Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 140
Filtrar
1.
Front Oncol ; 14: 1406144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39132506

RESUMO

Background: Several image-based diagnostic methods have been developed to examine the features of breast lesions among women, while the value of combining palpation imaging and ultrasound by a bimodal breast examination system is still unknown. Methods: A real-world study was conducted among 424 patients who visited Fujian Maternal and Child Health Hospital and Fujian Obstetrics and Gynecology Hospital, and used the Bimodal Breast Exam (BBE) systems which combines palpation imaging and ultrasound imaging. Among them, 97 patients had additional ultrasound, mammogram, or pathological examination. These patients were used to evaluate the consistency and efficacy of the BBE in interpreting the features of breast lesions as compared to results of ultrasound, mammogram, and pathological examinations. Results: The BBE system detected 1517 lesions with palpation imaging, 1126 lesions with ultrasound examination (950 solid lesions and 176 cysts), and 391 non mass lesions. Among them, 404 patients were diagnosed as benign and 20 were diagnosed as malignant tumor. However, 12, 9 and 4 cases were diagnosed as malignant tumors by ultrasound, mammogram and pathological examination, respectively. Compared with the integrative results of ultrasound, mammogram and pathology, the sensitivity of BBE is 55.6%, and the specificity is 90.9%, with a kappa coefficient of 0.387 (0.110, 0.665), indicating moderate consistency. Conclusions: In clinical practice, BBE can be used to evaluate features of breast lesions with a high specificity. The diagnostic efficacy is comparable to the integrative results of ultrasound, mammography, and pathological examination.

2.
Mol Neurobiol ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017976

RESUMO

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies. The important roles of circRNAs modified by m6A methylation have been reported in the pathogenesis of other autoimmune diseases, but remain unclear in MG. To address this point, we collected peripheral blood mononuclear cells from six MG patients and six healthy controls and performed m6A­circRNA epitranscriptomic microarray and RNA sequencing. Differentially m6A-modified circRNAs and differentially expressed genes (DEGs) were analyzed. A network was constructed containing 17 circRNAs, 30 miRNAs, and 34 DEGs. The GSE85452 dataset was downloaded. DEGs that were differentially expressed in the GSE85452 dataset were selected as seed genes. Finally, four candidate m6A-modified circRNAs (hsa_circ_0084735, hsa_circ_0018652, hsa_circ_0025731, and hsa_circ_0030997) were identified through a random walk with restart. We found that they had different degree correlations with different immune cells. The results of MeRIP-qPCR showed that the m6A methylated levels of hsa_circ_0084735 and hsa_circ_0025731 were downregulated in MG patients, while the other two circRNAs were not significantly different between MG and control group. For the first time, we explored the pathogenesis of MG at the epigenetic transcriptome level. Our results will open new perspectives for MG research and identify potential biomarkers and therapeutic targets for MG.

3.
Medicine (Baltimore) ; 103(25): e38081, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905385

RESUMO

A multicenter retrospective analysis of conventionally collected data. To identify the potential causes of hypoproteinemia after traumatic spinal cord injury (TSCI) and provide a diagnostic model for predicting an individual likelihood of developing hypoproteinemia. Hypoproteinemia is a complication of spinal cord injury (SCI), an independent risk factor for respiratory failure in elderly patients with SCI, and a predictor of outcomes in patients with cervical SCI. Few nomogram-based studies have used clinical indicators to predict the likelihood of hypoproteinemia following TSCI. This multicenter retrospective clinical analysis included patients with TSCI admitted to the First Affiliated Hospital of Guangxi Medical University, Wuzhou GongRen Hospital, and Dahua Yao Autonomous County People Hospital between 2016 and 2020. The data of patients from the First Affiliated Hospital of Guangxi Medical University were used as the training set, and those from the other 2 hospitals were used as the validation set. All patient histories, diagnostic procedures, and imaging findings were recorded. To predict whether patients with TSCI may develop hypoproteinemia, a least absolute shrinkage and selection operator regression analysis was conducted to create a nomogram. The model was validated by analyzing the consequences using decision curve analysis, calibration curves, the C-index, and receiver operating characteristic curves. After excluding patients with missing data, 534 patients were included in this study. Male/female sex, age ≥ 60 years, cervical SCI, pneumonia, pleural effusion, urinary tract infection (UTI), hyponatremia, fever, hypotension, and tracheostomy were identified as independent risk factors of hypoalbuminemia. A simple and easy-to-replicate clinical prediction nomogram was constructed using these factors. The area under the curve was 0.728 in the training set and 0.881 in the validation set. The predictive power of the nomogram was satisfactory. Hypoalbuminemia after TSCI may be predicted using the risk factors of male/female sex, age ≥ 60 years, cervical SCI, pneumonia, pleural effusion, UTI, hyponatremia, fever, hypotension, and tracheostomy.


Assuntos
Hipoproteinemia , Nomogramas , Traumatismos da Medula Espinal , Humanos , Feminino , Masculino , Traumatismos da Medula Espinal/complicações , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Adulto , Hipoproteinemia/etiologia , Fatores de Risco , Curva ROC , China/epidemiologia
4.
CNS Neurosci Ther ; 30(6): e14793, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38894580

RESUMO

BACKGROUND: We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). METHODS: This single-center prospective cohort study was based on patients from an MG registry study in China and conducted from February 10, 2021 to March 31, 2022. Adult refractory patients with AChR-Ab+ gMG were assigned to tocilizumab or conventional immunotherapy groups. The primary efficacy outcome was the mean difference of MG activities of daily living (MG-ADL) change at weeks 4, 8, 12, 16, 20, 24 corresponding to that at the baseline between the two groups. A generalized estimating equation model was used for the primary outcome analysis. Safety was assessed based on adverse events. RESULTS: Of 34 eligible patients, 20 (mean [standard deviation] age, 53.8 [21.9] years; 12 [60.0%] female) received tocilizumab and 14 received conventional immunotherapy (45.8 [18.0] years; 8 [57.1%] female). The tocilizumab group had greater reduction in MG-ADL score at week 4 (adjusted mean difference, -3.4; 95% CI, -4.7 to -2.0; p < 0.001) than the conventional immunotherapy group, with significant differences sustained through week 24 (adjusted mean difference, -4.5; 95% CI, -6.4 to -2.6; p < 0.001). At week 24, the proportion of patients achieving higher levels of MG-ADL (up to 7-point reduction) and QMG (up to 11-point reduction) scores improvement was significantly greater with tocilizumab. Tocilizumab had acceptable safety profiles without severe or unexpected safety issues. CONCLUSION: Tocilizumab is safe and effective in improving the MG-ADL score and reducing prednisone dose in refractory AChR-Ab+ gMG, suggesting tocilizumab has the potential to be a valuable therapeutic option for such patients.


Assuntos
Anticorpos Monoclonais Humanizados , Miastenia Gravis , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Feminino , Pessoa de Meia-Idade , Masculino , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/imunologia , Adulto , Idoso , Estudos Prospectivos , Resultado do Tratamento , Estudos de Coortes , Atividades Cotidianas , Imunoterapia/métodos , Imunoterapia/efeitos adversos , Sistema de Registros
5.
Nat Commun ; 15(1): 3828, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714653

RESUMO

Stabilization of topological spin textures in layered magnets has the potential to drive the development of advanced low-dimensional spintronics devices. However, achieving reliable and flexible manipulation of the topological spin textures beyond skyrmion in a two-dimensional magnet system remains challenging. Here, we demonstrate the introduction of magnetic iron atoms between the van der Waals gap of a layered magnet, Fe3GaTe2, to modify local anisotropic magnetic interactions. Consequently, we present direct observations of the order-disorder skyrmion lattices transition. In addition, non-trivial topological solitons, such as skyrmioniums and skyrmion bags, are realized at room temperature. Our work highlights the influence of random spin control of non-trivial topological spin textures.

6.
Am J Pathol ; 194(8): 1458-1477, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38777148

RESUMO

Idiopathic pulmonary fibrosis, a fatal interstitial lung disease, is characterized by fibroblast activation and aberrant extracellular matrix accumulation. Effective therapeutic development is limited because of incomplete understanding of the mechanisms by which fibroblasts become aberrantly activated. Here, we show aldehyde dehydrogenase 2 (ALDH2) in fibroblasts as a potential therapeutic target for pulmonary fibrosis. A decrease in ALDH2 expression was observed in patients with idiopathic pulmonary fibrosis and bleomycin-treated mice. ALDH2 deficiency spontaneously induces collagen accumulation in the lungs of aged mice. Furthermore, young ALDH2 knockout mice exhibited exacerbated bleomycin-induced pulmonary fibrosis and increased mortality compared with that in control mice. Mechanistic studies revealed that transforming growth factor (TGF)-ß1 induction and ALDH2 depletion constituted a positive feedback loop that exacerbates fibroblast activation. TGF-ß1 down-regulated ALDH2 through a TGF-ß receptor 1/Smad3-dependent mechanism. The subsequent deficiency in ALDH2 resulted in fibroblast dysfunction that manifested as impaired mitochondrial autophagy and senescence, leading to fibroblast activation and extracellular matrix production. ALDH2 overexpression markedly suppressed fibroblast activation, and this effect was abrogated by PTEN-induced putative kinase 1 (PINK1) knockdown, indicating that the profibrotic effects of ALDH2 are PINK1- dependent. Furthermore, ALDH2 activated by N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide (Alda-1) reversed the established pulmonary fibrosis in both young and aged mice. In conclusion, ALDH2 expression inhibited the pathogenesis of pulmonary fibrosis. Strategies to up-regulate or activate ALDH2 expression could be potential therapies for pulmonary fibrosis.


Assuntos
Aldeído-Desidrogenase Mitocondrial , Bleomicina , Senescência Celular , Fibroblastos , Camundongos Knockout , Mitocôndrias , Animais , Fibroblastos/metabolismo , Fibroblastos/patologia , Aldeído-Desidrogenase Mitocondrial/metabolismo , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/deficiência , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Humanos , Bleomicina/toxicidade , Bleomicina/efeitos adversos , Fator de Crescimento Transformador beta1/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/genética , Transdução de Sinais , Pulmão/patologia , Pulmão/metabolismo
7.
Nat Mater ; 23(7): 944-950, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38783106

RESUMO

Thin-film materials with large electromechanical responses are fundamental enablers of next-generation micro-/nano-electromechanical applications. Conventional electromechanical materials (for example, ferroelectrics and relaxors), however, exhibit severely degraded responses when scaled down to submicrometre-thick films due to substrate constraints (clamping). This limitation is overcome, and substantial electromechanical responses in antiferroelectric thin films are achieved through an unconventional coupling of the field-induced antiferroelectric-to-ferroelectric phase transition and the substrate constraints. A detilting of the oxygen octahedra and lattice-volume expansion in all dimensions are observed commensurate with the phase transition using operando electron microscopy, such that the in-plane clamping further enhances the out-of-plane expansion, as rationalized using first-principles calculations. In turn, a non-traditional thickness scaling is realized wherein an electromechanical strain (1.7%) is produced from a model antiferroelectric PbZrO3 film that is just 100 nm thick. The high performance and understanding of the mechanism provide a promising pathway to develop high-performance micro-/nano-electromechanical systems.

8.
Eur Arch Otorhinolaryngol ; 281(8): 4191-4199, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38700538

RESUMO

OBJECTIVE: Identifying the biomarkers for uncontrolled chronic rhinosinusitis (CRS) is important for directing treatment decisions. Eosinophilia has been reported to be involved in the poor disease control of CRS and mucus eosinophil-derived neurotoxin (EDN) is potentially a biomarker of intense eosinophil activation. This study aimed to assess the relationship between mucus EDN levels, disease severity, and degree of CRS control. METHODS: A total of 150 adult patients with CRS and 25 healthy controls were prospectively enrolled. The nasal mucus and tissue specimens were collected to analyze EDN levels. Disease severity was assessed by Lund-Mackay score and 22-item Sino-Nasal Outcome Test (SNOT-22) score. Five CRS symptom severities during the prior month (nasal blockage, rhinorrhoea/postnasal drip, facial pain/pressure, smell, sleep disturbance or fatigue), use of rescue medications in the last six months, and the presence of diseased mucosa on nasal endoscopy were obtained. Consistent with the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 CRS control criteria, uncontrolled CRS was defined as meeting at least three items. RESULTS: 40% of patients with CRS presented with uncontrolled status. Patients with uncontrolled CRS had significantly higher nasal mucus EDN levels (P = 0.010), percentage of blood eosinophil (P = 0.015), SNOT-22 score (P < 0.001), Lund-Mackay score (P = 0.008), and a more eosinophilic dominant phenotype of CRS (P < 0.001) than patients with controlled CRS. Furthermore, mucus EDN levels were positively correlated with blood eosinophils (r = 0.541, P = 0.005), SNOT-22 score (r = 0.460, P = 0.021), and Lund-Mackay score (r = 0.387, P = 0.039). Mucus EDN levels were the significant parameter related to uncontrolled CRS in multivariable analysis after adjusting for patient demographics and comorbidities (odds ratio = 1.323; P = 0.004). CONCLUSIONS: Mucus EDN levels may be a potential biomarker for identifying the CRS control status.


Assuntos
Biomarcadores , Neurotoxina Derivada de Eosinófilo , Muco , Rinite , Sinusite , Humanos , Sinusite/complicações , Sinusite/metabolismo , Rinite/metabolismo , Rinite/complicações , Masculino , Feminino , Doença Crônica , Pessoa de Meia-Idade , Adulto , Muco/metabolismo , Neurotoxina Derivada de Eosinófilo/metabolismo , Biomarcadores/metabolismo , Estudos Prospectivos , Estudos de Casos e Controles , Índice de Gravidade de Doença , Mucosa Nasal/metabolismo , Teste de Desfecho Sinonasal , Idoso , Rinossinusite
9.
Nat Mater ; 23(7): 898-904, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38622325

RESUMO

A magnon is a collective excitation of the spin structure in a magnetic insulator and can transmit spin angular momentum with negligible dissipation. This quantum of a spin wave has always been manipulated through magnetic dipoles (that is, by breaking time-reversal symmetry). Here we report the experimental observation of chiral spin transport in multiferroic BiFeO3 and its control by reversing the ferroelectric polarization (that is, by breaking spatial inversion symmetry). The ferroelectrically controlled magnons show up to 18% modulation at room temperature. The spin torque that the magnons in BiFeO3 carry can be used to efficiently switch the magnetization of adjacent magnets, with a spin-torque efficiency comparable to the spin Hall effect in heavy metals. Utilizing such controllable magnon generation and transmission in BiFeO3, an all-oxide, energy-scalable logic is demonstrated composed of spin-orbit injection, detection and magnetoelectric control. Our observations open a new chapter of multiferroic magnons and pave another path towards low-dissipation nanoelectronics.

10.
Nat Commun ; 15(1): 2903, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575570

RESUMO

Bismuth ferrite (BiFeO3) is a multiferroic material that exhibits both ferroelectricity and canted antiferromagnetism at room temperature, making it a unique candidate in the development of electric-field controllable magnetic devices. The magnetic moments in BiFeO3 are arranged into a spin cycloid, resulting in unique magnetic properties which are tied to the ferroelectric order. Previous understanding of this coupling has relied on average, mesoscale measurements. Using nitrogen vacancy-based diamond magnetometry, we observe the magnetic spin cycloid structure of BiFeO3 in real space. This structure is magnetoelectrically coupled through symmetry to the ferroelectric polarization and this relationship is maintained through electric field switching. Through a combination of in-plane and out-of-plane electrical switching, coupled with ab initio studies, we have discovered that the epitaxy from the substrate imposes a magnetoelastic anisotropy on the spin cycloid, which establishes preferred cycloid propagation directions. The energy landscape of the cycloid is shaped by both the ferroelectric degree of freedom and strain-induced anisotropy, restricting the spin spiral propagation vector to changes to specific switching events.

11.
Toxicology ; 504: 153762, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38403151

RESUMO

Recent research has hinted at a potential connection between silicosis, a fibrotic lung disease caused by exposure to crystalline silica particles, and cuproptosis. The aim of the study was to explore how cuproptosis-related genes (CRGs) may influence the development of silicosis and elucidate the underlying mechanisms. An analysis of genes associated with both silicosis and cuproptosis was conducted. Key gene identification was achieved through the application of two machine learning techniques. Additionally, the correlation between these key genes and immune cell populations was explored and the critical pathways were discerned. To corroborate our findings, the expression of key genes was verified in both a publicly available silica-induced mouse model and our own silicosis mouse model. A total of 12 differentially expressed CRGs associated with silicosis were identified. Further analysis resulted in the identification of 6 CRGs, namely LOX, SPARC, MOXD1, ALB, MT-CO2, and AOC2. Elevated immune cell infiltration of CD8 T cells, regulatory T cells, M0 macrophages, and neutrophils in silicosis patients compared to healthy controls was indicated. Validation in a silica-induced pulmonary fibrosis mouse model supported SPARC and MT-CO2 as potential signature genes for the prediction of silicosis. These findings highlight a strong association between silicosis and cuproptosis. Among CRGs, LOX, SPARC, MOXD1, ALB, MT-CO2, and AOC2 emerged as pivotal players in the context of silicosis by modulating CD8 T cells, regulatory T cells, M0 macrophages, and neutrophils.


Assuntos
Dióxido de Silício , Silicose , Silicose/genética , Silicose/imunologia , Silicose/patologia , Animais , Dióxido de Silício/toxicidade , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Humanos , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/imunologia , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/genética , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Aprendizado de Máquina , Osteonectina/genética
12.
BMC Cancer ; 24(1): 208, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360584

RESUMO

BACKGROUND: Despite the known association between healthy lifestyles and reduced risk of breast cancer, it remains unclear whether systemic inflammation, as a consequence of unhealthy lifestyles, may mediate the association. METHODS: A cohort study of 259,435 female participants in the UK Biobank was conducted to estimate hazard ratio (HR) for breast cancer according to 9 inflammation markers using Cox regression models. We further estimated the percentage of total association between healthy lifestyle index (HLI) and breast cancer that is mediated by these inflammation markers. RESULTS: During 2,738,705 person-years of follow-up, 8,889 cases of breast cancer were diagnosed among 259,435 women in the UK Biobank cohort. Higher level of C-reactive protein (CRP), systemic immune-inflammation index (SII), CRP-to-albumin Ratio (CAR), CRP-to-lymphocyte Ratio (CLR), monocyte-to-HDL-c ratio (MHR), and neutrophil-to-HDL-c ratio (NHR) were associated with increased breast cancer risk, while a higher lymphocyte-to-monocyte ratio (LMR) was associated with a lower risk. The inverse association between HLI and breast cancer was weakly mediated by CRP (8.5%), SII (1.71%), CAR (8.66%), CLR (6.91%), MHR (6.27%), and NHR (7.33%). When considering individual lifestyle factors, CRP and CAR each mediated 16.58% and 17.20%, respectively, of the associations between diet score and breast cancer risk, while the proportion mediated for physical activity and breast cancer were 12.13% and 11.48%, respectively. Furthermore, MHR was found to mediate 13.84% and 12.01% of the associations between BMI, waist circumference, and breast cancer. CONCLUSION: The association of HLI and breast cancer is weakly mediated by the level of inflammation, particularly by CRP and CAR. Systemic inflammatory status may be an intermediate in the biological pathway of breast cancer development.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Coortes , Análise de Mediação , Inflamação/complicações , Proteína C-Reativa/análise , Estilo de Vida Saudável
13.
Inflammation ; 47(4): 1109-1126, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38265677

RESUMO

Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid derived from Stephania tetrandra S. Moor, known for its potential use in attenuating the progression of silicosis. However, the precise effects and underlying mechanisms of TET remain controversial. In this study, we aimed to elucidate the pharmacological mechanism of TET using a network pharmacology approach, while also evaluating its effect on silica-induced lung fibrosis in mice and TGF-ß1-stimulated pulmonary fibroblasts in vitro. We employed network pharmacology to unravel the biological mechanisms through which TET may exert its therapeutic effects on pulmonary fibrosis and silicosis. In a silica-induced mouse model of lung fibrosis, TET was administered orally either during the early or late stage of fibrotic progression. Additionally, we examined the effects of TET on fibroblasts stimulated by TGF-ß1 in vitro. Through the analysis, we identified a total of 101 targets of TET, 7,851 genes associated with pulmonary fibrosis, and 80 overlapping genes. These genes were primarily associated with key pathways such as epidermal growth factor receptor tyrosine kinase inhibitor resistance, the vascular endothelial growth factor signaling pathway, and the phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or AKT) signaling pathway. Furthermore, molecular docking analysis revealed the binding of TET to AKT1, the catalytic subunit of phosphatidylinositol-3 kinase, and KDR. In vivo experiments demonstrated that TET significantly alleviated silica-induced pulmonary fibrosis and reduced the expression of fibrotic markers. Moreover, TET exhibited inhibitory effects on the migration, proliferation, and differentiation of TGF-ß1-induced lung fibroblasts in vitro. Notably, TET mitigated silica-induced pulmonary fibrosis by suppressing the PI3K/AKT pathway. In conclusion, our findings suggest that TET possesses the ability to suppress silica-induced pulmonary fibrosis by targeting the PI3K/AKT signaling pathway. These results provide valuable insights into the therapeutic potential of TET in the treatment of pulmonary fibrosis and silicosis.


Assuntos
Benzilisoquinolinas , Farmacologia em Rede , Proteínas Proto-Oncogênicas c-akt , Fibrose Pulmonar , Transdução de Sinais , Dióxido de Silício , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Benzilisoquinolinas/farmacologia , Benzilisoquinolinas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Dióxido de Silício/toxicidade , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Silicose/tratamento farmacológico , Silicose/metabolismo , Silicose/patologia , Masculino , Fator de Crescimento Transformador beta1/metabolismo , Camundongos Endogâmicos C57BL
14.
Adv Mater ; 36(9): e2308555, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38016700

RESUMO

2D layered materials with broken inversion symmetry are being extensively pursued as  spin source layers to realize high-efficiency magnetic switching. Such low-symmetry layered systems are, however, scarce. In addition, most layered magnets with perpendicular magnetic anisotropy show a low Curie temperature. Here, the experimental observation of spin-orbit torque magnetization self-switching at room temperature in a layered polar ferromagnetic metal, Fe2.5 Co2.5 GeTe2 is reported. The spin-orbit torque is generated from the broken inversion symmetry along the c-axis of the crystal. These results provide a direct pathway toward applicable 2D spintronic devices.

15.
J Thromb Thrombolysis ; 57(1): 67-81, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37940761

RESUMO

BACKGROUND: Accumulating evidence links the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement to venous thromboembolism (VTE) in non-small cell lung cancer (NSCLC) patients. However, the corresponding mechanisms remain unclear. METHOD: High-throughput sequencing analysis of H3122 human ALK-positive NSCLC cells treated with ALK inhibitor/ dimethyl sulfoxide (DMSO) was performed to identify coagulation-associated differential genes between EML4-ALK fusion protein inhibited cells and control cells. Sequentially, we confirmed its expression in NSCLC patients' tissues and in the plasma of a subcutaneous xenograft mouse model. An inferior vena cava (IVC) ligation model was used to assess clot formation potential. Additionally, pathways involved in tissue factor (TF) regulation were explored in ALK-positive cell lines H3122 and H2228. Statistical significance was determined by Student t-test and one-way ANOVA using SPSS. RESULTS: Sequencing analysis identified a significant downregulation of TF after inhibiting EML4-ALK fusion protein activity in H3122 cells. In clinical NSCLC cases, TF expression was increased especially in ALK-positive NSCLC tissues. Meanwhile, H3122 and H2228 with high TF expression exhibited shorter plasma clotting time and higher TF activity versus ALK-negative H1299 and A549 in cell culture supernatant. Mice bearing H2228 tumor showed a higher concentration of tumor-derived TF and TF activity in plasma and the highest adjusted IVC clot weights. Limiting EML4-ALK protein phosphorylation downregulated extracellular regulated protein kinases 1/2 (ERK1/2)-activating the protein-1(AP-1) signaling pathway and thus attenuated TF expression. CONCLUSION: EML4-ALK fusion protein may enhance venous thrombogenicity by regulating coagulation factor TF expression. There was potential involvement of the pERK1/2-AP-1 pathway in this process.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/uso terapêutico , Tromboplastina/genética , Fator de Transcrição AP-1/uso terapêutico , Proliferação de Células , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/análise , Proteínas de Fusão Oncogênica/metabolismo
16.
Breast ; 73: 103603, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38000092

RESUMO

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer-related death among women. However, evidence concerning hematological and biochemical markers influencing the natural history of breast cancer from in situ breast cancer to mortality is limited. METHODS: In the UK Biobank cohort, 260,079 women were enrolled during 2006-2010 and were followed up until 2019 to test the 59 hematological and biochemical markers associated with breast cancer risk and mortality. The strengths of these associations were evaluated using the multivariable Cox regression models. To understand the natural history of breast cancer, multi-state survival models were further applied to examine the effects of biomarkers on transitions between different states of breast cancer. RESULTS: Eleven biomarkers were found to be significantly associated with the risk of invasive breast cancer, including mainly inflammatory-related biomarkers and endogenous hormones, while serum testosterone was also associated with the risk of in-situ breast cancer. Among them, C-reactive protein (CRP) was more likely to be associated with invasive breast cancer and its transition to death from breast cancer (HR for the highest quartile = 1.46, 95 % CI = 1.07-1.97), while testosterone and insulin-like growth factor-1 (IGF-1) were more likely to impact the early state of breast cancer development (Testosterone: HR for the highest quartile = 1.31, 95 % CI = 1.12-1.53; IGF-1: HR for the highest quartile = 1.17, 95 % CI = 1.00-1.38). CONCLUSION: Serum CRP, testosterone, and IGF-1 have different impacts on the transitions of different breast cancer states, confirming the role of chronic inflammation and endogenous hormones in breast cancer progression. This study further highlights the need of closer surveillance for these biomarkers during the breast cancer development course.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Estudos Prospectivos , Fatores de Risco , Bancos de Espécimes Biológicos , Biobanco do Reino Unido , Biomarcadores , Testosterona , Proteína C-Reativa
17.
Int J Surg ; 110(3): 1637-1644, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38079604

RESUMO

BACKGROUND: There are challenges for beginners to identify standard biliopancreatic system anatomical sites on endoscopic ultrasonography (EUS) images. Therefore, the authors aimed to develop a convolutional neural network (CNN)-based model to identify standard biliopancreatic system anatomical sites on EUS images. METHODS: The standard anatomical structures of the gastric and duodenal regions observed by EUS was divided into 14 sites. The authors used 6230 EUS images with standard anatomical sites selected from 1812 patients to train the CNN model, and then tested its diagnostic performance both in internal and external validations. Internal validation set tests were performed on 1569 EUS images of 47 patients from two centers. Externally validated datasets were retrospectively collected from 16 centers, and finally 131 patients with 85 322 EUS images were included. In the external validation, all EUS images were read by CNN model, beginners, and experts, respectively. The final decision made by the experts was considered as the gold standard, and the diagnostic performance between CNN model and beginners were compared. RESULTS: In the internal test cohort, the accuracy of CNN model was 92.1-100.0% for 14 standard anatomical sites. In the external test cohort, the sensitivity and specificity of CNN model were 89.45-99.92% and 93.35-99.79%, respectively. Compared with beginners, CNN model had higher sensitivity and specificity for 11 sites, and was in good agreement with the experts (Kappa values 0.84-0.98). CONCLUSIONS: The authors developed a CNN-based model to automatically identify standard anatomical sites on EUS images with excellent diagnostic performance, which may serve as a potentially powerful auxiliary tool in future clinical practice.


Assuntos
Inteligência Artificial , Endossonografia , Humanos , Estudos Retrospectivos , Redes Neurais de Computação , Sensibilidade e Especificidade
18.
BMC Gastroenterol ; 23(1): 426, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049722

RESUMO

OBJECTIVE: This study aims to assess the prevalence of Helicobacter pylori (Hp) infection at the household level in Hainan Province in China and identify the factors that contribute to its spread. The findings of this study have significant implications for public health prevention strategies in the Hainan region. METHODS: A total of 421 families, comprising 1355 individuals, were tested for Hp infection across five cities in Hainan Province between July 2021 and April 2022. The study utilized questionnaires that included questions about personal characteristics, household shared lifestyle and dietary habits, and potential pathways of Hp infection in children to identify potential factors linked to household Hp infection and transmission patterns. RESULTS: The prevalence of Hp infection on an individual basis was 46.72% (629/1355), with age ≥ 20 years, being married and having junior secondary education and above as risk factors for Hp infection. The prevalence of Hp infection in households was 80.29% (338/421), household size of 5, 6 and above were risk factors for Hp infection with Odds Ratios (ORs) of 4.09 (1.17-14.33) and 15.19 (2.01-114.73), respectively, household income ≥ 100,000 yuan and drinking boiled water from a tap source were protective factors for Hp infection with ORs of 0.52 (0.31-0.89) and 0.51 (0.28-0.95), respectively. The prevalence of Hp infection among minors in the household was 24.89% (58/233), with paternal infection and maternal infection as risk factors for child infection, with ORs of 2.93 (1.29-6.62) and 2.51 (1.07-5.89), respectively. CONCLUSION: Hp infection was prevalent among Hainan families, and interaction with infected family members may be the primary cause of transmission.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Criança , Humanos , Adulto Jovem , Adulto , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/complicações , Comportamento Alimentar , China/epidemiologia , Inquéritos e Questionários , Prevalência , Fatores de Risco
19.
Cancer Epidemiol ; 87: 102490, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37976632

RESUMO

BACKGROUND: Systemic inflammatory markers have been widely used in cancer prognosis prediction recently. However, there is limited knowledge regarding their impact on breast cancer risk and their interaction with polygenic risk scores. METHODS: A cohort study of 202,403 female participants from the UK Biobank were analyzed to estimate the hazard ratio (HR) for the incidence and mortality of breast cancer based on inflammatory markers using Cox regression models. Additionally, we stratified the analysis by polygenic risk scores (PRS) for breast cancer, and examined the interaction between these markers and PRS through likelihood ratio tests and relative excess risk due to interaction (RERI). RESULTS: Women in the highest tertile of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and C-reactive protein (CRP) showed an increased risk of breast cancer [HR (95 %CI) = 1.10 (1.02-1.18), 1.09 (1.01-1.17) and 1.15 (1.05-1.25), respectively], as compared to those in the lowest tertile. Regarding breast cancer mortality, only NLR and CRP exhibited consistent results in the univariate model [HR (95 %CI) = 1.25 (0.99-1.58) and 1.39 (1.10-1.77), respectively]. When stratified by PRS, stronger associations between inflammatory markers and breast cancer risk were observed in the high PRS group. Furthermore, there was a significant additive interaction between CRP and PRS [RERI (95 % CI) = 0.30 (0.06-0.53)]. CONCLUSION: NLR and CRP are associated with breast cancer risk and mortality, and the effect of CRP is influenced by PRS. Systematic inflammatory markers, together with PRS, might be applied in combined screening for breast cancer.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Estudos de Coortes , Bancos de Espécimes Biológicos , Biomarcadores Tumorais/genética , Fatores de Risco , Proteína C-Reativa , Reino Unido/epidemiologia
20.
Phys Rev Lett ; 130(26): 266801, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37450818

RESUMO

[BaTiO_{3}]_{m}/[BaZrO_{3}]_{n} (m, n=4-12) superlattices are used to demonstrate the fabrication and deterministic control of an artificial relaxor. X-ray diffraction and atomic-resolution imaging studies confirm the production of high-quality heterostructures. With decreasing BaTiO_{3} layer thickness, dielectric measurements reveal systematically lower dielectric-maximum temperatures, while hysteresis loops and third-harmonic nonlinearity studies suggest a transition from ferroelectriclike to relaxorlike behavior driven by tuning the random-field strength. This system provides a novel platform for studying the size effect and interaction length scale of the nanoscale-polar structures in relaxors.


Assuntos
Compostos de Bário , Temperatura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA