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1.
J Immunol ; 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39400236

RESUMO

Hepatitis B virus (HBV) is the most common chronic viral infection globally, affecting ∼360 million people and causing about 1 million deaths annually due to end-stage liver disease or hepatocellular carcinoma. Current antiviral treatments rarely achieve a functional cure for chronic hepatitis B, highlighting the need for improved monitoring and intervention strategies. This study explores the role of the sphingosine kinase 1 (SphK1)-sphingosine-1-phosphate (S1P) axis in HBV-related liver injury. We investigated the association between serum S1P concentration and HBV DNA levels in chronic hepatitis B patients, finding a significant positive correlation. Additionally, SphK1 was elevated in liver tissues of HBV-positive hepatocellular carcinoma patients, particularly in HBsAg-positive regions. HBV infection models in HepG2-sodium taurocholate cotransporting polypeptide cells confirmed that HBV enhances SphK1 expression and S1P production. Inhibition of HBV replication through antiviral agents and the CRISPR-Cas9 system reduced SphK1 and S1P levels. Further, we identified the transcription factor USF1 as a key regulator of SphK1 expression during HBV infection. USF1 binds to the SphK1 promoter, increasing its transcriptional activity, and is upregulated in response to HBV infection. In vivo studies in mice demonstrated that HBV exposure promotes the expression of USF1 and SphK1-S1P. These findings suggest that the SphK1-S1P axis, regulated by HBV-induced USF1, could serve as a potential biomarker and therapeutic target for HBV-related liver injury.

2.
Proc Natl Acad Sci U S A ; 119(3)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042776

RESUMO

Sympathetic innervation regulates energy balance, and the nerve density in the adipose tissues changes under various metabolic states, resulting in altered neuronal control and conferring resilience to metabolic challenges. However, the impact of the immune milieu on neuronal innervation is not known. Here, we examined the regulatory role on nerve plasticity by eosinophils and found they increased cell abundance in response to cold and produced nerve growth factor (NGF) in the white adipose tissues (WAT). Deletion of Ngf from eosinophils or depletion of eosinophils impairs cold-induced axonal outgrowth and beiging process. The spatial proximity between sympathetic nerves, IL-33-expressing stromal cells, and eosinophils was visualized in both human and mouse adipose tissues. At the cellular level, the sympathetic adrenergic signal induced calcium flux in the stromal cells and subsequent release of IL-33, which drove the up-regulation of IL-5 from group 2 innate lymphoid cells (ILC2s), leading to eosinophil accretion. We propose a feed-forward loop between sympathetic activity and type 2 immunity that coordinately enhances sympathetic innervation and promotes energy expenditure.


Assuntos
Tecido Adiposo/metabolismo , Axônios/metabolismo , Plasticidade Celular/fisiologia , Eosinófilos/imunologia , Tecido Adiposo Branco/metabolismo , Adulto , Animais , Cálcio , Feminino , Humanos , Imunidade Inata , Interleucina-33/metabolismo , Linfócitos/imunologia , Camundongos , Pessoa de Meia-Idade , Fator de Crescimento Neural/metabolismo , Células Estromais/metabolismo , Sistema Nervoso Simpático/fisiologia
3.
Anal Chem ; 96(19): 7697-7705, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38697043

RESUMO

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.


Assuntos
Elementos da Série dos Lantanídeos , Imageamento por Ressonância Magnética , Nanopartículas , Polímeros , Semicondutores , Imageamento por Ressonância Magnética/métodos , Animais , Elementos da Série dos Lantanídeos/química , Polímeros/química , Nanopartículas/química , Camundongos , Humanos , Gadolínio/química , Luminescência , Oxigênio Singlete/química , Ítrio/química , Fluoretos/química , Camundongos Nus
4.
Small ; 20(30): e2311827, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38381114

RESUMO

The expeditious growth of wearable electronic devices has boomed the development of versatile smart textiles for personal health-related applications. In practice, integrated high-performance systems still face challenges of compromised breathability, high cost, and complicated manufacturing processes. Herein, a breathable fibrous membrane with dual-driven heating and electromagnetic interference (EMI) shielding performance is developed through a facile process of electrospinning followed by targeted conformal deposition. The approach constructs a robust hierarchically coaxial heterostructure consisting of elastic polymers as supportive "core" and dual-conductive components of polypyrrole and copper sulfide (CuS) nanosheets as continuous "sheath" at the fiber level. The CuS nanosheets with metal-like electrical conductivity demonstrate the promising potential to substitute the expensive conductive nano-materials with a complex fabricating process. The as-prepared fibrous membrane exhibits high electrical conductivity (70.38 S cm-1), exceptional active heating effects, including solar heating (saturation temperature of 69.7 °C at 1 sun) and Joule heating (75.2 °C at 2.9 V), and impressive EMI shielding performance (50.11 dB in the X-band), coupled with favorable air permeability (161.4 mm s-1 at 200 Pa) and efficient water vapor transmittance (118.9 g m-2 h). This work opens up a new avenue to fabricate versatile wearable devices for personal thermal management and health protection.

5.
BMC Cancer ; 24(1): 1232, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375615

RESUMO

There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Humanos , Colangiocarcinoma/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/mortalidade , Colangiocarcinoma/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Idoso , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/diagnóstico , Adulto , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Biomarcadores Tumorais/genética , Reparo de Erro de Pareamento de DNA , Imuno-Histoquímica
6.
Dis Colon Rectum ; 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39329380

RESUMO

BACKGROUND: Scant data are available on heterogenous staining of mismatch repair protein in colorectal cancer. OBJECTIVE: This study aimed to improve insights into clinicopathologic features and prognosis of colorectal cancer harboring heterogenous mismatch repair protein staining. DESIGN: A single-center retrospective observational study. SETTING: This study was conducted in a tertiary referral center in China between 2014 and 2018. PATIENTS: Colorectal cancers with heterogenous staining of mismatch repair protein were included. MAIN OUTCOMES MEASURES: Clinicopathologic and molecular features, and survival outcomes were analyzed. RESULTS: A total of 151 out of 6721 colorectal cancers (2.2%) exhibited heterogenous staining for at least one mismatch repair protein, with intraglandular heterogeneity being the most common pattern (89.4%). Heterogenous MLH1 staining was significantly associated with distant metastasis (p = 0.03), while heterogenous MSH2 staining was associated with left-sided (p = 0.03) and earlier pT stage tumors (p = 0.02). The rates of microsatellite instability-high, KRAS and BRAF mutation were 12.6%, 47.3% and 3.4%, respectively. Microsatellite instability-high was significantly associated with higher intraglandular MSH6 heterogeneity frequency (p < 0.001) and decreased MSH6 expression level (< 27.5%, p = 0.01). BRAF mutation was associated with the coexistence of intraglandular and clonal heterogeneity (p = 0.003) and decreased PMS2 expression level (p = 0.01). Multivariable analysis revealed that progression-free survival was significantly associated with tumor stage (p = 0.003), stroma fraction (p = 0.004), and heterogenous PMS2 staining (p = 0.02). Overall survival was linked to tumor stage (p = 0.006) and BRAF mutation (p = 0.01). LIMITATIONS: The limitations of this study include the absence of testing for MLH1 promoter methylation and mismatch repair gene mutations, its retrospective design, and insufficient data related to direct comparison with deficient mismatch repair and proficient mismatch repair colorectal cancer. CONCLUSIONS: Heterogenous mismatch repair protein staining in colorectal cancer exhibits distinct associations with tumor location, stage, microsatellite instability, BRAF mutation and prognosis. It is recommended to report MSH6 heterogeneity as it may indicate microsatellite instability-high. See Video Abstract.

7.
Chem Rev ; 122(6): 6850-6918, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35234464

RESUMO

Photoacoustic (PA) imaging technology, a three-dimensional hybrid imaging modality that integrates the advantage of optical and acoustic imaging, has great application prospects in molecular imaging due to its high imaging depth and resolution. To endow PA imaging with the ability for real-time molecular visualization and precise biomedical diagnosis, numerous activatable molecular PA probes which can specifically alter their PA intensities upon reacting with the targets or biological events of interest have been developed. This review highlights the recent developments of activatable PA probes for precise biomedical applications including molecular detection of the biotargets and imaging of the biological events. First, the generation mechanism of PA signals will be given, followed by a brief introduction to contrast agents used for PA probe design. Then we will particularly summarize the general design principles for the alteration of PA signals and activatable strategies for developing precise PA probes. Furthermore, we will give a detailed discussion of activatable PA probes in molecular detection and biomedical imaging applications in living systems. At last, the current challenges and outlooks of future PA probes will be discussed. We hope that this review will stimulate new ideas to explore the potentials of activatable PA probes for precise biomedical applications in the future.


Assuntos
Imagem Molecular , Técnicas Fotoacústicas , Imagem Molecular/métodos , Sondas Moleculares/química , Técnicas Fotoacústicas/métodos , Análise Espectral
8.
BMC Pregnancy Childbirth ; 24(1): 288, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637738

RESUMO

BACKGROUND: Uniparental disomy is the inheritance of a homologous chromosome pair or part of homologous chromosomes from only one parent. However, the clinical significance of uniparental disomy and the difference among the prognosis of involvement of different chromosomes remain unclear. OBJECTIVE: To assess the associated prenatal ultrasound presentations and clinical outcomes of uniparental disomy on different chromosomes and to analyze the relationship between prenatal ultrasound markers and clinical outcomes. STUDY DESIGN: We retrospectively analyzed data from fetuses with uniparental disomy diagnosed using chromosome microarray analysis with the Affymetrix CytoScan HD array at our institution between January 2013 and September 2022. The relationship between prenatal ultrasound findings, the involved chromosome(s), and clinical outcomes was evaluated. RESULTS: During the study period, 36 fetuses with uniparental disomy were diagnosed, and two cases were excluded for non-available postnatal data. Finally, 34 fetuses were included in our study, of which 30 (88.2%) had uniparental disomy occurring on a single chromosome, while four (11.8%) were identified with uniparental disomy on different chromosomes. The most frequently involved chromosomes were chromosomes 16, X and 2, which presented in 8 (23.5%), 5 (14.7%) and 4 (11.8%), respectively. Prenatal ultrasound abnormalities were detected in 21 fetuses, with the most common category being multiple abnormalities (12 (57.1%)). Fetal growth restriction was identified in 14 (41.2%) fetuses, all of which coexisted with other abnormal findings. The rate of adverse perinatal outcomes in patients with uniparental disomy and fetal abnormalities was significantly higher than those without abnormalities (76.2% versus 15.4%, P = 0.002). The incidence of fetal or neonatal death was significantly higher in fetuses with fetal growth restriction than those without (85.7% versus 30.0%, P = 0.004). CONCLUSIONS: The prognosis of fetuses with uniparental disomy combined with fetal abnormalities, especially fetal growth restriction, was much poorer than those without.


Assuntos
Anormalidades Múltiplas , Dissomia Uniparental , Feminino , Recém-Nascido , Gravidez , Humanos , Dissomia Uniparental/genética , Estudos Retrospectivos , Retardo do Crescimento Fetal/genética , Ultrassonografia Pré-Natal , Diagnóstico Pré-Natal
9.
Ann Noninvasive Electrocardiol ; 29(6): e70012, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39425897

RESUMO

INTRODUCTION: The efficacy and safety of Ivabradine for patients with acute heart failure (AHF) is controversial, and there are few clinical trials addressing this topic. METHODS: We performed this meta-analysis to evaluate efficacy and safety of Ivabradine treatment for patients with acute heart failure. We obtained data for controlled trials using the PubMed, Cochrane Library, EMBASE, and Clinical Trials.gov databases. The efficacy endpoints included change in heart rate, brain natriuretic peptide (BNP) levels, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, ejection fraction (EF) values, and a 6-min walk distance. The safety endpoints included mortality, cardiogenic mortality, incidents of hospital readmission, bradycardia, and atrial fibrillation. Ten randomized controlled trials (RCTs) met our criteria, and data from 656 patients were included for the study. RESULTS: Ivabradine treatment significantly decreased heart rate and BNP and NT-proBNP levels compared with those seen in the control group. EF values were significantly increased upon ivabradine treatment. No significant differences were observed in the endpoints of the 6-min walk distance, all-cause mortality, cardiogenic mortality, incidents of hospital readmission, bradycardia, and atrial fibrillation data between ivabradine treated and control groups. CONCLUSIONS: Ivabradine can reduce heart rate and BNP and NT-pro BNP levels and elevate EF values and 6-min walk distance data significantly in acute heart failure patients. It also exhibits a stable safety profile, with similar risks of all-cause mortality, cardiogenic mortality, incidents of readmission, and major adverse cardiovascular effects compared with those of the control group.


Assuntos
Insuficiência Cardíaca , Ivabradina , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Ivabradina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Doença Aguda , Resultado do Tratamento , Fármacos Cardiovasculares/uso terapêutico , Peptídeo Natriurético Encefálico/sangue , Frequência Cardíaca/efeitos dos fármacos , Fragmentos de Peptídeos
10.
Acta Radiol ; 65(7): 700-707, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38856151

RESUMO

BACKGROUND: Focal liver lesions (FLLs) are a common form of liver disease, and identifying accurate pathological types is required to guide treatment and evaluate prognosis. PURPOSE: To compare and analyze the application effect of contrast-enhanced ultrasound (CEUS) and conventional ultrasound (US) in the clinical diagnosis of focal liver lesions. MATERIAL AND METHODS: A retrospective analysis was performed on 682 patients with space-occupying liver lesions admitted to our hospital between December 2015 and August 2021. Of these, 280 underwent CEUS-guided biopsies and 402 underwent conventional US biopsies, with the results of each biopsy subsequently compared between the two groups. The success rate and accuracy of the biopsies and their relationship with different pathological features were also analyzed. RESULTS: The success rate, sensitivity, diagnostic accuracy, positive predictive value, and negative predictive value of the CEUS group were significantly higher than those of the US group (P < 0.05). Lesion size accuracy in the CEUS group was significantly higher than that in the US group (89.29% vs. 40.55%; P < 0.05). Lesion type accuracy in the CEUS group was significantly higher than that in the US group (86.49% vs. 43.59%), and the difference between the two groups was statistically significant (P < 0.05). The logistic regression analysis indicated that malignant lesions, lesions ≥5 cm, and lesions ≤1 cm were independent factors affecting the success rate of the puncture procedure (P < 0.05). CONCLUSION: The sensitivity, specificity, and diagnostic accuracy of lesion size and type in the CEUS group were higher than those in the US group.


Assuntos
Meios de Contraste , Sensibilidade e Especificidade , Ultrassonografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto , Idoso , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Valor Preditivo dos Testes , Adulto Jovem
11.
Nano Lett ; 23(22): 10579-10586, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37934045

RESUMO

Two-dimensional (2D) nanomaterials have been widely applied as building blocks of nanoporous materials for high-precision separations. However, most existing 2D nanomaterials suffer from poor continuity and a lack of interior linking, resulting in deteriorated performance when assembled into macroscopic bulk structures. Here, a unique superspreading-based phase inversion technique is proposed to directly construct 2D nanofibrous networks (NFNs) from a polymer solution. By tailoring capillary behavior, polymer solution droplets evolve into ultrathin liquid films through superspreading; manipulating phase instability, subsequently, enables the liquid film to phase invert into continuous nanostructured networks. The assembled single-layered NFNs possess integrated structural superiorities of 1D nanoscale fiber diameter (∼40 nm) and 2D lateral infinity, exhibiting a weblike nanoarchitecture with extremely small through-pores (∼100 nm). Our NFNs show remarkable performances in air filtration (PM0.3 removal) and water purification (microfiltration level). This creation of such attractive 2D fibrous nanomaterials can pave the way for versatile high-performance separation applications.

12.
Nano Lett ; 23(7): 2659-2668, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-36940420

RESUMO

The targeting of tumor metabolism as a novel strategy for cancer therapy has attracted tremendous attention. Herein, we develop a dual metabolism inhibitor, Zn-carnosine metallodrug network nanoparticles (Zn-Car MNs), which exhibits good Cu-depletion and Cu-responsive drug release, causing potent inhibition of both OXPHOS and glycolysis. Notably, Zn-Car MNs can decrease the activity of cytochrome c oxidase and the content of NAD+, so as to reduce ATP production in cancer cells. Thereby, energy deprivation, together with the depolarized mitochondrial membrane potential and increased oxidative stress, results in apoptosis of cancer cells. In result, Zn-Car MNs exerted more efficient metabolism-targeted therapy than the classic copper chelator, tetrathiomolybdate (TM), in both breast cancer (sensitive to copper depletion) and colon cancer (less sensitive to copper depletion) models. The efficacy and therapy of Zn-Car MNs suggest the possibility to overcome the drug resistance caused by metabolic reprogramming in tumors and has potential clinical relevance.


Assuntos
Neoplasias da Mama , Carnosina , Humanos , Feminino , Carnosina/metabolismo , Carnosina/farmacologia , Cobre/farmacologia , Glicólise , Zinco
13.
J Am Chem Soc ; 145(49): 26736-26746, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38015824

RESUMO

Afterglow materials-based biological imaging has promising application prospects, due to negligible background. However, currently available afterglow materials mainly include inorganic materials as well as some organic nanoparticles, which are difficult to translate to the clinic, resulting from non-negligible metabolic toxicity and even leakage risk of inorganic heavy metals. Although building small organic molecules could solve such obstacles, organic small molecules with afterglow ability are extremely scarce, especially with a sufficient renal metabolic capacity. To address these issues, herein, we designed water-soluble zwitterion Cy5-NF with renal metabolic capacity and afterglow luminescence, which relied on an intramolecular cascade reaction between superoxide anion (O2•-, instead of 1O2) and Cy5-NF to release afterglow luminescence. Of note, compared with different reference contrast agents, zwitterion Cy5-NF not only had excellent afterglow properties but also had a rapid renal metabolism rate (half-life period, t1/2, around 10 min) and good biocompatibility. Unlike prior afterglow nanosystems possessing a large size, for the first time, zwitterion Cy5-NF has achieved the construction of water-soluble renal metabolic afterglow contrast agents, which showed higher sensitivity and signal-to-background ratio in afterglow imaging than fluorescence imaging for the kidney. Moreover, zwitterion Cy5-NF had a longer kidney retention time in renal-failure mice (t1/2 more than 15 min). More importantly, zwitterion Cy5-NF can be metabolized very quickly even in severe renal-failure mice (t1/2 around 25-30 min), which greatly improved biosecurity. Therefore, we are optimistic that the O2•--mediated afterglow mechanism-based water-soluble zwitterion Cy5-NF is very promising for clinical application, especially rapid detection of kidney failure.


Assuntos
Insuficiência Renal , Superóxidos , Animais , Camundongos , Água , Meios de Contraste
14.
Br J Cancer ; 128(11): 2054-2062, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36997661

RESUMO

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a challenging disease due to its intrinsic chemoresistance. Immunotherapy is an emerging treatment option but currently impeded by insufficient understanding of OCCC immunophenotypes and their molecular determinants. METHODS: Whole-genome sequencing on 23 pathologically confirmed patients was employed to depict the genomic profile of primary OCCCs. APOBEC3B expression and digital pathology-based Immunoscore were assessed by performing immunohistochemistry and correlated with clinical outcomes. RESULTS: An APOBEC-positive (APOBEC+) subtype was identified based on the characteristic mutational signature and prevalent kataegis events. APOBEC + OCCC displayed favourable prognosis across one internal and two external patient cohorts. The improved outcome was ascribable to increased lymphocytic infiltration. Similar phenomena of APOBEC3B expression and T-cell accumulation were observed in endometriotic tissues, suggesting that APOBEC-induced mutagenesis and immunogenicity could occur early during OCCC pathogenesis. Corroborating these results, a case report was presented for an APOBEC + patient demonstrating inflamed tumour microenvironment and clinical response to immune checkpoint blockade. CONCLUSIONS: Our findings implicate APOBEC3B as a novel mechanism of OCCC stratification with prognostic value and as a potential predictive biomarker that may inform immunotherapeutic opportunities.


Assuntos
Adenocarcinoma de Células Claras , Carcinoma , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/genética , Prognóstico , Mutação , Linfócitos T/patologia , Adenocarcinoma de Células Claras/genética , Microambiente Tumoral , Citidina Desaminase , Antígenos de Histocompatibilidade Menor
15.
Small ; 19(2): e2205067, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36403221

RESUMO

Waterproof and breathable membranes that prevent liquid water penetration, while allowing air and moisture transmission, have attracted significant attention for various applications. Electrospun nanofiber materials with adjustable pore structures, easily tunable wettability, and good pore connectivity, have shown significant potential for constructing waterproof and breathable membranes. Herein, a systematic overview of the recent progress in the design, fabrication, and application of waterproof and breathable nanofibrous membranes is provided. The various strategies for fabricating the membranes mainly including one-step electrospinning and post-treatment of nanofibers are given as a starting point for the discussion. The different design concepts and structural characteristics of each type of waterproof and breathable membrane are comprehensively analyzed. Then, some representative applications of the membranes are highlighted, involving personal protection, desalination, medical dressing, and electronics. Finally, the challenges and future perspectives associated with waterproof and breathable nanofibrous membranes are presented.


Assuntos
Membranas Artificiais , Nanofibras , Propriedades de Superfície , Bandagens , Nanofibras/química , Água/química , Molhabilidade , Equipamento de Proteção Individual , Eletrônica , Teste de Materiais
16.
Brief Bioinform ; 22(4)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079984

RESUMO

OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Proteínas do Tecido Nervoso , Doença de Parkinson , Mapas de Interação de Proteínas , Vesículas Sinápticas , Autopsia , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Vesículas Sinápticas/genética , Vesículas Sinápticas/metabolismo
17.
Inorg Chem ; 62(25): 9945-9963, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37311103

RESUMO

A flexible polydentate Salamo-Salen-Salamo hybrid ligand H4L was designed and synthesized, which has rich pockets (salamo and salen pockets) so that it may have fascinating coordination patterns with transition metal(II) ions. Four multinuclear transition metal(II) complexes, novel butterfly-shaped homotetranuclear [Ni4(L)(µ1-OAc)2(µ1,3-OAc)2(H2O)0.5(CH3CH2OH)3.5]·4CH3CH2OH (1), helical homotrinuclear [Zn3(L)(µ1-OAc)2]·2CH3CH2OH (2), double-helical homotrinuclear [Cu2(H2L)2]·2CH3CN (3), and mononuclear [Ni(H2L)]·1.5CH3COCH3 (4), have been synthesized and characterized by single-crystal X-ray diffraction. The effects of different anions [OAc- and (O2C5H7)2-] on the complexation behavior of H4L with transition metal(II) ions were studied by UV-vis spectrophotometry. The fluorescent properties of the four complexes were studied with zebrafish, which are expected to be a potential light-emitting material. Ultimately, interaction region indicator (IRI) valuations, Hirshfeld surface analyses, density functional theory (DFT & TD-DFT), electrostatic potential analyses (ESP), and simulations were carried out to further demonstrate the weak interactions and electronic properties of the free ligand and its four complexes.

18.
Nano Lett ; 22(4): 1609-1617, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35138852

RESUMO

Traffic noise has been regarded as one of the most annoying pollutions that induce severe hazards to human health, both physiological and psychological. The commonly used fibrous noise absorption materials are limited by their large density, poor sound absorption ability at low frequencies, and unsatisfactory fire-resistant ability. Here, we develop hierarchically structured elastic ceramic electrospun nanofibrous aerogels, which possess lightweight properties (density of 13.29 mg cm-3) and superior low-frequency sound absorption ability (NRC value of 0.59). Specifically, the obtained ceramic electrospun nanofibrous aerogel is nonflammable on exposure to fire and can be compressed and quickly recover to its original height without any visible damage. Moreover, the resultant aerogels could be facilely and efficiently manufactured into designed shapes on a large scale, demonstrating their potential for industrialization. The successful design of such ceramic-based bulk materials may provide new insights for the further development of the next-generation high-efficiency sound-absorbing products.


Assuntos
Nanofibras , Cerâmica , Humanos , Som
19.
Nano Lett ; 22(8): 3228-3235, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35380847

RESUMO

Theranostic agents based on inorganic nanomaterials are still suffered from the nonbiodegradable substances with long-term retention in body and unavoidable biological toxicity, as well as nonspecificity biodistribution with potential damage toward normal tissues. Here, we develop magnetic ions (FeIII, FeII, GdIII, MnII, and MnIII) coordinated nanoplatform (MICN) with framework structure and modify them with PEG (MICN-PEG). Notably, MICN-PEG demonstrates hydroxide ions (OH-) triggered the structure collapse along with responsive near-infrared photoacoustic (PA) signal, magnetic resonance imaging (MRI), and photothermal therapy (PTT) performances. Thereby, MICN-PEG is able to remain stable in tumors and exert excellent PA/MRI and PTT effects for multimodal imaging-guided cancer treatment. In contrast, MICN-PEG is gradually collapsed in normal tissues, resulting in the significant improvement of imaging accuracy and treatment specificity. MICN-PEG is gradually cleared after administration, minimizing concerns about the long-term toxicity.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Compostos Férricos , Hidróxidos , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fototerapia , Medicina de Precisão , Nanomedicina Teranóstica/métodos , Distribuição Tecidual
20.
Angew Chem Int Ed Engl ; 62(25): e202302161, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37072376

RESUMO

Monitoring the early stage of atherosclerosis (AS) without plaque formation is of great significance. Herein, we developed a metal organic framework (MOF)-based fluorescence nanoprobe to analyze the progression of AS by assessing the levels of protein phosphorylation and glucose in blood and tissue. The probe was prepared by post-modification of the MOF with iodine (I3 - )-rhodamine B (RhB) associate, which realizes the specific recognition of target object through the metal joint ZrIV and I3 - -RhB, respectively. We investigated different stages of target object changes in the early non-plaque stage of AS in blood. It was found that the levels of phosphate and glucose in the blood were higher than those of the normal mice. The results of two-photon images showed that early AS mice had higher levels of protein phosphorylation and glucose than that of the normal mice. The present study provides a suitable fluorescence tool for further revealing the pathogenesis and progression of AS.


Assuntos
Aterosclerose , Camundongos , Animais , Fluorescência , Fosforilação , Aterosclerose/diagnóstico por imagem , Diagnóstico por Imagem , Glucose , Corantes Fluorescentes
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