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1.
J Agric Food Chem ; 72(37): 20458-20469, 2024 Sep 18.
Article de Anglais | MEDLINE | ID: mdl-39230615

RÉSUMÉ

Our previous study proved that epicatechin (EC) and ß-glucan (BG) from whole-grain highland barley synergistically modulate glucose metabolism in insulin-resistant HepG2 cells. However, the main target and the mechanism underlying the modulation of glucose metabolism in vivo remain largely unknown. In this study, cell transfection assay and microscale thermophoresis analysis revealed that EC and BG could directly bind to the insulin receptor (IR) and mammalian receptor for rapamycin (mTOR), respectively. Molecular dynamic analysis indicated that the key amino acids of binding sites were Asp, Met, Val, Lys, Ser, and Tys. EC supplementation upregulated the IRS-1/PI3K/Akt pathway, while BG upregulated the mTOR/Akt pathway. Notably, supplementation with EC + BG significantly increased Akt and glucose transporter type 4 (GLUT4) protein expressions, while decreasing glycogen synthase kinase 3ß (GSK-3ß) expression in liver cells as compared to the individual effects of EC and BG, indicating their synergistic effect on improving hepatic glucose uptake and glycogen synthesis. Consistently, supplementation with EC + BG significantly decreased blood glucose levels and improved oral glucose tolerance compared to EC and BG. Therefore, combined supplementation with EC and BG may bind to corresponding receptors, targeting synergistic activation of Akt expression, leading to the improvement of hepatic glucose metabolism and thereby ameliorating hyperglycemia in vivo.


Sujet(s)
Catéchine , Glucose , Hordeum , Hyperglycémie , Foie , Souris de lignée C57BL , bêta-Glucanes , Hordeum/composition chimique , bêta-Glucanes/pharmacologie , bêta-Glucanes/composition chimique , Animaux , Souris , Catéchine/pharmacologie , Catéchine/administration et posologie , Foie/métabolisme , Foie/effets des médicaments et des substances chimiques , Mâle , Humains , Glucose/métabolisme , Hyperglycémie/traitement médicamenteux , Hyperglycémie/métabolisme , Synergie des médicaments , Protéines proto-oncogènes c-akt/métabolisme , Protéines proto-oncogènes c-akt/génétique , Transporteur de glucose de type 4/métabolisme , Transporteur de glucose de type 4/génétique , Glycogen synthase kinase 3 beta/métabolisme , Glycogen synthase kinase 3 beta/génétique , Glycémie/métabolisme , Sérine-thréonine kinases TOR/métabolisme , Sérine-thréonine kinases TOR/génétique , Extraits de plantes/pharmacologie , Extraits de plantes/administration et posologie , Cellules HepG2
2.
Food Funct ; 15(18): 9272-9283, 2024 Sep 16.
Article de Anglais | MEDLINE | ID: mdl-39162187

RÉSUMÉ

Highland barley is a natural source for the development of phenolic compounds that exhibit potential in preventing type 2 diabetes, which is important for the agricultural and industrial utilization of highland barley. However, very few studies have focused on their effect on small intestinal absorption and barrier dysfunction, as well as the direct target for the modulation of hepatic glucose metabolism. In this study, procyanidin B1 (PB) and p-coumaric acid (CA) isolated from highland barley supplementation in impaired glucose tolerance (IGT) mice significantly increased lactase-phlorizin hydrolase (LPH), sulfotransferase 1A1 (SULT1A1), UDP glucuronosyltransferase 1A (UGT1A) families and sodium-dependent glucose transporter 1 (SGLT1) expression in the small intestine of IGT mice, indicating beneficial effects on polyphenol deglycosylation and transportation. Supplementation with PB and CA also exhibited attenuation of small intestinal barrier dysfunction by improving the mucus layer and tight junctions, which was closely related to the transportation of phenolic compounds. In addition, PB and CA supplementation were explored directly to bind to the insulin receptor and activate the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, thereby modulating hepatic glucose metabolism and ameliorating hyperglycemic in IGT mice. These results offer crucial insights into the potential development of PB and CA as non-food nutraceuticals, as well as the extensive utilization of highland barley as an industrial crop.


Sujet(s)
Biflavonoïdes , Catéchine , Acides coumariques , Intolérance au glucose , Glucose , Hordeum , Intestin grêle , Foie , Proanthocyanidines , Animaux , Hordeum/composition chimique , Proanthocyanidines/pharmacologie , Souris , Mâle , Intolérance au glucose/traitement médicamenteux , Intolérance au glucose/métabolisme , Biflavonoïdes/pharmacologie , Acides coumariques/pharmacologie , Catéchine/pharmacologie , Foie/métabolisme , Foie/effets des médicaments et des substances chimiques , Intestin grêle/métabolisme , Intestin grêle/effets des médicaments et des substances chimiques , Glucose/métabolisme , Alimentation riche en graisse/effets indésirables , Souris de lignée C57BL , Propionates , Transporteur-1 sodium-glucose/métabolisme , Transporteur-1 sodium-glucose/génétique , Humains
3.
Brief Bioinform ; 25(5)2024 Jul 25.
Article de Anglais | MEDLINE | ID: mdl-39073829

RÉSUMÉ

With the exponential growth of digital data, there is a pressing need for innovative storage media and techniques. DNA molecules, due to their stability, storage capacity, and density, offer a promising solution for information storage. However, DNA storage also faces numerous challenges, such as complex biochemical constraints and encoding efficiency. This paper presents Explorer, a high-efficiency DNA coding algorithm based on the De Bruijn graph, which leverages its capability to characterize local sequences. Explorer enables coding under various biochemical constraints, such as homopolymers, GC content, and undesired motifs. This paper also introduces Codeformer, a fast decoding algorithm based on the transformer architecture, to further enhance decoding efficiency. Numerical experiments indicate that, compared with other advanced algorithms, Explorer not only achieves stable encoding and decoding under various biochemical constraints but also increases the encoding efficiency and bit rate by ¿10%. Additionally, Codeformer demonstrates the ability to efficiently decode large quantities of DNA sequences. Under different parameter settings, its decoding efficiency exceeds that of traditional algorithms by more than two-fold. When Codeformer is combined with Reed-Solomon code, its decoding accuracy exceeds 99%, making it a good choice for high-speed decoding applications. These advancements are expected to contribute to the development of DNA-based data storage systems and the broader exploration of DNA as a novel information storage medium.


Sujet(s)
Algorithmes , ADN , ADN/génétique , ADN/composition chimique , Logiciel , Analyse de séquence d'ADN/méthodes , Biologie informatique/méthodes
4.
FEBS Open Bio ; 14(6): 922-941, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38710666

RÉSUMÉ

The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single-cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non-parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment.


Sujet(s)
Hépatectomie , Hépatocytes , Régénération hépatique , Macrophages , Granulocytes neutrophiles , Régénération hépatique/génétique , Animaux , Granulocytes neutrophiles/métabolisme , Souris , Macrophages/métabolisme , Hépatocytes/métabolisme , Foie/métabolisme , Foie/cytologie , Souris de lignée C57BL , Mâle
5.
BMC Oral Health ; 24(1): 635, 2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38811930

RÉSUMÉ

BACKGROUND: Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the development of T2D and the underlain mechanism have not been fully elucidated. METHODS: A Mendelian randomization (MR) was performed to estimate the causality between two diseases. Bioinformatics tools, including gene ontology and pathway enrichment analyses, were employed to analyze the common differentially expressed genes (DEGs) in periodontitis and T2D. MR and colocalization analyses were then utilized to investigate the causal associations between potential pathogenic gene expression and the risk of T2D. Single cell-type expression analysis was further performed to detect the cellular localization of these genes. RESULTS: Genetically predicted periodontitis was associated with a higher risk of T2D (OR, 1.469; 95% CI, 1.117-1.930; P = 0.006) and insulin resistance (OR 1.034; 95%CI 1.001-1.068; P = 0.041). 79 common DEGs associated with periodontitis and T2D were then identified and demonstrated enrichment mainly in CXC receptor chemokine receptor binding and interleutin-17 signaling pathway. The integration of GWAS with the expression quantitative trait locis of these genes from the peripheral blood genetically prioritized 6 candidate genes, including 2 risk genes (RAP2A, MCUR1) and 4 protective genes (WNK1, NFIX, FOS, PANX1) in periodontitis-related T2D. Enriched in natural killer cells, RAP2A (OR 4.909; 95% CI 1.849-13.039; P = 0.001) demonstrated high risk influence on T2D, and exhibited strong genetic evidence of colocalization (coloc.abf-PPH4 = 0.632). CONCLUSIONS: This study used a multi-omics integration method to explore causality between periodontitis and T2D, and revealed molecular mechanisms using bioinformatics tools. Periodontitis was associated with a higher risk of T2D. MCUR1, RAP2A, FOS, PANX1, NFIX and WNK1 may play important roles in the pathogenesis of periodontitis-related T2D, shedding light on the development of potential drug targets.


Sujet(s)
Biologie informatique , Diabète de type 2 , Analyse de randomisation mendélienne , Parodontite , Humains , Diabète de type 2/génétique , Diabète de type 2/complications , Parodontite/génétique , Parodontite/complications , Étude d'association pangénomique
6.
Mol Ther Nucleic Acids ; 35(2): 102190, 2024 Jun 11.
Article de Anglais | MEDLINE | ID: mdl-38721279

RÉSUMÉ

RNA base editors should ideally be free of immunogenicity, compact, efficient, and specific, which has not been achieved for C > U editing. Here we first describe a compact C > U editor entirely of human origin, created by fusing the human C > U editing enzyme RESCUE-S to Cas inspired RNA targeting system (CIRTS), a tiny, human-originated programmable RNA-binding domain. This editor, CIRTS-RESCUEv1 (V1), was inefficient. Remarkably, a short histidine-rich domain (HRD), which is derived from the internal disordered region (IDR) in the human CYCT1, a protein capable of liquid-liquid phase separation (LLPS), enhanced V1 editing at on-targets as well as off-targets, the latter effect being minor. The V1-HRD fusion protein formed puncta characteristic of LLPS, and various other IDRs (but not an LLPS-impaired mutant) could replace HRD to effectively induce puncta and potentiate V1, suggesting that the diverse domains acted via a common, LLPS-based mechanism. Importantly, the HRD fusion strategy was applicable to various other types of C > U RNA editors. Our study expands the RNA editing toolbox and showcases a general method for stimulating C > U RNA base editors.

7.
Pediatr Cardiol ; 2024 Apr 25.
Article de Anglais | MEDLINE | ID: mdl-38662212

RÉSUMÉ

Anthracycline chemotherapy is associated with the left ventricular (LV) dysfunction, but the conventional echocardiographic parameter is insensitive in detecting subclinical cardiac dysfunction, and the role of echocardiography in children cancer survivors (CCSs) has not been well established. Here, the myocardial work (MW) was employed to evaluate the early effect of the anthracyclines on LV function in children lymphoma survivors, as well as to explore the clinical application value of this modality. 51 children lymphoma survivors treated with anthracyclines were included. During the treatments, the echocardiography was performed at baseline (T0 phase), the 3rd (T1 phase) and 6th (T2 phase) chemotherapeutic cycle, respectively. After that, the conventional echocardiographic parameters, LV global longitudinal strain (GLS), and global myocardial work (GMW) parameters were obtained. Finally, these echocardiographic parameters were compared to distinguish the differences among three groups, and correlation analysis was used to identify relationship between GMW parameters and LV GLS. Compared with the baseline, we found that there are no significant differences for LVEF and other conventional echocardiographic parameters after chemotherapy, but the value of LV lateral E/E' increased at T1 and T2 group. The GLS, global work index, global constructed work, and global work efficiency were decreased, while the global wasted work was increased after chemotherapy (all P < 0.05). The correlation analysis showed that the GLS has significant correlation with GMW parameters (all P < 0.001). The MW, as a new noninvasive echocardiography modality, could be used to quantitatively evaluate the LV MW in children lymphoma survivors treated with anthracyclines, which providing a sensitive method to early detect the children's LV dysfunction after the chemotherapy.

8.
Eur J Med Chem ; 271: 116395, 2024 May 05.
Article de Anglais | MEDLINE | ID: mdl-38626523

RÉSUMÉ

The transforming growth factor ß1 (TGFß1)/SMAD signaling pathway regulates many vital physiological processes. The development of potent inhibitors targeting activin receptor-like kinase 5 (ALK5) would provide potential treatment reagents for various diseases. A significant number of ALK5 inhibitors have been discovered, and they are currently undergoing clinical evaluation at various stages. However, the clinical demands were far from being met. In this study, we utilized an alternative conformation-similarity-based virtual screening (CSVS) combined with a fragment-based drug designing (FBDD) strategy to efficiently discover a potent and active hit with a novel chemical scaffold. After structural optimization in the principle of group replacement, compound 57 was identified as the most promising ALK5 inhibitor. Compound 57 demonstrated significant inhibitory effects against the TGF-ß1/SMAD signaling pathway. It could markedly attenuate the production of extracellular matrix (ECM) and deposition of collagen. Also, the lead compound showed adequate pharmacokinetic (PK) properties and good in vivo tolerance. Moreover, treatment with compound 57 in two different xerograph models showed significant inhibitory effects on the growth of pancreatic cancer cells. These results suggested that lead compound 57 refers as a promising ALK5 inhibitor both in vitro and in vivo, which merits further validation.


Sujet(s)
Conception de médicament , Inhibiteurs de protéines kinases , Pyrazoles , Pyrimidines , Récepteur de type I du facteur de croissance transformant bêta , Récepteur de type I du facteur de croissance transformant bêta/antagonistes et inhibiteurs , Récepteur de type I du facteur de croissance transformant bêta/métabolisme , Humains , Pyrazoles/pharmacologie , Pyrazoles/composition chimique , Pyrazoles/synthèse chimique , Pyrimidines/pharmacologie , Pyrimidines/composition chimique , Pyrimidines/synthèse chimique , Relation structure-activité , Inhibiteurs de protéines kinases/pharmacologie , Inhibiteurs de protéines kinases/synthèse chimique , Inhibiteurs de protéines kinases/composition chimique , Animaux , Structure moléculaire , Facteur de croissance transformant bêta-1/métabolisme , Facteur de croissance transformant bêta-1/antagonistes et inhibiteurs , Antinéoplasiques/pharmacologie , Antinéoplasiques/synthèse chimique , Antinéoplasiques/composition chimique , Prolifération cellulaire/effets des médicaments et des substances chimiques , Relation dose-effet des médicaments , Souris , Lignée cellulaire tumorale , Tests de criblage d'agents antitumoraux , Récepteurs TGF-bêta/antagonistes et inhibiteurs , Récepteurs TGF-bêta/métabolisme
9.
Int J Biol Sci ; 20(4): 1375-1388, 2024.
Article de Anglais | MEDLINE | ID: mdl-38385066

RÉSUMÉ

Gingival inflammation and alveolar bone loss are characteristic manifestations of periodontitis. Interleukin (IL)-1ß, the maturation of which is mainly regulated by NOD-like receptor protein (NLRP) 3 inflammasome, not only amplifies the inflammatory response but also triggers osteoclastogenesis, thereby accelerating the progression of periodontitis. Dioscin, a natural steroid saponin, has been shown to inhibit NLRP3 inflammasome. Nevertheless, research on the effectiveness of Dioscin for the management of periodontitis remains scarce. In this study, Dioscin was found to dramatically reduce the integral components of NLRP3 inflammasome, ultimately limiting IL-1ß secretion. Notably, the inhibitory impact of Dioscin on NLRP3 inflammasome might be exerted by curbing the generation of mitochondrial (mt) reactive oxygen species (ROS) and oxidized (ox) mtDNA, which were mediated by inhibition of K+ efflux. Furthermore, Dioscin effectively alleviated periodontitis in mice. Overall, the results established that Dioscin could alleviate periodontitis by inhibiting NLRP3 inflammasome via modulation of the K+ efflux-mtROS-ox-mtDNA pathway, holding the potential to treat periodontitis and other NLRP3-driven inflammatory diseases.


Sujet(s)
Diosgénine/analogues et dérivés , Inflammasomes , Parodontite , Animaux , Souris , Inflammasomes/métabolisme , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Parodontite/traitement médicamenteux , Parodontite/métabolisme , Mitochondries/métabolisme , Homéostasie , ADN mitochondrial/métabolisme , Espèces réactives de l'oxygène/métabolisme , Interleukine-1 bêta/métabolisme
10.
Acad Radiol ; 31(1): 187-198, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-37316368

RÉSUMÉ

RATIONALE AND OBJECTIVES: This project aims to investigate the diagnostic performance of multiple overlapping-echo detachment imaging (MOLED) technique-derived transverse relaxation time (T2) maps in predicting progesterone receptor (PR) and S100 expression in meningiomas. MATERIALS AND METHODS: 63 meningioma patients were enrolled from October 2021 to August 2022, who underwent a complete routine magnetic resonance imaging and T2 MOLED, which can characterize the whole brain transverse relaxation time within 32 seconds in a single scan. After the surgical resection of meningiomas, the expression levels of PR and S100 were determined by an experienced pathologist using immunohistochemistry techniques. Histogram analysis was performed in tumor parenchyma based on the parametric maps. Independent t test and Mann-Whitney U test were applied for the comparison of histogram parameters between different groups, with a significance level of P < .05. Logistic regression and receiver operating characteristic (ROC) analysis with 95% confidence interval were conducted for the diagnostic efficiency evaluation. RESULTS: PR-positive group had significantly elevated T2 histogram parameters (P = .001-.049) compared to the PR-negative group. The multivariate logistic regression model with T2 showed the highest area under the ROC curve (AUC) for predicting PR expression (AUC=0.818). Additionally, the multivariate model also had the best diagnostic performance for predicting meningioma S100 expression (AUC=0.768). CONCLUSION: The MOLED technique-derived T2 maps can distinguish PR and S100 status in meningiomas preoperatively.


Sujet(s)
Tumeurs des méninges , Méningiome , Humains , Méningiome/imagerie diagnostique , Méningiome/chirurgie , Méningiome/anatomopathologie , Imagerie par résonance magnétique de diffusion/méthodes , Études prospectives , Récepteurs à la progestérone , Imagerie par résonance magnétique/méthodes , Tumeurs des méninges/imagerie diagnostique , Tumeurs des méninges/chirurgie , Tumeurs des méninges/anatomopathologie , Études rétrospectives
11.
J Magn Reson Imaging ; 60(3): 964-976, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38112331

RÉSUMÉ

BACKGROUND: Meningioma subtype is crucial in treatment planning and prognosis delineation, for grade 1 meningiomas. T2 relaxometry could provide detailed microscopic information but is often limited by long scanning times. PURPOSE: To investigate the potential of T2 maps derived from multiple overlapping-echo detachment imaging (MOLED) for predicting meningioma subtypes and Ki-67 index, and to compare the diagnostic efficiency of two different region-of-interest (ROI) placements (whole-tumor and contrast-enhanced, respectively). STUDY TYPE: Prospective. PHANTOM/SUBJECTS: A phantom containing 11 tubes of MnCl2 at different concentrations, eight healthy volunteers, and 75 patients with grade 1 meningioma. FIELD STRENGTH/SEQUENCE: 3 T scanner. MOLED, T2-weighted spin-echo sequence, T2-dark-fluid sequence, and postcontrast T1-weighted gradient echo sequence. ASSESSMENT: Two ROIs were delineated: the whole-tumor area (ROI1) and contrast-enhanced area (ROI2). Histogram parameters were extracted from T2 maps. Meningioma subtypes and Ki-67 index were reviewed by a neuropathologist according to the 2021 classification criteria. STATISTICAL TESTS: Linear regression, Bland-Altman analysis, Pearson's correlation analysis, independent t test, Mann-Whitney U test, Kruskal-Wallis test with Bonferroni correction, and multivariate logistic regression analysis with the P-value significance level of 0.05. RESULTS: The MOLED T2 sequence demonstrated excellent accuracy for phantoms and volunteers (Meandiff = -1.29%, SDdiff = 1.25% and Meandiff = 0.36%, SDdiff = 2.70%, respectively), and good repeatability for volunteers (average coefficient of variance = 1.13%; intraclass correlation coefficient = 0.877). For both ROI1 and ROI2, T2 variance had the highest area under the curves (area under the ROC curve = 0.768 and 0.761, respectively) for meningioma subtyping. There was no significant difference between the two ROIs (P = 0.875). Significant correlations were observed between T2 parameters and Ki-67 index (r = 0.237-0.374). DATA CONCLUSION: MOLED T2 maps can effectively differentiate between meningothelial, fibrous, and transitional meningiomas. Moreover, T2 histogram parameters were significantly correlated with the Ki-67 index. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.


Sujet(s)
Imagerie par résonance magnétique , Tumeurs des méninges , Méningiome , Fantômes en imagerie , Humains , Méningiome/imagerie diagnostique , Femelle , Mâle , Tumeurs des méninges/imagerie diagnostique , Tumeurs des méninges/anatomopathologie , Adulte d'âge moyen , Imagerie par résonance magnétique/méthodes , Adulte , Études prospectives , Sujet âgé , Antigène KI-67/métabolisme , Produits de contraste , Courbe ROC , Grading des tumeurs
12.
Oral Dis ; 2023 Oct 27.
Article de Anglais | MEDLINE | ID: mdl-37890080

RÉSUMÉ

OBJECTIVES: Periodontitis and peri-implantitis are oral infectious-inflammatory diseases associated with oral microbial dysbiosis. Microbiome-based therapies, characterized by manipulation of the microbiota, are emerging as promising therapeutic approaches to resolve the microbial dysbiosis and associated dysregulation of immune system. This review aims at summarizing recent progress on microbiome-based therapies in periodontitis and peri-implantitis, promoting a further understanding of the related therapeutic mechanisms. SUBJECTS AND METHODS: Pertinent literatures focused on microbiome-based therapies for periodontitis and peri-implantitis are obtained from PubMed and Web of Science. RESULTS: In this article, we review the roles and therapeutic mechanisms of four microbiome-based therapies, including probiotics, postbiotics, predatory bacteria and phages, and microbiota transplantation, in the management of periodontitis and peri-implantitis. Challenges facing this field are also discussed, highlighting the areas that require more attention and investigation. CONCLUSIONS: Microbiome-based therapies may serve as effective treatment for periodontitis and peri-implantitis. This review presents a new viewpoint to this field.

13.
J Neurosci ; 43(44): 7276-7293, 2023 11 01.
Article de Anglais | MEDLINE | ID: mdl-37684032

RÉSUMÉ

The parabrachial nucleus (PBN) interfaces between taste and feeding systems and is also an important hub for relaying distress information and threats. Despite that the PBN sends projections to the ventral tegmental area (VTA), a heterogeneous brain region that regulates motivational behaviors, the function of the PBN-to-VTA connection remains elusive. Here, by using male mice in several behavioral paradigms, we discover that VTA-projecting PBN neurons are significantly engaged in contextual fear, restraint or mild stress but not palatable feeding, visceral malaise, or thermal pain. These results suggest that the PBN-to-VTA input may relay negative emotions under threat. Consistent with this notion, optogenetic activation of PBN-to-VTA glutamatergic input results in aversion, which is sufficient to override palatable feeding. Moreover, in a palatable food-reinforced operant task, we demonstrate that transient optogenetic activation of PBN-to-VTA input during food reward retrieval disengages instrumental food-seeking behaviors but spares learned action-outcome association. By using an activity-dependent targeting approach, we show that VTA DA neurons are disengaged by the PBN afferent activation, implicating that VTA non-DA neurons may mediate PBN afferent regulation. We further show that optogenetic activation of VTA neurons functionally recruited by the PBN input results in aversion, dampens palatable feeding, and disengages palatable food self-administration behavior. Finally, we demonstrate that transient activation of VTA glutamatergic, but not GABAergic, neurons recapitulates the negative regulation of the PBN input on food self-administration behavior. Together, we reveal that the PBN-to-VTA input conveys negative affect, likely through VTA glutamatergic neurons, to disengage instrumental food-seeking behaviors.SIGNIFICANCE STATEMENT The PBN receives multiple inputs and thus is well positioned to route information of various modalities to engage different downstream circuits to attend or respond accordingly. We demonstrate that the PBN-to-VTA input conveys negative affect and then triggers adaptive prioritized responses to address pertinent needs by withholding ongoing behaviors, such as palatable food seeking or intake shown in the present study. It has evolutionary significance because preparing to cope with stressful situations or threats takes priority over food seeking to promote survival. Knowing how appropriate adaptive responses are generated will provide new insights into circuitry mechanisms of various coping behaviors to changing environmental stimuli.


Sujet(s)
Noyau parabrachial , Aire tegmentale ventrale , Souris , Mâle , Animaux , Aire tegmentale ventrale/physiologie , Noyau parabrachial/physiologie , Aliments , Neurones GABAergiques , Émotions , Récompense
14.
Chem Commun (Camb) ; 59(81): 12132-12135, 2023 Oct 10.
Article de Anglais | MEDLINE | ID: mdl-37740302

RÉSUMÉ

Electrochemical nitrogen fixation provides a sustainable alternative to the Haber-Bosch technique. Herein, nanoporous AuCu alloys are fabricated with more active sites and accessible channels, which promote N2 absorbability and activation. Our catalyst displays superior efficiency of 45.7%, ammonia yield of 25.7 µg h-1 cm-2 and selectivity of 98%, overcoming solid Au and Cu nanoparticles.

15.
FASEB J ; 37(9): e23148, 2023 09.
Article de Anglais | MEDLINE | ID: mdl-37606556

RÉSUMÉ

Episcleral vasculature malformation is a significant feature of Sturge-Weber syndrome (SWS) secondary glaucoma, the density and diameter of which are correlated with increased intraocular pressure. We previously reported that the GNAQ R183Q somatic mutation was located in the SWS episclera. However, the mechanism by which GNAQ R183Q leads to episcleral vascular malformation remains poorly understood. In this study, we investigated the correlation between GNAQ R183Q and episcleral vascular malformation via surgical specimens, human umbilical vein endothelial cells (HUVECs), and the HUVEC cell line EA.hy926. Our findings demonstrated a positive correlation between episcleral vessel diameter and the frequency of the GNAQ R183Q variant. Furthermore, the upregulation of genes from the Notch signaling pathway and abnormal coexpression of the arterial marker EphrinB2 and venous marker EphB4 were demonstrated in the scleral vasculature of SWS. Analysis of HUVECs overexpressing GNAQ R183Q in vitro confirmed the upregulation of Notch signaling and arterial markers. In addition, knocking down of Notch1 diminished the upregulation of arterial markers induced by GNAQ R183Q. Our findings strongly suggest that GNAQ R183Q leads to malformed episcleral vasculatures through Notch-induced aberrant arteriovenous specification. These insights into the molecular basis of episcleral vascular malformation will provide new pathways for the development of effective treatments for SWS secondary glaucoma.


Sujet(s)
Glaucome , Syndrome de Sturge-Weber , Humains , Syndrome de Sturge-Weber/génétique , Transduction du signal , Cellules endothéliales de la veine ombilicale humaine , Mutation , Sous-unités alpha Gq-G11 des protéines G/génétique
17.
Ophthalmic Res ; 66(1): 958-967, 2023.
Article de Anglais | MEDLINE | ID: mdl-37331334

RÉSUMÉ

INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of combined trabeculotomy-non-penetrating deep sclerectomy (CTNS) in the treatment of Sturge-Weber syndrome (SWS) secondary glaucoma. METHODS: This retrospective study reviewed cases that underwent CTNS as initial surgery for SWS secondary glaucoma at our Ophthalmology Department center from April 2019 to August 2020. Surgical success was defined as an intraocular pressure (IOP) ≤ 21 mm Hg with (qualified success) or without (complete success) the use of anti-glaucoma medications. IOP >21 mm Hg or <5 mm Hg despite 3 or more applications of anti-glaucoma medications on 2 consecutive follow-up visits or at the last follow-up, performance of additional glaucoma (IOP-lowering) surgery, or with vision-threatening complications were classified as failure. RESULTS: A total of 22 eyes of 21 patients were included. Twenty-one eyes were of early-onset type and 1 eye was of adulthood onset. For Kaplan-Meier survival analysis, the overall success rates at 1st and 2nd years were 95.2% and 84.9%, while the complete success rates at 1st and 2nd years were 42.9% and 36.7%. At the last follow-up (22.3 ± 4.0 months, range: 11.2∼31.2), overall success was achieved in 19 (85.7%) eyes and complete success in 12 (52.4%) eyes. Postoperative complications included transient hyphema (11/22, 50.0%) and transient Ⅰ degree shallow anterior chamber (1/22, 4.5%), and retinal detachment (1/22, 4.5%). No other severe com plications were detected during the follow-up. CONCLUSION: CTNS significantly reduces IOP in SWS secondary glaucoma patients who have serious episcleral vascular malformation. CTNS in SWS secondary glaucoma patients is safe and effective for short and medium periods. A randomized controlled study comparing the long-term prognosis of SWS early-onset and late-onset glaucoma underwent CTNS is worth conducting.


Sujet(s)
Glaucome , Syndrome de Sturge-Weber , Trabéculectomie , Humains , Adulte , Trabéculectomie/effets indésirables , Syndrome de Sturge-Weber/complications , Syndrome de Sturge-Weber/diagnostic , Syndrome de Sturge-Weber/chirurgie , Études rétrospectives , Antiglaucomateux , Résultat thérapeutique , Glaucome/chirurgie , Glaucome/étiologie , Pression intraoculaire , Sclère/chirurgie , Études de suivi
18.
BMC Ophthalmol ; 23(1): 256, 2023 Jun 07.
Article de Anglais | MEDLINE | ID: mdl-37286943

RÉSUMÉ

PURPOSE: To perform an in vivo evaluation of the changes in Schlemm's canal (SC) among patients with primary angle-closure disease (PACD) using swept-source optical coherence tomography (SS-OCT). METHODS: Patients diagnosed with PACD who had not undergone surgery were recruited. The SS-OCT quadrants scanned herein included the nasal and temporal sections at 3 and 9 o'clock, respectively. The diameter and cross-sectional area of the SC were measured. A linear mixed-effects model was performed to analyze the effects of parameters on the SC changes. The hypothesis of interest was related to the angle status (iridotrabecular contact, ITC/open angle, OPN), which was further explored with pairwise comparisons of the estimated marginal means (EMMs) of the SC diameter and SC area. In the ITC regions, the relationship between the trabecular-iris contact length (TICL) percentage and SC parameters was also studied by a mixed model. RESULTS: A total of 49 eyes of 35 patients were included for measurements and analysis. The percentage of observable SCs in the ITC regions was only 58.5% (24/41), whereas it was 86.0% (49/57) in the OPN regions (χ2 = 9.44, p = 0.002). ITC was significantly associated with a decreasing SC size. The EMMs for the diameter and cross-sectional area of SC at the ITC and OPN regions were 203.34 µm versus 261.41 µm (p = 0.006) and 3174.43 µm2 versus 5347.63 µm2 (p = 0.022), respectively. Sex, age, spherical equivalent refraction, intraocular pressure, axial length, extent of angle closure, history of acute attack and treatment with LPI were not significantly associated with SC parameters. In the ITC regions, a larger TICL percentage was significantly associated with a decrease in SC diameter and area (p = 0.003 and 0.019, respectively). CONCLUSIONS: The morphologies of SC could be affected by the angle status (ITC/OPN) in patients with PACD, and ITC was significantly associated with a decreasing SC size. These changes in SC as described by OCT scans might help to elucidate the progression mechanisms of PACD.


Sujet(s)
Glaucome à angle fermé , Réseau trabéculaire de la sclère , Humains , Tomographie par cohérence optique/méthodes , Sinus veineux de la sclère , Sclère , Tonométrie oculaire , Pression intraoculaire , Glaucome à angle fermé/diagnostic , Glaucome à angle fermé/chirurgie
19.
Molecules ; 28(6)2023 Mar 20.
Article de Anglais | MEDLINE | ID: mdl-36985753

RÉSUMÉ

Electrochemical nitrogen reduction reaction (ENRR) offers a sustainable alternative to the environmentally hazardous Haber-Bosch process for producing ammonia. However, it suffers from an unsatisfactory performance due to its limited active sites and competitive hydrogen evolution reaction. Herein, we design a hydrophobic oleylamine-modified zeolitic imidazolate framework-coated nanoporous silver composite structure (NPS@O-ZIF). The composite achieves a high ammonia yield of (41.3 ± 0.9) µg·h-1·cm-2 and great Faradaic efficiency of (31.7 ± 1.2)%, overcoming the performances of NPS@ZIF and traditional silver nanoparticles@O-ZIF. Our strategy affords more active sites and accessible channels for reactant species due to the porous structure of NPS cores and restrains the evolution of hydrogen by introducing the hydrophobic molecule coated on the ZIF surfaces. Hence, the design of the hydrophobic core-shell composite catalyst provides a valuably practical strategy for ENRR as well as other water-sensitive reactions.

20.
Adv Sci (Weinh) ; 10(15): e2206933, 2023 May.
Article de Anglais | MEDLINE | ID: mdl-36995064

RÉSUMÉ

Electrocatalytic nitrogen reduction reaction (NRR) represents a promising sustainable approach for NH3 synthesis. However, the poor NRR performance of electrocatalysts is a great challenge at this stage, mainly owing to their low activity and the competitive hydrogen evolution reaction (HER). Herein, 2D ferric covalent organic framework/MXene (COF-Fe/MXene) nanosheets with controllable hydrophobic behaviors are successfully prepared via a multiple-in-one synthetic strategy. The boosting hydrophobicity of COF-Fe/MXene can effectively repel water molecules to inhibit the HER for enhanced NRR performances. By virtue of the ultrathin nanostructure, well-defined single Fe sites, nitrogen enrichment effect, and high hydrophobicity, the 1H,1H,2H,2H-perfluorodecanethiol modified COF-Fe/MXene hybrid shows a NH3 yield of 41.8 µg h-1 mgcat. -1 and a Faradaic efficiency of 43.1% at -0.5 V versus RHE in a 0.1 m Na2 SO4 water solution, which are vastly superior to the known Fe-based catalysts and even to the noble metal catalysts. This work provides a universal strategy to design and synthesis of non-precious metal electrocatalysts for high-efficiency N2 reduction to NH3 .

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