Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 2.358
Filter
1.
Nanoscale ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896041

ABSTRACT

Dissolution of poly-sulfide/selenides (p-S/Ses) intermediates into electrolytes, commonly known as the shuttle effect, has posed a significant challenge in the development of more efficient and reliable Na-S/Se batteries. Single-atom catalysts (SACs) play a crucial role in mitigating the shuttling of Na-pS/Ses and in promoting Na2S/Se redox processes at the cathode. In this work, single transition metal atoms Co, Fe, Ir, Ni, Pd, Pt, and Rh supported in nitrogen-deficient graphitic carbon nitride (rg-C3N4) are investigated to explore the charging and discharging kinetics of Na-S and Na-Se batteries using Density Functional Theory calculations. We find that SAs adsorbed on reduced g-C3N4 monolayers are substantially more effective in trapping higher-order Na2Xn than pristine g-C3N4 surfaces. Moreover, our ab initio molecular dynamics calculations indicate that the structure of X8 (X = S, Se) remains almost intact when adsorbed on Fe, Co, Ir, Ni, Pt, and Rh SACs, suggesting that there is no significant S or Se poisoning in these cases. Additionally, SACs reduce the free energies of the rate-determining step during discharge and present a lower decomposition barrier of Na2X during charging of Na-X electrode. The underlying mechanisms behind this fast kinetics are thoroughly examined using charge transfer, bonding strength, and d-band center analysis. Our work demonstrates an effective strategy for designing single-atom catalysts and offers solutions to the performance constraints caused by the shuttle effect in sodium-sulfur and sodium-selenium batteries.

2.
Nat Genet ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886587

ABSTRACT

Polygenic scores (PGS) have emerged as the tool of choice for genomic prediction in a wide range of fields. We show that PGS performance varies broadly across contexts and biobanks. Contexts such as age, sex and income can impact PGS accuracy with similar magnitudes as genetic ancestry. Here we introduce an approach (CalPred) that models all contexts jointly to produce prediction intervals that vary across contexts to achieve calibration (include the trait with 90% probability), whereas existing methods are miscalibrated. In analyses of 72 traits across large and diverse biobanks (All of Us and UK Biobank), we find that prediction intervals required adjustment by up to 80% for quantitative traits. For disease traits, PGS-based predictions were miscalibrated across socioeconomic contexts such as annual household income levels, further highlighting the need of accounting for context information in PGS-based prediction across diverse populations.

3.
J Appl Clin Med Phys ; : e14432, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38889335

ABSTRACT

PURPOSE: To investigate the beam complexity of stereotactic Volumetric Modulated Arc Therapy (VMAT) plans quantitively and predict gamma passing rates (GPRs) using machine learning. METHODS: The entire dataset is exclusively made of stereotactic VMAT plans (301 plans with 594 beams) from Varian Edge LINAC. The GPRs were analyzed using Varian's portal dosimetry with 2%/2 mm criteria. A total of 27 metrics were calculated to investigate the correlation between metrics and GPRs. Random forest and gradient boosting models were developed and trained to predict the GPRs based on the extracted complexity features. The threshold values of complexity metric were obtained to predict a given beam to pass or fail from ROC curve analysis. RESULTS: The three moderately significant values of Spearman's rank correlation to GPRs were 0.508 (p < 0.001), 0.445 (p < 0.001), and -0.416 (p < 0.001) for proposed metric LAAM, the ratio of the average aperture area over jaw area (AAJA) and index of modulation, respectively. The random forest method achieved 98.74% prediction accuracy with mean absolute error of 1.23% using five-fold cross-validation, and 98.71% with 1.25% for gradient boosting regressor method, respectively. LAAM, leaf travelling distance (LT), AAJA, LT modulation complexity score (LTMCS) and index of modulation, were the top five most important complexity features. The LAAM metric showed the best performance with AUC value of 0.801, and threshold value of 0.365. CONCLUSIONS: The calculated metrics were effective in quantifying the complexity of stereotactic VMAT plans. We have demonstrated that the GPRs could be accurately predicted using machine learning methods based on extracted complexity metrics. The quantification of complexity and machine learning methods have the potential to improve stereotactic treatment planning and identify the failure of QA results promptly.

4.
Ann Hematol ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862793

ABSTRACT

Natural killer (NK) cells are equipped with anti-Epstein-Barr virus (EBV) function, however, whether EBV infection will affect NK cells reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To identify the characteristics of NK cells, we prospectively enrolled 11 patients who occurred EBV reactivation post allo-HSCT and 11 patients without EBV infection as control. We found that that EBV infection induced the expansion of CD56bright and NKG2A+KIR- NK subsets,and decreased the cytotoxicity function of NK cells. The frequency of NKG2A+KIR- NK cells were higher in patients who progressed into post-transplant lymphoproliferative disorder (PTLD) than EBV viremia patients, which also correlated with decreased proliferation and cytotoxic function. By screening the activation receptors of NK cells, we found the DNAM-1+CD56bright NK cells is significantly increased after EBV stimulation, further we demonstrated that DNAM-1 is essential for EBV induced NK cells activation as the cytokine release against EBV-transformed lymphoblastoid cell lines(EBV-LCLs) of CD56bright NK cells were significantly decreased after DNAM-1 blockade. NK cells infusion suppressed the progression of EBV-related tumor mice model. A prospective cohort indicated that old donor age was an independent risk factor for EBV infection. Rapid CD56bri expansion and high expression of DNAM-1 on CD56bri NK cells in response to EBV reactivation correlated with rapid EBV clearance post allo-HSCT in patients with younger donors. In summary, our data showed that high expression of DNAM-1 receptors on NK cell may participate protective CD56bri NK cells response to EBV infection after allo-HSCT.

5.
Nat Immunol ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872000

ABSTRACT

Natural killer (NK) cells function by eliminating virus-infected or tumor cells. Here we identified an NK-lineage-biased progenitor population, referred to as early NK progenitors (ENKPs), which developed into NK cells independently of common precursors for innate lymphoid cells (ILCPs). ENKP-derived NK cells (ENKP_NK cells) and ILCP-derived NK cells (ILCP_NK cells) were transcriptionally different. We devised combinations of surface markers that identified highly enriched ENKP_NK and ILCP_NK cell populations in wild-type mice. Furthermore, Ly49H+ NK cells that responded to mouse cytomegalovirus infection primarily developed from ENKPs, whereas ILCP_NK cells were better IFNγ producers after infection with Salmonella and herpes simplex virus. Human CD56dim and CD56bright NK cells were transcriptionally similar to ENKP_NK cells and ILCP_NK cells, respectively. Our findings establish the existence of two pathways of NK cell development that generate functionally distinct NK cell subsets in mice and further suggest these pathways may be conserved in humans.

6.
Mol Neurobiol ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38823000

ABSTRACT

In this study, we aimed to work through the key genes involved in the process of pyroptosis in Alzheimer's disease (AD) to identify potential biomarkers using bioinformatics technology and further explore the underlying molecular mechanisms. The transcriptome data of brain tissue in AD patients were screened from the GEO database, and pyroptosis-related genes were analyzed. The functions of differential genes were analyzed by enrichment analysis and protein-protein interaction. The diagnostic model was established using LASSO and logistic regression analysis, and the correlation of clinical data was analyzed. Based on single-cell analysis of brain tissues of patients with AD, immunofluorescence and western blotting were used to explore the key cells affected by the hub gene. After GSEA, qRT-PCR, western blotting, LDH, ROS, and JC-1 were used to investigate the potential mechanism of the hub gene on pyroptosis. A total of 15 pyroptosis differentially expressed genes were identified. A prediction model consisting of six genes was established by LASSO and logistic regression analysis, and the area under the curve was up to 0.81. As a hub gene, CHMP4B was negatively correlated with the severity of AD. CHMP4B expression was decreased in the hippocampal tissue of patients with AD and mice. Single-cell analysis showed that CHMP4B was downregulated in AD microglia. Overexpression of CHMP4B reduced the release of LDH and ROS and restored mitochondrial membrane potential, thereby alleviating the inflammatory response during microglial pyroptosis. In summary, CHMP4B as a hub gene provides a new strategy for the diagnosis and treatment of AD.

7.
Hum Mol Genet ; 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38879759

ABSTRACT

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium genome-wide association studies meta-analyses of European- (71 771 cases and 1 059 740 controls) and African-ancestry samples (7482 cases and 129 975 controls). We used LDpred2 and PRS-CSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6781 cases and 103 016 controls) and African-ancestry sample (1385 cases and 12 569 controls). Multi-ancestry PRSs with weights tuned in European-ancestry samples slightly outperformed ancestry-specific PRSs in European-ancestry test samples (e.g. the area under the receiver operating curve [AUC] was 0.609 for PRS-CSx_combinedEUR and 0.608 for PRS-CSxEUR [P = 0.00029]). Multi-ancestry PRSs with weights tuned in African-ancestry samples also outperformed ancestry-specific PRSs in African-ancestry test samples (PRS-CSxAFR: AUC = 0.58, PRS-CSx_combined AFR: AUC = 0.59), although this difference was not statistically significant (P = 0.34). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS might be used to improve performance across diverse populations to identify individuals at highest risk for VTE.

8.
Front Oncol ; 14: 1372424, 2024.
Article in English | MEDLINE | ID: mdl-38884079

ABSTRACT

Introduction: Young cervical cancer patients who require ovarian transposition usually have their ovaries moved away from the pelvic radiotherapy (RT) field before radiotherapy. The dose of ovaries during radiotherapy is closely related to the location of the ovaries. To protect ovarian function and avoid ovarian dose exceeding the limits, a safe location of transposed ovary must be determined prior to surgery. Methods: For this purpose, we input the patient's preoperative CT into a neural network model to predict the dose distribution. Surgeons were able to quickly locate low-dose regions based on the dose distribution before surgery, thus determining the safe location of the transposed ovary. In this work, we proposed a new progressive refinement transformer model PRT-Net that can generate dose prediction at multiple scale resolutions in one forward propagation, and refine the dose prediction using prediction details from low to high resolution based on a deep supervision strategy. A multi-loss function fusion algorithm was also built to fit the prediction results under different loss dimensions. The clinical feasibility of the method was verified through an actual cases. Results and discussion: Therefore, using PRT-Net to predict the dose distribution by preoperative CT in cervical cancer patients can assist clinicians to perform ovarian transposition surgery and prevent patients' ovaries from exceeding the prescribed dose limit in postoperative radiotherapy.

9.
Biomed Pharmacother ; 176: 116938, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38878684

ABSTRACT

Spinal cord injury (SCI) is a serious and disabling central nervous system injury. Its complex pathological mechanism can lead to sensory and motor dysfunction. It has been reported that signaling pathway plays a key role in the pathological process and neuronal recovery mechanism of SCI. Such as PI3K/Akt, MAPK, NF-κB, and Wnt/ß-catenin signaling pathways. According to reports, various stimuli and cytokines activate these signaling pathways related to SCI pathology, thereby participating in the regulation of pathological processes such as inflammation response, cell apoptosis, oxidative stress, and glial scar formation after injury. Activation or inhibition of relevant pathways can delay inflammatory response, reduce neuronal apoptosis, prevent glial scar formation, improve the microenvironment after SCI, and promote neural function recovery. Based on the role of signaling pathways in SCI, they may be potential targets for the treatment of SCI. Therefore, understanding the signaling pathway and its inhibitors may be beneficial to the development of SCI therapeutic targets and new drugs. This paper mainly summarizes the pathophysiological process of SCI, the signaling pathways involved in SCI pathogenesis, and the potential role of specific inhibitors/activators in its treatment. In addition, this review also discusses the deficiencies and defects of signaling pathways in SCI research. It is hoped that this study can provide reference for future research on signaling pathways in the pathogenesis of SCI and provide theoretical basis for SCI biotherapy.


Subject(s)
Signal Transduction , Spinal Cord Injuries , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/physiopathology , Humans , Signal Transduction/drug effects , Animals
10.
Front Oncol ; 14: 1364306, 2024.
Article in English | MEDLINE | ID: mdl-38835375

ABSTRACT

Spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) has rapidly developed in recent years. The application scope is still being continuously explored. We describe a case in which a 40-year-old woman with mixed ground-glass opacity (GGO) and an esophageal leiomyoma successfully underwent simultaneous segmentectomy and leiomyoma resection through spontaneous ventilation video-assisted thoracoscopic surgery. The perioperative course was uneventful. Postoperative pathology revealed minimally invasive adenocarcinoma and esophageal leiomyoma.

11.
Regen Biomater ; 11: rbae058, 2024.
Article in English | MEDLINE | ID: mdl-38854682

ABSTRACT

Periodontitis-induced periodontal bone defects significantly impact patients' daily lives. The guided tissue regeneration and guided bone regeneration techniques, which are based on barrier membranes, have brought hope for the regeneration of periodontal bone defects. However, traditional barrier membranes lack antimicrobial properties and cannot effectively regulate the complex oxidative stress microenvironment in periodontal bone defect areas, leading to unsatisfactory outcomes in promoting periodontal bone regeneration. To address these issues, our study selected the collagen barrier membrane as the substrate material and synthesized a novel barrier membrane (PO/4-BPBA/Mino@COL, PBMC) with an intelligent antimicrobial coating through a simple layer-by-layer assembly method, incorporating reactive oxygen species (ROS)-scavenging components, commercial dual-functional linkers and antimicrobial building blocks. Experimental results indicated that PBMC exhibited good degradability, hydrophilicity and ROS-responsiveness, allowing for the slow and controlled release of antimicrobial drugs. The outstanding antibacterial, antioxidant and biocompatibility properties of PBMC contributed to resistance to periodontal pathogen infection and regulation of the oxidative balance, while enhancing the migration and osteogenic differentiation of human periodontal ligament stem cells. Finally, using a rat periodontal bone defect model, the therapeutic effect of PBMC in promoting periodontal bone regeneration under infection conditions was confirmed. In summary, the novel barrier membranes designed in this study have significant potential for clinical application and provide a reference for the design of future periodontal regenerative functional materials.

12.
Phytopathology ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809697

ABSTRACT

Dendrobium officinale soft rot is a widespread and destructive disease caused by Fusarium oxysporum that can seriously affect its yield and quality. To better understand the fungal infection and colonization, we successfully created an F. oxysporum labeled with green fluorescent protein (GFP) using Agrobacterium tumefaciens-mediated transformation (ATMT) method. Transformants had varying fluorescence intensities, but their pathogenicity did not differ from that of the wild type (WT). Fluorescence microscopy revealed that F. oxysporum primarily entered the aboveground portion of D. officinale through the leaf margin, stomata, or by direct penetration of leaf surface. It then colonized the mesophyll and spreads along its vascular bundles. After 14 d of culture, D. officinale exhibited typical symptoms of decay and wilting, accompanied by a pronounced fluorescence signal in the affected area. The initial colonization of F. oxysporum in the subterranean region primarily involved attachment to the root hair and epidermis, which progressed to the medullary vascular bundle. At 14 days post inoculation (dpi), the root vascular bundles of D. officinale exhibited significant colonization by F. oxysporum. Macroconidia were also observed in black rot D. officinale tissue. In particular, the entire root was surrounded by a significant number of chlamydospore-producing F. oxysporum mycelia at 28 dpi. This approach allowed the visualization of the complete infection process of F. oxysporum and provided a theoretical foundation for the development of field control strategies.

13.
Cell Death Dis ; 15(5): 375, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811536

ABSTRACT

ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is frequently mutated in various cancer types and has emerged as a potential therapeutic target. In this study, we observed that ARID1A-deficient colorectal cancer (CRC) cells showed synthetic lethal effects with a p53 activator, RITA (reactivating p53 and inducing tumor apoptosis). RITA, an inhibitor of the p53-MDM2 interaction, exhibits increased sensitivity in ARID1A-deficient cells compared to ARID1A wild-type cells. Mechanistically, the observed synthetic lethality is dependent on both p53 activation and DNA damage accumulation, which are regulated by the interplay between ARID1A and RITA. ARID1A loss exhibits an opposing effect on p53 targets, leading to decreased p21 expression and increased levels of proapoptotic genes, PUMA and NOXA, which is further potentiated by RITA treatment, ultimately inducing cell apoptosis. Meanwhile, ARID1A loss aggravates RITA-induced DNA damage accumulation by downregulating Chk2 phosphorylation. Taken together, ARID1A loss significantly heightens sensitivity to RITA in CRC, revealing a novel synthetic lethal interaction between ARID1A and RITA. These findings present a promising therapeutic approach for colorectal cancer characterized by ARID1A loss-of-function mutations.


Subject(s)
Apoptosis , Colorectal Neoplasms , DNA-Binding Proteins , Transcription Factors , Tumor Suppressor Protein p53 , Humans , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/deficiency , Apoptosis/drug effects , Transcription Factors/metabolism , Transcription Factors/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Cell Line, Tumor , DNA Damage , Animals , Mice , HCT116 Cells , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Mice, Nude , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cyclin-Dependent Kinase Inhibitor p21/genetics , Furans , Proto-Oncogene Proteins
14.
Article in English | MEDLINE | ID: mdl-38722724

ABSTRACT

The olfactory system enables humans to smell different odors, which are closely related to emotions. The high temporal resolution and non-invasiveness of Electroencephalogram (EEG) make it suitable to objectively study human preferences for odors. Effectively learning the temporal dynamics and spatial information from EEG is crucial for detecting odor-induced emotional valence. In this paper, we propose a deep learning architecture called Temporal Attention with Spatial Autoencoder Network (TASA) for predicting odor-induced emotions using EEG. TASA consists of a filter-bank layer, a spatial encoder, a time segmentation layer, a Long Short-Term Memory (LSTM) module, a multi-head self-attention (MSA) layer, and a fully connected layer. We improve upon the previous work by utilizing a two-phase learning framework, using the autoencoder module to learn the spatial information among electrodes by reconstructing the given input with a latent representation in the spatial dimension, which aims to minimize information loss compared to spatial filtering with CNN. The second improvement is inspired by the continuous nature of the olfactory process; we propose to use LSTM-MSA in TASA to capture its temporal dynamics by learning the intercorrelation among the time segments of the EEG. TASA is evaluated on an existing olfactory EEG dataset and compared with several existing deep learning architectures to demonstrate its effectiveness in predicting olfactory-triggered emotional responses. Interpretability analyses with DeepLIFT also suggest that TASA learns spatial-spectral features that are relevant to olfactory-induced emotion recognition.


Subject(s)
Algorithms , Attention , Deep Learning , Electroencephalography , Emotions , Neural Networks, Computer , Odorants , Humans , Electroencephalography/methods , Emotions/physiology , Attention/physiology , Male , Adult , Female , Smell/physiology , Memory, Short-Term/physiology , Young Adult
15.
J Ethnopharmacol ; 332: 118397, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-38806137

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: WuHuTang (WHT) is a traditional Chinese medicine compound for treating asthma, and the evidence supports that it has a good effect on acute asthma attacks in children and adults. Respiratory syncytial virus (RSV) is an important factor in the pathogenesis of acute asthma attacks, and the effect on dendritic cells is the key to its pathogenesis. Previous studies have confirmed that the pathogenesis of viruses is related to exosomes. However, there are few studies on the exosomes induced by RSV. Whether WHT can improve the changes caused by RSV-induced exosomes or not is worthy of further exploration. AIM OF THE STUDY: We aim to study the effects of RSV-induced exosomes on the function and autophagy of dendritic cells, and to observe the intervention effect of WHT serum on the above effects. METHODS: The co-culture model of exosomes derived from bone marrow mesenchymal stem cells induced by RSV (BMSCs-Exo-RSV) and dendritic cells was established, and then WHT serum was used to intervene. After 24 h of intervention, the CCK-8 method, flow cytometry, Elisa, RT-qCPR, and Western blot were used to detect the above-mentioned culture model. RESULTS: RSV-induced exosomes had certain effects on viability, apoptosis, and costimulatory molecules generation of dendritic cells. At the same time, the levels of IL-6, IL-12, TNF-α, and autophagy increased, while the levels of IL-4, IL-10, and TGF-ß decreased, and the AKT/TSC/mTOR pathway was inhibited. WHT serum could activate this pathway and reverse the above changes in dendritic cells. CONCLUSION: This study reveals that the pathogenic effect of RSV is related to the exosomes induced by RSV. The exosomes induced by RSV affect the function of dendritic cells by inhibiting the AKT/TSC/mTOR pathway, which can be activated by WHT to reverse the effects caused by RSV-induced exosomes.


Subject(s)
Autophagy , Dendritic Cells , Drugs, Chinese Herbal , Exosomes , TOR Serine-Threonine Kinases , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Exosomes/metabolism , Exosomes/drug effects , Autophagy/drug effects , Drugs, Chinese Herbal/pharmacology , Animals , TOR Serine-Threonine Kinases/metabolism , Apoptosis/drug effects , Coculture Techniques , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Respiratory Syncytial Viruses/drug effects , Respiratory Syncytial Viruses/physiology , Cells, Cultured , Proto-Oncogene Proteins c-akt/metabolism , Cytokines/metabolism , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/drug therapy , Cell Survival/drug effects
16.
Cell Signal ; 120: 111220, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38740234

ABSTRACT

Synovitis and cartilage destruction are crucial characteristics of osteoarthritis (OA). Inflammatory cytokines, such as IL-1ß, are secreted by synovial macrophages, leading to cartilage destruction. Pyroptosis is a lytic form of programmed cell death, which could be triggered by the NLRP3 inflammasome of macrophages. Pyroptosis promotes the secretion of IL-1ß and is supposed as a potential biomarker for OA. However, the function of Pyroptosis and NLRP3 inflammasome and its regulatory mechanism for activation is unclear in OA. In this study, we found that Degrasyn could alleviate the GSDMD-mediated pyroptosis of macrophages and the release of IL-1ß, caspase-1, and LDH. Furthermore, it selectively impedes the form of ASC oligomer and speckle to effectively suppress the NLRP3 inflammasome during its assembly phase. Notably, Degrasyn exhibited potential chondroprotective effects in a co-culture system. Additionally, these results also indicate that Degrasyn mitigates synovitis and cartilage damage in a murine model of destabilization of the medial meniscus (DMM)-induced OA. In summary, Degrasyn emerges as a promising pharmaceutical agent for synovitis, paving the way for innovative therapeutic approaches to OA. Our findings underscore the potential of Degrasyn as a viable candidate for OA therapeutics, demonstrating its ability to regulate pyroptosis and NLRP3 inflammasome activation.


Subject(s)
Chondrocytes , Intracellular Signaling Peptides and Proteins , Macrophages , NLR Family, Pyrin Domain-Containing 3 Protein , Osteoarthritis , Phosphate-Binding Proteins , Pyroptosis , Signal Transduction , Pyroptosis/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Animals , Osteoarthritis/metabolism , Osteoarthritis/pathology , Osteoarthritis/drug therapy , Chondrocytes/metabolism , Chondrocytes/drug effects , Chondrocytes/pathology , Mice , Signal Transduction/drug effects , Macrophages/metabolism , Macrophages/drug effects , Phosphate-Binding Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Inflammasomes/metabolism , Mice, Inbred C57BL , Male , Humans , RAW 264.7 Cells , Interleukin-1beta/metabolism , Gasdermins
17.
HGG Adv ; 5(3): 100302, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38704641

ABSTRACT

Polygenic scores (PGSs) summarize the combined effect of common risk variants and are associated with breast cancer risk in patients without identifiable monogenic risk factors. One of the most well-validated PGSs in breast cancer to date is PGS313, which was developed from a Northern European biobank but has shown attenuated performance in non-European ancestries. We further investigate the generalizability of the PGS313 for American women of European (EA), African (AFR), Asian (EAA), and Latinx (HL) ancestry within one institution with a singular electronic health record (EHR) system, genotyping platform, and quality control process. We found that the PGS313 achieved overlapping areas under the receiver operator characteristic (ROC) curve (AUCs) in females of HL (AUC = 0.68, 95% confidence interval [CI] = 0.65-0.71) and EA ancestry (AUC = 0.70, 95% CI = 0.69-0.71) but lower AUCs for the AFR and EAA populations (AFR: AUC = 0.61, 95% CI = 0.56-0.65; EAA: AUC = 0.64, 95% CI = 0.60-0.680). While PGS313 is associated with hormone-receptor-positive (HR+) disease in EA Americans (odds ratio [OR] = 1.42, 95% CI = 1.16-1.64), this association is lost in African, Latinx, and Asian Americans. In summary, we found that PGS313 was significantly associated with breast cancer but with attenuated accuracy in women of AFR and EAA descent within a singular health system in Los Angeles. Our work further highlights the need for additional validation in diverse cohorts prior to the clinical implementation of PGSs.

18.
J Colloid Interface Sci ; 671: 100-109, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38795531

ABSTRACT

There is significant anticipation for high-efficiency and cost-effective non-precious metal-based catalysts to advance the industrial application of the anodic oxygen evolution reaction (OER) for hydrogen production. This study introduces an efficient strategy that utilizes ligand-induced metal-organic framework (MOF) building blocks for the synthesis of hollow binary zeolitic imidazolate frameworks 67 (ZIF-67) and Prussian blue analogues (PBAs) (ZIF-67@PBA) heterostructures through a hybrid MOF-on-MOF approach. Manipulating the Co2+/Zn2+ ratio in the precursor ZIF-67 allows for the convenient synthesis of the final product, denoted as CoxFe-ZP, after pyrolysis, where the inclusion of Zn effectively modulates the distribution of Co in the catalyst. The resulting CoxFe-ZP catalysts exhibit a positive synergistic effect between hollow graphitic carbon nanomaterials and Fe-doped Co nanoparticles. The optimal Co0.3Fe-ZP catalyst demonstrates satisfactory OER performance, achieving an overpotential of 302 mV at 10 mA cm-2 and a small Tafel slope of 60.0 mV dec-1. Further analysis of the activation energy confirms that the enhanced OER activity of Co0.3Fe-ZP can be reasonably attributed to the combined influence of its morphology and composition. This study demonstrates a ligand-induced method for examining the morphology and electrochemical properties of grown binary MOF-on-MOF heterostructures for OER applications.

19.
Arch Oral Biol ; 164: 105989, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38718466

ABSTRACT

OBJECTIVE: To investigate the expression and secretion of epidermal growth factor (EGF) in major and minor salivary gland tissues of human subjects and to examine the potential influence of sex and age on EGF expression and secretion. DESIGN: Saliva samples from the oral cavity at rest and after citric acid stimulation, as well as serum samples, were collected from 150 healthy subjects, and the concentrations of EGF were measured with enzyme-linked immunosorbent assay (ELISA) and compared. The expression of EGF mRNA and protein in normal salivary gland tissues was measured by real-time polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemistry (IHC). RESULTS: The EGF concentration in acid-stimulated saliva was significantly higher than that in resting saliva (P < 0.001), and significantly higher than that in serum (P < 0.001). No sex difference was observed in EGF levels of whole saliva and serum, whereas the EGF levels in saliva and serum were decreased with age (P < 0.001 and P < 0.001, respectively). The EGF concentration and compound secretion rate (CSR) in resting submandibular glands saliva were significantly higher than those in resting parotid glands saliva (P = 0.002 and P < 0.001, respectively). The EGF was expressed in all major and minor salivary glands and ranked in order of submandibular, parotid, sublingual, and labial glands. CONCLUSION: All salivary glands have the function of secreting EGF, and the submandibular gland is the main source of salivary EGF. Aging is a factor influencing the expression and secretion of EGF.


Subject(s)
Blotting, Western , Enzyme-Linked Immunosorbent Assay , Epidermal Growth Factor , Immunohistochemistry , Real-Time Polymerase Chain Reaction , Saliva , Salivary Glands , Humans , Female , Male , Epidermal Growth Factor/metabolism , Adult , Saliva/metabolism , Saliva/chemistry , Middle Aged , Salivary Glands/metabolism , Sex Factors , Aged , Age Factors , RNA, Messenger/metabolism , Adolescent , Submandibular Gland/metabolism , Salivary Glands, Minor/metabolism , Citric Acid/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...