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Optoelectronic devices consist of heterointerfaces formed between dissimilar semiconducting materials. The relative energy-level alignment between contacting semiconductors determinately affects the heterointerface charge injection and extraction dynamics. For perovskite solar cells (PSCs), the heterointerface between the top perovskite surface and a charge-transporting material is often treated for defect passivation1-4 to improve the PSC stability and performance. However, such surface treatments can also affect the heterointerface energetics1. Here we show that surface treatments may induce a negative work function shift (that is, more n-type), which activates halide migration to aggravate PSC instability. Therefore, despite the beneficial effects of surface passivation, this detrimental side effect limits the maximum stability improvement attainable for PSCs treated in this way. This trade-off between the beneficial and detrimental effects should guide further work on improving PSC stability via surface treatments.
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In perovskite solar cells, the interfaces between the perovskite and charge-transporting layers contain high concentrations of defects (about 100 times that within the perovskite layer), specifically, deep-level defects, which substantially reduce the power conversion efficiency of the devices1-3. Recent efforts to reduce these interfacial defects have focused mainly on surface passivation4-6. However, passivating the perovskite surface that interfaces with the electron-transporting layer is difficult, because the surface-treatment agents on the electron-transporting layer may dissolve while coating the perovskite thin film. Alternatively, interfacial defects may not be a concern if a coherent interface could be formed between the electron-transporting and perovskite layers. Here we report the formation of an interlayer between a SnO2 electron-transporting layer and a halide perovskite light-absorbing layer, achieved by coupling Cl-bonded SnO2 with a Cl-containing perovskite precursor. This interlayer has atomically coherent features, which enhance charge extraction and transport from the perovskite layer, and fewer interfacial defects. The existence of such a coherent interlayer allowed us to fabricate perovskite solar cells with a power conversion efficiency of 25.8 per cent (certified 25.5 per cent)under standard illumination. Furthermore, unencapsulated devices maintained about 90 per cent of their initial efficiency even after continuous light exposure for 500 hours. Our findings provide guidelines for designing defect-minimizing interfaces between metal halide perovskites and electron-transporting layers.
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Anaplerosis refers to enzymatic reactions or pathways replenishing metabolic intermediates in the tricarboxylic acid (TCA) cycle. Pyruvate carboxylase (PYC) plays an important anaplerotic role by catalyzing pyruvate carboxylation, forming oxaloacetate. Although PYC orthologs are well conserved in prokaryotes and eukaryotes, their pathobiological functions in filamentous pathogenic fungi have yet to be fully understood. Here, we delve into the molecular functions of the ortholog gene PYC1 in Fusarium graminearum and F. oxysporum, prominent fungal plant pathogens with distinct pathosystems, demonstrating variations in carbon metabolism for pathogenesis. Surprisingly, the PYC1 deletion mutant of F. oxysporum exhibited pleiotropic defects in hyphal growth, conidiation, and virulence, unlike F. graminearum, where PYC1 deletion did not significantly impact virulence. To further explore the species-specific effects of PYC1 deletion on pathogenicity, we conducted comprehensive metabolic profiling. Despite shared metabolic changes, distinct reprogramming in central carbon and nitrogen metabolism was identified. Specifically, alpha-ketoglutarate, a key link between the TCA cycle and amino acid metabolism, showed significant down-regulation exclusively in the PYC1 deletion mutant of F. oxysporum. The metabolic response associated with pathogenicity was notably characterized by S-methyl-5-thioadenosine and S-adenosyl-L-methionine. This research sheds light on how PYC1-mediated anaplerosis affects fungal metabolism and reveals species-specific variations, exemplified in F. graminearum and F. oxysporum.
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Proteínas Fúngicas , Fusarium , Doenças das Plantas , Fusarium/patogenicidade , Fusarium/genética , Fusarium/metabolismo , Doenças das Plantas/microbiologia , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Virulência , Ciclo do Ácido Cítrico , Ácido Oxaloacético/metabolismo , Piruvato Carboxilase/metabolismo , Piruvato Carboxilase/genéticaRESUMO
Deregulated cyclin-dependent kinase 5 (Cdk5) activity closely correlates with hyperphosphorylated tau, a common pathology found in neurodegenerative diseases. Previous postmortem studies had revealed increased Cdk5 immunoreactivity in amyotrophic lateral sclerosis (ALS); hence, we investigated the effects of Cdk5 inhibition on ALS model mice and neurons in this study. For the in vitro study, motor neuron cell lines with wild-type superoxide dismutase 1 (SOD1) or SOD1G93A and primary neuronal cultures from SOD1G93A transgenic (TG) mice or non-TG mice were compared for the expression of proteins involved in tau pathology, neuroinflammation, apoptosis, and neuritic outgrowth by applying Cdk5-small interfering RNA or Cdk5-short hairpin RNA (shRNA). For the in vivo study, SOD1G93A mice and non-TG mice were intrathecally injected with adeno-associated virus 9 (AAV9)-scramble (SCR)-shRNA or AAV9-Cdk5-shRNA at the age of 5 weeks. Weight and motor function were measured three times per week from 60 days of age, longevity was evaluated, and the tissues were collected from 90-day-old or 120-day-old mice. Neurons with SOD1G93A showed increased phosphorylated tau, attenuated neuritic growth, mislocalization of SOD1, and enhanced neuroinflammation and apoptosis, all of which were reversed by Cdk5 inhibition. Weights did not show significant differences among non-TG and SOD1G93A mice with or without Cdk5 silencing. SOD1G93A mice treated with AAV9-Cdk5-shRNA showed significantly delayed disease onset, delayed rotarod failure, and prolonged survival compared with those treated with AAV9-SCR-shRNA. The brain and spinal cord of SOD1G93A mice intrathecally injected with AAV9-Cdk5-shRNA exhibited suppressed tau pathology, neuroinflammation, apoptosis, and an increased number of motor neurons compared to those of SOD1G93A mice injected with AAV9-SCR-shRNA. Cdk5 inhibition could be an important mechanism in the development of a new therapeutic strategy for ALS.
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Esclerose Lateral Amiotrófica , Quinase 5 Dependente de Ciclina , Superóxido Dismutase-1 , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/metabolismo , Células Cultivadas , Quinase 5 Dependente de Ciclina/metabolismo , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/antagonistas & inibidores , Modelos Animais de Doenças , Camundongos Transgênicos , Neurônios Motores/patologia , Neurônios Motores/metabolismo , Degeneração Neural/patologia , Degeneração Neural/genética , Degeneração Neural/metabolismo , Superóxido Dismutase , Superóxido Dismutase-1/genética , Proteínas tau/metabolismo , Proteínas tau/genéticaRESUMO
As persistent elevation of transforming growth factor-ß (TGF-ß) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF-ß would be effective against both exacerbations. The effects of TGF-ß and its inhibitor on myoblasts and fibroblasts were tested in vitro and confirmed in vivo, and the dual action of a TGF-ß inhibitor in ameliorating the pathogenic role of TGF-ß in ALS mice was identified. In the peripheral neuromuscular system, fibrosis in the muscles and joint cavities induced by excessive TGF-ß causes joint contracture and muscular degeneration, which leads to motor dysfunction. In an ALS mouse model, an increase in TGF-ß in the central nervous system (CNS), consistent with astrocyte activity, was associated with M1 microglial activity and pro-inflammatory conditions, as well as with neuronal cell death. Treatment with the TGF-ß inhibitor halofuginone could prevent musculoskeletal fibrosis, resulting in the alleviation of joint contracture and delay of motor deterioration in ALS mice. Halofuginone could also reduce glial cell-induced neuroinflammation and neuronal apoptosis. These dual therapeutic effects on both the neuromuscular system and the CNS were observed from the beginning to the end stages of ALS; as a result, treatment with a TGF-ß inhibitor from the early stage of disease delayed the time of symptom exacerbation in ALS mice, which led to prolonged survival.
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Esclerose Lateral Amiotrófica , Contratura , Fator de Crescimento Transformador beta , Animais , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/metabolismo , Camundongos , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/antagonistas & inibidores , Contratura/tratamento farmacológico , Contratura/prevenção & controle , Camundongos Transgênicos , Masculino , Camundongos Endogâmicos C57BL , Piperidinas/farmacologia , Piperidinas/uso terapêutico , HumanosRESUMO
Liver fibrosis, a common feature of most chronic liver diseases, poses significant health risks and results from various etiologies. While microRNAs (miRNAs) have demonstrated promising anti-fibrotic potential through the direct regulation of target genes, their therapeutic mechanisms remain incompletely understood. In this study, we identified miR-199a, initially discovered in anti-liver fibrotic exosomes, as a key modulator that alleviates thioacetamide-induced liver fibrosis in a mouse model. Consistent with its in vivo effects, treatment with an miR-199a mimic effectively inhibited the activation and function of human hepatic stellate cells (HSCs)-central drivers of liver fibrosis-as well as HSC proliferation and viability in vitro. Notably, miR-199a-3p exerted these anti-fibrotic effects by directly downregulating its biologically relevant target, cyclin-dependent kinase 17 (CDK17). Depletion of CDK17 alone in activated HSCs was sufficient to suppress their activation, function, proliferation, and viability, mirroring the effects of miR-199a mimic treatment. Conversely, overexpression of CDK17 reversed all cellular effects induced by miR-199a mimic treatment. Our findings highlight the miR-199a-3p-CDK17 regulatory axis and suggest that targeting CDK17 in activated HSCs could be a promising therapeutic strategy for liver fibrosis.
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Proliferação de Células , Células Estreladas do Fígado , Cirrose Hepática , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Animais , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Quinases Ciclina-Dependentes/metabolismo , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/antagonistas & inibidores , Masculino , Tioacetamida/toxicidade , Linhagem CelularRESUMO
BACKGROUND: E2F/DP (Eukaryotic 2 transcription factor/dimerization partner) family proteins play an essential function in the cell cycle development of higher organisms. E2F/DP family genes have been reported only in a few plant species. However, comprehensive genome-wide characterization analysis of the E2F/DP gene family of Solanum lycopersicum has not been reported so far. RESULTS: This study identified eight nonredundant SlE2F/DP genes that were classified into seven groups in the phylogenetic analysis. All eight genes had a single E2F-TDP domain and few genes had additional domains. Two segmental duplication gene pairs were observed within tomato, in addition to cis-regulatory elements, miRNA target sites and phosphorylation sites which play an important role in plant development and stress response in tomato. To explore the three-dimensional (3D) models and gene ontology (GO) annotations of SlE2F/DP proteins, we pointed to their putative transporter activity and their interaction with several putative ligands. The localization of SlE2F/DP-GFP fused proteins in the nucleus and endoplasmic reticulum suggested that they may act in other biological functions. Expression studies revealed the differential expression pattern of most of the SlE2F/DP genes in various organs. Moreover, the expression of E2F/DP genes against abiotic stress, particularly SlE2F/DP2 and/or SlE2F/DP7, was upregulated in response to heat, salt, cold and ABA treatment. Furthermore, the co-expression analysis of SlE2F/DP genes with multiple metabolic pathways was co-expressed with defence genes, transcription factors and so on, suggested their crucial role in various biological processes. CONCLUSIONS: Overall, our findings provide a way to understand the structure and function of SlE2F/DP genes; it might be helpful to improve fruit development and tolerance against abiotic stress through marker-assisted selection or transgenic approaches.
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Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Solanum lycopersicum , Estresse Fisiológico , Solanum lycopersicum/genética , Solanum lycopersicum/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Família Multigênica , Filogenia , Genoma de Planta , Fatores de Transcrição E2F/genética , Fatores de Transcrição E2F/metabolismoRESUMO
The tunable properties of 2D transition-metal dichalcogenide (TMDs) materials are extensively investigated for high-performance and wavelength-tunable optoelectronic applications. However, the precise modification of large-scale systems for practical optoelectronic applications remains a challenge. In this study, a wafer-scale atomic assembly process to produce 2D multinary (binary, ternary, and quaternary) TMDs for broadband photodetection is demonstrated. The large-area growth of homogeneous MoS2, Ni0.06Mo0.26S0.68, and Ni0.1Mo0.9S1.79Se0.21 is carried out using a succinct coating of the single-source precursor and subsequent thermal decomposition combined with thermal evaporation of the chalcogen powder. The optoelectrical properties of the multinary TMDs are dependent on the combination of heteroatoms. The maximum photoresponsivity of the MoS2-, Ni0.06Mo0.26S0.68-, and Ni0.1Mo0.9S1.79Se0.21-based photodetectors is 3.51 × 10-4, 1.48, and 0.9 A W-1 for 532 nm and 0.063, 0.42, and 1.4 A W-1 for 1064 nm, respectively. The devices exhibited excellent photoelectrical properties, which is highly beneficial for visible and near-infrared (NIR) photodetection.
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BACKGROUND: Mechanical power (MP), the rate of mechanical energy (ME) delivery, is a recently introduced unifying ventilator parameter consisting of tidal volume, airway pressures, and respiratory rates, which predicts pulmonary complications in several clinical contexts. However, ME has not been previously studied in the perioperative context, and neither parameter has been studied in the context of thoracic surgery utilizing one-lung ventilation. METHODS: The relationships between ME variables and postoperative pulmonary complications were evaluated in this post hoc analysis of data from a multicenter randomized clinical trial of lung resection surgery conducted between 2020 and 2021 (n = 1,170). Time-weighted average MP and ME (the area under the MP time curve) were obtained for individual patients. The primary analysis was the association of time-weighted average MP and ME with pulmonary complications within 7 postoperative days. Multivariable logistic regression was performed to examine the relationships between energy variables and the primary outcome. RESULTS: In 1,055 patients analyzed, pulmonary complications occurred in 41% (431 of 1,055). The median (interquartile ranges) ME and time-weighted average MP in patients who developed postoperative pulmonary complications versus those who did not were 1,146 (811 to 1,530) J versus 924 (730 to 1,240) J (P < 0.001), and 6.9 (5.5 to 8.7) J/min versus 6.7 (5.2 to 8.5) J/min (P = 0.091), respectively. ME was independently associated with postoperative pulmonary complications (ORadjusted, 1.44 [95% CI, 1.16 to 1.80]; P = 0.001). However, the association between time-weighted average MP and postoperative pulmonary complications was time-dependent, and time-weighted average MP was significantly associated with postoperative pulmonary complications in cases utilizing longer periods of mechanical ventilation (210 min or greater; ORadjusted, 1.46 [95% CI, 1.11 to 1.93]; P = 0.007). Normalization of ME and time-weighted average MP either to predicted body weight or to respiratory system compliance did not alter these associations. CONCLUSIONS: ME and, in cases requiring longer periods of mechanical ventilation, MP were independently associated with postoperative pulmonary complications in thoracic surgery.
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Ventilação Monopulmonar , Respiração com Pressão Positiva , Humanos , Respiração com Pressão Positiva/efeitos adversos , Pulmão , Respiração Artificial/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Volume de Ventilação Pulmonar , Ventilação Monopulmonar/efeitos adversosRESUMO
The aim of this study was to explore the taxonomic identification and evaluate the safety of a bacterium, Enterococcus lactis IDCC 2105, isolated from homemade cheese in Korea, using whole genome sequence (WGS) analysis. It sought to identify the species level of this Enterococcus spp., assess its antibiotic resistance, and evaluate its virulence potential. WGS analysis confirmed the bacterial strain IDCC 2105 as E. lactis and identified genes responsible for resistance to erythromycin and clindamycin, specifically msrC, and eatAv, which are chromosomally located, indicating a minimal risk for horizontal gene transfer. The absence of plasmids in E. lactis IDCC 2105 further diminishes the likelihood of resistance gene dissemination. Additionally, our investigation into seven virulence factors, including hemolysis, platelet aggregation, biofilm formation, hyaluronidase, gelatinase, ammonia production, and ß-glucuronidase activity, revealed no detectable virulence traits. Although bioinformatic analysis suggested the presence of collagen adhesion genes acm and scm, these were not corroborated by phenotypic virulence assays. Based on these findings, E. lactis IDCC 2105 presents as a safe strain for potential applications, contributing valuable information on its taxonomy, antibiotic resistance profile, and lack of virulence factors, supporting its use in food products.
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Antibacterianos , Queijo , Enterococcus , Genoma Bacteriano , Fatores de Virulência , Sequenciamento Completo do Genoma , Enterococcus/genética , Enterococcus/isolamento & purificação , Enterococcus/classificação , Enterococcus/efeitos dos fármacos , Enterococcus/patogenicidade , Fatores de Virulência/genética , Antibacterianos/farmacologia , Queijo/microbiologia , Microbiologia de Alimentos , República da Coreia , Virulência/genética , Farmacorresistência Bacteriana/genética , Laticínios/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
Prior to January 2023, women living with HIV (WLWH) in the United States (US) were discouraged from breastfeeding due to the potential risk of mother-to-child HIV transmission through breastfeeding. Lack of breastfeeding decision-making and experience among WLWH may negatively affect maternal mental health. We implemented a quality improvement initiative to screen WLWH for postpartum depression (PPD), evaluate their attitudes toward breastfeeding, and assess their experience with breastfeeding decision-making. We collected quantitative data from WLWH using a voluntary, self-administered 6-item breastfeeding decision-making and experience survey (administered 1 month postpartum) and a 10-item Edinburgh Postnatal Depression Scale (EPDS, negative = 0-9; administered 1 and 4 months postpartum) tool. We conducted descriptive statistics and cross tabulation analysis. We analyzed 106 WLWH (93.4% non-Hispanic Black/African American; mean age 33.1 years; 82.1% HIV RNA < 200 copies/mL). One in five (19.1%) WLWH had a positive baseline EPDS screen, with the mean EPDS scores decreasing from 5.3 ± 5.4 (baseline) to 4.6 ± 4.8 (follow-up). Among 55 WLWH who provided baseline and follow-up EPDS scores, only 3/13 with a positive baseline EPDS screen had resolved depressive symptoms at follow-up. Over one-third (37.7%) of WLWH indicated feeling "sadness" when asked whether lack of breastfeeding negatively affected their feelings or emotions. Over half of WLWH (51.9%) were aware of the US breastfeeding recommendations, but the majority (60.4%) had never discussed breastfeeding options with a medical provider. Improved provider-patient discussions on infant feeding options among WLWH is needed to increase awareness of breastfeeding choices and promote informed, autonomous breastfeeding decision-making among WLWH.
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Depressão Pós-Parto , Infecções por HIV , Lactente , Feminino , Humanos , Adulto , Aleitamento Materno , Saúde Mental , Infecções por HIV/psicologia , Transmissão Vertical de Doenças Infecciosas , Período Pós-Parto , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/psicologiaRESUMO
The importance of light management for perovskite solar cells (PSCs) has recently been emphasized because their power conversion efficiency approaches their theoretical thermodynamic limits. Among optical strategies, anti-reflection (AR) coating is the most widely used method to reduce reflectance loss and thus increase light-harvesting efficiency. Monolayer MgF2is a well-known AR material because of its optimal refractive index, simple fabrication process, and physical and chemical durabilities. Nevertheless, quantitative estimates of the improvement achieved by the MgF2AR layer are lacking. In this study, we conducted theoretical and experimental evaluations to assess the AR effect of MgF2on the performance of formamidinium lead-triiodide PSCs. A sinusoidal tendency to enhance the short-circuit current density (JSC) was observed depending on the thickness, which was attributed to the interference of the incident light. A transfer matrix method-based simulation was conducted to calculate the optical losses, demonstrating the critical impact of reflectance loss on theJSCimprovement. The predictedJSCs values, depending on the perovskite thickness and the incident angle, are also presented. The combined use of experimental and theoretical approaches offers notable advantages, including accurate interpretation of photocurrent generation, detailed optical analysis of the experimental results, and device performance predictions under unexplored conditions.
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This study investigates the effect of silicon carbon nitride (SiCN) as an interlayer for ZnO-based resistive random access memory (RRAM). SiCN was deposited using plasma-enhanced chemical vapor deposition (PECVD) with controlled carbon content, achieved by varying the partial pressure of tetramethylsilane (4MS). Our results indicate that increasing the carbon concentration enhances the endurance of RRAM devices but reduces the on/off ratio. Devices with SiCN exhibited lower operating voltages and more uniform resistive switching behavior. Oxygen migration from ZnO to SiCN is examined by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analyses, promoting the formation of conductive filaments (CFs) and lowering set voltages. Additionally, we examined the impact of top electrode oxidation on RRAM performance. The oxidation of the Ti top electrode was found to reduce endurance and increase low resistive state (LRS) resistance, potentially leading to device failure through the formation of an insulating layer between the electrode and resistive switching material. The oxygen storage capability of SiCN was further confirmed through high-temperature stress tests, demonstrating its potential as an oxygen reservoir. Devices with a 20 nm SiCN interlayer showed significantly improved endurance, with over 500 switching cycles, compared to 62 cycles in those with a 5 nm SiCN layer. However, the thicker SiCN layer resulted in a notably lower on/off ratio due to reduced capacitance. These findings suggest that SiCN interlayers can effectively enhance the performance and endurance of ZnO-based RRAM devices by acting as an oxygen reservoir and mitigating the top electrode oxidation effect.
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AIM: Cholesterol homeostasis is associated with Alzheimer's disease (AD). Despite the multitude of cholesterol metabolites, little is known about which metabolites are directly involved in AD pathogenesis and can serve as its potential biomarkers. METHODS: To identify "hit" metabolites, steroid profiling was conducted in mice with different age, diet, and genotype and also in humans with normal cognition, mild cognitive impairment, and AD using gas chromatography-mass spectrometry. Then, using one of the "hit" molecules (7ß-hydroxycholesterol; OHC), molecular and histopathological experiment and behavioral testing were conducted in normal mice following its intracranial stereotaxic injection to see whether this molecule drives AD pathogenesis and causes cognitive impairment. RESULTS: The serum levels of several metabolites, including 7ß-OHC, were increased by aging in the 3xTg-AD unlike normal mice. Consistently, the levels of 7ß-OHC were increased in the hairs of patients with AD and were correlated with clinical severity. We found that 7ß-OHC directly affects AD-related pathophysiology; intrahippocampal injection of 7ß-OHC induced astrocyte and microglial cell activation, increased the levels of pro-inflammatory cytokines (TNF-alpha, IL-1ß, IL-6), and enhanced amyloidogenic pathway. Mice treated with 7ß-OHC also exhibited deficits in memory and frontal/executive functions assessed by object recognition and 5-choice serial reaction time task, respectively. CONCLUSIONS: Our results suggest that 7ß-OHC could serve as a convenient, peripheral biomarker of AD. As directly involved in AD pathogenesis, 7ß-OHC assay may help actualize personalized medicine in a way to identify an at-risk subgroup as a candidate population for statin-based AD treatment.
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Doença de Alzheimer , Biomarcadores , Disfunção Cognitiva , Hidroxicolesteróis , Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Hidroxicolesteróis/sangue , Animais , Camundongos , Biomarcadores/sangue , Humanos , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Masculino , Idoso , Camundongos Transgênicos , Feminino , Camundongos Endogâmicos C57BL , Hipocampo/metabolismo , Hipocampo/patologia , Modelos Animais de DoençasRESUMO
BACKGROUND: Workplace-based learning (WPBL) has emerged as an essential practice in healthcare education. However, WPBL is rarely implemented in Korean medicine (KM) due to the passive attitude of teachers and possible violation of medical laws that limit the participation of trainees in medical treatment. In this study, we implemented WPBL in the clinical clerkship of Acupuncture and Moxibustion Medicine at a single College of KM and explored the barriers and future improvements of WPBL. METHODS: The WPBL was implemented from January to July 2019. During the clerkship, each senior student was assigned an inpatient at the university hospital. WPBL was conducted as follows: patient presentation by the supervisor, interaction with the patient at the bedside, preparation of medical records, oral case presentation, and discussion with feedback. The student performed a physical examination and review of systems as a clinical task. In addition, six doctors of KM who are currently practicing after three years of WPBL were interviewed in September 2022 to investigate the real-world effects and unmet needs of WPBL in their workplaces. RESULTS: Two major themes identified from the interview were: "the experience of novice doctors of KM with KM practice" and "Current state of KM clinical education." The five subcategories were: "Clinical competency priorities vary according to the KM workplace," "Difficulties faced by doctors of KM immediately after graduation," "WPBL experience of the interviewees," "Necessary but difficult to implement real patient learning," and "Unmet needs for clinical clerkship in KM." CONCLUSION: It is essential to consider the unique characteristics of KM practice and the duties required in various workplaces for successful WPBL. We anticipate our study to be a starting point for improving the WPBL and addressing the unmet needs in KM clinical education.
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Estágio Clínico , Local de Trabalho , Humanos , República da Coreia , Competência Clínica , Estudantes de Medicina/psicologia , Acupuntura/educaçãoRESUMO
INTRODUCTION: Rare variants in ABCA1 increase the risk of developing Alzheimer's disease (AD). ABCA1 facilitates the lipidation of apolipoprotein E (apoE). This study investigated whether microRNA-33 (miR-33)-mediated regulation of this ABCA1-APOE pathway affects phenotypes of an amyloid mouse model. METHODS: We generated mir-33+/+;APP/PS1 and mir-33-/-;APP/PS1 mice to determine changes in amyloid pathology using biochemical and histological analyses. We used RNA sequencing and mass spectrometry to identify the transcriptomic and proteomic changes between our genotypes. We also performed mechanistic experiments by determining the role of miR-33 in microglial migration and amyloid beta (Aß) phagocytosis. RESULTS: Mir-33 deletion increases ABCA1 levels and reduces Aß accumulation and glial activation. Multi-omics studies suggested miR-33 regulates the activation and migration of microglia. We confirm that the inhibition of miR-33 significantly increases microglial migration and Aß phagocytosis. DISCUSSION: These results suggest that miR-33 might be a potential drug target by modulating ABCA1 level, apoE lipidation, Aß level, and microglial function. HIGHLIGHTS: Loss of microRNA-33 (miR-33) increased ABCA1 protein levels and the lipidation of apolipoprotein E. Loss of miR-33 reduced amyloid beta (Aß) levels, plaque deposition, and gliosis. mRNAs and proteins dysregulated by miR-33 loss relate to microglia and Alzheimer's disease. Inhibition of miR-33 increased microglial migration and Aß phagocytosis in vitro.
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As the electron mobility of two-dimensional (2D) materials is dependent on an insulating substrate, the nonuniform surface charge and morphology of silicon dioxide (SiO2) layers degrade the electron mobility of 2D materials. Here, we demonstrate that an atomically thin single-crystal insulating layer of silicon oxynitride (SiON) can be grown epitaxially on a SiC wafer at a wafer scale and find that the electron mobility of graphene field-effect transistors on the SiON layer is 1.5 times higher than that of graphene field-effect transistors on typical SiO2 films. Microscale and nanoscale void defects caused by heterostructure growth were eliminated for the wafer-scale growth of the single-crystal SiON layer. The single-crystal SiON layer can be grown on a SiC wafer with a single thermal process. This simple fabrication process, compatible with commercial semiconductor fabrication processes, makes the layer an excellent replacement for the SiO2/Si wafer.
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Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood-immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.
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Receptores ErbB , Proteínas Proto-Oncogênicas c-bcl-2 , Pontos Quânticos , RNA Interferente Pequeno , Pontos Quânticos/química , Animais , Receptores ErbB/genética , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Humanos , RNA Interferente Pequeno/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Camundongos , Linhagem Celular Tumoral , Nanopartículas/química , Lipídeos/química , Nanomedicina Teranóstica/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , MicelasRESUMO
mRNA vaccines have emerged as a pivotal tool in combating COVID-19, offering an advanced approach to immunization. A key challenge with these vaccines is their need for extremely-low-temperature storage, which affects their stability and shelf life. Our research addresses this issue by enhancing the stability of mRNA vaccines through a novel cationic lipid, O,O'-dimyristyl-N-lysyl aspartate (DMKD). DMKD effectively binds with mRNA, improving vaccine stability. We also integrated phosphatidylserine (PS) into the formulation to boost immune response by promoting the uptake of these nanoparticles by immune cells. Our findings reveal that DMKD-PS nanoparticles maintain structural integrity under long-term refrigeration and effectively protect mRNA. When tested, these nanoparticles containing green fluorescent protein (GFP) mRNA outperformed other commercial lipid nanoparticles in protein expression, both in immune cells (RAW 264.7 mouse macrophage) and non-immune cells (CT26 mouse colorectal carcinoma cells). Importantly, in vivo studies show that DMKD-PS nanoparticles are safely eliminated from the body within 48 h. The results suggest that DMKD-PS nanoparticles present a promising alternative for mRNA vaccine delivery, enhancing both the stability and effectiveness of these vaccines.
Assuntos
Lipossomos , Nanopartículas , Vacinas , Animais , Camundongos , RNA Mensageiro/química , Vacinas de mRNA , Transfecção , Células Apresentadoras de Antígenos , Nanopartículas/químicaRESUMO
Background and Objective: This study aimed to identify the incidence of sarcopenia and disease risk factors in Korean adults and to provide data for sarcopenia prevention. Materials and Methods: Based on the Korea National Health and Nutrition Survey, 2008-2011, we selected 14,185 adults over the age of 20 who participated in sarcopenia diagnostic tests and health surveys. We analyzed sarcopenia risk factors using complex sample multi-logistic regression analysis. Results: The prevalence of sarcopenia in Korea was 31.3%, with 20.2% in men and 40.4% in women. In men, there was a higher risk of sarcopenia in those of older age, without a spouse, with a low body mass index (BMI), who never engage in resistance exercise, or who do mid-level intensity resistance exercises. In women, sarcopenia risk was higher in those in their 20s compared to those in their 60s, and risk factors included a low BMI, high-density lipoprotein cholesterol and waist circumference measurements, alcohol consumption, aerobic exercise, and resistance exercise. Conclusions: Interventions and lifestyle improvements will help prevent the onset of sarcopenia in elderly men and young women with risk factors such as a low BMI.