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1.
Sci Data ; 11(1): 644, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886364

RESUMO

The Mediterranean mussel, Mytilus galloprovincialis, is a significant marine bivalve species that has ecological and economic importance. This species is robustly resilient and highly invasive. Despite the scientific and commercial interest in studying its biology and aquaculture, there remains a need for a high-quality, chromosome-scale reference genome. In this study, we have assembled a high-quality chromosome-scale reference genome for M. galloprovincialis. The total length of our reference genome is 1.41 Gb, with a scaffold N50 sequence length of 96.9 Mb. BUSCO analysis revealed a 97.5% completeness based on complete BUSCOs. Compared to the four other available M. galloprovincialis assemblies, the assembly described here is dramatically improved in both contiguity and completeness. This new reference genome will greatly contribute to a deeper understanding of the resilience and invasiveness of M. galloprovincialis.


Assuntos
Cromossomos , Genoma , Mytilus , Mytilus/genética , Animais
2.
BMC Nurs ; 23(1): 404, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886795

RESUMO

BACKGROUND: As indispensable reserves for the nursing workforce, undergraduate nursing students must possess self-directed learning abilities to consistently update their professional knowledge and adapt to the evolving demands of professional development. The acquisition of self-directed learning abilities can help undergraduate nursing students augment their theoretical knowledge and refine their clinical practice skills, thus fulfilling the demand from patients for high-quality nursing services. Hence, comprehending and investigating the factors that influence the development of self-directed learning abilities in nursing students is of paramount importance for nursing education and advancement of the nursing profession. OBJECTIVES: This study investigated the status of and associations between perceived stress, psychological capital, and self-directed learning abilities among undergraduate nursing students. Additionally, it examines the mediating role of psychological capital in the relationship between perceived stress and self-directed learning abilities. Thus, aiming to provide nursing educators with new directions for enhancing self-directed learning abilities. DESIGN: A cross-sectional descriptive study. METHODS: In February and March 2023, 900 undergraduate nursing students from 10 nursing schools completed an online questionnaire. The questionnaire included measures of perceived stress, psychological capital, and self-directed learning ability. Data were analyzed using SPSS 27.0 and the PROCESS macro tool. RESULTS: The scores for perceived stress, psychological capital, and self-directed learning ability among undergraduate nursing students were 40.07 ± 5.90, 99.89 ± 16.59, and 87.12 ± 9.20, respectively. Self-directed learning abilities were negatively correlated with perceived stress (r = -0.415, p < 0.001) and positively correlated with psychological capital (r = 0.465, p < 0.001). Perceived stress was negatively correlated with psychological capital (r = -0.630, p < 0.001). Psychological capital partially mediated the relationship between perceived stress and self-directed learning abilities among undergraduate nursing students, with a mediation effect of -0.166, accounting for 49.55% of the total effect. CONCLUSION: This study found that undergraduate nursing students perceived high levels of stress, possessed low levels of psychological capital, and had moderate levels of self-directed learning. Perceived stress and psychological capital directly influenced undergraduate nursing students' self-directed learning abilities, and perceived stress indirectly affected self-directed learning abilities through psychological capital. Nursing managers and educators should alleviate the perceived stress of undergraduate nursing students and cultivate their positive psychological capital to enhance self-directed learning abilities.

3.
Front Psychol ; 15: 1373102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887626

RESUMO

Background: Theoretically, stress is positively correlated with posttraumatic growth (PTG). However, evidence for a correlation between fear of cancer recurrence (FCR), a cancer-specific stressor, and PTG is mixed. The present study aimed to systematically investigate the overall effect size between the two and to explore moderators that may influence this relationship. Methods: From the earliest available date to October 2023, a comprehensive search was conducted in seven databases. Correlation coefficients (r) were calculated using Stata software. Publication type, continent, trauma role, gender, FCR measurements, PTG measurements, sample size, age, and time since diagnosis were used to examine moderating effects. The National Heart, Lung, and Blood Institute's (NHLBI) assessment tool was used to evaluate study quality. Results: A total of 14 studies, involving 17 samples and 3,701 participants, were included. The studies found a small association between FCR and PTG (r = 0.161, 95% CI: 0.070-0.249, p < 0.01) and large heterogeneity (I2 = 85.5%). The strength of the association varied according to the publication type and FCR measurement. Conclusion: The current review suggests a small but significant positive correlation between FCR and PTG. Future studies would benefit from exploring additional moderators and the use of standardized, validated FCR measurement tools. Systematic review registration: PROSPERO, identifier CRD42023460407.

4.
Pain Ther ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890239

RESUMO

INTRODUCTION: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. METHODS: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. RESULTS: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. CONCLUSIONS: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. TRIAL REGISTRATION: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

5.
Chem Sci ; 15(23): 8993-8999, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38873081

RESUMO

Aromatization-driven deconstruction and functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis is developed. The aromatization effect was introduced to synergistically drive unstrained cyclic C-C bond cleavage, with the aim of overcoming the ring-size limitation of nitrogen-centered radical induced deconstruction of carbocycles. Herein, we demonstrate the synergistic photoredox/nickel catalyzed deconstructive cross-coupling of spiro dihydroquinazolinones with organic halides. Remarkably, structurally diverse organic halides including aryl, alkenyl, alkynyl, and alkyl bromides were compatible for the coupling. In addition, this protocol is also characterized by its mild and redox-neutral conditions, excellent functional group compatibility, high atom economy, and easy scalability. A telescoped procedure involving condensation and ring-opening/coupling was found to be accessible. This work provides a complementary strategy to the existing radical-mediated C-C bond cleavage of unstrained carbocycles.

6.
Front Microbiol ; 15: 1410368, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873146

RESUMO

Ganoderic acids (GAs) are major functional components of Ganoderma lucidum. The study aimed to breed a new G. lucidum strain with increased contents of individual GAs. Two mating-compatible monokaryotic strains, G. 260125 and G. 260124, were successfully isolated from the dikaryotic G. lucidum CGMCC 5.0026 via protoplast formation and regeneration. The Vitreoscilla hemoglobin gene (vgb) and squalene synthase gene (sqs) were overexpressed in the monokaryotic G. 260124 and G. 260125 strain, respectively. Mating between the G. 260124 strain overexpressing vgb and the G. 260125 strain overexpressing sqs resulted in the formation of the new hybrid dikaryotic G. lucidum strain sqs-vgb. The maximum contents of ganoderic acid (GA)-T, GA-Me, and GA-P in the fruiting body of the mated sqs-vgb strain were 23.1, 15.3, and 39.8 µg/g dry weight (DW), respectively, 2.23-, 1.75-, and 2.69-fold greater than those in G. lucidum 5.0026. The squalene and lanosterol contents increased 2.35- and 1.75-fold, respectively, in the fruiting body of the mated sqs-vgb strain compared with those in the G. lucidum 5.0026. In addition, the maximum expression levels of the sqs and lanosterol synthase gene (ls) were increased 3.23- and 2.13-fold, respectively, in the mated sqs-vgb strain. In summary, we developed a new G. lucidum strain with higher contents of individual GAs in the fruiting body by integrating genetic engineering and mono-mono crossing.

7.
Int J Biol Macromol ; : 132970, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876239

RESUMO

Bone defects can interfere with bone healing by disrupting the local environment, resulting in vascular damage and hypoxia. Under these conditions, insufficient oxygen availability is a significant factor that exacerbates disease by blocking angiogenesis or osteogenesis. Exosomes play a crucial role in intercellular communication and modulation of inflammation to aid bone regeneration. However, the distance between exosomes and areas of damage can hinder efficient bone generation and cell survival. To overcome this limitation, we fabricated a continuous oxygen-supplying composite scaffold, with the encapsulation of calcium peroxide in a polylactic acid three-dimensional (3D) printing construct (CPS), as both an oxygen source and hydroxyapatite (HAP) precursor. Furthermore, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were incorporated into hyaluronic acid (HA) hydrogels to stimulate cell growth and modulate inflammation. The release of exosomes into cells leads to an increase in alkaline phosphatase production. In vivo results demonstrated that the composite scaffold regulated the inflammatory microenvironment, relieved tissue hypoxia, and promoted new bone formation. These results indicate that the synergistic effect of exosomes and oxygen promoted the proliferation of BMSCs, alleviated inflammation and exhibited excellent osteogenic properties. In conclusion, this osteogenic functional composite scaffold material offers a highly effective approach for bone repair.

8.
J Inflamm Res ; 17: 3655-3670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863903

RESUMO

Background: Crohn's disease (CD) is a persistent inflammatory condition that impacts the gastrointestinal system and is characterized by a multifaceted pathogenesis involving genetic, immune, and environmental components. This study primarily investigates the relationship between gene expression and immune cell infiltration in CD, focusing on disulfidptosis-a novel form of cell death caused by abnormal disulfide accumulation-and its impact on various immune cell populations. By identifying key disulfidptosis-related genes (DRGs) and exploring their association with distinct gene expression subtypes, this research aims to enhance our understanding of CD and potentially other autoimmune diseases. Methods: Gene expression data from intestinal biopsy samples were collected from both individuals with CD and healthy controls, and these data were retrieved from the GEO database. Through gene expression level comparisons, various differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to reveal the biological processes and pathways linked to these DEGs. Later, immune cell infiltration was evaluated. Hub candidate DRGs were identified using machine learning algorithms. Validation of the expression of hub DRGs was carried out using quantitative real-time polymerase chain reaction. The hub DRGs were subjected to unsupervised hierarchical clustering to classify CD patients into subtypes. The characteristics of each subtype were then analyzed. Results: Two hub DRGs (NDUFA11 and LRPPRC) were identified. NDUFA11 showed a significantly positive association with the abundance of Th17 cells. Conversely, higher expression levels of LRPPRC were associated with a reduced abundance of various immune cells, particularly monocytes. CD patients were classified into two disulfidptosis-related subtypes. Cluster B patients exhibited lower immune infiltration and milder clinical presentation. Conclusion: LRPPRC and NDUFA11 are identified as hub DRGs in CD, with potential roles in disulfidptosis and immune regulation. The disulfidptosis subtypes provide new insights into disease progression.

9.
Eur J Oncol Nurs ; 71: 102617, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38865852

RESUMO

PURPOSE: This study aims to explore heterogeneous trajectories of psychosocial adjustment among young to middle-aged women with breast cancer and determine the predictive factors influencing these trajectories. METHODS: This study was conducted from October 2019 to October 2022 across two hospitals in Guangzhou. Demographic and disease characteristics, psychosocial adjustment, self-efficacy, social support, and coping modes were collected at baseline. Follow-up evaluations of psychosocial adjustment occurred at 1, 3, and 6 months post-surgery. Latent class growth modeling identified distinct patterns of psychosocial adjustment trajectories. Logistic regression analysis determined the predictive factors. RESULTS: A total of 377 young to middle-aged women with breast cancer participated in this study, with 289 participants completing the 6-month follow-up. Three distinct trajectories of psychosocial adjustment were identified including a "sustained severe maladjustment" trajectory, comprising 22.5% of participants, a "sustained moderate maladjustment" trajectory, comprising 50.4% of participants, and a "well-adjusted class" trajectory, comprising 27.1% of participants. Predictors of psychosocial adjustment trajectories included affected side, surgical type, chemotherapy, self-efficacy, social support, and coping modes. CONCLUSIONS: This study revealed three distinct trajectories of psychosocial adjustment among young to middle-aged women with breast cancer. Those with right-sided breast cancer, undergoing total mastectomy, receiving chemotherapy, low self-efficacy, limited social support, and relying on confrontation or avoidance coping modes may experience sustained maladjustment.

10.
Respir Care ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866418

RESUMO

BACKGROUND: The flow reaching the vocal folds may be lower than that at the output of high-flow nasal cannula (HFNC) system. This could be due to upper-respiratory obstruction, oxygen leakage, or other factors. The objective of this study was to observe the effect of flow through a nasopharyngeal airway on intrapharyngeal pressure (IPP) in subjects undergoing fiberoptic bronchoscopy (FOB). METHODS: Patients scheduled for FOB were invited to participate. Measurements were performed at flows of 0-60 L/min; the subjects wore WN-N95 folding medical protective masks (N95) and either underwent FOB or not. IPP at each flow was recorded following 15 s of ventilation, and the cross-sectional area (CSA) of the gastric sinus was measured before and after FOB. Hypoxemia, reflux aspiration, and other pertinent events were recorded. RESULTS: Sixty subjects undergoing FOB at the Affiliated Hospital of Jiaxing University participated in this trial from October 2022-September 2023. IPP increased significantly with an increase in flow and also increased after placing the N95 mask with the same flow (P < .001). When results from before to after FOB were compared, the difference in CSA was statistically significant 263.6 (220.7-300.5) mm2 vs 305.5 (275.4-329.5) mm2, P < .001, but the difference in the risk of reflux aspiration was not statistically significant (0% vs 6.7%, P = .13). Complication rates during treatment were 8.3% for hypoxemia, 0% for reflux aspiration, 1.7% for hypertension, 1.7% for hypotension, 6.7% for tachycardia, 5% for bradycardia, and 10% for postoperative nausea and vomiting. CONCLUSIONS: HFNC can provide effective oxygen therapy for people undergoing FOB, and increases in IPP with flow in the range of 0-60 L/min may not increase the risk of reflux aspiration.

11.
Adv Sci (Weinh) ; : e2401990, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38868931

RESUMO

Photocatalytic CO2 reduction is considered as a promising strategy for CO2 utilization and producing renewable energy, however, it remains challenge in the improvement of photocatalytic performance for wide-band-gap photocatalyst with controllable product selectivity. Herein, the sulfur-doped In(OH)3 (In(OH)xSy-z) nanocubes are developed for selective photocatalytic reduction of CO2 to CH4 under simulated light irradiation. The CH4 yield of the optimal In(OH)xSy-1.0 can be enhanced up to 39 times and the CH4 selectivity can be regulated as high as 80.75% compared to that of pristine In(OH)3. The substitution of sulfur atoms for hydroxyl groups in In(OH)3 enhances the visible light absorption capability, and further improves the hydrophilicity behavior, which promotes the H2O dissociation into protons (H*) and accelerates the dynamic proton-feeding CO2 hydrogenation. In situ DRIFTs and DFT calculation confirm that the non-metal sulfur sites significantly weaken the over-potential of the H2O oxidation and prevent the formation of ·OH radicals, enabling the stabilization of *CHO intermediates and thus facilitating CH4 production. This work highlights the promotion effect of the non-metal doping engineering on wide-band-gap photocatalysts for tailoring the product selectivity in photocatalytic CO2 reduction.

12.
J Chem Inf Model ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861660

RESUMO

Hepatitis C virus (HCV) is a major cause of chronic liver disease and hepatocellular carcinoma. Antibody development efforts mainly revolve around HCV envelope glycoprotein 2 (E2), which mediates host cell entry by interacting with several cell surface receptors, including CD81. We still have limited knowledge about the structural ensembles and the dynamic behavior of both the CD81 binding sites and the glycans on E2. Here, multiple microsecond-long, all-atom molecular dynamics (MD) simulations, as well as a Markov state model (MSM), were performed to provide an atomistic perspective on the dynamic nature of E2 and its glycans. End-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of E2, which may be exploited in therapeutic efforts. Additionally, the Markov state model built from the simulation maps four metastable states for AS412 and three metastable states for the front layer in CD81 binding sites, while binding with HEPC3 would induce a conformation selection for both of them. Overall, this work presents hitherto unseen functional and structural insights into E2 and its glycan coat, providing a new theoretical foundation to control the conformational plasticity of E2 that could be harnessed for vaccine development.

13.
Cells Dev ; : 203932, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38852677

RESUMO

Tooth morphogenesis is a critically ordered process manipulated by a range of signaling factors. Particularly, the involvement of fine-tuned signaling mediated by non-coding RNAs has been of longstanding interest. Here, we revealed a double-negative feedback loop acted by a long non-coding RNA (LOC102159588) and a microRNA (miR-133b) that modulated tooth morphogenesis of miniature swine. Mechanistically, miR-133b repressed the transcription of LOC102159588 through downstream target Sp1. Conversely, LOC102159588 not only inhibited the transport of pre-miR-133b from the nucleus to the cytoplasm by regulating exportin-5 but also served as a sponge in the cytoplasm, suppressing functional miR-133b. Together, the double-negative feedback loop maintained normal tooth morphogenesis by modulating endogenous apoptosis. Related disruptions would lead to an arrest of tooth development and may result in tooth malformations.

14.
JCI Insight ; 9(11)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38855866

RESUMO

TANGO2-deficiency disorder (TDD) is an autosomal-recessive genetic disease caused by biallelic loss-of-function variants in the TANGO2 gene. TDD-associated cardiac arrhythmias are recalcitrant to standard antiarrhythmic medications and constitute the leading cause of death. Disease modeling for TDD has been primarily carried out using human dermal fibroblast and, more recently, in Drosophila by multiple research groups. No human cardiomyocyte system has been reported, which greatly hinders the investigation and understanding of TDD-associated arrhythmias. Here, we established potentially novel patient-derived induced pluripotent stem cell differentiated cardiomyocyte (iPSC-CM) models that recapitulate key electrophysiological abnormalities in TDD. These electrophysiological abnormalities were rescued in iPSC-CMs with either adenoviral expression of WT-TANGO2 or correction of the pathogenic variant using CRISPR editing. Our natural history study in patients with TDD suggests that the intake of multivitamin/B complex greatly diminished the risk of cardiac crises in patients with TDD. In agreement with the clinical findings, we demonstrated that high-dose folate (vitamin B9) virtually abolishes arrhythmias in TDD iPSC-CMs and that folate's effect was blocked by the dihydrofolate reductase inhibitor methotrexate, supporting the need for intracellular folate to mediate antiarrhythmic effects. In summary, data from TDD iPSC-CM models together with clinical observations support the use of B vitamins to mitigate cardiac crises in patients with TDD, providing potentially life-saving treatment strategies during life-threatening events.


Assuntos
Arritmias Cardíacas , Ácido Fólico , Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ácido Fólico/metabolismo , Ácido Fólico/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/genética , Masculino , Feminino , Criança
15.
Asian J Androl ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38856299

RESUMO

ABSTRACT: Male infertility is a global issue caused by poor sperm quality, particularly motility. Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology (ART) treatment. Scriptaid, with a novel human sperm motility-stimulating activity, has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART. We evaluated the effects of Scriptaid on asthenozoospermic (AZS) semen, including its impact on motility stimulation and protective effects on cryopreservation and duration of motility, by computer-aided sperm analysis (CASA). Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity, tyrosine phosphorylation, adenosine triphosphate (ATP) concentration, mitochondrial membrane potential, and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection (ICSI) experiments. Furthermore, our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function. In summary, Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality, prolongs sperm viability, and increases the fertilization rate.

16.
Talanta ; 277: 126351, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38850802

RESUMO

Multiplex, sensitive, and rapid detection of pathogens is crucial for ensuring food safety and safeguarding human health, however, it remains a significant challenge. This study proposes a concanavalin A-assisted multiplex digital amplification (CAMDA) assay for simultaneous quantitative detection of multiple foodborne bacteria. The CAMDA assay enables the simultaneous detection of six foodborne pathogens within 1.1 h and the limit of detection is 101 CFU/mL. Furthermore, the CAMDA assay exhibits high specificity, with a rate of 97 % for Bacillus cereus and 100 % for other pathogens tested in this study. Moreover, practical application validation using eight milk powder samples demonstrates that the accuracy of the CAMDA assay reaches 100 % when compared to qPCR results. Therefore, our developed CAMDA assay holds great potential for accurate and rapid detection of multiple pathogens in complex food matrices while also promoting the utilization of microfluidic chips in food investigation.

17.
J Org Chem ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874168

RESUMO

A visible-light-initiated C-H trifluoromethylation of quinoxalin-2(1H)-ones was established using a Z-scheme V2O5/g-C3N4 heterojunction as a recyclable photocatalyst in an inert atmosphere at room temperature under additive-free and mild conditions. A variety of trifluoromethylated quinoxalin-2-(1H)-one derivatives were heterogeneously generated in moderate to high yields, exhibiting good functional group tolerance. Remarkably, the recyclable V2O5/g-C3N4 catalyst could be reused five times with a slight loss of catalytic activity.

18.
Adv Sci (Weinh) ; : e2400560, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874331

RESUMO

Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input-output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to NaV1.2 sodium channels, facilitating NEDD4L-mediated ubiquitination, and endocytosis of NaV1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented NaV1.2-mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno-associated virus-mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage-gated sodium channels. Collectively, PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility, suggesting a potential strategy for precise modulation of NaV1.2 channels' function.

19.
PeerJ ; 12: e17416, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832037

RESUMO

Background: The importance of the gut microbiota in maintaining bone homeostasis has been increasingly emphasized by recent research. This study aimed to identify whether and how the gut microbiome of postmenopausal women with osteoporosis and osteopenia may differ from that of healthy individuals. Methods: Fecal samples were collected from 27 individuals with osteoporosis (OP), 44 individuals with osteopenia (ON), and 23 normal controls (NC). The composition of the gut microbial community was analyzed by 16S rRNA gene sequencing. Results: No significant difference was found in the microbial composition between the three groups according to alpha and beta diversity. At the phylum level, Proteobacteria and Fusobacteriota were significantly higher and Synergistota was significantly lower in the ON group than in the NC group. At the genus level, Roseburia, Clostridia_UCG.014, Agathobacter, Dialister and Lactobacillus differed between the OP and NC groups as well as between the ON and NC groups (p < 0.05). Linear discriminant effect size (LEfSe) analysis results showed that one phylum community and eighteen genus communities were enriched in the NC, ON and OP groups, respectively. Spearman correlation analysis showed that the abundance of the Dialister genus was positively correlated with BMD and T score at the lumbar spine (p < 0.05). Functional predictions revealed that pathways relevant to amino acid biosynthesis, vitamin biosynthesis, and nucleotide metabolism were enriched in the NC group. On the other hand, pathways relevant to metabolites degradation and carbohydrate metabolism were mainly enriched in the ON and OP groups respectively. Conclusions: Our findings provide new epidemiologic evidence regarding the relationship between the gut microbiota and postmenopausal bone loss, laying a foundation for further exploration of therapeutic targets for the prevention and treatment of postmenopausal osteoporosis (PMO).


Assuntos
Doenças Ósseas Metabólicas , Fezes , Microbioma Gastrointestinal , Osteoporose Pós-Menopausa , Humanos , Feminino , China/epidemiologia , Doenças Ósseas Metabólicas/microbiologia , Doenças Ósseas Metabólicas/epidemiologia , Pessoa de Meia-Idade , Idoso , Fezes/microbiologia , Osteoporose Pós-Menopausa/microbiologia , Osteoporose Pós-Menopausa/epidemiologia , RNA Ribossômico 16S/genética , Pós-Menopausa , Estudos de Casos e Controles , Densidade Óssea
20.
Int J Biol Macromol ; : 132807, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825289

RESUMO

It is proverbial that Rosa roxburghii, as a homology of medicine and food, is rich in polysaccharides. To discover bioactive macromolecules for combating cancer, the polysaccharides in R. roxburghii were investigated, leading to the purification of a polysaccharide (RRTP80-1). RRTP80-1 was measured to have an average molecular weight of 8.65 × 103 g/mol. Monosaccharide composition analysis revealed that RRTP80-1 was formed from three types of monosaccharides including arabinose, glucose, and galactose. Combination of methylation and GC-MS analysis suggested that the backbone of RRTP80-1 consisted of →5)-α-l-Araf-(1→, →6)-α-d-Glcp-(1→, →2,5)-α-l-Araf-(1→, →4,6)-ß-d-Galp-(1→, and →3)-α-l-Araf-(1→, with branch chains, α-l-Araf-(1→. In vivo studies indicated that RRTP80-1 exhibited inhibitory activity against the growth and proliferation of neoplasms in the zebrafish tumor xenograft model by suppressing angiogenesis. Additionally, RRTP80-1 was found to upregulate reactive oxygen species (ROS) and nitric oxide (NO) production levels in zebrafish models. All these studies suggest that RRTP80-1 activates the immune system to inhibit tumors. The potential role of the newly discovered homogeneous polysaccharide RRTP80-1 in cancer treatment was preliminarily clarified in this study.

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