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1.
Front Psychol ; 15: 1414736, 2024.
Article de Anglais | MEDLINE | ID: mdl-38984283

RÉSUMÉ

Objective: To explore the relationship among boredom proneness, the behavioral inhibition system, and anxiety among college students based on variable-centered and person-centered analytic approaches. Methods: A questionnaire survey was conducted on 1,102 college students from a university in Hebei Province using the Boredom Proneness Questionnaire (BPQ) for College Students, the Behavioral Inhibition System Scale (BIS), and the General Anxiety Disorder-7 scale (GAD-7). Results: The results reveal that boredom proneness was negatively correlated with scores on the behavioral inhibition system (r = -0.100, p < 0.01), and positively correlated with anxiety (r = 0.457, p < 0.001), while the behavioral inhibition system was positively correlated with anxiety (r = 0.086, p < 0.01). In the variable-centered analyses study, it was found that the behavioral inhibition system partially mediated the association between boredom proneness and anxiety. In the person-centered analyses study, three subtypes were identified: the high boredom-low inhibition group (9.35%), the moderate boredom-inhibition group (66.70%), and the low boredom-high inhibition group (23.95%). Individuals in these subtypes showed significant differences in anxiety scores (F = 4.538, p < 0.05), with the low boredom-high inhibition group scoring the highest. Conclusion: The results showed that the behavioral inhibition system partially mediates the relationship between boredom proneness and anxiety in college students; boredom proneness and the behavioral inhibition system exhibit group heterogeneity, with distinct classification features closely related to anxiety.

2.
Article de Anglais | MEDLINE | ID: mdl-39023401

RÉSUMÉ

Objective: [68Ga]Ga-DOTA-FGFR1-peptide is a novel positron emission tomography (PET) radiotracer targeting fibroblast growth factor receptor 1 (FGFR1). This study aimed to evaluate the safety, biodistribution, radiation dosimetry, and imaging potential of [68Ga]Ga-DOTA-FGFR1-peptide. Methods: The FGFR1-targeting peptide DOTA-(PEG2)-KAEWKSLGEEAWHSK was synthesized by manual solid-phase peptide synthesis and high-performance liquid chromatography purification, and labeled with 68Ga with DOTA as chelating agent. We recruited 14 participants and calculated the radiation dose of 4 of these pathologically confirmed nontumor subjects using OLINDA/EXM 2.2.0 software. At the same time, the imaging potential in 10 of these lung cancer patients was evaluated. Results: The biodistribution of [68Ga]Ga-DOTA-FGFR1-peptide in 4 subjects showed the highest uptake in the bladder and kidney. Dosimetry analysis indicated that the bladder wall received the highest effective dose (3.73E-02 mSv/MBq), followed by the lungs (2.36E-03 mSv/MBq) and red bone marrow (2.09E-03 mSv/MBq). No normal organs were found to have excess specific absorbed doses. The average systemic effective dose was 4.97E-02 mSv/MBq. The primary and metastatic tumor lesions were clearly visible on PET/computed tomography (CT) images in 10 patients. Conclusion: Our results indicate that [68Ga]Ga-DOTA-FGFR1-peptide has a good dosimetry profile and can be used safely in humans, and it has significant potential value for clinical PET/CT imaging.

3.
Front Microbiol ; 15: 1396894, 2024.
Article de Anglais | MEDLINE | ID: mdl-38873162

RÉSUMÉ

Porcine epidemic diarrhea virus (PEDV) is a single-stranded RNA virus with a capsid membrane that causes acute infectious gastrointestinal disease characterized by vomiting, diarrhea, and dehydration in swine. Piglets are more susceptible to PEDV than adults, with an infection rate reaching 90% and a fatality rate as high as 100%. Moreover, PEDV has a rapid transmission rate and broad transmission range. Consequently, PEDV has caused considerable economic losses and negatively impacted the sustainability of the pig industry. The surface spike (S) glycoprotein is the largest structural protein in PEDV virions and is closely associated with host cell fusion and virus invasion. As such, the S protein is an important target for vaccine development. In this article, we review the genetic variation, immunity, apoptosis-induction function, virulence, vaccine potential, and other aspects of the PEDV S protein. This review provides a theoretical foundation for preventing and controlling PEDV infection and serves as a valuable resource for further research and development of PEDV vaccines.

4.
Br J Cancer ; 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38906970

RÉSUMÉ

BACKGROUND: This randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta®) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative. METHODS: Eligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32. RESULTS: Among the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups. CONCLUSIONS: QL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer. TRIAL REGISTRATION: Chinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.

5.
Autophagy ; : 1-21, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38873925

RÉSUMÉ

Thoracic aortic dissection (TAD) is a severe disease, characterized by numerous apoptotic vascular smooth muscle cells (VSMCs). EDIL3/Del-1 is a secreted protein involved in macrophage efferocytosis in acute inflammation. Here, we aimed to investigate whether EDIL3 promoted the internalization and degradation of apoptotic VSMCs during TAD. The levels of EDIL3 were decreased in the serum and aortic tissue from TAD mice. Global edil3 knockout (edil3-/-) mice and edil3-/- bone marrow chimeric mice exhibited a considerable exacerbation in ß-aminopropionitrile monofumarate (BAPN)-induced TAD, accompanied with increased apoptotic VSMCs accumulating in the damaged aortic tissue. Two types of phagocytes, RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were used for in vitro efferocytosis assay. edil3-deficient phagocytes exhibited inefficient internalization and degradation of apoptotic VSMCs. Instead, EDIL3 promoted the internalization phase through interacting with phosphatidylserine (PtdSer) on apoptotic VSMCs and binding to the macrophage ITGAV/αv-ITGB3/ß3 integrin. In addition, EDIL3 accelerated the degradation phase through activating LC3-associated phagocytosis (LAP). Mechanically, following the engulfment, EDIL3 enhanced the activity of SMPD1/acid sphingomyelinase in the phagosome through blocking ITGAV-ITGB3 integrin, which facilitates phagosomal reactive oxygen species (ROS) production by NAPDH oxidase CYBB/NOX2. Furthermore, exogenous EDIL3 supplementation alleviated BAPN-induced TAD and promoted apoptotic cell clearance. EDIL3 may be a novel factor for the prevention and treatment of TAD.Abbreviations: BAPN: ß-aminopropionitrile monofumarate; BMDM: bone marrow-derived macrophage; C12FDG: 5-dodecanoylaminofluorescein-di-ß-D-galactopyranoside; CTRL: control; CYBB/NOX2: cytochrome b-245, beta polypeptide; DCFH-DA: 2',7'-dichlorofluorescin diacetate; EDIL3/Del-1: EGF-like repeats and discoidin I-like domains 3; EdU: 5-ethynyl-2'-deoxyuridine; EVG: elastic van Gieson; H&E: hematoxylin and eosin; IL: interleukin; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NAC: N-acetylcysteine; PtdSer: phosphatidylserine; rEDIL3: recombinant EDIL3; ROS: reactive oxygen species; SMPD1: sphingomyelin phosphodiesterase 1; TAD: thoracic aortic dissection; TEM: transmission electron microscopy; VSMC: vascular smooth muscle cell; WT: wild-type.

6.
Vet Microbiol ; 295: 110121, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38889617

RÉSUMÉ

Porcine reproductive and respiratory syndrome (PRRS) is one of the most detrimental contagious swine ailments worldwide. Currently, no effective drugs are available for its treatment. Targeting the structural and non-structural proteins (NSP) of the type 2 PRRS virus (PRRSV-2) with small interfering RNA (siRNA) is an effective approach to inhibit PRRSV replication. NSP4, which is highly conserved and possesses 3 C-like serine protease activity (3CLSP), can cleave PRRSV self-proteins, thereby contributing to viral replication. To investigate the mechanism by which NSP4 regulates PRRSV-2 replication and screen for effective siRNA inhibitors of PRRSV-2 replication, the recombinant plasmid pEGFP-C1-NSP4 was constructed, and a control siRNA pair and two siRNA pairs targeting the PRRSV-2 NSP4 gene (shRNA-ctr, shRNA-150, and shRNA-536) were synthesized and cloned into the pSilencer4.1-CMV vector. After 24 h of incubation, Marc-145 cells were transfected with recombinant plasmids, and subsequently infected with different PRRSV-2 (XH-GD, ZQ-GD, GDr180, and JXA1-R). Subsequently, the effects of NSP4 overexpression, shRNA on PRRSV-2 replication were evaluated by assessing cytopathic effects (CPE), TCID50, quantitative real-time PCR (qPCR), immunofluorescence assays (IFA), and Western blotting. The data from these CPE, TCID50, qPCR, and IFA experiments revealed that NSP4 overexpression significantly enhanced PRRSV-2 replication and shRNA targeting NSP4 can inhibit PRRSV-2 replication in Marc-145 cells, indicating that shRNA could serve as candidate molecules for fundamental research on PRRSV-2.


Sujet(s)
Virus du syndrome respiratoire et reproducteur porcin , Petit ARN interférent , Protéines virales non structurales , Réplication virale , Virus du syndrome respiratoire et reproducteur porcin/physiologie , Virus du syndrome respiratoire et reproducteur porcin/génétique , Animaux , Suidae , Lignée cellulaire , Protéines virales non structurales/génétique , Protéines virales non structurales/métabolisme , Petit ARN interférent/génétique , Petit ARN interférent/métabolisme , Syndrome dysgénésique et respiratoire porcin/virologie
7.
Front Microbiol ; 15: 1391697, 2024.
Article de Anglais | MEDLINE | ID: mdl-38741730

RÉSUMÉ

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV exhibits genetic diversity and complexity in terms of immune responses, posing challenges for eradication. The nucleocapsid (N) protein of PRRSV, an alkaline phosphoprotein, is important for various biological functions. This review summarizes the structural characteristics, genetic evolution, impact on PRRSV replication and virulence, interactions between viral and host proteins, modulation of host immunity, detection techniques targeting the N protein, and progress in vaccine development. The discussion provides a theoretical foundation for understanding the pathogenic mechanisms underlying PRRSV virulence, developing diagnostic techniques, and designing effective vaccines.

8.
J Cancer Res Clin Oncol ; 150(5): 234, 2024 May 06.
Article de Anglais | MEDLINE | ID: mdl-38710918

RÉSUMÉ

BACKGROUND: The pathogenesis and treatment of colorectal cancer (CRC) continue to be areas of ongoing research, especially the benefits of traditional Chinese medicine (TCM) in slowing the progression of CRC. This study was conducted to investigate the effectiveness and mechanism of action of modified Lichong decoction (MLCD) in inhibiting CRC progression. METHODS: We established CRC animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) and administered high, medium, or low doses of MLCD or mesalazine (MS) for 9 weeks to observe MLCD alleviation of CRC. The optimal MLCD dose group was then subjected to metagenomic and RNA sequencing (RNA-seq) to explore the differentially abundant flora and genes in the control, model and MLCD groups. Finally, the mechanism of action was verified using WB, qRT‒PCR, immunohistochemistry and TUNEL staining. RESULTS: MLCD inhibited the progression of CRC, and the optimal effect was observed at high doses. MLCD regulated the structure and function of the intestinal flora by decreasing the abundance of harmful bacteria and increasing that of beneficial bacteria. The differentially expressed genes were mainly associated with the Wnt/ß-catenin pathway and the cell cycle. Molecular biology analysis indicated that MLCD suppressed the Wnt/ß-catenin pathway and the epithelial-mesenchymal transition (EMT), inhibited abnormal cell proliferation and promoted intestinal epithelial cell apoptosis. CONCLUSION: MLCD mitigated the abnormal growth of intestinal epithelial cells and promoted apoptosis, thereby inhibiting the progression of CRC. This inhibition was accomplished by modifying the intestinal microbiota and disrupting the Wnt/ß-catenin pathway and the EMT. Therefore, MLCD could serve as a potential component of TCM prescriptions for CRC treatment.


Sujet(s)
Tumeurs colorectales , Médicaments issus de plantes chinoises , Microbiome gastro-intestinal , Voie de signalisation Wnt , Voie de signalisation Wnt/effets des médicaments et des substances chimiques , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Animaux , Tumeurs colorectales/traitement médicamenteux , Tumeurs colorectales/anatomopathologie , Tumeurs colorectales/métabolisme , Médicaments issus de plantes chinoises/pharmacologie , Souris , Humains , Mâle , Apoptose/effets des médicaments et des substances chimiques , Transition épithélio-mésenchymateuse/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Sulfate dextran , bêta-Caténine/métabolisme , Modèles animaux de maladie humaine
9.
Eur J Pharmacol ; 974: 176602, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38677538

RÉSUMÉ

BACKGROUND: The interleukin (IL) -12 p40 subunit is the common subunit of IL-12 and IL-23. It affects the immune inflammatory response, which may be closely related to cardiac remodeling. In this study, the regulatory effect of IL-12p40 knockout (KO) on cardiac remodeling was investigated, and the underlying mechanism was explored. METHODS AND RESULTS: Mice were subjected to transverse aortic constriction (TAC) to establish a model of cardiac remodeling. First, IL-12p40 was deleted to observe its effects on cardiac remodeling and cardiac inflammation, and the results showed that IL-12p40 deletion reduced both T helper 17 (Th17) and γδT17 cell differentiation, decreased proinflammatory macrophage differentiation, alleviated cardiac remodeling, and relieved cardiac dysfunction in TAC mice. Next, we explored whether IL-17 regulated TAC-induced cardiac remodeling, and the results showed that IL-17 neutralization alleviated proinflammatory macrophage differentiation and cardiac remodeling in IL-12p40 knockout mice and WT mice. Neutralization with cluster of differentiation 4 receptor (CD4) and γδ T-cell receptor (γδTCR) antibodies inhibited pro-inflammatory macrophage polarization and improved cardiac remodeling, and CD4 neutralizing antibody (NAb) had more significant effects. Finally, adoptive transfer of Th17 cells aggravated proinflammatory macrophage differentiation and cardiac remodeling in TAC-treated CD4 KO mice, while neutralization with the IL-12p40 antibody alleviated these pathological changes. CONCLUSION: Mainly Th17 cells but not γδT17 cells secrete IL-17, which mediates IL-12p40, promotes the polarization of proinflammatory macrophages, and exacerbates cardiac remodeling in TAC mice. IL-12p40 may be a potential target for the prevention and treatment of cardiac remodeling.


Sujet(s)
Différenciation cellulaire , Sous-unité p40 de l'interleukine-12 , Macrophages , Souris de lignée C57BL , Souris knockout , Cellules Th17 , Remodelage ventriculaire , Animaux , Mâle , Souris , Polarité de la cellule/effets des médicaments et des substances chimiques , Délétion de gène , Sous-unité p40 de l'interleukine-12/métabolisme , Sous-unité p40 de l'interleukine-12/génétique , Interleukine-17/métabolisme , Macrophages/immunologie , Macrophages/métabolisme , Récepteur lymphocytaire T antigène, gamma-delta/métabolisme , Récepteur lymphocytaire T antigène, gamma-delta/génétique , Cellules Th17/immunologie
10.
Epidemiol Infect ; 152: e75, 2024 Apr 18.
Article de Anglais | MEDLINE | ID: mdl-38634450

RÉSUMÉ

This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 µg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 µg/ml and ≤ 1 µg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.


Sujet(s)
Antibactériens , Résistance bactérienne aux médicaments , Macrolides , Mycoplasma pneumoniae , Pneumopathie à mycoplasmes , Mycoplasma pneumoniae/effets des médicaments et des substances chimiques , Mycoplasma pneumoniae/génétique , Mycoplasma pneumoniae/isolement et purification , Humains , Chine/épidémiologie , Macrolides/pharmacologie , Études rétrospectives , Enfant , Antibactériens/pharmacologie , Enfant d'âge préscolaire , Adolescent , Adulte , Femelle , Mâle , Pneumopathie à mycoplasmes/épidémiologie , Pneumopathie à mycoplasmes/microbiologie , Pneumopathie à mycoplasmes/traitement médicamenteux , Adulte d'âge moyen , Jeune adulte , Tests de sensibilité microbienne , Sujet âgé , Nourrisson , Prévalence , ARN ribosomique 23S/génétique , Sujet âgé de 80 ans ou plus
11.
FASEB J ; 38(7): e23591, 2024 Apr 15.
Article de Anglais | MEDLINE | ID: mdl-38572579

RÉSUMÉ

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.


Sujet(s)
microARN , Tumeurs du pancréas , Humains , Lignée cellulaire tumorale , Prolifération cellulaire/génétique , Régulation de l'expression des gènes tumoraux , microARN/génétique , Invasion tumorale/génétique , Tumeurs du pancréas/génétique , ARN circulaire/génétique , ARN circulaire/métabolisme
12.
Microorganisms ; 12(3)2024 Mar 11.
Article de Anglais | MEDLINE | ID: mdl-38543603

RÉSUMÉ

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious and pathogenic infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). It manifests as reproductive disorders in sows and respiratory disorders in piglets. PRRSV infects swine herds with symptoms such as abortions, stillbirths, and mummified fetuses in gestating sows. Piglets mainly experience abdominal respiration and respiratory symptoms. To date, the prevention of PRRS relies primarily on vaccination and the implementation of various preventive and control measures. Swine deaths caused by PRRS have resulted in significant economic losses to the pig industry worldwide. Non-structural protein 10 (NSP10) has helicase and adenosine triphosphatase (ATPase) activities that unwind DNA and RNA and play important roles in viral replication and transcription. Hence, it can be potentially used to develop novel reagents for the detection of PPRSV. This article reviews genetic variations, interaction with viral and host proteins, effects on PRRSV replication, immunomodulation, apoptosis, and viral virulence of NSP10, with the aim of providing a theoretical basis for the prevention and control of PRRS and drug development in the future.

13.
Front Neurol ; 15: 1355546, 2024.
Article de Anglais | MEDLINE | ID: mdl-38497043

RÉSUMÉ

Objective: To explore the effect of cognitive reserve (CR) on brain volume and cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and healthy elders (HE). Methods: 31 HE and 50 MCI patients were collected in this study to obtain structural MRI, cognitive function, and composite CR scores. Educational attainment, leisure time, and working activity ratings from two groups were used to generate cognitive reserve index questionnaire (CRIq) scores. The different volumes of brain regions and CSF were obtained using uAI research portal in both groups, which were taken as the regions of interest (ROI), the correlation analysis between ROIs and CRIq scores were conducted. Results: The scores of CRIq, CRIq-leisure time, and CRIq-education in HE group were significantly higher than patients in MCI group, and the montreal cognitive assessment (MoCA) and minimum mental state examination (MMSE) scores were positively correlated with the CRIq, CRIq-education in both groups, and were positively correlated with CRIq-leisure time in MCI group. The scores of auditory verbal learning test (AVLT) and verbal fluency test (VFT) were also positively correlated with CRIq, CRIq-leisure time, and CRIq-education in MCI group, but the score of AVLT was only positively correlated with CRIq in HE group. Moreover, in MCI group, the volume of the right middle cingulate cortex and the right parahippocampal gyrus were negatively correlated with the CRIq, and the volume of CSF, peripheral CSF, and third ventricle were positively correlated with the CRIq-leisure time score. The result of mediation analysis suggested that right parahippocampal gryus mediated the main effect of the relationship between CRIq and MoCA score in MCI group. Conclusion: People with higher CR show better levels of cognitive function, and MCI patients with higher CR showed more severe volume atrophy of the right middle cingulate cortex and the right parahippocampal gyrus, but more CSF at a given level of global cognition.

14.
J Am Heart Assoc ; 13(6): e031283, 2024 Mar 19.
Article de Anglais | MEDLINE | ID: mdl-38456416

RÉSUMÉ

BACKGROUND: Dilated cardiomyopathy (DCM) is the leading cause of heart failure with a poor prognosis. Recent studies suggest that endothelial to mesenchymal transition (EndMT) may be involved in the pathogenesis and cardiac remodeling during DCM development. EDIL3 (epidermal growth factor-like repeats and discoidin I-like domains 3) is an extracellular matrix glycoprotein that has been reported to promote EndMT in various diseases. However, the roles of EDIL3 in DCM still remain unclear. METHODS AND RESULTS: A mouse model of DCM and human umbilical vein endothelial cells were used to explore the roles and mechanisms of EDIL3 in DCM. The results indicated that EndMT and EDIL3 were activated in DCM mice. EDIL3 deficiency attenuated cardiac dysfunction and remodeling in DCM mice. EDIL3 knockdown alleviated EndMT by inhibiting USP10 (ubiquitin specific peptidase 10) dependent Smad4 deubiquitination in vivo and in vitro. Recombinant human EDIL3 promoted EndMT via reinforcing deubiquitination of Smad4 in human umbilical vein endothelial cells treated with IL-1ß (interleukin 1ß) and TGF-ß (transforming growth factor beta). Inhibiting USP10 abolished EndMT exacerbated by EDIL3. In addition, recombinant EDIL3 also aggravates doxorubicin-induced EndMT by promoting Smad4 deubiquitination in HUVECs. CONCLUSIONS: Taken together, these results indicate that EDIL3 deficiency attenuated EndMT by inhibiting USP10 dependent Smad4 deubiquitination in DCM mice.


Sujet(s)
Cardiomyopathie dilatée , Animaux , Humains , Souris , Protéines de liaison au calcium/métabolisme , Cardiomyopathie dilatée/métabolisme , Molécules d'adhérence cellulaire/métabolisme , Discoidines , Facteur de croissance épidermique , Transition épithélio-mésenchymateuse , Cellules endothéliales de la veine ombilicale humaine/métabolisme , Facteur de croissance transformant bêta/métabolisme , Ubiquitin thiolesterase , Ubiquitin-specific proteases/métabolisme
15.
MedComm (2020) ; 5(3): e491, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38463394

RÉSUMÉ

Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin-1 (MaR1), one of metabolites from Omega-3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effect of MaR1 on hypertensive vascular remodeling. Here, we found serum MaR1 levels were reduced in hypertensive patients and was negatively correlated with systolic blood pressure (SBP). The treatment of MaR1 reduced the elevation of blood pressure and alleviated vascular remodeling in the angiotensin II (AngII)-infused mouse model. In addition, MaR1-treated vascular smooth muscle cells (VSMCs) exhibited reduced excessive proliferation, migration, and phenotype switching, as well as impaired pyroptosis. However, the knockout of the receptor of MaR1, leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6), was seen to aggravate pathological vascular remodeling, which could not be reversed by additional MaR1 treatment. The mechanisms by which MaR1 regulates vascular remodeling through LGR6 involves the Ca2+/calmodulin-dependent protein kinase II/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. Overall, supplementing MaR1 may be a novel therapeutic strategy for the prevention and treatment of hypertension.

16.
Molecules ; 29(5)2024 Feb 29.
Article de Anglais | MEDLINE | ID: mdl-38474582

RÉSUMÉ

Graphene quantum dots (GQDs) possess the photosensitive absorption for photoelectrochemical hydrogen evolution owing to special band structures, whereas they usually confront with photo-corrosion or undesired charge recombination during photoelectrochemical reactions. Hence, we establish the heterojunction between GQDs and MoSe2 sheets via a hydrothermal process for improved stability and performance. Photoanodic water splitting with hydrogen evolution boosted by the heteroatom doped N,S-GQDs/MoSe2 heterojunction has been attained due to the abundant active sites, promoted charge separation and transfer kinetics with reduced energy barriers. Diphasic 1T and 2H MoSe2 sheet-hybridized quantum dots contribute to the Schottky heterojunction, which can play a key role in expedited carrier transport to inhibit accumulative photo-corrosion and increase photocurrent. Heteroatom dopants lead to favored energy band matching, bandgap narrowing, stronger light absorption and high photocurrent density. The external quantum efficiency of the doped heterojunction has been elevated twofold over that of the non-doped pristine heterojunction. Modification of the graphene quantum dots and MoSe2 heterojunction demonstrate a viable and adaptable platform toward photoelectrochemical hydrogen evolution processes.

17.
Sensors (Basel) ; 24(5)2024 Feb 26.
Article de Anglais | MEDLINE | ID: mdl-38475058

RÉSUMÉ

Time series anomaly detection is very important to ensure the security of industrial control systems (ICSs). Many algorithms have performed well in anomaly detection. However, the performance of most of these algorithms decreases sharply with the increase in feature dimension. This paper proposes an anomaly detection scheme based on Graph Attention Network (GAT) and Informer. GAT learns sequential characteristics effectively, and Informer performs excellently in long time series prediction. In addition, long-time forecasting loss and short-time forecasting loss are used to detect multivariate time series anomalies. Short-time forecasting is used to predict the next time value, and long-time forecasting is employed to assist the short-time prediction. We conduct a large number of experiments on industrial control system datasets SWaT and WADI. Compared with most advanced methods, we achieve competitive results, especially on higher-dimensional datasets. Moreover, the proposed method can accurately locate anomalies and realize interpretability.

18.
Front Immunol ; 15: 1380517, 2024.
Article de Anglais | MEDLINE | ID: mdl-38515746

RÉSUMÉ

As a canonical cytoplasmic DNA sensor, cyclic GMP-AMP synthase (cGAS) plays a key role in innate immunity. In recent years, a growing number of studies have shown that cGAS can also be located in the nucleus and plays new functions such as regulating DNA damage repair, nuclear membrane repair, chromosome fusion, DNA replication, angiogenesis and other non-canonical functions. Meanwhile, the mechanisms underlying the nucleo-cytoplasmic transport and the regulation of cGAS activation have been revealed in recent years. Based on the current understanding of the structure, subcellular localization and canonical functions of cGAS, this review focuses on summarizing the mechanisms underlying nucleo-cytoplasmic transport, activity regulation and non-canonical functions of cGAS in the nucleus. We aim to provide insights into exploring the new functions of cGAS in the nucleus and advance its clinical translation.


Sujet(s)
ADN , Nucleotidyltransferases , Nucleotidyltransferases/génétique , Immunité innée , Cytosol , Cytoplasme
19.
Spine J ; 24(6): 1121-1131, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38316364

RÉSUMÉ

BACKGROUND CONTEXT: With the aging population, osteoporosis, which leads to poor fusion, has become a common challenge for lumbar surgery. In addition, most people with osteoporosis are elderly individuals with poor surgical tolerance, and poor bone quality can also weaken the stability of internal fixation. PURPOSE: This study compared the fixation strength of the bilateral traditional trajectory screw structure (TT-TT), the bilateral cortical bone trajectory screw structure (CBT-CBT), and the hybrid CBT-TT (CBT screws at the cranial level and TT screws at the caudal level) structure under different bone mineral density conditions. STUDY DESIGN: A finite element (FE) analysis study. METHODS: Above all, we established a healthy adult lumbar spine model. Second, under normal and osteoporotic conditions, three transforaminal lumbar interbody fusion (TLIF) models were established: bilateral traditional trajectory (TT-TT) screw fixation, bilateral cortical bone trajectory (CBT-CBT) screw fixation, and hybrid cortical bone trajectory screw and traditional trajectory screw (CBT-TT) fixation. Finally, a 500-N compression load with a torque of 10 N/m was applied to simulate flexion, extension, lateral bending, and axial rotation. We compared the range of motion (ROM), adjacent disc stress, cage stress, and posterior fixation stress of the different fusion models. RESULTS: Under different bone mineral density conditions, the range of motion of the fusion segment was significantly reduced. Compared to normal bone conditions, the ROM of the L4-L5 segment, the stress of the adjacent intervertebral disc, the surface stress of the cage, and the maximum stress of the posterior fixation system were all increased in osteoporosis. Under most loads, the ROM and surface stress of the cage and the maximum stress of the posterior fixation system of the TT-TT structure are the lowest under normal bone mineral density conditions. However, under osteoporotic conditions, the fixation strength of the CBT-CBT and CBT-TT structures are higher than that of the TT-TT structures under certain load conditions. At the same time, the surface stress of the intervertebral fusion cage and the maximum stress of the posterior fixation system for the two structures are lower than those of the TT-TT structure. CONCLUSION: Under normal bone mineral density conditions, transforaminal lumbar interbody fusion combined with TT-TT fixation provides the best biomechanictability. However, under osteoporotic conditions, CBT-CBT and CBT-TT structures have higher fixed strength compared to TT-TT structures. The hybrid CBT-TT structure exhibits advantages in minimal trauma and fixation strength. Therefore, this seems to be an alternative fixation method for patients with osteoporosis and degenerative spinal diseases. CLINICAL SIGNIFICANCE: This study provides biomechanical support for the clinical application of hybrid CBT-TT structure for osteoporotic patients undergoing TLIF surgery.


Sujet(s)
Analyse des éléments finis , Vertèbres lombales , Ostéoporose , Arthrodèse vertébrale , Humains , Arthrodèse vertébrale/méthodes , Arthrodèse vertébrale/instrumentation , Vertèbres lombales/chirurgie , Ostéoporose/chirurgie , Phénomènes biomécaniques , Densité osseuse , Adulte , Vis orthopédiques
20.
Food Chem ; 443: 138611, 2024 Jun 15.
Article de Anglais | MEDLINE | ID: mdl-38309025

RÉSUMÉ

The effects of rice bran rancidity-induced protein oxidation and heating time on the stability of rice bran protein fibril aggregates (RBPFA)-high internal phase Pickering emulsions (HIPPEs) were investigated. The optimal conditions for RBPFA-HIPPEs were 8 mg/mL RBPFA with an oil phase volume fraction of 75 %. Moderate oxidation (rice bran stored for 3 d) and moderate heating (8 h) enhanced the wettability, flexibility, diffusion rate, and adsorption rate of RBPFA, meanwhile, the rheological properties of RBPFA-HIPPEs increased. RBPFA-HIPPEs could be stably stored for 50 d at 25 °C. Moderate oxidized and moderate heated RBPFA-stabilized HIPPEs could remain stable after heat treatment and could be re-prepared after freeze-thaw (3 cycles). Additionally, the stability of RBPFA-HIPPEs was significantly related to the structural characteristics and interfacial properties of RBPFA. Overall, moderate oxidation and moderate heating enhanced the storage, thermal, and freeze-thaw stability of RBPFA-HIPPEs by improving the interfacial properties of RBPFA.


Sujet(s)
Oryza , Émulsions/composition chimique , Agrégats de protéines , Adsorption , Oxydoréduction , Taille de particule
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