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1.
Can J Cardiol ; 2024 Jul 22.
Article de Anglais | MEDLINE | ID: mdl-39230550

RÉSUMÉ

BACKGROUND: The relationship between mobile phone use and incident cardiovascular disease (CVD) is uncertain. We aimed to examine the association of regular mobile phone use with incident CVD and explore the mediating effects of sleep and mental health. METHODS: A total of 444,027 individuals from the UK Biobank without a history of CVD were included. Regular mobile phone use was defined as at least 1 call per week. Weekly mobile phone usage time was self-reported as the average time of calls per week over the previous 3 months. The primary outcome was incident CVD. The secondary outcomes included each component of CVD and increased carotid intima-media thickness (CIMT). We applied Cox proportional hazard models to assess the association between mobile phone use and incident CVD, and mediation analyses to investigate the role of sleep patterns, psychologic distress, and neuroticism. RESULTS: In a median follow-up period of 12.3 years, 56,181 individuals developed incident CVD. Compared with nonregular mobile phone users, regular mobile phone users had a significantly higher risk of incident CVD (hazard ratio 1.04, 95% confidence interval 1.02-1.06) and increased CIMT (odds ratio 1.11, 95% CI 1.04-1.18). Among regular mobile phone users, weekly mobile phone usage time was positively associated with the risk of incident CVD, especially in current smokers (P for interaction = 0.001) and diabetic individuals (P for interaction = 0.037). Of the relationship between weekly mobile phone usage time and incident CVD, 5.11% was mediated by sleep patterns, 11.5% by psychological distress, and 2.25% by neuroticism. CONCLUSIONS: Weekly mobile phone usage time was positively associated with incident CVD risk, which was partly explained by poor sleep, psychologic distress, and neuroticism.

2.
Anal Chem ; 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39238086

RÉSUMÉ

Tumor cells undergo an epithelial-mesenchymal transition (EMT) accompanied by a reduction in elasticity to initiate metastasis. However, in vivo, tumor cells typically exhibit partial EMT rather than fully EMT. Whether cell mechanics can accurately identify the status of partial EMT, especially the dynamic process, remains unclear. To elucidate the relationship between cell mechanics and partial EMT, we employed scanning ion conductance microscopy (SICM) to analyze the dynamic changes in cell mechanics during the TGFß-induced partial EMT of HCT116 colon cancer cells. Cells undergoing partial EMT, characterized by increased expression of EMT transcription factors, Snai1 and Zeb1, and EMT-related genes, Fn1 and MMP9, while retaining the expression of the epithelial markers E-cadherin (E-cad) and EpCAM, did not exhibit significant changes in cell morphology, suggesting that morphological changes alone were inadequate for identifying partial EMT status. However, cell elasticity markedly decreased in partial EMT cells, and this reduction was reversed with the reversible transition of partial EMT. These findings suggest a strong correlation between cell mechanics and the dynamic process of partial EMT, indicating that cell mechanics could serve as a valuable label-free marker for identifying the status of partial EMT while preserving the physiological characteristics of tumor cells.

3.
Nurs Open ; 11(9): e2127, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39219185

RÉSUMÉ

AIM: The purpose of the study was to investigate and analyse inner strength of patients with peritoneal dialysis, explore the associations among inner strength, coping self-efficacy (CSE) and medial coping modes. DESIGN: This was a cross-sectional study which was conducted in nephrology departments of two affiliated hospitals of a comprehensive university in China. Convenience sampling was chosen to collect data. METHODS: A total of 191 patients undergoing peritoneal dialysis were recruited by convenience sampling in two hospitals. Data involved of sociodemographic and clinical materials, inner strength, CSE and medical coping modes were collected from the patients. IBM SPSS Statistics 21.0 was used to process and analyse the data. RESULTS: The averaged score of inner strength was 95.74 (SD = 13.52). The inner strength, CSE and confrontation coping had positive associations with each other. Besides, inner strength and CSE was negatively associated with acceptance-resignation coping strategy, respectively.


Sujet(s)
Adaptation psychologique , Dialyse péritonéale , Auto-efficacité , Humains , Études transversales , Mâle , Femelle , Dialyse péritonéale/psychologie , Adulte d'âge moyen , Chine , Adulte , Enquêtes et questionnaires , Sujet âgé ,
4.
Aging Cell ; : e14330, 2024 Sep 09.
Article de Anglais | MEDLINE | ID: mdl-39252463

RÉSUMÉ

We aimed to develop and validate a protein risk score for predicting Alzheimer's disease (AD) and compare its performance with a validated clinical risk model (Cognitive Health and Dementia Risk Index for AD [CogDrisk-AD]) and apolipoprotein E (APOE) genotypes. The development cohort, consisting of 35,547 participants from England in the UK Biobank, was randomly divided into a 7:3 training-testing ratio. The validation cohort included 4667 participants from Scotland and Wales in the UK Biobank. In the training set, an AD protein risk score was constructed using 31 proteins out of 2911 proteins. In the testing set, the AD protein risk score had a C-index of 0.867 (95% CI, 0.828, 0.906) for AD prediction, followed by CogDrisk-AD risk factors (C-index, 0.856; 95% CI, 0.823, 0.889), and APOE genotypes (C-index, 0.705; 95% CI, 0.660, 0.750). Adding the AD protein risk score to CogDrisk-AD risk factors (C-index increase, 0.050; 95% CI, 0.008, 0.093) significantly improved the predictive performance for AD. However, adding CogDrisk-AD risk factors (C-index increase, 0.040; 95% CI, -0.007, 0.086) or APOE genotypes (C-index increase, 0.000; 95% CI, -0.054, 0.055) to the AD protein risk score did not significantly improve the predictive performance for AD. The top 10 proteins with the highest coefficients in the AD protein risk score contributed most of the predictive power for AD risk. These results were verified in the external validation cohort. EGFR, GFAP, and CHGA were identified as key proteins within the protein network. Our result suggests that the AD protein risk score demonstrated a good predictive performance for AD risk.

5.
Heart ; 2024 Sep 04.
Article de Anglais | MEDLINE | ID: mdl-39237126

RÉSUMÉ

BACKGROUND: Proteomic biomarkers have shown promise in predicting various cardiovascular conditions, but their utility in assessing the risk of atrial fibrillation (AF) remains unclear. This study aimed to develop and validate a protein-based risk score for predicting incident AF and to compare its predictive performance with traditional clinical risk factors and polygenic risk scores in a large cohort from the UK Biobank. METHODS: We analysed data from 36 129 white British individuals without prior AF, assessing 2923 plasma proteins using the Olink Explore 3072 assay. The cohort was divided into a training set (70%) and a test set (30%) to develop and validate a protein risk score for AF. We compared the predictive performance of this score with the HARMS2-AF risk model and a polygenic risk score. RESULTS: Over an average follow-up of 11.8 years, 2450 incident AF cases were identified. A 47-protein risk score was developed, with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) being the most significant predictor. In the test set, the protein risk score (per SD increment, HR 1.94; 95% CI 1.83 to 2.05) and NT-proBNP alone (HR 1.80; 95% CI 1.70 to 1.91) demonstrated superior predictive performance (C-statistic: 0.802 and 0.785, respectively) compared with HARMS2-AF and polygenic risk scores (C-statistic: 0.751 and 0.748, respectively). CONCLUSIONS: A protein-based risk score, particularly incorporating NT-proBNP, offers superior predictive value for AF risk over traditional clinical and polygenic risk scores, highlighting the potential for proteomic data in AF risk stratification.

6.
Int J Biol Macromol ; 279(Pt 4): 135108, 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39244123

RÉSUMÉ

The application of camellia oil is limited by its susceptibility to oxidation and insolubility in water, particularly under high humidity and temperature conditions. In order to effectively reduce the oxidation rate of camellia oil, prolong the shelf life in order to improve the stability in storage under different conditions, this study encapsulates camellia oil in Pickering emulsions stabilized by Octenyl succinic acid (OSA) starch, achieving a 100-fold reduction in release rate and enhanced lipid oxidation stability. The smooth surface and complete particles of the emulsion were observed and no new chemical bonds were formed. The minimum particle sizes were 1.72 µm and 2.73 µm, when the Pickering emulsion was set at pH 6 and 0.1 M NaCl. In the digestion process, the microstructures observed that Pickering emulsion possessed super stability against oral and gastric digestions, prolonged the release time and improved the bioavailability compared with camellia oil, and the digestibility of the emulsion was 56.16 % within 120 min. All these results indicate that OSA-starch stabilized camellia oil can effectively increase solubility, improve stability and expand the application range.

7.
Diabetes Obes Metab ; 2024 Aug 19.
Article de Anglais | MEDLINE | ID: mdl-39161069

RÉSUMÉ

AIM: To assess the association of intake of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with new-onset atrial fibrillation (AF) in people with prediabetes or diabetes. METHODS: A total of 31 433 participants with prediabetes and diabetes from the UK Biobank were included. Information on the intake of SSBs, ASBs and NJs was accessed by 24-hour dietary recalls from 2009 to 2012. The study outcome was new-onset AF. RESULTS: During a median follow-up of 12.0 years, 2470 (7.9%) AF cases were documented. Both the intake of SSBs (per 1 unit/day increment; adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.04-1.18) and ASBs (per 1 unit/day increment; adjusted HR = 1.08; 95% CI: 1.02-1.14) were linearly and positively associated with new-onset AF, while NJ intake was not significantly associated with new-onset AF (per 1 unit/day increment; adjusted HR = 1.00; 95% CI: 0.93-1.08). Accordingly, compared with non-consumers, participants who consumed more than one unit per day of SSBs (adjusted HR = 1.30; 95% CI: 1.11-1.53) or ASBs (adjusted HR = 1.21; 95% CI:1.05-1.40) had an increased risk of AF. Substituting 1 unit/day of NJs for SSBs was associated with a 9% (adjusted HR = 0.91; 95% CI: 0.83-0.99) lower risk of new-onset AF, while replacing SSBs with ASBs was not significantly associated with new-onset AF (adjusted HR = 0.97; 95% CI: 0.89-1.06). CONCLUSIONS: Both the intake of SSBs and ASBs were linearly and positively associated with new-onset AF, while NJ intake did not show a significant association with AF in people with prediabetes or diabetes. Replacing an equivalent amount of SSB intake with NJs, but not ASBs, was associated with a lower risk of AF.

8.
Article de Anglais | MEDLINE | ID: mdl-39168802

RÉSUMÉ

BACKGROUND AND AIM: The association between lung function with non-alcoholic fatty liver disease (NAFLD) in the general population remains unknown. We aimed to examine the association between lung function and NAFLD among the general population in an observational and Mendelian randomization (MR) study. METHODS AND RESULTS: 340, 253 participants without prior liver diseases were included from the UK Biobank. Of these, 30,397 participants had liver proton density fat fraction (PDFF) measurements by magnetic resonance image (MRI). Lung function parameters included forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). The primary outcome was the presence of NAFLD, defined as a PDFF greater than 5.5%. The secondary outcome included incident severe NAFLD and severe liver diseases (including liver cirrhosis, liver failure, hepatocellular carcinoma and liver-related death), defined by the International Classification of Disease codes with different data sources. During a media follow-up duration of 9.3 years, 7335 (24.1%) the presence of NAFLD cases were documented. There was an inverse association of FEV1 (% predicted) (Per SD increment, adjusted OR = 0.91, 95%CI: 0.88-0.94) and FVC (% predicted) (Per SD increment, adjusted OR = 0.90, 95%CI: 0.87-0.92) with the presence of NAFLD. Similar results were found for incident severe NAFLD, severe liver disease, liver cirrhosis, liver failure and liver-related death. MR analyses showed that the genetically predicted FEV1 (adjusted OR = 0.63, 95%CI: 0.46-0.87) and FVC (adjusted OR = 0.69, 95%CI: 0.51-0.95) were both inversely associated with the presence of NAFLD. CONCLUSIONS: There was an inverse causal relationship between lung function and NAFLD in the general population.

9.
J Food Sci ; 2024 Aug 31.
Article de Anglais | MEDLINE | ID: mdl-39215526

RÉSUMÉ

Under high humidity and high temperature conditions, the quality of pepper essential oil easily deteriorates, and the oxidation of oil restricts its application, especially for the insolubility in water. This study investigated pepper essential oil encapsulated in Pickering emulsion with octenyl succinic acid starch, which was effectively able to reduce 100 times of the release rate. The smooth surface and complete particles of the emulsion were observed and no new chemical bonds were formed. The minimum particle sizes were 2.05 µm and 1.89 µm, when the Pickering emulsion was set to different storage conditions at pH 5 and 0.1 M NaCl, respectively. During gastrointestinal digestion, the release of essential oils was effectively delayed in the Pickering emulsion and the digestibility of the emulsion was 16.93% in 120 min. Compared with untreated cells, Pickering emulsion can effectively inhibit the proliferation of MCF-7 (52.71%). All these results indicate that OSA starch stabilized pepper essential oil can effectively increase solubility, improve stability, and expand the application range. Therefore, it can provide a theoretical basis for applications of pepper essential oil, especially for the functional drug application.

10.
Animals (Basel) ; 14(16)2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-39199832

RÉSUMÉ

This study aimed to estimate the genetic and non-genetic factors that affect the nine early growth traits of Dumeng sheep, as well as to estimate the variance components and genetic parameters associated with these traits. A dataset containing detailed information on 17,896 preweaning trait records of 4474 lambs was collected. In addition, 5015 postweaning trait records of 1003 lambs were documented. The effects of recipient dam age, sex, year, season, and herd on the early growth traits were assessed using the general linear model procedure of the statistical analysis system, revealing different levels of significance across different traits. To determine the most suitable model for estimating the genetic parameters, the likelihood ratio (LR) test was employed, fitting six animal models that either excluded or included maternal genetic and maternal permanent environmental effects within the average information restricted maximum likelihood (AIREML) framework using WOMBAT software (Version: 23/11/23). The model incorporating direct additive genetic effects, maternal genetic effects, and maternal permanent environment effects as random effects (model 6) provided the best fit for birth weight (BW) estimation. In contrast, the model combining direct additive genetic effects and maternal permanent environment effects as random effects (model 2) demonstrated a superior fit for estimating the genetic parameters of weaning weight (WW), average daily gain weight from birth to weaning (ADG1), and Kleiber ratio from birth to weaning (KR1). With regard to the genetic parameters of body weight at 6 months of age (6MW), average daily gain weight from weaning to 6 months (ADG2), average daily gain weight from birth to 6 months (ADG3), Kleiber ratio from weaning to 6 months (KR2), and Kleiber ratio from birth to 6 months (KR3), model 1, which incorporates only direct additive genetic effects, was identified as the optimal choice. With the optimal model, the heritability estimates ranged from 0.010 ± 0.033 for 6MW to 0.1837 ± 0.096 for KR3. The bivariate analysis method was employed to estimate the correlation between various traits using the most suitable model. The absolute values of genetic correlation coefficients among the traits spanned a range from 0.1460 to 0.9998, highlighting both weak and strong relationships among the studied traits. Specifically, the estimated genetic correlations between WW and ADG1, ADG3, KR1, and KR3 were 0.9859, 0.9953, 0.9911, and 0.9951, respectively, while the corresponding phenotypic correlations were 0.9752, 0.7836, 0.8262, and 0.5767. These findings identified that WW could serve as an effective selection criterion for enhancing early growth traits.

11.
Mol Nutr Food Res ; : e2400373, 2024 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-39192471

RÉSUMÉ

SCOPE: This study aims to assess the association between intake of different types of fruit (citrus, pomes, tropical fruits, berries, gourds, drupes, dried fruits, and other fruits), the intake diversity of fruit types, and risk of new-onset kidney stones in general population. METHODS AND RESULTS: A total of 205 896 participants with at least one completed 24-h dietary recall from the UK Biobank are included. During a median follow-up of 11.6 years, 2074 cases of kidney stones are documented. Compared with nonconsumers, participants with higher intake of citrus (50-<100 g day-1; hazards ratio [HR] = 0.78; 95% confidence interval [CI], 0.66-0.91; ≥100 g day-1; HR = 0.75; 95%CI, 0.63-0.89), pomes (≥100 g day-1; HR = 0.86; 95%CI, 0.77-0.96), or tropical fruits (50-<100 g day-1; HR = 0.86; 95%CI, 0.75-0.99; ≥100 g day-1; HR = 0.88; 95%CI, 0.79-0.99) have a lower risk of new-onset kidney stones. However, there is no significant association of intake of berries, gourds, drupes, dried fruits, and other fruits with kidney stones. A higher fruit variety score is significantly associated with a lower risk of new-onset kidney stones (per 1-score increment, HR = 0.86; 95%CI, 0.81-0.91). CONCLUSIONS: Higher intake of citruses (≥50 g day-1), pomes (≥100 g day-1), and tropical fruits (≥50 g day-1), as well as increasing diversity of intake of these three fruits, are associated with a lower risk of new-onset kidney stones.

12.
Prev Med ; 187: 108120, 2024 Aug 24.
Article de Anglais | MEDLINE | ID: mdl-39187133

RÉSUMÉ

OBJECTIVE: To examine the relationship between an accelerometer-derived "weekend warrior" pattern, characterized by achieving the most moderate to vigorous physical activity (MVPA) over 1-2 days, as opposed to more evenly distributed patterns, with risk of chronic kidney disease (CKD) and acute kidney injury (AKI). METHODS: 77,977 participants without prior kidney diseases and with usable accelerometer data (collected between 2013 and 2015) were included from the UK Biobank. Three physical activity patterns were compared: active weekend warrior pattern (achieving ≥150 min MVPA per week and accumulating ≥50 % of total MVPA in 1-2 days), active regular pattern (achieving ≥150 min MVPA but not meeting active weekend warrior criteria per week), and inactive pattern (<150 min MVPA per week). The study outcomes included incident CKD and AKI, ascertained through self-report data and data linkage with primary care, hospital admissions, and death registry records. RESULTS: During a median follow-up of 6.8 years, 1324 participants developed CKD and 1515 developed AKI. In multivariable-adjusted models, when compared with inactive participants, individuals with active weekend warrior pattern (CKD: hazard ratio [HR], 0.79, 95 % confidence interval [CI], 0.69-0.89; AKI: HR, 0.70, 95 %CI, 0.62-0.79) and those with active regular pattern (CKD: HR, 0.81, 95 %CI, 0.69-0.95; AKI: HR, 0.79, 95 %CI, 0.68-0.91) exhibited a similar and significantly lower risk of incident CKD and AKI. Similar findings were observed at the median threshold of ≥230.4 min of MVPA per week. CONCLUSION: Concentrated MVPA within 1 to 2 days is as effective as distributed ones in decreasing the risk of renal outcomes.

13.
Brain Behav Immun ; 122: 604-616, 2024 Aug 24.
Article de Anglais | MEDLINE | ID: mdl-39187048

RÉSUMÉ

The prevalence of bacterial infections significantly increases among patients with severe traumatic brain injury (STBI), leading to a notable rise in mortality rates. While immune dysfunctions are linked to the incidence of pneumonia, our observations indicate that endogenous pathogens manifest in the lungs post-STBI due to the migration of gut commensal bacteria. This translocation involves gut-innervating nociceptor sensory neurons, which are crucial for host defense. Following STBI, the expression of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons significantly decreases, despite an initial brief increase. The timing of TRPV1 defects coincides with the occurrence of pulmonary infections post-STBI. This alteration in TRPV1+ neurons diminishes their ability to signal bacterial injuries, weakens defense mechanisms against intestinal bacteria, and increases susceptibility to pulmonary infections via bacterial translocation. Experimental evidence demonstrates that pulmonary infections can be successfully replicated through the chemical ablation and gene interference of TRPV1+ nociceptors, and that these infections can be mitigated by TRPV1 activation, thereby confirming the crucial role of nociceptor neurons in controlling intestinal bacterial migration. Furthermore, TRPV1+ nociceptors regulate the immune response of microfold cells by releasing calcitonin gene-related peptide (CGRP), thereby influencing the translocation of gut bacteria to the lungs. Our study elucidates how changes in nociceptive neurons post-STBI impact intestinal pathogen defense. This new understanding of endogenous risk factors within STBI pathology offers novel insights for preventing and treating pulmonary infections.

14.
Mayo Clin Proc ; 99(9): 1399-1410, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39115510

RÉSUMÉ

OBJECTIVE: To investigate the causal dose-response association between cognitive function and the risk of chronic kidney disease (CKD) by a longitudinal cohort and mendelian randomization study. METHODS: The longitudinal cohort study included 396,600 participants without prior dementia and CKD from the UK Biobank. Cognitive function (including prospective memory, numeric memory, visuospatial memory, reaction time, and reasoning ability) was assessed by computerized touchscreen tests. Global cognitive function was defined as a composite score of those specific cognitive domains. A 2-stage mendelian randomization analysis was conducted with 12,979 cases of CKD and 379,424 controls. Genetically predicted global cognitive function was instrumented with 91 confirmed genome-wide significant variants. The study outcome was new-onset CKD. The study was conducted from March 13, 2006, to September 30, 2021. RESULTS: During a median follow-up of 12.5 years, new-onset CKD developed in 13,090 participants. Per 1 SD score increments in reaction time (adjusted hazard ratio [HR], 0.97; 95% CI, 0.95 to 0.99), reasoning ability (adjusted HR, 0.91; 95% CI, 0.88 to 0.94), and global cognitive function (adjusted HR, 0.96; 95% CI, 0.95 to 0.98) were associated with a significantly lower risk of new-onset CKD. Compared with an incorrect answer in the prospective memory test, a correct answer was associated with a lower risk of new-onset CKD (adjusted HR, 0.82; 95% CI, 0.76 to 0.88). Mendelian randomization analyses found that per 1 SD score increments in genetically predicted global cognitive function resulted in a significantly (7%; 95% CI, 2% to 12%) lower risk of new-onset CKD. CONCLUSION: A better cognitive function is causally associated with a lower risk of CKD in participants without prior dementia.


Sujet(s)
Cognition , Analyse de randomisation mendélienne , Insuffisance rénale chronique , Humains , Insuffisance rénale chronique/épidémiologie , Insuffisance rénale chronique/génétique , Femelle , Mâle , Études longitudinales , Adulte d'âge moyen , Cognition/physiologie , Sujet âgé , Royaume-Uni/épidémiologie , Facteurs de risque
15.
Bioorg Chem ; 151: 107683, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39121595

RÉSUMÉ

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 µM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 µM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.


Sujet(s)
Acide oléanolique , Souris , Animaux , Cellules RAW 264.7 , Acide oléanolique/pharmacologie , Acide oléanolique/composition chimique , Acide oléanolique/isolement et purification , Acide oléanolique/analogues et dérivés , Structure moléculaire , Relation structure-activité , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/composition chimique , Anti-inflammatoires/isolement et purification , Monoxyde d'azote/antagonistes et inhibiteurs , Monoxyde d'azote/biosynthèse , Monoxyde d'azote/métabolisme , Lipopolysaccharides/pharmacologie , Lipopolysaccharides/antagonistes et inhibiteurs , Relation dose-effet des médicaments , Anti-inflammatoires non stéroïdiens/pharmacologie , Anti-inflammatoires non stéroïdiens/composition chimique , Anti-inflammatoires non stéroïdiens/isolement et purification , Nitric oxide synthase type II/antagonistes et inhibiteurs , Nitric oxide synthase type II/métabolisme , Cyclooxygenase 2/métabolisme
16.
Nat Commun ; 15(1): 7585, 2024 Aug 31.
Article de Anglais | MEDLINE | ID: mdl-39217172

RÉSUMÉ

Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.


Sujet(s)
Anticorps neutralisants , Anticorps antiviraux , COVID-19 , Épitopes , SARS-CoV-2 , Glycoprotéine de spicule des coronavirus , SARS-CoV-2/immunologie , SARS-CoV-2/génétique , Humains , Glycoprotéine de spicule des coronavirus/immunologie , Glycoprotéine de spicule des coronavirus/génétique , COVID-19/immunologie , COVID-19/virologie , Anticorps antiviraux/immunologie , Anticorps neutralisants/immunologie , Épitopes/immunologie , Épitopes/génétique , Chaines légères des immunoglobulines/génétique , Chaines légères des immunoglobulines/immunologie
17.
Phys Med Biol ; 69(18)2024 Sep 13.
Article de Anglais | MEDLINE | ID: mdl-39191290

RÉSUMÉ

Objective.In this study, we propose a semi-supervised learning (SSL) scheme using a patch-based deep learning (DL) framework to tackle the challenge of high-precision classification of seven lung tumor growth patterns, despite having a small amount of labeled data in whole slide images (WSIs). This scheme aims to enhance generalization ability with limited data and reduce dependence on large amounts of labeled data. It effectively addresses the common challenge of high demand for labeled data in medical image analysis.Approach.To address these challenges, the study employs a SSL approach enhanced by a dynamic confidence threshold mechanism. This mechanism adjusts based on the quantity and quality of pseudo labels generated. This dynamic thresholding mechanism helps avoid the imbalance of pseudo-label categories and the low number of pseudo-labels that may result from a higher fixed threshold. Furthermore, the research introduces a multi-teacher knowledge distillation (MTKD) technique. This technique adaptively weights predictions from multiple teacher models to transfer reliable knowledge and safeguard student models from low-quality teacher predictions.Main results.The framework underwent rigorous training and evaluation using a dataset of 150 WSIs, each representing one of the seven growth patterns. The experimental results demonstrate that the framework is highly accurate in classifying lung tumor growth patterns in histopathology images. Notably, the performance of the framework is comparable to that of fully supervised models and human pathologists. In addition, the framework's evaluation metrics on a publicly available dataset are higher than those of previous studies, indicating good generalizability.Significance.This research demonstrates that a SSL approach can achieve results comparable to fully supervised models and expert pathologists, thus opening new possibilities for efficient and cost-effective medical images analysis. The implementation of dynamic confidence thresholding and MTKD techniques represents a significant advancement in applying DL to complex medical image analysis tasks. This advancement could lead to faster and more accurate diagnoses, ultimately improving patient outcomes and fostering the overall progress of healthcare technology.


Sujet(s)
Adénocarcinome pulmonaire , Traitement d'image par ordinateur , Tumeurs du poumon , Humains , Tumeurs du poumon/imagerie diagnostique , Tumeurs du poumon/anatomopathologie , Adénocarcinome pulmonaire/imagerie diagnostique , Adénocarcinome pulmonaire/anatomopathologie , Traitement d'image par ordinateur/méthodes , Apprentissage machine supervisé , Apprentissage profond
18.
Vet Sci ; 11(7)2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-39057993

RÉSUMÉ

The purpose of this study was to investigate the effects of non-genetic factors on the growth and development performance of Inner Mongolia white cashmere goats (Erlanghan type), such as birth weight (BW), weaning weight (WW), 6-month weight (6 WT), 12-month weight (12 WT), body height (BH), and body length (BL), and wool production performance, such as cashmere fineness (CF), cashmere thickness (CT), and cashmere yield (CY). The research objects were 4654 kids produced by 45 buck goats and 2269 doe goats in the Erlang Mountain Ranch of Beiping Textile Co., Ltd., Inner Mongolia, from 2020 to 2023. Based on the generalized linear model, ANOVA was used to analyze the effects of non-genetic factors, such as birth year (Y), birth month (M), sex (S), birth type (T), birth herd (H), assay flock (F), age at measurement (MA), and the age of doe goats at lambing (DLA), on growth and development traits and cashmere traits. The results show that the birth weight (BW), weaning weight (WW), 6-month weight (6 WT), 12-month weight (12 WT), body length (BL), body height (BH), chest depth (CD), chest width (CW), chest circumference (CC), cannon circumference (CNC), wool length (WL), and cashmere yield (CY) of buck goats were significantly higher than those of doe goats (p < 0.01), and the fineness of the cashmere produced by doe goats was significantly finer than that produced by buck goats (p < 0.01). The birth weight, weaning weight, and 6-month weight of single kids were significantly higher than those of multiple kids (p < 0.01), but the effect on the 12-month weight was not significant (p > 0.05). The age of doe goats at lambing had significant effects on birth weight, weaning weight, and 6-month weight (p < 0.01). Assay flock and age at measurement had significant effects on cashmere fineness, cashmere thickness, and cashmere yield (p < 0.01). This study will provide a basis for the scientific breeding and management of cashmere goats and lay a foundation for the setting of fixed effects in the genetic evaluation model of Inner Mongolia white cashmere goats (Erlangshan type).

19.
Sci Rep ; 14(1): 17717, 2024 Jul 31.
Article de Anglais | MEDLINE | ID: mdl-39085627

RÉSUMÉ

The evolution and mechanism of ground collapse caused by underground water pipeline leakage have become increasingly significant as more urban areas experience collapses. Based on the principle of similarity, and considering the engineering context of road collapses in Anqing City, Anhui Province, this study designed a 3 m × 2 m × 2 m rupture-collapse model test device. Digital Image Correlation (DIC) technology was employed to investigate the erosion process and collapse mechanisms caused by underground pipeline leakage. The results indicate that groundwater seepage provides the driving force for collapses, combined with the migration space provided by defects, collectively triggering the collapses. When groundwater seepage is minimal, the cohesive forces between soil particles maintain soil stability. As groundwater seepage increases, the soil particle framework is eroded, leading to soil structure destabilization and collapse initiation. The depth of collapse significantly influences stress evolution: stress evolution intensity beneath and above the collapse pit is positively correlated with the distance from the collapse pit bottom, but negatively correlated with the distance from the defect. The research provides insights for the early warning and management of ground collapse.

20.
Pathol Res Pract ; 260: 155449, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38981345

RÉSUMÉ

Parathyroid carcinoma(PC) is an extremely rare malignant tumor of the parathyroid glands. The lung is the most common target organ for PC distant metastases. In this study, twelve patients diagnosed with PC with lung metastases were enrolled in the study. Hematoxylin and Eosin(H&E) stained, immunohistochemical stained and next-generation sequencing (NGS) of a 425-gene panel were performed on tumor tissue samples. At the same time, we also evaluated its histopathologic characteristics. The results indicate that the microscopic examination of metastatic lesions reveals the same structure and characteristics as PC; the tumor was composed of relatively uniform cells organized in nests and separated by thin fibrous bands and abundant blood vessels. Immunohistochemical evaluation of Ki67, CyclinD1, PTH, SYN, CgA, and CD56 was useful in diagnosing PC with lung metastases. The most frequently genetic alterations were mutations of CDC73 and copy number variation (CNV) of MCL1, with a mutation rate of 25 %. In addition, the mutations of CDC73, ATM, TP53, ALK, ERBB2, MAP3K4, TSC1, CCND1 and CNV of CDK4, MCL1, SMARCB1 overlap between metastatic lesions and primary lesions. In conclusions, PC is a rare endocrine malignant tumor that is very difficult to diagnose preoperatively and prone to clinical recurrence or distant metastasis. Genetic mutations, presentation and histological characteristic were the basis for diagnosing PC with lung metastases.


Sujet(s)
Tumeurs du poumon , Tumeurs de la parathyroïde , Humains , Tumeurs du poumon/anatomopathologie , Tumeurs du poumon/secondaire , Tumeurs du poumon/génétique , Tumeurs de la parathyroïde/anatomopathologie , Tumeurs de la parathyroïde/génétique , Mâle , Femelle , Adulte d'âge moyen , Adulte , Sujet âgé , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/analyse , Mutation , Séquençage nucléotidique à haut débit
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