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1.
Brain Behav ; 14(10): e70053, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39350430

ABSTRACT

OBJECTIVE: This study aimed to analyze the features of resting-state functional magnetic resonance imaging (rs-fMRI) and clinical relevance in patients with benign paroxysmal positional vertigo (BPPV) that have undergone repositioning maneuvers. METHODS: A total of 38 patients with BPPV who have received repositioning maneuvers and 38 matched healthy controls (HCs) were enrolled in the present study from March 2018 to August 2021. Imaging analysis software was employed for functional image preprocessing and indicator calculation, mainly including the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), and seed-based functional connectivity (FC). Statistical analysis of the various functional indicators in patients with BPPV and HCs was also conducted, and correlation analysis with clinical data was performed. RESULTS: Patients with BPPV displayed decrease in ALFF, fALFF, and PerAF values, mainly in the bilateral occipital lobes in comparison with HCs. Additionally, their ALFF and fALFF values in the proximal vermis region of the cerebellum increased relative to HCs. The PerAF values in the bilateral paracentral lobules, the right supplementary motor area (SMA), and the left precuneus decreased in patients with BPPV and were negatively correlated with dizziness visual analog scale (VAS) scores 1 week after repositioning (W1). In addition, in the left fusiform gyrus and lingual gyrus, the PerAF values show a negative correlation with dizziness handicap inventory (DHI) scores at initial visit (W0). Seed-based FC analysis using the seeds from differential clusters of fALFF, ALFF, and PerAF showed reductions between the left precuneus and bilateral occipital lobe, the left precuneus and left paracentral lobule, and within the occipital lobes among patients with BPPV. CONCLUSION: The spontaneous activity of certain brain regions in the bilateral occipital and frontoparietal lobes of patients with BPPV was reduced, whereas the activity in the cerebellar vermis was increased. Additionally, there were reductions in FC between the precuneus and occipital cortex or paracentral lobule, as well as within the occipital cortex. The functional alterations in these brain regions may be associated with the inhibitory interaction and functional integration of visual, vestibular, and sensorimotor systems. The functional alterations observed in the visual cortex and precuneus may represent adaptive responses associated with residual dizziness.


Subject(s)
Benign Paroxysmal Positional Vertigo , Magnetic Resonance Imaging , Humans , Male , Female , Benign Paroxysmal Positional Vertigo/physiopathology , Benign Paroxysmal Positional Vertigo/diagnostic imaging , Middle Aged , Adult , Brain/physiopathology , Brain/diagnostic imaging , Patient Positioning/methods , Aged
2.
Sci Total Environ ; 954: 176669, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39362558

ABSTRACT

Recognition of biotic and abiotic factors affecting biomass of natural mixed forests is of great importance for forest carbon estimation and management. When estimating stand biomass using models, different variable selection methods often yield inconsistent results, and there is lack of systematic analysis. This study aimed to combine multiple feature selection methods with structural equation modelling (SEM) to identify a set of variables affecting stand biomass more reasonably. Eight methods were applied for feature selection based on data from 286 permanent sample plots in natural coniferous-broad leaved mixed forests in northeast China. These methods included Pearson correlation analysis, two methods derived from principal component analysis (PCA), stepwise regression, redundancy analysis (RDA), generalized additive model (GAM), random forest (RF), and boosted regression tree (BRT). A total of 56 candidate variables were considered, covering stand, biodiversity, climate and soil features. Significant variability was observed in the variables selected, however, there were 6 variables consistently identified across all methods, including tree species diversity (N_Sp_Div), stand structural diversity (N_ Size_ Div), nearest taxon index (NRI), community weighted mean based on dry matter mass of leaves (CWM.LDMC), soil pH, and degree-days above 18 °C (DD18). Then, these variables were included in the SEM with stand average age and additive stand density index (aSDI) to explore the direction and magnitude of their impacts on stand biomass. The SEM results showed that aSDI and average age had the greatest positive effects on stand biomass, and structural diversity also had a significant positive effect. DD18 affected stand biomass both directly and indirectly, with the total negative effect. Soil pH indirectly affected stand biomass via aSDI. Our findings demonstrated that combining multiple feature selection methods with SEM was an effective approach for understanding multiple factors affecting stand biomass, and provided valuable insights for forest biomass estimation and carbon management.

3.
Front Med (Lausanne) ; 11: 1485061, 2024.
Article in English | MEDLINE | ID: mdl-39351003

ABSTRACT

[This corrects the article DOI: 10.3389/fmed.2024.1361437.].

4.
Exp Dermatol ; 33(10): e15182, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39367575

ABSTRACT

Stress may play a key role in alopecia areata (AA), though the exact interactions of stress with AA remain undefined. Corticotropin-releasing hormone (CRH), the proximal regulator of the stress axis, has been recognized as an immunomodulatory factor in tissues and peripheral blood mononuclear cells (PBMCs). We used multicolour flow cytometry to identify receptor CRHR1 expression on PBMC subsets in AA patients (n = 54) and controls (n = 66). We found that CRHR1 was primarily expressed by circulating monocytes. CRHR1 expression on monocytes was enhanced in AA compared with controls (3.17% vs. 1.44%, p = 0.002, chi-squared test). AA incidence was correlated to elevated CD14+ monocyte numbers (R = 0.092, p = 0.036) and markedly independently correlated with increased CRHR1 expression (R = 0.215, p = 0.027). High CRHR1 expression was significantly related to chronic AA (disease duration >1 year; p = 0.003, chi-squared test), and large lesion area (AA area >25%; p = 0.049, chi-squared test). We also observed enhanced percentages of active monocytes and reduced CD16+ CD3- NK cell numbers in AA patients' PBMCs (p = 0.010; 0.025, respectively). In vitro CRH treatment of PBMCs and human monocyte cell line THP-1 promoted CD86 upregulation. The findings imply that stress-related factors CRH and CRHR1 contribute to AA development and progression where higher CRHR1 expression is associated with chronic AA and larger lesions.


Subject(s)
Alopecia Areata , Corticotropin-Releasing Hormone , Monocytes , Receptors, Corticotropin-Releasing Hormone , Humans , Receptors, Corticotropin-Releasing Hormone/metabolism , Corticotropin-Releasing Hormone/metabolism , Monocytes/metabolism , Adult , Male , Female , Middle Aged , Alopecia Areata/metabolism , Lipopolysaccharide Receptors/metabolism , Young Adult , Case-Control Studies , Flow Cytometry , Receptors, IgG/metabolism , Killer Cells, Natural/metabolism
5.
Clin Exp Med ; 24(1): 237, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39365401

ABSTRACT

The aim was to evaluate predictors of clinical outcomes in infliximab (IFX)-treated Crohn's disease (CD) patients in western China and provide evidence for future treatment optimization. Our retrospective study included CD patients at Chongqing General Hospital from July 2022 to July 2023. Clinical data of CD patients at baseline and the endpoint (the seventh IFX treatment, 38 weeks) were collected. Baseline variables of IFX-treated patients with regard to clinical remission [Crohn's Disease Activity Index (CDAI) < 150] at endpoint were assessed, and the correlation of serum vitamin D (Vit-D) levels before initiating IFX therapy and CDAI at week 38 was analyzed. Sixty patients with IFX-treated CD were included. The Vit-D-deficient rate was 51.7% at baseline, 81.7% of patients achieved clinical remission, and 66.7% achieved endoscopic remission at week 38 of IFX treatment. Vit-D level at baseline was an independent predictors of clinical remission after IFX treatment (P < 0.05). Receiver operating characteristic curve analysis showed that when Vit-D concentration was 15.81 ng/ml, the area under the curve was 0.711 (95% CI 0.523-0.899, P = 0.03). The sensitivity and specificity were 81.6% and 63.6%, respectively. Vit-D level in the normal BMI, non-smoking, immunosuppressant-treated subgroup had independent predictive value for CDAI at endpoint (P < 0.05). Baseline Vit-D level predicted clinical remission in CD patients after IFX treatment, especially in those with normal body mass index, who do not smoke, and who take IFX in combination with immunosuppressants.


Subject(s)
Crohn Disease , Infliximab , Vitamin D , Humans , Crohn Disease/drug therapy , Crohn Disease/blood , Infliximab/therapeutic use , Female , Male , Adult , Vitamin D/blood , Vitamin D/therapeutic use , Retrospective Studies , China , Treatment Outcome , Young Adult , Middle Aged , ROC Curve , Gastrointestinal Agents/therapeutic use , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/blood , Adolescent , Remission Induction
6.
Front Pharmacol ; 15: 1457614, 2024.
Article in English | MEDLINE | ID: mdl-39380905

ABSTRACT

Background: The main challenges faced when using sirolimus in children with vascular anomalies (VAs) still include significant pharmacokinetic (PK) variability, uncertainty in the target concentration range, as well as inconsistencies in initial dosing and dosing frequency. The aim of this study is to establish a new population pharmacokinetic (PPK) model for children with VAs to guide the individualized use of sirolimus. Methods: A PPK study was performed using data from children with VAs who received sirolimus between July 2017 and April 2022. A nonlinear mixed-effect modeling with a one-compartment model structure was applied. Monte Carlo simulation was employed to propose specific dosing recommendations to achieve the target trough concentrations (C trough) of 5-15 ng/mL. Results: In total, 134 blood concentrations from 49 pediatric patients were used to characterize the sirolimus pharmacokinetics. Covariate analysis identified body weight (BW) as a significant factor affecting clearance (CL) in the final PPK model. The typical clearance rate and distribution volume, standardized to a BW of 16 kg, were 4.06 L/h (4% relative standard error, RSE) and 155 L (26% RSE), respectively. Optimal dosing regimens were simulated for different BWs. For a twice-daily regimen, the recommended doses were 0.05, 0.06, 0.07, and 0.08 mg/kg/day for BW of <10, 10-20, 20-40, and ≥40 kg, respectively; for a once-daily regimen, the recommended doses were 0.06, 0.07, 0.08, and 0.09 mg/kg/day for BW of <10, 10-30, 30-50, and ≥50 kg, respectively. Notably, sirolimus C trough could be maintained between 5-15 ng/mL across various dosing frequencies based on the recommended dosing regimen. Conclusion: We established a PPK model of sirolimus for children with VAs and proposed an initial dosing strategy. Integrating initial dose and medication frequency recommendations into sirolimus' guidelines will broaden its clinical options and simplify the clinical management for childhood VAs.

7.
Expert Opin Drug Discov ; : 1-18, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39360759

ABSTRACT

INTRODUCTION: The autoimmune hair loss condition alopecia areata (AA) exacts a substantial psychological and socioeconomic toll on patients. Biotechnology companies, dermatology clinics, and research institutions are dedicated to understanding AA pathogenesis and developing new therapeutic approaches. Despite recent efforts, many knowledge gaps persist, and multiple treatment development avenues remain unexplored. AREAS COVERED: This review summarizes key AA disease mechanisms, current therapeutic methods, and emerging treatments, including Janus Kinase (JAK) inhibitors. The authors determine that innovative drug discovery strategies for AA are still needed due to continued unmet medical needs and the limited efficacy of current and emerging therapeutics. For prospective AA treatment developers, the authors identify the pre-clinical disease models available, their advantages, and limitations. Further, they outline treatment development opportunities that remain largely unmapped. EXPERT OPINION: While recent advancements in AA therapeutics are promising, challenges remain, including the lack of consistent treatment efficacy, long-term use and safety issues, drug costs, and patient compliance. Future drug development research should focus on patient stratification utilizing robust biomarkers of AA disease activity and improved quantification of treatment response. Investigating superior modes of drug application and developing combination therapies may further improve outcomes. Spirited innovation will be needed to advance more effective treatments for AA.


Alopecia areata (AA) is an autoimmune condition that causes hair loss. It significantly affects a patient's emotional well-being and quality of life. Companies, clinics, and researchers are working hard to understand AA and create better treatments. Despite these efforts, there are still many unanswered questions, and new treatment methods still need to be explored.This review summarizes how AA develops, current treatment options, and new therapies like Janus Kinase (JAK) inhibitor drugs. JAK inhibitors show promise, but they are not fully effective for everyone. We emphasize that there is still a need for new and innovative drug discovery strategies to meet the medical needs of AA patients, as current treatments often fall short.For researchers and developers of AA treatments, we discuss the available pre-clinical models used to test new drugs, highlighting their strengths and weaknesses. We also point out new areas for treatment development that have not been thoroughly investigated.Although recent advancements in AA treatments are encouraging, several challenges remain. These include inconsistent effectiveness of treatments, safety concerns with long-term use, high drug costs, and issues with patient adherence to treatment programs. We believe future research should focus on identifying biomarkers that can help tailor treatments to individual patients and improving measurements of treatment success. Additionally, exploring better ways to apply drugs and combining different therapies together may enhance treatment outcomes.Ultimately, innovative approaches and spirited efforts will be required to develop more effective treatments for AA to improve the lives of those affected by this challenging condition.

8.
Eur J Med Chem ; 278: 116813, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39226705

ABSTRACT

Tumor proliferation and metastasis are intricately linked to blood vessel formation, with vascular endothelial growth factor (VEGF) playing a pivotal role in orchestrating angiogenesis throughout tumor progression. Pseudolaric acid B (PAB) has emerged as a potent inhibitor of tumor cell proliferation, migration, and angiogenesis. In efforts to enhance its efficacy, 37 derivatives of PAB were synthesized and assessed for their capacity to suppress VEGF secretion in SiHa cells under hypoxic conditions. Notably, majority of these derivatives exhibited significant inhibition of VEGF protein secretion without inducing cytotoxicity. Among them, compound M2 displayed the most potent inhibitory activity, with an IC50 value of 0.68 µM, outperforming the lead compound PAB (IC50 = 5.44 µM). Compound M2 not only curbed the migration and angiogenesis of HUVECs under hypoxic conditions but also hindered the invasion of SiHa cells. Mechanistic investigations unveiled that compound M2 may impede the accumulation and nuclear translocation of hypoxia-inducible factor 1α (HIF-1α) in SiHa cells, thereby downregulating VEGF expression. This inhibitory effect on HIF-1α was corroborated by experiments utilizing the protease inhibitor MG-132 and protein synthesis inhibitor CHX, indicating that compound M2 diminishes HIF-1α levels by reducing its synthesis. Furthermore, compound M2 was observed to modulate the PI3K/AKT/mTOR and MAPK signaling pathways in tumor cells, thereby regulating HIF-1α translation and synthesis. In vivo studies demonstrated that compound M2 exhibited low toxicity and effectively curbed tumor growth. Immunohistochemistry analyses validated that compound M2 effectively suppressed the expression of HIF-1α and VEGF in tumor tissues, underscoring its potential as a promising therapeutic agent for targeting tumor angiogenesis.


Subject(s)
Angiogenesis Inhibitors , Antineoplastic Agents , Cell Proliferation , Diterpenes , Drug Design , Hypoxia-Inducible Factor 1, alpha Subunit , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Vascular Endothelial Growth Factor A , Humans , Vascular Endothelial Growth Factor A/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Phosphatidylinositol 3-Kinases/metabolism , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/chemical synthesis , Angiogenesis Inhibitors/chemistry , Cell Proliferation/drug effects , Structure-Activity Relationship , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Diterpenes/pharmacology , Diterpenes/chemical synthesis , Diterpenes/chemistry , Signal Transduction/drug effects , Drug Screening Assays, Antitumor , Molecular Structure , Dose-Response Relationship, Drug , Cell Line, Tumor , Animals , Cell Movement/drug effects , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/metabolism
9.
Eur J Pharm Biopharm ; : 114484, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39251033

ABSTRACT

BACKGROUND: Several population pharmacokinetic (PopPK) models of caffeine in preterm infants have been published, but the extrapolation of these models to facilitate model-informed precision dosing (MIPD) in clinical practice is uncertain. This study aimed to comprehensively evaluate their predictive performance using an external, independent dataset. METHODS: Data used for external evaluation were based on an independent cohort of preterm infants. Currently available PopPK models for caffeine in preterm infants were identified and re-established. Prediction- and simulation-based diagnostics were used to assess model predictability. The influence of prior information was assessed using Bayesian forecasting. RESULTS: 120 plasma samples from 76 preterm infants were included in the evaluation dataset. Twelve PopPK models of caffeine in preterm infants were re-established based on our previously published study. Although two models showed superior predictive performance, none of the 12 PopPK models met all the clinical acceptance criteria of these external evaluation items. Besides, the external predictive performances of most models were unsatisfactory in prediction- and simulation-based diagnostics. Nevertheless, the application of Bayesian forecasting significantly improved the predictive performance, even with only one prior observation. CONCLUSIONS: Two models that included the most covariates had the best predictive performance across all external assessments. Inclusion of different covariates, heterogeneity of preterm infant characteristics, and different study designs influenced predictive performance. Thorough evaluation is needed before these PopPK models can be implemented in clinical practice. The implementation of MIPD for caffeine in preterm infants could benefit from the combination of PopPK models and Bayesian forecasting as a helpful tool.

10.
Digit Health ; 10: 20552076241277033, 2024.
Article in English | MEDLINE | ID: mdl-39224792

ABSTRACT

Objective: The internet has become a preferred source for people seeking health information, including diet recommendations which are pivotal in the management of inflammatory bowel disease (IBD). Hence, we aimed to assess the quality of online information in China regarding IBD dietary recommendations. Methods: The search engines Baidu and Bing were used to screen for their top 25 webpages using the keywords "inflammatory bowel disease diet," "ulcerative colitis diet," "Crohn's disease diet," "inflammatory bowel disease nutrition," "ulcerative colitis nutrition," and "Crohn's disease nutrition." The quality of information was assessed by two physicians according to the Journal of the American Medical Association (JAMA) benchmark, the Global Quality Score (GQS), and the DISCERN instrument. Results: One hundred and eight webpages were selected for evaluation. The mean scores for JAMA, GQS, and DISCERN were 1.48, 3.11, and 36.20, respectively. Articles from professionals and non-profit organizations demonstrated superior quality compared to those from commercial and health portal websites. Many webpages failed to provide an explicit source of information or support for shared decision-making. The information on several pages lacked comprehensive descriptions of food types for IBD, with some pages even containing inaccuracies. No statistically significant differences in scores were observed between Baidu and Bing. Conclusions: The quality of online information on IBD dietary recommendations in China is moderate to low and exhibits significant variation across different sources. This warrants joint efforts from online authors, internet platforms, and regulators, to improve the quality of popular medical information.

11.
Phys Rev Lett ; 133(9): 093201, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39270199

ABSTRACT

We propose and demonstrate a radio-frequency (rf) atomic magnetometer based on parametric resonances. Previously, most rf atomic magnetometers are based on magnetic resonances and their sensitivities are often limited by spin-exchange relaxation. Here, we introduce a novel scheme for an rf magnetometer where the rf magnetic field is measured by exciting the parametric resonances instead of magnetic resonances using parametric modulation fields. In this way, the spin-exchange relaxation is almost eliminated. Benefiting from the low spin relaxation rate, the parametric resonance scheme exhibits a narrower linewidth and stronger signal, which results in a higher sensitivity. With a 6×6×3 mm^{3} Rb atomic vapor cell, we developed an rf atomic magnetometer with a noise floor of 2 fT/Hz^{1/2}, which is about one order of magnitude higher than the sensitivity achieved in the magnetic-resonance-based scheme. The presented rf detection scheme holds promise in advancing rf atomic magnetometers and brings new insight into their various applications.

12.
HPB (Oxford) ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39271376

ABSTRACT

BACKGROUND: When considering hepatectomy for elderly HCC patients, it's essential to assess surgical safety and survival benefits. This study investigated the impact of preoperative frailty, assessed with the Clinical Frailty Scale (CFS), on outcomes for octogenarians undergoing HCC hepatectomy. METHODS: A retrospective cohort study of octogenarians who had hepatectomy for HCC between 2010 and 2022 at 16 hepatobiliary centers was conducted. Patients were categorized as frail or non-frail based on preoperative CFS, with frailty defined as CFS ≥5. The primary endpoints were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), with perioperative outcomes as secondary endpoints. RESULTS: Among 240 octogenarians, 105 were characterized as being frail. Frail patients had a higher incidence of postoperative 30-day morbidity and postoperative 30-day and 90-day mortality versus non-frail patients. Meanwhile, 5-year OS, RFS and CSS among frail patients were lower compared with non-frail patients. Univariable and multivariable analysis revealed that preoperative frailty was an independent risk factor of postoperative 30-day morbidity (OR: 2.060), OS (HR: 2.384), RFS (HR: 2.190) and CSS (HR: 2.203). CONCLUSION: Preoperative frailty, as assessed by the CFS, was strongly associated with both short-term outcomes and long-term survival among octogenarians undergoing hepatectomy for HCC. Incorporating frailty assessment into the preoperative evaluation may help optimize patient selection and perioperative care.

13.
Front Pharmacol ; 15: 1447560, 2024.
Article in English | MEDLINE | ID: mdl-39323644

ABSTRACT

Background: Chronic alcoholic liver disease (CALD) is a global health problem which includes multiple pathological processes such as immune inflammation and oxidative stress. 4-hydroxy-2(3H)-benzoxazolone (HBOA), an alkaloid isolated from Acanthus ilicifolius L, has been shown to exert hepatoprotective and immunomodulatory effects. However, its effects on CALD remain unclear. This study aimed to investigate the effects and underlying mechanisms of HBOA on CALD. Methods: Rats were administered alcohol by gavage continuously for 12 weeks to establish the CALD model, and then treated with HBOA by gavage for 4 weeks. Transcriptomics and metabolomics were used to predict the potential mechanisms of the effects of HBOA on CALD. Liver histology and function, oxidative stress, inflammatory cytokines, and the TLR4/NF-κB pathway components were evaluated. Results: HBOA significantly improved alcohol-induced liver injury and steatosis. It decreased the expression levels of pro-inflammatory cytokines (tumour necrosis factor-α [TNF-α], interleukin (IL)-1ß, and IL-6), and increased the activities of antioxidant enzymes (superoxide dismutase [SOD], glutathione [GSH], and glutathione peroxidase [GSH-Px]). Western blotting confirmed that HBOA treatment largely diminished NF-κBp65 nuclear translocation. Comprehensive transcriptomics and metabolomics analyses indicated that HBOA regulated the glycerophospholipid metabolism pathway to achieve therapeutic effects in rats with CALD. Conclusion: HBOA has a therapeutic effect on rats with CALD. Its mechanism of action mainly affects the glycerophospholipid metabolic pathway to promote lipid metabolism homeostasis by regulating the expression of Etnppl, Gpcpd1, and Pla2g4c. In addition, it may also inhibit the TLR4/NF-κB signaling pathway, thereby reducing the immune-inflammatory response.

14.
Curr Ther Res Clin Exp ; 101: 100756, 2024.
Article in English | MEDLINE | ID: mdl-39257480

ABSTRACT

Managing pediatric Crohn's disease (PCD) presents challenges due to severe complications and higher biologic therapy needs. Transitioning from anti-tumor necrosis factor agents to off-label therapies adds complexity. Although upadacitinib has demonstrated efficacy and tolerability in adult inflammatory bowel disease and pediatric atopic dermatitis, there are limited data for its application in PCD. This case report delineates successful remission with upadacitinib in a child with CD refractory to infliximab, ustekinumab, adalimumab, thalidomide, and prednisone. Notably, the patient carried an ataxia telangiectasia mutated (ATM) gene mutation. These findings provide valuable evidence for PCD management and highlight the potential benefits of upadacitinib in this population.

15.
Lipids Health Dis ; 23(1): 301, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285295

ABSTRACT

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is acknowledged as an independent risk factor (IRF) for atherosclerotic cardiovascular disease. Nevertheless, studies on the impact of LDL-C on microvasculature are still scarce. The retina, abundant in microvasculature, can now be examined for microvascular alterations through the novel, non-invasive, and quantitative optical coherence tomography angiography (OCTA) technique. METHODS: In this cross-sectional study, 243 patients from the geriatric department were recruited (between December 2022 and December 2023). Individuals were classified into four groups based on their LDL-C levels: Group 1 (≤ 1.8 mmol/L), Group 2 (> 1.8 mmol/L to ≤ 2.6 mmol/L), Group 3 (> 2.6 mmol/L to ≤ 3.4 mmol/L), and Group 4 (> 3.4 mmol/L). The OCTA results including retinal vessel density (VD), foveal avascular zone (FAZ) area, macula thickness, and retinal nerve fiber layer (RNFL) thickness were contrasted across these groups. T-tests, analysis of variance, Welch's tests, or rank-sum tests were employed for statistical comparisons. In cases where significant differences between groups were found, post-hoc multiple comparisons or rank-sum tests were performed for pairwise group comparisons. Spearman's correlation coefficient was employed to perform bivariate correlation analysis to evaluate the relationship between LDL-C levels and various OCTA measurements. Multivariable regression analysis was used to evaluate the association between LDL-C levels and various OCTA measurements. Linear regression analysis or mixed-effects linear models were applied. RESULTS: It was discovered that individuals with LDL-C levels exceeding 2.6 mmol/L (Groups 3 and 4) exhibited reduced VD in the retina, encompassing both the optic disc and macular regions, compared to those with LDL-C levels at or below 2.6 mmol/L (Groups 1 and 2). A negative correlation among LDL-C levels and retinal VD was identified, with r values spanning from - 0.228 to -0.385. Further regression analysis presented ß values between - 0.954 and - 2.378. Additionally, no notable disparities were detected among the groups regarding FAZ area, macular thickness, and RNFL thickness. CONCLUSIONS: The outcomes of this study suggest that elevated LDL-C levels constitute an IRF for decreased VD across the entire retina. TRIAL REGISTRATION: NCT05644548, December 1, 2022.


Subject(s)
Cholesterol, LDL , Retinal Vessels , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Male , Female , Retinal Vessels/diagnostic imaging , Cholesterol, LDL/blood , Aged , Cross-Sectional Studies , Middle Aged , Aged, 80 and over , Macula Lutea/diagnostic imaging , Macula Lutea/blood supply , Risk Factors
16.
Huan Jing Ke Xue ; 45(9): 5188-5195, 2024 Sep 08.
Article in Chinese | MEDLINE | ID: mdl-39323137

ABSTRACT

Aiming at the problem that the single machine learning model has low prediction accuracy of daily average ozone concentration, an ozone concentration prediction method based on the fusion class Stacking algorithm (FSOP) was proposed, which combined the statistical method ordinary least squares (OLS) with machine learning algorithms and improved the prediction accuracy of the ozone concentration prediction model by integrating the advantages of different learners. Based on the principle of the Stacking algorithm, the observation data of the daily maximum 8h ozone average concentration and meteorological reanalysis data in Hangzhou from January 2017 to December 2022 were used. Firstly, the specific ozone concentration prediction models based on the light gradient boosting machine (LightGBM) algorithm, long short-term memory model (LSTM), and Informer model were established, respectively. Then, the prediction results of the above models were used as meta-features, and the OLS algorithm was used to obtain the prediction expression of ozone concentration to fit the observed ozone concentration. The results showed that the prediction accuracy of the model combined with the class Stacking algorithm was improved, and the fitting effect of ozone concentration was better. Among them, R2, RMSE, and MAE were 0.84, 19.65 µg·m-3, and 15.50 µg·m-3, respectively, which improved the prediction accuracy by approximately 8% compared with that of the single machine learning model.

17.
Nanomicro Lett ; 17(1): 21, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39325321

ABSTRACT

Regulation the electronic density of solid-state electrolyte by donor-acceptor (D-A) system can achieve highly-selective Li+ transportation and conduction in solid-state Li metal batteries. This study reports a high-performance solid-state electrolyte thorough D-A-linked covalent organic frameworks (COFs) based on intramolecular charge transfer interactions. Unlike other reported COF-based solid-state electrolyte, the developed concept with D-A-linked COFs not only achieves electronic modulation to promote highly-selective Li+ migration and inhibit Li dendrite, but also offers a crucial opportunity to understand the role of electronic density in solid-state Li metal batteries. The introduced strong electronegativity F-based ligand in COF electrolyte results in highly-selective Li+ (transference number 0.83), high ionic conductivity (6.7 × 10-4 S cm-1), excellent cyclic ability (1000 h) in Li metal symmetric cell and high-capacity retention in Li/LiFePO4 cell (90.8% for 300 cycles at 5C) than substituted C- and N-based ligands. This is ascribed to outstanding D-A interaction between donor porphyrin and acceptor F atoms, which effectively expedites electron transferring from porphyrin to F-based ligand and enhances Li+ kinetics. Consequently, we anticipate that this work creates insight into the strategy for accelerating Li+ conduction in high-performance solid-state Li metal batteries through D-A system.

18.
Microorganisms ; 12(9)2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39338440

ABSTRACT

Nematode-trapping (NT) fungi are a major resource for controlling parasitic nematodes. Arthrobotrys flagrans, as a typical NT fungus, can capture nematodes by producing three-dimensional nets. The APSES transcription factor Swi6 plays a vital role in fungal growth and the pathogenicity of pathogens. In this study, we characterized AfSwi6 via gene disruption using the homologous recombinant method and transcriptome sequencing. Knockout of the AfSwi6 gene caused defects in mycelial growth, trap formation and pathogenicity, chlamydospore production, and stress response. Moreover, the transcriptome data indicated that AfSwi6 was related to DNA repair, stress response, and plasma membrane fusion. The result showed that AfSwi6 has a significant effect on trap development and chlamydospore production in A. flagrans.

19.
Clin Ophthalmol ; 18: 2697-2704, 2024.
Article in English | MEDLINE | ID: mdl-39346970

ABSTRACT

Objective: To explore the distribution and influence factors of non-invasive tear film break-up time (NIBUT) in children. Methods: This is a hospital-based cross-sectional study. Spherical equivalent error (SER) was measured with cycloplegia. NIBUT was measured by an ocular surface integrated analyzer. Results: A total of 1269 children (1269 eyes) were included in this study. Participants' median age was 11 (range 6-18) years. 47.1% (598/1269) of participants were boys. The median NIBUT of myopic children and non-myopic children were 9.9 seconds (s) (Inter-quartile range, IQR: 6.4 to 16.1) and 10.9 s (IQR: 8.8 to 17.9), respectively, which was statistically significant (p = 0.004). In myopic children, 49.9% (573/1148) were able to achieve NIBUT of 10 s or more, compared to 67.8% (82/121) in non-myopic children, which was statistically significant (p < 0.001). There were 41 (3.57%) children in the myopic group and none (0%) in the non-myopic group with dry eye disease (p = 0.028). There was a positive correlation between NIBUT and age: NIBUT = 9.256 + 0.352*Age. 71.8% (824/1148) of myopic children used electronic products almost every day, compared to 37.2% (45/121) of non-myopic children, which was statistically significant (p < 0.001). Conclusion: The NIBUT of myopic children was significantly shorter than that of non-myopic children. Children with myopia are more likely to have dry eyes. NIBUT increases with age. High frequency of electronic product use may be an important cause to NIBUT shortening in children.

20.
Dalton Trans ; 53(37): 15608-15617, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39233653

ABSTRACT

With an electron-deficient rigid planar structure and excellent π-π stacking ability, hexaazatriphenylene (HAT) and its derivatives are widely used as basic building blocks for constructing covalent organic frameworks (COFs), components of organic light-emitting diodes and solar cells, and electrode materials for lithium-ion batteries (LIBs). Here, a HAT derivative, hexaazatriphenylenehexacarbonitrile, is explored as an anode material for LIBs. The HAT anode exhibited high initial reversible capacities of 672 mA h g-1 at 100 mA g-1 and 550 mA h g-1 at 400 mA g-1 and stable cycling with a capacity of 503 mA h g-1 after 1000 cycles at 400 mA g-1 corresponding to a capacity retention of 91.5%. Furthermore, the lithium storage mechanism and the cause of the first irreversible capacity loss of the HAT anode were investigated by X-ray photoelectron spectroscopy (XPS) analysis and density functional theory (DFT) calculations. We have carried out a series of analyses on the mechanism of initial capacity loss. This study provides new insight on initial capacity loss and provides valuable insights into the molecular design and the electrochemical properties of HAT-based anode materials.

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