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The overexpression of HER2 is pivotal in the initiation and progression of breast cancer. Developing HER2-targeted radiotracers is crucial for noninvasive assessment of HER2 expression, patient selection for HER2-targeted therapy, monitoring treatment response, and identifying resistance. Here, we reported a nonsite-specific coupled radiotracer, 68Ga-NOTA-SNA004-His6, and a site-specific coupled radiotracer, 68Ga-NODAGA-SNA004-GSC, based on a novel HER2 nanobody, SNA004. Both radiotracers exhibited high affinity, specific targeting, and rapid clearance in vitro and in vivo. Additionally, these tracers and trastuzumab showed noncompetitive binding to HER2. Compared to 68Ga-NOTA-SNA004-His6, 68Ga-NODAGA-SNA004-GSC demonstrated significantly reduced renal and liver uptake. PET/CT imaging with 68Ga-NODAGA-SNA004-GSC sensitively detected the responsiveness of various tumor models to trastuzumab and its antibody-drug conjugates (ADCs). Overall, the site-specific coupled radiotracer 68Ga-NODAGA-SNA004-GSC offered significant advantages in biodistribution and signal-to-noise ratio, making it a valuable tool for monitoring HER2 expression levels before, during, and after trastuzumab and ADC treatment.
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Radioisótopos de Galio , Compuestos Heterocíclicos con 1 Anillo , Inmunoconjugados , Receptor ErbB-2 , Anticuerpos de Dominio Único , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Humanos , Inmunoconjugados/química , Inmunoconjugados/farmacocinética , Inmunoconjugados/farmacología , Animales , Radioisótopos de Galio/química , Femenino , Compuestos Heterocíclicos con 1 Anillo/química , Anticuerpos de Dominio Único/química , Ratones , Distribución Tisular , Línea Celular Tumoral , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Acetatos/química , Acetatos/farmacología , Radiofármacos/química , Ratones Desnudos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
BACKGROUND: This study examines the extent to which depressive symptoms mediate the link between childhood friendship (CF) and physical function among middle-aged and older adults in China. METHODS: China Health and Retirement Longitudinal Study (CHARLS) data were used; specifically, CHARLS life history survey (conducted from June 1-December 31, 2014) and follow-up health survey (conducted from July 1-September 30, 2015) data were used. The Sobel test, Bootstrap test and multivariable logistic regression were performed to examine the mediating role of depressive symptoms (measured by the 10-item Center for Epidemiologic Studies Depression Scale) in the association between CF (measured by a standardized retrospective questionnaire) and physical function, which was measured by basic activities of daily living (BADL) disability, instrumental activities of daily living (IADL) disability, and grip strength. RESULTS: A total of 12,170 participants aged 45 years or older were included in this cross-sectional study. After controlling for covariates, low-quality CF was associated with an increased prevalence of BADL disability (OR = 1.18; 95 % CI = 1.05-1.32), IADL disability (OR = 1.25; 95 % CI = 1.12-1.40), and low grip strength (OR = 1.21; 95 % CI = 1.09-1.34). The proportion of the mediating effect of depressive symptoms was 48 % for CF and BADL, 40 % for CF and IADL, and 11 % for CF and grip strength. Depressive symptoms and worse CF have a joint effect on BADL disability (OR = 3.30; 95 % CI = 2.82-3.85), IADL disability (OR = 3.52; 95 % CI = 3.03-4.09), and low grip strength (OR = 1.65; 95 % CI = 1.43-1.92). LIMITATIONS: Not all potential confounding factors (such as childhood behavioural problems, genetic factors, and memory function) were measured in the analysis, and there may have been recall bias in the retrospective collection of CF data. CONCLUSIONS: Individuals with high-quality CF were more likely to have a decreased prevalence of impaired physical function in later life. Depressive symptoms acted as a mediator associated with the development of CF.
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Actividades Cotidianas , Depresión , Amigos , Humanos , Masculino , Femenino , China/epidemiología , Estudios Longitudinales , Depresión/epidemiología , Anciano , Persona de Mediana Edad , Estudios Transversales , Amigos/psicología , Jubilación/estadística & datos numéricos , Jubilación/psicología , Fuerza de la Mano , PrevalenciaRESUMEN
Unsupervised domain adaptation has been extensively researched in rotating-machinery cross-domain fault diagnosis. A multi-source domain adaptive network based on local kernelized higher-order moment matching is constructed in this research for rotating-machinery fault diagnosis. Firstly, a multi-branch network is designed to map each source-target pair to a domain-specific shared space and to extract domain-invariant features using domain adversarial thought. Then, a local kernelized higher-order moment matching algorithm is proposed to perform fine-grained matching in shared category subspace. Finally, a feature fusion strategy based on the local domain distribution deviation is applied to synthesize the output features of multiple classifiers to obtain diagnostic results. The experimental validation of two-branch and three-branch networks on two public datasets is carried out and average diagnostic accuracies both exceed 99%. The results demonstrate the effectiveness and superiority of the approach.
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BACKGROUND: Cardiometabolic multimorbidity (CM) has been found to be associated with higher mortality and functional limitations. However, few studies have investigated the longitudinal association between CM and disability in the Chinese population and whether these associations vary by smoking status. METHODS: The study included 16,754 participants from four waves (2011, 2013, 2015, and 2018) of China Health and Retirement Longitudinal Study (CHARLS) (mean age: 59, female: 51%). CM was assesed at baseline and defined as having two or more of diabetes, stroke, or heart disease. Disability was repeatedly measured by summing the number of impaired activities of daily living (ADL) and instrumental activities of daily living (IADL) during the 7-year follow-up. Linear mixed-effects model was used to determine the association of CM and trajectories of disability and to assess the modification effect of smoking status in these associations. RESULTS: Participants with CM at baseline had a faster progression of disability compared to those without CM (CM: ß = 0.13, 95% CI: 0.05 to 0.21). Current smokers with CM developed disability faster than their counterparts (Pinteraction for smoking=0.011). In addition, there was a significant association between CM and the annual change of disability in current smokers (ß = 0.34, 95% CI: 0.17 to 0.50) while no such association was observed in current non-smokers (ß = 0.08, 95% CI: -0.02 to 0.17). CONCLUSION: CM was associated with more a rapid disability progression. Notably, being current smokers may amplify the adverse effects of CM on disability progression.
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Cardiopatías , Multimorbilidad , Humanos , Femenino , Actividades Cotidianas , Estudios Longitudinales , Fumar/efectos adversos , Fumar/epidemiología , China/epidemiologíaRESUMEN
Itinerant ferromagnetism at room temperature is a key factor for spin transport and manipulation. Here, we report the realization of near-room temperature itinerant ferromagnetism in Co doped Fe5GeTe2 thin flakes. The ferromagnetic transition temperature TC (â¼323 K-337 K) is almost unchanged when the thickness is as low as 12 nm and is still about 284 K at 2 nm (bilayer thickness). Theoretical calculations further indicate that the ferromagnetism persists in monolayer Fe4CoGeTe2. In addition to the robust ferromagnetism down to the ultrathin limit, Fe4CoGeTe2 exhibits an unusual temperature- and thickness-dependent intrinsic anomalous Hall effect. We propose that it could be ascribed to the dependence of the band structure on thickness that changes the Berry curvature near the Fermi energy level subtly. The near-room temperature ferromagnetism and tunable anomalous Hall effect in atomically thin Fe4CoGeTe2 provide opportunities to understand the exotic transport properties of two-dimensional van der Waals magnetic materials and explore their potential applications in spintronics.
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Rationale: Although programmed death-ligand 1 (PD-L1) inhibitors have achieved efficacy in cancer therapy, their response rate is low. Differences in the prognosis of patients with cancer under anti-PD-L1 treatment are related to the PD-L1 level in tumors. Accurate PD-L1 detection can optimize the accuracy of tumor immunotherapy and avoid ineffective clinical diagnosis and treatments. Methods: We investigated the imaging efficiency and therapy monitoring capacity of [89Zr]Zr-DFO-KN035 immunoPET for tumors. We labeled the monodomain anti-PD-L1 antibody KN035 with the radionuclide zirconium-89 and used this tracer for PET imaging. [89Zr]Zr-DFO-KN035 uptakes in patients with PD-L1-positive tumors, including primary and metastatic tumors, as well as in normal tissues, were comparatively assessed by using positron emission tomography/computed tomography imaging. Results: In PD-L1-positive patients, [89Zr]Zr-DFO-KN035 was sensitive in tumor-targeting imaging and could detect multiple metastatic foci, including multiple bone metastases (tumor-to-muscle ratios of 7.102 and 6.118 at 55 and 120 h, respectively) and lymph-node metastases (tumor-to-muscle ratios of 11.346 and 6.542 at 55 and 120 h, respectively). The needed radioactive dose of [89Zr]Zr-DFO-KN035 (55.5-92.5 MBq) used in this study was considerably lower than that of [18F]FDG (370-555 MBq). [89Zr]Zr-DFO-KN035 monitored and predicted the site of adverse reactions in antitumor immunotherapy. Moreover, after antitumor treatment, [89Zr]Zr-DFO-KN035 enabled observational imaging for therapeutic efficacy evaluation, which can help predict patient prognosis. Conclusion: [89Zr]Zr-DFO-KN035 can be used for the diagnosis and therapy monitoring of PD-L1-positive tumors and provide noninvasive and comprehensive observations for tumor diagnostic imaging, prognosis prediction, and efficacy evaluation.
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Anticuerpos Monoclonales Humanizados , Antígeno B7-H1 , Humanos , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Línea Celular Tumoral , CirconioRESUMEN
PURPOSE: Prostate-specific membrane antigen (PSMA) is a promising diagnostic biomarker for prostate cancer (PCa). NYM016, a novel small-molecule PSMA-targeted fluorescence probe for the surgical navigation of PCa, was designed in this work. Furthermore, the potential of the PET agent [68Ga]Ga-NYM016 for the radionuclide imaging of PCa was evaluated. METHODS: NYM016 was designed with the near-infrared fluorescent group Cyanine 7 (Cy7) and the chelating group NOTA. The radioactive probe [68Ga]Ga-NYM016 was designed and synthesized on the basis of NYM016. The abovementioned probes were assessed in PSMA-positive xenograft-bearing models and patients diagnosed with PCa. RESULTS: NYM016 obviously aggregated in the tumor site of the mouse model, and its fluorescence intensity was stable within 24 h. NYM016 was well-tolerated, and no adverse events were found in the clinical study. Moreover, it was also observed in the excised lesions from the patient with PCa, and its fluorescence aggregated at the same site where PSMA was highly expressed. In addition, the PSMA xenograft demonstrated intense [68Ga]Ga-NYM016 uptake at 2.5 min after injection. At 3 h after injection, [68Ga]Ga-NYM016 uptake by the PSMA xenograft gradually increased to 6.40 ± 0.19%ID/g, which was higher that by the blocked and negative groups (2.28 ± 0.07%ID/g, P < 0.05; 2.28 ± 0.22%ID/g, P < 0.05). In the clinical study, [68Ga]Ga-NYM016 was well-tolerated and no adverse events were observed. Substantial accumulation was observed in primary and metastatic lesions in a patient with recurrence with the maximum standardized uptake value of 18.93. Meanwhile, negative [68Ga]Ga-NYM016 uptake was observed at the prostate site of a patient with prostatitis. CONCLUSION: The novel fluorescence probe NYM016 and the radioactive tracer [68Ga]Ga-NYM016 are promising candidates for the surgical navigation and radionuclide imaging of PCa, respectively. TRIAL REGISTRATION: The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT05623878) on 21 Dec, 2022.
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The integration of abiotic materials with live cells has emerged as an exciting strategy for the control of cellular functions. Exoskeletons consisting ofmetal-organic frameworks are generated to produce partial-coated bone marrow stem cells (BMSCs) to overcome low cell survival leading to disappointing effects for cell-based cardiac therapy. Partially coated exoskeletons can promote the survival of suspended BMSCs by integrating the support of exoskeletons and unimpaired cellular properties. In addition, partial exoskeletons exhibit protective effects against detrimental environmental conditions, including reactive oxygen species, pH changes, and osmotic pressure. The partial-coated cells exhibit increased intercellular adhesion forces to aggregate and adhere, promoting cell survival and preventing cell escape during cell therapy. The exoskeletons interact with cell surface receptors integrin α5ß1, leading to augmented biological functions with profitable gene expression alteration, such as Vegfa, Cxcl12, and Adm. The partial-coated BMSCs display enhanced cell retention in infarcted myocardium through non-invasive intravenous injections. The repair of myocardial infarction has been achieved with improved cardiac function, myocardial angiogenesis, proliferation, and inhibition of cell apoptosis. This discovery advances the elucidation of potential molecular and cellular mechanisms for cell-exoskeleton interactions and benefits the rational design and manufacture of next-generation nanobiohybrids.
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Dispositivo Exoesqueleto , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Infarto del Miocardio , Humanos , Miocardio/metabolismo , Infarto del Miocardio/metabolismo , Células Madre/metabolismoRESUMEN
Integrin α6 has been considered a promising biomarker, is overexpressed in many tumors, and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we identified a novel high-affinity integrin α6-targeted peptide named RD2 (Arg-Trp-Tyr-Asp-PEG4)2-Lys-Lys and developed a 18F-radiolabeled peptide tracer ([18F]-AlF-NOTA-RD2) and evaluated its potential application in positron emission tomography (PET) imaging of pancreatic cancer. [18F]-AlF-NOTA-RD2 was produced using GMP (Good Manufacturing Practice of Medical Products)-compliant automatic radiosynthesis on a single GE FASTLab2 cassette-type synthesis module. The stability of [18F]-AlF-NOTA-RD2 was analyzed in phosphate-buffered saline (PBS) and fetal bovine serum (FBS). The cell uptake assay of the tracer was assessed using PANC-1 cells. In addition, small-animal PET imaging and biodistribution studies of [18F]-AlF-NOTA-RD2 were performed in pancreatic cancer subcutaneous tumor-bearing mice. The PET tracer [18F]-AlF-NOTA-RD2 was obtained with a radiochemical yield of 23.7 ± 4.7%, radiochemical purity of >99%, and molar activity of 165.7 ± 59.1 GBq/µmol. [18F]-AlF-NOTA-RD2 exhibited good in vitro stability in PBS and FBS. LogP octanol water value for the tracer was -2.28 ± 0.05 (n = 3). The binding affinity of RD2 to the integrin α6 protein (Kd = 0.13 ± 3.65 µM, n = 3) was significantly higher than that of the RWY (CRWYDENAC) (Kd = 6.97 ± 1.44 µM, n = 3). Small-animal PET imaging and biodistribution also revealed that [18F]-AlF-NOTA-RD2 displayed rapid and good tumor uptake and lower liver background uptake in PANC-1 tumor-bearing mice. [18F]-AlF-NOTA-RD2 showed significant radioactivity accumulation in tumors and was successfully blocked by NOTA-RD2. Compared with [18F]-FDG, [18F]-AlF-NOTA-RD2 PET imaging and biodistribution studies in PANC-1 xenograft tumor-bearing mice confirmed a good tumor-to-muscle ratio (8.69 ± 2.03 vs 1.41 ± 0.23, respectively) at 0.5 h and (2.99 ± 3.02 vs 1.43 ± 0.17, respectively) at 1 h post injection. Autoradiography of human pancreatic cancer tumor tissues further confirmed high accumulation of [18F]-AlF-NOTA-RD2. In summary, we developed an optimized integrin α6-targeted imaging tracer and obtained high radioactivity products with a cassette-type synthesis module; moreover, the tracer exhibited good binding affinity with integrin α6 and good target specificity for PANC-1 cells in xenograft pancreatic tumor-bearing mice, demonstrating its promising application as a noninvasive PET radiotracer of integrin α6 expression in pancreatic cancer.
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Compuestos Heterocíclicos con 1 Anillo , Neoplasias Pancreáticas , Humanos , Ratones , Animales , Integrina alfa6 , Distribución Tisular , Radioisótopos de Flúor , Línea Celular Tumoral , Tomografía de Emisión de Positrones/métodos , Péptidos , Fluorodesoxiglucosa F18 , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias PancreáticasRESUMEN
One of the hallmarks of multicomponent metal-organic frameworks (MOFs) is to finely tune their active centers to achieve product selectivity. In particular, obtaining bimetallic MOF hollow structures with precisely tailored redox centers under the same topology is still challenging despite a recent surge of such efforts. Herein, we present an engineering strategy named "cluster labilization" to generate hierarchically porous MOF composites with hollow structures and tunable active centers. By partially replacing zirconium with cerium in the hexanuclear clusters of UiO-66, unevenly distributed yolk-shell structures (YSS) were formed. Through acid treatment or annealing of the YSS precursor, single-shell hollow structures (SSHS) or double-shell hollow structures (DSHS) can be obtained, respectively. The active centers in SSHS and DSHS differ in their species, valence, and spatial locations. More importantly, YSS, SSHS, and DSHS with distinct active centers and microenvironments exhibit tunable catalytic activity, reversed selectivity, and high stability in the tandem reaction and the photoreaction.
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Osteomyelitis, caused by purulent bacteria invading bone tissue, often occurs in long bones and seriously affects the physical and mental health and working ability of patients; it can even endanger life. However, due to bone cavity structure, osteomyelitis tends to occur inside the bone and thus lacks an effective treatment; anti-inflammatory treatment and repair of bone defects are necessary. Here, we developed injectable hydrogel microspheres loaded with naringin and bone marrow mesenchymal stem cells, which have anti-inflammatory and osteogenic properties. These homogeneous microspheres, ranging from 200 to 1000µm, can be rapidly fabricated using an electro-assisted bio-fabrication method. Interestingly, it was found that microspheres with relatively small diameters (200µm) were more conducive to the initial cell attachment, growth, spread, and later osteogenic differentiation. The developed microspheres can effectively treat tibial osteomyelitis in rats within six weeks, proving their prospects for clinical application.
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Flavanonas , Hidrogeles , Ratas , Animales , Hidrogeles/química , Osteogénesis , Microesferas , Flavanonas/farmacología , Flavanonas/uso terapéutico , Diferenciación CelularRESUMEN
In this study, the synergistic effect of glutaraldehyde-cross-linking and remineralization on the strength and durability of resin-dentin bonds was investigated. Dentin surfaces were etched with 35% phosphoric acid. The control specimens were bonded with Adper Single Bond 2 using wet bonding without pretreatment. The experimental specimens were pretreated with 5% (v/v) glutaraldehyde solution for 3 min and placed in a remineralizing solution for 0, 12, and 24 h, followed by dry bonding. After performing composite build-ups on the specimens, they were longitudinally sectioned, immediately, and after aging for 3 h with sodium hypochlorite (NaOCl), to evaluate microtensile bond strength (µTBS). The cross-linked specimens exhibited µTBS values comparable with those of the control group, but the µTBS decreased significantly after NaOCl aging. The cross-linked dentin remineralized for 24 h exhibited an increase in µTBS. After aging in NaOCl, the µTBS of the specimens remineralized for 24 h did not decrease and was significantly higher than for the other experimental groups. Cross-linking with dry bonding maintained µTBS in specimens before aging in NaOCl, but the bonding durability was compromised. Remineralization of cross-linked dentin for 24 h followed by dry bonding increased the immediate µTBS and improved bond durability. Therefore, combining cross-linking with remineralization of collagen fibrils progressively increased resistance to degradation, improving bond durability.
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Recubrimiento Dental Adhesivo , Recubrimientos Dentinarios , Recubrimientos Dentinarios/química , Glutaral/farmacología , Cementos de Resina/química , Ensayo de Materiales , Colágeno , Dentina , Resistencia a la TracciónRESUMEN
Biotin receptor (BR) is overexpressed in several human tumor cell lines and has become an important biomarker for tumor diagnosis and treatment. Therefore, much attention has been attracted in the field of developing BR-targeting agents. In clinical practice, a multifunctional platform that can be used for both diagnosis and treatment is much desirable. In this study, to improve diagnostic and therapeutic efficacy of BR-positive tumors, we developed a multifunctional platform RT-H2 to combine with the cyanine scaffold for near infrared (NIR) imaging and the radioisotope 131I for targeted radionuclide therapy (TRT). In vitro experiments showed that RT-H2 possessed favorable NIR properties and could selectively accumulate in BR-positive HeLa cells. In vivo NIR imaging of HeLa tumor-bearing mice exhibited high accumulation and long retention time (72 h) of RT-H2 in the tumor. Furthermore, RT-H2 was also employed as a carrier to develop 131I-labeled TRT agent due to its favorable properties in vivo. The radiolabeling conditions were optimized and the optimal conditions determined to be 1.2 equiv of Idogen, reaction time 4 min and room temperature, yielding the radiotracer [131I]I-RT-H2 with the radiochemical purity (RCP) of > 95% after a simple purification by a C18 column. In vitro cell experiments indicated that [131I]I-RT-H2 could specifically target Hela cells and displayed dose-dependent antitumor effect. In vivo experiments demonstrated that [131I]I-RT-H2 obviously inhibited the tumor proliferation in HeLa tumor-bearing mice within 4 weeks. All these results indicate that RT-H2 has the potential to serve as a multifunctional platform for tumor diagnosis and treatment.
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Radioisótopos de Yodo , Humanos , Animales , Ratones , Células HeLa , Línea Celular TumoralRESUMEN
BACKGROUND: There is limited longitudinal evidence supporting the association between the hypertriglyceridemic-waist (HTGW) phenotype and hyperuricemia. This study aimed to examine the longitudinal relationship between hyperuricemia and the HTGW phenotype among males and females. METHODS: A total of 5562 hyperuricemia-free participants aged 45 or over from the China Health and Retirement Longitudinal Study (mean age: 59.0) were followed for 4 years. The HTGW phenotype was defined as having elevated triglyceride levels and enlarged waist circumference (cutoffs for males: 2.0 mmol/L and 90 cm; females: 1.5 mmol/L and 85 cm). Hyperuricemia was determined by uric acid cutoffs (males: 7 mg/dl; females: 6 mg/dl. Multivariate logistic regression models were used to assess the association between the HTGW phenotype and hyperuricemia. The joint effect of the HTGW phenotype and sex on hyperuricemia was quantified, and the multiplicative interaction was assessed. RESULTS: During the four-year follow-up, 549 (9.9%) incident hyperuricemia cases were ascertained. Compared with those with normal levels of triglycerides and waist circumference, participants with the HTGW phenotype had the highest risk of hyperuricemia (OR: 2.67; 95% CI: 1.95 to 3.66), followed by an OR of 1.96 (95% CI: 1.40 to 2.74) for only higher triglyceride levels and 1.39 (95% CI: 1.03 to 1.86) for only greater waist circumference. The association between HTGW and hyperuricemia was more prominent among females (OR = 2.36; 95% CI: 1.77 to 3.15) than males (OR = 1.29; 95% CI: 0.82 to 2.04), with evidence of a multiplicative interaction (P = 0.006). CONCLUSIONS: Middle-aged and older females with the HTGW phenotype may at the highest risk of hyperuricemia. Future hyperuricemia prevention interventions should be primarily targeted for females with the HTGW phenotype.
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Cintura Hipertrigliceridémica , Masculino , Femenino , Humanos , Estudios Longitudinales , Cintura Hipertrigliceridémica/complicaciones , Fenotipo , Triglicéridos , Modelos Logísticos , Factores de Riesgo , Circunferencia de la CinturaRESUMEN
PURPOSE: Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp (AVRTSAD) and developed three EDBp-based probes, Cy5-PEG4-EDBp(Cy5-EDBp), [18F]-NOTA-PEG4-EDBp([18F]-EDBp), and [177Lu]-DOTA-PEG4-EDBp ([177Lu]-EDBp), for the surgical navigation, radionuclide imaging, and therapy of TC. METHODS: Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy. Three EDBp-based probes, Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging, and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [18F]-EDBp was evaluated in two TC patients. RESULTS: The binding affinity of EDBp to the EDB fragment protein (Kd = 14.4 ± 1.4 nM, n = 3) was approximately 336-fold greater than that of the ZD2 (Kd = 4839.7 ± 361.7 nM, n = 3). Fluorescence imaging with Cy5-EDBp facilitated the complete removal of TC tumors. [18F]-EDBp PET imaging clearly delineated TC tumors, with high tumor uptake (16.43 ± 1.008%ID/g, n = 6, at 1-h postinjection). Radiotherapy with [177Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: saline vs. EDBp vs. ABRAXANE vs. [177Lu]-EDBp = 8.00 d vs. 8.00 d vs. 11.67 d vs. 22.33 d, ***p < 0.001). Importantly, the first-in-human evaluation of [18F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety. CONCLUSION: Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging, and radionuclide therapy of TC, respectively.
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Cirugía Asistida por Computador , Neoplasias de la Tiroides , Humanos , Animales , Ratones , Fibronectinas/metabolismo , Tomografía de Emisión de Positrones , Péptidos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/terapia , Línea Celular TumoralRESUMEN
AIM: To quantify the association between subjective cognitive complaints and balance impairment in relation to the occurrence of disability. METHODS: In total, 6885 adults aged ≥45 who participated in the China Health and Retirement Longitudinal Study (CHARLS) were followed for 7 years. Subjective cognitive complaints were evaluated by self-reported memory problems. Balance impairment was tested by side-by-side stand, semi-tandem stand and full tandem stand. Disability was measured by activities of daily living (ADL) and instrumental activities of daily living (IADL). Multivariate logistic regression models were applied to test the joint effect between baseline subjective cognitive complaints and balance impairment on disability. The multiplicative interaction was examined. RESULTS: A joint effect of experiencing both subjective cognitive complaints and balance impairment was identified, showing a 1.63-fold higher risk of ADL and IADL disability than those experienced by neither of the two (odds ratio = 1.63, 95% confidence interval: 1.36-1.95). There was evidence of multiplicative interaction (P = 0.004). CONCLUSIONS: Among middle-aged and older people, the coexistence of subjective cognitive complaints and balance impairment may lead to a higher disability risk, which is much higher than the simple sum of the two individual effects. Future interventions are required to target these symptoms simultaneously to reduce the risks of disability. Geriatr Gerontol Int 2022; 22: 1025-1031.
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Actividades Cotidianas , Personas con Discapacidad , Humanos , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Estudios Longitudinales , CogniciónRESUMEN
Developing hierarchical ordered systems is challenging. Using organo-macrocycles to construct metal-organic frameworks (MOFs) and porous coordination cages (PCCs) provides an efficient way to obtain hierarchical assemblies. Macrocycles, such as crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillararenes, can be incorporated within MOFs/PCCs and they also endow the resultant composites with enhanced properties and functionalities. This review summarizes recent developments of organo-macrocycle-containing hierarchical MOFs/PCCs, emphasizing applications and structure-property relationships of these hierarchically porous materials. This review provides insights for future research on hierarchical self-assembly using macrocycles as building blocks and functional ligands to extend the applications of the composites.
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Calixarenos , Éteres Corona , Ciclodextrinas , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , PorosidadRESUMEN
Shewanella putrefaciens is a typical spoilage bacteria organism in seafood. The adhesion ability of three S. putrefaciens strains (HR-15, JR-18, HC-71) isolated from putrefied tilapia were evaluated by mucus adhesion in vitro and intestinal adhesion in vivo. The results of the spoilage of the inoculated fish fillets and spoilage of the refrigerated fish both showed that the adhesion ability of S. putrefaciens was positively correlated with the spoilage ability. High-throughput sequencing and GC-MS results showed that S. putrefaciens with high adhesion ability also significantly changed the intestinal flora of fish, causing an increase in the intestinal bacteria such as Plesionomas, Macellibacteroides, Acinetobacter, and Legionella, which then led to the increase in volatile substances such as low-grade aldehydes, alcohols, and ketones in the fish, serious fatty acid oxidation, and excitement of the fishy smell.
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BACKGROUND: Healthy aging index (HAI) could predict adverse health consequences including mortality and disability independent of age and comorbidity. We investigated the role of HAI on trajectories of disability throughout later life based on a nationally representative sample. METHODS: We examined 1733 participants aged over 60 years from the China Health and Retirement Longitudinal Study (CHARLS) followed for 7 years/4 waves repeatedly. Systolic blood pressure [SBP], cognitive function, cystatin C, peak expiratory flow [PEF], and fasting glucose were categorized using tertile or clinical reference range, and scored as 0 (healthiest), 1 (less healthy) and 2 (least healthy) respectively to further generate HAI summary scores (range 0-10). Disability was defined as the sum of impaired activities of daily living (ADL) and instrumental activities of daily living (IADL). We used linear mixed-effects model to study the association between HAI and trajectories of disability. RESULTS: A total of 10.5% of participants represented in the healthiest group and 22.5% ended up as the least healthy. After adjusting for all potential confounders, disability progression was significantly faster (ß = 0.27, 95% CI 0.11-0.42) in the least healthy group when comparing with the healthiest. CONCLUSION: Our findings suggest that HAI is associated with disability progression among adults aged over 60 years old. It might be beneficial for future interventions to specifically target older adults with high HAI scores as a means of reducing disability.
Asunto(s)
Personas con Discapacidad , Envejecimiento Saludable , Actividades Cotidianas , Anciano , China/epidemiología , Estudios de Cohortes , Evaluación de la Discapacidad , Humanos , Estudios LongitudinalesRESUMEN
OBJECTIVE: Neuroblastoma is a common extracranial solid tumor of childhood. Recently, multiple treatments have been practiced including Iodine-131-metaiodobenzylguanidine radiation (131I-MIBG) therapy. However, the outcomes of efficacy and safety vary greatly among different studies. The aim of this meta-analysis is to evaluate the efficacy and safety of 131I-MIBG in the treatment of neuroblastoma and to provide evidence and hints for clinical decision-making. METHODS: Medline, EMBASE database and the Cochrane Library were searched for relevant studies. Eligible studies utilizing 131I-MIBG in the treatment of neuroblastoma were included. The pooled outcomes (response rates, adverse events rates, survival rates) were calculated using either a random-effects model or a fixed-effects model considering of the heterogeneity. RESULTS: A total of 26 clinical trials including 883 patients were analyzed. The pooled rates of objective response, stable disease, progressive disease, and minor response of 131I-MIBG monotherapy were 39%, 31%, 22% and 15%, respectively. The pooled objective response rate of 131I-MIBG in combination with other therapies was 28%. The pooled 1-year survival and 5-year survival rates were 64% and 32%. The pooled occurrence rates of thrombocytopenia and neutropenia in MIBG monotherapy studies were 53% and 58%. In the studies of 131I-MIBG combined with other therapies, the pooled occurrence rates of thrombocytopenia and neutropenia were 79% and 78%. CONCLUSION: 131I-MIBG treatment alone or in combination of other therapies is effective on clinical outcomes in the treatment of neuroblastoma, individualized 131I-MIBG is recommended on a clinical basis.