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1.
Front Psychol ; 15: 1402021, 2024.
Article in English | MEDLINE | ID: mdl-39355289

ABSTRACT

Introduction: Children are naturally curious and often have limited self-control, leading them to imitate both safe and dangerous actions. This study aimed to investigate whether dangerous cues could effectively inhibit children's imitation of hazardous behaviors and to compare the effectiveness of picture cues versus word cues in reducing this imitation. Methods: Seventy-six children were divided into two groups: one group received picture cues, and the other received word cues. Both groups observed an agent grasping an object and were instructed to perform a corresponding keystroke response when a number appeared. A comparable group of adults was also included for reference. Results: The results demonstrated that picture cues were significantly more effective than word cues in reducing the children's tendency to imitate dangerous actions. Discussion: These findings suggest that picture cues are a more effective method for preventing imitation of risky behaviors in children, which has important implications for improving safety education and accident prevention strategies through the use of visual danger cues.

3.
Clin Nucl Med ; 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39354687

ABSTRACT

ABSTRACT: Solitary fibrous tumors (SFTs) are fibroblast tumors that occur mainly in the pleura. Hepatic SFT with skeleton metastases was rarely documented. In this case, we report the contrast-enhanced CT, 18F-FDG, and 68Ga-FAPI-46 PET/CT findings of a rare hepatic SFT with bone metastases. 68Ga-FAPI-46 PET/CT showed much higher tumor-to-background contrast of hepatic tumors and revealed more metastatic bone lesions than 18F-FDG PET/CT. This case demonstrated the superiority of 68Ga-FAPI-46 PET/CT over 18F-FDG for identifying metastatic lesions in malignant SFTs. This observation may add information on the benefit of FAPI PET/CT in SFT staging.

4.
Emerg Med Int ; 2024: 6397444, 2024.
Article in English | MEDLINE | ID: mdl-39224863

ABSTRACT

Objective: To conduct a systematic review and meta-analysis of the all-cause mortality associated with the most commonly used hemostatic treatments in patients with hemodynamically unstable pelvic fractures. Methods: Up to April 30, 2023, we searched PubMed, Embase, Web of Science, and Cochrane, including the references to qualified papers. A meta-analysis was performed on studies that reported odds ratios (ORs) or the number of events needed to calculate them. The PROSPERO registration number was CRD42023421137. Results: Of the 3452 titles identified in our original search, 29 met our criteria. Extraperitoneal packing (EPP) (OR = 0.626 and 95% CI = 0.413-0.949), external fixation (EF) (OR = 0.649 and 95% CI = 0.518-0.814), and arterial embolism (AE) (OR = 0.459 and 95% CI = 0.291-0.724) were associated with decreased mortality. Resuscitative endovascular balloon occlusion of the aorta (REBOA) (OR = 2.824 and 95% CI = 1.594-5.005) was associated with increased mortality. A random effect model meta-analysis of eight articles showed no difference in mortality between patients with AE and patients with EPP for the initial treatments for controlling blood loss (OR = 0.910 and 95% CI = 0.623-1.328). Conclusion: This meta-analysis collectively suggested EF, AE, or EPP as life-saving procedures for patients with hemodynamically unstable pelvic fractures.

5.
J Am Chem Soc ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39316512

ABSTRACT

Sustainable electricity-to-chemical conversion via the utilization of artificial catalysts inspired by redox biological systems holds great significance for catalyzing synthesis. Herein, we develop a biomimetic electrosynthesis strategy mediated by a nicotinamide adenine dinucleotide (NADH) mimic-containing coordination capsule for efficiently producing α-hydroxy/amino esters. The coordination saturated metal centers worked as an electron relay to consecutively accept single electrons while donating two electrons to the NAD+ mimics simultaneously. The protonation of the intermediate generated active NADH mimics for biomimetic hydrogenation of the substrates via the conventional enzymatic manifold with or without the presence of natural enzymes. The pocket of the capsule encapsulated the substrate and enforced the close proximity between the substrate and the NADH mimics, forming a preorganized intermediate to shift the redox potential by 0.4 V anodically. The cobalt capsule gave methyl mandelate over a range of applied potentials, with an improved yield of 92% when operated at -1.2 V compared to that of Hantzsch ester or natural NADH. Kinetic experiments revealed a Michaelis-Menten mechanism with a Km of 7.5 mM and a Kcat of 1.1 × 10-2 s-1. This extended strategy in tandem with an enzyme exhibited a TON of 650 molE-1 with an initial TOF of 185 molE-1·h-1, outperforming relevant Rh-mediated enzymatic electrosynthesis systems and providing an attractive avenue toward advanced artificial electrosynthesis.

6.
Article in English | MEDLINE | ID: mdl-39316524

ABSTRACT

Objectives: The therapeutic effect of platelet-rich plasma on lower extremity venous ulcers was systematically analyzed. Methods: A computerized system search was conducted to screen literature that met the inclusion criteria using the method of "subject words + free words." Keywords included "platelet-rich plasma," "lower extremity venous disease," "lower extremity chronic venous insufficiency," "venous ulcer," and "lower extremity venous ulcer." Literature that met the inclusion criteria was searched in four commonly used Chinese databases (HowNet, Chinese biomedical literature, Wanfang, and VIP) and three commonly used foreign databases (Embase, PubMed, and Cochrane Library). The search period extended from the establishment of the databases to December 2021. After extracting the relevant data, a meta-analysis was performed using RevMan 5.3 software to compare the overall effective rate and adverse effects of platelet-rich plasma in the treatment of lower extremity venous ulcers. Results: The meta-analysis of the overall efficacy rate in the four selected papers showed no heterogeneity among the studies (P = .35 > 0.1, I2 = 0% < 50%); therefore, a fixed-effect model was used to combine the statistical data. The software analysis results indicated a significant difference in the overall efficacy rate between the experimental group and the control group (OR = 2.09, 95% CI = 1.23-3.34, P = .002), with the experimental group showing better results than the control group. The analysis of the four selected papers also suggested potential differences in adverse reactions between the two groups after treatment, but the comparison of safety differences was not significant (OR = 2.13, 95% CI = 0.45-6.79, P = .17). Conclusion: Platelet-rich plasma is effective in the treatment of lower extremity venous ulcers; however, there is no clear safety advantage. This finding needs to be confirmed by large-scale, multi-center research.

7.
Ultramicroscopy ; 267: 114048, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39303670

ABSTRACT

Imaging nanomaterials in hybrid systems is critical to understanding the structure and functionality of these systems. However, current technologies such as scanning electron microscopy (SEM) may obtain high resolution/contrast images at the cost of damaging or contaminating the sample. For example, to prevent the charging of organic substrate/matrix, a very thin layer of metal is coated on the surface, which will permanently contaminate the sample and eliminate the possibility of reusing it for following processes. Conversely, examining the sample without any modifications, in pursuit of high-fidelity digital images of its unperturbed state, can come at the cost of low-quality images that are challenging to process. Here, a solution is proposed for the case where no brightness threshold is available to reliably judge whether a region is covered with nanomaterials. The method examines local brightness variability to detect nanomaterial deposits. Very good agreement with manually obtained values of the coverage is observed, and a strong case is made for the method's automatability. Although the developed methodology is showcased in the context of SEM images of Polydimethylsiloxane (PDMS) substrates on which silicone dioxide (SiO2) nanoparticles are assembled, the underlying concepts may be extended to situations where straightforward brightness thresholding is not viable.

8.
Neural Netw ; 180: 106708, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39276589

ABSTRACT

Neural network pruning provides a promising prospect for the deployment of neural networks on embedded or mobile devices with limited resources. Although current structured strategies are unconstrained by specific hardware architecture in the phase of forward inference, the decline in classification accuracy of structured methods is beyond the tolerance at the level of general pruning rate. This inspires us to develop a technique that satisfies high pruning rate with a small decline in accuracy and has the general nature of structured pruning. In this paper, we propose a new pruning method, namely KEP (Kernel Elements Pruning), to compress deep convolutional neural networks by exploring the significance of elements in each kernel plane and removing unimportant elements. In this method, we apply a controllable regularization penalty to constrain unimportant elements by adding a prior knowledge mask and obtain a compact model. In the calculation procedure of forward inference, we introduce a sparse convolution operation which is different from the sliding window to eliminate invalid zero calculations and verify the effectiveness of the operation for further deployment on FPGA. A massive variety of experiments demonstrate the effectiveness of KEP on two datasets: CIFAR-10 and ImageNet. Specially, with few indexes of non-zero weights introduced, KEP has a significant improvement over the latest structured methods in terms of parameter and float-point operation (FLOPs) reduction, and performs well on large datasets.

9.
Patient Prefer Adherence ; 18: 1979-1989, 2024.
Article in English | MEDLINE | ID: mdl-39345757

ABSTRACT

Aim: Patients with lung cancer often experience a high level of self-perceived burden, which significantly affects their quality of life and psychological health. Social support is closely related to the self-perceived burden, yet there is scant research on the relationship between social support, facilitation of patient involvement, and self-perceived burden. This study aims to understand the current situation of self-perceived burden in postoperative lung cancer patients and to explore the mediating role of social support between facilitation of patient involvement and self-perceived burden. Methods: A cross-sectional design was used in this study. Using a convenience sampling method, a total of 331 lung cancer patients who were hospitalized for surgical treatment at a tertiary cancer hospital in Beijing, China, from August 2022 to May 2023, were selected to participate in this survey. The survey included a self-designed sociodemographic questionnaire, the Facilitation of Patient Involvement Scale (FPIS), the Perceived Social Support Scale (PSSS), and the Self-Perceived Burden Scale (SPBS). Data were analyzed using SPSS 24.0 for statistical description and Pearson correlation analysis, while AMOS 24.0 was utilized to construct a structural equation model to examine the mediation effect. Results: The score of self-perceived burden in lung cancer patients was 26.42 ±8.23 points. Bot facilitation of patient involvement and social support was negatively correlated with self-perceived burden (r = -0.313, r = -0.332, P < 0.001). Social support plays a partially mediated role in the relationship between facilitation of patient involvement and self-perceived burden, accounting for 44.3% of the total effect. Conclusion: The self-perceived burden of patients after lung cancer surgery was at a moderate level, and social support partially mediates the relationship between facilitation of patient involvement and self-perceived burden. Medical staff should encourage patient participation in their own treatment decisions and alleviate the burden associated with lung cancer and surgical treatment by enhancing their social support.

10.
Redox Biol ; 77: 103370, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39342744

ABSTRACT

Bronchopulmonary dysplasia (BPD) is a severe lung disease in preterm infants, the abnormal proliferate and differentiate ability of type II epithelial cells (AEC II) is the key to the pathological basis of BPD. Mechanisms regarding abnormal AEC II in BPD remain unclear. The present work investigated the role and mechanisms of invariant natural killer T (iNKT) cells in lung disorder in BPD using public datasets, clinical samples, a hyperoxia-induced BPD mouse model and AEC II-iNKT cells transwell co-culture system. Firstly, we found that the NKT cells development factor IL-15 increased over time in patients with BPD in public databases, and clinically collected peripheral blood NKT cells in patients with BPD were increased. Subsequently, the percentage of iNKT cells increased in hyperoxia group compared with normoxia group, with the highest at P7, accompanied by increased activation with abnormal lung development. The administration of anti-CD1d neutralizing antibody to inhibit iNKT cells could alleviate the abnormal lung development of hyperoxia group mice, while α-GalCer administration could aggravate lung injury in hyperoxia group mice, and adoptive transfer of iNKT cells could aggravate the abnormal lung development in hyperoxia group mice. In addition, to further verify the role of iNKT cells on AEC II, AEC II-iNKT cells co-culture system was established. The presence of iNKT cells could aggravate the abnormal expression of SP-C and T1α under hyperoxia. Meanwhile, RNA-seq analysis showed that ferroptosis-related genes were highly expressed in AEC II co-cultured with iNKT cells under hyperoxia. We further validated the effect of the presence of iNKT cells under hyperoxia environment on AEC II ferroptosis levels, suggested that iNKT cells promote AEC II ferroptosis under hyperoxia, accompanied by decreased expression of SP-C and T1α. Our study found that the recruitment of iNKT cells in the lung may be an important cause of alveolarization disorder in BPD.

11.
Environ Sci Technol ; 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39344309

ABSTRACT

This paper describes one of the first studies applying wastewater surveillance to monitor Chlamydia and Syphilis and back-estimate infections in the community, based on bacterial shedding and wastewater surveillance data. Molecular biology laboratory methods were optimized, and a workflow was designed to implement wastewater surveillance tracking Chlamydia and Syphilis in the Detroit metro area (DMA), one of the most populous metropolitan areas in the U.S. Untreated composite wastewater samples were collected weekly from the three main interceptors that service DMA, which collect wastewater and discharge it to the Great Lakes Water Authority Water Resource Recovery Facility. Additionally, untreated wastewater was also collected from street manholes in three neighborhood sewersheds in Wayne, Macomb, and Oakland counties. Centrifugation, DNA extraction, and ddPCR methods were optimized and performed, targeting Chlamydia trachomatis and Treponema pallidum, the causative agents of Chlamydia and Syphilis, respectively. The limit of blank and limit of detection methods were determined experimentally for both targets. Both targets were detected and monitored in wastewater between December 25th, 2023, and April 22nd, 2024. The magnitudes of C. trachomatis and T. pallidum concentrations observed in neighborhood sewersheds were higher as compared to the concentrations observed in the interceptors. Infections of Chlamydia and Syphilis were back-estimated through an optimized formula based on shedding dynamics and wastewater surveillance data, which indicated potentially underreported conditions relative to publicly available clinical data.

12.
Int J Mol Sci ; 25(17)2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39273445

ABSTRACT

Limb muscle is responsible for physical activities and myogenic cell migration during embryogenesis is indispensable for limb muscle formation. Maternal obesity (MO) impairs prenatal skeletal muscle development, but the effects of MO on myogenic cell migration remain to be examined. C57BL/6 mice embryos were collected at E13.5. The GeoMx DSP platform was used to customize five regions along myogenic cell migration routes (myotome, dorsal/ventral limb, limb stroma, limb tip), and data were analyzed by GeomxTools 3.6.0. A total of 2224 genes were down-regulated in the MO group. The GO enrichment analysis showed that MO inhibited migration-related biological processes. The signaling pathways guiding myogenic migration such as hepatocyte growth factor signaling, fibroblast growth factor signaling, Wnt signaling and GTPase signaling were down-regulated in the MO E13.5 limb tip. Correspondingly, the expression levels of genes involved in myogenic cell migration, such as Pax3, Gab1, Pxn, Tln2 and Arpc, were decreased in the MO group, especially in the dorsal and ventral sides of the limb. Additionally, myogenic differentiation-related genes were down-regulated in the MO limb. MO impedes myogenic cell migration and differentiation in the embryonic limb, providing an explanation for the impairment of fetal muscle development and offspring muscle function due to MO.


Subject(s)
Cell Differentiation , Cell Movement , Muscle Development , Obesity, Maternal , Animals , Cell Movement/genetics , Mice , Female , Muscle Development/genetics , Cell Differentiation/genetics , Pregnancy , Obesity, Maternal/metabolism , Obesity, Maternal/genetics , Mice, Inbred C57BL , Gene Expression Regulation, Developmental , Transcriptome , Embryonic Development/genetics , Extremities/embryology , Gene Expression Profiling , Signal Transduction , Muscle, Skeletal/metabolism , Muscle, Skeletal/embryology
13.
Article in English | MEDLINE | ID: mdl-39327976

ABSTRACT

Children with extracranial high-risk neuroblastoma (NB) have a poor prognosis due to resistance against apoptosis. Recently, ferroptosis, another form of programmed cell death, has been tested in clinical trials for high-risk NB; however, drug resistance and side effects have also been observed. Here, we find that the gold element in gold nanoclusters can significantly affect iron metabolism and sensitize high-risk NB cells to ferroptosis. Accordingly, we developed a gold nanocluster conjugated with a modified NB-targeting peptide. This gold nanocluster, namely, NANT, shows excellent NB targeting efficiency and dramatically promotes ferroptosis. Surprisingly, this effect is exerted by elevating the noncanonical ferroptosis pathway, which is dependent on heme oxygenase-1-regulated Fe(II) accumulation. Furthermore, NANT dramatically inhibits the growth of high-risk NB in both tumor spheroid and xenograft models by promoting noncanonical ferroptosis evidenced by enhanced intratumoral Fe(II) and heme oxygenase-1. Importantly, this strategy shows excellent cardiosafety, offering a promising strategy to overcome ferroptosis resistance for the efficient and safe treatment of children with high-risk neuroblastoma.

14.
Sheng Wu Gong Cheng Xue Bao ; 40(9): 2934-2947, 2024 Sep 25.
Article in Chinese | MEDLINE | ID: mdl-39319716

ABSTRACT

Cardiovascular diseases are major diseases, and there is lack of artificial blood vessels with small diameters which can be applied in coronary artery bypass surgery. The conventional vascular scaffold preparation techniques in tissue engineering have shortcomings in regulating the diameter, geometric shape, and interconnectivity of the scaffold. 3D bioprinting can simulate the natural structure of the vascular tissue, accurately print live cells and biomaterials, and regulate the microstructure and porosity of scaffolds on the nanoscale, providing new ideas for vascular tissue engineering. This article systematically evaluates the classification of 3D bioprinting technologies and reviews the latest research progress of 3D bioprinting in vascular tissue engineering. It summarizes the advantages of 3D bioprinting and points out the problems that need to be solved, such as the immune rejection of blood vessel materials, providing reference for the further research.


Subject(s)
Bioprinting , Printing, Three-Dimensional , Tissue Engineering , Tissue Scaffolds , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Humans , Blood Vessels , Biocompatible Materials , Blood Vessel Prosthesis
15.
Foods ; 13(17)2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39272460

ABSTRACT

Diabetes mellitus (DM), a major cause of mortality, is characterized by insulin resistance and ß-cell dysfunction. The increasing prevalence of DM is linked to lifestyle changes and there is a need for alternative approaches to conventional oral hypoglycemic agents. Polysaccharides, particularly non-starch polysaccharides (NSPs), have been identified as promising hypoglycemic agents. Cereals, especially wheat, are key sources of dietary polysaccharides, with NSPs derived from wheat beer attracting significant interest. This study aimed to investigate the hypoglycemic and hypolipidemic effects of NSPs extracted from wheat beer in STZ-induced diabetic C57BL/6J male mice. The results showed that NSPs extract positively influenced blood glucose regulation, lipid profiles, and liver and kidney functions, by attenuating liver AST and kidney CRE levels in a dose-dependent manner. The NSPs demonstrated anti-oxidative and anti-inflammatory properties, potentially providing significant benefits in managing diabetes and its complications. Moreover, the study revealed the histoprotective effects of NSPs on the liver and pancreas, reducing lipid deposition, necrosis, and inflammation. These findings highlight the multifaceted advantages of NSPs and suggest their potential as effective agents in diabetes management. This study supports the need for further research into the therapeutic potential of NSPs and their application in developing innovative treatments for diabetes and its associated complications.

16.
Theranostics ; 14(13): 5316-5335, 2024.
Article in English | MEDLINE | ID: mdl-39267778

ABSTRACT

Background: Enhancing white adipose tissue (WAT) browning combats obesity. The RIIß subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RIIß gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored. Methods: This study investigates the mechanisms underlying WAT browning in RIIß-KO mice. Genetic approaches such as ß3-adrenergic receptors (ß3ARs) deletion and sympathetic denervation of WAT were utilized. Genome-wide transcriptomic sequencing and bioinformatic analysis were employed to identify potential mediators of WAT browning. siRNA assays were employed to knock down mTOR and lipin1 in vitro, while AAV-shRNAs were used for the same purpose in vivo. Results: We found that WAT browning substantially contributes to the lean and obesity-resistant phenotypes of RIIß-KO mice. The WAT browning can be dampened by ß3ARs deletion or WAT sympathetic denervation. We identified that adipocytic mTOR and lipin1 may act as mediators of the WAT browning. Inhibition of mTOR or lipin1 abrogates WAT browning and hinders the lean phenotype of RIIß-KO mice. In human subcutaneous white adipocytes and mouse white adipocytes, ß3AR stimulation can activate mTOR and causes lipin1 nuclear translocation; knockdown of mTOR and Lipin1 mitigates WAT browning-associated gene expression, impedes mitochondrial activity. Moreover, mTOR knockdown reduces lipin1 level and nuclear translocation, indicating that lipin1 may act downstream of mTOR. Additionally, in vivo knockdown of mTOR and Lipin1 diminished WAT browning and increased adiposity. Conclusions: The ß3AR-activated mTOR-lipin1 axis mediates WAT browning, offering new insights into the molecular basis of PKA-regulated WAT browning. These findings provide potential adipose target candidates for the development of drugs to treat obesity.


Subject(s)
Adipose Tissue, Brown , Adipose Tissue, White , Mice, Knockout , Phosphatidate Phosphatase , TOR Serine-Threonine Kinases , Animals , TOR Serine-Threonine Kinases/metabolism , Mice , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Phosphatidate Phosphatase/metabolism , Phosphatidate Phosphatase/genetics , Obesity/metabolism , Obesity/genetics , Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit/metabolism , Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit/genetics , Receptors, Adrenergic, beta-3/metabolism , Receptors, Adrenergic, beta-3/genetics , Signal Transduction , Male , Mice, Inbred C57BL , Humans , Cyclic AMP-Dependent Protein Kinases/metabolism
17.
Article in English | MEDLINE | ID: mdl-39251449

ABSTRACT

Perfusion cell-culture mode has caught industrial interest in the field of biomanufacturing in recent years. Thanks to new technology, perfusion-culture processes can support higher cell densities, higher productivities and longer process times. However, due to the inherent operational complexity and high running costs, the development and design of perfusion-culture processes remain challenging. Here, we present a model-based approach to design optimized perfusion cultures of Chinese Hamster Ovary cells. Initially, four batches of bench-top reactor continuous-perfusion-culture data were used to fit the model parameters. Then, we proposed the model-based process design approach, aiming to quickly find out the "theoretically optimal" operational parameters combinations (perfusion rate and the proportion of feed medium in perfusion medium) which could achieve the target steady-state VCD while minimizing both medium cost and perfusion rate during steady state. Meanwhile, we proposed a model-based dynamic operational parameters-adjustment strategy to address the issue of cell-growth inhibition due to the high osmolality of concentrated perfusion medium. In addition, we employed a dynamic feedback control method to aid this strategy in preventing potential nutrient depletion scenarios. Finally, we test the feasibility of the model-based process design approach in both shake flask semi-perfusion culture (targeted at 5 × 107 cells/ml) and bench-top reactor continuous perfusion culture (targeted at 1.1 × 108 cells/ml). This approach significantly reduces the number of experiments needed for process design and development, thereby accelerating the advancement of perfusion-mode cell-culture processes.

18.
Neural Netw ; 180: 106649, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39236410

ABSTRACT

Selecting a set of initial users from a social network in order to maximize the envisaged number of influenced users is known as influence maximization (IM). Researchers have achieved significant advancements in the theoretical design and performance gain of several classical approaches, but these advances are almost reaching their pinnacle. Learning-based IM approaches have emerged recently with a higher generalization to unknown graphs than conventional methods. The development of learning-based IM methods is still constrained by a number of fundamental hardships, including (1) solving the objective function efficiently, (2) struggling to characterize the diverse underlying diffusion patterns, and (3) adapting the solution to different node-centrality-constrained IM variants. To address the aforementioned issues, we design a novel framework DeepIM for generatively characterizing the latent representation of seed sets, as well as learning the diversified information diffusion pattern in a data-driven and end-to-end way. Subsequently, we design a novel objective function to infer optimal seed sets under flexible node-centrality-based budget constraints. Extensive analyses are conducted over both synthetic and real-world datasets to demonstrate the overall performance of DeepIM.

19.
Int Immunopharmacol ; 142(Pt A): 113062, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39244898

ABSTRACT

Indoleamine 2,3-dioxygenase-1 (IDO-1) is an enzyme that catalyzes the metabolism of tryptophan (Trp). It is expressed in limited amounts in normal tissues but significantly upregulated during inflammation and infection. Various inflammatory factors, especially IFN-γ, can induce the expression of IDO-1. While extensive research has been conducted on the role of IDO-1 in tumors, its specific role in complex central nervous system tumors such as glioblastoma (GBM) remains unclear. This study aims to explore the role of IDO-1 in the development of GBM and analyze its association with tryptophan levels and CD8+T cell exhaustion in the tumor region. To achieve this, we constructed an orthotopic mouse glioblastoma tumor model to investigate the specific mechanisms between IDO-1, GBM, and CD8+T cell exhaustion. Our results showed that IDO-1 can promote CD8+T cell exhaustion by reducing tryptophan levels. When IDO-1 was knocked down in glioblastoma cells, other cells within the tumor microenvironment upregulated IDO-1 expression to compensate for the loss and enhance immunosuppressive effects. Therefore, the data suggest that the GBM microenvironment controls tryptophan levels by regulating IDO-1 expression, which plays a critical role in immune suppression. These findings support the use of immune therapy in combination with IDO-1 inhibitors or tryptophan supplementation as a potential treatment strategy.

20.
J Biosci ; 492024.
Article in English | MEDLINE | ID: mdl-39234946

ABSTRACT

Atherosclerosis is a common cardiovascular disease in which the arteries are thickened due to buildup of plaque. This study aims to identify programmed cell death (PCD)-related biomarkers and explore the crucial regulatory mechanisms of atherosclerosis. Gene expression profiles of atherosclerosis and control groups from GSE20129 and GSE23746 were obtained. Necroptosis was elevated in atherosclerosis. Weighted gene coexpression network analysis (WGCNA) was conducted in GSE23746 and GSE56045 to identify PCD-related modules and to perform enrichment analysis. Two necroptosis-related genes (IRF9 and STAT1) were identified and considered as biomarkers. Enrichment analysis showed that these gene modules were mainly related to immune response regulation. In addition, single-cell RNA sequencing data from GSE159677 were obtained and the characteristic cell types of atherosclerosis were identified. A total of 11 immune cell types were identified through UMAP dimension reduction. Most immune cells were mainly enriched in plaque samples, and STAT1 and IRF9 were primarily expressed in T-cells and macrophages. Moreover, the roles of IRF9 and STAT1 were assessed and found to be significantly upregulated in atherosclerosis, which was associated with increased risk of atherosclerosis. This study provides a molecular feature of atherosclerosis, offering an important basis for further research on its pathological mechanisms and the search for new therapeutic targets.


Subject(s)
Atherosclerosis , Biomarkers , Interferon-Stimulated Gene Factor 3, gamma Subunit , STAT1 Transcription Factor , T-Lymphocytes , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/metabolism , Humans , Atherosclerosis/genetics , Atherosclerosis/immunology , Atherosclerosis/pathology , Biomarkers/metabolism , Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics , Interferon-Stimulated Gene Factor 3, gamma Subunit/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Gene Regulatory Networks , Gene Expression Profiling , Gene Expression Regulation , Macrophages/immunology , Macrophages/metabolism , Transcriptome/genetics , Plaque, Atherosclerotic/genetics , Plaque, Atherosclerotic/pathology , Plaque, Atherosclerotic/immunology
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