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Kawasaki disease (KD) is a systemic vasculitis with an unknown cause that primarily affects children. The objective of this study was to explore the function and underlying mechanism of mitophagy in Mycoplasma pneumoniae (MP)-induced KD. To create MP-induced KD models, Human coronary endothelial cells (HCAECs) and DBA/2 mice were employed and treated with Mp-Lipid-associated membrane proteins ï¼LAMPsï¼. Lactate dehydrogenase (LDH) levels were tested to determine cellular damage or death. The inflammatory cytokines tumor necrosis factor (TNF)--α and interleukin (IL)-6 were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. RT-qPCR and Western blotting were used to determine the expression of Intercellular Adhesion Molecule(ICAM)-1, vascular cell adhesion molecule (VCAM)-1, inducible nitric oxide synthase(iNOS), LC3, p62, PINK1(a mitochondrial serine/threonine-protein kinase), and PARKIN(a cytosolic E3-ubiquitin ligase). The adenosine triphosphate ï¼ATPï¼, reactive oxygen species ï¼ROSï¼, and mitochondrial membrane potentialï¼MMPï¼ levels were measured to determine mitochondrial function. Mitophagy was investigated using immunofluorescence and a mitophagy detection test. Autophagosome and mitochondrial morphology were examined using transmission electron microscopy. To identify inflammatory cell infiltration, hematoxylin and eosin staining was utilized. Mp-LAMPs increased the levels of TNF-α, IL-6, ICAM-1, VCAM-1, and iNOS in an HCAEC cell model, along with LDH release. After Mp-LAMPs exposure, there was a rise in LC3 and a reduction in p62. Meanwhile, the expression of PINK1 and Parkin was increased. Cyclosporin A dramatically increased ATP synthesis and MMP in HCAEC cells treated with Mp-LAMPs, while suppressing ROS generation, demonstrating excessive mitophagy-related mitochondrial dysfunction. Additionally, neither body weight nor artery tissue were affected due to PINK1 and Parkin suppression Cyclosporin A in Mp-LAMPs-treated mice. These findings indicated that PINK1/Parkin-mediated mitophagy inhibition may be a therapeutic target for MP-induced KD.
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Mitofagia , Síndrome Mucocutáneo Linfonodular , Mycoplasma pneumoniae , Proteínas Quinasas , Ubiquitina-Proteína Ligasas , Animales , Síndrome Mucocutáneo Linfonodular/metabolismo , Síndrome Mucocutáneo Linfonodular/patología , Proteínas Quinasas/metabolismo , Humanos , Ratones , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Mycoplasma pneumoniae/patogenicidad , Ratones Endogámicos DBA , Células Endoteliales/metabolismo , Células Endoteliales/patología , Neumonía por Mycoplasma/metabolismo , Neumonía por Mycoplasma/patología , Neumonía por Mycoplasma/microbiología , Mitocondrias/metabolismo , Mitocondrias/patología , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana MitocondrialRESUMEN
A central principle of synaptic transmission is that action potential-induced presynaptic neurotransmitter release occurs exclusively via Ca2+ -dependent secretion (CDS). The discovery and mechanistic investigations of Ca2+ -independent but voltage-dependent secretion (CiVDS) have demonstrated that the action potential per se is sufficient to trigger neurotransmission in the somata of primary sensory and sympathetic neurons in mammals. One key question remains, however, whether CiVDS contributes to central synaptic transmission. Here, we report, in the central transmission from presynaptic (dorsal root ganglion) to postsynaptic (spinal dorsal horn) neurons in vitro, (i) excitatory postsynaptic currents (EPSCs) are mediated by glutamate transmission through both CiVDS (up to 87%) and CDS; (ii) CiVDS-mediated EPSCs are independent of extracellular and intracellular Ca2+ ; (iii) CiVDS is faster than CDS in vesicle recycling with much less short-term depression; (iv) the fusion machinery of CiVDS includes Cav2.2 (voltage sensor) and SNARE (fusion pore). Together, an essential component of activity-induced EPSCs is mediated by CiVDS in a central synapse.
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Ganglios Espinales , Células del Asta Posterior , Animales , Células del Asta Posterior/fisiología , Transmisión Sináptica/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Sinapsis , MamíferosRESUMEN
Current models emphasize that membrane voltage (Vm) depolarization-induced Ca2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Gißγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca2+, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y12 receptors. D76 and D127 in P2Y12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm â P2Y12(D76/D127) â Gißγ â QS â myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.
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Catecolaminas/metabolismo , Células Cromafines/fisiología , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Vesículas Secretoras/fisiología , Potenciales de Acción , Animales , Femenino , Células HEK293 , Humanos , Masculino , Ratones Noqueados , Cultivo Primario de Células , Ratas Sprague-Dawley , Receptores Purinérgicos P2Y12/metabolismo , Transducción de SeñalRESUMEN
Background: Hepatocellular carcinoma (HCC) is a highly malignant tumor, which is difficult to treat and has a poor prognosis. Immunotherapy has been a hot topic in liver cancer treatment in recent years, and macrophages play an important role in liver cancer immunotherapy. In this paper, we will use bioinformatics to analyze the significance of macrophage-associated genes (Mags) in hepatocellular carcinoma. Our goal is to determine the impact of macrophage-related genes on the immunotherapy, prognosis, and tumor microenvironment of HCC patients. Methods: 343 HCC patients with complete survival data were selected from RNA sequencing data from the Cancer Genome Atlas Hepatocellular carcinoma (TCGA-LIHC) database. Using univariate Cox regression analysis and Lasso regression analysis to identify macrophage-related genetic markers for prognostic HCC and constructed risk scores. Kaplan-Meier survival analysis helped to determine the relationship between genetic markers and overall survival (OS). Kaplan-Meier analysis was used to compare OS in stratified high-risk and low-risk groups. Risk scores and other clinical features were included to develop a prognostic profile of HCC. The accuracy of the model was evaluated by the receiver operating curve and calibration curve, respectively. Results: A prognostic risk model consisting of 7 Mags was constructed to accurately predict OS in the TCGA cohort. In univariate and multivariate Cox regression analyses, risk scores were prognostic factors independent of other clinical factors. The prognostic histogram showed that risk score had a good prognostic effect on survival risk stratification. The expression of immunotherapy markers such as CTLA4 and TNFRSF9 was upregulated in high-risk patients, indicating an underlying immunotherapy response in these patients. Conclusion: Our study constructs a macrophage-associated genetic marker for predicting OS in HCC patients, which may help guide clinical immunotherapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Microambiente Tumoral/genética , Marcadores Genéticos , Neoplasias Hepáticas/genética , PronósticoRESUMEN
Action potential-induced vesicular exocytosis is considered exclusively Ca2+ dependent in Katz's Ca2+ hypothesis on synaptic transmission. This long-standing concept gets an exception following the discovery of Ca2+-independent but voltage-dependent secretion (CiVDS) and its molecular mechanisms in dorsal root ganglion sensory neurons. However, whether CiVDS presents only in sensory cells remains elusive. Here, by combining multiple independent recordings, we report that [1] CiVDS robustly presents in the sympathetic nervous system, including sympathetic superior cervical ganglion neurons and slice adrenal chromaffin cells, [2] uses voltage sensors of Ca2+ channels (N-type and novel L-type), and [3] contributes to catecholamine release in both homeostatic and fight-or-flight like states; [4] CiVDS-mediated catecholamine release is faster than that of Ca2+-dependent secretion at the quantal level and [5] increases Ca2+ currents and contractility of cardiac myocytes. Together, CiVDS presents in the sympathetic nervous system with potential physiological functions, including cardiac muscle contractility.
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Calcio/metabolismo , Catecolaminas/metabolismo , Células Cromafines/metabolismo , Sistema Nervioso Simpático/metabolismo , Potenciales de Acción , Animales , Mamíferos , Modelos Biológicos , Células Musculares/metabolismo , Neuronas/metabolismo , Asta Dorsal de la Médula Espinal/citología , Asta Dorsal de la Médula Espinal/metabolismo , Transmisión SinápticaRESUMEN
Dynamin 1 (dyn1) is required for clathrin-mediated endocytosis in most secretory (neuronal and neuroendocrine) cells. There are two modes of Ca2+-dependent catecholamine release from single dense-core vesicles: full-quantal (quantal) and subquantal in adrenal chromaffin cells, but their relative occurrences and impacts on total secretion remain unclear. To address this fundamental question in neurotransmission area using both sexes of animals, here we report the following: (1) dyn1-KO increased quantal size (QS, but not vesicle size/content) by ≥250% in dyn1-KO mice; (2) the KO-increased QS was rescued by dyn1 (but not its deficient mutant or dyn2); (3) the ratio of quantal versus subquantal events was increased by KO; (4) following a release event, more protein contents were retained in WT versus KO vesicles; and (5) the fusion pore size (dp) was increased from ≤9 to ≥9 nm by KO. Therefore, Ca2+-induced exocytosis is generally a subquantal release in sympathetic adrenal chromaffin cells, implying that neurotransmitter release is generally regulated by dynamin in neuronal cells.SIGNIFICANCE STATEMENT Ca2+-dependent neurotransmitter release from a single vesicle is the primary event in all neurotransmission, including synaptic/neuroendocrine forms. To determine whether Ca2+-dependent vesicular neurotransmitter release is "all-or-none" (quantal), we provide compelling evidence that most Ca2+-induced secretory events occur via the subquantal mode in native adrenal chromaffin cells. This subquantal release mode is promoted by dynamin 1, which is universally required for most secretory cells, including neurons and neuroendocrine cells. The present work with dyn1-KO mice further confirms that Ca2+-dependent transmitter release is mainly via subquantal mode, suggesting that subquantal release could be also important in other types of cells.
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Glándulas Suprarrenales/metabolismo , Células Cromafines/metabolismo , Dinamina I/fisiología , Neurotransmisores/metabolismo , Transmisión Sináptica/fisiología , Vesículas Sinápticas/metabolismo , Glándulas Suprarrenales/citología , Animales , Calcio/farmacología , Catecolaminas/metabolismo , Dinamina I/genética , Endocitosis/fisiología , Exocitosis/efectos de los fármacos , Femenino , Técnicas In Vitro , Masculino , Ratones , Ratones Noqueados , Mutación/genética , Vesículas Secretoras/metabolismoRESUMEN
Recent studies have suggested that intransitive competition, as opposed to hierarchical competition, allows more species to coexist. Furthermore, it is recognized that the prevalent paradigm, which assumes that species interactions are exclusively pairwise, may be insufficient. More importantly, whether and how habitat loss, a key driver of biodiversity loss, can alter these complex competition structures (and therefore species coexistence) remain unclear. We thus present a new, simple yet comprehensive metapopulation framework that can account for any competition pattern and more complex higher-order interactions (HOIs) among species. We find that competitive intransitivity increases community diversity and that HOIs generally enhance this effect. Essentially, intransitivity promotes species richness by preventing the dominance of a few species, unlike the hierarchical competition, while HOIs facilitate species coexistence through stabilizing community fluctuations. However, variation in species' vital rates and habitat loss can weaken or even reverse such higher-order effects, as their interaction can lead to a more rapid decline in competitive intransitivity under HOIs. Thus, it is essential to correctly identify the most appropriate interaction model for a given system before models are used to inform conservation efforts. Overall, our simple model framework provides a more parsimonious explanation for biodiversity maintenance than the existing theory.
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Biodiversidad , Ecosistema , Conducta Competitiva , Humanos , Dinámica PoblacionalRESUMEN
This study aims to explore the core symptoms of Non-Suicidal Self-Injury (NSSI) in adolescents with depressive disorders and the relationship between childhood maltreatment (CM) and NSSI symptoms by using network analysis. A total of 689 adolescents with depressive disorders participated in the survey. The Chinese version of the Adolescent Non-Suicidal Self-Injury Assessment Questionnaire (ANSAQ) and the Short Form of the Childhood Trauma Questionnaire (CTQ-SF) were employed to measure NSSI and the symptoms of CM, respectively. Using network analysis, the NSSI network and the CM-NSSI network were constructed to identify the most central symptoms and the bridge symptoms within the networks. Within the NSSI network, "Intentional scratches", " Intentionally hitting hard objects with your head ", " Intentionally hitting oneself with fists or harder objects ", and " Intentional pinching " were identified as the primary symptoms of NSSI. "emotional abuse", "sexual abuse", and " Intentionally cut yourself " emerged as three key bridge symptoms linking CM with NSSI. This research is the first to investigate the symptom network of CM-NSSI in a sample of adolescents with depressive disorders, providing a foundation for subsequent NSSI prevention and the development of targeted intervention strategies.
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Maltrato a los Niños , Trastorno Depresivo , Conducta Autodestructiva , Adolescente , Niño , Humanos , Maltrato a los Niños/psicología , Conducta Autodestructiva/psicologíaRESUMEN
The Zr(IV) ions are easily hydrolyzed to form oxides, which severely limits the discovery of new structures and applications of Zr-based compounds. In this work, three ferrocene (Fc)-functionalized Zr-oxo clusters (ZrOCs), Zr9Fc6, Zr10Fc6 and Zr12Fc8 were synthesized through inhibiting the hydrolysis of Zr(IV) ions, which show increased nuclearity and regular structural variation. More importantly, these Fc-functionalized ZrOCs were used as heterogeneous catalysts for the transfer hydrogenation of levulinic acid (LA) and phenol oxidation reactions for the first time, and displayed outstanding catalytic activity. In particular, Zr12Fc8 with the largest number of Zr active sites and Fc groups can achieve > 95% yield for LA-to-γ-valerolactone within 4 h (130 °C) and > 98% yield for 2,3,6-trimethylphenol-to-2,3,5-trimethyl-p-benzoquinone within 30 min (80 °C), showing the best catalytic performance. Catalytic characterization combined with theory calculations reveal that in the Fc-functionalized ZrOCs, the Zr active sites could serve as substrate adsorption sites, while the Fc groups could act as hydrogen transfer reagent or Fenton reagent, and thus achieve effectively intramolecular metal-ligand synergistic catalysis. This work develops functionalized ZrOCs as catalysts for thermal-triggered redox reactions.
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Background: Non-suicidal self-injury (NSSI) is a significant social issue, especially among adolescents with major depressive disorder (MDD). This study aimed to construct a risk prediction model using machine learning (ML) algorithms, such as XGBoost and random forest, to identify interventions for healthcare professionals working with adolescents with MDD. Methods: This study investigated 488 adolescents with MDD. Adolescents was randomly divided into 75% training set and 25% test set to testify the predictive value of risk prediction model. The prediction model was constructed using XGBoost and random forest algorithms. We evaluated the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, recall, F Score of the two models for comparing the performance of the two models. Results: There were 161 (33.00%) participants having NSSI. Compared without NSSI, there were statistically significant differences in gender (P=0.035), age (P=0.036), depressive symptoms (P=0.042), sleep quality (P=0.030), dysfunctional attitudes (P=0.048), childhood trauma (P=0.046), interpersonal problems (P=0.047), psychoticism (P) (P=0.049), neuroticism (N) (P=0.044), punishing and Severe (F2) (P=0.045) and Overly-intervening and Protecting (M2) (P=0.047) with NSSI. The AUC values for random forest and XGBoost were 0.780 and 0.807, respectively. The top five most important risk predictors identified by both machine learning methods were dysfunctional attitude, childhood trauma, depressive symptoms, F2 and M2. Conclusion: The study demonstrates the suitability of prediction models for predicting NSSI behavior in Chinese adolescents with MDD based on ML. This model improves the assessment of NSSI in adolescents with MDD by health care professionals working. This provides a foundation for focused prevention and interventions by health care professionals working with these adolescents.
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Since precisely sensing the underwater environment is a challenging prerequisite for safe and reliable underwater operation, interest in underwater image processing is growing at a rapid pace. In engineering applications, there are redundant underwater images addressed in real-time on the remotely operated vehicle (ROV). It puts the equipment or operators under great pressure. To relieve this pressure by transmitting images selectively according to the degradation degree, we propose an end-to-end hybrid-input convolutional neural network (HI-CNN) to predict the degradation of underwater images. First, we propose a feature extraction module to extract the features of original underwater images and saliency maps concurrently, which is composed of two branches with the same structure and shared parameters. Second, we design an end-to-end model to predict the quality scores of original images, which consists of a feature extraction module and a prediction module. Finally, we establish a real-world dataset to make the proposed model be duplicated in the practical underwater environment. Through several experiments, we demonstrate that the proposed model outperforms existing models in predicting underwater image quality.
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Pneumonia is a severe inflammatory disease of the lung. Forkhead box protein A2 (FOXA2) has been demonstrated to serve an important regulatory role in various pulmonary diseases; however, the role of FOXA2 in pneumonia remains to be elucidated. The present study aimed to explore the functional effects and regulatory mechanism of FOXA2 in pneumonia. An in vitro pneumonia model was induced using lipopolysaccharide (LPS) in WI-38 cells. The mRNA and protein expression levels of FOXA2 were determined by reverse transcription-quantitative PCR and western blotting, respectively. Cell viability was assessed using a Cell Counting Kit-8 assay. Inflammatory cytokines were evaluated using ELISA kits and oxidative stress markers were assessed using a malondialdehyde assay kit, superoxide dismutase assay kit and CATalase assay kit. Cell apoptosis was evaluated using flow cytometry and the caspase3 activity was determined. Western blotting was performed to examine the protein expression levels of endoplasmic reticulum stress (ERS)-associated factors. For a rescue assay, a p38 MAPK activator, U46619, was used to investigate the regulatory mechanism of FOXA2 involving p38/STAT3 signaling. FOXA2 was downregulated in LPS-induced WI-38 cells. FOXA2 overexpression alleviated LPS-induced inflammation, oxidative stress, apoptosis and ERS in WI-38 cells. Furthermore, the inhibitory effects of FOXA2 on inflammation, oxidative stress and apoptosis, as well as ERS in LPS-induced WI-38 cells were partly weakened by additional treatment with U46619. In conclusion, FOXA2 served a protective role against LPS-induced pneumonia by regulating p38/STAT3 signaling, providing a novel idea for the development of targeted therapeutic strategies for pneumonia.
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The polysaccharides in honeysuckle leaves (PHL) were separated and characterized for the first time. The nano-emulsion stabilized by PHL and whey protein isolate (WPI) were also fabricated based on the ultrasonic method. The results indicated that PHL was mainly composed of glucose (47.40 mol%), galactose (19.21 mol%) and arabinose (20.21 mol%) with the weight-average molecular weight of 137.97 ± 4.31 kDa. The emulsifier concentration, WPI-to-PHL ratio, ultrasound power and ultrasound time had significant influence on the droplet size of PHL-WPI nano-emulsion. The optimal preparation conditions were determined as following: emulsifier concentration, 1.7%; WPI/PHL ratio, 3:1; ultrasonic power, 700 W; ultrasonic time, 7 min. Under the above conditions, the median diameter of the obtained nano-emulsion was 317.70 ± 5.26 nm, close to the predicted value of 320.20 nm. The protective effect of PHL-WPI emulsion on ß-carotene against UV irradiation was superior to that of WPI emulsion. Our results can provide reference for the development of honeysuckle leaves.
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Purpose: Nonsuicidal self-injury (NSSI) is related to childhood trauma, negative life events, and coping style, but the interaction among these factors and the mechanism by which they interact in adolescents with depressive disorder remain unclear. This paper explores how these factors interact to influence NSSI and provides evidence to develop prevention efforts and interventions for adolescents with depressive disorder with NSSI. Patients and Methods: A cross-sectional design and convenient sampling method were used in this study. The Childhood Trauma Questionnaire, Adolescent Self-Rating Life Events Checklist, Trait Coping Style Questionnaire, and Adolescent Nonsuicidal Self-injury Assessment Questionnaire were completed by 540 adolescents with depressive disorder. Descriptive analysis, chi-square tests, t-tests, Pearson correlations, and serial mediation analyses were used in the data analysis. Results: A total of 398 (79.442%) adolescents with depressive disorders reported experiences of NSSI. The results of serial mediation analyses determined that childhood trauma has a direct (estimate = 0.209, 95% CI: 0.063, 0.334) and indirect (estimate = 0.271, 95% CI: 0.199, 0.371) impact on NSSI. The indirect impact of childhood trauma on NSSI through negative life events alone (estimate = 0.096, 95% CI: 0.007, 0.169), coping styles alone (estimate = 0.088, 95% CI: 0.034, 0.183), and negative life events on coping styles (estimate = 0.086, 95% CI: 0.042, 0.162) was significant. Conclusion: This study demonstrates that screening for childhood trauma should be considered when preventing and treating NSSI behavior in adolescents with depressive disorder. Managing negative life events and coping style may mitigate the negative impact of childhood trauma on NSSI behavior in adolescents with depressive disorder.
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Background: Neurodegenerative retinal diseases such as retinitis pigmentosa are serious disorders that may cause irreversible visual impairment. Ferroptosis is a novel type of programmed cell death, and the involvement of ferroptosis in retinal degeneration is still unclear. This study aimed to investigate the related ferroptosis genes in a mice model of retinal degeneration induced by light damage. Methods: A public dataset of GSE10528 deriving from the Gene Expression Omnibus database was analyzed to identify the differentially expressed genes (DEGs). Gene set enrichment analysis between light damage and control group was conducted. The differentially expressed ferroptosis-related genes (DE-FRGs) were subsequently identified by intersecting the DEGs with a ferroptosis genes dataset retrieved from the FerrDb database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were further performed using the DE-FRGs. A protein-protein interaction (PPI) network was constructed to identify hub ferroptosis-related genes (HFRGs). The microRNAs (miRNAs)-HFRGs, transcription factors (TFs)-HFRGs networks as well as target drugs potentially interacting with HFRGs were analyzed utilizing bioinformatics algorithms. Results: A total of 932 DEGs were identified between the light damage and control group. Among these, 25 genes were associated with ferroptosis. GO and KEGG analyses revealed that these DE-FRGs were mainly enriched in apoptotic signaling pathway, response to oxidative stress and autophagy, ferroptosis, necroptosis and cytosolic DNA-sensing pathway. Through PPI network analysis, six hub ferroptosis-related genes (Jun, Stat3, Hmox1, Atf3, Hspa5 and Ripk1) were ultimately identified. All of them were upregulated in light damage retinas, as verified by the GSE146176 dataset. Bioinformatics analyses predicated that 116 miRNAs, 23 TFs and several potential therapeutic compounds might interact with the identified HFRGs. Conclusion: Our study may provide novel potential biomarkers, therapeutic targets and new insights into the ferroptosis landscape in retinal neurodegenerative diseases.
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Large dense-core vesicles (LDCVs) are larger in volume than synaptic vesicles, and are filled with multiple neuropeptides, hormones, and neurotransmitters that participate in various physiological processes. However, little is known about the mechanism determining the size of LDCVs. Here, it is reported that secretogranin II (SgII), a vesicle matrix protein, contributes to LDCV size regulation through its liquid-liquid phase separation in neuroendocrine cells. First, SgII undergoes pH-dependent polymerization and the polymerized SgII forms phase droplets with Ca2+ in vitro and in vivo. Further, the Ca2+ -induced SgII droplets recruit reconstituted bio-lipids, mimicking the LDCVs biogenesis. In addition, SgII knockdown leads to significant decrease of the quantal neurotransmitter release by affecting LDCV size, which is differently rescued by SgII truncations with different degrees of phase separation. In conclusion, it is shown that SgII is a unique intravesicular matrix protein undergoing liquid-liquid phase separation, and present novel insights into how SgII determines LDCV size and the quantal neurotransmitter release.
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Neuropéptidos , Secretogranina II , Vesículas de Núcleo Denso , Hormonas , Lípidos , Neurotransmisores/metabolismo , Secretogranina II/metabolismoRESUMEN
Purpose: Re-cellularization of the trabecular meshwork (TM) using stem cells is a potential novel treatment for ocular hypertension associated with glaucoma. To assess the therapeutic efficacy of this approach, improved in vivo and ex vivo models of TM pathophysiology are needed. Here, we investigate whether oxidative stress, induced by hydrogen peroxide (H2O2), can model glaucomatous ocular hypertension in the readily available porcine anterior segment organ culture model. Methods: The impact of H2O2 on TM cell viability and function was first evaluated in vitro using primary porcine TM cells. Oxidative stress was then induced by H2O2 infusion into perfused porcine anterior segments. Trabecular meshwork function was assessed by tracking matrix metalloproteinase (MMP) activity and the ability of the preparation to maintain intraocular pressure (IOP) homeostasis after a flow challenge (doubled fluid infusion rate). Finally, the TM was evaluated histologically. Results: H2O2 treatment resulted in a titratable reduction in cellularity across multiple primary TM cell donor strains. In organ culture preparations, H2O2-treated eyes showed impaired IOP homeostasis (i.e., IOPs stabilized at higher levels after a flow challenge vs. control eyes). This result was consistent with reduced MMP activity and TM cellularity; however, damage to the TM microstructure was not histologically evident in anterior segments receiving H2O2. Conclusions: Titrated H2O2 infusion resulted in TM cellular dysfunction without destruction of TM structure. Thus, this porcine organ culture model offers a useful platform for assessing trabecular meshwork therapies to treat ocular hypertension associated with glaucoma.
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Modelos Animales de Enfermedad , Glaucoma de Ángulo Abierto/inducido químicamente , Peróxido de Hidrógeno/farmacología , Estrés Oxidativo/efectos de los fármacos , Malla Trabecular/efectos de los fármacos , Animales , Supervivencia Celular , Glaucoma de Ángulo Abierto/enzimología , Glaucoma de Ángulo Abierto/patología , Presión Intraocular/efectos de los fármacos , Metaloproteinasas de la Matriz/metabolismo , Técnicas de Cultivo de Órganos , Fagocitosis/fisiología , Porcinos , Malla Trabecular/enzimología , Malla Trabecular/patologíaRESUMEN
OBJECTIVE: To understand the function of diaphragm and analyze the clinical factors affecting the function of diaphragm by measuring twitch tracheal pressure (TwPtr) in patients with mechanical ventilation and in the weaning phase. METHODS: Patients with more than 48 hours of invasive mechanical ventilation admitted to the department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from December 2015 to March 2017 were enrolled. After the patient entered the weaning stage, TwPtr of patients was monitored by two-way non repetitive automatic respiratory trigger device, the effects of duration of mechanical ventilation, severe pulmonary infection, sedative application and chronic obstructive pulmonary disease (COPD) on weaning were analyzed. RESULTS: A total of 62 patients were included, of which 45 were male and 17 were female. The average age was (66.8±11.7) years old. Twenty-three cases had severe pneumonia. The absolute value of TwPtr in severe pneumonia group was lower than that in non-severe pneumonia group [cmH2O (1 cmH2O = 0.098 kPa): 10.40±5.81 vs. 14.35±5.22, P = 0.021]. However, there was no significant difference in the duration of mechanical ventilation between the severe pneumonia group and non-severe pneumonia group [days: 26 (17, 43) vs. 15 (11, 36), P = 0.091]. In 62 patients with mechanical ventilation, there was a negative correlation between TwPtr and duration of mechanical ventilation (r = 0.414, P = 0.002), there was also a negative correlation between the duration of mechanical ventilation and TwPtr after the assessment of diaphragm function (r = 0.277, P = 0.039). There was a linear relationship between TwPtr and sedatives (r = 0.220, P = 0.040), but there was no correlation between TwPtr and COPD (r = -0.178, P = 0.166). CONCLUSIONS: For patients in the weaning stage of mechanical ventilation, severe pulmonary infection is one of the factors that affect the diaphragm dysfunction. There is a certain correlation between the diaphragm dysfunction and the use of sedatives.
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Enfermedad Pulmonar Obstructiva Crónica , Respiración Artificial , Anciano , Diafragma , Femenino , Humanos , Pulmón , Masculino , Persona de Mediana Edad , Presión , Respiración Artificial/efectos adversos , Tráquea , Desconexión del VentiladorRESUMEN
Exacum affine Balf.f. ex Regel is a traditional medicinal plant in Yemen and also a popular potted plant. In this study, we sequenced the complete chloroplast genome of E. affine on the Illumina HiSeq Platform. The plastome sequence is 153,311 bp in length with a typical quadripartite structure, containing a pair of inverted repeated (IR) regions of 26,079 bp that are separated by a large single copy (LSC) region of 83,724 bp, and a small single copy (SSC) region of 17,509 bp. The GC content of the whole cp genome was 43.14%. A total of 132 functional genes were annotated, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The complete plastome sequence of E. affine will provide genetic and genomic information to promote its horticulture, officinal utilisation and systematics research of Gentianaceae (especially the tribe Exaceae).
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Castanea henryiï¼Skamï¼Rehd. et Wils is an important woody plant producing nuts in China. In this study, the complete chloroplast genome sequence of C. henryi was reported by using the Illumina Hiseq 2500 platform. The complete chloroplast sequence is 160,807 bp, including large single-copy (LSC) region of 90,394 bp, small single-copy (SSC) region of 18,963 bp, and a pair of invert repeats (IR) regions of 25,725 bp. Plastid genome contains 112 genes, 78 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Based on 26 chloroplast genomes, phylogenetic analysis indicates that C. henryi is closely related to C. mollissima in Fagaceae.