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1.
Front Public Health ; 12: 1355638, 2024.
Article in English | MEDLINE | ID: mdl-39086814

ABSTRACT

Introduction: Identifying the knowledge, attitudes, and practices (KAP) gaps of healthy eating can inform the design of effective interventions. This study aimed to test the validity and psychometric properties of a KAP of Healthy Eating Questionnaire (KAP-HEQ) tailored to the Chinese culture. Methods: The dimensions and potential items of each KAP scale were identified from published KAP and health literacy questionnaires, which were supplemented by the findings of a previous qualitative healthy eating study. Content validity of the KAP-HEQ was evaluated by eight experts and eight Chinese parent-adolescent dyads in Hong Kong through content validity ratio (CVR), content validity index (CVI), and qualitative feedback. The feasibility, construct validity, reliability, and sensitivity of the KAP-HEQ were evaluated in this pilot study among 60 adolescent-parent dyads (120 persons) through an online survey. The first 30 dyads who completed the KAP-HEQ were invited to repeat the KAP-HEQ 2 weeks later to assess the test-retest reliability. Results: The final 44-item KAP-HEQ was completed in 10-15 min by both adolescents and their adult parents. The CVR ranged from -0.38 to 1, and the CVI ranged from 0.56 to 1. Over 80% of the items achieved convergent validity (a significantly positive correlation with its hypothesized scale) and discriminant validity (a higher correlation with its hypothesized scale than with the other two scales). Cronbach's alpha for the internal consistency of the Overall, Attitude, and Practice scales was >0.7, while that of the Knowledge scale was 0.54. The intraclass correlation coefficient (ICC) on test-retest reliability of the Overall and individual scales were all >0.75 except that of the Knowledge scale (ICC = 0.58). The significant differences in KAP scale scores with small to large effect sizes were found between known groups as hypothesized, except the Attitude score between groups by household income, which supported the sensitivity of the KAP-HEQ. Conclusion: The KAP-HEQ has shown good validity, reliability, and sensitivity among Chinese adolescents and adults, which can be applied to evaluate KAP status and gaps to inform the design and assess the effectiveness of healthy eating interventions.


Subject(s)
Diet, Healthy , Health Knowledge, Attitudes, Practice , Psychometrics , Humans , Surveys and Questionnaires/standards , Pilot Projects , Male , Female , Adolescent , Hong Kong , Reproducibility of Results , Adult , Parents/psychology , Middle Aged , East Asian People
2.
Clin Nutr ; 43(9): 2057-2068, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39088962

ABSTRACT

BACKGROUND: The controlled nutritional status score (CONUT) and handgrip strength (HGS) were both predictive indexes for the prognosis of cancers. However, the combination of CONUT and HGS for predicting the prognosis of gastrointestinal cancer had not been developed. This study aimed to explore the combination of CONUT and HGS as the potential predictive prognosis in patients with gastric and colorectal cancer. METHODS: A cohort study was conducted with gastric and colorectal cancer patients in multicenter in China. Based on the optimal HGS cutoff value for different sex, the HGS cutoff value was determined. The patients were divided into high and low HGS groups based on their HGS scores. A CONUT score of 4 or less was defined as a low CONUT, whereas scores higher than 4 were defined as high CONUT. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). RESULTS: A total 2177 gastric and colorectal patients were enrolled in this study, in which 1391 (63.9%) were men (mean [SD] age, 66.11 [11.60] years). Multivariate analysis revealed that patients with high HGS had a lower risk of death than those with low HGS (hazard ratio [HR],0.87; 95% confidence interval [CI], 0.753-1.006, P = 0.06), while high CONUT had a higher risk of death than those with low CONUT (HR, 1.476; 95% CI, 1.227-1.777, P < 0.001). Patients with both low HGS and high CONUT had 1.712 fold increased risk of death (HR, 1.712; 95% CI, 1.364-2.15, P < 0.001). Moreover, cancer type and sex were stratified and found that patients with high CONUT and low HGS had lower survival rate than those with low CONUT and high HGS in both gastric or colorectal cancer, and both male and female. CONCLUSION: A combination of low HGS and high CONUT was associated with poor prognosis in patients with gastrointestinal cancer, which could probably predict the prognosis of gastrointestinal cancer more accurate than HGS or CONUT alone.

3.
Adv Mater ; : e2406343, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39096067

ABSTRACT

To improve the performance of Lithium-Sulfur (Li-S) batteries, the reaction catalysts of lithium polysulfides (LiPSs) reactions should have the characteristics of large surface area, efficient atomic utilization, high conductivity, small size, good stability, and strong adjustability. Herein, Anderson-type polyoxometalate ([TMMo6O24]n-, TM = Co, Ni, Fe, represented by TMMo6 POMs) are used as the modified materials for Li-S battery separator. By customizing the central metal atoms, this work gains insights into the layer-by-layer electron transfer mechanism between TMMo6 units and LiPSs, similar to the collision effect of a bowling ball. Theoretical analysis and in situ experimental characterization show that the changes of CoMo6 units with moderate binding energy and lowest Gibbs free energy result in the formation of robust polar bonds and prolonged S─S bonds after adsorption. Hence, the representative Li-S battery with CoMo6 and graphene composite modified separator has a high initial capacity of 1588.6 mA h g-1 at 0.2 C, excellent cycle performance of more than 3000 cycles at 5 C, and uniform Li+ transport over 1900 h. More importantly, this work has revealed the inherent contradiction between the kinetics and thermodynamics, achieving a stable cycle in the temperature range of -20 to 60 °C.

4.
Org Lett ; 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39159424

ABSTRACT

A cascade reaction of cyclopropyl alcohols, DABSO (1,4-diazoniabicyclo[2.2.2]octane-1,4-disulfinate), and N-(sulfonyl)acrylamides has been developed. This tandem process went through a cyclopropanol ring opening and Michael addition sequence. The γ-keto sulfinate generated from the reaction between cyclopropanol and DABSO serves as the nucleophilic reagent, and N-(sulfonyl)acrylamide is used as the Michael addition acceptor. By utilizing this strategy, multitudinous sulfone-bridged 1,7-dicarbonyl compounds that contain both a ß-sulfonyl amide unit and γ-keto sulfone skeleton were conveniently synthesized.

5.
Nanoscale ; 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39158040

ABSTRACT

The electrochemical reduction of carbon dioxide (CO2RR) to carbon monoxide represents a cost-effective pathway towards realizing carbon neutrality. To suppress the hydrogen evolution reaction (HER), the presence of alkali cations is critical, which can however lead to precipitate formation on the electrode, adversely impacting the device stability. Employing pure water as the electrolyte in zero-gap CO2 electrolyzers can address this challenge, albeit at the cost of diminished catalyst performance due to the absence of alkali cations. In this study, we introduce a novel approach by implementing amino modifications on the catalyst surface to mimic the function of alkali metal cations, while simultaneously working in pure water. This modification enhances the adsorption of carbon dioxide and protons, thereby facilitating the CO2RR while concurrently suppressing the HER. Utilizing this strategy in a zero-gap CO2 electrolyzer with pure water as the anolyte resulted in an impressive carbon monoxide faradaic efficiency (FECO) of 95.5% at a current density of 250 mA cm-2, while maintaining stability for over 180 hours without any maintenance.

6.
IEEE Trans Med Imaging ; PP2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120989

ABSTRACT

Diagnosing malignant skin tumors accurately at an early stage can be challenging due to ambiguous and even confusing visual characteristics displayed by various categories of skin tumors. To improve diagnosis precision, all available clinical data from multiple sources, particularly clinical images, dermoscopy images, and medical history, could be considered. Aligning with clinical practice, we propose a novel Transformer model, named Remix-Former++ that consists of a clinical image branch, a dermoscopy image branch, and a metadata branch. Given the unique characteristics inherent in clinical and dermoscopy images, specialized attention strategies are adopted for each type. Clinical images are processed through a top-down architecture, capturing both localized lesion details and global contextual information. Conversely, dermoscopy images undergo a bottom-up processing with two-level hierarchical encoders, designed to pinpoint fine-grained structural and textural features. A dedicated metadata branch seamlessly integrates non-visual information by encoding relevant patient data. Fusing features from three branches substantially boosts disease classification accuracy. RemixFormer++ demonstrates exceptional performance on four single-modality datasets (PAD-UFES-20, ISIC 2017/2018/2019). Compared with the previous best method using a public multi-modal Derm7pt dataset, we achieved an absolute 5.3% increase in averaged F1 and 1.2% in accuracy for the classification of five skin tumors. Furthermore, using a large-scale in-house dataset of 10,351 patients with the twelve most common skin tumors, our method obtained an overall classification accuracy of 92.6%. These promising results, on par or better with the performance of 191 dermatologists through a comprehensive reader study, evidently imply the potential clinical usability of our method.

7.
Article in English | MEDLINE | ID: mdl-39117325

ABSTRACT

Objectives To compare the gender differences in isolated mitral regurgitation (MR) repair. Methods Of 381 adults aged 54.8±12.3 years undergoing mitral valve repair (MVP) for isolated MR from 01/2019-12/2022, the baseline and operative data, and outcomes were compared between 161 women (42.3%) and 220 men (57.7%). Results Women tended to be non-smoker (98.1% vs 45%, P<0.001), and have more cerebrovascular accidents (38.5% vs 24.1%, P=0.004), lower creatinine (70.0±19.5 vs 86.3±19.9 µmol/dL, P<0.001), smaller LVEDD (54.4±6.7 vs 57.8±6.6 mm, P<0.001) and isolated annular dilatation (19.3% vs 9.1%, P=0.010). One female died of stroke at 2 days (0.3%). Another female (0.3%) underwent MV replacement for failed repair. Stroke occurred in 4 (1.0%). Two underwent re-exploration for bleeding (0.5%). Women were more likely to have less 24-hour drainage (290±143 vs 385±196 mL, P<0.001). Over a mean follow-up of 2.1±1.1 years (100% complete), one woman died, one man underwent a reoperation; 28 had moderate MR, and 9 had severe MR. Neither did early and late mortality and reoperation, nor freedom from late moderate/severe MR (71.6% vs 71.4% at 5 years; P=0.992) differ significantly between two genders. Predictors for late moderate/severe MR were anterior leaflet prolapse (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.18-16.72; P=0.027) and isolated annular dilation (HR 5.47, 95% CI 1.29-23.25; P=0.021). Conclusions Despite significant differences in smoking, cerebrovascular accidents, creatinine, LVEDD, and isolated annular dilatation at baseline, and 24-hour drainage, women and men did not show significant difference in early and late survival, reoperation and freedom from late moderate/severe MR.

8.
Osteoporos Int ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120624

ABSTRACT

Identifying dysregulated plasma proteins in osteoporosis (OP) progression offers insights into prevention and treatment. This study found 8 such proteins associated with OP, suggesting them as therapy targets. This discovery may cut drug development costs and improve personalized treatments. PURPOSE: This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets. METHODS: To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein-protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets. RESULTS: In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets. CONCLUSIONS: The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs.

9.
Food Res Int ; 193: 114855, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39160046

ABSTRACT

Pepper (Capsicum spp.) is an important fruit vegetable worldwide, and it is a rich dietary source of minerals for human being. Yet, the spatio-temporal distribution of pepper fruit mineral composition and the factors influencing such variations at global scale remain unknown. A global meta-analysis of 140 publications providing 649, 562, 690, 811 datapoints was conducted to quantify and evaluate the nutritional quality, comprising potassium (K), magnesium (Mg), iron (Fe) and zinc (Zn), of pepper fruits and its influencing variables. The analysis showed that the global average of K, Mg, Fe and Zn content in pepper fruits was 20-25 g kg-1, 1-1.5 g kg-1, 80-100 mg kg-1, and 20-40 mg kg-1, respectively. There had been a downward trend in pepper fruit nutritional quality over the last decade, especially for Fe and Zn. And, the concentration of all these four nutrients were at lower levels in less developed regions, especially in Africa. Our results showed that the vegetable "green pepper" contains more K, Mg, Fe and Zn than the "hot pepper" used as spice. The concentration of K, Mg, Fe and Zn were increased with fruit yield but that of Fe and Zn were decreased with increase in single fruit weight. Nutritional quality was optimal at mean annual temperature of 10 ℃ - 20 ℃, and was adversely affected when mean annual precipitation was < 500 mm. Pepper fruits produced at pH 6.5-7.5 had higher fruit K concentration while acidic soils (pH<6.5) favored higher Fe and Zn concentrations. The higher soil organic matter (SOM) generally improved the nutritional quality of the pepper. Our results suggest that systematic selection of superior varieties and soil amelioration (adjusting pH and SOM) of the soil-crop system are needed to achieve higher nutritional quality of pepper fruit.


Subject(s)
Capsicum , Fruit , Nutritive Value , Capsicum/chemistry , Fruit/chemistry , Minerals/analysis , Spatio-Temporal Analysis , Potassium/analysis , Magnesium/analysis , Zinc/analysis , Iron/analysis
10.
Front Immunol ; 15: 1418792, 2024.
Article in English | MEDLINE | ID: mdl-39100667

ABSTRACT

Background: T lymphocytes in tumor microenvironment play a pivotal role in the anti-tumor immunity, and the memory of T cells contributes to the long-term protection against tumor antigens. Compared to solid tumors, studies focusing on the T-cell differentiation in the acute myeloid leukemia (AML) bone marrow (BM) microenvironment remain limited. Patients and methods: Fresh BM specimens collected from 103 adult AML patients at diagnosis and 12 healthy donors (HDs) were tested T-cell differentiation subsets by multi-parameter flow cytometry. Results: CD4 and CD8 T-cell compartments had different constituted profiles of T-cell differentiated subsets, which was similar between AML patients and HDs. Compared to HDs, AML patients as a whole had a significantly higher proportion of CD8 effector T cells (Teff, P = 0.048). Moreover, the T-cell compartment of AML patients with no DNMT3A mutations skewed toward terminal differentiation at the expense of memory T cells (CD4 Teff: P = 0.034; CD8 Teff: P = 0.030; CD8 memory T: P = 0.017), whereas those with mutated DNMT3A had a decrease in CD8 naïve T (Tn) and CD4 effector memory T cells (Tem) as well as an increase in CD4 central memory T cells (Tcm) (P = 0.037, 0.053 and 0.053). Adverse ELN genetic risk correlated with a lower proportion of CD8 Tn. In addition, the low proportions of CD4 Tem and CD8 Tn independently predicted poorer relapse-free survival (RFS, HR [95%CI]: 5.7 (1.4-22.2), P = 0.017 and 4.8 [1.3-17.4], P = 0.013) and event-free survival (EFS, HR [95% CI]: 3.3 (1.1-9.5), P = 0.029; 4.0 (1.4-11.5), P = 0.010), respectively. Conclusions: AML patients had abnormal profiles of BM T-cell differentiation subsets at diagnosis, which was related to DNMT3A mutations. The low proportions of CD4 Tem and CD8 Tn predicted poor outcomes.


Subject(s)
Cell Differentiation , Leukemia, Myeloid, Acute , T-Lymphocyte Subsets , Humans , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Male , Female , Middle Aged , Adult , Cell Differentiation/immunology , Prognosis , Aged , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Young Adult , CD8-Positive T-Lymphocytes/immunology , Mutation , Tumor Microenvironment/immunology , Memory T Cells/immunology , CD4-Positive T-Lymphocytes/immunology , DNA Methyltransferase 3A , Aged, 80 and over , Adolescent
11.
Front Pharmacol ; 15: 1432520, 2024.
Article in English | MEDLINE | ID: mdl-39170701

ABSTRACT

Introduction: Ferroptosis is a new mode of programmed cell death distinct from necrosis, apoptosis, and autophagy, induced by iron-ion-dependent lipid peroxide accumulation. Circular RNAs are a class of endogenous non-coding RNAs that regulate the biological behavior of tumors. However, the role of circ-CDK8 in regulating ferroptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) remains unknown. Methods: The effect of circ-CDK8 on OSCC cell ferroptosis, migration, and invasion was evaluated using CCK-8, wound healing, transwell, reactive oxygen species (ROS), malondialdehyde (MDA), and GSH assays and Western blotting. Bioinformatics analyses and luciferase reporter assays were performed and revealed targeted relationships between circ-CDK8 and miR-615-5p, miR-615-5p and SLC7A11. Interference with circ-CDK8 expression reduced SLC7A11 expression by sponging miR-615-5p, suppressed OSCC cell migration and invasion, and promoted ferroptosis by increasing ROS, MDA, and iron levels and decreasing GSH and GPX4 levels in OSCC cells. Furthermore, in vivo, animal experiments confirmed that circ-CDK8 interference inhibited OSCC cell proliferation and SLC7A11 expression. Results: Collectively, this study revealed a novel strategy to upregulate erastin-induced ferroptosis in OSCC cells via the circ-CDK8/miR-615-5p/SLC7A11 axis, providing new insights into OSCC and a potential therapeutic strategy for OSCC.

12.
Am J Otolaryngol ; 45(6): 104454, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39142078

ABSTRACT

OBJECTIVE: This study aims to analyze the safety and effectiveness of a new model of surgery combined with Photodynamic therapy for treating Recurrent Respiratory Papillomatosis (RRP). METHODS: Review the case data of patients with RRP who opted for comprehensive surgery combined with Photodynamic therapy at the Nanjing BenQ Medical Center, from January 2021 to May 2023. The efficacy of this program was evaluated by comparing the annual number of surgeries and Derkay scores before and after the surgery. RESULTS: A total of 23 RRP patients were included in the study. After treatment, the recurrence rate was 65.2 % (15/23), with an average recurrence time of 94.3 ± 50.8 days. The average Derkay score at the time of recurrence was significantly lower than the average pre-treatment Derkay score (P < 0.001). The average annual recurrence rate before treatment was 2.2 ± 1.3, compared to 1.5 ± 1.5 after treatment, with no significant difference (P = 0.16). However, subgroup analysis revealed a significant decrease in the annual recurrence rate of adult-onset RRP after treatment (P = 0.01). The most common adverse reaction was mild pharyngeal pain (11/23). There were 3 cases of new-onset vocal cord adhesions. No patients experienced serious respiratory-related adverse reactions, anesthesia-related adverse reactions, or systemic phototoxic reactions. CONCLUSION: In conclusion, this study indicates that surgery combined with Photodynamic therapy (PDT) might be a safe and effective option for treating RRP, especially in patients with Adult-Onset Recurrent Respiratory Papillomatosis (AORRP).

13.
Front Pharmacol ; 15: 1421635, 2024.
Article in English | MEDLINE | ID: mdl-39148543

ABSTRACT

Introduction: Angong Niuhuang Wan (AGNHW), developed during the Qing dynasty (18th century) for the treatment of consciousness disturbances caused by severe infections, has been used to treat brain edema caused by ischemia‒reperfusion. However, it remains unclear whether AGNHW can ameliorate vascular-origin brain edema caused by lipopolysaccharides (LPS). This study explored the ameliorative effects of AGNHW on LPS-induced cerebrovascular edema in mice, as well as the potential underlying mechanisms. Methods: A cerebrovascular edema model was established in male C57BL/6N mice by two intraperitoneal injections of LPS (15 mg/kg), at 0 and 24 h. AGNHW was administered by gavage at doses of 0.2275 g/kg, 0.455 g/kg, and 0.91 g/kg, 2 h after LPS administration. In control mice, normal saline (NS) or AGNHW (0.455 g/kg) was administered by gavage 2 h after intraperitoneal injection of NS. The survival rate, cerebral water content, cerebral venous FITC-dextran leakage, Evans blue extravasation, and expression of vascular endothelial cadherin (VE-cadherin), zonula occludens-1 (ZO-1), claudin-5, phosphorylated caveolin-1 (CAV-1), and cytomembrane and cytoplasmic aquaporin 1 (AQP1) and aquaporin 4 (AQP4) were evaluated. The cerebral tissue phosphoproteome, blood levels of AGNHW metabolites, and the relationships between these blood metabolites and differentially phosphorylated proteins were analyzed. Results: AGNHW inhibited the LPS-induced decrease in survival rate, increase in cerebral water content, decrease in VE-Cadherin expression and increase in phosphorylated CAV-1 (P-CAV-1). AGNHW treatment increased the expression of AQP4 on astrocyte membrane after LPS injection. AGNHW also inhibited the LPS-induced increases in the phosphorylation of 21 proteins, including protein kinase C-α (PKC-α) and mitogen-activated protein kinase 1 (MAPK1), in the cerebral tissue. Eleven AGNHW metabolites were detected in the blood. These metabolites might exert therapeutic effects by regulating PKC-α and MAPK1. Conclusion: AGNHW can ameliorate cerebrovascular edema caused by LPS. This effect is associated with the inhibition of VE-Cadherin reduction and CAV-1 phosphorylation, as well as the upregulation of AQP4 expression on the astrocyte membrane, following LPS injection.

14.
Clin Transl Med ; 14(7): e1771, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39073027

ABSTRACT

BACKGROUND: Clustering approaches using single omics platforms are increasingly used to characterise molecular phenotypes of eosinophilic and neutrophilic asthma. Effective integration of multi-omics platforms should lead towards greater refinement of asthma endotypes across molecular dimensions and indicate key targets for intervention or biomarker development. OBJECTIVES: To determine whether multi-omics integration of sputum leads to improved granularity of the molecular classification of severe asthma. METHODS: We analyzed six -omics data blocks-microarray transcriptomics, gene set variation analysis of microarray transcriptomics, SomaSCAN proteomics assay, shotgun proteomics, 16S microbiome sequencing, and shotgun metagenomic sequencing-from induced sputum samples of 57 severe asthma patients, 15 mild-moderate asthma patients, and 13 healthy volunteers in the U-BIOPRED European cohort. We used Monti consensus clustering algorithm for aggregation of clustering results and Similarity Network Fusion to integrate the 6 multi-omics datasets of the 72 asthmatics. RESULTS: Five stable omics-associated clusters were identified (OACs). OAC1 had the best lung function with the least number of severe asthmatics with sputum paucigranulocytic inflammation. OAC5 also had fewer severe asthma patients but the highest incidence of atopy and allergic rhinitis, with paucigranulocytic inflammation. OAC3 comprised only severe asthmatics with the highest sputum eosinophilia. OAC2 had the highest sputum neutrophilia followed by OAC4 with both clusters consisting of mostly severe asthma but with more ex/current smokers in OAC4. Compared to OAC4, there was higher incidence of nasal polyps, allergic rhinitis, and eczema in OAC2. OAC2 had microbial dysbiosis with abundant Moraxella catarrhalis and Haemophilus influenzae. OAC4 was associated with pathways linked to IL-22 cytokine activation, with the prediction of therapeutic response to anti-IL22 antibody therapy. CONCLUSION: Multi-omics analysis of sputum in asthma has defined with greater granularity the asthma endotypes linked to neutrophilic and eosinophilic inflammation. Modelling diverse types of high-dimensional interactions will contribute to a more comprehensive understanding of complex endotypes. KEY POINTS: Unsupervised clustering on sputum multi-omics of asthma subjects identified 3 out of 5 clusters with predominantly severe asthma. One severe asthma cluster was linked to type 2 inflammation and sputum eosinophilia while the other 2 clusters to sputum neutrophilia. One severe neutrophilic asthma cluster was linked to Moraxella catarrhalis and to a lesser extent Haemophilus influenzae while the second cluster to activation of IL-22.


Subject(s)
Asthma , Sputum , Humans , Sputum/microbiology , Sputum/metabolism , Asthma/microbiology , Asthma/immunology , Asthma/genetics , Male , Female , Adult , Middle Aged , Neutrophils/metabolism , Neutrophils/immunology , Eosinophils/metabolism , Multiomics
15.
Heliyon ; 10(13): e34094, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39071619

ABSTRACT

Multiple myeloma (MM) is a Ubiquitin Proteasome System (UPS)-dysfunction disease. We previously reported that high PRAME transcript levels associated with unfavorable progression free survival (PFS) in patients with no bortezomib therapy, and bortezomib-containing regimen significantly improved PFS in patients with high PRAME transcript levels, which indicated that PRAME expression was prognostic for MM patients, and was related to proteasome inhibitor treatment. However, molecular mechanisms underlying the above clinical performance remain unclear. In the present study, MM cell models with PRAME knockdown and overexpression were established, and PRAME was identified to play the role of promoting proliferation in MM cells. P-Akt signaling was found to be activated as PRAME overexpressed. As a substrate recognizing subunit (SRS) of the E3 ubiquitin ligase, PRAME targets substrate proteins and mediates their degradation. CTMP and p21 were found to be the novel targets of PRAME in the Cul2-dependent substrate recognition process. PRAME interacted with and mediated ubiquitination and degradation of CTMP and p21, which led to accumulation of p-Akt and CCND3 proteins, and thus promoted cell proliferation and increased bortezomib sensitivity in MM cells.

16.
JACC CardioOncol ; 6(3): 421-435, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38983386

ABSTRACT

Background: Modifiable cardiovascular risk factors constitute a significant cause of cardiovascular disease and mortality among patients with cancer. Recent studies suggest a potential link between neighborhood walkability and favorable cardiovascular risk factor profiles in the general population. Objectives: This study aimed to investigate whether neighborhood walkability is correlated with favorable cardiovascular risk factor profiles among patients with a history of cancer. Methods: We conducted a cross-sectional study using data from the Houston Methodist Learning Health System Outpatient Registry (2016-2022) comprising 1,171,768 adults aged 18 years and older. Neighborhood walkability was determined using the 2019 Walk Score and divided into 4 categories. Patients with a history of cancer were identified through International Classification of Diseases-10th Revision-Clinical Modification codes (C00-C96). We examined the prevalence and association between modifiable cardiovascular risk factors (hypertension, diabetes, smoking, dyslipidemia, and obesity) and neighborhood walkability categories in cancer patients. Results: The study included 121,109 patients with a history of cancer; 56.7% were female patients, and 68.8% were non-Hispanic Whites, with a mean age of 67.3 years. The prevalence of modifiable cardiovascular risk factors was lower among participants residing in the most walkable neighborhoods compared with those in the least walkable neighborhoods (76.7% and 86.0%, respectively). Patients with a history of cancer living in very walkable neighborhoods were 16% less likely to have any risk factor compared with car-dependent-all errands neighborhoods (adjusted OR: 0.84, 95% CI: 0.78-0.92). Sensitivity analyses considering the timing of events yielded similar results. Conclusions: Our findings demonstrate an association between neighborhood walkability and the burden of modifiable cardiovascular risk factors among patients with a medical history of cancer. Investments in walkable neighborhoods may present a viable opportunity for mitigating the growing burden of modifiable cardiovascular risk factors among patients with a history of cancer.

17.
Phys Rev Lett ; 132(24): 246503, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38949334

ABSTRACT

Novel critical phenomena beyond the Landau-Ginzburg-Wilson paradigm have been long sought after. Among many candidate scenarios, the deconfined quantum critical point (DQCP) constitutes the most fascinating one, and its lattice model realization has been debated over the past two decades. Here we apply the spherical Landau level regularization upon the exact (2+1)D SO(5) nonlinear sigma model with a topological term to study the potential DQCP therein. We perform a density matrix renormalization group (DMRG) simulation with SU(2)_{spin}×U(1)_{charge}×U(1)_{angular-momentum} symmetries explicitly implemented. Using crossing point analysis for the critical properties of the DMRG data, accompanied by quantum Monte Carlo simulations, we accurately obtain the comprehensive phase diagram of the model and find various novel quantum phases, including Néel, ferromagnet (FM), valence bond solid (VBS), valley polarized (VP) states and a gapless quantum disordered phase occupying an extended area of the phase diagram. The VBS-disorder and Néel-disorder transitions are continuous with non-Wilson-Fisher exponents. Our results show the VBS and Néel states are separated by either a weakly first-order transition or the disordered region with a multicritical point in between, thus opening up more interesting questions on the two-decade long debate on the nature of the DQCP.

18.
J Dent Sci ; 19(3): 1525-1532, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39035284

ABSTRACT

Background/purpose: Oral lichen planus (OLP) is a chronic inflammatory disease with unknown mechanisms of pathogenesis. Keratin 17 (KRT17) is a protein that regulates numerous cellular processes. This study aimed to explore the expression of KRT17 in OLP and its correlation with the severity of OLP. Materials and methods: RNA sequencing using epithelium from 5 OLP patients and 5 health control (HC) was performed, followed by functional analysis. The validation cohort of 20 OLP and 20 HC tissues were used to investigate positive area value of KRT17 by immunohistochemical analysis. Reticular, erosive and ulcerative (REU) scores were used for measuring the severity of OLP. Results: A total of 15493 genes were detected, of which 1492 genes were significantly up-regulated in OLP and 622 were down-regulated. The mRNA expression of KRT17 was elevated by 13.09-fold in OLP compared to that in HC. Pathway analysis demonstrated high KRT17 expression was associated with multiple biological processes. The median of percentage of KRT17 positive area value was 19.30 % in OLP and 0.01 % in HC (P < 0.001). Percentage of KRT17 positive area value was higher in erosive OLP patients (27.25 %) compared to that in non-erosive patients (15.02 %, P = 0.006). REU scores were positively correlated with percentage of KRT17 positive area value (r = 0.628, P = 0.003). Conclusion: The mRNA expression of KRT17 was elevated in OLP tissues compared to that in HC. KRT17 was positively correlated with the severity of OLP, indicating KRT17 might play a vital role in the pathogenesis of OLP.

20.
Front Plant Sci ; 15: 1404772, 2024.
Article in English | MEDLINE | ID: mdl-39055359

ABSTRACT

Accurate detection and counting of flax plant organs are crucial for obtaining phenotypic data and are the cornerstone of flax variety selection and management strategies. In this study, a Flax-YOLOv5 model is proposed for obtaining flax plant phenotypic data. Based on the solid foundation of the original YOLOv5x feature extraction network, the network structure was extended to include the BiFormer module, which seamlessly integrates bi-directional encoders and converters, enabling it to focus on key features in an adaptive query manner. As a result, this improves the computational performance and efficiency of the model. In addition, we introduced the SIoU function to compute the regression loss, which effectively solves the problem of mismatch between predicted and actual frames. The flax plants grown in Lanzhou were collected to produce the training, validation, and test sets, and the detection results on the validation set showed that the average accuracy (mAP@0.5) was 99.29%. In the test set, the correlation coefficients (R) of the model's prediction results with the manually measured number of flax fruits, plant height, main stem length, and number of main stem divisions were 99.59%, 99.53%, 99.05%, and 92.82%, respectively. This study provides a stable and reliable method for the detection and quantification of flax phenotypic characteristics. It opens up a new technical way of selecting and breeding good varieties.

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