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1.
Sci Rep ; 14(1): 22659, 2024 09 30.
Article in English | MEDLINE | ID: mdl-39349536

ABSTRACT

The prognosis of extensive-stage small cell lung cancer is usually poor. In this study, a combined model based on pre-treatment CT radiomics and clinical features was constructed to predict the OS of extensive-stage small cell lung cancer after chemotherapy with immunotherapy.Clinical data of 111 patients with extensive stage small-cell lung cancer who received first-line immunotherapy combined with chemotherapy in our hospital from December 2019 to December 2021 were retrospectively collected. Finally, 93 patients were selected for inclusion in the study, and CT images were obtained through PACS system before treatment. All patients were randomly divided into a training set (n = 66) and a validation set (n = 27). Images were imported into ITK-SNAP to outline areas of interest, and Python software was used to extract radiomics features. A total of 1781 radiomics features were extracted from each patient's images. The feature dimensions were reduced by MRMR and LASSO methods, and the radiomics features with the greatest predictive value were screened. The weight coefficient of radiomics features was calculated, and the linear combination of the feature parameters and the weight coefficient was used to calculate Radscore. Univariate cox regression analysis was used to screen out the factors significantly associated with prognosis from the radiomics and clinical features, and multivariate cox regression analysis was performed to establish the prognosis prediction model of extensive stage small cell lung cancer. The degree of metastases was selected as a significant clinical prognostic factor by univariate cox regression analysis. Seven radiomics features with significance were selected by LASSO-COX regression analysis, and the Radscore was calculated according to the coefficient of the radiomics features. An alignment diagram survival prediction model was constructed by combining Radscore with the number of metastatic lesions. The study population was stratified into those who survived less than 11 months, and those with a greater than 11 month survival. The C-index was 0.722 (se = 0.044) and 0.68(se = 0.074) in the training and the validation sets, respectively. The Log_rank test results of the combination model were as follows: training set: p < 0.0001, validation set: p = 0.00042. In this study, a combined model based on radiomics and clinical features could predict OS in patients with extensive stage small cell lung cancer after chemotherapy with immunotherapy, which could help guide clinical treatment strategies.


Subject(s)
Immunotherapy , Lung Neoplasms , Small Cell Lung Carcinoma , Tomography, X-Ray Computed , Humans , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/mortality , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Small Cell Lung Carcinoma/diagnostic imaging , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/therapy , Small Cell Lung Carcinoma/mortality , Small Cell Lung Carcinoma/drug therapy , Male , Female , Middle Aged , Immunotherapy/methods , Tomography, X-Ray Computed/methods , Aged , Prognosis , Retrospective Studies , Neoplasm Staging , Risk Assessment , Adult , Radiomics
2.
ACS Appl Mater Interfaces ; 16(36): 48395-48405, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39223074

ABSTRACT

The degeneration of retinal photoreceptors is one of the primary causes of blindness, and the implantation of retinal prostheses offers hope for vision restoration in individuals who are completely blind. Flexible bioelectronic devices present a promising avenue for the next generation of retinal prostheses owing to their soft mechanical properties and tissue friendliness. In this study, we developed flexible composite films of ferroelectric BiFeO3-BaTiO3 (BFO-BTO) particles synthesized by the hydrothermal method and ferroelectric poly(vinyldene difluoride-trifluoroethylene) (P(VDF-TrFE)) polymer and investigated their applications in artificial retinas. Owing to the coupling of the photothermal effect of BFO-BTO particles and the pyroelectric effect of the P(VDF-TrFE) polymer, the composite films demonstrate a strong photoelectric response (a maximum peak-to-peak photovoltage > 80 V under blue light of 100 mW/cm2) in a wide wavelength range of light (from visible to infrared) with the inherent flexibility and ease of preparation, making it an attractive candidate for artificial retinal applications. Experimental results showed that blind rats implanted with artificial retinas of the composites display light-responsive behavior, showcasing the effectiveness of vision restoration. This study demonstrates a novel approach for employing ferroelectric materials in vision restoration and offers insights into future artificial retina design.

4.
Materials (Basel) ; 17(15)2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39124413

ABSTRACT

In this study, the crystal plasticity finite element method was established by coupling the crystal plasticity and finite element method (FEM). The effect of rolling deformation and slip system of polycrystalline Al-Mg-Si aluminum alloy was investigated. The results showed that there was a pronounced heterogeneity in the stress and strain distribution of the material during cold rolling. The maximum strain and shear strain occurred at surface of the material. The smaller the grain size, the lower the strain concentration at the grain boundary. Meanwhile, a smaller strain difference existed between the grain interior and near the boundary. The rotation of grains leads to significant differences in deformation and rotation depending on their initial orientations during the rolling process. The slip system of (11-1)<-110> had a large effect on the plastic deformation, (111)<10-1> is second, and the effect of (1-11)<011> slip system on the plastic deformation is the smallest. After deformation, the grain orientation concentration was increased with deformation. Therefore, both the strength and volume fraction of texture were increased with the increase in rolling deformation. The experimental results of EBSD indicated that the large rolling reduction resulted in severe grain twisting, so the texture strength was increased. The simulation results were in close agreement with the experimental results. This study provides a theoretical basis for the rolling process, microstructure, and performance control of aluminum alloys.

5.
Opt Lett ; 49(15): 4262-4265, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090909

ABSTRACT

Topological edge state, a unique mode for manipulating electromagnetic waves (EMs), has been extensively studied in both fundamental and applied physics. Up to now, the work on topological edge states has focused on manipulating linearly polarized waves. Here, we realize chirality-dependent topological edge states in one-dimensional photonic crystals (1DPCs) to manipulate circularly polarized waves. By introducing the magneto-electric coupling term (chirality), the degeneracy Dirac point (DP) is opened in PCs with symmetric unit cells. The topological properties of the upper and lower bands are different in the cases of left circularly polarized (LCP) and right circularly polarized (RCP) waves by calculating the Zak phase. Moreover, mapping explicitly 1D Maxwell's equations to the Dirac equation, we demonstrate that the introduction of chirality can lead to different topological properties of bandgaps for RCP and LCP waves. Based on this chirality-dependent topology, we can further realize chirality-dependent topological edge states in photonic heterostructures composed of two kinds of PCs. Finally, we propose a realistic structure for the chirality-dependent topological edge states by placing metallic helixes in host media. Our work provides a method for manipulating topological edge states for circularly polarized waves, which has a broad range of potential applications in designing optical devices including polarizers, filters, and sensors with robustness against disorder.

6.
Gen Physiol Biophys ; 43(5): 423-434, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39140685

ABSTRACT

This study was designed to dissect the function of plasmacytoma variant translocation 1 (PVT1) in hippocampal neuron injury in epilepsy and its possible molecular basis. Status epilepticus (SE) mouse model was built and primary hippocampal neurons were isolated. qRT-PCR and Western blot were applied to quantify the levels of related genes and proteins. Cell proliferation and apoptosis were examined by CCK-8, EdU, and flow cytometry assays. Inflammatory factors were detected using ELISA analysis. Dual-luciferase reporter and RIP assays were carried out to validate the relationship between miR-206-3p and PVT1 or CAMK4. PVT1 and CAMK4 were increased, and miR-206-3p was downregulated in the hippocampus and hippocampal neurons of SE mice. Knockdown of PVT1 or CAMK4 abated SE-induced proliferation inhibition, apoptosis, and inflammation in hippocampal neurons. Mechanistically, PVT1 could sponge miR-206-3p to upregulate the expression of CAMK4 in hippocampal neurons. Moreover, downregulation of miR-206-3p reversed the inhibitory effects of PVT1 knockdown on SE-induced apoptosis and inflammation in hippocampal neurons. Similarly, overexpression of CAMK4 abolished miR-206-3p-evoked arrest of apoptosis and inflammation in hippocampal neurons under SE condition. Collectively, PVT1 contributed to SE-induced apoptosis and inflammation in hippocampal neurons by modulating the miR-206-3p/CAMK4 axis, offering a novel insight into the prevention of epilepsy.


Subject(s)
Apoptosis , Calcium-Calmodulin-Dependent Protein Kinase Type 4 , Epilepsy , Hippocampus , MicroRNAs , Neurons , Animals , MicroRNAs/metabolism , MicroRNAs/genetics , Calcium-Calmodulin-Dependent Protein Kinase Type 4/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 4/genetics , Hippocampus/metabolism , Hippocampus/pathology , Apoptosis/genetics , Mice , Neurons/metabolism , Epilepsy/genetics , Epilepsy/metabolism , Inflammation/metabolism , Inflammation/genetics , Mice, Inbred C57BL , Cells, Cultured , Male
7.
Bioact Mater ; 40: 148-167, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38962659

ABSTRACT

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-ß1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1ß) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

8.
Compr Rev Food Sci Food Saf ; 23(4): e13400, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39030813

ABSTRACT

During food production, food processing, and supply chain, large amounts of food byproducts are generated and thrown away as waste, which to a great extent brings about adverse consequences on the environment and economic development. The sweet potato (Ipomoea batatas L.) is cultivated and consumed in many countries. Sweet potato peels (SPPs) are the main byproducts generated by the tuber processing. These residues contain abundant nutrition elements, bioactive compounds, and other high value-added substances; therefore, the reutilization of SPP holds significance in improving their overall added value. SPPs contain abundant phenolic compounds and carotenoids, which might contribute significantly to their nutraceutical properties, including antioxidant, antimicrobial, anticancer, prebiotic, anti-inflammatory, wound-healing, and lipid-lowering effects. It has been demonstrated that SPP could be promisingly revalorized into food industry, including: (1) applications in diverse food products; (2) applications in food packaging; and (3) applications in the recovery of pectin and cellulose nanocrystals. Furthermore, SPP could be used as promising feedstocks for the bioconversion of diverse value-added bioproducts through biological processing.


Subject(s)
Dietary Supplements , Ipomoea batatas , Nutritive Value , Phytochemicals , Ipomoea batatas/chemistry , Dietary Supplements/analysis , Phytochemicals/chemistry , Phytochemicals/analysis , Food Handling/methods , Plant Tubers/chemistry
9.
Drug Dev Res ; 85(5): e22230, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38967729

ABSTRACT

The CDK4/CDK6 inhibitor palbociclib has shown the encouraging promise in the treatment of glioma. Here, we elucidated how palbociclib exerts suppressive functions in the M2 polarization of glioma-related microglia and the progression of glioma. Xenograft experiments were used to evaluate the function in vivo. The mRNA levels of transcription factor 12 (TCF12) and VSIG4 were detected by RT-qPCR, and their protein levels were assessed by immunoblotting. Cell migration was tested by wound-healing assay. Cell cycle distribution and M1/M2 microglia phenotype analysis were performed by flow cytometry. The levels of IFN-γ, TNF-α, IL-6,and TGF-ß were measured by ELISA. The TCF12/VSIG4 association was verified by luciferase reporter and chromatin immunoprecipitation (ChIP) assays. In U251 and LN229 glioma cells, TCF12 and VSIG4 were overexpressed, and palbociclib reduced their expression levels. TCF12 upregulation enhanced the proliferation and migration of glioma cells and the M2 polarization of glioma-associated microglia in vitro as well as the tumorigenicity of U251 glioma cells in vivo, which could be reversed by palbociclib. Mechanistically, TCF12 could enhance VSIG4 transcription and expression by binding to the VSIG4 promoter. TCF12 deficiency led to repression in glioma cell proliferation and migration as well as microglia M2 polarization, which could be abolished by increased VSIG4 expression. Our study reveals the novel TCF12/VSIG4 axis responsible for the efficacy of palbociclib in combating glioma, offering a rationale for the application of palbociclib in glioma treatment.


Subject(s)
Cell Movement , Cell Proliferation , Glioma , Microglia , Piperazines , Pyridines , Humans , Glioma/drug therapy , Glioma/metabolism , Glioma/pathology , Cell Movement/drug effects , Piperazines/pharmacology , Pyridines/pharmacology , Cell Proliferation/drug effects , Microglia/drug effects , Microglia/metabolism , Animals , Cell Line, Tumor , Mice , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Mice, Nude , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Xenograft Model Antitumor Assays , Mice, Inbred BALB C , Antineoplastic Agents/pharmacology , Basic Helix-Loop-Helix Transcription Factors
10.
Pathol Res Pract ; 260: 155438, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38964117

ABSTRACT

The function of glioma stem cells (GSCs) is closely related to the progression of glioblastoma multiforme (GBM). Centromere protein A (CENPA) has been confirmed to be related to the poor prognosis of GBM patients. However, whether CENPA regulates GSCs function to mediate GBM progression is still unclear. GSCs were isolated from GBM cells. The expression of CENPA and guanylate-binding protein 2 (GBP2) was examined by quantitative real-time PCR and western blot. GSCs proliferation and stemness were assessed using EdU assay and sphere formation assay. Cell ferroptosis was evaluated by detecting related factors. The interaction between CENPA and GBP2 was analyzed by ChIP assay and dual-luciferase reporter assay. Animal experiments were conducted to measure the effect of CENPA knockdown on the tumorigenicity of GSCs in vivo. CENPA was upregulated in GBM tissues and GSCs. CENPA knockdown inhibited GSCs proliferation, stemnness, and promoted ferroptosis. GBP2 was overexpressed in GBM tissues and GSCs, and CENPA enhanced GBP2 transcription by binding to its promoter region. CENPA overexpression accelerated GSCs proliferation and stemnness and suppressed ferroptosis, while GBP2 knockdown reversed these effects. Downregulation of CENPA reduced the tumorigenicity of GSCs by decreasing GBP2 expression in vivo. In conclusion, CENPA enhanced GBP2 transcription to increase its expression, thus accelerating GSCs proliferation and stemnness and repressing ferroptosis. Our findings promote a new idea for GBM treatment.


Subject(s)
Brain Neoplasms , Ferroptosis , Glioblastoma , Neoplastic Stem Cells , Ferroptosis/genetics , Ferroptosis/physiology , Humans , Glioblastoma/pathology , Glioblastoma/genetics , Glioblastoma/metabolism , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Animals , GTP-Binding Proteins/metabolism , GTP-Binding Proteins/genetics , Disease Progression , Chromosomal Proteins, Non-Histone/metabolism , Chromosomal Proteins, Non-Histone/genetics , Gene Expression Regulation, Neoplastic/genetics , Mice , Cell Proliferation/genetics , Cell Line, Tumor , Mice, Nude
11.
Cancer Med ; 13(11): e7374, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38864473

ABSTRACT

PURPOSE: Radical surgery, the first-line treatment for patients with hepatocellular cancer (HCC), faces the dilemma of high early recurrence rates and the inability to predict effectively. We aim to develop and validate a multimodal model combining clinical, radiomics, and pathomics features to predict the risk of early recurrence. MATERIALS AND METHODS: We recruited HCC patients who underwent radical surgery and collected their preoperative clinical information, enhanced computed tomography (CT) images, and whole slide images (WSI) of hematoxylin and eosin (H & E) stained biopsy sections. After feature screening analysis, independent clinical, radiomics, and pathomics features closely associated with early recurrence were identified. Next, we built 16 models using four combination data composed of three type features, four machine learning algorithms, and 5-fold cross-validation to assess the performance and predictive power of the comparative models. RESULTS: Between January 2016 and December 2020, we recruited 107 HCC patients, of whom 45.8% (49/107) experienced early recurrence. After analysis, we identified two clinical features, two radiomics features, and three pathomics features associated with early recurrence. Multimodal machine learning models showed better predictive performance than bimodal models. Moreover, the SVM algorithm showed the best prediction results among the multimodal models. The average area under the curve (AUC), accuracy (ACC), sensitivity, and specificity were 0.863, 0.784, 0.731, and 0.826, respectively. Finally, we constructed a comprehensive nomogram using clinical features, a radiomics score and a pathomics score to provide a reference for predicting the risk of early recurrence. CONCLUSIONS: The multimodal models can be used as a primary tool for oncologists to predict the risk of early recurrence after radical HCC surgery, which will help optimize and personalize treatment strategies.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Machine Learning , Neoplasm Recurrence, Local , Tomography, X-Ray Computed , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Liver Neoplasms/diagnostic imaging , Male , Female , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Aged , Hepatectomy , Adult , Radiomics
12.
Int J Biol Macromol ; 273(Pt 1): 132889, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38844288

ABSTRACT

HZMP-1 is a new polysaccharide isolated from Huang Zhen mycoplasm that contains seven monosaccharides, and it has an average molecular weight of 16.817 kDa. Its structural characteristics indicate that the surface of HZMP-1 is dense and rough, with some irregular protrusions. Animal experiments have shown that HZMP-1 can enhance liver protection, affect lipid-lowering indicators by reducing those related to lipid accumulation and damage in the serum and liver, upregulate genes that accelerate liver lipid oxidation and transport, downregulate genes that promote lipid deposition in the liver, increase the expression of lipid degradation proteins in the liver, and reduce the expression of lipid synthesis proteins. The improvement effect of HZMP-1 on NAFLD was further demonstrated using metabolomics methods. The results of this study indicated that HZMP-1 extracted from Huang Zhen mycoplasm significantly alleviates HFD-induced NAFLD in mice and has good potential for preventing and treating NAFLD.


Subject(s)
Diet, High-Fat , Liver , Metabolomics , Non-alcoholic Fatty Liver Disease , Polysaccharides , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/prevention & control , Diet, High-Fat/adverse effects , Mice , Liver/drug effects , Liver/metabolism , Liver/pathology , Polysaccharides/pharmacology , Polysaccharides/chemistry , Male , Lipid Metabolism/drug effects
13.
Curr Probl Cancer ; 50: 101098, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38704949

ABSTRACT

OBJECTIVE: To investigate the relationship between clinical pathological characteristics, pretreatment CT radiomics, and major pathologic response (MPR) of non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy, and to establish a combined model to predict the major pathologic response of neoadjuvant chemoimmunotherapy. METHODS: A retrospective study of 211 patients with NSCLC who underwent neoadjuvant chemoimmunotherapy and surgical treatment from January 2019 to April 2021 was conducted. The patients were divided into two groups: the MPR group and the non-MPR group. Pre-treatment CT images were segmented using ITK SNAP software to extract radiomics features using Python software. Then a radiomics model, a clinical model, and a combined model were constructed and validated using a receiver operating characteristic (ROC) curve. Finally, Delong's test was used to compare the three models. RESULTS: The radiomics model achieved an AUC of 0.70 (95 % CI: 0.62-0.78) in the training group and 0.60 (95 % CI: 0.45-0.76) in the validation group. RECIST assessment results were screened from all clinical characteristics as independent factors for MPR with multivariate logistic regression analysis. The AUC of the clinical model for predicting MPR was 0.66 (95 % CI: 0.59-0.73) in the training group and 0.77 (95 % CI: 0.66-0.87) in the validation group. The combined model with combined radiomics and clinicopathological characteristics achieved an AUC was 0.76 (95 % CI: 0.68-0.84) in the training group, and 0.80 (95 % CI: 0.67-0.92) in the validation group. Delong's test showed that the AUC of the combined model was significantly higher than that of the radiomics model alone in both the training group (P = 0.0067) and the validation group (P = 0.0009).The calibration curve showed good agreement between predicted and actual MPR. Clinical decision curve analysis showed that the combined model was superior to radiomics alone. CONCLUSIONS: Radiomics model can predict MPR in NSCLC after neoadjuvant chemoimmunotherapy with similar accuracy to RECIST assessment criteria. The combined model based on pretreatment CT radiomics and clinicopathological features showed better predictive power than independent radiomics model or independent clinicopathological features, suggesting that it may be more useful for guiding personalized neoadjuvant chemoimmunotherapy treatment strategies.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neoadjuvant Therapy , Tomography, X-Ray Computed , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Male , Female , Neoadjuvant Therapy/methods , Retrospective Studies , Middle Aged , Tomography, X-Ray Computed/methods , Aged , Immunotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis , Adult , Radiomics
14.
Redox Biol ; 73: 103196, 2024 07.
Article in English | MEDLINE | ID: mdl-38772149

ABSTRACT

Hippocampal neural stem/progenitor cells (NSPCs) are highly vulnerable to different stress stimuli, resulting in adult neurogenesis decline and eventual cognitive defects. Our previous study demonstrated that NOD-like receptor family pyrin domain-containing 6 (Nlrp6) highly expressed in NSPCs played a critical role in sustaining hippocampal neurogenesis to resist stress-induced depression, but the underlying mechnistms are still unclear. Here, we found that Nlrp6 depletion led to cognitive defects and hippocampal NSPC loss in mice. RNA-sequencing analysis of the primary NSPCs revealed that Nlrp6 deficiency altered gene expression profiles of mitochondrial energy generation and ferroptotic process. Upon siNlrp6 transfection, as well as corticosterone (CORT) exposure, downregulation of Nlrp6 suppressed retinoic acid-inducible gene I (RIG-1)/mitochondrial antiviral signaling proteins (MAVS)-mediated autophagy, but drove NSPC ferroptotic death. More interesting, short chain fatty acids (SCFAs) upregulated Nlrp6 expression and promoted RIG-1/MAVS-mediated mitophagy, preventing CORT-induced NSPC ferroptosis. Our study further demonstrates that Nlrp6 should be a sensor for RIG-1/MAVS-mediated mitophagy and play a critical role in maintain mitochondrial homeostasis of hippocampal NSPCs. These results suggests that Nlrp6 should be a potential drug target to combat neurodegenerative diseases relative with chronic stress.


Subject(s)
Adaptor Proteins, Signal Transducing , Corticosterone , DEAD Box Protein 58 , Ferroptosis , Mitophagy , Neural Stem Cells , Animals , Mice , DEAD Box Protein 58/metabolism , DEAD Box Protein 58/genetics , Corticosterone/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Neural Stem Cells/metabolism , Hippocampus/metabolism , Mitochondria/metabolism , Signal Transduction , Receptors, Cell Surface
15.
Materials (Basel) ; 17(3)2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38591593

ABSTRACT

To solve problems in dissimilarly light metal joints, refilled friction stir spot welding (RFSSW) is proposed instead of resistance spot welding. However, rotation speed, dwell time, plunge depth, and the diameter of welding tools all have a great influence on joints, which brings great challenges in optimizing welding parameters to ensure their mechanical properties. In this study, the 1.5 mm thick 2A12Al and 2 mm thick 7B04Al lap joints were prepared by Taguchi orthogonal experiment design and RFSSW. The welding tool (shoulder) diameters were 5 mm and 7 mm, respectively. The macro/microstructures of the cross-section, the geometrical characteristics of the effective welding depth (EWD), the stir zone area (SZA), and the stir zone volume (SZV) were characterized. The shear strength and failure mode of the lap joint were analyzed using an optical microscope. It was found that EWD, SZA, and SZV had a good correlation with tensile-shear force. The optimal welding parameters of 5 mm diameter joints are 1500 rpm of rotation speed, 2.5 mm of plunge depth, and 0 s of dwell time, which for 7 mm joints are 1200 rpm, 1.5 mm, and 2 s. The tensile-shear force of 5 mm and 7 mm joints welded with these optical parameters was 4965 N and 5920 N, respectively. At the same time, the 5 mm diameter joints had better strength and strength stability.

17.
Int J Immunogenet ; 51(3): 157-163, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38441233

ABSTRACT

Genome-wide association study identified common variants within the ALDH1A2 gene as the susceptible loci of hand osteoarthritis (HOA) in UK and Iceland populations. Located in chromosome 15, ALDH1A2 encodes aldehyde dehydrogenase family 1 member A2, which is an enzyme that catalyses the synthesis of retinoic acid from retinaldehyde. Our purposes were to replicate the association of functional variant in ALDH1A2 with the development of HOA in the Chinese population. Variant rs12915901 of ALDH1A2 was genotyped in 872 HOA patients and 1223 healthy controls. Subchondral bone samples were collected from 40 patients who had undergone a trapeziectomy, and the tissue expression of ALDH1A2 was analysed. The chi-square analysis was used to compare the frequency of genotype and risk allele between the HOA cases and controls. The Student t test was used to compare the mRNA expression of ALDH1A2 between patients with genotype AA/AG and those with genotype GG. The frequency of genotype AA was significantly higher in HOA patients than in the controls (7.6% vs. 5.1%, p = .01). The frequency of allele A was significantly higher in the patients than in the controls (28.9% vs. 24.6%, p = .005). The mRNA expression of ALDH1A2 was 1.31-folds higher in patients with genotype GG than in the patients with genotype AA/AG (0.000617 ± 0.000231 vs. 0.000471 ± 0.000198, p = .04). Variant rs12915901 of ALDH1A2 contributed to the susceptibility of HOA in the Chinese population. Allele A of rs12915901 can add to the risk of HOA possibly via down-regulation of ALDH1A2 expression.


Subject(s)
Aldehyde Dehydrogenase 1 Family , Asian People , Genetic Predisposition to Disease , Genotype , Osteoarthritis , Polymorphism, Single Nucleotide , Adult , Aged , Female , Humans , Male , Middle Aged , Aldehyde Dehydrogenase 1 Family/genetics , Alleles , Asian People/genetics , Case-Control Studies , China , East Asian People , Gene Frequency , Genome-Wide Association Study , Hand/pathology , Osteoarthritis/genetics , Osteoarthritis/pathology
18.
Phys Rev Lett ; 132(6): 066602, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38394559

ABSTRACT

It is commonly believed that topologically nontrivial one-dimensional systems support edge states rather than bulk states at zero energy. In this work, we find an unanticipated case of topological Anderson insulator (TAI) phase where two bulk modes are degenerate at zero energy, in addition to degenerate edge modes. We term this "ungapped TAI" to distinguish it from the previously known gapped TAIs. Our experimental realization of both gapped and ungapped TAIs relies on coupled photonic resonators, in which the disorder in coupling is judiciously engineered by adjusting the spacing between the resonators. By measuring the local density of states both in the bulk and at the edges, we demonstrate the existence of these two types of TAIs, together forming a TAI plateau in the phase diagram. Our experimental findings are well supported by theoretical analysis. In the ungapped TAI phase, we observe stable coexistence of topological edge states and localized bulk states at zero energy, highlighting the distinction between TAIs and traditional topological insulators.

19.
Nat Commun ; 15(1): 1131, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38326351

ABSTRACT

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.


Subject(s)
Artificial Intelligence , Liver Neoplasms , Humans , Retrospective Studies , Radiologists , Liver Neoplasms/diagnostic imaging
20.
Neurochirurgie ; 70(2): 101538, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38311218

ABSTRACT

BACKGROUND: Genetic polymorphism of KIAA1217 has been reported to be associated with lumbar disc herniation (LDH) in different populations such as Japanese population and Finnish population. This study aimed to explore whether the genetic polymorphism of KIAA1217 is functionally associated with LDH in Chinese population. METHODS: SNP rs16924573 of KIAA1217 was genotyped in 1272 patients and 1248 healthy controls. The mRNA expression of KIAA1217 in the intervertebral disc was analyzed for 84 patients and 32 controls. The differences of genotype and allele distributions between LDH patients and healthy controls were evaluated using the Chi-square test. One-way ANOVA test was used to compare the relationship between genotypes and tissue expression of KIAA1217. RESULTS: Patients were found to have significantly higher frequency of genotype GG of rs16924573 than the controls (64.2% vs. 52.8%, p<0.001). The frequency of allele G was remarkably higher in the patients than in the controls (79.8% vs. 73.2%, p<0.001), with an OR of 1.45 (95% confidential interval=1.27-1.66). Compared with the controls, LDH patients were observed to have significantly decreased expression of KIAA1217. Patients with genotype GG had remarkably lower mRNA expression of KIAA1217 than those with genotype AG or AA (p=0.01). CONCLUSIONS: SNP rs16924573 of KIAA1217 could be functionally associated with LDH in the Chinese population. More in vivo and vitro experiments need to be carried out to further clarify the regulatory mechanism of functional variants in KIAA1217.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Humans , Case-Control Studies , China/epidemiology , Genetic Predisposition to Disease/genetics , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Displacement/genetics , Lumbar Vertebrae , Polymorphism, Single Nucleotide/genetics , RNA, Messenger
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