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2.
Eur Geriatr Med ; 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39361190

RESUMEN

PURPOSE: Sarcopenia is a geriatric syndrome characterized by progressive loss of muscle mass and function. Meteorin-like (Metrnl) is a secretory protein that has protective effects on skeletal muscle injury. However, the association of Metrnl level with sarcopenia remains unclear. METHODS: A total of 772 community-dwelling older adults (median age = 76 years), comprising 409 males and 363 females, from both urban and rural areas were enrolled. Serum Metrnl was measured by enzyme-linked immunosorbent assay. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were measured for the assessment of sarcopenia. RESULTS: We found that serum Metrnl levels were lower in patients with sarcopenia [median (IQR) = 180.1 (151.3-220.3) pg/mL] than older adults without sarcopenia [211.9 (163.2-270.0) pg/mL, P < 0.001]. Receiver-operating characteristic curve analysis showed that the optimal cut-off value of serum Metrnl level that predicted sarcopenia was 197.2 pg/mL with a sensitivity of 59.2% and a specificity of 63.8% (AUC = 0.63, 95% CI = 0.59-0.67, P < 0.001). Multivariate logistic regression analyses showed that lower serum Metrnl level (< 197.2 pg/mL) was significantly associated with increased risk of sarcopenia (adjusted OR = 2.358, 2.36, 95% CI = 1.528-3.685, P < 0.001). Moreover, serum Metrnl concentration was positively correlated with the components of sarcopenia including ASMI (r = 0.135, P < 0.001), grip strength (r = 0.102, P = 0.005), and gait speed (r = 0.106, P = 0.003). CONCLUSIONS: Taken together, our findings demonstrate that low serum Metrnl level is correlated with increased risk of sarcopenia in the older adults.

3.
Opt Lett ; 49(19): 5635-5638, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39353025

RESUMEN

Multipath interference (MPI) noise induces drastic fluctuations in high-speed 4-level pulse amplitude modulation (PAM4) intensity modulation direct detection (IMDD) systems, severely degrading the transmission performance. Here, we propose a bias-aided decision-directed least mean square (DD-LMS) equalizer to eliminate the MPI noise. In the simulation, the proposed bias-aided DD-LMS equalizer could adeptly track and compensate the MPI-impaired PAM4 signal, markedly improving the bit error rate (BER) performance under different MPI levels and laser linewidths. Within a 112 Gbps PAM4 transmission system, the proposed equalizer achieves a MPI tolerance over 4 dB at the KP4-forward error correction (FEC) threshold (2.4 × 10-4), outperforming existing MPI suppression techniques.

4.
J Colloid Interface Sci ; 678(Pt C): 24-34, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39277950

RESUMEN

Small molecule prodrugs self-assembled nano-delivery systems with tumor responsive linkages are emerging as an effective platform. However, the heterogeneity of tumor microenvironment may limit the anti-tumor effect of prodrug nanomedicines with a single response module. Here, we chose disulfide bond as the response module and branched chain alcohol as the self-assembly modification module to construct a single-responsive prodrug. We also constructed a double-responsive paclitaxel prodrug combining triglyceride and disulfide bond, taking into account of the highly expressed lipase and glutathione levels in tumor cells. The results showed that the anti-tumor effect of single-responsive branched chain alcohol modified prodrug nanoparticles was inferior to triglyceride prodrug nanoparticles with dual response modules. The triglyceride structure can not only serve as a self-assembly modification module, but also serve as a response module for intelligent drug release in tumor. Such dual roles will facilitate the efficient delivery of small molecule self-assembled prodrugs to tumor sites.

5.
Food Chem ; 463(Pt 2): 141249, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39293382

RESUMEN

In this study, the isolation and purification of melanin pigment from Mesona chinensis (MCM) were conducted, and the structural characterization and stability evaluation of MCM were performed. The results indicate that MCM is consistent with the spectral features of catechins and polyphenols, identified the stretching vibrations of functional groups such as OH, CH, CO, and CO. It is inferred that the structure of MCM is consistent with that of theophylline and it is mainly composed of phenolic acids, terpenoids, and organic acids. Stability evaluations indicate that MCM exhibits stability under white light, ultraviolet (UV) light, neutral, and alkaline environments, and it shows low sensitivity to reducing agents.

7.
J Cachexia Sarcopenia Muscle ; 15(4): 1601-1615, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39031684

RESUMEN

BACKGROUNDS: Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. METHODS: Denervation-induced muscle atrophy model was constructed in wild-type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) or oral gavage of RBP4 inhibitor A1120. Holo-RBP4-stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross-sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. RESULTS: The expression levels of RBP4 in skeletal muscles were significantly up-regulated more than 2-fold from 7 days and sustained for 28 days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation-induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin-1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol-bound holo-RBP4 aggregated denervation-induced ectopic fat accumulation and muscle atrophy. Consistently, holo-RBP4 stimulation also had a dose-dependent effect on the reduction of C2C12 myotube diameter and myofibre cross-sectional area, as well as on the increase of Atrogin-1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo-RBP4 treatment increased the expression of its membrane receptor STRA6 (>3-fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin-1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3-fold) in holo-RBP4-treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation-induced muscle atrophy (30% increased myofibre cross-sectional area) in mice. CONCLUSIONS: In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6-dependent and JAK2/STAT3 pathway-mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.


Asunto(s)
Atrofia Muscular , Proteínas Plasmáticas de Unión al Retinol , Transducción de Señal , Animales , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Ratones , Atrofia Muscular/metabolismo , Atrofia Muscular/etiología , Proteínas de la Membrana/metabolismo , Ratones Noqueados , Modelos Animales de Enfermedad , Factor de Transcripción STAT3/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Masculino , Janus Quinasa 2/metabolismo
8.
Langmuir ; 40(32): 16804-16812, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39081049

RESUMEN

Flexible environmental phase change gel (EPCG) is a promising and attractive material for borehole sealing due to its relatively lower usage, tunable cross-linking time, and potential degradable properties. However, conventional borehole sealing materials lack a lower manufacturing cost, lower reaction temperature, remarkable antimold function, and admirable hole sealing performance for long-term high-performance borehole sealing. Hence, it remains a critical challenge to realize a flexible phase-change gel featuring tunable cross-linking time, antimold ability and degradability, and long-lasting moist performance for high-performance borehole sealing. Herein, we illustrate a facile approach to fabricate the borehole sealing materials based on environmentally friendly, antimold, long-lasting moist composite phase-change gel fabricated from a modified cellulose gel polymer network. The prepared phase change gel presents adjustable cross-linking time with the initial setting time of 30-60 min, which could be used to seal holes with different drilling parameters. Furthermore, the fabricated gel illustrates reliable water retentiveness performance and antimold ability, assuring the long-period borehole sealing effect. Furthermore, EPCG has been applied for borehole sealing and shows great sealing ability and gas extraction performance. Therefore, this work paves the way to fabricate a flexible phase-change gel featuring tunable cross-linking time, antimold ability, and long-lasting moist performance for high performance borehole sealing.

9.
J Imaging Inform Med ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980623

RESUMEN

Malposition of a nasogastric tube (NGT) can lead to severe complications. We aimed to develop a computer-aided detection (CAD) system to localize NGTs and detect NGT malposition on portable chest X-rays (CXRs). A total of 7378 portable CXRs were retrospectively retrieved from two hospitals between 2015 and 2020. All CXRs were annotated with pixel-level labels for NGT localization and image-level labels for NGT presence and malposition. In the CAD system, DeepLabv3 + with backbone ResNeSt50 and DenseNet121 served as the model architecture for segmentation and classification models, respectively. The CAD system was tested on images from chronologically different datasets (National Taiwan University Hospital (National Taiwan University Hospital)-20), geographically different datasets (National Taiwan University Hospital-Yunlin Branch (YB)), and the public CLiP dataset. For the segmentation model, the Dice coefficients indicated accurate delineation of the NGT course (National Taiwan University Hospital-20: 0.665, 95% confidence interval (CI) 0.630-0.696; National Taiwan University Hospital-Yunlin Branch: 0.646, 95% CI 0.614-0.678). The distance between the predicted and ground-truth NGT tips suggested accurate tip localization (National Taiwan University Hospital-20: 1.64 cm, 95% CI 0.99-2.41; National Taiwan University Hospital-Yunlin Branch: 2.83 cm, 95% CI 1.94-3.76). For the classification model, NGT presence was detected with high accuracy (area under the receiver operating characteristic curve (AUC): National Taiwan University Hospital-20: 0.998, 95% CI 0.995-1.000; National Taiwan University Hospital-Yunlin Branch: 0.998, 95% CI 0.995-1.000; CLiP dataset: 0.991, 95% CI 0.990-0.992). The CAD system also detected NGT malposition with high accuracy (AUC: National Taiwan University Hospital-20: 0.964, 95% CI 0.917-1.000; National Taiwan University Hospital-Yunlin Branch: 0.991, 95% CI 0.970-1.000) and detected abnormal nasoenteric tube positions with favorable performance (AUC: 0.839, 95% CI 0.807-0.869). The CAD system accurately localized NGTs and detected NGT malposition, demonstrating excellent potential for external generalizability.

10.
J Med Chem ; 67(14): 11751-11768, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38989847

RESUMEN

Despite being a highly sought-after therapeutic target for human malignancies, myelocytomatosis viral oncogene homologue (MYC) has been considered intractable due to its intrinsically disordered nature, making the discovery of in vivo effective inhibitors that directly block its function challenging. Herein, we report structurally novel alkynyl-substituted phenylpyrazole derivatives directly perturbing MYC function. Among them, compound 37 exhibited superior antiproliferative activities to those of MYCi975 against multiple malignant cell lines. It induced dose-dependent MYC degradation in cells with degradation observed at the concentration as low as 1.0 µM. Meanwhile, its direct suppression of MYC function was confirmed by the capability to inhibit the binding of MYC/MYC-associated protein X (MAX) heterodimer to DNA consensus sequence, induce MYC thermal instability, and disturb MYC/MAX interaction. Moreover, 37 demonstrated enhanced therapeutic efficacy over MYCi975 in a mouse allograft model of prostate cancer. Overall, 37 deserves further development for exploring MYC-targeting cancer therapeutics.


Asunto(s)
Antineoplásicos , Proteínas Proto-Oncogénicas c-myc , Pirazoles , Humanos , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Animales , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ratones , Masculino , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proteolisis/efectos de los fármacos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Relación Estructura-Actividad , Unión Proteica , Ratones Desnudos
11.
J Pharm Biomed Anal ; 249: 116387, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39083919

RESUMEN

Baloxavir marboxil (BXM) is a cap-dependent nucleic acid endonuclease inhibitor, which exerts its antiviral effects after being metabolized to its active form baloxavir acid (BXA). Ethylenediamine tetra-acetic acid (EDTA) and heparin are the two most used anticoagulants in clinical blood sample collection to estimate drug levels in plasma. However, compared to heparin plasma, there is a lack of clinical pharmacokinetic data of BXA using EDTA anticoagulant tubes for blood collection. In the present study, an efficient, rapid, and sensitive ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for simultaneous quantification of BXM and its active metabolite BXA in human plasma with its isotopic baloxavir-d5 (BXA-d5) as internal standard (IS). Plasma samples (50 µL) were undergone using acetonitrile containing 0.1 % formic acid a precipitant. Chromatographic separation was achieved by a Waters XBridge®C8 (2.1 mm × 50 mm, 2.5 µm) column. The gradient mobile phase was 0.1 % formic acid in water (A, pH 2.8) and 0.1 % formic acid in acetonitrile (B) and delivered at a flow rate of 0.6 mL/min for 4.5 min. BXM and BXA were monitored using a positive electrospray triple quadrupole mass spectrometer (TRIPLE QUAD™ 6500+) via multiple reaction monitoring mode. The mass-to-charge ratios (m/z) were 572.2→247.0, 484.2→247.0 and 489.2→252.0 for BXM, BXA, and BXA-d5 (IS). Calibration curves exhibited excellent linearity in the range of 0.1-10 ng/mL for BXM (r2 > 0.996), and 0.3-300 ng/mL for BXA (r2 > 0.998). Within-run and between-run precisions in coefficients of variations were less than 11.62 % for BXM and less than 7.47 % for BXA, and accuracies in relative error were determined to be within -7.78 % to 5.70 % for BXM and -6.67 % to 8.56 % for BXA. Extraction recovery efficiency was 92.76 % for BXM, 95.32 % for BXA, and 99.26 % for BXA-d5, respectively. The matrix effect of BXM and BXA was in line with the requirements, where the relative deviation of the accuracy was less than 6.67 % and the precision was less than 6.69 %. The validated efficient and simple UHPLC-MS/MS method was successfully used in the pharmacokinetic study of BXM and BXA in healthy human volunteers with K2EDTA and heparin tubes for blood collection. EDTA might compete with BXA for chelating metal ions and thereby decrease the plasma ratio in whole blood, leading to approximately 50 % lower measurement of pharmacokinetic parameters as compared with those obtained from heparin plasma anticoagulant tubes.


Asunto(s)
Anticoagulantes , Dibenzotiepinas , Oxazinas , Piridinas , Piridonas , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Anticoagulantes/sangre , Anticoagulantes/farmacocinética , Dibenzotiepinas/farmacocinética , Dibenzotiepinas/sangre , Piridonas/farmacocinética , Piridonas/sangre , Piridinas/farmacocinética , Piridinas/sangre , Oxazinas/farmacocinética , Oxazinas/sangre , Morfolinas/farmacocinética , Morfolinas/sangre , Triazinas/farmacocinética , Triazinas/sangre , Reproducibilidad de los Resultados , Ácido Edético/farmacocinética , Límite de Detección , Heparina/sangre , Heparina/farmacocinética
12.
Opt Lett ; 49(11): 3166-3169, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824354

RESUMEN

To monitor the health of the fiber network and its ambient environment in densely populated access/metro network areas, in this Letter, an endogenous distributed acoustic sensing (DAS) has been proposed and achieved in a coherent digital subcarrier multiplexing (DSCM) system. Rather than specially allocating a sensing probe in general integrated communication and sensing schemes, the fractional Fourier transformed (FrFT) training sequence (TS) designated for time/frequency synchronization in DSCM coherent communications has been repurposed for sensing. While achieving excellent synchronization performance of communication, the FrFT-based TS can also be concurrently utilized to perform distributed vibration sensing. Experimental results demonstrate that the FrFT-based timing/frequency synchronization sequence is repurposed to achieve a DAS sensitivity of 70 p ε/Hz at a spatial resolution of 5 m, along with 100-Gb/s 16 quadrature amplitude modulation (QAM) DSCM transmission, without a loss of spectral efficiency.

13.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1435-1446, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38886443

RESUMEN

As regulators of the surface land processes, soil fauna communities are the vital foundations for healthy terrestrial ecosystems. Soil fauna have been studied in China for more than 70 years. Great progresses have been achieved in exploring soil fauna species composition and geographical distribution patterns. Soil fauna eco-geography, as a bridge between soil fauna geographic patterns and ecosystem services, has a new development opportunity with the deep recognition of soil fauna ecological functions. Soil fauna eco-geography research could be partitioned into four dimensions including the spatio-temporal patterns of: 1) the apparent characteristics of soil fauna community, such as species composition, richness and abundance; 2) the intrinsic characteristics of soil fauna community, such as dietary and habits; 3) soil fauna-related biotic and abiotic interactions especially those indicating drivers of soil fauna community structure or shaping the roles of soil fauna in ecosystems; and 4) soil fauna-related or -regulated key ecological processes. Current studies focus solely on soil fauna themselves and their geographical distributions. To link soil fauna geography more closely with ecosystem services, we suggested that: 1) converting the pure biogeography studies to those of revealing the spatio-temporal patterns of the soil fauna-related or regulated key relationships and ecological processes;2) expanding the temporal and spatial scales in soil fauna geographical research;3) exploring the integrated analysis approach for soil fauna-related data with multi-scales, multi-factors, and multi-processes;and 4) establishing standard reference systems for soil fauna eco-geographical researches. Hence, the change patterns of ecological niche of soil fauna communities could be illustrated, and precision mani-pulations of soil fauna communities and their ecological functions would become implementable, which finally contributes to ecosystem health and human well-being.


Asunto(s)
Biodiversidad , Ecosistema , Suelo , China , Suelo/química , Animales , Invertebrados/clasificación , Invertebrados/crecimiento & desarrollo , Geografía
14.
Nat Commun ; 15(1): 4984, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862481

RESUMEN

More than 10 million people suffer from lung diseases caused by the pathogenic fungus Aspergillus fumigatus. Azole antifungals represent first-line therapeutics for most of these infections but resistance is rising, therefore the identification of antifungal targets whose inhibition synergises with the azoles could improve therapeutic outcomes. Here, we generate a library of 111 genetically barcoded null mutants of Aspergillus fumigatus in genes encoding protein kinases, and show that loss of function of kinase YakA results in hypersensitivity to the azoles and reduced pathogenicity. YakA is an orthologue of Candida albicans Yak1, a TOR signalling pathway kinase involved in modulation of stress responsive transcriptional regulators. We show that YakA has been repurposed in A. fumigatus to regulate blocking of the septal pore upon exposure to stress. Loss of YakA function reduces the ability of A. fumigatus to penetrate solid media and to grow in mouse lung tissue. We also show that 1-ethoxycarbonyl-beta-carboline (1-ECBC), a compound previously shown to inhibit C. albicans Yak1, prevents stress-mediated septal spore blocking and synergises with the azoles to inhibit A. fumigatus growth.


Asunto(s)
Antifúngicos , Aspergillus fumigatus , Quinasas DyrK , Proteínas Fúngicas , Proteínas Serina-Treonina Quinasas , Proteínas Tirosina Quinasas , Aspergillus fumigatus/genética , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/enzimología , Animales , Antifúngicos/farmacología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/antagonistas & inhibidores , Ratones , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Azoles/farmacología , Aspergilosis/microbiología , Aspergilosis/tratamiento farmacológico , Pulmón/microbiología , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/genética , Femenino
16.
ACS Omega ; 9(18): 20410-20424, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38737081

RESUMEN

The droplet-to-iron electrochemical reaction is common in nature and industrial production, and it causes damage to the economy, safety, and the environment. The electrochemical reaction of droplet-to-iron is a coupling process of wetting and corrosion. Presently, investigations into electrochemical reactions mainly focus on the corrosions caused by a solution, and wetting is rarely considered. However, for the droplet-to-iron electrochemical reaction, the mechanism of charge transfer in the process is still unclear. In this paper, a reactive molecular dynamics simulation model for the droplet-to-iron electrochemical reaction is developed for the first time. The electrochemical reaction of droplet-to-iron is studied, and the interaction between droplet wetting and corrosion on iron is investigated. The effects of temperature, electric field strength, and salt concentration on the electrochemical reaction are explored. Results show that droplet wetting on the iron surface and the formation of a single-molecular-layer ordered structure are prerequisites for corrosion. The hydroxyl radicals that penetrate the ordered structure acquire electrons from iron atoms on the substrate surface under the action of Coulomb forces and form iron-containing oxides with these iron atoms. The corrosion products and craters lead to a reduced droplet height, which promotes droplet wetting on iron and further intensifies the droplet-to-iron electrochemical reaction.

17.
Am J Nucl Med Mol Imaging ; 14(2): 110-121, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737640

RESUMEN

Molecular imaging enables visualization and characterization of biological processes that influence tumor behavior and response to therapy. The TMTP1 (NVVRQ) peptide has shown remarkable affinity to highly metastatic tumors and and its potential receptor is aminopeptidase P2. In this study, we have designed and synthesized a 68Ga-labeled cyclic TMTP1 radiotracer (68Ga-DOTA-TMTP1), for PET imaging of cervical cancer. The goal of this study was to investigate the properties of this radiotracer and its tumor diagnostic potential. The radiochemical yield of 68Ga-DOTA-TMTP1 was high and the radiochemical purity was greater than 95%. The octanol-water partition coefficient for 68Ga-DOTA-TMTP1 was -2.76 ± 0.08 and 68Ga-DOTA-TMTP1 has showed excellent stability in in vitro studies. The cellular uptake and efflux of 68Ga-DOTA-TMTP1 in paired highly metastatic and lowly metastatic cervical cancer cell line HeLa and C-33A as well as normal cervical epithelial cell line End1 were measured in a γ counter. 68Ga-DOTA-TMTP1 exhibited higher uptake in HeLa cells than in C-33A cells. The binding to HeLa and C-33A cells could be blocked by excess TMTP1. On microPET images, HeLa tumors were clearly visualized within 60 min and the uptake of the radiotracer in HeLa tumors was higher than that of C-33A tumors. After blocking with TMTP1, HeLa tumors uptake was significantly reduced and the specificity 68Ga-DOTA-TMTP1 was thus validated. Overall, we have successfully synthesized 68Ga-DOTA-TMTP1 with high yield and high specific activity and have demonstrated its potential role for highly metastatic tumor-targeted diagnosis.

18.
Adv Mater ; 36(29): e2401585, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38696723

RESUMEN

The processing of visual information occurs mainly in the retina, and the retinal preprocessing function greatly improves the transmission quality and efficiency of visual information. The artificial retina system provides a promising path to efficient image processing. Here, graphene/InSe/h-BN heterogeneous structure is proposed, which exhibits negative and positive photoconductance (NPC and PPC) effects by altering the strength of a single wavelength laser. Moreover, a modified theoretical model is presented based on the power-dependent photoconductivity effect of laser: I ph = - mP α 1 + nP α 2 ${\rm I}_{\rm ph}\,=\,-{\rm mP}^{\alpha _{1}} + {\rm nP}^{\alpha _{2}}$ , which can reveal the internal physical mechanism of negative/positive photoconductance effects. The present 2D structure design allows the field effect transistor (FET) to exhibit excellent photoelectric performance (RNPC = 1.1× 104 AW-1, RPPC = 13 AW-1) and performance stability. Especially, the retinal pretreatment process is successfully simulated based on the negative and positive photoconductive effects. Moreover, the pulse signal input improves the device responsivity by 167%, and the transmission quality and efficiency of the visual signal can also be enhanced. This work provides a new design idea and direction for the construction of artificial vision, and lay a foundation for the integration of the next generation of optoelectronic devices.

19.
Graefes Arch Clin Exp Ophthalmol ; 262(9): 2961-2970, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38587654

RESUMEN

PURPOSE: This study is to evaluate the correlation between retrobulbar perfusion deficits and glaucomatous visual field defects. METHODS: Eighty-four patients with glaucoma and 17 normal subjects serving as controls were selected. Color Doppler imaging (CDI) was used to measure the changes in blood flow parameters in the retrobulbar ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs). Visual field testing was performed using a Humphrey perimeter, categorizing the visual field deficits into four stages according to the Advanced Glaucoma Intervention Study (AGIS) scoring method. Subsequently, the correlation of retrobulbar hemodynamic parameter alterations among glaucomatous patients with varying visual field defects was examined. RESULTS: The higher the visual field stage, the lower the peak systolic velocity (PSV) of the OA, CRA, and SPCAs in glaucomatous patients. The CRA had the highest sensitivity to changes in its PSV. The PSV of the temporal SPCA (TSPCA-PSV) was lower in advanced glaucoma than in early-stage glaucoma. The PSVs of the OA, CRA, and TSPCA, as well as the resistance index of the CRA (CRA-RI), were positively correlated with the visual field index and the mean deviation. Except for that of OA, the PSV of the retrobulbar vessels was negatively correlated with the pattern standard deviation (PSD). The OA-PSV and end-diastolic velocity (EDV) of the CRA and TSPCA were lower in patients with superior visual field defects than in those with inferior visual field defects. CONCLUSIONS: Greater severity of visual field defects corresponded to poorer retrobulbar blood flow in glaucomatous patients. Patients suffered significant perfusion impairments in the CRA at the early stage, accompanied by SPCA perfusion disorder at the advanced stage. The presence of a bow-shaped defect in the superior or inferior region of the visual field in moderate-stage glaucoma was closely correlated with retrobulbar vascular EDV. TRIAL REGISTRATION: ChiCTR2200059048 (2022-04-23).


Asunto(s)
Arterias Ciliares , Presión Intraocular , Arteria Oftálmica , Flujo Sanguíneo Regional , Arteria Retiniana , Ultrasonografía Doppler en Color , Pruebas del Campo Visual , Campos Visuales , Humanos , Campos Visuales/fisiología , Masculino , Femenino , Arteria Oftálmica/fisiopatología , Arterias Ciliares/fisiopatología , Arterias Ciliares/fisiología , Persona de Mediana Edad , Presión Intraocular/fisiología , Arteria Retiniana/fisiopatología , Flujo Sanguíneo Regional/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Anciano , Trastornos de la Visión/fisiopatología , Trastornos de la Visión/diagnóstico , Glaucoma/fisiopatología , Glaucoma/diagnóstico , Órbita/irrigación sanguínea , Órbita/fisiopatología , Glaucoma de Ángulo Abierto/fisiopatología , Glaucoma de Ángulo Abierto/diagnóstico
20.
Chem Sci ; 15(15): 5775-5785, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38638235

RESUMEN

Bacterial infections, as the second leading cause of global death, are commonly treated with antibiotics. However, the improper use of antibiotics contributes to the development of bacterial resistance. Therefore, the accurate differentiation between bacterial and non-bacterial inflammations is of utmost importance in the judicious administration of clinical antibiotics and the prevention of bacterial resistance. However, as of now, no fluorescent probes have yet been designed for the relevant assessments. To this end, the present study reports the development of a novel fluorescence probe (CyQ) that exhibits dual-enzyme responsiveness. The designed probe demonstrated excellent sensitivity in detecting NTR and NAD(P)H, which served as critical indicators for bacterial and non-bacterial inflammations. The utilization of CyQ enabled the efficient detection of NTR and NAD(P)H in distinct channels, exhibiting impressive detection limits of 0.26 µg mL-1 for NTR and 5.54 µM for NAD(P)H, respectively. Experimental trials conducted on living cells demonstrated CyQ's ability to differentiate the variations in NTR and NAD(P)H levels between A. baumannii, S. aureus, E. faecium, and P. aeruginosa-infected as well as LPS-stimulated HUVEC cells. Furthermore, in vivo zebrafish experiments demonstrated the efficacy of CyQ in accurately discerning variations in NTR and NAD(P)H levels resulting from bacterial infection or LPS stimulation, thereby facilitating non-invasive detection of both bacterial and non-bacterial inflammations. The outstanding discriminatory ability of CyQ between bacterial and non-bacterial inflammation positions it as a promising clinical diagnostic tool for acute inflammations.

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