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1.
Br J Haematol ; 204(4): 1402-1413, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38327115

RESUMO

To investigate the clinical characteristics and risk factors of specific human leukocyte antigen loss (HLA loss) in relapsed acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT), and compare the responses of patients with HLA loss relapse with those without HLA loss (non-HLA loss) to different treatment regimens. Clinical data of traceable patients with AML/MDS after myeloablative allo-HSCT in our centre between January 2010 and June 2021, who experienced disease relapse after the transplantation, were collected. The patients were divided into the HLA loss relapse group and the non-HLA loss relapsed group based on HLA loss gene test findings by next-generation sequencing. The patients' median overall survival (OS) after the relapse were compared, and univariate and multivariate analyses were performed using the Kaplan-Meier survival curve and Cox proportional hazard model to explore the responses to different treatments after relapse. A total of 2359 patients were selected. Retrospective HLA gene loss gene detection was performed for the deoxyribonucleic acid in 179 relapsed patients, including 47 patients in the HLA loss group (27.2%), 126 patients in the non-HLA loss group (72.8%) and 6 patients were excluded due to a lack of confirmed results. There was no significant statistical difference in the baseline characteristics of patients between the two groups, but as to transplantation-related characteristics, the donor-recipient relationship and HLA mismatched loci were statistically different between the two groups (both p < 0.001). Multivariate Cox analysis showed that more HLA mismatched loci ≥3 (HR = 3.66; 95% CI: 1.61-8.31; p = 0.002), time (≤6 months) from HSCT to relapse (HR = 7.92; 95% CI: 3.35-18.74; p < 0.001) and donor chimerism (CD3) in bone marrow at relapse (HR = 1.02; 95% CI: 1.00-1.03; p = 0.036) were independent factors affecting HLA loss relapse. The ratio of negative conversion of FLT3-ITD or CEBPA mutation was significantly lower in patients with post-transplantation HLA loss relapse than in the non-HLA loss group (0.0% vs. 45.5%, p = 0.003; 0.0% vs. 80.0%, p = 0.035), with none of the patients with FLT3-ITD or CEBPA mutation turned negative in the HLA loss group. The number of gene mutations turned negative when relapse in the non-HLA loss group was remarkably higher than that in the HLA loss group (p = 0.001). Using donor lymphocyte infusion (DLI) could not prolong OS for the HLA loss group (p = 0.42). Nevertheless, second transplantation had a significant positive impact on OS in the HLA loss group (p = 0.017), although only five patients in the HLA loss group underwent second transplantation. However, patients in the non-HLA loss group using DLI had a relatively longer OS time than those without DLI (p = 0.017). Second transplantation could also prolong OS in the non-HLA loss group, but the effect was not as significant as in the HLA loss group (p = 0.053). In summary, HLA loss detection is essential for patients with recurrence after transplantation, especially for those with more HLA mismatched loci and non-sibling donor. Furthermore, the detection of HLA loss has a guiding role in choosing subsequent therapy when relapsed, as secondary transplantation is more suitable than DLI for those with HLA loss.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Antígenos HLA/genética , Fatores de Risco , Antígenos de Histocompatibilidade Classe II , Modelos de Riscos Proporcionais , Recidiva
2.
Chembiochem ; : e202400501, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923378

RESUMO

Molecular engineering enables the creation of aptamers with novel functions, but the prerequisite is a deep understanding of their structure and recognition mechanism. The cellular-mesenchymal epithelial transition factor (c-MET) is garnering significant attention due to the critical role of the c-MET/HGF signaling pathway in tumor development and invasion. This study reports a strategy for constructing novel chimeric aptamers that bind to both c-MET and other specific proteins. c-MET was identified to be the molecular target of a DNA aptamer, HF3-58, selected through cell-SELEX. The binding structure and mechanism of HF3-58 with c-MET were systematically studied, revealing the scaffold, recognition, and redundancy regions. Through molecular engineering design, the redundancy region was replaced with other aptamers possessing stem-loop structures, yielding novel chimeric aptamers with bispecificity for binding to c-MET and specific proteins. A chimeric bispecific aptamer HF-3b showed the ability to mediate the adhesion of T-cells to tumor cells, suggesting the prospective utility in tumor immunotherapy. These findings suggest that aptamer HF3-58 can serve as a molecular engineering platform for the development of diverse multifunctional ligands targeting c-MET. Moreover, comprehensive understanding of the binding mechanisms of aptamers will provide guidance for the design of functional aptamers, significantly expanding their potential applications.

3.
Blood ; 139(4): 554-571, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-34582557

RESUMO

Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, undergo large-cell transformation (LCT) in the late stage, manifesting aggressive behavior, resistance to treatments, and poor prognosis, but the mechanisms involved remain unclear. To identify the molecular driver of LCT, we collected tumor samples from 133 MF patients and performed whole-transcriptome sequencing on 49 advanced-stage MF patients, followed by integrated copy number inference and genomic hybridization. Tumors with LCT showed unique transcriptional programs and enriched expressions of genes at chr7q. Paternally expressed gene 10 (PEG10), an imprinted gene at 7q21.3, was ectopically expressed in malignant T cells from LCT, driven by 7q21.3 amplification. Mechanistically, aberrant PEG10 expression increased cell size, promoted cell proliferation, and conferred treatment resistance by a PEG10/KLF2/NF-κB axis in in vitro and in vivo models. Pharmacologically targeting PEG10 reversed the phenotypes of proliferation and treatment resistance in LCT. Our findings reveal new molecular mechanisms underlying LCT and suggest that PEG10 inhibition may serve as a promising therapeutic approach in late-stage aggressive T-cell lymphoma.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Transformação Celular Neoplásica/genética , Proteínas de Ligação a DNA/genética , Linfoma Cutâneo de Células T/genética , Proteínas de Ligação a RNA/genética , Neoplasias Cutâneas/genética , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/patologia , Feminino , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Impressão Genômica , Humanos , Linfoma Cutâneo de Células T/patologia , Camundongos Endogâmicos NOD , Camundongos SCID , Micose Fungoide/genética , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia
4.
Phys Chem Chem Phys ; 26(14): 10850-10867, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38525533

RESUMO

Photothermal materials generally suffer from challenges such as low photothermal conversion efficiency and inefficient full-spectrum utilization of solar energy. This paper proposes gradient refractive index transparent ceramics (GRITCs) integrated with subwavelength nanostructure arrays and simulates the synergistic anti-reflection effect by an admittance recursive model. An innovative subwavelength structure, possessing a superior light-trapping capability, is initially crafted based on this model. Subsequently, various intelligent optimization algorithms including genetic algorithm, particle swarm optimization, and simulated annealing are employed to optimize the structure of gradient refractive index films respectively. Finally, the photothermal conversion efficiencies of devices based on different photothermal materials are calculated. The simulations and finite-difference time-domain calculations demonstrate that the three-layer GRITCs integrated with an optimal SNA exhibit outstanding full-spectrum and omnidirectional anti-reflection performance. The solar transmittance of the devices can exceed 97% for light wavelengths ranging from 300 to 2500 nm over the full angle of incidence. Our results reveal that the synergistic anti-reflection effect in the SNAs and GRITCs can enhance the photothermal conversion efficiency by more than 20%.

5.
Phys Chem Chem Phys ; 26(10): 8397-8407, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38407410

RESUMO

An amorphous layer is commonly found at the interfaces of heterostructures due to lattice and thermal mismatch between dissimilar materials. While existing research has explored the impact of these layers on interfacial thermal transport, a comprehensive understanding of the underlying microscopic mechanisms remains essential for advancing thermal nanodevice development. Through phonon wave packet simulations, we investigated the dynamic behaviors of phonons crossing the amorphous interlayer at the GaN/AlN interface from the mode level. Our results highlight the amorphous layer's capability to notably adjust the polarization properties of incoming phonons, culminating in phonon localization. By examining transmission outcomes on a per-mode basis, we demonstrate the amorphous layer's impediment on phonon transport. Notably, this resistance escalates with an increase in the amorphous layer thickness (L), with certain high-frequency TA phonons showing unexpectedly high transmissivity due to polarization conversion and inelastic scattering at the amorphous interface. In addition, we observe that the amorphous layer prompts multiple reflections of incident phonons, instigating discernible from the two-beam interference equation. Finally, in pursuit of enhanced phonon transport, we employ annealing techniques to optimize the interface morphology, leading to the recrystallization of the amorphous layer. This optimization yields a substantial enhancement of interfacial thermal conductance by up to 38% for L = 3 nm.

6.
Anal Chem ; 95(2): 1228-1233, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36594741

RESUMO

Cell-SELEX is a powerful tool to generate aptamers that specifically bind the native molecules on living cells. Here, we report an aptamer ZAJ4a generated by cell-SELEX. The molecular target of ZAJ4a was pulled down by the enriched cell-SELEX pool and identified to be the receptor-type tyrosine-protein phosphatase F (PTPRF) through a stable isotope labeling using amino acids in cell culture (SILAC)-based quantitative proteomic method. ZAJ4a showed high binding affinity with nanomolar range to cancer cells expressing PTPRF. Meanwhile, PTPRF was proven to highly express on several cancer cell lines using ZAJ4a as a molecular probe and to highly express in many kinds of cancer samples using gene expression profiling interactive analysis (GEPIA2) from the TCGA and GTEx databases. These results indicate that the aptamer generated by cell-SELEX showed good specificity at the molecular level. This cell-SELEX and target identification strategies show great potential for identifying biomarkers on the cell surface.


Assuntos
Aptâmeros de Nucleotídeos , Aptâmeros de Nucleotídeos/química , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Proteômica , Biomarcadores , Sondas Moleculares , Técnica de Seleção de Aptâmeros/métodos
7.
Anal Chem ; 95(50): 18595-18602, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38048047

RESUMO

Cellular prion protein (PrPC) is highly expressed in a variety of tumor cells and plays a crucial role in neurodegenerative diseases. Its N-terminal domain contains a conserved octapeptide (PHGGGWGQ) repeat sequence. The number of repeats has been correlated with the species as well as the development of associated diseases. Herein, PrPC was identified to be the molecular target of a high-affinity DNA aptamer HA5-68 obtained by cell-SELEX. Aptamer HA5-68 was further optimized to two short sequences (HA5-40-1 and HA5-40-2), and its binding site to PrPC was identified to be located in the loop-stem-loop region of the head of its secondary structure. HA5 series aptamers were demonstrated to bind the octapeptide repeat region of PrPC, as well as the synthesized peptides containing different numbers of octapeptide repeats. The PrPC expression on 42 cell lines was measured by using aptamer HA5-68 as a molecular probe. The clear understanding of the molecular structure and binding mechanism of this set of aptamers will provide information for the design of diagnostic methods and therapeutic drugs targeting PrPC.


Assuntos
Aptâmeros de Nucleotídeos , Doenças Priônicas , Príons , Humanos , Proteínas Priônicas , Aptâmeros de Nucleotídeos/química , Ligação Proteica , Príons/genética , Sítios de Ligação , Doenças Priônicas/metabolismo
8.
J Virol ; 96(19): e0094622, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36154611

RESUMO

Laryngopharynx epithelium neoplasia induced by HPV6/11 infection in juvenile-onset recurrent respiratory papillomatosis (JO-RRP) causes a great health issue characteristic of frequent relapse and aggressive disease progression. Local cell-mediated immunity shaped by the recruitment and activation of cytotoxic effector cells is critical for viral clearance. In this study, we found that NK cells in the papillomas of aggressive JO-RRP patients, in contrast to massive infiltrated T cells, were scarce in number and impaired in activation and cytotoxicity as they were in peripheral blood. Data from cell infiltration analysis indicated that the migration of NK cell to papilloma was restricted in aggressive JO-RRP patients. Further study showed that the skewed chemokine expression in the papillomas and elevated ICAM-1 expression in hyperplastic epithelia cells favored the T cell but not NK cell recruitment in aggressive JO-RRP patients. In parallel to the increased CD3+ T cells, we observed a dramatical increase in Tregs and Treg-promoting cytokines such as IL-4, IL-10 and TGFß in papillomas of aggressive JO-RRP patients. Our study suggested that likely initialized by the intrinsic change in neoplastic epithelial cells with persistent HPV infection, the aggressive papillomas built an entry barrier for NK cell infiltration and formed an immunosuppressive clump to fend off the immune attack from intra-papillomas NK cells. IMPORTANCE Frequent relapse and aggressive disease progression of juvenile-onset recurrent respiratory papillomatosis (JO-RRP) pose a great challenge to the complete remission of HPV 6/11 related laryngeal neoplasia. Local immune responses in papillomas are more relevant to the disease control considering the locale infected restriction of HPV virus in epitheliums. In our study, the restricted NK cell number and reduced expression of activating NKp30 receptor suggested one possible mechanism underlying impaired NK cell defense ability in aggressive JO-RRP papillomas. Meanwhile, the negative impact of HPV persistent infection on NK cell number and function represented yet another example of a chronic pathogen subverting NK cell behavior, affirming a potentially important role for NK cells in viral containment. Further, the skewed chemokine/cytokine expression in the papillomas and the elevated adhesion molecules expression in hyperplastic epithelia cells provided important clues for understanding blocked infiltration and antiviral dysfunction of NK cells in papilloma.


Assuntos
Células Matadoras Naturais , Papiloma , Infecções por Papillomavirus , Infecções Respiratórias , Progressão da Doença , Papillomavirus Humano 11 , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-10/imunologia , Interleucina-4/imunologia , Células Matadoras Naturais/imunologia , Receptor 3 Desencadeador da Citotoxicidade Natural/metabolismo , Recidiva Local de Neoplasia , Papiloma/imunologia , Papiloma/virologia , Infecções por Papillomavirus/imunologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologia , Fator de Crescimento Transformador beta/imunologia
9.
Phys Chem Chem Phys ; 25(3): 2349-2358, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36598036

RESUMO

Accurate interatomic force fields are of paramount importance for molecular dynamics simulations to explore the thermal transport at the GaN/AlN heterogenous interface, which is a key factor hindering heat dissipation and limiting the performance of GaN power electronic devices. In this work, an interatomic potential (force field) based on a deep neural network technique and first-principles calculations is developed for N-Ga-Al semiconductors to predict the elastic and thermodynamic properties. Using our deep neural network potential (NNP), the precise structural features, elastic constants, and thermal conductivities of GaN, AlN, and their alloy are obtained, which are well consistent with those from experiments and first-principles calculations. The interfacial thermal conductance of GaN/AlN heterostructures with different interfacial morphologies are further studied using molecular dynamics simulations with the NNP. It is found that atomic interdiffusion and disorder at the interfaces dramatically reduces the interfacial thermal conductance. The developed NNP exhibits a larger effective dimension with respect to classical empirical potentials and reaches competitive performances, thus pointing towards attractive advantages in the study of GaN heterostructures and devices with the NNP.

10.
Aging Clin Exp Res ; 35(11): 2453-2462, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37620639

RESUMO

BACKGROUND: The relationship between preoperative frailty and pulmonary complications after cardiac surgery in elderly patients is unclear. This study was designed to evaluate the relationship between frailty and postoperative pulmonary complications (PPCs) in elderly patients undergoing cardiac surgery and to provide a basis for their prevention and treatment. AIMS: This study aimed to investigate the predictive value of preoperative frailty on pulmonary complications after cardiac surgery in elderly patients. METHODS: Frailty was assessed using the CAF. The diagnosis of PPCs was based on the criteria defined by Hulzebos et al., and patients were classified into a PPCs group and a non-PPCs group. Factors with clinical significance and P < 0.05 in univariate regression analysis were included in multivariate logistic regression analysis to determine the relationship between preoperative frailty and PPCs. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare the predictive effects of the CAF, EuroSCORE II, and ASA + age on the occurrence of PPCs. RESULTS: A total of 205 patients were enrolled in this study, 31.7% of whom developed PPCs. Univariate logistic regression analysis showed that frailty, ASA grade, EuroSCORE II, hemoglobin concentration, FVC, time of operation, and postoperative AKI were associated with the development of PPCs. However, after adjustments for all possible confounding factors, multivariate logistic regression results showed that frailty, prolonged operation time, and postoperative AKI were risk factors for PPCs, and the risk of postoperative PPCs in frail patients was approximately 4.37 times that in nonfrail patients (OR = 4.37, 95%CI: 1.6-11.94, P < 0.05). The predictive efficacy of the traditional perioperative risk assessment tools EuroSCORE II and ASA + age was lower than that of CAF. CONCLUSIONS: Frailty before surgery, prolonged operation time, and postoperative AKI were independent risk factors for pulmonary complications after heart surgery in elderly individuals, and CAF was more effective than the traditional risk predictors EuroSCORE II and ASA + age.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Fragilidade , Humanos , Idoso , Fragilidade/epidemiologia , Estudos Prospectivos , Fatores de Risco , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/etiologia
11.
Int J Mol Sci ; 24(10)2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37239955

RESUMO

The L1 cell adhesion molecule (L1CAM) plays important roles in the development and plasticity of the nervous system as well as in tumor formation, progression, and metastasis. New ligands are necessary tools for biomedical research and the detection of L1CAM. Here, DNA aptamer yly12 against L1CAM was optimized to have much stronger binding affinity (10-24 fold) at room temperature and 37 °C via sequence mutation and extension. This interaction study revealed that the optimized aptamers (yly20 and yly21) adopted a hairpin structure containing two loops and two stems. The key nucleotides for aptamer binding mainly located in loop I and its adjacent area. Stem I mainly played the role of stabilizing the binding structure. The yly-series aptamers were demonstrated to bind the Ig6 domain of L1CAM. This study reveals a detailed molecular mechanism for the interaction between yly-series aptamers and L1CAM and provides guidance for drug development and detection probe design against L1CAM.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Molécula L1 de Adesão de Célula Nervosa , Humanos , Aptâmeros de Nucleotídeos/química , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Neoplasias/metabolismo
12.
Anal Chem ; 94(15): 6044-6049, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35380789

RESUMO

Expansion microscopy (ExM) is a newly developed technology in recent years that enables nanoscale imaging under conventional microscopes. Herein, we report an aptamer-based ExM imaging strategy. A nucleus-targeting aptamer Ch4-1 was chemically labeled with a dye and an acrydite at each end to perform the functions of molecular recognition, fluorescence reporting, and gel anchoring. After binding cell nucleus, the dual labeled aptamer Ac-Ch4-1-FAM directly participated in gelation and anchored in polyacrylamide gel. After expanding the gel, high-resolution imaging was achieved by confocal microscopy. Multicolor ExM imaging was also realized by combining Ac-Ch4-1-FAM, antibodies and fluorescent dyes. This aptamer-based ExM could clearly image the chromatin morphology at different mitotic stages. The expansion process is simple and the aptamer labeling is easy. The aptamer-based ExM holds great promise in super-resolution imaging of cells and tissues.


Assuntos
Corantes Fluorescentes , Oligonucleotídeos , Anticorpos/química , Núcleo Celular/metabolismo , Corantes Fluorescentes/química , Microscopia de Fluorescência/métodos
13.
Small ; 18(2): e2105130, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34862720

RESUMO

Edge termination plays a vital role in determining the properties of 2D materials. By performing compelling ab initio simulations, a lowest-energy U-edge [ZZ(U)] reconstruction is revealed in the bilayer phosphorene. Such reconstruction reduces 60% edge energy compared with the pristine one and occurs almost without an energy barrier, implying it should be the dominating edge in reality. The electronic band structure of phosphorene nanoribbon with such reconstruction resembles that of an intrinsic 2D layer, exhibiting nearly edgeless band characteristics. Although ZZ(U) changes the topology of phosphorene nanoribbons, simulated transmission electron microscope, scanning transmission electron microscope and scanning tunneling microscope images indicate it is very hard to be identified. One possible identified method is infrared/Raman analyses because the ZZ(U) edge alters vibrational modes dramatically. In addition, it also increases the thermal conductivity of PNR 1.4 and 2.3 times than the pristine and Klein edges.

14.
Nanotechnology ; 33(26)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35325884

RESUMO

Grain boundaries (GBs) widely exist in black phosphorene (BP), which plays a vital role in determining the properties of 2D materials. Significant GB effect on the thermal boundary resistance in BP structures is found by using molecular dynamics calculations and lattice dynamic analysis. A remarkably high interface thermal resistance is observed. By analyzing the strain distribution and phonon vibrational spectra, we reveal this high thermal resistance originates from phonon localization and strong phonon boundary scattering induced by the local stress at the GB area. Particularly, it is interesting to find that the partial phonon modes display weak localization when GBs present. The fraction of atoms participating in a particular phonon vibrational mode has been quantified through the calculation of phonon participation ratio. In addition, the thermal boundary resistance is found size-dependent, which further induces interesting thermal rectification effect in the BP structures. A high rectification ratio is obtained by adjusting the structural length and temperature bias. These findings provide a through insight into the GB effects on individual phonon mode transmission across the GBs, and highlight that the GB effect is an important factor and should be taken into account for the applications of BP-based phononic devices.

15.
J Craniofac Surg ; 33(3): 906-909, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34907949

RESUMO

ABSTRACT: We aimed to evaluate the quality of life of Chinese patients after immediate reconstruction surgery on individuals with oral cavity cancer. In addition, we compared the differences between radial forearm free flap and pectoralis major myocuta- neous flap. Using the University of Washington quality of life v4 questionnaire, 1:1 matched research was performed on patients received PMM or RFF flap. Chi-square test was used to analyze the variables. One hundred twenty four of 179 questionnaires were returned (69.3%). Age, N stage, and postoperative radiotherapy were similar for both groups. However, there were significant differences between two groups in gender, T stage, operation duration, and complication rate. Oral cavity cancer patients reconstructed with radial forearm free flap had better shoulder and speech functions but worse appearance domains. The results of our research provide important information for patients and physicians during their discussion of treatment programs for oral cavity cancers.


Assuntos
Retalhos de Tecido Biológico , Neoplasias Bucais , Retalho Miocutâneo , Procedimentos de Cirurgia Plástica , Antebraço/cirurgia , Retalhos de Tecido Biológico/cirurgia , Humanos , Neoplasias Bucais/cirurgia , Retalho Miocutâneo/cirurgia , Qualidade de Vida , Procedimentos de Cirurgia Plástica/métodos
16.
Acta Derm Venereol ; 101(12): adv00613, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34853863

RESUMO

Cutaneous T cell lymphoma is a generally indolent disease derived from skin-homing mature T cells. However, in advanced stages, cutaneous T cell lymphoma may manifest aggressive clinical behaviour and lead to a poor prognosis. The mechanism of disease progression in cutaneous T cell lymphoma remains unknown. This study, based on a large clinical cohort, found that IKZF2, an essential transcription factor during T cell development and differentiation, showed stage- dependent overexpression in the malignant T cells in mycosis fungoides lesions. IKZF2 is specifically over- expressed in advanced-stage mycosis fungoides lesions, and correlates with poor prognosis. Mechanistically, overexpression of IKZF2 promotes cutaneous T cell lymphoma progression via inhibiting malignant cell apoptosis and may contribute to tumour immune escape by downregulating major histocompatibility complex II molecules and up-regulating the production of anti-inflammatory cytokine interleukin-10 by malignant T cells. These results demonstrate the important role of IKZF2 in high-risk cutaneous T cell lymphoma and pave the way for future targeted therapy.


Assuntos
Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Progressão da Doença , Humanos , Linfoma Cutâneo de Células T/genética , Neoplasias Cutâneas/genética , Linfócitos T
17.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445629

RESUMO

General cancer-targeted ligands that can deliver drugs to cells have been given considerable attention. In this paper, a high-affinity DNA aptamer (HG1) generally binding to human tumor cells was evolved by cell-SELEX, and was further optimized to have 35 deoxynucleotides (HG1-9). Aptamer HG1-9 could be taken up by live cells, and its target protein on a cell was identified to be human transferrin receptor (TfR). As a man-made ligand of TfR, aptamer HG1-9 was demonstrated to bind at the same site of human TfR as transferrin with comparable binding affinity, and was proved to cross the epithelium barrier through transferrin receptor-mediated transcytosis. These results suggest that aptamer HG1-9 holds potential as a promising ligand to develop general cancer-targeted diagnostics and therapeutics.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Neoplasias/metabolismo , Receptores da Transferrina/metabolismo , Técnica de Seleção de Aptâmeros/métodos , Aptâmeros de Nucleotídeos/química , Humanos , Ligantes , Neoplasias/patologia , Transcitose , Células Tumorais Cultivadas
18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(2): 361-368, 2021 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-33913297

RESUMO

In order to solve the current problems in medical equipment maintenance, this study proposed an intelligent fault diagnosis method for medical equipment based on long short term memory network(LSTM). Firstly, in the case of no circuit drawings and unknown circuit board signal direction, the symptom phenomenon and port electrical signal of 7 different fault categories were collected, and the feature coding, normalization, fusion and screening were preprocessed. Then, the intelligent fault diagnosis model was built based on LSTM, and the fused and screened multi-modal features were used to carry out the fault diagnosis classification and identification experiment. The results were compared with those using port electrical signal, symptom phenomenon and the fusion of the two types. In addition, the fault diagnosis algorithm was compared with BP neural network (BPNN), recurrent neural network (RNN) and convolution neural network (CNN). The results show that based on the fused and screened multi-modal features, the average classification accuracy of LSTM algorithm model reaches 0.970 9, which is higher than that of using port electrical signal alone, symptom phenomenon alone or the fusion of the two types. It also has higher accuracy than BPNN, RNN and CNN, which provides a relatively feasible new idea for intelligent fault diagnosis of similar equipment.


Assuntos
Memória de Curto Prazo , Redes Neurais de Computação , Algoritmos , Eletricidade
19.
Anal Chem ; 92(7): 5370-5378, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32134248

RESUMO

Circulating tumor-related materials (CTRMs) shed from original or metastatic tumors, carry a lot of tumor information and are considered as important markers for cancer diagnosis and metastasis prognosis. Herein, we report a colorimetric detection strategy for CTRMs based on aptamer-based magnetic isolation and endogenous alkaline phosphatase (AP)-signal amplification. This strategy exhibited high sensitivity and selectivity toward the CTRMs that express AP heterodimers (the target of aptamer, a potential tumor marker). For clinical samples, this CTRM assay significantly discriminated colorectal cancer patients (n = 50) from healthy individuals (n = 39, p < 0.0001). The receiver operating characteristic (ROC) analysis indicated the sensitivity and specificity reached 92% and 82%, respectively, at the optimal cutoff point, the area under the curve of ROC reached 0.93, suggesting great potential for colorectal cancer diagnosis and therapeutic monitoring. Compared with CTC assays, this strategy is simple and has the potential for point-of-care testing.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Técnicas Biossensoriais/métodos , Animais , Aptâmeros de Nucleotídeos/genética , Sequência de Bases , Linhagem Celular Tumoral , Colorimetria , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
20.
Analyst ; 145(20): 6549-6555, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32776047

RESUMO

Hydrogen sulfide (H2S) in mitochondria plays important roles in many mitochondria-related physiological and pathological processes. Herein, a cyanine/naphthalimide hybrid fluorescent probe, L1, was designed for the ratiometric detection and imaging of mitochondrial H2S, in which cyanine and naphthalimide were used as the mitochondria-targeting group and H2S response group, respectively. Besides its good mitochondria-targeting ability, L1 also showed high sensitivity and good selectivity for H2S. Moreover, on the basis of the fluorescence ratio of naphthalimide to cyanine fluorophore, it was successfully applied to monitor the endogenous and exogenous mitochondrial H2S in live cells. Additionally, the endogenous mitochondrial H2S in different cell lines was measured by probe L1.


Assuntos
Corantes Fluorescentes , Sulfeto de Hidrogênio , Mitocôndrias , Naftalimidas/toxicidade , Imagem Óptica
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