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1.
Ecotoxicol Environ Saf ; 277: 116387, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663193
2.
Sci Rep ; 14(1): 9510, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664443

RESUMO

Clinical ulcerative colitis (UC) is a heterogeneous condition. Moreover, medical interventions are nonspecific, and thus, treatment responses are inconsistent. The aim of this study was to explore the molecular subtypes and biological characteristics of UC based on ferroptosis and neutrophil gene sets. Multiple intestinal mucosa gene expression profiles of UC patients in the Gene Expression Omnibus (GEO) database were downloaded. Unsupervised clustering methods were used to identify potential molecular subtypes based on ferroptosis and neutrophil gene sets. Multiple immune infiltration algorithms were used to evaluate the biological characteristics of the molecular subtypes. Machine learning identifies hub genes for molecular subtypes and analyses their diagnostic efficacy for UC and predictive performance for drug therapy. The relevant conclusions were verified by clinical samples and animal experiments. Four molecular subtypes were identified according to the ferroptosis and neutrophil gene sets: neutrophil, ferroptosis, mixed and quiescent. The subtypes have different biological characteristics and immune infiltration levels. Multiple machine learning methods jointly identified four hub genes (FTH1, AQP9, STEAP3 and STEAP4). Receiver operating characteristic (ROC) curve analysis revealed that the four hub genes could be used as diagnostic markers for UC. The clinical response profile data of infliximab treatment patients showed that AQP9 and STEPA4 were reliable predictors of infliximab treatment response. In human samples the AQP9 and STEAP4 protein were shown to be increased in UC intestinal samples. In animal experiments, the ferroptosis and neutrophil phenotype were confirmed. Dual analysis of ferroptosis and neutrophil gene expression revealed four subgroups of UC patients. The molecular subtype-associated hub genes can be used as diagnostic markers for UC and predict infliximab treatment response.


Assuntos
Colite Ulcerativa , Ferroptose , Infiltração de Neutrófilos , Ferroptose/genética , Colite Ulcerativa/genética , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Humanos , Animais , Infiltração de Neutrófilos/genética , Neutrófilos/metabolismo , Neutrófilos/imunologia , Infliximab/uso terapêutico , Infliximab/farmacologia , Aprendizado de Máquina , Camundongos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Perfilação da Expressão Gênica/métodos , Masculino , Feminino
3.
ACS Nano ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627898

RESUMO

PD-1 blockade is a first-line treatment for recurrent/metastatic cervical cancer but benefits only a small number of patients due to low preexisting tumor immunogenicity. Using immunogenic cell death (ICD) inducers is a promising strategy for improving immunotherapy, but these compounds are limited by the hypoxic environment of solid tumors. To overcome this issue, the nanosensitizer AIBA@MSNs were designed based on sonodynamic therapy (SDT), which induces tumor cell death under hypoxic conditions through azo free radicals in a method of nonoxygen radicals. Mechanistically, the azo free radicals disrupt both the structure and function of tumor mitochondria by reversing the mitochondrial membrane potential and facilitating the collapse of electron transport chain complexes. More importantly, the AIBA@MSN-based SDT serves as an effective ICD inducer and improves the antitumor immune capacity. The combination of an AIBA@MSN-based SDT with a PD-1 blockade has the potential to improve response rates and provide protection against relapse. This study provides insights into the use of azo free radicals as a promising SDT strategy for cancer treatment and establishes a basic foundation for nonoxygen-dependent SDT-triggered immunotherapy in cervical cancer treatment.

4.
J Affect Disord ; 354: 1-10, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38452936

RESUMO

BACKGROUND: Prenatal depression, associated with adverse effects on mothers and fetuses, has received little attention. We conducted a large-sample study to investigate the risk factors of, and develop a predictive model for, prenatal depression in the Chinese population. METHODS: This study enrolled 14,329 pregnant women who delivered at the West China Second University Hospital, Sichuan University from January 2017 to December 2020. Participants were divided into a training or validation cohort. Multiple variables were collected and selected using univariate logistic regression and least absolute shrinkage and selection operator penalty regression. After multivariate logistic analysis, a predictive model was developed and validated internally and externally. RESULTS: Nine variables (employment, planned pregnancy, pregnancy number, conception methods, gestational diabetes mellitus, twin pregnancy, placenta previa, umbilical cord encirclement, and educational attainment) were identified as independent risk factors for prenatal depression. Receiver operating characteristic curves in both the training and validation cohorts showed excellent discrimination of the predictive model (the area under the curve: 0.746 and 0.732, respectively). LIMITATIONS: The results of this retrospective study may be affected by confounding and information bias. Some important variables were excluded, such as family history of mental disorders. The study was conducted in China; its results may not be generalizable to other regions. CONCLUSION: Our study identified nine significant risk factors for prenatal depression and constructed an accurate predictive model. This model could be applied as a clinical decision aid for individualized risk estimates and prevention of prenatal depression.


Assuntos
Depressão , Diabetes Gestacional , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Depressão/epidemiologia , Fatores de Risco , Modelos Logísticos , Vitaminas , China/epidemiologia
5.
Carbohydr Polym ; 334: 122035, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38553204

RESUMO

Inspired from human skin, micro- and nano-wrinkled wood surface with skin-tactile performance was designed and developed using a waterborne UV-curable polyurethane acrylate coating and cellulose nofibers (CNF). To further improve the properties, the CNF was diacetylated to D-CNF and further grafted with a hyperbranched polymer containing rich end amino groups (HB-CNF). The surface structure and chemical reactions were characterized, and the skin-tactile performance of the coating was comprehensively investigated. The HB-CNF exhibited excellent dispersion in the coating, and extensive reactions occurred between the two through the -NH2 and terminal -NCO groups, resulting in much improved mechanical properties and durability. Micro-wrinkles with a width of approximately 12-15 µm and a height of 8-14 µm were created, and nano-protrusions of wrinkles ranging from to 50-100 nm were obtained. The coated surface was hydrophobic and exhibited high resilience after compression, with a gloss of 3.3 GU at an incident angle of 60° and a static friction coefficient of 0.26, both of which were similar to those of human skin. The results presented an effective strategy for high-performance wood products with a good feeling, which is helpful to improve the market competitiveness and meet the people's pursuit of a better life.

6.
Front Psychiatry ; 15: 1277415, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525255

RESUMO

Background: Postpartum depression (PPD) is one of the most common complications of delivery and is usually disregarded. Several risk factors of PPD have been identified, but its pathogenesis has not been completely understood. Serum bilirubin has been found to be a predictor of depression, whose relationship with PPD has not been investigated. Methods: Observational research was performed followed by a two-sample Mendelian randomization (MR) analysis. From 2017 to 2020, the clinical data of pregnant women were retrospectively extracted. Logistic regression and random forest algorithm were employed to assess the risk factors of PPD, including the serum levels of total bilirubin and direct bilirubin. To further explore their potential causality, univariable and multivariable Mendelian randomization (MVMR) were conducted. Sensitivity analyses for MR were performed to test the robustness of causal inference. Results: A total of 1,810 patients were included in the PPD cohort, of which 631 (34.87%) were diagnosed with PPD. Compared with the control group, PPD patients had a significantly lower level of total bilirubin (9.2 µmol/L, IQR 7.7, 11.0 in PPD; 9.7 µmol/L, IQR 8.0, 12.0 in control, P < 0.001) and direct bilirubin (2.0 µmol/L, IQR 1.6, 2.6 in PPD; 2.2 µmol/L, IQR 1.7, 2.9 in control, P < 0.003). The prediction model identified eight independent predictive factors of PPD, in which elevated total bilirubin served as a protective factor (OR = 0.94, 95% CI 0.90-0.99, P = 0.024). In the MR analyses, genetically predicted total bilirubin was associated with decreased risk of PPD (IVW: OR = 0.86, 95% CI 0.76-0.97, P = 0.006), which remained consistent after adjusting educational attainment, income, and gestational diabetes mellitus. Conversely, there is a lack of solid evidence to support the causal relationship between PPD and bilirubin. Conclusion: Our results suggested that decreased total bilirubin was associated with the incidence of PPD. Future studies are warranted to investigate its potential mechanisms and illuminate the pathogenesis of PPD.

7.
Clin Transl Oncol ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512449

RESUMO

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. METHODS: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. RESULTS AND CONCLUSIONS: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.

8.
Ophthalmic Res ; 67(1): 211-220, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38484716

RESUMO

INTRODUCTION: This study aimed to compare retinal vascular parameters and density in patients with moyamoya disease using the optical coherence tomography angiography. METHODS: This clinical trial totally enrolls 78 eyes from 39 participants, and all these patients with moyamoya disease (N = 13) are set as experimental group and participants with health who matched with age and gender are considered as the control group (N = 26). Then all these participants receive optical coherence tomography angiography detection. Participants' general data are collected and analyzed. Skeleton density (SD) value, vessel density (VD) value, fractal dimension (FD) value, vessel diameter index (VDI) value, foveal avascular zone (FAZ) value are analyzed. RESULTS: A total of 39 participants are included in this study. The SD value in the experimental group was significantly lower than that in control group (0.175 [0.166, 0.181] vs. 0.184 [0.175, 0.188], p = 0.017). Similarly, the VD value in the experimental group was significantly lower than that in the control group (0.333 [0.320, 0.350] vs. 0.354 [0.337, 0.364], p = 0.024). Additionally, the FD value in the experimental group was significantly lower than that in the control group (2.088 [2.083, 2.094] vs. 2.096 [2.090, 2.101], p = 0.022). As for the VDI and FAZ, VDI and FAZ values in the experimental group were lower than those in the control group, there was no significant difference in VDI and FAZ values between the two groups. CONCLUSIONS: Our study, using non-invasive and rapid OCTA imaging, confirmed decreased retinal vascular parameters and density in patients with moyamoya disease.


Assuntos
Angiofluoresceinografia , Fundo de Olho , Doença de Moyamoya , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/fisiopatologia , Doença de Moyamoya/diagnóstico por imagem , Feminino , Masculino , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos , Angiofluoresceinografia/métodos , Adulto , Pessoa de Meia-Idade , Acuidade Visual , Adulto Jovem , Adolescente , Seguimentos
10.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38342685

RESUMO

Perinatal depression, with a prevalence of 10 to 20% in United States, is usually missed as multiple symptoms of perinatal depression are common in pregnant women. Worse, the diagnosis of perinatal depression still largely relies on questionnaires, leaving the objective biomarker being unveiled yet. This study suggested a safe and non-invasive technique to diagnose perinatal depression and further explore its underlying mechanism. Considering the non-invasiveness and clinical convenience of electroencephalogram for mothers-to-be and fetuses, we collected the resting-state electroencephalogram of pregnant women at the 38th week of gestation. Subsequently, the difference in network topology between perinatal depression patients and healthy mothers-to-be was explored, with related spatial patterns being adopted to achieve the classification of pregnant women with perinatal depression from those healthy ones. We found that the perinatal depression patients had decreased brain network connectivity, which indexed impaired efficiency of information processing. By adopting the spatial patterns, the perinatal depression could be accurately recognized with an accuracy of 87.88%; meanwhile, the depression severity at the individual level was effectively predicted, as well. These findings consistently illustrated that the resting-state electroencephalogram network could be a reliable tool for investigating the depression state across pregnant women, and will further facilitate the clinical diagnosis of perinatal depression.


Assuntos
Depressão , Transtorno Depressivo , Feminino , Gravidez , Humanos , Depressão/diagnóstico , Couro Cabeludo , Gestantes , Eletroencefalografia
11.
BMC Cancer ; 24(1): 244, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389061

RESUMO

BACKGROUND: Identifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients. METHODS: A total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors. RESULTS: Most PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p < 0.05). Other factors (age, gender, family history of thyroid cancer, history of autoimmune thyroiditis, and BRAFV600E mutation) had no significant correlation with adverse pathologic features (p > 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAFV600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580-0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit. CONCLUSION: Tumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Tireoidite Autoimune , Humanos , Nomogramas , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Fatores de Risco
12.
J Cardiovasc Comput Tomogr ; 18(2): 179-186, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38262851

RESUMO

BACKGROUND: Quadricuspid aortic valve (QAV) is a rare congenital heart disease with a limited body of literature. This retrospective cohort study investigates QAV morphology, function, and clinical outcomes. METHODS: Echocardiography was used to assess valvular function. Morphological characteristics such as phenotypes, raphe, regurgitant orifice area (ROA), and aortic dilation (diameter >40 â€‹mm) were assessed by cardiac CT. Patients were followed up for the combined event of all-cause death and aortic valve replacement (AVR). RESULTS: Ninety QAV patients (screened from 322385 CT scans) were included (mean age 55.2 â€‹± â€‹13.6 years, 61.1 â€‹% male). Isolated significant aortic regurgitation (AR) was present in 75.6 â€‹% of patients. The cohort was dominated by type I (four equal leaflets, 37.8 â€‹%) and type II (3 larger and 1 smaller leaflets, 42.2 â€‹%) QAV. Fused raphe was present in 26.7 â€‹% of patients. ROACT was correlated with AR severity and aortic dilation (41.1 â€‹%, n â€‹= â€‹37). Among patients without AVR at baseline (n â€‹= â€‹60), one died and 17 underwent AVR during a median follow-up of 35.0 months (IQR:17.3-62.8). ROACT was associated with an increasing risk of combined event (as a categorical variable with a cut-off of 21.4 â€‹mm2, HR â€‹= â€‹4.25, 95%CI 1.49-12.17, p â€‹= â€‹0.007; as a continuous variable (per mm2 increment), HR â€‹= â€‹1.04, 95%CI 1.01-1.07, p â€‹= â€‹0.003). Additionally, ROACT had incremental prognostic value when added to the AR severity model (area under the receiver-operating characteristic curve increased from 86.8 to 88.4, p â€‹= â€‹0.004). CONCLUSION: QAV is characterized by variable anatomy, progressive AR, concomitant cusp fusion and aortic enlargement. ROACT may be a potential ancillary prognostic marker in patients with QAV.


Assuntos
Doenças da Aorta , Insuficiência da Valva Aórtica , Válvula Aórtica Quadricúspide , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Estudos Retrospectivos , Valor Preditivo dos Testes , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Valva Aórtica/anormalidades , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/cirurgia , Hemodinâmica
13.
Quant Imaging Med Surg ; 14(1): 932-943, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38223087

RESUMO

Background: As the retinal microvasculature shares similarities with the cerebral microvasculature, numerous studies have shown that retinal vascular is associated with cognitive decline. In addition, several population-based studies have confirmed the association between retinal vascular and cerebral small vessel disease (CSVD) burden. However, the association of retinal vascular with CSVD burden as well as cognitive function has not been explored simultaneously. This study investigated the relations of retinal microvascular parameters (RMPs) with CSVD burden and cognitive function. Methods: We conducted a cross-sectional study of participants in the KaiLuan study. Data were collected from subjects aged ≥18 years old who could complete retinal photography and brain magnetic resonance imaging (MRI) between December 2020 to October 2021 in the Kailuan community of Tangshan. RMPs were evaluated using a deep learning system. The cognitive function was measured using the Montreal Cognitive Assessment (MoCA). We conducted logistic regression models, and mediation analysis to evaluate the associations of RMPs with CSVD burden and cognitive decline. Results: Of the 905 subjects (mean age: 55.42±12.02 years, 54.5% female), 488 (53.9%) were classified with cognitive decline. The fractal dimension (FD) [odds ratio (OR), 0.098, 95% confidence interval (CI): 0.015-0.639, P=0.015] and global vein width (OR: 1.010, 95% CI: 1.005-1.015, P<0.001) were independent risk factors for cognitive decline after adjustment for potential confounding factors. The global artery width was significantly associated with severe CSVD burden (OR: 0.985, 95% CI: 0.974-0.997, P=0.013). The global vein width was sightly associated with severe CSVD burden (OR: 1.005, 95% CI: 1.000-1.010, P=0.050) after adjusting for potential confounders. The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of global vein width were 1.290 (0.901-1.847) for cognitive decline and 1.546 (1.004-2.290) for severe CSVD burden, respectively. Moreover, CSVD burden played a partial mediating role in the association between global vein width and cognitive function (mediating effect 6.59%). Conclusions: RMPs are associated with cognitive decline and the development of CSVD. A proportion of the association between global vein width and cognitive decline may be attributed to the presence of CSVD burden.

14.
BMC Geriatr ; 24(1): 28, 2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184539

RESUMO

BACKGROUND: The current literature shows a strong relationship between retinal neuronal and vascular alterations in dementia. The purpose of the study was to use NFN+ deep learning models to analyze retinal vessel characteristics for cognitive impairment (CI) recognition. METHODS: We included 908 participants from a community-based cohort followed for over 15 years (the prospective KaiLuan Study) who underwent brain magnetic resonance imaging (MRI) and fundus photography between 2021 and 2022. The cohort consisted of both cognitively healthy individuals (N = 417) and those with cognitive impairment (N = 491). We employed the NFN+ deep learning framework for retinal vessel segmentation and measurement. Associations between Retinal microvascular parameters (RMPs: central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension) and CI were assessed by Pearson correlation. P < 0.05 was considered statistically significant. The correlation between the CI and RMPs were explored, then the correlation coefficients between CI and RMPs were analyzed. Random Forest nonlinear classification model was used to predict whether one having cognitive decline or not. The assessment criterion was the AUC value derived from the working characteristic curve. RESULTS: The fractal dimension (FD) and global vein width were significantly correlated with the CI (P < 0.05). Age (0.193), BMI (0.154), global vein width (0.106), retinal vessel FD (0.099), and CRAE (0.098) were the variables in this model that were ranked in order of feature importance. The AUC values of the model were 0.799. CONCLUSIONS: Establishment of a predictive model based on the extraction of vascular features from fundus images has a high recognizability and predictive power for cognitive function and can be used as a screening method for CI.


Assuntos
Disfunção Cognitiva , Aprendizado Profundo , Humanos , Estudos Prospectivos , Disfunção Cognitiva/diagnóstico por imagem , Retina , Vasos Retinianos/diagnóstico por imagem , Biomarcadores
15.
Bioact Mater ; 34: 366-380, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38269308

RESUMO

Oxidative stress, infection, and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus (DM). In recent times, the discovery of neddylation, a new type of post-translational modification, has been found to regulate various crucial biological processes including cell metabolism and the cell cycle. Nevertheless, its capacity to control the healing of wounds in diabetic patients remains unknown. This study shows that MLN49224, a compound that inhibits neddylation at low concentrations, enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors. Moreover, it concurrently stimulates the growth, movement, and formation of blood vessel endothelial cells, leading to expedited healing of wounds in individuals with diabetes. The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles (M-NPs/MLN4924). The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area. The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes, along with the polarization of macrophages towards the anti-inflammatory M2 phenotype. By loading M-NPs/MLN4924 into a hydrogel, the final formulation is able to meaningfully repair a diabetic wound, suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.

16.
Sci Rep ; 14(1): 2213, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278873

RESUMO

Field observations in sedimentation and erosion-prone areas indicate that most natural sand deposits may contain a certain amount of non-plastic fines and are often under anisotropic stress conditions. A series of triaxial compression tests were performed on clean and silty sand with fines content fc ranging from 0 to 20% at an initial mean effective stress of p0' = 100 kPa and varying consolidation conditions to understand the impact of initial stress anisotropy on undrained shear behavior. The results indicate that the state parameter ψ is a superior predictor for characterizing the responses of sand-fines mixtures compared to the global void ratio and relative density. A comparison of the behavior of clean and silty sand with a constant ψ (= - 0.03) confirms that the sample with 10% fc exhibits the strongest dilation and greatest shear resistance, irrespective of the consolidation conditions. It is also demonstrated that the initial stress anisotropy with a comparably higher static stress ratio ηs typically diminishes the shear strength of mixtures. However, the influence of initial stress anisotropy on soil stiffness is not unilateral. The sample consolidated to a negative ηs is stiffer than that under isotropic consolidation, while the presence of a positive ηs leads to a decrease in the secant Young's modulus.

17.
Small ; 20(6): e2303494, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37794621

RESUMO

Insufficient bone formation and excessive bone resorption caused by estrogen deficiency are the major factors resulting in the incidence of postmenopausal osteoporosis (PMOP). The existing drugs usually fail to re-establish the osteoblast/osteoclast balance from both sides and generate side-effects owing to the lack of bone-targeting ability. Here, engineered cell-membrane-coated nanogels PNG@mR&C capable of scavenging receptor activator of nuclear factor-κB ligand (RANKL) and responsively releasing therapeutic PTH 1-34 in the bone microenvironment are prepared from RANK and CXCR4 overexpressed bone mesenchymal stem cell (BMSC) membrane-coated chitosan biopolymers. The CXCR4 on the coated-membranes confer bone-targeting ability, and abundant RANK effectively absorb RANKL to inhibit osteoclastogenesis. Meanwhile, the release of PTH 1-34 triggered by osteoclast-mediated acid microenvironment promote osteogenesis. In addition, the dose and frequency are greatly reduced due to the smart release property, prolonged circulation time, and bone-specific accumulation. Thus, PNG@mR&C exhibits satisfactory therapeutic effects in the ovariectomized (OVX) mouse model. This study provides a new paradigm re-establishing the bone metabolic homeostasis from multitargets and shows great promise for the treatment of PMOP.


Assuntos
Osteoclastos , Osteoporose Pós-Menopausa , Humanos , Animais , Camundongos , Feminino , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/metabolismo , Nanogéis , Biomimética , Diferenciação Celular , Osteoblastos , Osteogênese , NF-kappa B/metabolismo
18.
J Gastroenterol ; 59(1): 75-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37994950

RESUMO

The protective effect of indigo on intestinal epithelial cells remains unclear. Yokote Akihito et al. preliminarily investigated the anti-ferroptosis effect of indigo in inflammatory bowel disease. Here, we further discuss and evaluate the role of indigo based on the results.


Assuntos
Colite Ulcerativa , Ferroptose , Humanos , Colite Ulcerativa/tratamento farmacológico , Índigo Carmim/farmacologia , Ferroptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos
19.
Comput Biol Med ; 168: 107715, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38007975

RESUMO

Sizing of flow diverters (FDs) is a challenging task in the treatment of intracranial aneurysms due to their foreshortening behavior. The purpose of this study is to evaluate the difference between the sizing results from the AneuGuide™ software and from conventional 2D measurement. Ninety-eight consecutive patients undergoing pipeline embolization device (PED) treatment between October 2018 and April 2023 in the First Medical Center of Chinese PLA General Hospital (Beijing, China) were retrospectively analyzed. For all cases, the optimal PED dimensions were both manually determined through 2D measurements on pre-treatment 3D-DSA and computed by AneuGuide™ software. The inter-rater reliability between the two sets of sizing results for each methodology was analyzed using intraclass correlation coefficient (ICC). The degree of agreement between manual sizing and software sizing were analyzed with the Bland-Altman plot and Pearson's test. Differences between two methodologies were analyzed with Wilcoxon signed rank test. Statistical significance was defined as p < 0.05. There was better inter-rater reliability between AneuGuide™ measurements both for diameter (ICC 0.92, 95%CI 0.88-0.95) and length (ICC 0.93, 95%CI 0.89-0.96). Bland-Altman plots showed a good agreement for diameter selection between two methodologies. However, the median length proposed by software group was significantly shorter (16 mm versus 20 mm, p < 0.001). No difference was found for median diameter (4.25 mm versus 4.25 mm). We demonstrated that the AneuGuide™ software provides highly reliable results of PED sizing compared with manual measurement, with a shorter stent length. AneuGuide™ may aid neurointerventionalists in selecting optimal dimensions for FD treatment.


Assuntos
Prótese Vascular , Software , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Stents
20.
J Pharm Biomed Anal ; 239: 115911, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38091818

RESUMO

Polygonatum odoratum (Yu-Zhu) can be utilized to treat the digestive and respiratory illness. Previous studies have revealed that the underlying therapeutic mechanism of P. odoratum polysaccharides (POPs) is associated with remodeling the gut microbiota. However, POPs in terms of the chemical composition and fermentation activities have been understudied. Here we developed the three-level fingerprinting approaches to characterize the structures of POPs and probed into the beneficial effects on promoting the growth and fermentation of Lactobacillus johnsonii. POPs were prepared by water decoction followed by alcohol sedimentation, while trifluoroacetic acid under different conditions to prepare the hydrolyzed oligosaccharides and monosaccharides. POPs exhibited three main molecular distribution of 601-620 kDa, 4.12-6.09 kDa, and 3.57-6.02 kDa. Hydrolyzed oligosaccharides with degree of polymerization (DP) 2-13 got primarily characterized by analyzing the rich fragmentation information obtained by hydrophilic interaction chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (HILIC/IM-QTOF-MS). Amongst them, the DP5 oligosaccharide was characterized as 1,6,6-kestopentaose. The molecular ratio of Fru: Ara: Glc: Gal: Xyl was 87.72: 0.30: 11.56: 0.19: 0.23. In vitro fermentation demonstrated that 4.5 mg/mL of POPs could significantly promote the growth of L. johnsonii. Co-cultivated with 4.5 mg/mL of POPs, L. johnsonii exhibited stronger antimicrobial activity against Klebsiella pneumoniae. The concentrations of short-chain fatty acids in the POPs-lactobacilli fermented products, including acetic acid, isobutyric acid, and isovaleric acid, were increased. Conclusively, POPs represent the promising prebiotic candidate to facilitate lactobacilli, which is associated with exerting the health benefits.


Assuntos
Microbioma Gastrointestinal , Lactobacillus johnsonii , Polygonatum , Polygonatum/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Oligossacarídeos , Lactobacillus
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