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1.
Anal Chim Acta ; 1312: 342764, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38834269

ABSTRACT

BACKGROUND: Osteopontin (OPN) is closely associated with tumorigenesis, growth, invasion, and immune escape and it serves as a plasma biomarker for hepatocellular carcinoma (HCC). Nevertheless, the accurate and rapid detection of low-abundance OPN still poses significant challenges. Currently, the majority of protein detection methods rely heavily on large precision instruments or involve complex procedures. Therefore, developing a simple, enzyme-free, rapid colorimetric analysis method with high sensitivity is imperative. RESULTS: In this study, we have developed a portable colorimetric biosensor by integrating the triple-helix aptamer probe (THAP) and catalytic hairpin assembly (CHA) strategy, named as T-CHA. After binding to the OPN, the trigger probe can be released from THAP, then initiates the CHA reaction and outputs the signal through the formation of a G-quadruplex/Hemin DNAzyme with horseradish peroxidase-like activity. Consequently, this colorimetric sensor achieves visual free-labeled detection without additional fluorophore modification and allows for accurate quantification by measuring the optical density of the solution at 650 nm. Under optimal conditions, the logarithmic values of various OPN concentrations exhibit satisfactory linearity in the range of 5 pg mL-1 to 5 ng mL-1, with a detection limit of 2.04 pg mL-1. Compared with the widely used ELISA strategy, the proposed T-CHA strategy is rapid (∼105 min), highly sensitive, and cost-effective. SIGNIFICANCE: The T-CHA strategy, leveraging the low background leakage of THAP and the high catalytic efficiency of CHA, has been successfully applied to the detection of OPN in plasma, demonstrating significant promise for the early diagnosis of HCC in point-of-care testing. Given the programmability of DNA and the universality of T-CHA, it can be readily modified for analyzing other useful tumor biomarkers.


Subject(s)
Aptamers, Nucleotide , Colorimetry , Osteopontin , Colorimetry/methods , Aptamers, Nucleotide/chemistry , Humans , Osteopontin/blood , Osteopontin/chemistry , Osteopontin/analysis , Biosensing Techniques/methods , DNA, Catalytic/chemistry , DNA, Catalytic/metabolism , Limit of Detection , G-Quadruplexes
2.
Environ Res ; 257: 119332, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838753

ABSTRACT

Indoor air quality is a critical factor influencing athletic performance, particularly in professional sports settings, yet its impact remains underexplored. This study utilizes a panel dataset from 2516 Chinese Basketball Association (CBA) matches across 20 cities in China between 2014 and 2019. We integrate daily air pollution metrics with player efficiency ratings (PER) to investigate the effects of air quality on individual performance. We find that a 10% increase in the air quality index (AQI) corresponds to a 1.4223 decrease in PER, indicating a strong negative effect of poor air quality on player productivity. Different pollutants have varying effects, with some exacerbating the decline in both overall performance and precision in tasks. Notably, older players and international players exhibit greater resilience to air pollution. These insights contribute to the development of a comprehensive index for assessing work efficiency under varying air quality conditions and suggest targeted strategies to mitigate the negative impacts of air pollution in competitive athletic settings.

3.
J Inflamm Res ; 17: 2609-2621, 2024.
Article in English | MEDLINE | ID: mdl-38689797

ABSTRACT

Background: Diabetes mellitus predisposes individuals to respiratory infections. The airway epithelial barrier provides defense against inhaled antigens and pathogens. Ezrin, is a component of the membrane-cytoskeleton that maintains the cellular morphology, intercellular adhesion, and barrier function of epithelial cells. This study aimed to explore the role of ezrin in airway epithelial barrier damage and correlate its expression and activation with diabetes mellitus. Methods: This study was performed in a murine model of diabetes mellitus and with human bronchial epithelial BEAS-2B cells using real-time PCR, Western blotting, immunohistochemical and immunofluorescence staining. Ezrin was knocked down in BEAS-2B cells using siRNA. Ezrin phosphorylation levels were measured to determine activation status. The integrity of the airway epithelial barrier was assessed in vivo by characterizing morphological structure, and in vitro in BEAS-2B cells by measuring tight junction protein expression, transepithelial electrical resistance (TER) and permeability. Results: We demonstrated that ezrin expression levels were lower in the lung tissue and airway epithelium of diabetic mice than those in control mice. The morphological structure of the airway epithelium was altered in diabetic mice. High glucose levels downregulated the expression and distribution of ezrin and connexin 43, reduced the expression of tight junction proteins, and altered the epithelial barrier characteristics of BEAS-2B cells. Ezrin knockdown had effects similar to those of high glucose levels. Moreover, a specific inhibitor of ezrin Thr567 phosphorylation (NSC305787) inhibited epithelial barrier formation. Conclusion: These results demonstrate that ezrin expression and activation are associated with airway epithelial damage in diabetes mellitus. These findings provide new insights into the molecular pathogenesis of pulmonary infections in diabetes mellitus and may lead to novel therapeutic interventions for airway epithelial barrier damage.

4.
J Hazard Mater ; 472: 134565, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38743974

ABSTRACT

Biochar shows great potential in soil cadmium pollution treatment, however, the effect and mechanisms of biochar on cadmium passivation (CP) during the long-term process of soil from flooding to natural air-drying are not clear. In this study, a 300-day experiment was conducted to keep the flooded water level constant for the first 100 days and then dried naturally. Mechanisms of CP by lignin biochar (LBC) were analyzed through chemical analysis, FTIR-2D-COS, EEMs-PARAFAC, ultraviolet spectroscopy characterizations, and microbial community distribution of soil. Results showed that application of LBC results in rapid CP ratio in soil within 35 days, mainly in the residual and Fe-Mn bound states (total 72.80%). CP ratio further increased to 90.89% with water evaporation. The CP mechanisms include precipitation, electrostatic effect, humus complexation, and microbial remediation by promoting the propagation of fungi such as Penicillium and Trichoderma. Evaporation of water promoted the colonization of aerobic microorganisms and then increased the degree of soil humification and aromatization, thereby enhancing the cadmium passivation. Simultaneously, the biochar could reduce the relative abundance of plant pathogens in soil from 1.8% to 0.03% and the freshness index (ß/α) from 0.64 to 0.16, favoring crop growth and promoting carbon sequestration and emission reduction.


Subject(s)
Cadmium , Charcoal , Lignin , Soil Microbiology , Soil Pollutants , Charcoal/chemistry , Cadmium/chemistry , Soil Pollutants/chemistry , Lignin/chemistry , Floods , Soil/chemistry , Desiccation
5.
J Hazard Mater ; 472: 134518, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38749244

ABSTRACT

Nowadays, numerous environmental risk substances in soil worldwide have exhibited serious germination inhibition of crop seeds, posing a threat to food supply and security. This review provides a comprehensive summary and discussion of the inhibitory effects of environmental risk substances on seed germination, encompassing heavy metals, microplastics, petroleum hydrocarbons, salinity, phenols, essential oil, agricultural waste, antibiotics, etc. The impacts of species, concentrations, and particle sizes of various environmental risk substances are critically investigated. Furthermore, three primary inhibition mechanisms of environmental risk substances are elucidated: hindering water absorption, inducing oxidative damage, and damaging seed cells/organelles/cell membranes. To address these negative impacts, diverse effective coping measures such as biochar/compost addition, biological remediation, seed priming, coating, and genetic modification are proposed. In brief, this study systematically analyzes the negative effects of environmental risk substances on seed germination, and provides a basis for the comprehensive understanding and future implementation of efficient treatments to address this significant challenge and ensure food security and human survival.


Subject(s)
Germination , Seeds , Soil Pollutants , Germination/drug effects , Seeds/drug effects , Seeds/growth & development , Soil Pollutants/toxicity , Metals, Heavy/toxicity , Microplastics/toxicity , Phenols/toxicity
6.
Insect Sci ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769889

ABSTRACT

Disruption of the circadian clock can affect starvation resistance, but the molecular mechanism is still unclear. Here, we found that starvation resistance was significantly reduced in the core gene BmPer deficient mutant silkworms (Per-/-), but the mutant's starvation resistance increased with larval age. Under natural physiological conditions, the weight of mutant 5th instar larvae was significantly increased compared to wild type, and the accumulation ability of triglycerides and glycogen in the fat bodies was upregulated. However, under starvation conditions, the weight consumption of mutant larvae was increased and cholesterol utilization was intensified. Transcriptome analysis showed that beta-oxidation was significantly upregulated under starvation conditions, fatty acid synthesis was inhibited, and the expression levels of genes related to mitochondrial function were significantly changed. Further investigations revealed that the redox balance, which is closely related to mitochondrial metabolism, was altered in the fat bodies, the antioxidant level was increased, and the pentose phosphate pathway, the source of reducing power in cells, was activated. Our findings suggest that one of the reasons for the increased energy burden observed in mutants is the need to maintain a more robust redox balance in metabolic tissues. This necessitates the diversion of more glucose into the pentose phosphate pathway to ensure an adequate supply of reducing power.

7.
Mol Carcinog ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607240

ABSTRACT

DNA methylation, an epigenetic regulatory mechanism dictating gene transcription, plays a critical role in the occurrence and development of cancer. However, the molecular underpinnings of LINC00987 methylation in the regulation of lung adenocarcinoma (LUAD) remain elusive. This study investigated LINC00987 expression in LUAD patients through analysis of The Cancer Genome Atlas data sets. Quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assays were used to assess LINC00987 expression in LUAD. The bisulfite genomic sequence PCR (BSP) assay was used to determine the methylation levels of the LINC00987 promoter. The interaction between LINC00987 and SND1 was elucidated via immunoprecipitation and RNA pull-down assays. The functional significance of LINC00987 and SND1 in Calu-3 and NCI-H1688 cells was evaluated in vitro through CCK-8, EdU, Transwell, flow cytometry, and vasculogenic mimicry (VM) tube formation assays. LINC00987 expression decreased in LUAD concomitant with hypermethylation of the promoter region, while hypomethylation of the LINC00987 promoter in LUAD tissues correlated with tumor progression. Treatment with 5-Aza-CdR augmented LINC00987 expression and inhibited tumor growth. Mechanistically, LINC00987 overexpression impeded LUAD progression and VM through direct binding with SND1, thereby facilitating its phosphorylation and subsequent degradation. Additionally, overexpression of SND1 counteracted the adverse effects of LINC00987 downregulation on cell proliferation, apoptosis, cell migration, invasion, and VM in LUAD in vitro. In conclusion, this pioneering study focuses on the expression and function of LINC00987 and reveals that hypermethylation of the LINC00987 gene may contribute to LUAD progression. LINC00987 has emerged as a potential tumor suppressor gene in tumorigenesis through its binding with SND1 to facilitate its phosphorylation and subsequent degradation.

8.
J Cardiothorac Surg ; 19(1): 187, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38582871

ABSTRACT

OBJECTIVE: To analyze the relationship between the thickness of the left atrial posterior wall and the low and no voltage zones in the left atrial posterior wall in patients with atrial fibrillation (AF). METHODS: 61 patients admitted to our cardiology department for AF and radiofrequency ablation of AF from January 1, 2020 to May 30, 2022 were enrolled according to inclusion and exclusion criteria. The atrial wall thickness was measured by CT scan. Baseline data, preoperative cardiac ultrasound data, preoperative biochemical parameters, low voltage zone (fibrotic zone) and no voltage zone (scar zone) in the left atrial posterior wall area, and various parameters of posterior left atrial wall thickness were collected. RESULTS: The differences of the thickness between the upper, middle and lower mean levels of the left atrial posterior wall were statistically significant (P = 0.004). The results showed that body mass index was weakly positively correlated with the mean level of total left atrial posterior wall thickness (r = 0.426, P = 0.001) and was statistically significant. The remaining indices were positively or negatively correlated with the mean level of total left atrial posterior wall thickness, but none were statistically significant (P > 0.05). CONCLUSIONS: Both left atrial posterior wall low-voltage zone and voltage-free zone were positively correlated with the mean total left atrial posterior wall thickness, and left atrial posterior wall low-voltage zone and voltage-free zone were significantly positively correlated. Body mass index was weakly positively correlated with total left atrial posterior wall thickness.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Atrial Fibrillation/pathology , Catheter Ablation/methods , Heart Atria/pathology , Fibrosis , Cicatrix , Treatment Outcome
9.
Open Life Sci ; 19(1): 20220832, 2024.
Article in English | MEDLINE | ID: mdl-38585637

ABSTRACT

Acute myeloid leukemia (AML) is a blood system malignancy where sirtuin 5 (SIRT5) is abnormally expressed in AML cell lines. This study aimed to investigate the SIRT5 effects on the viability and apoptosis of AML cell lines. The mRNA and protein expression levels of succinylation regulatory enzyme in clinical samples and AML cell lines were detected by real-time quantitative polymerase chain reaction and western blotting while cell viability was measured using cell counting kit-8 assay. The apoptosis rate was assessed with flow cytometry. The interaction between SIRT5 and glycine decarboxylase (GLDC) was determined by co-immunoprecipitation and immunofluorescence staining techniques. Results indicated higher mRNA and protein expression levels of SIRT5 in clinical AML samples of AML than in normal subjects. Similarly, cell viability was inhibited, and apoptosis was promoted by downregulating SIRT5, in addition to inhibition of SIRT5-mediated GLDC succinylation. Moreover, rescue experiment results showed that GLDC reversed the effects of SIRT5 knockdown on cell viability and apoptosis. These results, in combination with SIRT5 and GLDC interactions, suggested that SIRT5 was involved in mediating AML development through GLDC succinylation. SIRT5 inhibits GLDC succinylation to promote viability and inhibit apoptosis of AML cells, suggesting that SIRT5 encourages the development of AML.

10.
BMC Nurs ; 23(1): 256, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649865

ABSTRACT

BACKGROUND: Abusive supervision by the nurse manager significantly influences nurses' withholding voice about patient safety. The role of impression management motivation and speak up-related climate is crucial in understanding their connection. This study aimed to explore the relationship between abusive supervision, impression management motivation, speak up-related climate, and withholding voice about patient safety. METHODS: This cross-sectional study employed a convenience sampling method to recruit 419 clinical nurses from Taizhou Hospital, Zhejiang Province, China, between 1 November 2022 and 31 January 2023. The study adhered to the STROBE checklist. Abusive supervision and impression management motivation were assessed using the Chinese versions of the Abusive Supervision Scale and the Impression Management Motivation Scale, respectively. Withholding voice about patient safety and speak up-related climate were identified using the Chinese version of the Speaking Up about Patient Safety Questionnaire. RESULTS: Nurse leaders' abusive supervision (ß=0.40, p<0.01) and nurses' impression management motivation (ß=0.10, p<0.01) significantly and positively influenced nurses' withholding voice about patient safety. We introduced impression management motivation as a mediating variable, and the effect of abusive supervision on nurses' withholding voice decreased (ß from 0.40 to 0.38, p< 0.01). Nurses' speak up-related climate played a moderating role between abusive supervision and impression management motivation (ß= 0.24, p<0.05). CONCLUSIONS: Abusive supervision by nursing leaders can result in nurses withholding voice about patient safety out of self-protective impression management motives. This phenomenon inhibits nurses' subjective initiative and undermines their proactive involvement in improving patient safety, and hinders the cultivation of a culture encouraging full participation in patient safety, which should warrant significant attention.

11.
J Med Chem ; 67(8): 6313-6326, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38574345

ABSTRACT

Coactivator-associated arginine methyltransferase 1 (CARM1), an important member of type I protein arginine methyltransferases (PRMTs), has emerged as a promising therapeutic target for various cancer types. In our previous study, we have identified a series of type I PRMT inhibitors, among which ZL-28-6 (6) exhibited increased activity against CARM1 while displaying decreased potency against other type I PRMTs. In this work, we conducted chemical modifications on compound 6, resulting in a series of (2-(benzyloxy)phenyl)methanamine derivatives as potent inhibitors of CARM1. Among them, compound 17e displayed remarkable potency and selectivity for CARM1 (IC50 = 2 ± 1 nM), along with notable antiproliferative effects against melanoma cell lines. Cellular thermal shift assay and western blot experiments confirmed that compound 6 effectively targets CARM1 within cells. Furthermore, compound 17e displayed good antitumor efficacy in a melanoma xenograft model, indicating that this compound warrants further investigation as a potential anticancer agent.


Subject(s)
Antineoplastic Agents , Melanoma , Protein-Arginine N-Methyltransferases , Humans , Protein-Arginine N-Methyltransferases/antagonists & inhibitors , Protein-Arginine N-Methyltransferases/metabolism , Animals , Melanoma/drug therapy , Melanoma/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Mice , Structure-Activity Relationship , Cell Proliferation/drug effects , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/therapeutic use , Xenograft Model Antitumor Assays , Mice, Nude , Drug Screening Assays, Antitumor
12.
J Phys Chem Lett ; 15(15): 4076-4081, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38587414

ABSTRACT

Elucidating the key factors that affect the localized excitons (LEs) photoluminescence (PL) in lead-free metal halide nanocrystals (NCs) is important for their optoelectronic applications. However, the effect of A-site cations on LEs based PL is not well understood. Herein, we varied the A-site cation ratio (Rb/Cs) to investigate the influence on LEs based PL in manganese-doped zinc chloride NCs. Through time-resolved photoluminescence (TR-PL) spectra and density functional theory (DFT) calculations, we discovered that Cl vacancy is energetically more favorable in Mn2+-doped Rb3ZnCl5 NCs compared to Mn2+-doped Cs3ZnCl5 NCs. The higher concentration of Cl vacancy increases the nonradiative recombination process in Rb3ZnCl5:Mn2+ NCs, ultimately determining the PL efficiency. This research enhances the understanding of the A-site cation effect on LEs-based PL in lead-free metal halide NCs.

13.
BMC Cancer ; 24(1): 404, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561648

ABSTRACT

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.


Subject(s)
Radiomics , Stomach Neoplasms , Humans , Cohort Studies , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Retrospective Studies , Microsatellite Instability , Immunotherapy , Tomography, X-Ray Computed , Immunoglobulins
14.
J Med Virol ; 96(5): e29634, 2024 May.
Article in English | MEDLINE | ID: mdl-38682578

ABSTRACT

Metabolic reprogramming induced by Epstein-Barr virus (EBV) often mirrors metabolic changes observed in cancer cells. Accumulating evidence suggests that lytic reactivation is crucial in EBV-associated oncogenesis. The aim of this study was to explore the role of metabolite changes in EBV-associated malignancies and viral life cycle control. We first revealed that EBV (LMP1) accelerates the secretion of the oncometabolite D-2HG, and serum D-2HG level is a potential diagnostic biomarker for NPC. EBV (LMP1)-driven metabolite changes disrupts the homeostasis of global DNA methylation and demethylation, which have a significantly inhibitory effect on active DNA demethylation and 5hmC content. We found that loss of 5hmC indicates a poor prognosis for NPC patients, and that 5hmC modification is a restriction factor of EBV reactivation. We confirmed a novel EBV reactivation inhibitor, α-KG, which inhibits the expression of EBV lytic genes with CpG-containing ZREs and the latent-lytic switch by enhancing 5hmC modification. Our results demonstrate a novel mechanism of which metabolite abnormality driven by EBV controls the viral lytic reactivation through epigenetic modification. This study presents a potential strategy for blocking EBV reactivation, and provides potential targets for the diagnosis and therapy of NPC.


Subject(s)
DNA Methylation , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Virus Activation , Humans , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/physiology , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/complications , Viral Matrix Proteins/metabolism , Viral Matrix Proteins/genetics , Epigenesis, Genetic , Disease Progression
15.
Biomol Biomed ; 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38683171

ABSTRACT

Advancements in artificial intelligence (AI) offer promising tools for improving diagnostic accuracy and patient outcomes in cardiovascular medicine. This study explores the potential of AI-assisted measurements in enhancing the prediction of major adverse cardiac events (MACE) in patients with coronary artery disease (CAD). We conducted a retrospective cohort study involving patients diagnosed with CAD who underwent coronary computed tomography angiography (CCTA). Participants were classified into MACE and non-MACE groups based on their clinical outcomes. Clinical characteristics and AI-assisted measurements of CCTA parameters, including CT-derived fractional flow reserve (CT-FFR) and fat attenuation index (FAI), were collected. Both univariate and multivariable logistic regression analyses were performed to identify independent predictors of MACE, which were used to build predictive models. Statistical analyses revealed three independent predictors of MACE: severe stenosis, CT-FFR ≤ 0.8, and mean FAI (P < 0.05). Seven predictive models incorporating various combinations of these predictors were developed. The model combining all three predictors demonstrated superior performance, as evidenced by the receiver operating characteristic (ROC) curve, with an area under the curve (AUC) of 0.811 (95% CI 0.774 - 0.847), a sensitivity of 0.776, and a specificity of 0.726. Our findings suggest that AI-assisted CCTA analysis, particularly using FFR and FAI, could significantly improve the prediction of MACE in CAD patients, thereby potentially aiding clinical decision-making.

16.
Nat Commun ; 15(1): 3531, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38670961

ABSTRACT

E6AP dysfunction is associated with Angelman syndrome and Autism spectrum disorder. Additionally, the host E6AP is hijacked by the high-risk HPV E6 to aberrantly ubiquitinate the tumor suppressor p53, which is linked with development of multiple types of cancer, including most cervical cancers. Here we show that E6AP and the E6AP/E6 complex exist, respectively, as a monomer and a dimer of the E6AP/E6 protomer. The short α1-helix of E6AP transforms into a longer helical structure when in complex with E6. The extended α1-helices of the dimer intersect symmetrically and contribute to the dimerization. The two protomers sway around the crossed region of the two α1-helices to promote the attachment and detachment of substrates to the catalytic C-lobe of E6AP, thus facilitating ubiquitin transfer. These findings, complemented by mutagenesis analysis, suggest that the α1-helix, through conformational transformations, controls the transition between the inactive monomer and the active dimer of E6AP.


Subject(s)
Protein Multimerization , Ubiquitin-Protein Ligases , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/chemistry , Ubiquitin-Protein Ligases/genetics , Humans , Ubiquitin/metabolism , Ubiquitin/chemistry , Ubiquitination , Models, Molecular , Crystallography, X-Ray , Oncogene Proteins, Viral/metabolism , Oncogene Proteins, Viral/chemistry , Oncogene Proteins, Viral/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/chemistry , Tumor Suppressor Protein p53/genetics , Protein Binding , Protein Conformation, alpha-Helical
17.
Brain Res Bull ; 211: 110949, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38615889

ABSTRACT

Cognitive impairment (CI) has been reported in 29-70% of patients with neuromyelitis optica spectrum disorder (NMOSD). Abnormal white matter (WM) functional networks that correlate with cognitive functions have not been studied well in patients with NMOSD. The aim of the current study was to investigate functional connectivity (FC), spontaneous activity, and functional covariance connectivity (FCC) abnormalities of WM functional networks in patients with NMOSD and their correlation with cognitive performance. Twenty-four patients with NMOSD and 24 healthy controls (HCs) were included in the study. Participants underwent brain resting-state functional magnetic resonance imaging (fMRI) and the Montreal Cognitive Assessment (MoCA). Eight WM networks and nine gray matter (GM) networks were created. In patients, WM networks, including WM1-4, WM1-8, WM2-6, WM2-7, WM2-8, WM4-8, WM5-8 showed reduced FC (P < 0.05). All WM networks except WM1 showed decreased spontaneous activity (P < 0.05). The major GM networks demonstrated increased/decreased FC (P < 0.05), whereas GM7-WM7, GM8-WM4, GM8-WM6 and GM8-WM8 displayed decreased FC (P < 0.05). The MoCA results showed that two-thirds (16/24) of the patients had CI. FC and FCC in WM networks were correlated negatively with the MoCA scores (P < 0.05). WM functional networks are multi-layered. Abnormal FC of WM functional networks and GM functional networks may be responsible for CI.


Subject(s)
Gray Matter , Magnetic Resonance Imaging , Nerve Net , Neuromyelitis Optica , White Matter , Humans , White Matter/diagnostic imaging , Female , Male , Gray Matter/diagnostic imaging , Gray Matter/physiopathology , Gray Matter/pathology , Adult , Magnetic Resonance Imaging/methods , Middle Aged , Neuromyelitis Optica/physiopathology , Neuromyelitis Optica/diagnostic imaging , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging , Brain/physiopathology , Brain/diagnostic imaging , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging
18.
Langmuir ; 40(18): 9490-9500, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38666488

ABSTRACT

The highly sensitive gas sensors used to monitor the decomposition of toxic gases in the dielectric materials of electrical equipment are vital in preventing safety problems arising from corrosion of the equipment. Recently, biphenylene (BPN) has been prepared through surface interpolymer hydrofluorination (HF zipper) reaction, whereas potential gas-sensitive devices based on the BPN monolayer have lacked in-depth investigation. The stable geometries, adsorption energies, interlayer distances, and charge transfers of small molecules of toxic gases (H2S, SO2, SOF2, SO2F2) produced by SF6 chalcogenide molecules of decomposition adsorbed on the original BPN monolayer are systematically researched by using nonequilibrium Green's function methods and density functional theory. The results indicated that all small molecules adsorbed on the BPN monolayer are physisorbed, while the type of adsorption turned from physisorption to chemisorption when BPN carried out adsorption with adsorbing a transition metal atom (TMA). In addition, the characteristics of current-voltage (I-V) curves of H2S and SO2 based on the TMA-BPN gas sensors revealed that the currents in BPN-based gas sensors displayed an obvious anisotropy, and the currents in the zigzag direction are larger than that in the armchair orientation regardless of the molecular adsorption cases. Moreover, the difference of currents for TMA-decorated BPN sensors changed more remarkably before and after the adsorption of H2S and SO2 in the zigzag direction. This work offers insights into the design of gas-sensitive devices through the adsorption of small molecules on the TMA-decorated BPN monolayer.

19.
Brain Res Bull ; 212: 110938, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38641153

ABSTRACT

Whole-brain dynamic functional connectivity is a growing area in neuroimaging research, encompassing data-driven methods for investigating how large-scale brain networks dynamically reorganize during resting states. However, this approach has been rarely applied to functional magnetic resonance imaging (fMRI) data acquired during task performance. In this study, we first combined the psychophysiological interactions (PPI) and sliding-window methods to analyze dynamic effective connectivity of fMRI data obtained from subjects performing the N-back task within the Human Connectome Project dataset. We then proposed a hypothetical model called Condition Activated Specific Trajectory (CAST) to represent a series of spatiotemporal synchronous changes in significantly activated connections across time windows, which we refer to as a trajectory. Our finding demonstrate that the CAST model outperforms other models in terms of intra-group consistency of individual spatial pattern of PPI connectivity, overall representational ability of temporal variability and hierarchy for individual task performance and cognitive traits. This dynamic view afforded by the CAST model reflects the intrinsic nature of coherent brain activities.


Subject(s)
Brain , Connectome , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Brain/physiology , Brain/diagnostic imaging , Connectome/methods , Male , Female , Adult , Brain Mapping/methods , Models, Neurological , Neural Pathways/physiology , Neural Pathways/diagnostic imaging , Young Adult , Nerve Net/physiology , Nerve Net/diagnostic imaging
20.
Int J Neural Syst ; 34(7): 2450031, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38623649

ABSTRACT

Schizophrenia is accompanied by aberrant interactions of intrinsic brain networks. However, the modulatory effect of electroencephalography (EEG) rhythms on the functional connectivity (FC) in schizophrenia remains unclear. This study aims to provide new insight into network communication in schizophrenia by integrating FC and EEG rhythm information. After collecting simultaneous resting-state EEG-functional magnetic resonance imaging data, the effect of rhythm modulations on FC was explored using what we term "dynamic rhythm information." We also investigated the synergistic relationships among three networks under rhythm modulation conditions, where this relationship presents the coupling between two brain networks with other networks as the center by the rhythm modulation. This study found FC between the thalamus and cortical network regions was rhythm-specific. Further, the effects of the thalamus on the default mode network (DMN) and salience network (SN) were less similar under alpha rhythm modulation in schizophrenia patients than in controls ([Formula: see text]). However, the similarity between the effects of the central executive network (CEN) on the DMN and SN under gamma modulation was greater ([Formula: see text]), and the degree of coupling was negatively correlated with the duration of disease ([Formula: see text], [Formula: see text]). Moreover, schizophrenia patients exhibited less coupling with the thalamus as the center and greater coupling with the CEN as the center. These results indicate that modulations in dynamic rhythms might contribute to the disordered functional interactions seen in schizophrenia.


Subject(s)
Cerebral Cortex , Electroencephalography , Magnetic Resonance Imaging , Nerve Net , Schizophrenia , Thalamus , Humans , Schizophrenia/physiopathology , Schizophrenia/diagnostic imaging , Thalamus/physiopathology , Thalamus/diagnostic imaging , Cerebral Cortex/physiopathology , Cerebral Cortex/diagnostic imaging , Adult , Male , Female , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Brain Waves/physiology , Young Adult , Neural Pathways/physiopathology , Default Mode Network/physiopathology , Default Mode Network/diagnostic imaging , Connectome
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