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1.
Soft Robot ; 11(3): 494-507, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38386775

RESUMEN

The bending stiffness modulation mechanism for soft grippers has gained considerable attention to improve grasping versatility, capacity, and stability. However, lateral stability is usually ignored or hard to achieve at the same time with good bending stiffness modulation performance. Therefore, this article presents a bioinspired bidirectional stiffening soft actuator (BISA), enabling compliant and stable performance. BISA combines the air tendon actuation (ATA) and a bone-like structure (BLS). The ATA is the main actuation of the BISA, and the bending stiffness can be modulated with a maximum stiffness of about 0.7 N/mm and a maximum magnification of three times when the bending angle is 45°. Inspired by the morphological structure of the phalanx, the lateral stiffness can be modulated by changing the pulling force of the BLS. The actuator with BLSs can improve the lateral stiffness by about 3.9 times compared to the one without BLSs. The maximum lateral stiffness can reach 0.46 N/mm. And the lateral stiffness can be modulated by decoupling about 1.3 times (e.g., from 0.35 to 0.46 N/mm when the bending angle is 45°). The test results show that the influence of the rigid structures on bending is small with about 1.5 mm maximum position errors of the distal point of the actuator in different pulling forces. The advantages brought by the proposed method enable versatile four-finger grasping. The performance of this gripper is characterized and demonstrated on multiscale, multiweight, and multimodal grasping tasks.


Asunto(s)
Diseño de Equipo , Fuerza de la Mano , Fuerza de la Mano/fisiología , Humanos , Robótica/instrumentación , Fenómenos Biomecánicos/fisiología , Biomimética/instrumentación , Tendones/fisiología
2.
Microsyst Nanoeng ; 9: 43, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37033108

RESUMEN

Achieving multiband camouflage covering both visible and infrared regions is challenging due to the broad bandwidth and differentiated regulation demand in diverse regions. In this work, we propose a programmable microfluidic strategy that uses dye molecules in layered fluids to manipulate visible light- and infrared-semitransparent solvent to manipulate infrared light. With three primary fluid inputs, we achieve 64 chromaticity values and 8 emissivities from 0.42 to 0.90. In view of the wide tuning range, we demonstrate that the microfluidic film can dynamically change its surface reflectance to blend into varying backgrounds in both visible and infrared images. Moreover, we fabricate the microfluidic device in a textile form and demonstrate its ability to match exactly with the colors of natural leaves of different seasons in the full hyperspectrum range. Considering the broadband modulation and ease of operation, the programmable microfluidic strategy provides a feasible approach for smart optical surfaces in long-span optical spectra.

3.
Eur Respir J ; 61(1)2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36229050

RESUMEN

OBJECTIVES: Discovering airway gene expression alterations associated with radiological bronchiectasis may improve the understanding of the pathobiology of early-stage bronchiectasis. METHODS: Presence of radiological bronchiectasis in 173 individuals without a clinical diagnosis of bronchiectasis was evaluated. Bronchial brushings from these individuals were transcriptomically profiled and analysed. Single-cell deconvolution was performed to estimate changes in cellular landscape that may be associated with early disease progression. RESULTS: 20 participants have widespread radiological bronchiectasis (three or more lobes). Transcriptomic analysis reflects biological processes associated with bronchiectasis including decreased expression of genes involved in cell adhesion and increased expression of genes involved in inflammatory pathways (655 genes, false discovery rate <0.1, log2 fold-change >0.25). Deconvolution analysis suggests that radiological bronchiectasis is associated with an increased proportion of ciliated and deuterosomal cells, and a decreased proportion of basal cells. Gene expression patterns separated participants into three clusters: normal, intermediate and bronchiectatic. The bronchiectatic cluster was enriched by participants with more lobes of radiological bronchiectasis (p<0.0001), more symptoms (p=0.002), higher SERPINA1 mutation rates (p=0.03) and higher computed tomography derived bronchiectasis scores (p<0.0001). CONCLUSIONS: Genes involved in cell adhesion, Wnt signalling, ciliogenesis and interferon-γ pathways had altered expression in the bronchus of participants with widespread radiological bronchiectasis, possibly associated with decreased basal and increased ciliated cells. This gene expression pattern is not only highly enriched among individuals with radiological bronchiectasis, but also associated with airway-related symptoms in those without discernible radiological bronchiectasis, suggesting that it reflects a bronchiectasis-associated, but non-bronchiectasis-specific lung pathophysiological process.


Asunto(s)
Bronquiectasia , Humanos , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/genética , Bronquios/diagnóstico por imagen , Radiografía , Tomografía Computarizada por Rayos X/métodos , Expresión Génica
4.
Molecules ; 27(22)2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36431829

RESUMEN

Cysteine is one of the least abundant amino acids in proteins of many organisms, which plays a crucial role in catalysis, signal transduction, and redox regulation of gene expression. The thiol group of cysteine possesses the ability to perform nucleophilic and redox-active functions that are not feasible for other natural amino acids. Cysteine is the most common covalent amino acid residue and has been shown to react with a variety of warheads, especially Michael receptors. These unique properties have led to widespread interest in this nucleophile, leading to the development of a variety of cysteine-targeting warheads with different chemical compositions. Herein, we summarized the various covalent warheads targeting cysteine residue and their application in drug development.


Asunto(s)
Cisteína , Desarrollo de Medicamentos , Cisteína/química , Aminoácidos/química , Compuestos de Sulfhidrilo/química , Oxidación-Reducción
5.
Biomaterials ; 290: 121811, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36201948

RESUMEN

Radiotherapy (RT), through the generation of reactive oxygen species (ROS) and DNA damage to tumor cells caused by high-energy irradiation, has been a widely applied cancer treatment strategy in clinic. However, the therapeutic effect of traditional RT is restricted by the insufficient radiation energy deposition and the side effects on normal tissues. Recently, multifunctional nano-formulations and synergistic therapy has been developed as attractive strategies for used to enhancing the efficacy and safety of RT. Herein, we show that a bimetallic nanozyme (copper-modified ruthenium nanoparticles, RuCu NPs), containing the high atomic number (Z) element Ru as a novel radiosensitizer, offers an ideal solution to RT sensitization, with ultrasensitive peroxidase (POD)-like activity and catalase (CAT)-like activity. Density functional theory (DFT) calculations also clarified the optimal POD-like catalytic ratio of RuCu NPs and further revealed the mechanism of its supper catalytic activity. Under X-ray exposure, RuCu NPs coated with poly(ethylene glycol) (PEG) exhibited simultaneously improved the ROS production and relieved tumor hypoxia in the acid tumor microenvironment (TME), and demonstrated remarkable therapeutic efficacy in the MDA-MB-231 breast cancer model. Our results provide a proof-of-concept for a RT sensitization strategy, which combine the intrinsic nature of high-Z element and the advantages of nanozymes to overcome the tricky drawbacks existed in radiotherapy, and further open a new direction of exploring novel nanozyme-based strategies for tumor catalytic therapy and synergistic radiotherapy.


Asunto(s)
Nanopartículas , Neoplasias , Fármacos Sensibilizantes a Radiaciones , Humanos , Especies Reactivas de Oxígeno , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Hipoxia Tumoral , Microambiente Tumoral , Línea Celular Tumoral
6.
Sci Rep ; 12(1): 18168, 2022 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-36307504

RESUMEN

SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments have not been fully characterized using matched samples from large cohorts. Gene expression data from 793 nasal and 1673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking status (current versus former) was the only clinical factor significantly and reproducibly associated with VE gene expression. The expression of ACE2 and TMPRSS2 was higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48+ secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the gene expression data confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose, these genes are not predominantly expressed in cell populations modulated by smoking. In individuals with elevated lung cancer risk, smoking-induced VE gene expression changes in the nose likely have minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.


Asunto(s)
COVID-19 , Neoplasias Pulmonares , Humanos , SARS-CoV-2/genética , Enzima Convertidora de Angiotensina 2/genética , COVID-19/genética , Detección Precoz del Cáncer , Peptidil-Dipeptidasa A/metabolismo , Neoplasias Pulmonares/metabolismo , Bronquios/metabolismo , Fumar/efectos adversos , Fumar/genética
7.
Biomaterials ; 289: 121793, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36126545

RESUMEN

Chemoradiotherapy is a widely used treatment for patients with malignancies such as hepatocellular carcinoma (HCC). However, it remains challenging to realize safe and synergistic chemotherapy and radiation sensitization. Herein, we design a self-targeting nano-assembly (STNA) based on platinum(IV)-lactose amphiphilic prodrug for synergistic and safe chemoradiotherapy of HCC. The Pt STNA would improve the tumor accumulation due to the targeting ability of lactose to HCC cells. After receptor-mediated endocytosis, Pt STNA would release cisplatin(II) in cancer cells to form DNA-binding, thus inducing DNA damage and cell apoptosis. Meanwhile, the DNA-binding also causes cell cycle arrest in the radiation-sensitive G2/M phase by the up-regulation of phosphorylated checkpoint kinase 1 (p-Chk1) expression. Furthermore, under X-ray irradiation, Pt STNA as radiosensitizer possesses a strong X-ray attenuation ability to deposit more energy, thus elevating the level of reactive oxygen species (ROS) to amplify the cell-killing effect of radiotherapy in the G2/M phase with increased DNA damage. As a result, Pt STNA exhibits significant synergistic therapeutic effects in chemoradiotherapy with no adverse effects in vitro and in vivo. Overall, we present a novel self-targeting nano-assembly strategy based on widely used Pt drugs for synergistic chemotherapy and radiation sensitization of HCC treatment.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Profármacos , Fármacos Sensibilizantes a Radiaciones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , Quimioradioterapia , Cisplatino/uso terapéutico , ADN/uso terapéutico , Humanos , Lactosa/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Platino (Metal)/uso terapéutico , Profármacos/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo
8.
Complex Intell Systems ; 8(4): 2983-2990, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35935807

RESUMEN

Task space mapping approaches for bilateral teleoperation, namely object-centered ones, have yielded the most promising results. In this paper, we propose an invertible mapping approach to realize teleoperation through online motion mapping by taking into account the locations of objects or tools in manipulation skills. It is applied to bilateral teleoperation, with the goal of handling different object/tool/landmark locations in the user and robot workspaces while the remote objects are moving online. The proposed approach can generate trajectories in an online manner to adapt to moving objects, where impedance controllers allow the user to exploit the haptic feedback to teleoperate the robot. Teleoperation experiments of pick-and-place tasks and valve turning tasks are carried out with two 7-axis torque-controlled Panda robots. Our approach shows higher efficiency and adaptability compared with traditional mappings.

9.
Bioorg Chem ; 124: 105829, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35490582

RESUMEN

Androgen signaling pathway plays an important role in the occurrence and development of prostate cancer (PCa), and anti-androgen drugs are one of the most effective therapies for PCa. Darolutamide 4 (ODM-201) is a promising second- generation antiandrogen because of its unique chemical structure and good activity against androgen receptor (AR). Herein, the structure-activity relationship of ODM-201 was studied, and 37 analogues were synthesized. Half of them exhibited similar or better anti-AR transcriptional activity compared to ODM-201. In addition, the inhibitory activity of compound 28t against the two resistant mutants (AR-F876L and AR-T877A) was superior to that of ODM-201. This study provides a new clue for the further optimization of ODM-201 and the development of anti-CRPC drugs.


Asunto(s)
Antagonistas de Receptores Androgénicos , Neoplasias de la Próstata , Antagonistas de Andrógenos/farmacología , Antagonistas de Receptores Androgénicos/química , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/uso terapéutico , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Pirazoles/química
10.
Exp Cell Res ; 416(2): 113180, 2022 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-35489384

RESUMEN

T-cell lymphoma (TCL) is a highly heterogeneous group of invasive non-Hodgkin lymphoma with adverse prognosis and limited treatment options. The relationship between TCL and Exportin-1 (XPO1), a major nuclear export receptor, has not been established yet. We here investigated the prognostic role and therapeutic implication of XPO1 in TCL. We analyzed XPO1 expression in a cohort of 69 TCL tumors and found that XPO1 was over-expressed in 76.8% of TCL and correlated with decreased progression-free survival (PFS) and overall survival (OS). In vitro treatment of TCL cell lines with KPT-8602, the second-generation selective inhibitor of nuclear export (SINE), inhibited XPO1 expression and showed significant anti-proliferative, cell-cycle arrest and pro-apoptotic efficacy. In mechanism, KPT-8602 restored the localization of cytoplasmic FOXO3A, p27, p21, IκBα and PP2A into the nucleus, leading to AKT and NF-κB deactivation. Our data demonstrate for the first time that XPO1 could be an unfavorable prognostic factor for TCL, and provide a rationale for further investigation of the efficacy of KPT-8602 in TCL patients.


Asunto(s)
Hidrazinas , Linfoma de Células T , Transporte Activo de Núcleo Celular , Apoptosis , Línea Celular Tumoral , Humanos , Hidrazinas/farmacología , Carioferinas/genética , Carioferinas/metabolismo , Pronóstico , Receptores Citoplasmáticos y Nucleares , Proteína Exportina 1
11.
Thorax ; 77(1): 31-39, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33972452

RESUMEN

BACKGROUND: COPD is characterised by progressive lung function decline. Leveraging prior work demonstrating bronchial airway COPD-associated gene expression alterations, we sought to determine if there are alterations associated with differences in the rate of FEV1 decline. METHODS: We examined gene expression among ever smokers with and without COPD who at baseline had bronchial brushings profiled by Affymetrix microarrays and had longitudinal lung function measurements (n=134; mean follow-up=6.38±2.48 years). Gene expression profiles associated with the rate of FEV1 decline were identified by linear modelling. RESULTS: Expression differences in 171 genes were associated with rate of FEV1 decline (false discovery rate <0.05). The FEV1 decline signature was replicated in an independent dataset of bronchial biopsies from patients with COPD (n=46; p=0.018; mean follow-up=6.76±1.32 years). Genes elevated in individuals with more rapid FEV1 decline are significantly enriched among the genes altered by modulation of XBP1 in two independent datasets (Gene Set Enrichment Analysis (GSEA) p<0.05) and are enriched in mucin-related genes (GSEA p<0.05). CONCLUSION: We have identified and replicated an airway gene expression signature associated with the rate of FEV1 decline. Aspects of this signature are related to increased expression of XBP1-regulated genes, a transcription factor involved in the unfolded protein response, and genes related to mucin production. Collectively, these data suggest that molecular processes related to the rate of FEV1 decline can be detected in airway epithelium, identify a possible indicator of FEV1 decline and make it possible to detect, in an early phase, ever smokers with and without COPD most at risk of rapid FEV1 decline.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Transcriptoma , Bronquios , Volumen Espiratorio Forzado , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Pruebas de Función Respiratoria , Fumar/efectos adversos
12.
Res Sq ; 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34729557

RESUMEN

Background : SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments has not been fully characterized using matched samples from large cohorts. Results : Gene expression data from 793 nasal and 1,673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking was the only clinical factor significantly and reproducibly associated with VE gene expression. ACE2 and TMPRSS2 expression were higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48 + secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the RNA-seq confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. Conclusions : The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose these genes are not predominantly expressed in cell populations modulated by smoking. Smoking-induced VE gene expression changes in the nose likely has minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.

13.
Adv Sci (Weinh) ; 8(18): e2100964, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34258884

RESUMEN

Stem cell senescence contributes to stem cell exhaustion and drives various aging-associated disorders. However, strategies to rejuvenate senescent stem cells are limited. The present study proposes an approach based on triboelectric stimulation to rejuvenate senescent bone marrow mesenchymal stromal cells (BMSCs) by fabricating a pulsed triboelectric nanogenerator (P-TENG) that can produce stable pulsed current output unaffected by the triggered frequency. The senescence phenotypes of aged BMSCs are reversed by triboelectric stimulation at 30 µA at 1.5 Hz. Triboelectric stimulation enhances the proliferation of aged BMSCs and increases their pluripotency and differentiation capacity. Additionally, mechanistic investigations reveal that pulsed triboelectric stimulation by P-TENG rejuvenates senescent BMSCs by enhancing MDM2-dependent p53 degradation, which is demonstrated by loss-of-function studies of MDM2 and p53. Overall, this study identifies a new approach for the rejuvenation of senescent BMSCs and describes a promising therapeutic intervention for many diseases associated with aged BMSCs.


Asunto(s)
Envejecimiento/fisiología , Senescencia Celular/fisiología , Estimulación Eléctrica/métodos , Células Madre Mesenquimatosas/fisiología , Rejuvenecimiento/fisiología , Adulto , Anciano , Animales , Diferenciación Celular , Femenino , Humanos , Masculino , Modelos Animales , Osteogénesis , Ratas , Ratas Sprague-Dawley , Adulto Joven
14.
Bioact Mater ; 6(12): 4707-4716, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34095627

RESUMEN

Despite extensive use of radiotherapy in nasopharyngeal carcinoma (NPC) treatment because of its high radiosensitivity, there have been huge challenges in further improving therapeutic effect, meanwhile obviously reducing radiation damage. To this end, synergistic chemoradiotherapy has emerged as a potential strategy for highly effective NPC therapy. Here, we developed RGD-targeted platinum-based nanoparticles (RGD-PtNPs, denoted as RPNs) to achieve targeted chemoradiotherapy for NPC. Such nanoparticles consist of an RGD-conjugated shell and a cis-platinum (CDDP) crosslinking core. Taking advantage of RGD, the RPNs may effectively accumulate in tumor, penetrate into tumor tissues and be taken by cancer cells, giving rise to a high delivery efficiency of CDDP. When they are fully enriched in tumor sites, the CDDP loaded RPNs can act as radiotherapy sensitizer and chemotherapy agents. By means of X-ray-promoted tumor cell uptake of nanoparticle and CDDP-induced cell cycle arrest in radiation-sensitive G2/M phases, RPNs may offer remarkable therapeutic outcome in the synergistic chemoradiotherapy for NPC.

15.
ChemMedChem ; 16(13): 2021-2033, 2021 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-33554455

RESUMEN

The androgen receptor (AR) plays a crucial role in the occurrence and development of prostate cancer (PCa), and its signaling pathway remains active in castration-resistant prostate cancer (CRPC) patients. The resistance against antiandrogen drugs in current clinical use is a major challenge for the treatment of PCa, and thus the development of new generations of antiandrogens is under high demand. Recently, strategies for downregulating the AR have attracted significant attention, given its potential in the discovery and development of new antiandrogens, including G-quadruplex stabilizers, ROR-γ inhibitors, AR-targeting proteolysis targeting chimeras (PROTACs), and other selective AR degraders (SARDs), which are able to overcome current resistance mechanisms such as acquired AR mutations, the expression of AR variable splices, or overexpression of AR. This review summarizes the various strategies for downregulating the AR protein, at either the mRNA or protein level, thus providing new ideas for the development of promising antiandrogen drugs.


Asunto(s)
Antagonistas de Andrógenos/farmacología , Regulación hacia Abajo/efectos de los fármacos , Desarrollo de Medicamentos , Neoplasias de la Próstata/tratamiento farmacológico , Receptores Androgénicos/metabolismo , Antagonistas de Andrógenos/síntesis química , Antagonistas de Andrógenos/química , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Estructura Molecular , Neoplasias de la Próstata/metabolismo , Relación Estructura-Actividad
16.
Chest ; 159(2): 549-563, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32946850

RESUMEN

BACKGROUND: Chronic tobacco smoke exposure results in a broad range of lung pathologies including emphysema, airway disease and parenchymal fibrosis as well as a multitude of extra-pulmonary comorbidities. Prior work using CT imaging has identified several clinically relevant subgroups of smoking related lung disease, but these investigations have generally lacked organ specific molecular correlates. RESEARCH QUESTION: Can CT imaging be used to identify clinical phenotypes of smoking related lung disease that have specific bronchial epithelial gene expression patterns to better understand disease pathogenesis? STUDY DESIGN AND METHODS: Using K-means clustering, we clustered participants from the COPDGene study (n = 5,273) based on CT imaging characteristics and then evaluated their clinical phenotypes. These clusters were replicated in the Detection of Early Lung Cancer Among Military Personnel (DECAMP) cohort (n = 360), and were further characterized using bronchial epithelial gene expression. RESULTS: Three clusters (preserved, interstitial predominant and emphysema predominant) were identified. Compared to the preserved cluster, the interstitial and emphysema clusters had worse lung function, exercise capacity and quality of life. In longitudinal follow-up, individuals from the emphysema group had greater declines in exercise capacity and lung function, more emphysema, more exacerbations, and higher mortality. Similarly, genes involved in inflammatory pathways (tumor necrosis factor-α, interferon-ß) are more highly expressed in bronchial epithelial cells from individuals in the emphysema cluster, while genes associated with T-cell related biology are decreased in these samples. Samples from individuals in the interstitial cluster generally had intermediate levels of expression of these genes. INTERPRETATION: Using quantitative CT imaging, we identified three groups of individuals in older ever-smokers that replicate in two cohorts. Airway gene expression differences between the three groups suggests increased levels of inflammation in the most severe clinical phenotype, possibly mediated by the tumor necrosis factor-α and interferon-ß pathways. CLINICAL TRIAL REGISTRATION: COPDGene (NCT00608764), DECAMP-1 (NCT01785342), DECAMP-2 (NCT02504697).


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Fumar/efectos adversos , Tomografía Computarizada por Rayos X , Centros Médicos Académicos , Anciano , Femenino , Hospitales de Veteranos , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fenotipo , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/genética , Estados Unidos/epidemiología
17.
ACS Appl Bio Mater ; 4(2): 1066-1076, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-35014468

RESUMEN

Multifunctional magnetic nanoagents (MMNs) have drawn increasing attention in cancer precision therapy, attributed to their good biocompatibility and the potential applications for multimodal imaging and multidisciplinary therapy. The noble metal or isotopes contained in MMNs could not only perform superparamagnetism, providing an outstanding magnetic targeting property for drug delivery, but also endow the MMNs with a magnetocaloric effect, photothermal performance, and radiotherapy sensitization, arriving at a multimode combination therapy for cancer. Also, the composite component can endow MMNs with various imaging performance, such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT), thereby achieving accurate image-guided therapy for cancer. However, the joint function of MMNs is closely correlated with their functional nanocomponents and nanostructures. In this article, we will systematically discuss the design, synthesis, and structure optimization of MMNs, as well as their potential in multimodal diagnosis and therapy, scientifically providing an integrated diagnosis and treatment of nanomedicine for the future cancer therapy.


Asunto(s)
Antineoplásicos/uso terapéutico , Medios de Contraste/uso terapéutico , Nanopartículas de Magnetita/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Línea Celular Tumoral , Terapia Combinada , Medios de Contraste/química , Humanos , Hipotermia Inducida , Nanopartículas de Magnetita/química , Imagen Multimodal , Nanomedicina Teranóstica
18.
Sensors (Basel) ; 20(17)2020 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-32878145

RESUMEN

Noise appears in images captured by real cameras. This paper studies the influence of noise on monocular feature-based visual Simultaneous Localization and Mapping (SLAM). First, an open-source synthetic dataset with different noise levels is introduced in this paper. Then the images in the dataset are denoised using the Fast and Flexible Denoising convolutional neural Network (FFDNet); the matching performances of Scale Invariant Feature Transform (SIFT), Speeded Up Robust Features (SURF) and Oriented FAST and Rotated BRIEF (ORB) which are commonly used in feature-based SLAM are analyzed in comparison and the results show that ORB has a higher correct matching rate than that of SIFT and SURF, the denoised images have a higher correct matching rate than noisy images. Next, the Absolute Trajectory Error (ATE) of noisy and denoised sequences are evaluated on ORB-SLAM2 and the results show that the denoised sequences perform better than the noisy sequences at any noise level. Finally, the completely clean sequence in the dataset and the sequences in the KITTI dataset are denoised and compared with the original sequence through comprehensive experiments. For the clean sequence, the Root-Mean-Square Error (RMSE) of ATE after denoising has decreased by 16.75%; for KITTI sequences, 7 out of 10 sequences have lower RMSE than the original sequences. The results show that the denoised image can achieve higher accuracy in the monocular feature-based visual SLAM under certain conditions.

19.
Front Neurorobot ; 14: 13, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32161531

RESUMEN

This paper focuses on the design, modeling, and control of a novel remote actuation, including a compact rotary series elastic actuator (SEA) and Bowden cable. This kind of remote actuation is used for an upper limb rehabilitation robot (ULRR) with four powered degrees of freedom (DOFs). The SEA mainly consists of a DC motor with planetary gearheads, inner/outer sleeves, and eight linearly translational springs. The key innovations include (1) an encoder for direct spring displacement measurement, which can be used to calculate the output torque of SEA equivalently, (2) the embedded springs can absorb the negative impact of backlash on SEA control performance, (3) and the Bowden cable enables long-distance actuation and reduces the bulky structure on the robotic joint. In modeling of this actuation, the SEA's stiffness coefficient, the dynamics of the SEA, and the force transmission of the Bowden cable are considered for computing the inputs on each powered joint of the robot. Then, both torque and impedance controllers consisting of proportional-derivative (PD) feedback, disturbance observer (DOB), and feedforward compensation terms are developed. Simulation and experimental results verify the performance of these controllers. The preliminary results show that this new kind of actuation can not only implement stable and friendly actuation over a long distance but also be customized to meet the requirements of other robotic system design.

20.
Front Neurorobot ; 13: 35, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31258472

RESUMEN

Variable Stiffness Actuators (VSAs) have been introduced to develop new-generation compliant robots. However, the control of VSAs is still challenging because of model perturbations such as parametric uncertainties and external disturbances. This paper proposed a non-linear disturbance observer (NDOB)-based composite control approach to control both stiffness and position of VSAs under model perturbations. Compared with existing non-linear control approaches for VSAs, the distinctive features of the proposed approach include: (1) A novel modeling method is applied to analysis the VSA dynamics under complex perturbations produced by parameter uncertainties, external disturbances, and flexible deflection; (2) A novel composite controller integrated feedback linearization with NDOB is developed to increase tracking accuracy and robustness against uncertainties. Both simulations and experiments have verified the effectiveness of the proposed method on VSAs.

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