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1.
Small ; : e2401045, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38948959

ABSTRACT

A cerebral ischemia-reperfusion injury is ensued by an intricate interplay between various pathological processes including excitotoxicity, oxidative stress, inflammation, and apoptosis. For a long time, drug intervention policies targeting a single signaling pathway have failed to achieve the anticipated clinical efficacy in the intricate and dynamic inflammatory environment of the brain. Moreover, inadequate targeted drug delivery remains a significant challenge in cerebral ischemia-reperfusion injury therapy. In this study, a multifunctional nanoplatform (designated as PB-006@MSC) is developed using ZL006-loaded Prussian blue nanoparticles (PBNPs) camouflaged by a mesenchymal stem cell (MSC) membrane (MSCm). ZL006 is a neuroprotectant. It can be loaded efficiently into the free radical scavenger PBNP through mesoporous adsorption. This can simultaneously modulate multiple targets and pathways. MSCm biomimetics can reduce the nanoparticle immunogenicity, efficiently enhance their homing capability to the cerebral ischemic penumbra, and realize active-targeting therapy for ischemic stroke. In animal experiments, PB-006@MSC integrated reactive oxygen species (ROS) scavenging and neuroprotection. Thereby, it selectively targeted the cerebral ischemic penumbra (about fourfold higher accumulation at 24 h than in the non-targeted group), demonstrated a remarkable therapeutic efficacy in reducing the volume of cerebral infarction (from 37.1% to 2.3%), protected the neurogenic functions, and ameliorated the mortality.

2.
Angew Chem Int Ed Engl ; : e202409283, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38962888

ABSTRACT

Achieving electronic/steric control and realizing selectivity regulation in nanocatalysis remains a formidable challenge, as the dynamic nature of metal-ligand interfaces, including dissolution (metal leaching) and structural reconstruction, poses significant obstacles. Herein, we disclose carboranyls (CBs) as unprecedented carbon-bonded functional ligands (Eads.CB-Au(111) = -2.90 eV) for gold nanoparticles (AuNPs), showcasing their exceptional stabilization capability that is attributed by strong Au-C bonds combined with B-H⋯Au interactions. The synthesized CB@AuNPs exhibit core(Aun)-satellite(CB2Au-) structure, showing high stability towards multiple stimuli (110oC, pH = 1-12, thiol etchants). In addition, different from conventional AuNP catalysts such as triphenylphosphine (PPh3) stabilized AuNPs, dissolution of catalytically active gold species was suppressed in CB@AuNPs under the reaction conditions. Leveraging these distinct features, CB@AuNPs realized outstanding p:o selectivities in aromatic bromination. Unbiased arenes including chlorobenzene (up to > 30:1), bromobenzene (15:1) and phenyl acrylate were examined using CB@AuNPs as catalysts to afford highly-selective p-products. Both carboranyl ligands and carboranyl derived counterions are crucial for such regioselective transformation. This work has provided valuable insights for AuNPs in realizing diverse regioselective transformations.

3.
Nano Lett ; 24(25): 7764-7773, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38864366

ABSTRACT

Inducing immunogenic cell death (ICD) during photothermal therapy (PTT) has the potential to effectively trigger photothermal immunotherapy (PTI). However, ICD induced by PTT alone is often limited by inefficient PTT, low immunogenicity of tumor cells, and a dysregulated redox microenvironment. Herein, we develop MoSe2 nanosheets with high-percentage metallic 1T phase and rich exposed active Mo centers through phase and defect engineering of MoSe2 as an effective nanoagent for PTI. The metallic 1T phase in MoSe2 nanosheets endows them with strong PTT performance, and the abundant exposed active Mo centers endow them with high activity for glutathione (GSH) depletion. The MoSe2-mediated high-performance PTT synergizing with efficient GSH depletion facilitates the release of tumor-associated antigens to induce robust ICD, thus significantly enhancing checkpoint blockade immunotherapy and activating systemic immune response in mouse models of colorectal cancer and triple-negative metastatic breast cancer.


Subject(s)
Immunotherapy , Molybdenum , Photothermal Therapy , Animals , Mice , Immunotherapy/methods , Humans , Molybdenum/chemistry , Female , Cell Line, Tumor , Nanostructures/chemistry , Nanostructures/therapeutic use , Glutathione/chemistry , Glutathione/metabolism , Colorectal Neoplasms/therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Immunogenic Cell Death/drug effects , Triple Negative Breast Neoplasms/therapy , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/pathology , Infrared Rays , Selenium/chemistry , Selenium/therapeutic use , Phototherapy/methods
4.
Ann Hematol ; 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879648

ABSTRACT

The patterns and biological functions of copper homeostasis-related genes (CHRGs) in acute myeloid leukemia (AML) remain unclear. We explored the patterns and biological functions of CHRGs in AML. Using independent cohorts, including TCGA-GTEx, GSE114868, GSE37642, and clinical samples, we identified 826 common differentially expressed genes. Specifically, 12 cuproptosis-related genes (e.g., ATP7A, ATP7B) were upregulated, while 17 cuproplasia-associated genes (e.g., ATOX1, ATP7A) were downregulated in AML. We used LASSO-Cox, Kaplan-Meier, and Nomogram analyses to establish prognostic risk models, effectively stratifying patients with AML into high- and low-risk groups. Subgroup analysis revealed that high-risk patients exhibited poorer overall survival and involvement in fatty acid metabolism, apoptosis, and glycolysis. Immune infiltration analysis indicated differences in immune cell composition, with notable increases in B cells, cytotoxic T cells, and memory T cells in the low-risk group, and increased monocytes and neutrophils in the high-risk group. Single-cell sequencing analysis corroborated the expression characteristics of critical CHRGs, such as MAPK1 and ATOX1, associated with the function of T, B, and NK cells. Drug sensitivity analysis suggested potential therapeutic agents targeting copper homeostasis, including Bicalutamide and Sorafenib. PCR validation confirmed the differential expression of 4 cuproptosis-related genes (LIPT1, SLC31A1, GCSH, and PDHA1) and 9 cuproplasia-associated genes (ATOX1, CCS, CP, MAPK1, SOD1, COA6, PDK1, DBH, and PDE3B) in AML cell line. Importantly, these genes serve as potential biomarkers for patient stratification and treatment. In conclusion, we shed light on the expression patterns and biological functions of CHRGs in AML. The developed risk models provided prognostic implications for patient survival, offering valuable information on the regulatory characteristics of CHRGs and potential avenues for personalized treatment in AML.

5.
Acta Psychol (Amst) ; 248: 104371, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38908227

ABSTRACT

The consumption value seems to be insufficient to explain consumers' domestic electric vehicle purchase behaviour, especially in a highly competitive global environment. This study aims to investigate how consumer ethnocentrism and perceived interactivity influence consumption value and pro-environmental value, subsequently affecting attitude and intention. A total of 353 valid questionnaires were collected through convenience sampling in Xuzhou, China, and the partial least square (PLS) path modelling approach was performed to test the hypotheses. The results show that consumer ethnocentrism and perceived interactivity positively influence function value, emotional value, and social value; perceived interactivity also positively influences altruistic value, biospheric value, and collectivistic value. Function value, social value, and collectivistic value positively influence attitude; however, emotional value, altruistic value and biospheric value did not find a correlation with attitude. Furthermore, attitude positively influences intention to adopt domestic electric vehicles. Finally, the theoretical and practical implications, as well as limitations were discussed accordingly.

6.
Int J Mol Sci ; 25(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38791126

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.


Subject(s)
Fatty Acid-Binding Proteins , Fatty Liver , Glutathione Transferase , Up-Regulation , Glutathione Transferase/metabolism , Glutathione Transferase/genetics , Animals , Humans , Mice , Fatty Acid-Binding Proteins/metabolism , Fatty Acid-Binding Proteins/genetics , Fatty Liver/metabolism , Fatty Liver/drug therapy , Up-Regulation/drug effects , Liver/metabolism , Liver/pathology , Liver/drug effects , Diet, High-Fat/adverse effects , Male , Mice, Inbred C57BL , Hepatocytes/metabolism , Hepatocytes/drug effects , Lipid Metabolism/drug effects , Oleic Acid/metabolism , Hep G2 Cells , Triglycerides/metabolism , Isoenzymes
7.
Materials (Basel) ; 17(9)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38730859

ABSTRACT

The wide size range and high tendency to agglomerate of in-situ TiB2 particles in reinforced Al matrix composites introduce great difficulties in their size characterization. In order to use a nanoparticle size analyzer (NSA) to obtain the precise size distribution of TiB2 particles, a controlled size characterization process has been explored. First, the extraction and drying processes for TiB2 particles were optimized. In the extraction process, alternated applications of magnetic stirring and normal ultrasound treatments were proven to accelerate the dissolution of the Al matrix in HCl solution. Furthermore, freeze-drying was found to minimize the agglomeration tendency among TiB2 particles, facilitating the acquisition of pure powders. Such powders were quantitatively made into an initial TiB2 suspension. Second, the chemical and physical dispersion technologies involved in initial TiB2 suspension were put into focus. Chemically, adding PEI (M.W. 10000) at a ratio of mPEI/mTiB2 = 1/30 into the initial suspension can greatly improve the degree of TiB2 dispersion. Physically, the optimum duration for high-energy ultrasound application to achieve TiB2 dispersion was 10 min. Overall, the corresponding underlying dispersion mechanisms were discussed in detail. With the combination of these chemical and physical dispersion specifications for TiB2 suspension, the bimodal size distribution of TiB2 was able to be characterized by NSA for the first time, and its number-average diameter was 111 ± 6 nm, which was reduced by 59.8% over the initial suspension. Indeed, the small-sized and large-sized peaks of the TiB2 particles characterized by NSA mostly match the results obtained from transmission electron microscopy and scanning electron microscopy, respectively.

8.
Front Cell Infect Microbiol ; 14: 1378804, 2024.
Article in English | MEDLINE | ID: mdl-38736749

ABSTRACT

Introduction: Seasonal human coronavirus NL63 (HCoV-NL63) is a frequently encountered virus linked to mild upper respiratory infections. However, its potential to cause more severe or widespread disease remains an area of concern. This study aimed to investigate a rare localized epidemic of HCoV-NL63-induced respiratory infections among pediatric patients in Guilin, China, and to understand the viral subtype distribution and genetic characteristics. Methods: In this study, 83 pediatric patients hospitalized with acute respiratory infections and positive for HCoV-NL63 were enrolled. Molecular analysis was conducted to identify the viral subgenotypes and to assess genetic variations in the receptor-binding domain of the spiking protein. Results: Among the 83 HCoV-NL63-positive children, three subgenotypes were identified: C4, C3, and B. Notably, 21 cases exhibited a previously unreported subtype, C4. Analysis of the C4 subtype revealed a unique amino acid mutation (I507L) in the receptor-binding domain of the spiking protein, which was also observed in the previously reported C3 genotype. This mutation may suggest potential increases in viral transmissibility and pathogenicity. Discussion: The findings of this study highlight the rapid mutation dynamics of HCoV-NL63 and its potential for increased virulence and epidemic transmission. The presence of a unique mutation in the C4 subtype, shared with the C3 genotype, raises concerns about the virus's evolving nature and its potential public health implications. This research contributes valuable insights into the understanding of HCoV-NL63's epidemiology and pathogenesis, which is crucial for effective disease prevention and control strategies. Future studies are needed to further investigate the biological significance of the observed mutation and its potential impact on the virus's transmissibility and pathogenicity.


Subject(s)
Coronavirus Infections , Coronavirus NL63, Human , Epidemics , Genotype , Phylogeny , Respiratory Tract Infections , Humans , Coronavirus NL63, Human/genetics , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Coronavirus Infections/transmission , Child , Female , Male , Child, Preschool , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , Infant , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Seasons , Mutation , Adolescent
9.
Article in English | MEDLINE | ID: mdl-38798220

ABSTRACT

BACKGROUND: In recent years, the incidence of rectal prolapse has increased significantly due to the sedentary lifestyle and irregular eating habits of modern life. However, there is a lack of clinical studies on the treatment of rectal prolapse with traditional Chinese medicine (TCM) with a large sample size. Therefore, this study investigated the characteristics of rectal prolapse treatment formulas and then studied the network pharmacology of their core therapeutic drugs, which can help to provide a reference for the treatment and postoperative care of rectal prolapse patients. OBJECTIVE: This study aimed to explore the prescription characteristics and the mechanism of action of core drugs in the treatment of rectal prolapse in Chinese medicine through data mining and bioinformatics techniques. METHODS: We collected the diagnosis and treatment information of patients with rectal prolapse from January 2014 to September 2021 in the electronic case database of Nanjing Hospital of TCM, mined the patient information and prescription features using R, screened the active ingredients of the core pairs of drugs and disease drug intersection targets using TCMSP and GnenCard databases, and constructed a Protein-protein interaction (PPI) network using STRING and Cytoscape, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the intersecting targets were performed using Metascape and R. RESULTS: We found that prolapse is easy to occur in people over 50 years old, preferably in autumn and winter. Commonly used therapeutic Chinese medicines include Glycyrrhiza glabra, Radix angelicae sinensis, Radix astragali, Atractylodes macrocephala, and Pericarpium citri reticulatae, which are mostly deficiency tonic medicines, warm in nature, and belong to spleen meridian. The core therapeutic medicinal pair was "Bupleuri radix-Cimicifugae rhizoma". There were 190 common targets of Bupleuri radix and Cimicifugae rhizoma, and 71 intersection targets of the drug pair and prolapse. The main components of the core drugs for the treatment of prolapse may be quercetin, kaempferol, Stigmasterol, etc, and the core targets may be CASP3, AKT1, HIF1A, etc. The total number of GO entries for the intersection targets of "Bupleuri radix-Cimicifugae rhizoma" and diseases was 3495, among which the molecular functions accounted for the largest proportion, mainly Pathways in cancer, IL-18 signaling pathway, etc. KEGG enriched pathway analysis yielded 168 results, and the major pathways were pathways in cancer, lipid and atherosclerosis, IL-17 signaling pathway, etc. Conclusion: This study adopted real-world research methodology and used data mining and bioinformatics technology to mine the medication law of rectal prolapse and its core drug action mechanism from the clinical information of Chinese medicine.

10.
Bioorg Chem ; 147: 107317, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38583252

ABSTRACT

By inducing steric activation of the 10CH bond with a 12-acyl group to form a key imine oxime intermediate, 20 novel (10S)-10,12-disubstituted aloperine derivatives were successfully synthesized and assessed for their antiviral efficacy against HCoV-OC43. Of them, compound 3i exhibited the moderate activities against HCoV-OC43, as well as against the SARS-CoV-2 variant EG.5.1 with the comparable EC50 values of 4.7 and 4.1 µM. A mechanism study revealed that it inhibited the protease activity of host TMPRSS2 by binding to an allosteric site, rather than the known catalytic center, different from that of camostat. Also, the combination of compound 3i and molnupiravir, as an RdRp inhibitor, showed an additive antiviral effect against HCoV-OC43. The results provide a new binding mode and lead compound for targeting TMPRSS2, with an advantage in combating broad-spectrum coronavirus.


Subject(s)
Allosteric Site , Antiviral Agents , Coronavirus OC43, Human , Quinolizidines , Serine Endopeptidases , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/chemical synthesis , Serine Endopeptidases/metabolism , Humans , Coronavirus OC43, Human/drug effects , Coronavirus OC43, Human/chemistry , Quinolizidines/chemistry , Quinolizidines/pharmacology , Quinolizidines/chemical synthesis , Allosteric Site/drug effects , Structure-Activity Relationship , Drug Discovery , SARS-CoV-2/drug effects , Molecular Structure , Microbial Sensitivity Tests , Dose-Response Relationship, Drug
11.
Signal Transduct Target Ther ; 9(1): 59, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38462638

ABSTRACT

Diet, serving as a vital source of nutrients, exerts a profound influence on human health and disease progression. Recently, dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, and metabolic disorders. These interventions have demonstrated substantial potential in modulating metabolism, disease trajectory, and therapeutic responses. Metabolic reprogramming is a hallmark of malignant progression, and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer eradication. Dietary intake, as a key environmental factor, can influence tumor metabolism. Emerging evidence indicates that dietary interventions might affect the nutrient availability in tumors, thereby increasing the efficacy of cancer treatments. However, the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is complex. Despite encouraging results, the mechanisms underlying diet-based therapeutic strategies remain largely unexplored, often resulting in underutilization in disease management. In this review, we aim to illuminate the potential effects of various dietary interventions, including calorie restriction, fasting-mimicking diet, ketogenic diet, protein restriction diet, high-salt diet, high-fat diet, and high-fiber diet, on cancer and the aforementioned diseases. We explore the multifaceted impacts of these dietary interventions, encompassing their immunomodulatory effects, other biological impacts, and underlying molecular mechanisms. This review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.


Subject(s)
Diet, Ketogenic , Neoplasms , Humans , Caloric Restriction , Diet , Fasting , Neoplasms/therapy
12.
BMC Cancer ; 24(1): 363, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38515051

ABSTRACT

OBJECTIVE: To investigate the value of differential diagnosis of hepatocellular carcinoma (HCC) and non-hepatocellular carcinoma (non-HCC) based on CT and MR multiphase radiomics combined with different machine learning models and compare the diagnostic efficacy between different radiomics models. BACKGROUND: Primary liver cancer is one of the most common clinical malignancies, hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer, accounting for approximately 90% of cases. A clear diagnosis of HCC is important for the individualized treatment of patients with HCC. However, more sophisticated diagnostic modalities need to be explored. METHODS: This retrospective study included 211 patients with liver lesions: 97 HCC and 124 non-hepatocellular carcinoma (non-HCC) who underwent CT and MRI. Imaging data were used to obtain imaging features of lesions and radiomics regions of interest (ROI). The extracted imaging features were combined to construct different radiomics models. The clinical data and imaging features were then combined with radiomics features to construct the combined models. Support Vector Machine (SVM), K-nearest Neighbor (KNN), RandomForest (RF), eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), Multilayer Perceptron (MLP) six machine learning models were used for training. Five-fold cross-validation was used to train the models, and ROC curves were used to analyze the diagnostic efficacy of each model and calculate the accuracy rate. Model training and efficacy test were performed as before. RESULTS: Statistical analysis showed that some clinical data (gender and concomitant cirrhosis) and imaging features (presence of envelope, marked enhancement in the arterial phase, rapid contouring in the portal phase, uniform density/signal and concomitant steatosis) were statistical differences (P < 0.001). The results of machine learning models showed that KNN had the best diagnostic efficacy. The results of the combined model showed that SVM had the best diagnostic efficacy, indicating that the combined model (accuracy 0.824) had better diagnostic efficacy than the radiomics-only model. CONCLUSIONS: Our results demonstrate that the radiomic features of CT and MRI combined with machine learning models enable differential diagnosis of HCC and non-HCC (malignant, benign). The diagnostic model with dual radiomic had better diagnostic efficacy. The combined model was superior to the radiomic model alone.


Subject(s)
Brain Neoplasms , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Retrospective Studies , Liver Neoplasms/diagnostic imaging , Diagnostic Imaging , Machine Learning
13.
J Am Heart Assoc ; 13(2): e031928, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38214265

ABSTRACT

BACKGROUND: We assessed the impact of pre- and postprocedural plasma corin levels on the recurrence of atrial fibrillation (AF) after catheter ablation (CA). METHODS AND RESULTS: This prospective, single-center, observational study included patients undergoing their first CA of AF. Corin was measured before and 1 day after CA. The primary end point was recurrent AF between 3 and 12 months after ablation. From April 2019 through May 2021, we analyzed 616 patients with AF (59.09% men) with a mean age of 62.86±9.42 years. Overall, 153 patients (24.84%) experienced recurrent AF. In the recurrence group, the pre- and postprocedure corin concentrations were 539.14 (329.24-702.08) and 607.37 (364.50-753.80) pg/mL, respectively, which were significantly higher than the nonrecurrence group's respective concentrations of 369.05 (186.36-489.28) and 489.12 (315.66-629.05) pg/mL (both P<0.0001). A multivariate Cox regression analysis with confounders found that elevated preablation corin levels were significantly associated with an increased risk of AF recurrence after CA. Receiver operating characteristic curve analysis identified that a preablation corin threshold of >494.85 pg/mL predicted AF recurrence at 1 year. An increase of 1 SD in corin concentrations before CA (264.94 pg/mL) increased the risk of recurrent AF by 54.3% after adjusting for confounding variables (hazard ratio, 1.465 [95% CI, 1.282-1.655]; P<0.0001). CONCLUSIONS: Plasma corin levels at baseline is a valuable predictor of AF recurrence after CA, independent of established conventional risk factors. Risk stratification before ablation for AF may be useful in selecting treatment regimens for patients.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Male , Humans , Middle Aged , Aged , Female , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Treatment Outcome , Prospective Studies , ROC Curve , Risk Factors , Catheter Ablation/adverse effects , Catheter Ablation/methods , Recurrence
14.
J Affect Disord ; 351: 250-258, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38280566

ABSTRACT

BACKGROUND: The relationship between chronotype and anxiety, depression, and insomnia was inconsistent. We aimed to assess the association between chronotype and mental health and the potential moderating effect of age and socioeconomic status (SES). METHODS: A multi-stage sampling cross-sectional study with 12,544 adults was conducted. Chronotype, anxiety, depression, and insomnia were investigated by 5-item Morning and Evening, 7-item Generalized Anxiety Disorder, 9-item Patient Health, and the 7-item Insomnia Severity Index Questionnaires. Logistic regression was conducted. RESULTS: The predominant chronotype was morning chronotype (69.2 %), followed by 27.6 % intermediate and 3.2 % evening chronotype. The prevalence of anxiety, depression, and insomnia was 0.7 %, 1.9 %, and 9.6 %, respectively. Compared with intermediate chronotype, morning chronotype participants had a lower risk of anxiety (OR = 0.28,95%CI:0.18-0.44), depression (OR = 0.54,95%CI:0.41-0.72) and insomnia (OR = 0.67,95%CI:0.58-0.77), while evening chronotype participants had a higher risk of depression (OR = 1.98,95%CI:1.06-3.71) but not anxiety or insomnia. Interactions between chronotype with age and SES on insomnia (Pinteraction < 0.05) were found. A more profound association between morning chronotype and insomnia was observed in <65 years participants (OR = 0.59,95%CI:0.50-0.71) and those with monthly household income ≥10,000yuan (OR = 0.21,95%CI:0.12-0.35), compared with their counterparts. LIMITATIONS: The cross-sectional design limited causal conclusions. Only adults were included; the findings could not be generalized to children. CONCLUSIONS: The morning chronotype might be protective for anxiety, depression, and insomnia, while the evening chronotype might be a risk factor for depression. Future studies are needed to assess the efficacy of chronotype-focused intervention for mental health. Insomnia prevention efforts should pay more attention to the elderly and those with lower incomes.


Subject(s)
Sleep Initiation and Maintenance Disorders , Adult , Child , Humans , Aged , Sleep Initiation and Maintenance Disorders/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Depression/psychology , Chronotype , Anxiety/epidemiology , Anxiety Disorders , China/epidemiology , Surveys and Questionnaires , Sleep , Circadian Rhythm
15.
Comput Biol Med ; 169: 107926, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38183706

ABSTRACT

Immune checkpoint blockade (ICB) therapy offers promise in the treatment of triple-negative breast cancer (TNBC); however, its limited efficacy in certain TNBC patients poses a challenge. In this study, we elucidated the metabolic mechanism at 'sub-subtype' resolution underlying the non-response to ICB therapy in TNBC. Here, an analytic pipeline was developed to reveal the metabolic heterogeneity, which is correlated with the ICB outcomes, within each immune cell subtype. First, we identified metabolic 'sub-subtypes' within certain cell subtypes, predominantly T cell subsets, which are enriched in ICB non-responders and named as non-responder-enriched (NR-E) clusters. Notably, most of NR-E T metabolic cells exhibit globally higher metabolic activities compared to other cells within the same individual subtype. Further, we investigated the extra-cellular signals that trigger the metabolic status of NR-E T cells. In detail, the prediction of cell-to-cell communication indicated that NR-E T cells are regulated by plasmatic dendritic cells (pDCs) through TNFSF9, as well as by macrophages expressing SIGLEC9. In addition, we also validate the communication between TNFSF9+ pDCs and NR-E T cells utilizing deconvolution of spatial transcriptomics analysis. In summary, our research identified specific metabolic 'sub-subtypes' associated with ICB non-response and uncovered the mechanisms of their regulation in TNBC. And the proposed analytical pipeline can be used to examine metabolic heterogeneity within cell types that correlate with diverse phenotypes.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Single-Cell Gene Expression Analysis , Immunotherapy , Gene Expression Profiling , Macrophages
16.
Acta Psychol (Amst) ; 243: 104162, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38280350

ABSTRACT

The bookings and revenues of youth hostels have significantly decreased because of the multiple effects of the COVID-19 pandemic. It is necessary to investigate young consumers' perceptions of visiting youth hostels aftermath this pandemic. The current study examines the relationship between multi-dimensions of perceived risk, three types of images, willingness to pay and visit intention. A convenience sampling was developed where 534 questionnaires were received, followed by subsequent empirical testing of the proposed hypotheses using SPSS and AMOS-SEM. Results showed that perceived risk negatively influenced cognitive and affective image, respectively. Cognitive and affective image positively influenced overall image and finally influenced willingness to pay and visit intention separately. In addition, cognitive image positively influenced affective image. The theoretical framework satisfactorily accounted for willingness to pay and intention, and our results help youth hostels practitioners invent efficient strategies to boost young consumers' willingness to pay and intention to visit youth hostels.


Subject(s)
COVID-19 , Humans , Adolescent , COVID-19/epidemiology , Pandemics , Intention , Surveys and Questionnaires , Consumer Behavior
17.
Luminescence ; 39(1): e4625, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37947027

ABSTRACT

A carboxylesterase fluorescent probe (Probe 1) was developed for determination of carboxylesterase to guide detection of carbamate pesticide. The probe uses benzothiazole as fluorescence group and phenyldimethyl carbamate as recognition group. The solution of the fluorescent probe gradually changes from light blue to dark blue as the concentration of carbamate pesticides increases. The concentration of carbamate pesticides can be quickly calculated according to the colour of the probe solution through Get Color software on a smartphone. It showed that Probe 1 can be used as a rapid detection tool to achieve rapid detection of carbamate pesticides in juice samples without professional personnel and equipment. Furthermore, the probe has been successfully used to detect carbamate pesticides in fruit juice and vegetable juice.


Subject(s)
Carboxylesterase , Pesticides , Fluorescent Dyes , Fluorescence , Pesticides/analysis , Carbamates
18.
Small ; 20(6): e2305062, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37803476

ABSTRACT

PtIr-based nanostructures are fascinating materials for application in bifunctional oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalysis. However, the fabrication of PtIr nanocatalysts with clear geometric features and structural configurations, which are crucial for enhancing the bifunctionality, remains challenging. Herein, PtCo@PtIr nanoparticles are precisely designed and fabricated with a quasi-octahedral PtCo nanocrystal as a highly atomically ordered core and an ultrathin PtIr atomic layer as a compressively strained shell. Owing to their geometric and core-shell features, the PtCo@PtIr nanoparticles deliver approximately six and eight times higher mass and specific activities, respectively, as an ORR catalyst than a commercial Pt/C catalyst. The half-wave potential of PtCo@PtIr exhibits a negligible decrease by 9 mV after 10 000 cycles, indicating extraordinary ORR durability because of the ordered arrangement of Pt and Co atoms. When evaluated using the ORR-OER dual reaction upon the introduction of Ir, PtCo@PtIr exhibits a small ORR-OER overpotential gap of 679 mV, demonstrating its great potential as a bifunctional electrocatalyst for fabricating fuel cells. The findings pave the way for designing precise intermetallic core-shell nanocrystals as highly functional catalysts.

19.
ACS Med Chem Lett ; 14(12): 1839-1847, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38116448

ABSTRACT

The novel 9-cinnamyl-9H-purine skeleton, inspired by resveratrol and curcumin, was developed to avoid a pan-assay interference compound (PAINS) related to invalid metabolic pancreas activity (IMPS). It replaced the phenol group with purine analogues, the building blocks of DNA and RNA. Alterations to the hydroxyl group in the cinnamyl group, such as H, Me, or F substitutions, were made to impede its oxidation to a PAINS-associated quinone. Among the compounds tested, 5e significantly inhibited nitric oxide production in LPS-induced macrophages (IC50: 6.4 vs 26.4 µM for resveratrol). 5e also reduced pro-inflammatory cytokine levels (IL-6, TNF-α, IL-1ß) and lowered iNOS and COX-2 protein levels. Mechanistically, 5e disrupted the TLR4-MyD88 protein interaction, leading to the suppression of the NF-κB signaling pathway suppression. In an atopic dermatitis mouse model, 5e reduced ear edema and inflammation. These findings indicate that the novel 9-cinnamyl-9H-purine skeleton provides therapeutic insight into treating various human diseases by regulating inflammation.

20.
Nanoscale ; 15(48): 19469-19474, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-37987086

ABSTRACT

High-entropy oxides (HEOs) are a special class of materials that utilize the concept of high-entropy alloys (HEAs) with five or more elements randomly distributing at a single sublattice in near-equiatomic proportions. HEOs have been attracting increasing attention owing to their many outstanding physical and chemical properties. However, unlike HEAs, for which local chemical compositions, order/disorder behaviors, and property-structure relationships have been comprehensively investigated, detailed information on the atomic-scale chemical and structural features and their correlations with functionalities in HEOs so far is still not sufficient. Herein, we select four typical HEOs with pyrochlore, spinel, perovskite and rock-salt type structures, and directly observe and quantify sub-Ångstrom-scale structure variations in different manners by means of advanced aberration-corrected scanning transmission electron microscopy techniques. Visualization and quantification of local structural variations and lattice distortions in the current work may show a valuable example for future investigations on local fluctuating structures and their relationships with properties in more systems of HEOs.

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