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De novo variants in the Cytoplasmic FMR1-interacting protein 2 (CYFIP2) have been repeatedly associated with neurodevelopmental disorders and epilepsy, underscoring its critical role in brain development and function. While CYFIP2's role in regulating actin polymerization as part of the WAVE regulatory complex (WRC) is well-established, its additional molecular functions remain relatively unexplored. In this study, we performed unbiased quantitative proteomic analysis, revealing 278 differentially expressed proteins (DEPs) in the forebrain of Cyfip2 knock-out embryonic mice compared to wild-type mice. Unexpectedly, these DEPs, in conjunction with previously identified CYFIP2 brain interactors, included not only other WRC components but also numerous proteins associated with membraneless organelles (MLOs) involved in mRNA processing and translation within cells, including the nucleolus, stress granules, and processing bodies. Additionally, single-cell transcriptomic analysis of the Cyfip2 knock-out forebrain revealed gene expression changes linked to cellular stress responses and MLOs. We also observed morphological changes in MLOs in Cyfip2 knock-out brains and CYFIP2 knock-down cells under basal and stress conditions. Lastly, we demonstrated that CYFIP2 knock-down in cells, potentially through WRC-dependent actin regulation, suppressed the phosphorylation levels of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), thereby enhancing protein synthesis. These results suggest a physical and functional connection between CYFIP2 and various MLO proteins and also extend CYFIP2's role within the WRC from actin regulation to influencing eIF2α phosphorylation and protein synthesis. With these dual functions, CYFIP2 may fine-tune the balance between MLO formation/dynamics and protein synthesis, a crucial aspect of proper mRNA processing and translation.
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ConspectusGas sensors are used in various applications to sense toxic gases, mainly for enhanced safety. Resistive sensors are particularly popular owing to their ability to detect trace amounts of gases, high stability, fast response times, and affordability. Semiconducting metal oxides are commonly employed in the fabrication of resistive gas sensors. However, these sensors often require high working temperatures, bringing about increased energy consumption and reduced selectivity. Furthermore, they do not have enough flexibility, and their performance is significantly decreased under bending, stretching, or twisting. To address these challenges, alternative materials capable of operating at lower temperatures with high flexibility are needed. Two-dimensional (2D) materials such as MXenes and transition-metal dichalcogenides (TMDs) offer high surface area and conductivity owing to their unique 2D structure, making them promising candidates for realization of resistive gas sensors. Nevertheless, their sensing performance in pristine form is typically weak and unacceptable, particularly in terms of response, selectivity, and recovery time (trec). To overcome these drawbacks, several strategies can be employed to enhance their sensing properties. Noble-metal decoration such as (Au, Pt, Pd, Rh, Ag) is a highly promising method, in which the catalytic effects of noble metals as well as formation of potential barriers with MXenes or TMDs eventually contribute to boosted response. Additionally, bimetallic noble metals such as Pt-Pd and Au/Pd with their synergistic properties can further improve sensor performance. Ion implantation is another feasible approach, involving doping of sensing materials with the desired concentration of dopants through control over the energy and dosage of the irradiation ions as well as creation of structural defects such as oxygen vacancies through high-energy ion-beam irradiation, contributing to enhanced sensing capabilities. The formation of core-shell structures is also effective, creating numerous interfaces between core and shell materials that optimize the sensing characteristics. However, the shell thickness needs to be carefully optimized to achieve the best sensing output. To reduce energy consumption, sensors can operate in a self-heating condition where an external voltage is applied to the electrodes, significantly lowering the power requirements. This enables sensors to function in energy-constrained environments, such as remote or low-energy areas. An important advantage of 2D MXenes and TMDs is their high mechanical flexibility. Unlike semiconducting metal oxides that lack mechanical flexibility, MXenes and TMDs can maintain their sensing performance even when integrated onto flexible substrates and subjected to bending, tilting, or stretching. This flexibility makes them ideal for fabricating flexible and portable gas sensors that rigid sensors cannot achieve.
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Many attempts have been made to develop new agents that target EGFR mutants or regulate downstream factors in various cancers. Cell-based screening showed that a natural small molecule, Ertredin, inhibited the growth of EGFRvIII mutant cancer cells. Previous studies have shown that Ertredin effectively inhibits anchorage-independent 3D growth of sphere-forming cells transfected with EGFRvIII mutant cDNA. However, the underlying mechanism remains unclear. In this study, we investigated the target protein of Ertredin by combining drug affinity-responsive target stability (DARTS) assays with liquid chromatography-mass spectrometry using label-free Ertredin as a bait and HepG2 cell lysates as a proteome pool. NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 (NDUFA12) was identified as an Ertredin-binding protein that was responsible for its biological activity. The interaction between NDUFA12 and Ertredin was validated by DARTS and cellular thermal shift assays. In addition, the genetic knockdown of the identified target, NDUFA12, was shown to suppress cell proliferation. NDUFA12 was identified as a biologically relevant target protein of Ertredin that is responsible for its antitumor activity, and these results provide insights into the role of NDUFA12 as a downstream factor in EGFRvIII mutants.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Proteômica/métodos , Proteínas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , NADPH DesidrogenaseRESUMO
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to the absence of diagnostic markers and molecular targets. Here, we took an unconventional approach to identify new molecular targets for pancreatic cancer. We chose uncharacterized protein evidence level 1 without function annotation from extensive proteomic research on pancreatic cancer and focused on proline and serine-rich 2 (PROSER2), which ranked high in the cell membrane and cytoplasm. In our study using cell lines and patient-derived orthotopic xenograft cells, PROSER2 exhibited a higher expression in cells derived from primary tumors than in those from metastatic tissues. PROSER2 was localized in the cell membrane and cytosol by immunocytochemistry. PROSER2 overexpression significantly reduced the metastatic ability of cancer cells, whereas its suppression had the opposite effect. Proteomic analysis revealed that PROSER2 interacts with STK25 and PDCD10, and their binding was confirmed by immunoprecipitation and immunocytochemistry. STK25 knockdown enhanced metastasis by decreasing p-AMPK levels, whereas PROSER2-overexpressing cells increased the level of p-AMPK, indicating that PROSER2 suppresses invasion via the AMPK pathway by interacting with STK25. This is the first demonstration of the novel role of PROSER2 in antagonizing tumor progression via the STK25-AMPK pathway in PDAC. LC-MS/MS data are available at MassIVE (MSV000092953) and ProteomeXchange (PXD045646).
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Proteínas Quinases Ativadas por AMP , Cromatografia Líquida , Proteômica , Proliferação de Células , Movimento Celular , Espectrometria de Massas em Tandem , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/genética , Modelos Animais de Doenças , Proteínas Serina-Treonina Quinases , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Peripheral vascular interventions (PVIs) offer several benefits to patients with lower extremity arterial diseases, including reduced pain, simpler anesthesia, and shorter recovery time, compared to open surgery. However, to monitor the endovascular tools inside the body, PVIs are conducted under X-ray fluoroscopy, which poses serious long-term health risks to physicians and patients. Shortwave infrared (SWIR) imaging of quantum dots (QDs) has shown great potential in bioimaging due to the non-ionizing penetration of SWIR light through tissues. In this paper, a QD-based magnetic guidewire and its system is introduced that allows X-ray-free detection under SWIR imaging and precise steering via magnetic manipulation. The QD magnetic guidewire contains a flexible silicone tube encapsulating a QD polydimethylsiloxane (PDMS) composite, where HgCdSe/HgS/CdS/CdZnS/ZnS/SiO2 core/multi-shell QDs are dispersed in the PDMS matrix for SWIR imaging upon near-infrared excitation, as well as a permanent magnet for magnetic steering. The SWIR penetration of the QD magnetic guidewire is investigated within an artificial tissue model (1% Intralipid) and explore the potential for non-fluoroscopic PVIs within a vascular phantom model. The QD magnetic guidewire is biocompatible in its entirety, with excellent resistance to photobleaching and chemical alteration, which is a promising sign for its future clinical implementation.
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Transition metal dichalcogenides (TMDs) with a two-dimensional (2D) structure and semiconducting features are highly favorable for the production of NH3gas sensors. Among the TMD family, WS2, WSe2, MoS2, and MoSe2exhibit high conductivity and a high surface area, along with high availability, reasons for which they are favored in gas-sensing studies. In this review, we have discussed the structure, synthesis, and NH3sensing characteristics of pristine, decorated, doped, and composite-based WS2, WSe2, MoS2, and MoSe2gas sensors. Both experimental and theoretical studies are considered. Furthermore, both room temperature and higher temperature gas sensors are discussed. We also emphasized the gas-sensing mechanism. Thus, this review provides a reference for researchers working in the field of 2D TMD gas sensors.
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BACKGROUND: Robust and accurate prediction of severity for patients with COVID-19 is crucial for patient triaging decisions. Many proposed models were prone to either high bias risk or low-to-moderate discrimination. Some also suffered from a lack of clinical interpretability and were developed based on early pandemic period data. Hence, there has been a compelling need for advancements in prediction models for better clinical applicability. OBJECTIVE: The primary objective of this study was to develop and validate a machine learning-based Robust and Interpretable Early Triaging Support (RIETS) system that predicts severity progression (involving any of the following events: intensive care unit admission, in-hospital death, mechanical ventilation required, or extracorporeal membrane oxygenation required) within 15 days upon hospitalization based on routinely available clinical and laboratory biomarkers. METHODS: We included data from 5945 hospitalized patients with COVID-19 from 19 hospitals in South Korea collected between January 2020 and August 2022. For model development and external validation, the whole data set was partitioned into 2 independent cohorts by stratified random cluster sampling according to hospital type (general and tertiary care) and geographical location (metropolitan and nonmetropolitan). Machine learning models were trained and internally validated through a cross-validation technique on the development cohort. They were externally validated using a bootstrapped sampling technique on the external validation cohort. The best-performing model was selected primarily based on the area under the receiver operating characteristic curve (AUROC), and its robustness was evaluated using bias risk assessment. For model interpretability, we used Shapley and patient clustering methods. RESULTS: Our final model, RIETS, was developed based on a deep neural network of 11 clinical and laboratory biomarkers that are readily available within the first day of hospitalization. The features predictive of severity included lactate dehydrogenase, age, absolute lymphocyte count, dyspnea, respiratory rate, diabetes mellitus, c-reactive protein, absolute neutrophil count, platelet count, white blood cell count, and saturation of peripheral oxygen. RIETS demonstrated excellent discrimination (AUROC=0.937; 95% CI 0.935-0.938) with high calibration (integrated calibration index=0.041), satisfied all the criteria of low bias risk in a risk assessment tool, and provided detailed interpretations of model parameters and patient clusters. In addition, RIETS showed potential for transportability across variant periods with its sustainable prediction on Omicron cases (AUROC=0.903, 95% CI 0.897-0.910). CONCLUSIONS: RIETS was developed and validated to assist early triaging by promptly predicting the severity of hospitalized patients with COVID-19. Its high performance with low bias risk ensures considerably reliable prediction. The use of a nationwide multicenter cohort in the model development and validation implicates generalizability. The use of routinely collected features may enable wide adaptability. Interpretations of model parameters and patients can promote clinical applicability. Together, we anticipate that RIETS will facilitate the patient triaging workflow and efficient resource allocation when incorporated into a routine clinical practice.
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Algoritmos , COVID-19 , Triagem , Humanos , Biomarcadores , COVID-19/diagnóstico , Mortalidade Hospitalar , Redes Neurais de Computação , Triagem/métodos , República da CoreiaRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is effective in preventing the disease transmission and progression. However, the relatively mild disease course of the omicron variant and the decrease in antibodies over time after vaccination raise questions about the effectiveness of vaccination, especially in young people. We compared the prevalence of pneumonia and chest X-ray severity score according to vaccination status among patients < 50 years old with COVID-19. METHODS: From January 17 to March 17, 2022, 579 patients with COVID-19, who were < 50 years old and had a known vaccination history in our institution, were all included in this study. All patients underwent initial chest radiography, and follow-up chest radiographs were obtained every two days until discharge. Pneumonia was scored from the radiographs using the Brixia scoring system. The scores of the six lung zones were added for a total score ranging from 0 to 18. Patients were divided into four groups according to 10-year age intervals. Differences between groups were analyzed using the χ² or Fisher's exact tests for categorical variables and the Kruskal-Wallis test or analysis of variance for continuous variables. RESULTS: Among patients aged 12-19 years, the prevalence of pneumonia did not differ depending on vaccination status (non-vaccinated vs. vaccinated, 1/47 [2.1%] vs. 1/18 [5.6%]; P = 0.577). Among patients in their 20s, the prevalence of pneumonia was significantly higher among non-vaccinated patients than among vaccinated patients (8/28, 28.6% vs. 7/138, 5.1%, P < 0.001), similar to patients in their 40s (32/52 [61.5%] vs. 18/138 [13.0%]; P < 0.001). The chest X-ray severity score was also significantly higher in non-vaccinated patients than that in vaccinated patients in their 20s to their 40s (P < 0.001), but not among patients aged 12-19 years (P = 0.678). CONCLUSION: In patients aged 20-49 years, vaccinated patients had a significantly lower prevalence of pneumonia and chest X-ray severity score than non-vaccinated patients.
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COVID-19 , Humanos , Adolescente , Pessoa de Meia-Idade , COVID-19/epidemiologia , SARS-CoV-2 , Prevalência , Estudos Retrospectivos , Radiografia , VacinaçãoRESUMO
Tomatoes contain many secondary metabolites such as ß-carotene, lycopene, phenols, flavonoids, and vitamin C, which are responsible for antioxidant activity. SlSGR1 encodes a STAY-GREEN protein that plays a critical role in the regulation of chlorophyll degradation in tomato leaves and fruits. Therefore, the present study was conducted to evaluate the sgr1 null lines based on their physicochemical characteristics, the content of secondary metabolites, and the γ-Aminobutyric acid (GABA) content. The total soluble solids (TSS), titrated acidity (TA), and brix acid ratio (BAR) of the sgr1 null lines were higher than those of the wild type(WT). Additionally, the sgr1 null lines accumulated higher levels of flavor-inducing ascorbic acid and total carotenoids compared to WT. Also, the total phenolic content, total flavonoids, GABA content, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical content of the sgr1 null lines were higher than those of the WT. Therefore, these studies suggest that the knockout of the SGR1 gene by the CRISPR/Cas9 system can improve various functional compounds in tomato fruit, thereby satisfying the antioxidant properties required by consumers.
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Antioxidantes , Sistemas CRISPR-Cas , Proteínas de Plantas , Solanum lycopersicum , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Carotenoides/metabolismo , Flavonoides/metabolismo , Frutas/genética , Frutas/metabolismo , Frutas/química , Ácido gama-Aminobutírico/metabolismo , Edição de Genes , Técnicas de Inativação de Genes , Fenóis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismoRESUMO
Solute carrier 40A1 (SLC40A1) encodes ferroportin, which is the only known transmembrane protein that exports elemental iron from mammalian cells and is essential for iron homeostasis. Mutations in SLC40A1 are associated with iron-overload disorders. In addition to ferroportin diseases, SLC40A1 expression is downregulated in various cancer types. Despite the clinical significance of the SLC40A1 transporter, only a few studies have investigated genetic variants in SLC40A1. The present study was performed to identify genetic variations in the SLC40A1 promoter and functionally characterize each variant using in vitro assays. We investigated four haplotypes and five variants in the SLC40A1 promoter. We observed that haplotype 3 (H3) had significantly lower promoter activity than H1, whereas the activity of H4 was significantly higher than that of H1. Luciferase activity of H2 was comparable to that of H1. In addition, four variants of SLC40A1, c.-1355G>C, c.-662C>T, c.-98G>C, and c.-8C>G, showed significantly increased luciferase activity compared to the wild type (WT), whereas c.-750G>A showed significantly decreased luciferase activity compared to the WT. Three transcription factors, cAMP response element-binding protein-1 (CREB-1), chicken ovalbumin upstream promoter transcription factor 1, and hepatic leukemia factor (HLF), were predicted to bind to the promoter regions of SLC40A1 near c.-662C>T, c.-98G>C, and c.-8C>G, respectively. Among these, CREB-1 and HLF bound more strongly to the variant sequences than to the WT and functioned as activators of SLC40A1 transcription. Collectively, our findings indicate that the two SLC40A1 promoter haplotypes affect SLC40A1 transcription, which is regulated by CREB-1 and HLF.
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PURPOSE: To identify risk factors for pupillary optic capture after sutureless flanged intraocular lens (IOL) fixation for IOL dislocation. METHODS: This retrospective comparative study enrolled consecutive patients who underwent flanged IOL fixation using 25-gauge pars plana vitrectomy. One hundred twenty-six eyes (126 patients) were divided into two groups according to the presence or absence of pupillary optic capture. A swept-source anterior segment optical coherence tomography and a rotating Scheimpflug camera were used to analyze and compare surgical parameters, including axial length, anterior chamber depth, differences in scleral tunnel angle and length, and IOL tilt and decentration, between the two groups. RESULTS: Compared with the nonpupillary optic capture group (106 eyes, 84.1%), the pupillary optic capture group (20 eyes, 15.9%) had larger differences in the nasal and temporal scleral tunnel angles and larger horizontal tilt (P < 0.05). Multivariate regression analysis demonstrated that these factors correlated with the occurrence of pupillary optic capture (P < 0.05). CONCLUSION: To prevent pupillary optic capture after flanged IOL fixation, surgeons should avoid asymmetry in the angles of the nasal and temporal scleral tunnels, which causes horizontal IOL tilt and subsequent pupillary capture.
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Subluxação do Cristalino , Lentes Intraoculares , Humanos , Implante de Lente Intraocular/métodos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Lentes Intraoculares/efeitos adversos , Esclera/cirurgia , Fatores de Risco , Subluxação do Cristalino/cirurgia , Técnicas de Sutura/efeitos adversosRESUMO
OBJECTIVE: This study examines the characteristics and effects of virtual reality (VR) intravenous injection training programs for nurses and nursing students, using Kirkpatrick's four-level model of educational evaluation. Kirkpatrick's framework is based on the premise that learning from training programs can be classified into four levels: reaction, learning, behavior, and results. DESIGN: A systematic review. DATA SOURCES: Literature searches were conducted of eight electronic databases (PubMed, CINAHL, Cochrane, EMBASE, DBpia, KISS, RISS, KoreaMed) to identify original research articles from each database's inception to March 2023. REVIEW METHODS: For the 13 selected articles, quality appraisal was performed using the RoB 2 and ROBINS-I tools for randomized controlled trials (RCTs) and non-RCTs, respectively. RESULTS: Virtual intravenous simulators and desktop and immersive VR technologies were utilized in intravenous injection training. These VR technologies were applied either alone or in conjunction with simulators, focusing on junior nursing students without intravenous injection experience. We found a positive effect on nursing students' intravenous injection performance (Level 2: learning evaluation) in approximately half the studies. However, results were inconsistent due to measurement tools' diversity. In all studies, the degree of evaluation for Levels 1 (reaction evaluation), 3 (behavior evaluation), and 4 (results evaluation) of the Kirkpatrick Model was low. CONCLUSIONS: Desktop or immersive VR with low-fidelity or high-fidelity simulators should be provided to senior nursing students and new nurses for intravenous injection training. Additionally, standardized tools should be developed to accurately measure training effects. Finally, the Kirkpatrick Model's four levels should be evaluated to demonstrate the training programs' value.
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Estudantes de Enfermagem , Realidade Virtual , Humanos , Injeções Intravenosas/enfermagem , Competência Clínica/normas , Treinamento por Simulação/métodos , Bacharelado em Enfermagem/métodos , Enfermeiras e EnfermeirosRESUMO
Mitogen-activated protein kinase (MAPK) pathways are fundamental to the regulation of biological processes in eukaryotic organisms. The basidiomycete Cryptococcus neoformans, known for causing fungal meningitis worldwide, possesses five MAPKs. Among these, Cpk1, Hog1, and Mpk1 have established roles in sexual reproduction, stress responses, and cell wall integrity. However, the roles of Cpk2 and Mpk2 are less understood. Our study elucidates the functional interplay between the Cpk1/Cpk2 and Mpk1/Mpk2 MAPK pathways in C. neoformans. We discovered that CPK2 overexpression compensates for cpk1Δ mating deficiencies via the Mat2 transcription factor, revealing functional redundancy between Cpk1 and Cpk2. We also found that Mpk2 is phosphorylated in response to cell wall stress, a process regulated by the MAPK kinase (MAP2K) Mkk2 and MAP2K kinases (MAP3Ks) Ssk2 and Ste11. Overexpression of MPK2 partially restores cell wall integrity in mpk1Δ by influencing key cell wall components, such as chitin and the polysaccharide capsule. Contrarily, MPK2 overexpression cannot restore thermotolerance and cell membrane integrity in mpk1Δ. These results suggest that Mpk1 and Mpk2 have redundant and opposing roles in the cellular response to cell wall and membrane stresses. Most notably, the dual deletion of MPK1 and MPK2 restores wild-type mating efficiency in cpk1Δ mutants via upregulation of the mating-regulating transcription factors MAT2 and ZNF2, suggesting that the Mpk1 and Mpk2 cooperate to negatively regulate the pheromone-responsive Cpk1 MAPK pathway. Our research collectively underscores a sophisticated regulatory network of cryptococcal MAPK signaling pathways that intricately govern sexual reproduction and cell wall integrity, thereby controlling fungal development and pathogenicity.IMPORTANCEIn the realm of fungal biology, our study on Cryptococcus neoformans offers pivotal insights into the roles of specific proteins called mitogen-activated protein kinases (MAPKs). Here, we discovered the cryptic functions of Cpk2 and Mpk2, two MAPKs previously overshadowed by their dominant counterparts Cpk1 and Mpk1, respectively. Our findings reveal that these "underdog" proteins are not just backup players; they play crucial roles in vital processes like mating and cell wall maintenance in C. neoformans. Their ability to step in and compensate when their dominant counterparts are absent showcases the adaptability of C. neoformans. This newfound understanding not only enriches our knowledge of fungal MAPK mechanisms but also underscores the intricate balance and interplay of proteins in ensuring the organism's survival and adaptability.
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Parede Celular , Cryptococcus neoformans , Proteínas Quinases Ativadas por Mitógeno , Cryptococcus neoformans/genética , Cryptococcus neoformans/enzimologia , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Parede Celular/metabolismo , Parede Celular/genética , Regulação Fúngica da Expressão Gênica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fosforilação , Sistema de Sinalização das MAP QuinasesRESUMO
Circadian clocks, generating daily rhythms in biological processes, maintain homeostasis in physiology, so clock alterations are considered detrimental. Studies in brain pathology support this by reporting abnormal circadian phenotypes in patients, but restoring the abnormalities by light therapy shows no dramatic effects. Recent studies on glial clocks report the complex effects of altered clocks by showing their beneficial effects on brain repairs. However, how neuronal clocks respond to brain pathology is elusive. This study shows that neuronal BMAL1, a core of circadian clocks, reduces its expression levels in neurodegenerative excitotoxicity. In the dentate gyrus of excitotoxic hippocampal lesions, reduced BMAL1 in granule cells precedes apoptosis. This subsequently reduces BMAL1 levels in neighbor neural stem cells and progenitors in the subgranular zone, enhancing proliferation. This shows the various BMAL1 roles depending on cell types, and its alterations can benefit brain repair. Thus, cell-type-specific BMAL1 targeting is necessary to treat brain pathology.
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In vivo models of brain pathology are crucial for studying neurological diseases. Here, we present a protocol to induce a pathological condition in a mouse brain area by local injection of neurotoxic stimulus. We describe steps for preparing reagents, stereotaxic injection procedures to induce neurodegeneration in the hippocampus, and preparation of brain sections to examine the induced model. This protocol is useful for studying how local pathology affects other brain areas and neighbor cells and its functional consequences in behavior. For complete details on the use and execution of this protocol, please refer to Zhang et al.1.
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Perovskite quantum dots (PQDs) have received considerable attention as fluorescent materials due to their excellent optical properties. However, because PQDs contain ionic bonds, they have the disadvantage of being vulnerable to environmental conditions, so improving their stability is essential. Indeed, recent research has focused on improving both the stability and luminescence of PQDs by mixing them with methyl acetate (MeOAc) to suppress surface defects via purification. MeOAc reacts with the surface ligands of PQDs, resulting in ligand-controlled purification. However, while the ligands are limited for the PQD synthesis, the effect of ligand alkyl-chain length has not been reported. Therefore, we report herein a strategy for obtaining stable PQDs with tunable performances by using amine ligands of various chain lengths. The amine ligand is selected because it is very effective in interacting with the halide vacancies present on the surface of the perovskite crystal structure. The results indicate that MeOAc becomes less effective as the chain length of the ligand is increased, and more effective as the chain length is decreased. Consequently, PQDs treated with MeOAc and a short-chain ligand afford a quantum yield (QY) of 79.2% and are highly stable when exposed to thermal and ambient conditions. Therefore, we suggest a facile approach to suppressing the degradation of PQDs during the fabrication process.
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Introduction: Previous research has highlighted the duality of self-consciousness, which simultaneously plays adaptive and maladaptive roles. This study aims to develop a measure that categorically distinguishes between different types of self-consciousness styles based on the Regulatory Focus Theory (RFT) and examines their relationship with mental health-related indicators. Methods: Data were gathered through an online mental health survey conducted at a University Student Counseling Center in Seoul. The study involved exploratory factor analysis, confirmatory factor analysis, and reliability and validity analysis, which resulted in the development of a 14-question Self-Consciousness Type Scale (SCTS). Results: Both exploratory and confirmatory factor analyses validated the two-factor structure of the SCTS. The fit indices of the final model indicated a good fit, with high internal consistency for both sub-factors. Convergent and discriminant validity were confirmed through correlations between the sub-scales. Cluster analysis identified four distinct subtypes of self-consciousness styles: Growth-oriented, Defensive, Ambivalent, and Low-focus self-consciousness. Group difference analysis revealed significant differences in mental health-related variables among the subtypes, supporting the 2 × 2 model of prevention-focused and promotion-focused self-consciousness. Discussion: The findings support the SCTS as a valid measurement tool capable of distinguishing four distinct types of self-consciousness, aligning with the multidimensional model of self-consciousness. The study's limitations and implications were discussed based on the results, emphasizing the potential applications of the SCTS in mental health research and practice.
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Solute carrier family (SLC) transporters are expressed in the digestive system and play important roles in maintaining physiological functions in the body. In addition, SLC transporters act as oncoproteins or tumor-suppressor proteins during the development, progression, and metastasis of various digestive system cancers. SLC22A18, a member of the SLC22 gene family, is an orphan transporter with an unknown endogenous substrate. Previous study revealed that SLC22A18 is downregulated in colorectal cancer tissues and that it acts as a suppressor in colorectal cancer, although the effects of SLC22A18 variants on colon cancer cell proliferation, migration, and invasion are unknown. Therefore, in this study, we identified SLC22A18 variants found in multiple populations by searching public databases and determined the in vitro effects of these missense variations on transporter expression and cancer progression. Our results indicated that three missense SLC22A18 variants-p.Ala6Thr, p.Arg12Gln, and p.Arg86His-had significantly lower cell expression than the wild type, possibly owing to intracellular degradation. Furthermore, these three variants caused significantly higher proliferation, migration, and invasion of colon cancer cells than the wild type. Our findings suggest that missense variants of SLC22A18 can potentially serve as biomarkers or prognostic tools that enable clinicians to predict colorectal cancer progression.
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Neoplasias do Colo , Proteínas de Transporte de Cátions Orgânicos , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Prognóstico , Proteínas Supressoras de Tumor/genética , Proteínas de Transporte de Cátions Orgânicos/genéticaRESUMO
Dogs that had splenectomy are predisposed to fatal thrombotic conditions, and thrombocytosis is a risk factor for post-splenectomy hypercoagulability. However, in veterinary medicine, there are no specific therapeutic approaches for managing this hypercoagulability. This study aimed to determine the preventive effect of clopidogrel on post-operative hypercoagulability during the first 2 weeks post-splenectomy in dogs with splenic masses. This study included 12 dogs that had splenectomy. Seven dogs received no treatment (group A), and five were treated with clopidogrel (group B). Clopidogrel was loaded at 10 mg/kg on day 2 and continued at 2 mg/kg until day 14. Blood samples were collected on the day of surgery and 2, 7, and 14 days after splenectomy in both groups. In group B, thromboelastography (TEG) was performed on the same days. In group A, there was significant elevation of platelet counts on days 7 (p = 0.007) and 14 (p = 0.001) compared to day 0. In group B, the platelet counts were significantly elevated on day 7 (p = 0.032) but no significant difference was found on day 14 compared to day 0. Platelet counts on day 14 were significantly higher in group A than in group B (p = 0.03). The lower platelet counts were correlated with alterations in TEG parameters, and no significant differences were found in the K and α-angle values at all postoperative assessment points compared to day 0. Our study suggests that clopidogrel may reduce post-operative thrombocytosis and hypercoagulability in dogs that undergo splenectomy for splenic masses.