models identified education, SLEDAI, and depression as important associated factors of nonadherence. CONCLUSIONS: This is the first time to evaluate demographic, clinical, and psychological related factors for medication adherence in Chinese SLE patients using SLEDAI and Hospital Anxiety and Depression Scale. Our study showed that 56.9% of SLE patients were not adherent, and education, SLEDAI, and depression were significantly related to medication adherence in SLE. These findings suggested that it was necessary to pay more attention to medication adherence of SLE patients, especially those with lower level of education, higher score of SLEDAI, and depression by effective intervention to improve SLE patients' adherence, so as to improve their quality of life.


Asunto(s)
Lupus Eritematoso Sistémico/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Adulto , Ansiedad/diagnóstico , Ansiedad/epidemiología , Pueblo Asiatico , Estudios Transversales , Depresión/diagnóstico , Depresión/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Calidad de Vida , Factores de Riesgo , Encuestas y Cuestionarios , Adulto Joven
12.
Sensors (Basel) ; 19(24)2019 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-31835900

RESUMEN

The opacity of conventional ultrasound transducers can impede the miniaturization and workflow of current photoacoustic systems. In particular, optical-resolution photoacoustic microscopy (OR-PAM) requires the coaxial alignment of optical illumination and acoustic-detection paths through complex beam combiners and a thick coupling medium. To overcome these hurdles, we developed a novel OR-PAM method on the basis of our recently reported transparent lithium niobate (LiNbO3) ultrasound transducer (Dangi et al., Optics Letters, 2019), which was centered at 13 MHz ultrasound frequency with 60% photoacoustic bandwidth. To test the feasibility of wearable OR-PAM, optical-only raster scanning of focused light through a transducer was performed while the transducer was fixed above the imaging subject. Imaging experiments on resolution targets and carbon fibers demonstrated a lateral resolution of 8.5 µm. Further, we demonstrated vasculature mapping using chicken embryos and melanoma depth profiling using tissue phantoms. In conclusion, the proposed OR-PAM system using a low-cost transparent LiNbO3 window transducer has a promising future in wearable and high-throughput imaging applications, e.g., integration with conventional optical microscopy to enable a multimodal microscopy platform capable of ultrasound stimulation.

13.
Psychol Health Med ; 23(1): 114-125, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28635309

RESUMEN

To systematically review the literature to identify the impact of rheumatoid arthritis (RA) on specific female sexual function domains. A meta-analysis was performed and the related literature were searched in MEDLINE, EMBASE, Cochrane Library, CNKI, CBM and Web of Science databases, and in reference lists of articles and systematic reviews. Score of the Female Sexual Function Index (FSFI) was used as the outcome measurement, and mean differences (MD) with 95% confidence intervals (CI) were calculated. Five studies were included, including 346 women with RA and 237 healthy female controls. Each domain of the FSFI score: lubrication (MD, -2.48; 95% CI, -3.69, -1.28), orgasm-1.71 (-2.09, -1.33), sexual desire-1.27 (-1.59, -0.95), satisfaction-1.67 (-2.18, -1.16), arousal-1.83 (-2.85, -0.82), pain-1.57 (-2.43, -0.70) and the total score -8.84 (-11.88, -5.79) were lower in RA women than healthy controls. Furthermore, lubrication dimension was most severely affected especially. This meta-analysis showed that female RA patients scored lower in each dimension of FSFI, mostly in the lubrication domain. It demonstrated that targeted interventions should be done to improve their sexual function. Future well-designed researches with larger sample sizes are necessary to evaluate the potential risk factors which determine female sexual dysfunction.


Asunto(s)
Nivel de Alerta , Artritis Reumatoide/psicología , Orgasmo , Adulto , Artritis Reumatoide/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Satisfacción Personal , Factores de Riesgo , Encuestas y Cuestionarios
14.
Psychol Health Med ; 23(7): 779-787, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29384702

RESUMEN

This study aimed (i) to complement existing research by focusing on body image disturbance issues in Chinese Systemic Lupus Erythematosus (SLE) patients; (ii) to investigate how Chinese patients make sense of disease diagnosis and perceived cultural influences within the context of their SLE. A total of 118 SLE patients underwent standardized laboratory examinations and completed several questionnaires. Independent sample t-test, Mann-Whitney U-test, Chi-square test, and multivariate analysis using backward stepwise logistic regression model were used to analyze these data. We found 18.3% SLE patients had BID, which were significantly higher than the control group (.8%). SLE patients are more concerned about their physical changes caused by disease. There were significant correlations among personal health insurance, complication of diabetes, appearance of new rash, depression, anxiety, self-esteem and BID in patients with SLE. Meanwhile, logistic regression analysis revealed that appearance of new rash and high anxiety were significantly associated with BID in SLE patients. In conclusion, it is beneficial to pay attention to the physical and mental health of patients with rheumatic disease from the perspective of body image, to understand their needs and to provide effective and effective service for them.


Asunto(s)
Ansiedad/psicología , Trastorno Dismórfico Corporal/psicología , Depresión/psicología , Lupus Eritematoso Sistémico/psicología , Calidad de Vida/psicología , Autoimagen , Apoyo Social , Adulto , Ansiedad/epidemiología , Pueblo Asiatico/psicología , Trastorno Dismórfico Corporal/epidemiología , Imagen Corporal/psicología , Estudios de Casos y Controles , Depresión/epidemiología , Femenino , Humanos , Seguro de Salud , Modelos Logísticos , Lupus Eritematoso Sistémico/epidemiología , Masculino , Salud Mental , Persona de Mediana Edad , Encuestas y Cuestionarios
15.
J Diabetes Investig ; 15(3): 288-299, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38013600

RESUMEN

AIMS: This research aimed to investigate the specific mechanism of methyltransferase like 3 (METTL3) in the progression of diabetic kidney disease (DKD). MATERIALS AND METHODS: The model of diabetic kidney disease was established with HK-2 cells and mice in vitro and in vivo. The N6 methyladenosine (m6A) contents in the cells and tissues were detected with a commercial kit and the m6A levels of PTEN induced putative kinase 1 (PINK2) were detected with a MeRIP kit. The mRNA and protein levels were determined with RT-qPCR and western blot. The ROS, TNF-α, and IL-6 levels were assessed with ELISA. The cell proliferative ability was measured by a CCK-8 assay and cell apoptosis was determined with TUNEL staining. The HE and Masson staining was performed to observe the renal morphology. The RIP assay was conducted to detect the interaction between METTL3/YTHDF2 and PINK1. RESULTS: The m6A content and METTL3 levels were prominently elevated in diabetic kidney disease. METTL3 silencing promoted the cell growth and the expression of LC3 II, PINK1, and Parkin, while inhibiting the cell apoptosis and the expression of LC3 I and p62 in the high glucose (HG) stimulated HK-2 cells. METTL3 silencing also decreased the ROS, TNF-α, and IL-6 levels in diabetic kidney disease. PINK1 silencing neutralized the function of sh-METTL3 in the HG stimulated HK-2 cells. The HE and Masson staining showed that METTL3 silencing alleviated the kidney injury induced by DKD. METTL3 silencing decreased the m6A levels of PINK1, while increased the mRNA levels of PINK1 which depended on YTHDF2. CONCLUSIONS: METTL3 silencing could inhibit the progression of diabetic nephropathy in vivo and in vitro by regulating the m6A modification of PINK1, which depends on YTHDF2. Our research lays the theoretical foundation for the precise treatment of diabetic kidney disease and the development of targeted drugs in the future.


Asunto(s)
Adenina , Diabetes Mellitus , Nefropatías Diabéticas , Animales , Ratones , Adenina/análogos & derivados , Nefropatías Diabéticas/genética , Interleucina-6 , Mitofagia , Proteínas Quinasas , Especies Reactivas de Oxígeno , ARN Mensajero , Factor de Necrosis Tumoral alfa , Humanos
16.
Curr Biol ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38944035

RESUMEN

By modulating stomatal opening and closure, plants control gas exchange, water loss, and photosynthesis in response to various environmental signals. During light-induced stomatal opening, the transport of ions and solutes across the plasma membrane (PM) of the surrounding guard cells results in an increase in turgor pressure, leading to cell swelling. Simultaneously, vesicles for exocytosis are delivered via membrane trafficking to compensate for the enlarged cell surface area and maintain an appropriate ion-channel density in the PM. In eukaryotic cells, soluble N-ethylmaleimide-sensitive factor adaptor protein receptors (SNAREs) mediate membrane fusion between vesicles and target compartments by pairing the cognate glutamine (Q)- and arginine (R)-SNAREs to form a core SNARE complex. Syntaxin of plants 121 (SYP121) is a known Q-SNARE involved in stomatal movement, which not only facilitates the recycling of K+ channels to the PM but also binds to the channels to regulate their activity. In this study, we found that the expression of a receptor-like cytoplasmic kinase, low-K+ sensitive 4/schengen 1 (LKS4/SGN1), was induced by light; it directly interacted with SYP121 and phosphorylated T270 within the SNARE motif. Further investigation revealed that LKS4-dependent phosphorylation of SYP121 facilitated the interaction between SYP121 and R-SNARE vesicle-associated membrane protein 722 (VAMP722), promoting the assembly of the SNARE complex. Our findings demonstrate that the phosphorylation of SNARE proteins is an important strategy adopted by plants to regulate the SNARE complex assembly as well as membrane fusion. Additionally, we discovered the function of LKS4/SGN1 in light-induced stomatal opening via the phosphorylation of SYP121.

17.
Adv Mater ; : e2313602, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38598847

RESUMEN

Organic luminescent materials that exhibit thermally activated delayed fluorescence (TADF) can convert non-emissive triplet excitons into emissive singlet states through a reverse intersystem crossing (RISC) process. Therefore, they have tremendous potential for applications in organic light-emitting diodes (OLEDs). However, with the development of ultra-high definition 4K/8K display technologies, designing efficient deep-blue TADF materials to achieve the Commission Internationale de l'Éclairage (CIE) coordinates fulfilling BT.2020 remains a significant challenge. Here, an effective approach is proposed to design deep-blue TADF molecules based on hybrid long- and short-range charge-transfer by incorporation of multiple donor moieties into organoboron multiple resonance acceptors. The resulting TADF molecule exhibits deep-blue emission at 414 nm with a full width at half maximum (FWHM) of 29 nm, together with a thousand-fold increase in RISC rate. OLEDs based on the champion material achieve a record maximum external quantum efficiency (EQE) of 22.8% with CIE coordinates of (0.163, 0.046), approaching the coordinates of the BT.2020 blue standard. Moreover, TADF-assisted fluorescence devices employing the designed material as a sensitizer exhibit an exceptional EQE of 33.1%. This work thus provides a blueprint for future development of efficient deep-blue TADF emitters, representing an important milestone towards meeting the blue color gamut standard of BT.2020.

18.
Adv Sci (Weinh) ; : e2401467, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884161

RESUMEN

Studying brain-wide hemodynamic responses to different stimuli at high spatiotemporal resolutions can help gain new insights into the mechanisms of neuro- diseases and -disorders. Nonetheless, this task is challenging, primarily due to the complexity of neurovascular coupling, which encompasses interdependent hemodynamic parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral oxygen saturation (SO2). The current brain imaging technologies exhibit inherent limitations in resolution, sensitivity, and imaging depth, restricting their capacity to comprehensively capture the intricacies of cerebral functions. To address this, a multimodal functional ultrasound and photoacoustic (fUSPA) imaging platform is reported, which integrates ultrafast ultrasound and multispectral photoacoustic imaging methods in a compact head-mountable device, to quantitatively map individual dynamics of CBV, CBF, and SO2 as well as contrast agent enhanced brain imaging at high spatiotemporal resolutions. Following systematic characterization, the fUSPA system is applied to study brain-wide cerebrovascular reactivity (CVR) at single-vessel resolution via relative changes in CBV, CBF, and SO2 in response to hypercapnia stimulation. These results show that cortical veins and arteries exhibit differences in CVR in the stimulated state and consistent anti-correlation in CBV oscillations during the resting state, demonstrating the multiparametric fUSPA system's unique capabilities in investigating complex mechanisms of brain functions.

19.
Sci Rep ; 13(1): 22899, 2023 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-38129529

RESUMEN

Accurate differentiation between bacterial and viral-induced pharyngitis is recognized as essential for personalized treatment and judicious antibiotic use. From a cohort of 693 patients with pharyngitis, data from 197 individuals clearly diagnosed with bacterial or viral infections were meticulously analyzed in this study. By integrating detailed hematological insights with several machine learning algorithms, including Random Forest, Neural Networks, Decision Trees, Support Vector Machine, Naive Bayes, and Lasso Regression, for potential biomarkers were identified, with an emphasis being placed on the diagnostic significance of the Monocyte-to-Lymphocyte Ratio. Distinct inflammatory signatures associated with bacterial infections were spotlighted in this study. An innovation introduced in this research was the adaptation of the high-accuracy Lasso Regression model for the TI-84 calculator, with an AUC (95% CI) of 0.94 (0.925-0.955) being achieved. Using this adaptation, pivotal laboratory parameters can be input on-the-spot and infection probabilities can be computed subsequently. This methodology embodies an improvement in diagnostics, facilitating more effective distinction between bacterial and viral infections while fostering judicious antibiotic use.


Asunto(s)
Aprendizaje Automático , Virosis , Humanos , Estudios Retrospectivos , Teorema de Bayes , Algoritmos , Máquina de Vectores de Soporte , Antibacterianos/uso terapéutico
20.
BMJ Open ; 13(10): e073868, 2023 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-37865408

RESUMEN

BACKGROUND: This study investigated the experiences of front-line healthcare workers who had been in close contact with COVID-19 patients and had been quarantined in order to provide guidance on quarantine measures with more humanistic care when dealing with future public health emergencies. METHODS: We conducted a qualitative study using semistructured, qualitative, in-depth interviews between April and June 2022. The interviews were recorded and transcribed, followed by a thematic analysis. The study followed the Standards for Reporting Qualitative Research. RESULTS: This study identified the following four themes: (1) personal psychological changes, (2) increased reflection on life and work during quarantine, (3) the important role of others' support and (4) different types of demands during quarantine and isolation. Each theme is supported by several subthemes that further illustrate the participants' experiences. CONCLUSIONS: Quarantine of close contacts is necessary to prevent outbreaks. Front-line doctors and nurses are at a greater risk of COVID-19 infection than others. The results showed the psychological reactions of ordinary close contacts, and the unique feelings and experiences of doctors and nurses during the epidemic. Therefore, future research should cooperate with multiple departments to assess their needs, provide them with individualised care and love and give them incentives in order to reduce their psychological burden, improve their quality of life and allow them to engage in healthcare with a healthy mind.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Cuarentena/psicología , Calidad de Vida , Personal de Salud/psicología , Investigación Cualitativa
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