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1.
Sensors (Basel) ; 24(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38475203

RESUMO

To satisfy the preference of each driver, the development of a Lane-Keeping Assistance (LKA) system that can adapt to individual drivers has become a research hotspot in recent years. However, existing studies have mostly relied on the assumption that the LKA characteristic aligned with the driver's preference is consistent with this driver's naturalistic driving characteristic. Nevertheless, this assumption may not always hold true, causing limitations to the effectiveness of this method. This paper proposes a novel method for a Driver-Adaptive Lane-Keeping Assistance (DALKA) system based on drivers' real preferences. First, metrics are extracted from collected naturalistic driving data using action point theory to describe drivers' naturalistic driving characteristics. Then, the subjective and objective evaluation method is introduced to obtain the real preference of each test driver for the LKA system. Finally, machine learning methods are employed to train a model that relates naturalistic driving characteristics to the drivers' real preferences, and the model-predicted preferences are integrated into the DALKA system. The developed DALKA system is then subjectively evaluated by the drivers. The results show that our DALKA system, developed using this method, can enhance or maintain the subjective evaluations of the LKA system for most drivers.

2.
IEEE Trans Med Imaging ; PP2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38090838

RESUMO

Blood vessel and surgical instrument segmentation is a fundamental technique for robot-assisted surgical navigation. Despite the significant progress in natural image segmentation, surgical image-based vessel and instrument segmentation are rarely studied. In this work, we propose a novel self-supervised pretraining method (SurgNet) that can effectively learn representative vessel and instrument features from unlabeled surgical images. As a result, it allows for precise and efficient segmentation of vessels and instruments with only a small amount of labeled data. Specifically, we first construct a region adjacency graph (RAG) based on local semantic consistency in unlabeled surgical images and use it as a self-supervision signal for pseudo-mask segmentation. We then use the pseudo-mask to perform guided masked image modeling (GMIM) to learn representations that integrate structural information of intraoperative objectives more effectively. Our pretrained model, paired with various segmentation methods, can be applied to perform vessel and instrument segmentation accurately using limited labeled data for fine-tuning. We build an Intraoperative Vessel and Instrument Segmentation (IVIS) dataset, comprised of ~3 million unlabeled images and over 4,000 labeled images with manual vessel and instrument annotations to evaluate the effectiveness of our self-supervised pretraining method. We also evaluated the generalizability of our method to similar tasks using two public datasets. The results demonstrate that our approach outperforms the current state-of-the-art (SOTA) self-supervised representation learning methods in various surgical image segmentation tasks.

3.
Sci Adv ; 9(51): eadj3822, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38134272

RESUMO

Emerging quantum technologies hold the promise of unravelling difficult problems ranging from condensed matter to high-energy physics while, at the same time, motivating the search for unprecedented phenomena in their setting. Here, we use a custom-built superconducting qubit ladder to realize non-thermalizing states with rich entanglement structures in the middle of the energy spectrum. Despite effectively forming an "infinite" temperature ensemble, these states robustly encode quantum information far from equilibrium, as we demonstrate by measuring the fidelity and entanglement entropy in the quench dynamics of the ladder. Our approach harnesses the recently proposed type of non-ergodic behavior known as "rainbow scar," which allows us to obtain analytically exact eigenfunctions whose ergodicity-breaking properties can be conveniently controlled by randomizing the couplings of the model without affecting their energy. The on-demand tunability of quantum correlations via disorder allows for in situ control over ergodicity breaking, and it provides a knob for designing exotic many-body states that defy thermalization.

4.
J Magn Reson Imaging ; 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37702125

RESUMO

BACKGROUND: In neuroscience, accurately quantifying individual brain regions in large cohorts is a challenge. Differences in intracranial structures can suggest functional differences, but they also reflect the effects of other factors. However, there is currently no standardized method for the correction of intracranial structure measurements. PURPOSE: To identify the optimal method to counteract the influence of total intracranial volume (TIV) and gender on the measurement of intracranial structures. STUDY TYPE: Prospective. POPULATION/SUBJECTS: One hundred forty-one healthy adult volunteers (70 male, mean age 21.8 ± 1.7 years). FIELD STRENGTH/SEQUENCE: T1-weighted 3D gradient-echo sequence at 3.0 T. ASSESSMENT: A radiologist with 5 years of work experience screened the raw images to exclude poor-quality images. Freesurfer then performed automated segmentation to obtain measurements of intracranial structures. Male-only, female-only, and TIV-matched sub-samples were created separately. Comparisons between the original data and these sub-samples were used to assess the effects of gender and TIV. Comparison the consistency between TIV-matched sample and corrected data that corrected by four methods: Proportion method, power-corrected proportion method, covariate regression method, and residual method. STATISTICAL TESTS: Cohen's d for examining group distribution disparities, t-tests for probing mean differences, correlation coefficients to assess the relationships between intracranial substructure measurements and TIV. Multiple comparison corrections were applied to the results. RESULTS: The correlation coefficients between TIV and the volumes of intracranial structures ranged from 0.033 to 0.883, with an average of 0.467. Thirty significant volume differences were found among 36 structures in the original sample, while no differences were observed in the TIV-matched sample. Among the four correction methods, the residual method had highest consistency (similarity 94.4%) with the TIV-matched group. DATA CONCLUSION: The variation in intracranial structure sizes between genders was largely attributable to TIV. The residual method offers a more accurate and effective approach for correcting the effects of TIV on intracranial structures. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

6.
Heliyon ; 9(8): e18843, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37600363

RESUMO

Increasing evidence indicated that mitophagy might play a crucial role in the occurrence and progression of liver diseases. In order to enhance our understanding of the intricate relationship between mitophagy and liver diseases, a comprehensive bibliometric analysis of the existing literature in this field was conducted. This analysis aimed to identify key trends, potential areas of future research, and forecast the development of this specific field. We systematically searched the Web of Science Core Collection (WoSCC) for publications related to mitophagy in liver diseases from 2000 to 2022. We conducted the bibliometric analysis and data visualization through VOSviewer and CiteSpace. The analysis of publication growth revealed a substantial increase in articles published in this field over the past years, indicating mitophagy's growing interest and significance in liver diseases. China and USA emerged as the leading contributors in the number of papers, with 294 and 194 independent papers, respectively. Exploring the mechanism of mitophagy in the initiation and procession of liver diseases was the main content of studies in this field, and Parkin-independent mediated mitophagy has attracted much attention recently. "Lipid metabolism," "cell death," "liver fibrosis" and "oxidative stress" were the primary keywords clusters. Additionally, "nlrp3 inflammasome", "toxicity" and "nonalcoholic steatohepatitis" were emerging research hotspots in this area and have the potential to continue to be focal areas of investigation in the future. This study represents the first systematic bibliometric analysis of research on mitophagy in liver diseases conducted over the past 20 years. By providing an overview of the existing literature and identifying current research trends, this analysis sheds light on the critical areas of investigation and paves the way for future studies in this field.

7.
Cell Oncol (Dordr) ; 46(6): 1855-1870, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37610690

RESUMO

PURPOSE: PARP inhibitors have revolutionized the treatment landscape for advanced prostate cancer (PCa) patients who harboring mutations in homologous recombination repair (HRR) genes. However, the molecular mechanisms underlying PARP inhibitors function beyond DNA damage repair pathways remain elusive, and identifying novel predictive targets that favorably respond to PARP inhibitors in PCa is an active area of research. METHODS: The expression of GSDME in PCa cell lines and human PCa samples was determined by western blotting. Targeted bisulfite sequencing, gene enrichment analysis (GSEA), clone formation, construction of the stably transfected cell lines, lactate dehydrogenase (LDH) assay, western blotting as well as a mouse model of subcutaneous xenografts were used to investigate the role of GSDME in PCa. The combinational therapeutic effect of olaparib and decitabine was determined using both in vitro and in vivo experiments. RESULTS: We have found low expression of GSDME in PCa. Interestingly, we demonstrated that GSDME activity is robustly induced in olaparib-treated cells undergoing pyroptosis, and that high methylation of the GSDME promoter dampens its activity in PCa cells. Intriguingly, genetically overexpressing GSDME does not inhibit tumor cell proliferation but instead confers sensitivity to olaparib. Furthermore, pharmacological treatment with the combination of olaparib and decitabine synergistically induces GSDME expression and cleavage through caspase-3 activation, thus promoting pyroptosis and enhancing anti-tumor response, ultimately resulting in tumor remission. CONCLUSION: Our findings highlight a novel therapeutic strategy for enhancing the long-term response to olaparib beyond HRR-deficient tumors in PCa, underscoring the critical role of GSDME in regulating tumorigenesis.


Assuntos
Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Masculino , Animais , Camundongos , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Piroptose , Decitabina/farmacologia , Linhagem Celular Tumoral , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética
8.
Oncogene ; 42(38): 2801-2815, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37582861

RESUMO

Tumor-secreted exosomes have a wide range of effects on the growth, metastasis, and drug resistance of cancer cells. However, whether and how the molecular mechanisms that regulate the secretion of exosomes could affect tumor progression remains poorly understood. Klotho beta (KLB) has been reported dysregulated in prostate cancer, but its function remains unknown. Herein, we first determined that KLB was upregulated in prostate cancer and its expression level was positively correlated with prostate cancer malignant phenotype both in vitro and in vivo. Intriguingly, KLB overexpression could impair the release of exosomes and cause the intracellular accumulation of multivesicular bodies (MVBs) in prostate cancer cells. Mechanistically, KLB attenuated exosomes secretion through a Rab8a-dependent pathway. Rab8a was downregulated in KLB overexpressing cells whereas overexpression of Rab8a could rescue the impaired release of exosomes and attenuate the KLB-induced malignant phenotype of prostate cancer both in vitro and in vivo. Taken together, this study has unveiled the tumor-promoting role of KLB mediated by its regulation on exosomes secretion through a Rab8a-dependent mechanism. These findings could be exploited to develop novel theranostic targets for prostate cancer.


Assuntos
Exossomos , Neoplasias da Próstata , Humanos , Masculino , Linhagem Celular Tumoral , Exossomos/metabolismo , Próstata/patologia , Neoplasias da Próstata/patologia
9.
Aging Cell ; 22(10): e13955, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37584418

RESUMO

Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer's disease (AD). Here, we investigate associations between a panel of inflammatory biomarkers and cognitive function and incident dementia outcomes in the well-characterized Framingham Heart Study Offspring cohort. Participants aged ≥40 years and dementia-free at Exam 7 who had a stored plasma sample were selected for profiling using the OLINK proteomics inflammation panel. Cross-sectional associations of the biomarkers with cognitive domain scores (N = 708, 53% female, 22% apolipoprotein E (APOE) ε4 carriers, 15% APOE ε2 carriers, mean age 61) and incident all-cause and AD dementia during up to 20 years of follow-up were tested. APOE genotype-stratified analyses were performed to explore effect modification. Higher levels of 12 and 3 proteins were associated with worse executive function and language domain factor scores, respectively. Several proteins were associated with more than one cognitive domain, including IL10, LIF-R, TWEAK, CCL19, IL-17C, MCP-4, and TGF-alpha. Stratified analyses suggested differential effects between APOE ε2 and ε4 carriers: most ε4 carrier associations were with executive function and memory domains, whereas most ε2 associations were with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with higher risks of incident all-cause and AD dementia. Our study found that TWEAK concentration was associated both with cognitive function and risks for AD dementia. The association of these inflammatory biomarkers with cognitive function and incident dementia may contribute to the discovery of therapeutic interventions for the prevention and treatment of cognitive decline.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Feminino , Masculino , Apolipoproteína E2 , Estudos Transversais , Genótipo , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Cognição , Apolipoproteínas E/genética , Disfunção Cognitiva/genética , Apolipoproteína E4 , Estudos Longitudinais , Biomarcadores , Antígenos de Neoplasias , Moléculas de Adesão Celular
10.
J Agric Food Chem ; 71(22): 8413-8424, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37222554

RESUMO

Extracellular vesicles (EVs) released from cells have shown robust efficacy in drug delivery compared with traditional synthetic carriers. Hampered by the high production cost and complex purification process, the clinical application of EVs as drug carriers is still limited. Nanoparticles isolated from plants with exosome-like morphology and similar delivery effects could be a new option for drug delivery. The celery exosome-like nanovesicles (CELNs) showed higher cellular uptake efficiency compared to the other three common plant-derived exosome-like nanovesicles, which is an essential advantage for CELNs as a drug carrier. The less toxicity and better tolerance of CELNs as biotherapeutic roles were verified in mice models. Then, doxorubicin (DOX) was encapsulated into CELNs to construct engineered CELNs (CELNs-DOX), which proved to be more efficient in treating tumors than conventional synthetic carriers like liposome both in vitro and in vivo. In conclusion, this study, for the first time, has proposed the emerging role of CELNs as a new-generation drug delivery carrier with distinct advantages.


Assuntos
Apium , Exossomos , Neoplasias , Animais , Camundongos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Doxorrubicina , Portadores de Fármacos , Proliferação de Células
11.
Aging (Albany NY) ; 15(10): 3939-3966, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37116193

RESUMO

Understanding the composition of circulating immune cells with aging and the underlying biologic mechanisms driving aging may provide molecular targets to slow the aging process and reduce age-related disease. Utilizing cryopreserved cells from 996 Framingham Heart Study (FHS) Offspring Cohort participants aged 40 and older (mean 62 years, 48% female), we report on 116 immune cell phenotypes including monocytes, T-, B-, and NK cells and their subtypes, across age groups, sex, cytomegalovirus (CMV) exposure groups, smoking and other cardiovascular risk factors. The major cellular differences with CMV exposure were higher Granzyme B+ cells, effector cells, and effector-memory re-expressing CD45RA (TEMRA) cells for both CD4+ and CD8+. Older age was associated with lower CD3+ T cells, lower naïve cells and naïve/memory ratios for CD4+ and CD8+. We identified many immune cell differences by sex, with males showing lower naïve cells and higher effector and effector memory cells. Current smokers showed lower pro-inflammatory CD8 cells, higher CD8 regulatory type cells and altered B cell subsets. No significant associations were seen with BMI and other cardiovascular risk factors. Our cross-sectional observations of immune cell phenotypes provide a reference to further the understanding of the complexity of immune cells in blood, an easily accessible tissue.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Masculino , Humanos , Feminino , Estudos Transversais , Linfócitos T CD8-Positivos , Fenótipo , Estudos Longitudinais , Fumar , Linfócitos T CD4-Positivos
12.
Cell Oncol (Dordr) ; 46(2): 437-450, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36598638

RESUMO

PURPOSE: Metastatic lung squamous cell carcinoma (LUSC) is one of the most common causes of cancer death worldwide. As yet, however, the molecular mechanism underlying LUSC metastasis remains elusive. In this study, we report a novel mechanism involving signaling interactions between FGF19 and GLI2 that could drive the progression of LUSC. METHODS: The expression of FGF19 in human LUSC samples was assessed by immunohistochemistry. The concentration of FGF19 in serum samples was assessed by ELISA. RNA sequencing, scratch wound-healing, trans-well, GO analysis, GSEA, luciferase reporter, Western blotting, immunofluorescence and immunohistochemistry assays, as well as an animal model were used to investigate the molecular mechanism underlying FGF19 driven LUSC progression. The therapeutic effect of a GLI2 inhibitor was determined using both in vitro cellular and in vivo animal experiments. RESULTS: We found that FGF19, a member of the fibroblast growth factor family, plays a crucial role in the invasion and metastasis of LUSC, and identified GLI2 as an important downstream effector of FGF19 involved in metastasis. Surprisingly, we found that FGF19 and GLI2 could reciprocally induce the expression of each other, and form a positive feedback loop to promote LUSC cell invasion and metastasis. These findings were corroborated by an association between a poor prognosis of LUSC patients and FGF19/GLI2 co-expression. In addition, we found that the GLI inhibitor GANT61 could effectively reduce FGF19-mediated LUSC invasion and metastasis. CONCLUSION: Our data suggest that FGF19 may serve as a novel biomarker for predicting metastatic LUSC. Intervening with the FGF19-GLI2 feedback loop may be a strategy for the treatment of FGF19-driven LUSC metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Transição Epitelial-Mesenquimal , Fatores de Crescimento de Fibroblastos , Neoplasias Pulmonares , Proteína Gli2 com Dedos de Zinco , Animais , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Fatores de Crescimento de Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Pulmão/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Nucleares/metabolismo , Transdução de Sinais/genética , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/metabolismo
13.
Nanomedicine ; 47: 102625, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36334896

RESUMO

Spinal cord injury (SCI) is a severe traumatic disease because of its complications and multi-organ dysfunction. After the injury, the disruption of microenvironment homeostasis in the lesion demolishes the surrounding healthy tissues via various pathways. The microenvironment regulation is beneficial for neural and functional recovery. Sustained release, cellular uptake, and long-term retention of therapeutic molecules at the impaired sites are important for continuous microenvironment improvement. In our study, a local-implantation system was constructed for SCI treatment by encapsulating exosomes derived from Flos Sophorae Immaturus (so-exos) in a polydopamine-modified hydrogel (pDA-Gel). So-exos are used as nanoscale natural vehicles of rutin, a flavonoid phytochemical that is effective in microenvironment improvement and nerve regeneration. Our study showed that the pDA-Gel-encapsulated so-exos allowed rapid improvement of the impaired motor function and alleviation of urination dysfunction by modulating the spinal inflammatory and oxidative conditions, thus illustrating a potential SCI treatment through a combinational delivery of so-exos.


Assuntos
Sophora , Regeneração da Medula Espinal , Antioxidantes/farmacologia , Hidrogéis , Estresse Oxidativo
14.
Res Sq ; 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38234796

RESUMO

Background: The global increase in human life expectancy is evident. The total number of individuals aged 60 or above is anticipated to reach 2 billion by 2050. Aging, an inherently complex process, manifests prominently in the changes observed in the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their significance, the connections between various ARIPs and mortality have not been thoroughly investigated. We prospectively investigated 16 different ARIPs using flow cytometry, namely, CD4/CD8 ratio, Granzyme B + CD8/Granyzme B + CD4, TN/TM = Tn / (Teff + Tem + Tcm) for TN/TM CD4 + and TN/TM CD8 + ratios, Th17/CD4 + Treg, Tc17/CD8 + Treg, Th17, Tc17, CD4 + Temra, CD8 + Temra, CD4 + CD25 + FoxP3+ (CD4 + Treg), CD8 + CD25 + FoxP3+ (CD8 + Treg) CD4 + CD27-, CD4 + CD28-CD27-, CD8 + CD27-, CD8 + CD28-CD27- and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998-2001). Results: Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the survival rate was 65% during 19 years of follow-up. For the model adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR:0.86 [0.76-0.96], 0.84 [0.74-0.94], respectively) and higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3+) were associated with higher all-cause mortality (HR = 1.17, [1.03-1.32]). Higher IL-6 levels were associated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26-1.62], 1.70 [1.31-2.21], and 1.36 [1.18-1.57], respectively).

15.
RSC Adv ; 12(54): 34837-34849, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36540211

RESUMO

The stability and grafting efficiency are important for polydopamine (pDA) coatings used as platforms for secondary grafting. In this work, polyethyleneimine (PEI) was co-deposited with dopamine on various materials (PP, PTFE and PVC), then immersed in a 1.0 M HCl solution or 1.0 M NaOH solution to investigate the detachment of the coatings using UV-vis spectroscopy, SEM, FTIR spectroscopy and XPS, and the effect of PEI molecular weight on the secondary grafting of heparin on the pDA/PEI coating was investigated through clotting time tests. The results showed that the detachment rates of the pDA/PEI coating (14.6%, 23.7%) co-deposited on PTFE in 1.0 M HCl or 1.0 M NaOH solutions were both lower than that of the pDA coating (35.0%, 74.6%), indicating that pDA/PEI coatings could better remain on substrates in a 1.0 M NaOH solution. Besides, pDA/PEI coatings on a PP membrane with both a higher deposition density and stability could be obtained when the mass ratio of DA/PEI was 2 : 1-1 : 1 and PEI molecular weight was 600 Da. After grafting heparin, it was found that the pDA/PEI coating with lower molecular weight (600 Da and 1800 Da) PEI could achieve a higher grafting density of heparin with a longer clotting time. Thus, the results provided better understanding about the stability of pDA/PEI coatings and efficiency of heparin grafting.

16.
Biomater Sci ; 10(19): 5744, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36069302

RESUMO

Correction for 'Implantation of a functional TEMPO-hydrogel induces recovery from rat spinal cord transection through promoting nerve regeneration and protecting bladder tissue' by Yu Zhang et al., Biomater. Sci., 2020, 8, 1695-1701, https://doi.org/10.1039/C9BM01530B.

17.
PLoS One ; 17(9): e0274350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36083988

RESUMO

Inflammatory cytokines and chemokines related to the innate and adaptive immune system have been linked to neuroinflammation in Alzheimer's Disease, dementia, and cognitive disorders. We examined the association of 11 plasma proteins (CD14, CD163, CD5L, CD56, CD40L, CXCL16, SDF1, DPP4, SGP130, sRAGE, and MPO) related to immune and inflammatory responses with measures of cognitive function, brain MRI and dementia risk. We identified Framingham Heart Study Offspring participants who underwent neuropsychological testing (n = 2358) or brain MRI (n = 2100) within five years of the seventh examination where a blood sample for quantifying the protein biomarkers was obtained; and who were followed for 10 years for incident all-cause dementia (n = 1616). We investigated the association of inflammatory biomarkers with neuropsychological test performance and brain MRI volumes using linear mixed effect models accounting for family relationships. We further used Cox proportional hazards models to examine the association with incident dementia. False discovery rate p-values were used to account for multiple testing. Participants included in the neuropsychological test and MRI samples were on average 61 years old and 54% female. Participants from the incident dementia sample (average 68 years old at baseline) included 124 participants with incident dementia. In addition to CD14, which has an established association, we found significant associations between higher levels of CD40L and myeloperoxidase (MPO) with executive dysfunction. Higher CD5L levels were significantly associated with smaller total brain volumes (TCBV), whereas higher levels of sRAGE were associated with larger TCBV. Associations persisted after adjustment for APOE ε4 carrier status and additional cardiovascular risk factors. None of the studied inflammatory biomarkers were significantly associated with risk of incident all-cause dementia. Higher circulating levels of soluble CD40L and MPO, markers of immune cell activation, were associated with poorer performance on neuropsychological tests, while higher CD5L, a key regulator of inflammation, was associated with smaller total brain volumes. Higher circulating soluble RAGE, a decoy receptor for the proinflammatory RAGE/AGE pathway, was associated with larger total brain volume. If confirmed in other studies, this data indicates the involvement of an activated immune system in abnormal brain aging.


Assuntos
Doença de Alzheimer , Envelhecimento Cognitivo , Disfunção Cognitiva , Idoso , Envelhecimento , Doença de Alzheimer/diagnóstico , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Ligante de CD40/metabolismo , Disfunção Cognitiva/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
18.
Stat Med ; 41(26): 5220-5241, 2022 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-36098057

RESUMO

Ultrahigh and high dimensional data are common in regression analysis for various fields, such as omics data, finance, and biological engineering. In addition to the problem of dimension, the data might also be contaminated. There are two main types of contamination: outliers and model misspecification. We develop an unique method that takes into account the ultrahigh or high dimensional issues and both types of contamination. In this article, we propose a framework for feature screening and selection based on the minimum Lq-likelihood estimation (MLqE), which accounts for the model misspecification contamination issue and has also been shown to be robust to outliers. In numerical analysis, we explore the robustness of this framework under different outliers and model misspecification scenarios. To examine the performance of this framework, we conduct real data analysis using the skin cutaneous melanoma data. When comparing with traditional screening and feature selection methods, the proposed method shows superiority in both variable identification effectiveness and parameter estimation accuracy.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Análise de Regressão , Probabilidade
19.
RSC Adv ; 12(33): 21041-21049, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35919839

RESUMO

In order to investigate the pore properties and effect of storage time on the microstructure of CO2-dried aerogels, chitosan aerogel beads were obtained from chitosan hydrogels with an initial concentration in the range of 1.5-3.0 wt% through SCCO2 drying and freeze-drying (as a comparison). The SCCO2-dried chitosan aerogels showed a three-dimensional network structure, and had higher BET surface area (200 m2 g-1) and higher crystallinity (0.62/XRD, 0.80/ATR-FTIR) than the freeze-dried aerogels. The stability of the microstructure of the SCCO2-dried chitosan aerogel beads during 10 months was studied. The BET surface area of the aerogel beads at each concentration declined by 30.5% at 2 months, 56.7% at 6 months and 67.2% at 10 months. Accelerated aging tests of the chitosan aerogel beads were carried out to study the effect of humidity on the chitosan aerogel beads. The average diameter of the chitosan aerogel decreased from 2.3 mm to 0.9 mm when stored at 65 °C with 90% relative humidity (RH). In contrast, there was no obvious change during storage at 65 °C with 20% RH. The amount of adsorbed water increased from 4% to 12% at 65 °C with 90% RH for 96 h, and the bound water content of the aerogel beads gradually increased. This study demonstrates that SCCO2-dried chitosan aerogel beads could be better at maintaining their mesoporous structure, and the adsorption of water from the surrounding air had a significant effect on the microstructure and shrinkage of the chitosan aerogel beads.

20.
Front Plant Sci ; 13: 954777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035716

RESUMO

Successive planting and monoculture, as common forest management methods, are widely used globally, especially in Chinese fir plantations in the subtropical areas of southern China. Although soil fertility depletion and productivity decline caused by successive planting have been widely reported, the underlying mechanism is still ambiguous. In this study, the composition and diversity of soil microorganisms (rhizosphere and bulk soils) in Chinese fir seedlings exposed to successive planting soils (first-generation Chinese fir seedings, FCP. second-generation Chinese fir seedings, SCP. third-generation Chinese fir seedings, TCP) and broadleaf tree species soil (Phoebe zhennan S. Lee et F. N. Wei, CK) were examined with high-throughput sequencing technology. Our findings revealed that the diversity and richness of bacterial and fungal communities were remarkably reduced in TCP than FCP and SCP, and were remarkably different between FCP and SCP. At the phylum level, the fungi with greatest relative abundance were Basidiomycota (5.74-32.88%) and Ascomycota (57.63-87.38%), while the bacteria with the greatest relative abundance were Acidobacteria (23.16-31.17%) and Proteobacteria (24.71-29.32%) for all treatments in both soil types. Additionally, the relative abundance of some pathogens (Penicillium and Burkholderia) was significantly higher in TCP than in FCP and SCP, suggesting that the presence of pathogens is an important factor in increasing the incidence of soil-borne sickness. Moreover, changes in fungal and bacterial communities were predominantly driven by soil dissolved organic carbon (DOC), DOC/DON ratio (DOCN), NO3 --N, microbial biomass carbon (MBC), and MBC/MBN ratio (MBCN). Overall, the long-term monoculture of Chinese fir promotes the microecological imbalance of rhizosphere and bulk soil, and remarkably reduced soil microbial community diversity. These results can provide a scientific support for the implementation of future management measures for fir plantations (e.g., fertilization, addition of microbial fungicides, and construction of mixed forests).

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