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1.
Sensors (Basel) ; 24(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38732782

RESUMO

In robot-assisted microsurgery (RAMS), surgeons often face the challenge of operating with minimal feedback, particularly lacking in haptic feedback. However, most traditional desktop haptic devices have restricted operational areas and limited dexterity. This report describes a novel, lightweight, and low-budget wearable haptic controller for teleoperated microsurgical robotic systems. We designed a wearable haptic interface entirely made using off-the-shelf material-PolyJet Photopolymer, fabricated using liquid and solid hybrid 3D co-printing technology. This interface was designed to resemble human soft tissues and can be wrapped around the fingertips, offering direct contact feedback to the operator. We also demonstrated that the device can be easily integrated with our motion tracking system for remote microsurgery. Two motion tracking methods, marker-based and marker-less, were compared in trajectory-tracking experiments at different depths to find the most effective motion tracking method for our RAMS system. The results indicate that within the 4 to 8 cm tracking range, the marker-based method achieved exceptional detection rates. Furthermore, the performance of three fusion algorithms was compared to establish the unscented Kalman filter as the most accurate and reliable. The effectiveness of the wearable haptic controller was evaluated through user studies focusing on the usefulness of haptic feedback. The results revealed that haptic feedback significantly enhances depth perception for operators during teleoperated RAMS.


Assuntos
Microcirurgia , Procedimentos Cirúrgicos Robóticos , Dispositivos Eletrônicos Vestíveis , Humanos , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Microcirurgia/instrumentação , Algoritmos , Robótica/instrumentação , Desenho de Equipamento , Impressão Tridimensional
2.
Arch Toxicol ; 98(6): 1919-1935, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38584193

RESUMO

Human liver-derived metabolically competent HepaRG cells have been successfully employed in both two-dimensional (2D) and 3D spheroid formats for performing the comet assay and micronucleus (MN) assay. In the present study, we have investigated expanding the genotoxicity endpoints evaluated in HepaRG cells by detecting mutagenesis using two error-corrected next generation sequencing (ecNGS) technologies, Duplex Sequencing (DS) and High-Fidelity (HiFi) Sequencing. Both HepaRG 2D cells and 3D spheroids were exposed for 72 h to N-nitrosodimethylamine (NDMA), followed by an additional incubation for the fixation of induced mutations. NDMA-induced DNA damage, chromosomal damage, and mutagenesis were determined using the comet assay, MN assay, and ecNGS, respectively. The 72-h treatment with NDMA resulted in concentration-dependent increases in cytotoxicity, DNA damage, MN formation, and mutation frequency in both 2D and 3D cultures, with greater responses observed in the 3D spheroids compared to 2D cells. The mutational spectrum analysis showed that NDMA induced predominantly A:T → G:C transitions, along with a lower frequency of G:C → A:T transitions, and exhibited a different trinucleotide signature relative to the negative control. These results demonstrate that the HepaRG 2D cells and 3D spheroid models can be used for mutagenesis assessment using both DS and HiFi Sequencing, with the caveat that severe cytotoxic concentrations should be avoided when conducting DS. With further validation, the HepaRG 2D/3D system may become a powerful human-based metabolically competent platform for genotoxicity testing.


Assuntos
Ensaio Cometa , Dano ao DNA , Dimetilnitrosamina , Sequenciamento de Nucleotídeos em Larga Escala , Testes para Micronúcleos , Mutagênicos , Humanos , Dimetilnitrosamina/toxicidade , Ensaio Cometa/métodos , Testes para Micronúcleos/métodos , Mutagênicos/toxicidade , Dano ao DNA/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Técnicas de Cultura de Células , Linhagem Celular , Hepatócitos/efeitos dos fármacos , Mutagênese/efeitos dos fármacos , Mutação , Relação Dose-Resposta a Droga
3.
Artigo em Inglês | MEDLINE | ID: mdl-38566478

RESUMO

There has been growing interest in the use of human-derived metabolically competent cells for genotoxicity testing. The HepaRG cell line is considered one of the most promising cell models because it is TP53-proficient and retains many characteristics of primary human hepatocytes. In recent years, HepaRG cells, cultured in both a traditional two-dimensional (2D) format and as more advanced in-vivo-like 3D spheroids, have been employed in assays that measure different types of genetic toxicity endpoints, including DNA damage, mutations, and chromosomal damage. This review summarizes published studies that have used HepaRG cells for genotoxicity assessment, including cell model evaluation studies and risk assessment for various compounds. Both 2D and 3D HepaRG models can be adapted to several high-throughput genotoxicity assays, generating a large number of data points that facilitate quantitative benchmark concentration modeling. With further validation, HepaRG cells could serve as a unique, human-based new alternative methodology for in vitro genotoxicity testing.

5.
J Gynecol Oncol ; 35(3): e81, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522951

RESUMO

BACKGROUND: Several risk factors have been identified that compromise the treatment outcome in patients with early-to-mid-stage cervical cancer (CC) who are primarily treated with radical surgery. However, there is no report on the impact of intraoperative frozen pathology examination of vaginal margins on the prognosis of patients with CC. This study aimed to conduct a randomized controlled trial (RCT) to determine whether selective vaginal resection can reduce the incidence of operative complications and the risk of postoperative radiotherapy. The impact of the length of the vagina removed in radical hysterectomy (RH) on prognosis and quality of life (QoL) for IB2-IIA2 CC patients will be investigated. METHODS: A multicenter, non-inferiority, RCT at 7 institutions in China is designed to investigate the effect of intraoperative frozen pathology exam of vaginal margin in RH on the survival outcomes for patients with IB2-IIA2 CC. Eligible patients aged 18-70 years will be randomly assigned online by one-to-one random allocation to receive intraoperative frozen pathology exam of vaginal margin or not. If frozen pathology indicates positive margin, continue resection of 1 centimeter of vaginal tissue until negative margin is achieved. The primary end point is 2-year disease-free survival (DFS). Adverse events (AEs) caused by further vagina resection, 5-year DFS, 2-year overall survival (OS), 5-year OS and AEs caused by radiotherapy and QoL are secondary end points. A total of 310 patients will be enrolled from 7 tertiary hospitals in China within 3-year period and followed up for 5 years. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2000035668.


Assuntos
Secções Congeladas , Histerectomia , Margens de Excisão , Qualidade de Vida , Neoplasias do Colo do Útero , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Intervalo Livre de Doença , Histerectomia/métodos , Estadiamento de Neoplasias , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Vagina/patologia , Vagina/cirurgia , Estudos Multicêntricos como Assunto
6.
FASEB J ; 38(6): e23557, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38498343

RESUMO

Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for atherosclerosis development. Circular RNA (circRNA) is a specific non-coding RNA that is produced as a closed-loop structure in mammals, and its specific expression pattern is closely related to its cell type and tissue. To clarify the roles of circTLK1 in VSMC phenotypic switching, we performed qRT-PCR, immunoblotting, and immunostaining. qRT-PCR revealed that circTLK1 was upregulated in both mouse models of atherosclerosis in vivo and PDGF (platelet-derived growth factor)-BB-induced VSMCs in vitro. Furthermore, the overexpression of circTLK1 promoted PDGF-BB-induced VSMC phenotypic switching. Conversely, experiments performed in vivo demonstrate that the knockdown of SMC-specific circTLK1 led to a reduction in the development of atherosclerosis. The relationship between circTLK1 and miR-513a-3p and Krüppel-like factor 4 (KLF4) was detected by RNA immunoprecipitation (RIP), luciferase reporter assay, RNA pull-down, and RNA fluorescence in situ hybridization (RNA FISH). Mechanistically, circTLK1 acted as a sponge for miR-513a-3p, leading to the upregulation of KLF4, a key transcription factor for phenotypic switching. Targeting the circTLK1/miR-513a-3p/KLF4 axis may provide a potential therapeutic strategy for atherosclerosis.


Assuntos
Aterosclerose , MicroRNAs , Camundongos , Animais , Músculo Liso Vascular/metabolismo , Hibridização in Situ Fluorescente , Aterosclerose/genética , Aterosclerose/metabolismo , Becaplermina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Miócitos de Músculo Liso/metabolismo , Movimento Celular/genética , Mamíferos/metabolismo
7.
Nature ; 627(8002): 80-87, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418888

RESUMO

Integrated microwave photonics (MWP) is an intriguing technology for the generation, transmission and manipulation of microwave signals in chip-scale optical systems1,2. In particular, ultrafast processing of analogue signals in the optical domain with high fidelity and low latency could enable a variety of applications such as MWP filters3-5, microwave signal processing6-9 and image recognition10,11. An ideal integrated MWP processing platform should have both an efficient and high-speed electro-optic modulation block to faithfully perform microwave-optic conversion at low power and also a low-loss functional photonic network to implement various signal-processing tasks. Moreover, large-scale, low-cost manufacturability is required to monolithically integrate the two building blocks on the same chip. Here we demonstrate such an integrated MWP processing engine based on a 4 inch wafer-scale thin-film lithium niobate platform. It can perform multipurpose tasks with processing bandwidths of up to 67 GHz at complementary metal-oxide-semiconductor (CMOS)-compatible voltages. We achieve ultrafast analogue computation, namely temporal integration and differentiation, at sampling rates of up to 256 giga samples per second, and deploy these functions to showcase three proof-of-concept applications: solving ordinary differential equations, generating ultra-wideband signals and detecting edges in images. We further leverage the image edge detector to realize a photonic-assisted image segmentation model that can effectively outline the boundaries of melanoma lesion in medical diagnostic images. Our ultrafast lithium niobate MWP engine could provide compact, low-latency and cost-effective solutions for future wireless communications, high-resolution radar and photonic artificial intelligence.


Assuntos
Micro-Ondas , Nióbio , Óptica e Fotônica , Óxidos , Fótons , Inteligência Artificial , Diagnóstico por Imagem/instrumentação , Diagnóstico por Imagem/métodos , Melanoma/diagnóstico por imagem , Melanoma/patologia , Óptica e Fotônica/instrumentação , Óptica e Fotônica/métodos , Radar , Tecnologia sem Fio , Humanos
8.
Dalton Trans ; 53(10): 4772-4780, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38363173

RESUMO

Controlled self-assembly of predetermined multi-nuclear lanthanide organic polyhedra (LOPs) still presents a challenge, primarily due to the unpredictable coordination numbers and labile coordination geometries of lanthanide ions. In this study, through introducing triazole-based chelates to increase the chelating angle of C2-symmetric linear ligands and stabilize the coordination geometry of Eu(III) centers, M4L6-type (M = EuIII, L = ligand) tetrahedra were efficiently synthesized, especially a biphenyl-bridged ligand which is well known to form M2L3-type helicates. A series of LOPs were formed and characterized by high-resolution electrospray ionization time-of-flight mass spectroscopy (ESI-TOF-MS) and X-ray crystallography. Moreover, the europium complexes exhibit bright emission (luminescence quantum yield up to 42.4%) and circularly polarized luminescence properties (|glum| up to 4.5 × 10-2). This study provides a feasible strategy for constructing multi-nuclear luminescent LOPs towards potential applications.

9.
J Med Virol ; 96(1): e29380, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38235849

RESUMO

Hepatic venous pressure gradient (HVPG) is the gold standard for evaluating clinically significant portal hypertension (CSPH). However, reliable noninvasive methods are limited. Our study aims to investigate the diagnostic value of serum Golgi protein 73 (GP73) for CSPH in patients with compensated cirrhosis. The study enrolled 262 consecutive patients with compensated cirrhosis from three centers in China from February 2021 to September 2023, who underwent both serum GP73 tests and HVPG measurements. CSPH was defined as HVPG ≥ 10 mmHg. Diagnostic accuracy was evaluated using the areas under the receiver operating characteristic curve (AUC). The prevalence of CSPH was 56.9% (n = 149). There were significant differences between the CSPH and non-CSPH groups in the median serum GP73 level (126.8 vs. 73.1 ng/mL, p < 0.001). GP73 level showed a significant positive linear correlation with HVPG (r = 0.459, p < 0.001). The AUC for the diagnosis of CSPH using serum GP73 alone was 0.75 (95% confidence interval [CI] 0.68-0.81). Multivariate logistic regression analysis determined that the levels of GP73, platelets and international normalized ratio were independently associated with CSPH. The combination of these three markers was termed "IP73" score with an AUC value of 0.85 (95% CI 0.80-0.89) for CSPH. Using 0 as a cut-off value, the specificity and sensitivity of IP73 score were 77.9% and 81.9%, respectively. The IP73 score offers a novel, simple and noninvasive method of assessing CSPH in patients with compensated cirrhosis. A cut-off value of the IP73 score at 0 can distinguish patients with or without CSPH.


Assuntos
Técnicas de Imagem por Elasticidade , Hipertensão Portal , Humanos , Biomarcadores , Hipertensão Portal/complicações , Hipertensão Portal/diagnóstico , Fígado , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Curva ROC , Fatores de Tempo
10.
IEEE Trans Med Imaging ; 43(5): 1816-1827, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38165794

RESUMO

The computer-aided diagnosis (CAD) for rare diseases using medical imaging poses a significant challenge due to the requirement of large volumes of labeled training data, which is particularly difficult to collect for rare diseases. Although Few-shot learning (FSL) methods have been developed for this task, these methods focus solely on rare disease diagnosis, failing to preserve the performance in common disease diagnosis. To address this issue, we propose the Disentangle then Calibrate with Gradient Guidance (DCGG) framework under the setting of generalized few-shot learning, i.e., using one model to diagnose both common and rare diseases. The DCGG framework consists of a network backbone, a gradient-guided network disentanglement (GND) module, and a gradient-induced feature calibration (GFC) module. The GND module disentangles the network into a disease-shared component and a disease-specific component based on gradient guidance, and devises independent optimization strategies for both components, respectively, when learning from rare diseases. The GFC module transfers only the disease-shared channels of common-disease features to rare diseases, and incorporates the optimal transport theory to identify the best transport scheme based on the semantic relationship among different diseases. Based on the best transport scheme, the GFC module calibrates the distribution of rare-disease features at the disease-shared channels, deriving more informative rare-disease features for better diagnosis. The proposed DCGG framework has been evaluated on three public medical image classification datasets. Our results suggest that the DCGG framework achieves state-of-the-art performance in diagnosing both common and rare diseases.


Assuntos
Algoritmos , Interpretação de Imagem Assistida por Computador , Doenças Raras , Humanos , Doenças Raras/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Bases de Dados Factuais , Imageamento por Ressonância Magnética/métodos , Aprendizado de Máquina
11.
Altern Lab Anim ; 52(1): 42-59, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38055860

RESUMO

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to develop recommendations for optimal scientific and technical approaches for conducting in vitro assays to assess potential toxicity within and across traditional tobacco and various tobacco and nicotine next-generation products (NGPs), including Heated Tobacco Products (HTPs) and Electronic Nicotine Delivery Systems (ENDS). This report was developed by a working group composed of attendees of the seventh IIVS workshop, 'Approaches and recommendations for conducting the mouse lymphoma gene mutation assay (MLA) and introduction to in vitro disease models', which was held virtually on 21-23 June 2022. This publication provides a background overview of the MLA, and includes the description of assay conduct and data interpretation, key challenges and recommended best practices for evaluating tobacco and nicotine products, with a focus on the evaluation of NGPs, and a summary of how the assay has been used to evaluate and compare tobacco and nicotine products.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Animais , Camundongos , Técnicas In Vitro , Nicotina , Projetos de Pesquisa , Produtos do Tabaco/toxicidade
12.
Neoplasma ; 70(5): 610-620, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38053378

RESUMO

Minichromosome maintenance complex component 2 (MCM2) is a member of the MCM family and is involved in various cancers. However, the role of MCM2 in endometrial cancer (EC) remains unclear. In this study, we aim to determine the biological function of MCM2 in EC cells and identify the potential underlying mechanisms. MCM2 expression and prognostic significance were analyzed in TCGA-UCEC datasets. Combining bioinformatics analyses and experiments, stemness-related molecules and phenotypes were examined to evaluate the impact of MCM2 on stemness in EC cells. The major findings of these analyses are as follows: 1) MCM2 is expressed at higher levels in EC tissues than in normal endometrial tissues. High expression of MCM2 is related to the characteristics of poorly differentiated EC. High MCM2 expression is correlated with poor overall survival in EC patients; 2) MCM2 knockdown was found to decrease sphere formation ability, downregulate the expression of stemness-related molecules, and reduce the proportion of CD133+ cells, while MCM2 overexpression elicited the opposite effect in EC cells; 3) MCM2-mediated stemness features are dependent on the activation of Akt/ß-catenin signaling pathways; and 4) MCM2 knockdown increases cisplatin sensitivity in EC cells. MCM2 regulates stemness by regulating the Akt/ß-catenin signaling pathway in EC cells.


Assuntos
Neoplasias do Endométrio , Proteínas Proto-Oncogênicas c-akt , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Linhagem Celular Tumoral , Neoplasias do Endométrio/genética , Proliferação de Células
13.
J Orthop Surg Res ; 18(1): 831, 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925428

RESUMO

BACKGROUND: Investigate the AMPK (protein kinase AMP-activated catalytic subunit alpha 1)/YAP (Yes1 associated transcriptional regulator)/NLRP3 (NLR family pyrin domain containing 3) signaling pathway's role in ankylosing spondylitis (AS) development using public database analysis, in vitro and in vivo experiments. METHODS: Retrieve AS dataset, analyze differential gene expression in R, conduct functional enrichment analysis, collect 30 AS patient and 30 normal control samples, and construct a mouse model. ELISA, IP, and knockdown experiments were performed to detect expression changes. RESULTS: NLRP3 was identified as a significant AS-related gene. Caspase-1, IL-1ß, IL-17A, IL-18, IL-23, YAP, and NLRP3 were upregulated in AS patients. Overexpressing AMPK inhibited YAP's blockade on NLRP3 ubiquitination, reducing ossification in fibroblasts. Inhibiting AMPK exacerbated AS symptoms in AS mice. CONCLUSION: AMPK may suppress YAP expression, leading to NLRP3 inflammasome inhibition and AS alleviation.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Espondilite Anquilosante , Humanos , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Espondilite Anquilosante/genética , Inflamassomos/metabolismo , Transdução de Sinais/genética , Interleucina-1beta/metabolismo
14.
Toxicol Sci ; 197(1): 69-78, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-37788138

RESUMO

Lapatinib, an oral tyrosine kinase inhibitor used as a first-line treatment for HER2-positive breast cancer, has been reported to be associated with hepatotoxicity; however, the underlying mechanisms remain unclear. In this study, we report that lapatinib causes cytotoxicity in multiple types of hepatic cells, including primary human hepatocytes, HepaRG cells, and HepG2 cells. A 24-h treatment with lapatinib induced cell cycle disturbances, apoptosis, and DNA damage, and decreased the protein levels of topoisomerase in HepG2 cells. We investigated the role of cytochrome P450 (CYP)-mediated metabolism in lapatinib-induced cytotoxicity using our previously established HepG2 cell lines, which express each of 14 CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). We demonstrate that lapatinib is metabolized by CYP1A1, 3A4, 3A5, and 3A7. Among these, lapatinib-induced cytotoxicity and DNA damage were attenuated in cells overexpressing CYP3A5 or 3A7. Additionally, we measured the production of three primary metabolites of lapatinib (O-dealkylated lapatinib, N-dealkylated lapatinib, and N-hydroxy lapatinib) in CYP1A1-, 3A4-, 3A5-, and 3A7-overexpressing HepG2 cells. We compared the cytotoxicity of lapatinib and its 3 metabolites in primary human hepatocytes, HepaRG cells, and HepG2 cells and demonstrated that N-dealkylated lapatinib is more toxic than the parent drug and the other metabolites. Taken together, our results indicate that lapatinib-induced cytotoxicity involves multiple mechanisms, such as apoptosis and DNA damage; that N-dealkylated lapatinib is a toxic metabolite contributing to the toxic effect of lapatinib; and that CYP3A5- and 3A7-mediated metabolism plays a role in attenuating the cytotoxicity of lapatinib.


Assuntos
Citocromo P-450 CYP1A1 , Citocromo P-450 CYP3A , Humanos , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Lapatinib/toxicidade , Lapatinib/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Fígado/metabolismo , Microssomos Hepáticos/metabolismo
16.
Mol Pharm ; 20(11): 5440-5453, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37819754

RESUMO

We investigated the therapeutic efficacy of umbilical cord blood (UCB)-derived M1 macrophage exosomes loaded with cisplatin (CIS) in ovarian cancer and platinum resistance. M1 macrophages were purified by using CD14 magnetic beads and characterized by flow cytometry. Our analyses included morphology, particle size, particle concentration, potential, drug loading capacity, counts of entry into cells, antitumor effect in vivo, and the ability to reverse drug resistance. A2780, SKOV3, and A2780/DDP, SKOV3/DDP ovarian cancer cells (CIS-sensitive and CIS-resistant cell lines, respectively) were treated with CIS or CIS-loaded M1 macrophage exosomes (M1exoCISs). The encapsulation efficiency of CIS loading into M1 macrophage exosomes was approximately 30%. In vitro, M1exoCIS treatment reduced the CIS IC50 values of both A2780, SKOV3, and A2780/DDP, SKOV3/DDP cells. We evaluated the effect of M1exoCIS on tumor growth using a mouse ovarian cancer subcutaneous transplantation tumor model inoculated with A2780/DDP cells. M1exoCIS was observed in the liver, spleen, and tumor sites 24 h posttreatment; the fluorescence intensity of M1exoCIS is higher than that of CIS. After 7 days, M1exoCIS significantly inhibited the growth of subcutaneously transplanted tumors compared with CIS alone and had a longer survival time. Moreover, the toxicity test shows that M1exoCIS has less hepatorenal toxicity than CIS. To investigate the mechanism of M1exoCIS targeting, homing, and reversing drug resistance, we performed RT-PCR, Western blotting, and Proteome Profiler Human Receptor Array analyses. We found that A2780 and A2780/DDP cells expressed the integrin ß1/CD29 receptor, while M1 exosomes expressed integrin ß1/CD29. In addition, M1exos carries long noncoding RNA H19, implicated in PTEN protein upregulation and miR-130a and Pgp gene downregulation, leading to the reversal of CIS drug resistance. Therefore, UCB-derived M1exoCIS target tumor sites of ovarian cancer in vivo and can be used to increase the CIS sensitivity and cytotoxicity.


Assuntos
Antineoplásicos , Exossomos , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Linhagem Celular Tumoral , Exossomos/metabolismo , Sangue Fetal/metabolismo , Integrina beta1/farmacologia , Integrina beta1/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células
17.
J Am Chem Soc ; 145(42): 23121-23130, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37844009

RESUMO

Upconversion (UC) is a fascinating anti-Stokes-like optical process with promising applications in diverse fields. However, known UC mechanisms are mainly based on direct energy transfer between metal ions, which constrains the designability and tunability of the structures and properties. Here, we synthesize two types of Ln8L12-type (Ln for lanthanide ion; L for organic ligand L1 or L2R/S) lanthanide-organic complexes with assembly induced excited-multimer states. The Yb8(L2R/S)12 assembly exhibits upconverted multimer green fluorescence under 980 nm excitation through a cooperative sensitization process. Furthermore, upconverted red emission from Eu3+ on the heterometallic (Yb/Eu)8L12 assemblies is also realized via excited-multimer mediated energy relay. Our findings demonstrate a new strategy for designing UC materials, which is crucial for exploiting photofunctions of multicomponent lanthanide-organic complexes.

18.
IEEE Trans Pattern Anal Mach Intell ; 45(8): 9846-9861, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37819830

RESUMO

This paper studies a practical domain adaptive (DA) semantic segmentation problem where only pseudo-labeled target data is accessible through a black-box model. Due to the domain gap and label shift between two domains, pseudo-labeled target data contains mixed closed-set and open-set label noises. In this paper, we propose a simplex noise transition matrix (SimT) to model the mixed noise distributions in DA semantic segmentation, and leverage SimT to handle open-set label noise and enable novel target recognition. When handling open-set noises, we formulate the problem as estimation of SimT. By exploiting computational geometry analysis and properties of segmentation, we design four complementary regularizers, i.e., volume regularization, anchor guidance, convex guarantee, and semantic constraint, to approximate the true SimT. Specifically, volume regularization minimizes the volume of simplex formed by rows of the non-square SimT, ensuring outputs of model to fit into the ground truth label distribution. To compensate for the lack of open-set knowledge, anchor guidance, convex guarantee, and semantic constraint are devised to enable the modeling of open-set noise distribution. The estimated SimT is utilized to correct noise issues in pseudo labels and promote the generalization ability of segmentation model on target domain data. In the task of novel target recognition, we first propose closed-to-open label correction (C2OLC) to explicitly derive the supervision signal for open-set classes by exploiting the estimated SimT, and then advance a semantic relation (SR) loss that harnesses the inter-class relation to facilitate the open-set class sample recognition in target domain. Extensive experimental results demonstrate that the proposed SimT can be flexibly plugged into existing DA methods to boost both closed-set and open-set class performance.

19.
Med Sci Monit ; 29: e940133, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37653724

RESUMO

BACKGROUND Understanding the blood supply pattern of cesarean scar pregnancy (CSP) can effectively help to determine the best choice of treatment. The aim of this study was to investigate the blood supply pattern and outcomes of patients with CSP through digital subtraction angiography (DSA) imaging. MATERIAL AND METHODS This was a retrospective cohort study. Patients were divided into 2 groups according to the type of CSP. The DSA images of these patients were reviewed, including the type of blood supply, dominant vessel, and collateral blood supply to the gestational sac. The clinical outcomes were analyzed between the 2 groups. RESULTS Thirty-seven patients with type I and 29 patients with type II CSP were enrolled in this study. Type II CSP showed a higher proportion of rich blood supply than type I (44.83% vs 29.72%, P>0.05). Compared with type II CSP, type I CSP tended to have bilateral dominant blood supply predominance (67.57% vs 41.38%, P<0.05). The incidence of collateral blood supply was 5.41% in the type I CSP group and 31.03% in the type II CSP group (P<0.05). In the type II CSP group, multiple collateral blood vessels were found in 4 patients. The superior vesicle artery was the most common source of collateral blood supply in both groups. Two patients with type II CSP suffered massive bleeding during surgery after uterine artery embolization (UAE). None of the patients received a hysterectomy. CONCLUSIONS UAE is safe and effective for both types of CSP. The blood supply pattern is more complex and abnormal in type II CSP. More attention should be paid to the collateral blood supply to achieve complete embolization during the UAE procedure in the case of type II CSP.


Assuntos
Cicatriz , Embolização da Artéria Uterina , Feminino , Gravidez , Humanos , Angiografia Digital , Cicatriz/diagnóstico por imagem , Estudos Retrospectivos , Artérias
20.
ACS Appl Mater Interfaces ; 15(39): 46379-46387, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37738229

RESUMO

With the rapid development of intelligent electronic devices, conductive fibers have become very critical to signal transmission devices. However, metal-based rigid conductive wires, such as high-modulus copper and silver wires, are prone to signal failure owing to tensile breakage under large strain conditions. Therefore, strain-insensitive stretchable conductive fibers for signal transmission are critical for next-generation wearable devices. Herein, a stretchable conductive fiber with a built-in helical structure is constructed by a "speed discrepancy" fiber-coating strategy with mass scalable production (60 cm/min). Such a "speed discrepancy" strategy is the key mechanism to template-free fabricate a built-in helical structure of the stretchable conductive fiber. The resultant fiber exhibits high conductivity (873 S/cm), stable insensitive signal transmission with a high quality factor (47.4), and a low relative resistance change (∼6%) under large strain. The built-in helical structure inspired by loofah whiskers endows the fiber with excellent strain insensitivity, and it can withstand large strains. On the proof of concept, our fiber can be seamlessly knitted, woven, and braided into smart textiles as an ideal signal transmission device under large strains, which will undoubtedly promote the development of intelligent electronic textiles and next-generation wearable devices.

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