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1.
J Am Chem Soc ; 146(22): 15053-15060, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38776531

RESUMO

Electrocatalysis is considered promising in renewable energy conversion and storage, yet numerous efforts rely on catalyst design to advance catalytic activity. Herein, a hydrodynamic single-particle electrocatalysis methodology is developed by integrating collision electrochemistry and microfluidics to improve the activity of an electrocatalysis system. As a proof-of-concept, hydrogen evolution reaction (HER) is electrocatalyzed by individual palladium nanoparticles (Pd NPs), with the development of microchannel-based ultramicroelectrodes. The controlled laminar flow enables the precise delivery of Pd NPs to the electrode-electrolyte interface one by one. Compared to the diffusion condition, hydrodynamic collision improves the number of active sites on a given electrode by 2 orders of magnitude. Furthermore, forced convection enables the enhancement of proton mass transport, thereby increasing the electrocatalytic activity of each single Pd NP. It turns out that the improvement in mass transport increases the reaction rate of HER at individual Pd NPs, thus a phase transition without requiring a high overpotential. This study provides new avenues for enhancing electrocatalytic activity by altering operating conditions, beyond material design limitations.

2.
PLoS Biol ; 19(7): e3001323, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34228711

RESUMO

Synaptotagmin-7 (Syt7) plays direct or redundant Ca2+ sensor roles in multiple forms of vesicle exocytosis in synapses. Here, we show that Syt7 is a redundant Ca2+ sensor with Syt1/Doc2 to drive spontaneous glutamate release, which functions uniquely to activate the postsynaptic GluN2B-containing NMDARs that significantly contribute to mental illness. In mouse hippocampal neurons lacking Syt1/Doc2, Syt7 inactivation largely diminishes spontaneous release. Using 2 approaches, including measuring Ca2+ dose response and substituting extracellular Ca2+ with Sr2+, we detect that Syt7 directly triggers spontaneous release via its Ca2+ binding motif to activate GluN2B-NMDARs. Furthermore, modifying the localization of Syt7 in the active zone still allows Syt7 to drive spontaneous release, but the GluN2B-NMDAR activity is abolished. Finally, Syt7 SNPs identified in bipolar disorder patients destroy the function of Syt7 in spontaneous release in patient iPSC-derived and mouse hippocampal neurons. Therefore, Syt7 could contribute to neuropsychiatric disorders through driving spontaneous glutamate release.


Assuntos
Transtorno Bipolar/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinaptotagminas/fisiologia , Animais , Transtorno Bipolar/genética , Cálcio/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Modelos Animais de Doenças , Predisposição Genética para Doença , Ácido Glutâmico/metabolismo , Células HEK293 , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Sinaptotagminas/genética
3.
Clin Exp Rheumatol ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38757282

RESUMO

OBJECTIVES: To investigate whether the interplay of anti-galectin-3 antibodies (anti-Gal3 Abs) with neutrophils contributes to the development of lupus cutaneous vasculitis. METHODS: Enzyme-linked immunosorbent assay was used to determine the serum level of anti-Gal3 Abs in lupus patients. Flow cytometry, quantitative PCR and western blot were performed to investigate the expression of cell surface receptors, proinflammatory cytokines and signalling molecules in neutrophils stimulated by serum from lupus patients or healthy controls (HCs) or anti-Gal3 Ab, respectively. Immunofluorescence was performed to visualise the formation of neutrophil extracellular traps (NETs). Human umbilical vein endothelial cells were co-cultured with the supernatants from neutrophils stimulated by anti-Gal3 Ab, and cytokine production was measured at mRNA and protein levels. Immunohistochemistry was adopted to reveal the distribution of Gal3, cytokines and myeloperoxidase within lupus skin lesions. REULTS: Serum levels of anti-Gal3 Abs were negatively correlated with peripheral counts of neutrophils. Anti-Gal3 Abs positive sera from SLE patients accelerated neutrophil death, altered cell phenotype and promoted formation of NETs with the involvement of p38 MAPK pathway. Supernatants collected from neutrophils co-cultured with anti-Gal3 Ab provoked endothelial cells to produce cytokines such as IL-1, ICAM-1, SELE and particularly IL-6. Consistently, IL-6 was higher in SLE patients with anti-Gal3 Ab positive sera and enriched in the area of vascular inflammation together with enhanced expression of Gal3 protein and infiltration of neutrophils. CONCLUSIONS: Overall, these findings suggested that neutrophils were crucial mediators in anti-Gal3 Ab induced lupus cutaneous vasculitis.

4.
J Gastroenterol Hepatol ; 39(3): 544-551, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38059883

RESUMO

BACKGROUND AND AIM: Chromoendoscopy with the use of indigo carmine (IC) dye is a crucial endoscopic technique to identify gastrointestinal neoplasms. However, its performance is limited by the endoscopist's skill, and no standards are available for lesion identification. Thus, we developed an artificial intelligence (AI) model to replace chromoendoscopy. METHODS: This pilot study assessed the feasibility of our novel AI model in the conversion of white-light images (WLI) into virtual IC-dyed images based on a generative adversarial network. The predictions of our AI model were evaluated against the assessments of five endoscopic experts who were blinded to the purpose of this study with a staining quality rating from 1 (unacceptable) to 4 (excellent). RESULTS: The AI model successfully transformed the WLI of polyps with different morphologies and different types of lesions in the gastrointestinal tract into virtual IC-dyed images. The quality ratings of the real IC-dyed and AI images did not significantly differ concerning surface structure (AI vs IC: 3.08 vs 3.00), lesion border (3.04 vs 2.98), and overall contrast (3.14 vs 3.02) from 10 sets of images (10 AI images and 10 real IC-dyed images). Although the score depended significantly on the evaluator, the staining methods (AI or real IC) and evaluators had no significant interaction (P > 0.05) with each other. CONCLUSION: Our results demonstrated the feasibility of employing AI model's virtual IC staining, increasing the possibility of being employed in daily practice. This novel technology may facilitate gastrointestinal lesion identification in the future.


Assuntos
Inteligência Artificial , Lesões Pré-Cancerosas , Humanos , Projetos Piloto , Endoscopia/métodos , Índigo Carmim , Carmim , Lesões Pré-Cancerosas/diagnóstico por imagem
5.
BMC Cardiovasc Disord ; 24(1): 123, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402377

RESUMO

BACKGROUND: Acute myocardial infarction (AMI) is indeed a significant cause of mortality and morbidity in individuals with coronary heart disease. Ferroptosis, an iron-dependent cell death, is characterized by the accumulation of intracellular lipid peroxides, which is implicated in cardiomyocyte injury. This study aims to identify biomarkers that are indicative of ferroptosis in the context of AMI, and to examine their potential roles in immune infiltration. METHODS: Firstly, the GSE59867 dataset was used to identify differentially expressed ferroptosis-related genes (DE-FRGs) in AMI. We then performed gene ontology (GO) and functional enrichment analysis on these DE-FRGs. Secondly, we analyzed the GSE76591 dataset and used bioinformatic methods to build ceRNA networks. Thirdly, we identified hub genes in protein-protein interaction (PPI) network. After obtaining the key DE-FRGs through the junction of hub genes with ceRNA and least absolute shrinkage and selection operator (LASSO). ImmucellAI was applied to estimate the immune cell infiltration in each sample and examine the relationship between key DE-FRGs and 24 immunocyte subsets. The diagnostic performance of these genes was further evaluated using the receiver operating characteristic (ROC) curve analysis. Ultimately, we identified an immune-related ceRNA regulatory axis linked to ferroptosis in AMI. RESULTS: Among 56 DE-FRGs identified in AMI, 41 of them were integrated into the construction of competitive endogenous RNA (ceRNA) networks. TLR4 and PIK3CA were identified as key DE-FRGs and PIK3CA was confirmed as a diagnostic biomarker for AMI. Moreover, CD4_native cells, nTreg cells, Th2 cells, Th17 cells, central-memory cells, effector-memory cells, and CD8_T cells had higher infiltrates in AMI samples compared to control samples. In contrast, exhausted cells, iTreg cells, and Tfh cells had lower infiltrates in AMI samples. Spearman analysis confirmed the correlation between 24 immune cells and PIK3CA/TLR4. Ultimately, we constructed an immune-related regulatory axis involving XIST and OIP5-AS1/miR-216a/PIK3CA. CONCLUSION: Our comprehensive analysis has identified PIK3CA as a robust and promising biomarker for this condition. Moreover, we have also identified an immune-related regulatory axis involving XIST and OIP5-AS1/miR-216a/PIK3CA, which may play a key role in regulating ferroptosis during AMI progression.


Assuntos
Ferroptose , MicroRNAs , Infarto do Miocárdio , Humanos , Ferroptose/genética , Receptor 4 Toll-Like/genética , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Classe I de Fosfatidilinositol 3-Quinases , Biomarcadores
6.
Proc Natl Acad Sci U S A ; 118(14)2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33782126

RESUMO

microRNA-218 (miR-218) has been linked to several cognition related neurodegenerative and neuropsychiatric disorders. However, whether miR-218 plays a direct role in cognitive functions remains unknown. Here, using the miR-218 knockout (KO) mouse model and the sponge/overexpression approaches, we showed that miR-218-2 but not miR-218-1 could bidirectionally regulate the contextual and spatial memory in the mice. Furthermore, miR-218-2 deficiency induced deficits in the morphology and presynaptic neurotransmitter release in the hippocampus to impair the long term potentiation. Combining the RNA sequencing analysis and luciferase reporter assay, we identified complement component 3 (C3) as a main target gene of miR-218 in the hippocampus to regulate the presynaptic functions. Finally, we showed that restoring the C3 activity in the miR-218-2 KO mice could rescue the synaptic and learning deficits. Therefore, miR-218-2 played an important role in the cognitive functions of mice through C3, which can be a mechanism for the defective cognition of miR-218 related neuronal disorders.


Assuntos
Complemento C3/genética , Hipocampo/metabolismo , Potenciação de Longa Duração , MicroRNAs/metabolismo , Vesículas Sinápticas/metabolismo , Regiões 3' não Traduzidas , Animais , Células Cultivadas , Complemento C3/metabolismo , Exocitose , Hipocampo/citologia , Hipocampo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Neurônios/metabolismo , Neurônios/fisiologia
7.
Angew Chem Int Ed Engl ; : e202404170, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781086

RESUMO

The key to rationally and rapidly designing high-performance materials is the monitoring and comprehension of dynamic processes within individual particles in real-time, particularly to gain insight into the anisotropy of nanoparticles. The intrinsic property of nanoparticles typically varies from one crystal facet to the next under realistic working conditions. Here, we introduce the operando collision electrochemistry to resolve the single silver nanoprisms (Ag NPs) anisotropy in photoelectrochemistry. We directly identify the effect of anisotropy on the plasmonic-assisted electrochemistry at the single NP/electrolyte interface. The statistical collision frequency shows that heterogeneous diffusion coefficients among crystal facets facilitate Ag NPs to undergo direction-dependent mass transfer toward the gold ultramicroelectrode. Subsequently, the current amplitudes of transient events indicate that the anisotropy enables variations in dynamic interfacial electron transfer behaviors during photothermal processes. The results presented here demonstrate that the measurement precision of collision electrochemistry can be extended to the sub-nanoparticle level, highlighting the potential for high-throughput material screening with comprehensive kinetics information at the nanoscale.

8.
Angew Chem Int Ed Engl ; 63(16): e202400562, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382041

RESUMO

Halide solid electrolytes, known for their high ionic conductivity at room temperature and good oxidative stability, face notable challenges in all-solid-state Li-ion batteries (ASSBs), especially with unstable cathode/solid electrolyte (SE) interface and increasing interfacial resistance during cycling. In this work, we have developed an Al3+-doped, cation-disordered epitaxial nanolayer on the LiCoO2 surface by reacting it with an artificially constructed AlPO4 nanoshell; this lithium-deficient layer featuring a rock-salt-like phase effectively suppresses oxidative decomposition of Li3InCl6 electrolyte and stabilizes the cathode/SE interface at 4.5 V. The ASSBs with the halide electrolyte Li3InCl6 and a high-loading LiCoO2 cathode demonstrated high discharge capacity and long cycling life from 3 to 4.5 V. Our findings emphasize the importance of specialized cathode surface modification in preventing SE degradation and achieving stable cycling of halide-based ASSBs at high voltages.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 559-566, 2024 Jun 15.
Artigo em Zh | MEDLINE | ID: mdl-38926371

RESUMO

OBJECTIVES: To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. METHODS: In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (n=49) and an SCIT group (n=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT. RESULTS: Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (P<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (P<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events. CONCLUSIONS: SCIT is an effective and safe treatment for allergic asthma in children.


Assuntos
Asma , Pyroglyphidae , Humanos , Asma/terapia , Asma/imunologia , Masculino , Criança , Feminino , Animais , Estudos Prospectivos , Injeções Subcutâneas , Pyroglyphidae/imunologia , Pré-Escolar , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/efeitos adversos , Adolescente
10.
J Am Chem Soc ; 145(46): 25043-25055, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37934860

RESUMO

Most relevant systems of interest to modern chemists rarely consist of a single phase. Real-world problems that require a rigorous understanding of chemical reactivity in multiple phases include the development of wearable and implantable biosensors, efficient fuel cells, single cell metabolic characterization techniques, and solar energy conversion devices. Within all of these systems, confinement effects at the nanoscale influence the chemical reaction coordinate. Thus, a fundamental understanding of the nanoconfinement effects of chemistry in multiphase environments is paramount. Electrochemistry is inherently a multiphase measurement tool reporting on a charged species traversing a phase boundary. Over the past 50 years, electrochemistry has witnessed astounding growth. Subpicoampere current measurements are routine, as is the study of single molecules and nanoparticles. This Perspective focuses on three nanoelectrochemical techniques to study multiphase chemistry under nanoconfinement: stochastic collision electrochemistry, single nanodroplet electrochemistry, and nanopore electrochemistry.

11.
J Am Chem Soc ; 145(13): 7397-7407, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36961942

RESUMO

Nickel-rich layered oxides (NLOs) are considered as one of the most promising cathode materials for next-generation high-energy lithium-ion batteries (LIBs), yet their practical applications are currently challenged by the unsatisfactory cyclability and reliability owing to their inherent interfacial and structural instability. Herein, we demonstrate an approach to reverse the unstable nature of NLOs through surface solid reaction, by which the reconstructed surface lattice turns stable and robust against both side reactions and chemophysical breakdown, resulting in improved cycling performance. Specifically, conformal La(OH)3 nanoshells are built with their thicknesses controlled at nanometer accuracy, which act as a Li+ capturer and induce controlled reaction with the NLO surface lattices, thereby transforming the particle crust into an epitaxial layer with localized Ni/Li disordering, where lithium deficiency and nickel stabilization are both achieved by transforming oxidative Ni3+ into stable Ni2+. An optimized balance between surface stabilization and charge transfer is demonstrated by a representative NLO material, namely, LiNi0.83Co0.07Mn0.1O2, whose surface engineering leads to a highly improved capacity retention and excellent rate capability with a strong capability to inhibit the crack of NLO particles. Our study highlights the importance of surface chemistry in determining chemical and structural behaviors and paves a research avenue in controlling the surface lattice for the stabilization of NLOs toward reliable high-energy LIBs.

12.
Skin Res Technol ; 29(7): e13416, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37522501

RESUMO

BACKGROUND: Acquired perforating dermatosis (APD) is a rare skin condition characterized by degenerated materials eliminated from the dermis. Several retrospective studies on APD have been reported; however, few data are available on Chinese APD and their features on dermoscopy and reflective confocal microscope (RCM) assays. OBJECTIVE: The aim of this study was to retrospectively evaluate the clinical and histopathologic data of 37 acquired perforating dermatosis cases, and assess their features on dermoscopy and RCM. METHODS: Thirty-seven APD patients were retrospectively enrolled in our study. We characterized the clinical histopathological features, concomitant diseases, treatment responses, and the dermoscopy and RCM findings. RESULTS: Pruritus was the most common symptom, with the lower extremities as the most predilection sites (86.5%, n = 32; 91.9%, n = 34, respectively). Concomitant diseases were found in 34 patients (92.6%), among which diabetes mellitus was the most common, followed by thyroid nodules, allergic dermatosis, and chronic renal insufficiency. Dermoscopy and RCM assays were performed in 11 patients. The typical RCM images were hyperreflective cord-like structures from the epidermis to dermis. Dermoscopy features of fully developed lesions showed central ulceration with peripheral hairpin-like or loop-like capillaries with characteristic garland arrangements. CONCLUSION: APD is an uncommon skin disorder associated with various systemic conditions in Chinese individuals. Thyroid disorders are an overlooked complication and may play an important role in the development of APD. The results of this study indicate that noninvasive dermoscopy and RCM examination are helpful in the rapid diagnosis and early intervention of APD.


Assuntos
Dermatopatias , Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Dermoscopia , Dermatopatias/patologia , Pele/patologia , Microscopia Confocal/métodos , Neoplasias Cutâneas/patologia
13.
Proc Natl Acad Sci U S A ; 117(49): 31438-31447, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33229564

RESUMO

Synaptotagmin-7 (Syt7) probably plays an important role in bipolar-like behavioral abnormalities in mice; however, the underlying mechanisms for this have remained elusive. Unlike antidepressants that cause mood overcorrection in bipolar depression, N-methyl-d-aspartate receptor (NMDAR)-targeted drugs show moderate clinical efficacy, for unexplained reasons. Here we identified Syt7 single nucleotide polymorphisms (SNPs) in patients with bipolar disorder and demonstrated that mice lacking Syt7 or expressing the SNPs showed GluN2B-NMDAR dysfunction, leading to antidepressant behavioral consequences and avoidance of overcorrection by NMDAR antagonists. In human induced pluripotent stem cell (iPSC)-derived and mouse hippocampal neurons, Syt7 and GluN2B-NMDARs were localized to the peripheral synaptic region, and Syt7 triggered multiple forms of glutamate release to efficiently activate the juxtaposed GluN2B-NMDARs. Thus, while Syt7 deficiency and SNPs induced GluN2B-NMDAR dysfunction in mice, patient iPSC-derived neurons showed Syt7 deficit-induced GluN2B-NMDAR hypoactivity that was rescued by Syt7 overexpression. Therefore, Syt7 deficits induced mania-like behaviors in mice by attenuating GluN2B activity, which enabled NMDAR antagonists to avoid mood overcorrection.


Assuntos
Comportamento Animal , Mania/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , Sinaptotagminas/deficiência , Adulto , Idoso , Animais , Transtorno Bipolar/genética , Transtorno Bipolar/patologia , Exocitose , Feminino , Ácido Glutâmico/metabolismo , Hipocampo/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Mania/fisiopatologia , Camundongos Knockout , Pessoa de Meia-Idade , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Vesículas Sinápticas/metabolismo , Sinaptotagminas/genética , Sinaptotagminas/metabolismo , Adulto Jovem
14.
Proc Natl Acad Sci U S A ; 117(8): 4392-4399, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32041882

RESUMO

The pathogenesis of bipolar disorder (BD) has remained enigmatic, largely because genetic animal models based on identified susceptible genes have often failed to show core symptoms of spontaneous mood cycling. However, pedigree and induced pluripotent stem cell (iPSC)-based analyses have implicated that dysfunction in some key signaling cascades might be crucial for the disease pathogenesis in a subpopulation of BD patients. We hypothesized that the behavioral abnormalities of patients and the comorbid metabolic abnormalities might share some identical molecular mechanism. Hence, we investigated the expression of insulin/synapse dually functioning genes in neurons derived from the iPSCs of BD patients and the behavioral phenotype of mice with these genes silenced in the hippocampus. By these means, we identified synaptotagmin-7 (Syt7) as a candidate risk factor for behavioral abnormalities. We then investigated Syt7 knockout (KO) mice and observed nocturnal manic-like and diurnal depressive-like behavioral fluctuations in a majority of these animals, analogous to the mood cycling symptoms of BD. We treated the Syt7 KO mice with clinical BD drugs including olanzapine and lithium, and found that the drug treatments could efficiently regulate the behavioral abnormalities of the Syt7 KO mice. To further verify whether Syt7 deficits existed in BD patients, we investigated the plasma samples of 20 BD patients and found that the Syt7 mRNA level was significantly attenuated in the patient plasma compared to the healthy controls. We therefore concluded that Syt7 is likely a key factor for the bipolar-like behavioral abnormalities.


Assuntos
Transtorno Bipolar/metabolismo , Transtorno Bipolar/psicologia , Sinaptotagminas/metabolismo , Adulto , Animais , Comportamento , Transtorno Bipolar/sangue , Transtorno Bipolar/genética , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Sinaptotagminas/genética , Adulto Jovem
15.
Immunopharmacol Immunotoxicol ; 45(6): 692-700, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37358143

RESUMO

OBJECTIVE: Treatment with TNF-α inhibitors improve psoriasis with minimize/minor neutrophils infiltration and CXCL-1/8 expression in psoriatic lesions. However, the fine mechanism of TNF-α initiating psoriatic inflammation by tuning keratinocytes is unclear. Our previous research identified the deficiency of intracellular galectin-3 was sufficient to promote psoriasis inflammation characterized by neutrophil accumulation. This study aims to investigate whether TNF-α participated in psoriasis development through dysregulating galectin-3 expression. METHODS: mRNA levels were assessed through quantitative real-time PCR. Flow cytometry was used to detect cell cycle/apoptosis. Western blot was used to evaluate the activation of the NF-κB signaling pathway. HE staining and immunochemistry were used to detect epidermal thickness and MPO expression, respectively. Specific small interfering RNA (siRNA) was used to knock down hsa-miR-27a-3p while plasmids transfection was used to overexpress galectin-3. Further, the multiMiR R package was utilized to predict microRNA-target interaction. RESULTS AND DISCUSSION: We found that TNF-α stimulation altered cell proliferation and differentiation and promoted the production of psoriasis-related inflammatory mediators along with the inhibition of galectin-3 expression in keratinocytes. Supplement of galectin-3 could counteract the rise of CXCL-1/8 but not the other phenotypes of keratinocytes induced by TNF-α. Mechanistically, inhibition of the NF-κB signaling pathway could counteract the decrease of galectin-3 and the increase of hsa-miR-27a-3p expression whereas silence of hsa-miR-27a-3p could counteract the decrease of galectin-3 expression induced by TNF-α treatment in keratinocytes. Intradermal injection of murine anti-CXCL-2 antibody greatly alleviated imiquimod-induced psoriasis-like dermatitis. CONCLUSION: TNF-α initiates psoriatic inflammation by increasing CXCL-1/8 in keratinocytes mediated by the axis of NF-κB-hsa-miR-27a-3p-galectin-3 pathway.


Assuntos
Galectina 3 , Queratinócitos , MicroRNAs , Psoríase , Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/farmacologia , Queratinócitos/metabolismo , Células HaCaT , Humanos , MicroRNAs/genética , Quimiocina CXCL1/metabolismo , Interleucina-8/metabolismo , Galectina 3/genética , Psoríase/genética , Psoríase/patologia , NF-kappa B/metabolismo , Transdução de Sinais , Feminino , Animais , Camundongos , Camundongos Endogâmicos C57BL
16.
BMC Med Educ ; 23(1): 616, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644528

RESUMO

BACKGROUND: Self-directed learning (SDL) is one of the most important abilities for medical students in terms of their future clinical medical practice. During the blended teaching process, teachers can design a variety of learning activities to cultivate students' SDL abilities. This study aimed to assess the differences between the SDL abilities of medical students using blended and traditional didactic teaching. METHODS: This study included 239 medical students from eight administrative classes. The students were divided into two groups: (1) the experimental group (EG), which included 119 students from four administrative classes, and (2) the control group (CG), which included 120 students from the remaining four classes. From February to July 2022, blended teaching methods were applied to the EG group, and SDL abilities were assessed in comparison to the CG group receiving traditional didactic teaching methods. RESULTS: At the end of the semester, significant differences (p < 0.05) were observed between EG and CG in all six SDL ability factors. Furthermore, when k-means cluster analysis was used to analyze the learning behavior of students in the EG after classifying them as comprehensive, interactive, and passive types, significant differences were observed in all six Self-directed learning factors of students with the comprehensive type, whereas significant differences were observed in four factors (setting learning goals and plans, self-monitoring and regulation, information processing, and communication and cooperation) of students with the interactive type. For students with passive type, only one factor of SDL (information processing) showed significant improvement. There were on differences between comprehensive, interactive, and passive types of CG. CONCLUSION: The blended teaching approach is better than the conventional didactic teaching for cultivating clinical medical students' SDL abilities.


Assuntos
Pessoal de Educação , Estudantes de Medicina , Humanos , Aprendizagem , Cognição , Análise por Conglomerados
17.
BMC Nurs ; 22(1): 218, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37357312

RESUMO

BACKGROUND: Neonatal nurses' working environments are highly stressful, and burnout is common. This study examines the effect of socioeconomic factors, perceived stress, and social support on neonatal nurse burnout. METHODS: A total of 311 neonatal nurses participated in this study. They were administered a validated Maslach Burnout Inventory. The study employed a 14-item perceived stress scale (PSS-14) and a social support rate scale (SSRS) to examine stress, socioeconomic factors, and lifestyles. RESULTS: Of the neonatal nurses, 40.19% had burnout, 89.60% had mild burnout, and 10.40% had moderate burnout; no neonatal nurse experienced severe burnout. Young nurses and those with low technical skills, poor interpersonal relationships, irregular diet, and insufficient rest were exposed to burnout (all p < 0.05).Most burnout nurses experienced moderate-severe perceived stress, and their PSS-14 scores were higher (all p < 0.05).The scores for objective social support, subjective social support, utilization of social support, total SSRS scores, and the level of social support were all lower in burnout nurses (all p < 0.05). Perceived stress was correlated positively and significantly with emotional exhaustion and personal accomplishment (all p < 0.05). Social support correlated significantly with and reduced personal accomplishments (p < 0.05). Age, poor interpersonal relationships, perceived stress, and social support were all independent factors associated with neonatal nurse burnout (all p < 0.05). CONCLUSION: The prevalence of burnout in neonatal nurses was higher than average. Socioeconomic factors, higher perceived stress, and lower social support contribute to neonatal nurse burnout. Nursing managers should pay attention to socioeconomic factors, perceived stress, and social support among neonatal nurses and employ strategies to reduce neonatal nurse burnout.

18.
Vet Med (Praha) ; 68(3): 106-115, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37981902

RESUMO

Porcine deltacoronavirus (PDCoV) and porcine sapelovirus (PSV) are two viruses that can cause diarrhoea in pigs and bring great economic loss to the pig industry. In this research, a duplex real-time quantitative polymerase chain reaction (qPCR) assay based on SYBR Green I was developed to simultaneously detect PDCoV and PSV. No specific melting peaks were found in other porcine diarrhoea-associated viruses, indicating that the method developed in this study had good specificity. The detection limits of PDCoV and PSV were 1.0 × 101 copies µl-1 and 1.0 × 102 copies µl-1, respectively. The duplex real-time qPCR assay tested two hundred and three (203) intestinal and faecal samples collected from diarrhoeal and asymptomatic pigs. The positive rates of PDCoV and PSV were 20.2% and 23.2%, respectively. The co-infection rate of PDCoV and PSV was 13.8%. To evaluate the accuracy of the developed method, conventional PCR and singular TaqMan real-time qPCR assays for PDCoV/PSV were also used to detect the samples. The results showed that the duplex real-time qPCR assay was consistent with the singular assays, but its sensitivity was higher than conventional PCR methods. This duplex real-time qPCR assay provides a rapid, sensitive and reliable method in a clinic to simultaneously detect PDCoV and PSV.

19.
Yi Chuan ; 45(9): 793-800, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37731233

RESUMO

Flowering represents the transition from vegetative stage to reproductive stage. As a photoperiod- sensitive crop, soybean can perceive changes in photoperiod to regulate flowering and reproductive periods, thereby influencing soybean yield and other agronomic traits, and determining the photoperiodic adaptability. Therefore, understanding the regulatory mechanisms of photoperiod on flowering and reproductive periods in soybean is one of the hotspots in soybean research. In this review, we introduce the molecular mechanisms of early flowering and early maturation during soybean domestication, and the molecular regulatory pathways of cultivated soybean expansion from the origin to high and low latitudes, respectively. At last, we summarize the research progress on photoperiod adaptability in wild soybean. Analyzing the regulatory mechanisms of photoperiod on soybean life history and domestication will provide valuable insights for the breeding of superior soybean varieties.


Assuntos
Glycine max , Fotoperíodo , Glycine max/genética , Melhoramento Vegetal , Agricultura , Domesticação
20.
J Aging Soc Policy ; : 1-25, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38149690

RESUMO

Studies have shown how generativity, the concern for establishing and guiding the next generation and safeguarding its wellbeing, functions as an intergenerational conduit, bridging the developmental stages of older individuals with those younger. Yet, applications of generativity, as a means to bridge generational gaps within rapid social change, remain underexplored in the intergenerational field. Using Singapore as a case study, and through focus group discussions with 103 older persons, this paper examines how older Singaporeans express their generative concern and internalize their generative capacities across different social settings and rapid socioeconomic transformation. Mismatch between older Singaporeans' generative concern and capacity contributes to ambivalence - mixed feelings about guiding younger generations - which emerges out of older Singaporeans' struggles with cultural change prompted by economic progress, as well as concerns about their place and value in a technologically advanced global city-state. The concept of generative ambivalence can add value to policy perspectives on intergenerational cohesion, as it considers people's attempts to forge commonalities and mutual reciprocity despite differences (e.g. gender, age, race, skills), as well as highlights intergenerational complexities beyond superficial binaries. Policies aimed at bringing generations together must be intentional in creating opportunity structures that go beyond categorical differences, where multiple generations can thrive interdependently.

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