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BACKGROUND: Existing research indicates that the Mediterranean diet has a positive impact on preventing and treating hypertension. However, its specific effect on hypertension among elderly Chinese individuals is unclear. AIMS: The objective of this research was to explore the association between the Chinese version of the Mediterranean-DASH Intervention for Neurodegenerative Delay (cMIND) diet and hypertension among elderly Chinese individuals, aiming to offer novel strategies for alleviating the burden of hypertension in this demographic. METHODS: In this study, we used cross-sectional data published in 2018 by the China Longitudinal Health and Longevity Survey (CLHLS) to develop a binary logistic regression model to investigate the correlation between cMIND diet and hypertension in a Chinese elderly population. Restricted cubic spline was used to test for linear associations, and further subgroup analyses were performed to test for interactions. RESULTS: In total, 7,103 older adults were included in the study, with a prevalence of hypertension of 39.0%. When the cMIND diet score was used as a continuous variable, a significant protective effect against hypertension was present (OR = 0.955, 95% CI:0.923-0.988, p = 0.008); when used as a categorical variable, this protective effect was still present at higher levels (compared to lower levels) of the cMIND diet (OR = 0.869, 95% CI: 0.760-0.995, p = 0.042). DISCUSSION: Although the Mediterranean diet has great potential to reduce the chance of hypertension, it should also consider the effect on the Chinese population. The results of this study provide new ways to reduce the disease burden of hypertension in Chinese older adults and improve quality of life in later life. CONCLUSION: The cMIND diet can considerably reduce the risk of hypertension among older adults in China.
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Régime méditerranéen , Hypertension artérielle , Humains , Hypertension artérielle/épidémiologie , Hypertension artérielle/prévention et contrôle , Sujet âgé , Mâle , Chine/épidémiologie , Femelle , Études transversales , Régime DASH , Sujet âgé de 80 ans ou plus , Adulte d'âge moyen , PrévalenceRÉSUMÉ
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension with a low incidence. Despite pulmonary endarterectomy(PEA) being the preferred treatment for CTEPH, for patients who failed medical therapy and who are not suitable candidates for PEA, lung transplantation (LT) is still the only effective treatment for end-stage CTEPH; however, there are currently very few reports on the efficacy of LT for CTEPH. METHODS: We retrospectively analyzed the clinical data of seven patients diagnosed with CTEPH between July 2019 and July 2021. The follow-up deadline was March, 2022. RESULTS: The mean age at admission was 54 ± 12 years. The average value of mean pulmonary artery pressure (mPAP) was 40 ± 5 mmHg. The mean preoperative oxygenation index(PaO2/FiO2) was 203 ± 56 mm Hg. After evaluation, one patient underwent left LT and the rest underwent bilateral LT. Three patients received intraoperative veno-venous extracorporeal membrane oxygenation (ECMO) support, and four patients received intraoperative veno-arterial ECMO support. The average postoperative mPAP was 19 ± 4 mmHg. The mean postoperative oxygenation index(PaO2/FiO2) was 388 ± 83 mmHg. There was a significant difference between the preoperative and postoperative mPAP and oxygenation index(PaO2/FiO2). All patients recovered well and were discharged 37 ± 19 days postoperatively. The mean follow-up duration was 19 ± 8 months. There was no recurrence of CTEPH. CONCLUSIONS: LT is an effective treatment for end-stage CTEPH, which can improve cardiopulmonary function and quality of life and prolong survival. Patients who are unable to tolerate PEA should be considered for LT as early as possible when internal medicine failed.
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Hypertension pulmonaire , Transplantation pulmonaire , Embolie pulmonaire , Humains , Adulte d'âge moyen , Femelle , Mâle , Études rétrospectives , Hypertension pulmonaire/chirurgie , Embolie pulmonaire/chirurgie , Embolie pulmonaire/complications , Adulte , Maladie chronique , Résultat thérapeutique , Oxygénation extracorporelle sur oxygénateur à membrane/méthodes , Sujet âgé , Endartériectomie/méthodesRÉSUMÉ
OBJECTIVES: In this study, we investigated whether neural precursor cell-expressed developmentally down-regulated gene 4-like (NEDD4L) is the E3 enzyme of angiotensin-converting enzyme 2 (ACE2) and whether NEDD4L degrades ACE2 via ubiquitination, leading to the progression of pulmonary arterial hypertension (PAH). METHODS: Bioinformatic analyses were used to explore the E3 ligase that ubiquitinates ACE2. Cultured pulmonary arterial smooth muscle cells (PASMCs) and specimens from patients with PAH were used to investigate the crosstalk between NEDD4L and ACE2 and its ubiquitination in the context of PAH. RESULTS: The inhibition of ubiquitination attenuated hypoxia-induced proliferation of PASMCs. The levels of NEDD4L were increased, and those of ACE2 were decreased in lung tissues from patients with PAH and in PASMCs. NEDD4L, the E3 ligase of ACE2, inhibited the expression of ACE2 in PASMCs, possibly through ubiquitination-mediated degradation. PAH was associated with upregulation of NEDD4L expression and downregulation of ACE2 expression. CONCLUSIONS: NEDD4L, the E3 ubiquitination enzyme of ACE2, promotes the proliferation of PASMCs, ultimately leading to PAH.
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Angiotensin-converting enzyme 2 , Ubiquitine protéine ligases NEDD4 , Hypertension artérielle pulmonaire , Ubiquitination , Angiotensin-converting enzyme 2/métabolisme , Angiotensin-converting enzyme 2/génétique , Angiotensin-converting enzyme 2/biosynthèse , Ubiquitine protéine ligases NEDD4/métabolisme , Ubiquitine protéine ligases NEDD4/génétique , Humains , Cellules cultivées , Mâle , Hypertension artérielle pulmonaire/métabolisme , Hypertension artérielle pulmonaire/génétique , Hypertension artérielle pulmonaire/anatomopathologie , Hypertension artérielle pulmonaire/enzymologie , Myocytes du muscle lisse/métabolisme , Myocytes du muscle lisse/enzymologie , Myocytes du muscle lisse/anatomopathologie , Animaux , Prolifération cellulaire/physiologie , Peptidyl-Dipeptidase A/métabolisme , Peptidyl-Dipeptidase A/génétique , Peptidyl-Dipeptidase A/biosynthèse , Artère pulmonaire/métabolisme , Artère pulmonaire/anatomopathologie , Artère pulmonaire/enzymologie , Femelle , Rats , Rat Sprague-DawleyRÉSUMÉ
BACKGROUND: Patients with airway stenosis (AS) are associated with considerable morbidity and mortality after lung transplantation (LTx). This study aims to develop and validate machine learning (ML) models to predict AS requiring clinical intervention in patients after LTx. METHODS: Patients who underwent LTx between January 2017 and December 2019 were reviewed. The conventional logistic regression (LR) model was fitted by the independent risk factors which were determined by multivariate LR. The optimal ML model was determined based on 7 feature selection methods and 8 ML algorithms. Model performance was assessed by the area under the curve (AUC) and brier score, which were internally validated by the bootstrap method. RESULTS: A total of 381 LTx patients were included, and 40 (10.5%) patients developed AS. Multivariate analysis indicated that male, pulmonary arterial hypertension, and postoperative 6-min walking test were significantly associated with AS (all P < 0.001). The conventional LR model showed performance with an AUC of 0.689 and brier score of 0.091. In total, 56 ML models were developed and the optimal ML model was the model fitted using a random forest algorithm with a determination coefficient feature selection method. The optimal model exhibited the highest AUC and brier score values of 0.760 (95% confidence interval [CI], 0.666-0.864) and 0.085 (95% CI, 0.058-0.117) among all ML models, which was superior to the conventional LR model. CONCLUSIONS: The optimal ML model, which was developed by clinical characteristics, allows for the satisfactory prediction of AS in patients after LTx.
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Transplantation pulmonaire , Apprentissage machine , Humains , Mâle , Études rétrospectives , Adulte d'âge moyen , Femelle , Adulte , Études cas-témoins , Sténose pathologique , Complications postopératoires , Facteurs de risqueRÉSUMÉ
Although the locus coeruleus (LC) is recognized as a crucial modulator for attention and perception by releasing norepinephrine into various cortical regions, the impact of LC-noradrenergic (NE) modulation on auditory discrimination behavior remains elusive. In this study, we firstly recorded local field potential (LFP) and single-unit activity (SUA) in multiple cortical regions associated with auditory-motor processing, including the auditory cortex (AC), posterior parietal cortex (PPC), secondary motor cortex (M2), anterior cingulate cortex (ACC), prefrontal cortex (PFC), and orbitofrontal cortex (OFC), in response to optogenetic activation (40Hz and 0.5s) of the LC-NE neurons in awake mice (male). We found that phasic LC stimulation induced a persistent high gamma oscillations (50 - 80Hz) in the OFC. Phasic activation of LC-NE neurons also resulted in a corresponding increase in NE levels in the OFC, accompanied by a pupillary dilation response. Furthermore, when mice were performing a Go/No-go auditory discrimination task, we optogeneticaly activated the neural projections from LC to OFC, and revealed a shortened latency in behavioral responses to sound stimuli and an increased false alarm rate. These impulsive behavioral responses may be associated with the gamma neural activity in the OFC. These findings have broadened our understanding of the neural mechanisms involved in the role of LC in auditory-motor processing.Significance Statement The locus coeruleus (LC) plays a vital role in mediating behaviors related to perception, but the underlying mechanisms remain unclear. Using optogenetic techniques, we selectively activated the neural projections from the norepinephrine (NE) neurons of LC to the orbitofrontal cortex (OFC). We found that phasical activation of LC neurons increased NE levels in the OFC and induced a gamma band neuronal activity, while also shortening the reaction latency of mice in auditory discrimination tasks, but at the cost of increased false alarm rates. These results reveal a neural mechanism involving the LC in auditory-motor processing, providing a new perspective for understanding attention and perception.
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Edge servers frequently manage their own offline digital twin (DT) services, in addition to caching online digital twin services. However, current research often overlooks the impact of offline caching services on memory and computation resources, which can hinder the efficiency of online service task processing on edge servers. In this study, we concentrated on service caching and task offloading within a collaborative edge computing system by emphasizing the integrated quality of service (QoS) for both online and offline edge services. We considered the resource usage of both online and offline services, along with incoming online requests. To maximize the overall QoS utility, we established an optimization objective that rewards the throughput of online services while penalizing offline services that miss their soft deadlines. We formulated this as a utility maximization problem, which was proven to be NP-hard. To tackle this complexity, we reframed the optimization problem as a Markov decision process (MDP) and introduced a joint optimization algorithm for service caching and task offloading by leveraging the deep Q-network (DQN). Comprehensive experiments revealed that our algorithm enhanced the utility by at least 14.01% compared with the baseline algorithms.
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BACKGROUND: Phosphoglycerate kinase 1 (PGK1) has been identified as a possible biomarker for breast cancer (BC) and may play a role in the development and advancement of triple-negative BC (TNBC). AIM: To explore the PGK1 and BC research status and PGK1 expression and mechanism differences among TNBC, non-TNBC, and normal breast tissue. METHODS: PGK1 and BC related literature was downloaded from Web of Science Core Collection Core Collection. Publication counts, key-word frequency, cooperation networks, and theme trends were analyzed. Normal breast, TNBC, and non-TNBC mRNA data were gathered, and differentially expressed genes obtained. Area under the summary receiver operating characteristic curves, sensitivity and specificity of PGK1 expression were determined. Kaplan Meier revealed PGK1's prognostic implication. PGK1 co-expressed genes were explored, and Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Disease Ontology applied. Protein-protein interaction networks were constructed. Hub genes identified. RESULTS: PGK1 and BC related publications have surged since 2020, with China leading the way. The most frequent keyword was "Expression". Collaborative networks were found among co-citations, countries, institutions, and authors. PGK1 expression and BC progression were research hotspots, and PGK1 expression and BC survival were research frontiers. In 16 TNBC vs non-cancerous breast and 15 TNBC vs non-TNBC datasets, PGK1 mRNA levels were higher in 1159 TNBC than 1205 non-cancerous breast cases [standardized mean differences (SMD): 0.85, 95% confidence interval (95%CI): 0.54-1.16, I² = 86%, P < 0.001]. PGK1 expression was higher in 1520 TNBC than 7072 non-TNBC cases (SMD: 0.25, 95%CI: 0.03-0.47, I² = 91%, P = 0.02). Recurrence free survival was lower in PGK1-high-expression than PGK1-low-expression group (hazard ratio: 1.282, P = 0.023). PGK1 co-expressed genes were concentrated in ATP metabolic process, HIF-1 signaling, and glycolysis/gluconeogenesis pathways. CONCLUSION: PGK1 expression is a research hotspot and frontier direction in the BC field. PGK1 may play a strong role in promoting cancer in TNBC by mediating metabolism and HIF-1 signaling pathways.
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Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer. Although it has a high mortality rate, there is currently no effective treatment for HCC. Lenvatinib has traditionally been used as the first-line treatment for advanced HCC (aHCC); however, resistance to this therapy is common. It can be difficult to select effective second-line drugs to overcome lenvatinib resistance when treating aHCC. For patients with aHCC, poor treatment efficacy can result in patients missing the optimal treatment window and can lead to an irreversible situation. Lenalidomide has begun to be used to treat HCC; however, to the best of our knowledge, its efficacy in patients with lenvatinib-resistant HCC remains to be reported on in the literature. The present case report, to the best of our knowledge, describes the first case in the literature of a patient with lenvatinib-resistant aHCC who achieved a partial response after the treatment regimen was switched to lenalidomide. The present case report provides a promising novel route for the treatment of lenvatinib-resistant HCC.
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Recent research indicated that ulcers and peripheral vascular disease resulting from drug-resistant bacterial infections are the main causes of delayed healing in chronic diabetic wounds. 5-Aminolevulinic acid (ALA) is a second-generation endogenous photosensitizer. The therapeutic effect and mechanism of ALA-mediated photodynamic therapy (ALA-PDT) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic rats were investigated in this study. The results revealed the promising antibacterial effects of ALA-PDT MRSA in vitro, with a minimum inhibitory concentration and minimum bactericidal concentration of 250 and 500⯵M, respectively. ALA-PDT also changed the permeability and structural integrity of bacterial cell membranes by producing reactive oxygen species. Meanwhile, ALA-PDT accelerated wound healing in MRSA-infected diabetic rats, with 5â¯% ALA-PDT achieving complete sterilization in 14 days and wound closure in 21 days. Treatment with 5â¯% ALA-PDT additionally improved the histopathological appearance of skin tissue, as well as fibrosis, inflammatory cytokine release, and angiogenesis-related protein expression. These findings indicated that ALA-PDT significantly promoted the healing of MRSA-infected wounds in diabetic rats by eliminating bacteria, inhibiting inflammation, generating granulation tissues, promoting neovascularization, and restoring damaged nerves. In addition, the healing mechanism was related to the activation of inflammatory and angiogenesis pathways through the regulation of tumor necrosis factor-alpha and interleukin-6 expression and upregulation of CD206, CD31, and VEGF. These findings underscored the potential role of ALA-PDT in promoting the healing of chronic diabetic wounds.
Sujet(s)
Acide amino-lévulinique , Diabète expérimental , Staphylococcus aureus résistant à la méticilline , Photothérapie dynamique , Rat Sprague-Dawley , Cicatrisation de plaie , Infection de plaie , Animaux , Acide amino-lévulinique/pharmacologie , Photothérapie dynamique/méthodes , Infection de plaie/traitement médicamenteux , Infection de plaie/microbiologie , Infection de plaie/anatomopathologie , Diabète expérimental/traitement médicamenteux , Diabète expérimental/complications , Mâle , Staphylococcus aureus résistant à la méticilline/effets des médicaments et des substances chimiques , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Rats , Photosensibilisants/pharmacologie , Photosensibilisants/usage thérapeutique , Maladie chronique , Infections à staphylocoques/traitement médicamenteux , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Tests de sensibilité microbienne , Espèces réactives de l'oxygène/métabolismeRÉSUMÉ
BACKGROUND: Dyslipidemia is increasingly recognized as an essential risk factor for cardiovascular diseases. However, few studies illustrated the effects of ambient temperature exposure (TE) on lipid levels in children. The study aimed to examine the association between ambient TE and lipid levels in children. METHODS: Based on a prospective cohort, a total of 2423 children (with 4466 lipids measure person-time) were collected from 2014 to 2019. The meteorological observation data and adjusted variables were collected. Mixed-effect models and generalized additive mixed model (GAMM) were applied to investigate the association between ambient TE and lipid levels. RESULTS: A significant negative association was observed between TE and low-density lipoprotein cholesterol (LDL-C) or total cholesterol (TC) levels both in all children [LDL-C, ß(95%CI) = -0.350(-0.434,-0.265), P < 0.001; TC, ß(95%CI) = -0.274(-0.389,-0.160), P < 0.001] and by different sex group. However, no significant association was found in low-density lipoprotein cholesterol (HDL-C) or triglycerides (TG) levels. The estimated optimal ambient TEs for LDL-C were 18.273 °C and 18.024 °C for girls and boys, respectively. For TC, the optimal ambient TEs were 17.949 °C and 18.024 °C, respectively. With ambient TE decreased, the risk of dyslipidemia increased for both boys [OR = 0.032(0.006,0.179), P < 0.001] and girls [OR = 0.582(0.576,0.587), P < 0.001]. CONCLUSION: This study provided a comprehensive illustration about the associations between ambient TE and lipid levels in different sex and ages from a prospective cohort study. The findings will provide evidence for the government to prevent dyslipidemia in vulnerable children through regulating TE.
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Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin-proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.
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Enzymes de désubiquitinylation , Tumeurs , Proteasome endopeptidase complex , Ubiquitination , Humains , Tumeurs/métabolisme , Tumeurs/traitement médicamenteux , Tumeurs/anatomopathologie , Animaux , Proteasome endopeptidase complex/métabolisme , Enzymes de désubiquitinylation/métabolisme , Protéolyse , Ubiquitine/métabolisme , Antinéoplasiques/usage thérapeutique , Antinéoplasiques/pharmacologie , Maturation post-traductionnelle des protéines , Thérapie moléculaire ciblée , Ubiquitin-protein ligases/métabolismeRÉSUMÉ
Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the central nervous system, yet their role in vestibular compensation remains elusive. To address this knowledge gap, we employed unilateral labyrinthectomy (UL) in rats to establish animal models of peripheral vestibular dysfunction. Utilizing ribonucleic acid sequencing (RNA-seq), we comprehensively analysed the expression profiles of genes dysregulated in the medial vestibular nucleus (MVN) of these rats at distinct time points: 4 h, 4 days, and 14 days post-UL. Through trans-target prediction analysis integrating differentially co-expressed messenger RNAs (mRNAs) and lncRNAs, we constructed lncRNA-mRNA regulatory networks. Validation of selected mRNAs and lncRNAs was performed using RT-qPCR. Our RNA-seq analysis revealed significant aberrant expression of 3054 lncRNAs and 1135 mRNAs compared to control samples. By applying weighted gene co-expression network analysis (WGCNA), we identified 11 co-expressed modules encompassing all genes. Notably, within the MEmagenta module, we observed an initial upregulation of differentially expressed genes (DEGs) at 4 h, followed by downregulation at 4- and 14-days post-UL. Our findings indicated that 3068 lncRNAs positively regulated 1259 DEGs, while 1482 lncRNAs negatively regulated 433 DEGs in the MVN. The RT-qPCR results corroborated the RNA-seq data, validating our findings. This study offers novel insights into the lncRNA-mRNA expression landscape during vestibular compensation, paving the way for further exploration of lncRNA functions in this context.
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Analyse de profil d'expression de gènes , Réseaux de régulation génique , ARN long non codant , ARN messager , Noyaux vestibulaires , Labyrinthe vestibulaire , Animaux , Noyaux vestibulaires/métabolisme , ARN long non codant/génétique , ARN long non codant/métabolisme , ARN messager/génétique , ARN messager/métabolisme , Rats , Mâle , Labyrinthe vestibulaire/chirurgie , Labyrinthe vestibulaire/métabolisme , Régulation de l'expression des gènes , Rat Sprague-Dawley , Transcriptome/génétiqueRÉSUMÉ
OBJECTIVE: To investigate the association between driving pressure (ΔP) and 90-day mortality in patients following lung transplantation (LTx) in patients who developed primary graft dysfunction (PGD). METHODS: This prospective, observational study involved consecutive patients who, following LTx, were admitted to our intensive care unit (ICU) from January 2022 to January 2023. Patients were separated into two groups according to ΔP at time of admission (i.e., low, ≤15 cmH2O or high, >15 cmH2O). Postoperative outcomes were compared between groups. RESULTS: In total, 104 patients were involved in the study, and of these, 69 were included in the low ΔP group and 35 in the high ΔP group. Kaplan-Meier analysis of 90-day mortality showed a statistically significant difference between groups with survival better in the low ΔP group compared with the high ΔP group. According to Cox proportional regression model, the variables independently associated with 90-day mortality were ΔP and pneumonia. Significantly more patients in the high ΔP group than the low ΔP group had PGD grade 3 (PGD3), pneumonia, required tracheostomy, and had prolonged postoperative extracorporeal membrane oxygenation (ECMO) time, postoperative ventilator time, and ICU stay. CONCLUSIONS: Driving pressure appears to have the ability to predict PGD3 and 90-day mortality of patients following LTx. Further studies are required to confirm our results.
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Transplantation pulmonaire , Humains , Transplantation pulmonaire/mortalité , Transplantation pulmonaire/effets indésirables , Mâle , Femelle , Études prospectives , Adulte d'âge moyen , Adulte , Dysfonction primaire du greffon/mortalité , Dysfonction primaire du greffon/étiologie , Unités de soins intensifs , Estimation de Kaplan-Meier , Complications postopératoires/mortalité , Pression , Oxygénation extracorporelle sur oxygénateur à membrane/mortalité , Facteurs de risqueRÉSUMÉ
BACKGROUND: The N6-methyladenosine (m6A) modification of RNA and its regulators have important roles in the pathogenesis of pulmonary hypertension (PH). Ythdf2 (YTH N6-methyladenosine RNA binding protein 2) is best known for its role in degrading m6A-modified mRNAs such as Hmox1 mRNA, which leads to alternative activation of macrophages in PH. Recent studies have also linked Ythdf2 to the proliferation of pulmonary artery smooth muscle cells (PASMCs). However, its specific roles in PASMCs and downstream targets during the development of PH remain unclear. METHODS: The expression and biological function of Ythdf2 in PASMCs were investigated in human and experimental models of PH. Smooth muscle cell-specific Ythdf2-deficient mice were used to assess the roles of Ythdf2 in PASMCs in vivo. Proteomic analysis, m6A sequencing, and RNA immunoprecipitation analysis were used to screen for potential downstream targets. RESULTS: Ythdf2 was significantly upregulated in human and rodent PH-PASMCs, and smooth muscle cell-specific Ythdf2 deficiency ameliorated PASMC proliferation, right ventricular hypertrophy, pulmonary vascular remodeling, and PH development. Higher expression of Ythdf2 promoted PASMC proliferation and PH by paradoxically stabilizing Myadm mRNA in an m6A-dependent manner. Loss of Ythdf2 decreased the expression of Myadm in PASMCs and pulmonary arteries, both in vitro and in vivo. Additionally, silencing Myadm inhibited the Ythdf2-dependent hyperproliferation of PASMCs by upregulating the cell cycle kinase inhibitor p21. CONCLUSIONS: We have identified a novel mechanism where the increased expression of Ythdf2 stimulates PH-PASMC proliferation through an m6A/Myadm/p21 pathway. Strategies targeting Ythdf2 in PASMCs might be useful additions to the therapeutic approach to PH.
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Prolifération cellulaire , Hypertension pulmonaire , Muscles lisses vasculaires , Myocytes du muscle lisse , Artère pulmonaire , Protéines de liaison à l'ARN , Remodelage vasculaire , Animaux , Humains , Mâle , Souris , Cellules cultivées , Modèles animaux de maladie humaine , Hypertension pulmonaire/métabolisme , Hypertension pulmonaire/génétique , Muscles lisses vasculaires/métabolisme , Muscles lisses vasculaires/anatomopathologie , Myocytes du muscle lisse/métabolisme , Artère pulmonaire/métabolisme , Stabilité de l'ARN , ARN messager/génétique , ARN messager/métabolisme , Protéines de liaison à l'ARN/métabolisme , Protéines de liaison à l'ARN/génétique , Remodelage vasculaire/physiologie , Remodelage vasculaire/génétiqueRÉSUMÉ
BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.
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Trouble autistique , Encéphale , Cognition , Comportement déviant , Humains , Femelle , Mâle , Enfant , Encéphale/croissance et développement , Adolescent , Cognition/physiologie , Conflit familial , Mères , Adulte , Grossesse , Jeune adulte , Grossesse de l'adolescente , Facteurs sexuelsRÉSUMÉ
Ginsenoside compound K (GCK) possesses a glucocorticoid (GC)-like structure and functions as an agonist of the glucocorticoid receptor (GR), thereby exerting anti-inflammatory effects through GR activation. However, it remains unclear whether GCK leads to hyperglycemia, which is a known adverse reaction associated with classical GCs. In this study, we have successfully demonstrated that GCK exerts its anti-inflammatory effects in a rat model of adjuvant arthritis without impacting gluconeogenesis and pentose phosphate pathways, thus avoiding any glucose metabolism disorders. By employing the GR mutant plasmid, we have identified the binding site between GCK and GR as GRM560T, which differs from the binding site shared by dexamethasone (DEX) and GR. Notably, compared to DEX, GCK induces distinct levels of phosphorylation at S211 on GR upon binding to activate steroid receptor coactivator 1 (SRC1)-a co-factor responsible for mediating anti-inflammatory effects-while not engaging peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-an associated coactivator involved in gluconeogenesis.
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Anti-inflammatoires , Arthrite expérimentale , Ginsénosides , Rat Sprague-Dawley , Récepteurs aux glucocorticoïdes , Animaux , Ginsénosides/pharmacologie , Rats , Anti-inflammatoires/pharmacologie , Arthrite expérimentale/traitement médicamenteux , Arthrite expérimentale/métabolisme , Mâle , Récepteurs aux glucocorticoïdes/métabolisme , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes/métabolisme , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes/génétique , Néoglucogenèse/effets des médicaments et des substances chimiques , Glucose/métabolisme , Humains , Dexaméthasone/pharmacologieRÉSUMÉ
The ATP-binding cassette subfamily A member 3 (ABCA3) protein plays a fundamental role in surfactant homeostasis. Most children with ABCA3 gene mutations develop pulmonary interstitial fibrosis leading to the development of interstitial lung disease. Since traditional medicine does not offer effective therapy, the best option is lung transplantations, especially bilateral lung transplantations. We are reporting the case of a successful bilateral lung transplantation in a five-year-old child with pulmonary interstitial fibrosis caused by ABCA3 gene mutations. This successful transplantation enabled the patient to get rid of chronic cough and tachypnea.
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Transporteurs ABC , Transplantation pulmonaire , Mutation , Humains , Transporteurs ABC/génétique , Enfant d'âge préscolaire , Mâle , Pneumopathies interstitielles/génétique , Pneumopathies interstitielles/chirurgie , Fibrose pulmonaire/génétique , Fibrose pulmonaire/chirurgie , Résultat thérapeutiqueRÉSUMÉ
Conventional antisolvents such as chlorobenzene and benzotrifluoride are highly toxic and volatile, and therefore not preferred for large-scale fabrication. As such, green antisolvents are favored for the eco-friendly fabrication of perovskite films. This review primarily discusses the impact of various green antisolvents on the fabrication of thin perovskite films and analyzes the main chemical characteristics of these green antisolvents. It also interprets the impact of green antisolvent treatment on crystal growth and nucleation crystallization mechanisms. It introduces the effective fabrication of large-area devices using green antisolvents and analyzes the mechanisms by which green antisolvents enhance device stability. Subsequently, several green antisolvents capable of preparing highly stable and efficient devices are listed. Finally, we outline the key challenges and future prospects of antisolvent treatment. This review paves the way for green fabrication of industrial perovskite solar cells.
RÉSUMÉ
AIMS: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. METHODS: Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. RESULTS: We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. CONCLUSIONS: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.
Sujet(s)
Neuroleptiques , Aripiprazole , Modèles animaux de maladie humaine , Maléate de dizocilpine , Hippocampe , Hypercinésie , Schizophrénie , Animaux , Aripiprazole/pharmacologie , Aripiprazole/usage thérapeutique , Schizophrénie/traitement médicamenteux , Hippocampe/effets des médicaments et des substances chimiques , Neuroleptiques/pharmacologie , Neuroleptiques/usage thérapeutique , Maléate de dizocilpine/pharmacologie , Souris , Hypercinésie/traitement médicamenteux , Mâle , Locomotion/effets des médicaments et des substances chimiques , Locomotion/physiologie , Antagonistes des acides aminés excitateurs/pharmacologie , Souris de lignée C57BL , Animaux nouveau-nés , Neurones/effets des médicaments et des substances chimiques , Rythme thêta/effets des médicaments et des substances chimiques , Rythme thêta/physiologieRÉSUMÉ
Prolonged mechanical ventilation (PMV) is commonly associated with increased post-operative complications and mortality. Nevertheless, the predictive factors of PMV after lung transplantation (LTx) using extracorporeal membrane oxygenation (ECMO) as a bridge remain unclear. The present study aimed to develop a novel nomogram for PMV prediction in patients using ECMO as a bridge to LTx. A total of 173 patients who used ECMO as a bridge following LTx from January 2022 to June 2023 were divided into the training (122) and validation sets (52). A mechanical ventilation density plot of patients after LTx was then performed. The training set was divided in two groups, namely PMV (95) and non-prolonged ventilation (NPMV) (27). For the survival analysis, the effect of PMV was assessed using the log-rank test. Univariate and multivariate logistic regression analyses were performed to assess factors associated with PMV. A risk nomogram was established based on the multivariate analysis, and model performance was further assessed in terms of calibration, discrimination, and clinical usefulness. Internal validation was additionally conducted. The difference in survival curves in PMV and NPMV groups was statistically significant (P < 0.001). The multivariate analysis and risk factors in the nomogram revealed four factors to be significantly associated with PMV, namely the body mass index (BMI), operation time, lactic acid at T0 (Lac), and driving pressure (DP) at T0. These four factors were used to develop a nomogram, with an area under the curve (AUC) of 0.852 and good calibration. After internal validation, AUC was 0.789 with good calibration. Furthermore, goodness-of-fit test and decision-curve analysis (DCA) indicated satisfactory performance in the training and internal validation sets. The proposed nomogram can reliably and accurately predict the risk of patients to develop PMV after LTx using ECMO as a bridge. Four modifiable factors including BMI, operation time, Lac, and DP were optimized, which may guide preventative measures and improve prognosis.