Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 836
Filtrar
1.
Biomimetics (Basel) ; 9(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39056844

RESUMO

Aerodynamic investigation of a bionic coaxial-rotors unmanned aerial vehicle (UAV) is performed. According to Chinese parasol seed features and flight requirements, the bionic conceptual design of a coaxial-rotors UAV is described. A solution procedure for the numerical simulation method, based on a multi-reference frame (MRF) model, is expressed, and a verification study is presented using the typical case. The aerodynamic design is conducted for airfoil, blade, and coaxial-rotors interference. The aerodynamic performance of the coaxial rotors is investigated by numerical simulation analysis. The rotor/motor integrated experiment verification is conducted to assess the performance of the coaxial-rotors UAV. The results indicate that the UAV has excellent aerodynamic performance and bionic configuration, allowing it to adapt to task requirements. The bionic UAV has a good cruise power load reach of 8.36 kg/kw, and the cruise flying thrust force is not less than 78 N at coaxial-rotor and rotor-balloon distance ratios of 0.39 and 1.12, respectively. It has the "blocks stability phenomenon" formed by the rotor downwash speed decreases and the balloon's additional negative pressure. The present method and the bionic configuration provide a feasible design and analysis strategy for coaxial-rotors UAVs.

2.
Transl Cancer Res ; 13(6): 2913-2937, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38988945

RESUMO

Background: Endometrial carcinoma (EC) is one of the most prevalent gynecologic malignancies and requires further classification for treatment and prognosis. Long non-coding RNAs (lncRNAs) and immunogenic cell death (ICD) play a critical role in tumor progression. Nevertheless, the role of lncRNAs in ICD in EC remains unclear. This study aimed to explore the role of ICD related-lncRNAs in EC via bioinformatics and establish a prognostic risk model based on the ICD-related lncRNAs. We also explored immune infiltration and immune cell function across prognostic groups and made treatment recommendations. Methods: A total of 552 EC samples and clinical data of 548 EC patients were extracted from The Cancer Genome Atlas (TCGA) database and University of California Santa Cruz (UCSC) Xena, respectively. A prognostic-related feature and risk model was developed using the least absolute shrinkage and selection operator (LASSO). Subtypes were classified with consensus cluster analysis and validated with t-Distributed Stochastic Neighbor Embedding (tSNE). Kaplan-Meier analysis was conducted to assess differences in survival. Infiltration by immune cells was estimated by single sample gene set enrichment analysis (ssGSEA), Tumor IMmune Estimation Resource (TIMER) algorithm. Quantitative polymerase chain reaction (qPCR) was used to detect lncRNAs expression in clinical samples and cell lines. A series of studies was conducted in vitro and in vivo to examine the effects of knockdown or overexpression of lncRNAs on ICD. Results: In total, 16 ICD-related lncRNAs with prognostic values were identified. Using SCARNA9, FAM198B-AS1, FKBP14-AS1, FBXO30-DT, LINC01943, and AL161431.1 as risk model, their predictive accuracy and discrimination were assessed. We divided EC patients into high-risk and low-risk groups. The analysis showed that the risk model was an independent prognostic factor. The prognosis of the high- and low-risk groups was different, and the overall survival (OS) of the high-risk group was lower. The low-risk group had higher immune cell infiltration and immune scores. Consensus clustering analysis divided the samples into four subtypes, of which cluster 4 had higher immune cell infiltration and immune scores. Conclusions: A prognostic signature composed of six ICD related-lncRNAs in EC was established, and a risk model based on this signature can be used to predict the prognosis of patients with EC.

3.
Cell Rep ; 43(8): 114529, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39046876

RESUMO

Neuronal activation is required for the formation of drug-associated memory, which is critical for the development, persistence, and relapse of drug addiction. Nevertheless, the metabolic mechanisms underlying energy production for neuronal activation remain poorly understood. In the study, a large-scale proteomics analysis of lysine crotonylation (Kcr), a type of protein posttranslational modification (PTM), reveals that cocaine promoted protein Kcr in the hippocampal dorsal dentate gyrus (dDG). We find that Kcr is predominantly discovered in a few enzymes critical for mitochondrial energy metabolism; in particular, pyruvate dehydrogenase (PDH) complex E1 subunit α (PDHA1) is crotonylated at the lysine 39 (K39) residue through P300 catalysis. Crotonylated PDHA1 promotes pyruvate metabolism by activating PDH to increase ATP production, thus providing energy for hippocampal neuronal activation and promoting cocaine-associated memory recall. Our findings identify Kcr of PDHA1 as a PTM that promotes pyruvate metabolism to enhance neuronal activity for cocaine-associated memory.

4.
J Nanobiotechnology ; 22(1): 408, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992664

RESUMO

BACKGROUND: Ovarian cancer (OC) has the highest fatality rate among all gynecological malignancies, necessitating the exploration of novel, efficient, and low-toxicity therapeutic strategies. Ferroptosis is a type of programmed cell death induced by iron-dependent lipid peroxidation and can potentially activate antitumor immunity. Developing highly effective ferroptosis inducers may improve OC prognosis. RESULTS: In this study, we developed an ultrasonically controllable two-dimensional (2D) piezoelectric nanoagonist (Bi2MoO6-MXene) to induce ferroptosis. A Schottky heterojunction between Bi2MoO6 (BMO) and MXene reduced the bandgap width by 0.44 eV, increased the carrier-separation efficiency, and decreased the recombination rate of electron-hole pairs under ultrasound stimulation. Therefore, the reactive oxygen species yield was enhanced. Under spatiotemporal ultrasound excitation, BMO-MXene effectively inhibited OC proliferation by more than 90%, induced lipid peroxidation, decreased mitochondrial-membrane potential, and inactivated the glutathione peroxidase and cystathionine transporter protein system, thereby causing ferroptosis in tumor cells. Ferroptosis in OC cells further activated immunogenic cell death, facilitating dendritic cell maturation and stimulating antitumor immunity. CONCLUSION: We have succeeded in developing a highly potent ferroptosis inducer (BMO-MXene), capable of inhibiting OC progression through the sonodynamic-ferroptosis-immunogenic cell death pathway.


Assuntos
Ferroptose , Morte Celular Imunogênica , Neoplasias Ovarianas , Ferroptose/efeitos dos fármacos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Humanos , Animais , Linhagem Celular Tumoral , Morte Celular Imunogênica/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Bismuto/farmacologia , Bismuto/química
5.
J Nanobiotechnology ; 22(1): 434, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044233

RESUMO

Pulmonary Fibrosis (PF) is a fatal disease in the interstitial lung associated with high mortality, morbidity, and poor prognosis. Transforming growth factor-ß1 (TGF-ß1) is a fibroblast-activating protein that promotes fibrous diseases. Herein, an inhalable system was first developed using milk exosomes (M-Exos) encapsulating siRNA against TGF-ß1 (MsiTGF-ß1), and their therapeutic potential for bleomycin (BLM)-induced PF was investigated. M-siTGF-ß1 was introduced into the lungs of mice with PF through nebulization. The collagen penetration effect and lysosomal escape ability were verified in vitro. Inhaled MsiTGF-ß1 notably alleviated inflammatory infiltration, attenuated extracellular matrix (ECM) deposition, and increased the survival rate of PF mice by 4.7-fold. M-siTGF-ß1 protected lung tissue from BLM toxicity by efficiently delivering specific siRNA to the lungs, leading to TGF-ß1 mRNA silencing and epithelial mesenchymal transition pathway inhibition. Therefore, M-siTGF-ß1 offers a promising avenue for therapeutic intervention in fibrosis-related disorders.


Assuntos
Bleomicina , Colágeno , Transição Epitelial-Mesenquimal , Exossomos , Pulmão , Leite , Fibrose Pulmonar , RNA Interferente Pequeno , Fator de Crescimento Transformador beta1 , Animais , Exossomos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Camundongos , Colágeno/metabolismo , Bleomicina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Leite/química , Camundongos Endogâmicos C57BL , Humanos , Permeabilidade , Masculino , Nebulizadores e Vaporizadores
6.
Abdom Radiol (NY) ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990301

RESUMO

BACKGROUND: Accurate detection of lymph node metastasis (LNM) is crucial for determining the tumor stage, selecting optimal treatment, and estimating the prognosis for cervical cancer. This study aimed to assess the diagnostic efficacy of multimodal diffusion-weighted imaging (DWI) and morphological parameters alone or in combination, for detecting LNM in cervical cancer. METHODS: In this prospective study, we enrolled consecutive cervical cancer patients who received multimodal DWI (conventional DWI, intravoxel incoherent motion DWI, and diffusion kurtosis imaging) before treatment from June 2022 to June 2023. The largest lymph node (LN) observed on each side on imaging was matched with that detected on pathology to improve the accuracy of LN matching. Comparison of the diffusion and morphological parameters of LNs and the primary tumor between the positive and negative LN groups. A combined diagnostic model was constructed using multivariate logistic regression, and the diagnostic performance was evaluated using receiver operating characteristic curves. RESULTS: A total of 93 cervical cancer patients were enrolled: 35 with LNM (48 positive LNs were collected), and 58 without LNM (116 negative LNs were collected). The area under the curve (AUC) values for the apparent diffusion coefficient, diffusion coefficient, mean diffusivity, mean kurtosis, long-axis diameter, short-axis diameter of LNs, and the largest primary tumor diameter were 0.716, 0.720, 0.716, 0.723, 0.726, 0.798, and 0.744, respectively. Independent risk factors included the diffusion coefficient, mean kurtosis, short-axis diameter of LNs, and the largest primary tumor diameter. The AUC value of the combined model based on the independent risk factors was 0.920, superior to the AUC values of all the parameters mentioned above. CONCLUSION: Combining multimodal DWI and morphological parameters improved the diagnostic efficacy for detecting cervical cancer LNM than using either alone.

7.
World J Gastrointest Surg ; 16(6): 1601-1608, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983328

RESUMO

BACKGROUND: This study was designed to investigate the clinical efficacy and safety of Gamma Knife® combined with transarterial chemoembolization (TACE) and immunotherapy in the treatment of primary liver cancer. AIM: To investigate the clinical efficacy and safety of Gamma Knife® combined with TACE and immune-targeted therapy in the treatment of primary liver cancer. METHODS: Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected. All patients underwent Gamma Knife® treatment combined with TACE and immunotherapy. The clinical efficacy, changes in liver function, overall survival (OS), and progression-free survival (PFS) of patients with different treatment responses were evaluated, and adverse reactions were recorded. RESULTS: The last follow-up for this study was conducted on October 31, 2023. Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response (PR) in 27 patients, accounting for 52.94% (27/51); stable disease (SD) in 16 patients, accounting for 31.37% (16/51); and progressive disease (PD) in 8 patients, accounting for 15.69% (8/51). The objective response rate was 52.94%, and the disease control rate was 84.31%. Alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment (all P = 0.000). The median OS was 26 months [95% confidence interval (95%CI): 19.946-32.054] in the PR group and 19 months (95%CI: 14.156-23.125) in the SD + PD group, with a statistically significant difference (P = 0.015). The median PFS was 20 months (95%CI: 18.441-34.559) in the PR group and 12 months (95%CI: 8.745-13.425) in the SD + PD group, with a statistically significant difference (P = 0.002). Common adverse reactions during treatment included nausea and vomiting (39.22%), thrombocytopenia (27.45%), and leukopenia (25.49%), with no treatment-related deaths reported. CONCLUSION: Gamma Knife® combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38963748

RESUMO

Pulse wave analysis, a non-invasive and cuffless approach, holds promise for blood pressure (BP) measurement in precision medicine. In recent years, pulse wave learning for BP estimation has undergone extensive scrutiny. However, prevailing methods still encounter challenges in grasping comprehensive features from pulse waves and generalizing these insights for precise BP estimation. In this study, we propose a general pulse wave deep learning (PWDL) approach for BP estimation, introducing the OVAR-BPnet model to powerfully capture intricate pulse wave features and showcasing its effectiveness on multiple types of pulse waves. The approach involves constructing population pulse waves and employing a model comprising an omni-scale convolution subnet, a Vision Transformer subnet, and a multilayer perceptron subnet. This design enables the learning of both single-period and multi-period waveform features from multiple subjects. Additionally, the approach employs a data augmentation strategy to enhance the morphological features of pulse waves and devise a label sequence regularization strategy to strengthen the intrinsic relationship of the subnets' output. Notably, this is the first study to validate the performance of the deep learning approach of BP estimation on three types of pulse waves: photoplethysmography, forehead imaging photoplethysmography, and radial artery pulse pressure waveform. Experiments show that the OVAR-BPnet model has achieved advanced levels in both evaluation indicators and international evaluation criteria, demonstrating its excellent competitiveness and generalizability. The PWDL approach has the potential for widespread application in convenient and continuous BP monitoring systems.

9.
J Imaging Inform Med ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977614

RESUMO

This study is to analyze and compare the diagnostic efficacy of the ADNEX model and O-RADS in Northeast China for benign and malignant ovarian-adnexal tumors. From July 2020 to February 2022, ultrasound images of 312 ovarian-adnexal masses included in the study were analyzed retrospectively, and the properties of these masses were identified using the ADNEX model and O-RADS. The diagnostic efficiency of the ADNEX model and O-RADS was analyzed using a ROC curve, and the capacities of the two models in differentiating benign and malignant ovarian masses at the optimum cutoff value were compared, as well as the consistency of their diagnosis results was evaluated. The study included 312 ovarian-adnexal masses, including 145 malignant masses and 167 benign masses from 287 patients with an average age of (46.8 ± 11.3) years. The AUC of the ADNEX model was 0.974, and the optimum cutoff value was the risk value > 24.2%, with the corresponding sensitivity and specificity being 97.93 and 86.83, respectively. The AUC of the O-RADS was 0.956, and the optimum cutoff value was > O-RADS 3, with the corresponding sensitivity and specificity being 97.24 and 85.03, respectively. The AUCs of the two models were 0.924 and 0.911 at the optimum cutoff values, with no statistical differences between them (P = 0.284). Consistency analysis: the kappa values of the two models for the determination and pathological results of masses were 0.840 and 0.815, respectively, and that for the diagnostic outcomes was 0.910. Both the ADNEX model and O-RADS had good diagnostic performance in people from Northeast China. Their diagnostic capabilities were similar, and diagnostic results were highly consistent at the optimum cutoff values.

10.
Hepatol Int ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965190

RESUMO

BACKGROUND AND AIMS: The risk of hepatocellular carcinoma (HCC) occurrence following antiviral therapy in patients with chronic hepatitis C (CHC) remains unclear. The current study aims to compare: (1) the HCC occurrence rate following sustained virological response (SVR) versus non-response (NR); (2) the HCC occurrence rate following direct-acting antiviral (DAA) therapy versus interferon (IFN)-based therapy, and (3) the HCC occurrence rate in SVR patients with or without cirrhosis. METHODS: A search was performed for articles published between January 2017 and July 2022. Studies were included if they assessed HCC occurrence rate in CHC patients following anti-HCV therapy. Random effects meta-analysis was used to synthesize the results from individual studies. RESULTS: A total of 23 studies including 29,395 patients (IFN-based = 6, DAA = 17; prospective = 10, retrospective = 13) were included in the review. HCC occurrence was significantly lower in CHC with SVR (1.54 per 100 person-years (py, 95% CI 1.52, 1.57) than those in non-responders (7.80 py, 95% CI 7.61, 7.99). Stratified by HCV treatment regimens, HCC occurrence following SVR was 1.17 per 100 py (95% CI 1.11, 1.22) and 1.60 per 100 py (95% CI 1.58, 1.63) in IFN- and DAA treatment-based studies. HCC occurrence was 0.85 per 100 py (95% CI 0.85, 0.86) in the non-cirrhosis population and rose to 2.47 per 100 py (95% CI 2.42, 2.52) in the cirrhosis population. Further meta-regression analysis showed that treatment types were not associated with a higher HCC occurrence rate, while cirrhosis status was an important factor of HCC occurrence rate. CONCLUSION: HCC occurrence was significantly lower in the SVR population than in the NR population. HCC risk following SVR occurred three times more frequently in patients with cirrhosis than patients without cirrhosis. However, we found no significant difference in HCC occurrence risk following SVR between DAA and IFN therapies. CLINICAL TRIAL NUMBER: CRD42023473033.

11.
Phytomedicine ; 131: 155758, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38843643

RESUMO

BACKGROUND: The adaptor protein apoptosis-associated speck-like protein (ASC) containing a caspase recruitment domain (CARD) can be activated through pyrin domain (PYD) interactions between sensors and ASC, and through CARD interactions between caspase-1 and ASC. Although the majority of ternary inflammasome complexes depend on ASC, drugs targeting ASC protein remain scarce. After screening natural compounds from Isatidis Radixin, we found that tryptanthrin (TPR) could inhibit NLRP3-induced IL-1ß and caspase-1 production, but the underlying anti-inflammatory mechanisms remain to be elucidated. PURPOSE: The purpose of this study was to determine the impact of TPR on the NLRP3, NLRC4, and AIM2 inflammasomes and the underlying mechanisms. Additionally, the efficacy of TPR was analysed in the further course of methionine- and choline-deficient (MCD)-induced NASH and lipopolysaccharide (LPS)-induced sepsis models of mice. METHODS: In vitro studies used bone marrow-derived macrophages to assess the anti-inflammatory activity of TPR, and the techniques included western blot, testing of intracellular K+ and Ca2+, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), co-immunoprecipitation, ASC oligomerization assay, surface plasmon resonance (SPR), and molecular docking. We used LPS-induced sepsis models and MCD-induced NASH models in vivo to evaluate the effectiveness of TPR in inhibiting inflammatory diseases. RESULTS: Our observations suggested that TPR could inhibit NLRP3, NLRC4, and AIM2 inflammasome activation. As shown in a mouse model of inflammatory diseases caused by MCD-induced NASH and LPS-induced sepsis, TPR significantly alleviated the progression of diseases. TPR interrupted the interactions between ASC and NLRP3/NLRC4/AIM2 in the co-immunoprecipitation experiment, and stable binding of TPR to ASC was also evident in SPR experiments. The underlying mechanisms of anti-inflammatory activities of TPR might be associated with targeting ASC, in particular, PYD domain of ASC. CONCLUSION: In general, the requirement for ASC in multiple inflammasome complexes makes TPR, as a novel broad-spectrum inflammasome inhibitor, potentially useful for treating a wide range of multifactorial inflammasome-related diseases.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Proteínas de Ligação ao Cálcio , Inflamassomos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Hepatopatia Gordurosa não Alcoólica , Quinazolinas , Animais , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Masculino , Proteínas de Ligação ao Cálcio/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Quinazolinas/farmacologia , Camundongos , Proteínas Reguladoras de Apoptose/metabolismo , Interleucina-1beta/metabolismo , Proteínas de Ligação a DNA/metabolismo , Caspase 1/metabolismo , Sepse/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Modelos Animais de Doenças
12.
Front Endocrinol (Lausanne) ; 15: 1412942, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919477

RESUMO

Medullary thyroid carcinoma (MTC) accounts for only 3% of all thyroid carcinomas: 75% as sporadic MTC (sMTC) and 25% as hereditary MTC (hMTC) in the context of multiple endocrine neoplasia type 2 (MEN2). Early diagnosis is possible by determining the tumour marker calcitonin (Ctn) when clarifying nodular goitre and by detecting the mutation in the proto-oncogene RET in the MEN2 families. If the Ctn level is only slightly elevated, up to 30 pg/ml in women and up to 60 pg/ml in men, follow-up checks are advisable. At higher levels, surgery should be considered; at a level of > 100 pg/ml, surgery is always advisable. The treatment of choice is total thyroidectomy, possibly with central lymphadenectomy. In the early stage, cure is possible with adequate surgery; in the late stage, treatment with tyrosine kinase inhibitors is an option. RET A mutation analysis should be performed on all patients with MTC. During follow-up, a biochemical distinction is made between: healed (Ctn not measurably low), biochemically incomplete (Ctn increased without tumour detection) and structural tumour detection (metastases on imaging). After MTC surgery, the following results should be available for classification in follow-up care: (i) histology, Ctn immunohistology if necessary, (ii) classification according to the pTNM scheme, (iii) the result of the RET analysis for categorisation into the hereditary or sporadic variant and (iiii) the postoperative Ctn value. Tumour progression is determined by assessing the Ctn doubling time and the RECIST criteria on imaging. In most cases, "active surveillance" is possible. In the case of progression and symptoms, the following applies: local (palliative surgery, radiotherapy) before systemic (tyrosine kinase inhibitors).


Assuntos
Carcinoma Medular , Neoplasia Endócrina Múltipla Tipo 2a , Proto-Oncogene Mas , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Carcinoma Medular/genética , Carcinoma Medular/congênito , Carcinoma Medular/diagnóstico , Carcinoma Medular/patologia , Carcinoma Medular/terapia , Neoplasia Endócrina Múltipla Tipo 2a/genética , Neoplasia Endócrina Múltipla Tipo 2a/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2a/patologia , Neoplasia Endócrina Múltipla Tipo 2a/terapia , Proteínas Proto-Oncogênicas c-ret/genética , Tireoidectomia , Mutação , Calcitonina/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/patologia
13.
ACS Omega ; 9(24): 26519-26539, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38911819

RESUMO

Increasing evidence indicates that peripheral blood vessels play a pivotal role in regulating tumor growth with the presence of new blood vessels facilitating tumor growth and metastasis. Nevertheless, the impact of specific molecule-mediated angiogenesis on the tumor immune microenvironment (TIME) and individual prognosis of uterine corpus endometrial carcinoma (UCEC) remains uncertain. The transcriptome information on 217 prognostic angiogenesis-related genes was integrated, and the angiogenesis patterns of 506 UCEC patients in The Cancer Genome Atlas (TCGA) cohort were comprehensively evaluated. We identified five angiogenic subtypes, namely, EC1, EC2, EC3, EC4, and EC5, which differed significantly in terms of prognosis, clinicopathological features, cancer hallmarks, genomic mutations, TIME patterns, and immunotherapy responses. Additionally, an angiogenesis-related prognostic risk score (APRS) was constructed to enable an individualized comprehensive evaluation. In multiple cohorts, APRS demonstrated a powerful predictive ability for the prognosis of UCEC patients. Likewise, APRS was confirmed to be associated with clinicopathological features, genomic mutations, cancer hallmarks, and TIME patterns in UCEC patients. The predictability of APRS for immune checkpoint inhibitor (ICI) therapy was also salient. Subsequently, the expression levels of four angiogenesis-related hub genes were verified by qRT-PCR, immunohistochemistry, and single-cell sequencing data analysis. The effects of four representative genes on angiogenesis were validated by Wound-Healing and Transwell assays, tube formation assay in vitro, and tumor xenograft model in vivo. This study proffered a new classification of UCEC patients based on angiogenesis. The established APRS may contribute to individualized prognosis prediction and immunotherapy selections that are better suited for UCEC patients.

14.
Front Biosci (Landmark Ed) ; 29(6): 208, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38940030

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.


Assuntos
Tecido Adiposo Marrom , Microbioma Gastrointestinal , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/microbiologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/terapia , Síndrome do Ovário Policístico/fisiopatologia , Humanos , Feminino , Microbioma Gastrointestinal/fisiologia , Tecido Adiposo Marrom/metabolismo , Animais , Resistência à Insulina , Transplante de Microbiota Fecal , Obesidade/microbiologia , Obesidade/metabolismo , Obesidade/terapia
15.
Int J Biol Macromol ; 274(Pt 1): 133387, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914384

RESUMO

Mixed-matrix membranes (MMMs) exhibit significant potential for dye/salt separation. However, overcoming the "trade-off" between permeability and selectivity, as well as membrane fouling, remains a formidable task. In this work, a biocatalytic membrane was prepared using polydopamine (PDA) as a "bridge" connecting the metal-organic framework (MOF)-based MMM and immobilized laccase. The MOF-based MMM featured an interconnected MOF anchoring on the polyvinylidene fluoride (PVDF) skeleton structure, effectively mitigating the "trade-off" phenomenon and enabling efficient separation of dyes and salts. Enzyme-MOF was in situ grown on the MOF-based MMM via coordination reactions between PDA and metal ion, effectively degrading the adhesion of organic pollutants and fouling, ensuring the long-term stable operation of the membrane. The Lac-MOF@PDA MMM exhibited excellent water permeability of 142.4 L·m-2·h-1, 100 % rejection for dye, and less than 10 % rejection for NaCl. Furthermore, the separation mechanism of Lac-MOF@PDA MMM was systematically investigated, and the results suggested a synergistic combination of rejection, adsorption and catalysis processes. This biocatalytic membrane with multiple sieving and biological catalysis is expected to pave a promising way for efficient wastewater treatment applications.

16.
Soft Robot ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38868951

RESUMO

The somatosensory system is crucial for living beings to survive and thrive in complex environments and to interact with their surroundings. Similarly, rapidly developed soft robots need to be aware of their own posture and detect external stimuli. Bending and force sensing are key for soft machines to achieve embodied intelligence. Here, we present a soft inductive bimodal sensor (SIBS) that uses the strain modulation of magnetic permeability and the eddy-current effect for simultaneous bidirectional bending and force sensing with only two wires. The SIBS is made of a flexible planar coil, a porous ferrite film, and a soft conductive film. By measuring the inductance at two different frequencies, the bending angle and force can be obtained and decoupled. Rigorous experiments revealed that the SIBS can achieve high resolution (0.44° bending and 1.09 mN force), rapid response, excellent repeatability, and high durability. A soft crawling robot embedded with one SIBS can sense its own shape and interact with and respond to external stimuli. Moreover, the SIBS is demonstrated as a wearable human-machine interaction to control a crawling robot via wrist bending and touching. This highlights that the SIBS can be readily implemented in diverse applications for reliable bimodal sensing.

17.
Sci Rep ; 14(1): 12605, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824246

RESUMO

The diagnostic value of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules is still controversial, so we used meta-analysis to seek controversial answers. The PubMed, OVID, and CNKI databases were searched according to the inclusion and exclusion criteria. The literature was selected from the establishment of each database to February 2024. The QUADAS-2 tool assessed diagnostic test accuracy. SROC curves and Spearman's correlation coefficient were made by Review Manager 5.4 software to assess the presence of threshold effects in the literature. Meta-Disc1.4 software was used for Cochrane-Q and χ2 tests, which be used to evaluate heterogeneity, with P-values and I2 indicating heterogeneity levels. The appropriate effect model was selected based on the results of the heterogeneity test. Stata18.0 software was used to evaluate publication bias. The diagnostic accuracy of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules was evaluated by calculating the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the SROC curve. A total of 31 studies included 3811 patients with 4718 nodules were analyzed. There is no heterogeneity caused by the threshold effect, but there is significant non-threshold heterogeneity. Combined diagnostic metrics were: sensitivity = 0.93, specificity = 0.91, DOR = 168.41, positive likelihood ratio = 10.60, and negative likelihood ratio = 0.07. The SROC curve area was 0.97. Contrast-enhanced ultrasound and elastography show high diagnostic accuracy for thyroid nodules, offering a solid foundation for early diagnosis and treatment.Trial registration. CRD42024509462.


Assuntos
Meios de Contraste , Técnicas de Imagem por Elasticidade , Nódulo da Glândula Tireoide , Ultrassonografia , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Técnicas de Imagem por Elasticidade/métodos , Ultrassonografia/métodos , Diagnóstico Diferencial , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico
18.
Hepatol Int ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740699

RESUMO

BACKGROUND: Evidence concerning long-term outcome of robotic liver resection (RLR) and laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) patients is scarce. METHODS: This study enrolled all patients who underwent RLR and LLR for resectable HCC between July 2016 and July 2021. Propensity score matching (PSM) was employed to create a 1:3 match between the RLR and LLR groups. A comprehensive collection and analysis of patient data regarding efficacy and safety have been conducted, along with the evaluation of the learning curve for RLR. RESULTS: Following PSM, a total of 341 patients were included, with 97 in the RLR group and 244 in the LLR group. RLR group demonstrated a significantly longer operative time (median [IQR], 210 [152.0-298.0] min vs. 183.5 [132.3-263.5] min; p = 0.04), with no significant differences in other perioperative and short-term postoperative outcomes. Overall survival (OS) was similar between the two groups (p = 0.43), but RLR group exhibited improved recurrence-free survival (RFS) (median of 65 months vs. 56 months, p = 0.006). The estimated 5-year OS for RLR and LLR were 74.8% (95% CI: 65.4-85.6%) and 80.7% (95% CI: 74.0-88.1%), respectively. The estimated 5-year RFS for RLR and LLR were 58.6% (95% CI: 48.6-70.6%) and 38.3% (95% CI: 26.4-55.9%), respectively. In the multivariate Cox regression analysis, RLR (HR: 0.586, 95% CI (0.393-0.874), p = 0.008) emerged as an independent predictor of reducing recurrence rates and enhanced RFS. The operative learning curve indicates that approximately after the 11th case, the learning curve of RLR stabilized and entered a proficient phase. CONCLUSIONS: OS was comparable between RLR and LLR, and while RFS was improved in the RLR group. RLR demonstrates oncological effectiveness and safety for resectable HCC.

19.
Cell Mol Life Sci ; 81(1): 226, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775844

RESUMO

Vemurafenib has been used as first-line therapy for unresectable or metastatic melanoma with BRAFV600E mutation. However, overall survival is still limited due to treatment resistance after about one year. Therefore, identifying new therapeutic targets for melanoma is crucial for improving clinical outcomes. In the present study, we found that lowering intracellular cholesterol by knocking down DHCR24, the limiting synthetase, impaired tumor cell proliferation and migration and abrogated the ability to xenotransplant tumors. More importantly, administration of DHCR24 or cholesterol mediated resistance to vemurafenib and promoted the growth of melanoma spheroids. Mechanistically, we identified that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol synthesized by the enzyme cytochrome P450 27A1 (CYP27A1), reproduces the phenotypes induced by DHCR24 or cholesterol administration and activates Rap1-PI3K/AKT signaling. Accordingly, CYP27A1 is highly expressed in melanoma patients and upregulated by DHCR24 induction. Dafadine-A, a CYP27A1 inhibitor, attenuates cholesterol-induced growth of melanoma spheroids and abrogates the resistance property of vemurafenib-resistant melanoma cells. Finally, we confirmed that the effects of cholesterol on melanoma resistance require its metabolite 27HC through CYP27A1 catalysis, and that 27HC further upregulates Rap1A/Rap1B expression and increases AKT phosphorylation. Thus, our results suggest that targeting 27HC may be a useful strategy to overcome treatment resistance in metastatic melanoma.


Assuntos
Proliferação de Células , Colestanotriol 26-Mono-Oxigenase , Colesterol , Hidroxicolesteróis , Melanoma , Células-Tronco Neoplásicas , Vemurafenib , Vemurafenib/farmacologia , Vemurafenib/uso terapêutico , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/metabolismo , Melanoma/genética , Hidroxicolesteróis/metabolismo , Hidroxicolesteróis/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Colestanotriol 26-Mono-Oxigenase/metabolismo , Colestanotriol 26-Mono-Oxigenase/genética , Colesterol/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Linhagem Celular Tumoral , Camundongos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Front Robot AI ; 11: 1383732, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774468

RESUMO

In traditional cardiac ultrasound diagnostics, the process of planning scanning paths and adjusting the ultrasound window relies solely on the experience and intuition of the physician, a method that not only affects the efficiency and quality of cardiac imaging but also increases the workload for physicians. To overcome these challenges, this study introduces a robotic system designed for autonomous cardiac ultrasound scanning, with the goal of advancing both the degree of automation and the quality of imaging in cardiac ultrasound examinations. The system achieves autonomous functionality through two key stages: initially, in the autonomous path planning stage, it utilizes a camera posture adjustment method based on the human body's central region and its planar normal vectors to achieve automatic adjustment of the camera's positioning angle; precise segmentation of the human body point cloud is accomplished through efficient point cloud processing techniques, and precise localization of the region of interest (ROI) based on keypoints of the human body. Furthermore, by applying isometric path slicing and B-spline curve fitting techniques, it independently plans the scanning path and the initial position of the probe. Subsequently, in the autonomous scanning stage, an innovative servo control strategy based on cardiac image edge correction is introduced to optimize the quality of the cardiac ultrasound window, integrating position compensation through admittance control to enhance the stability of autonomous cardiac ultrasound imaging, thereby obtaining a detailed view of the heart's structure and function. A series of experimental validations on human and cardiac models have assessed the system's effectiveness and precision in the correction of camera pose, planning of scanning paths, and control of cardiac ultrasound imaging quality, demonstrating its significant potential for clinical ultrasound scanning applications.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...