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1.
Nature ; 617(7960): 287-291, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37138079

RESUMO

MicroLED displays have been in the spotlight as the next-generation displays owing to their various advantages, including long lifetime and high brightness compared with organic light-emitting diode (OLED) displays. As a result, microLED technology1,2 is being commercialized for large-screen displays such as digital signage and active R&D programmes are being carried out for other applications, such as augmented reality3, flexible displays4 and biological imaging5. However, substantial obstacles in transfer technology, namely, high throughput, high yield and production scalability up to Generation 10+ (2,940 × 3,370 mm2) glass sizes, need to be overcome so that microLEDs can enter mainstream product markets and compete with liquid-crystal displays and OLED displays. Here we present a new transfer method based on fluidic self-assembly (FSA) technology, named magnetic-force-assisted dielectrophoretic self-assembly technology (MDSAT), which combines magnetic and dielectrophoresis (DEP) forces to achieve a simultaneous red, green and blue (RGB) LED transfer yield of 99.99% within 15 min. By embedding nickel, a ferromagnetic material, in the microLEDs, their movements were controlled by using magnets, and by applying localized DEP force centred around the receptor holes, these microLEDs were effectively captured and assembled in the receptor site. Furthermore, concurrent assembly of RGB LEDs were demonstrated through shape matching between microLEDs and receptors. Finally, a light-emitting panel was fabricated, showing damage-free transfer characteristics and uniform RGB electroluminescence emission, demonstrating our MDSAT method to be an excellent transfer technology candidate for high-volume production of mainstream commercial products.

2.
Nature ; 619(7971): 755-760, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37438523

RESUMO

Displays in which arrays of microscopic 'particles', or chiplets, of inorganic light-emitting diodes (LEDs) constitute the pixels, termed MicroLED displays, have received considerable attention1,2 because they can potentially outperform commercially available displays based on organic LEDs3,4 in terms of power consumption, colour saturation, brightness and stability and without image burn-in issues1,2,5-7. To manufacture these displays, LED chiplets must be epitaxially grown on separate wafers for maximum device performance and then transferred onto the display substrate. Given that the number of LEDs needed for transfer is tremendous-for example, more than 24 million chiplets smaller than 100 µm are required for a 50-inch, ultra-high-definition display-a technique capable of assembling tens of millions of individual LEDs at low cost and high throughput is needed to commercialize MicroLED displays. Here we demonstrate a MicroLED lighting panel consisting of more than 19,000 disk-shaped GaN chiplets, 45 µm in diameter and 5 µm in thickness, assembled in 60 s by a simple agitation-based, surface-tension-driven fluidic self-assembly (FSA) technique with a yield of 99.88%. The creation of this level of large-scale, high-yield FSA of sub-100-µm chiplets was considered a significant challenge because of the low inertia of the chiplets. Our key finding in overcoming this difficulty is that the addition of a small amount of poloxamer to the assembly solution increases its viscosity which, in turn, increases liquid-to-chiplet momentum transfer. Our results represent significant progress towards the ultimate goal of low-cost, high-throughput manufacture of full-colour MicroLED displays by FSA.

3.
Cell ; 146(6): 1016-28, 2011 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-21925322

RESUMO

We report the identification of 67 previously undescribed histone modifications, increasing the current number of known histone marks by about 70%. We further investigated one of the marks, lysine crotonylation (Kcr), confirming that it represents an evolutionarily-conserved histone posttranslational modification. The unique structure and genomic localization of histone Kcr suggest that it is mechanistically and functionally different from histone lysine acetylation (Kac). Specifically, in both human somatic and mouse male germ cell genomes, histone Kcr marks either active promoters or potential enhancers. In male germinal cells immediately following meiosis, Kcr is enriched on sex chromosomes and specifically marks testis-specific genes, including a significant proportion of X-linked genes that escape sex chromosome inactivation in haploid cells. These results therefore dramatically extend the repertoire of histone PTM sites and designate Kcr as a specific mark of active sex chromosome-linked genes in postmeiotic male germ cells.


Assuntos
Regulação da Expressão Gênica , Código das Histonas , Animais , Células HeLa , Histonas/química , Histonas/metabolismo , Humanos , Lisina/metabolismo , Masculino , Meiose , Camundongos , Processamento de Proteína Pós-Traducional , Testículo/citologia , Testículo/metabolismo
4.
Bioconjug Chem ; 35(9): 1324-1334, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39197031

RESUMO

Inhibitors of the epithermal growth factor receptor (EGFR) were screened from an autodisplayed Fv-antibody library using an anti-EGF antibody. The Fv-antibody library was expressed on the outer membrane of Escherichia coli, which corresponds to the heavy chain VH region of immunoglobulin G. The library was constructed by randomizing the CDR3 region of expressed VH regions (11 amino acid residues) by site-directed mutagenesis. Using an anti-EGF antibody as a screening probe, amino acid sequences (CDR3 region) with antibody binding affinity were screened from the Fv-antibody library. These amino acid sequences were considered to have similar chemical properties to EGF, which can bind to EGFR. Two autodisplayed clones with Fv-antibodies against EGFR were screened from the Fv-antibody library, and the screened Fv-antibodies were expressed as soluble proteins. The binding affinity (KD) was estimated using an SPR biosensor, and the inhibitory activity of expressed Fv-antibodies was observed for PANC-1 pancreatic tumor cells and T98G glioblastoma cells using Western blot analysis of proteins in the EGFR-mediated signaling pathway. The viability of PANC-1 and T98G cells was observed to decrease via the inhibitory activity of expressed Fv-antibodies. Finally, interactions between Fv-antibodies and EGFR were analyzed by using molecular docking simulations.


Assuntos
Receptores ErbB , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Humanos , Linhagem Celular Tumoral , Biblioteca de Peptídeos
5.
Acta Neuropathol ; 148(1): 46, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316141

RESUMO

Tauopathy, including frontotemporal lobar dementia and Alzheimer's disease, describes a class of neurodegenerative diseases characterized by the aberrant accumulation of Tau protein due to defects in proteostasis. Upon generating and characterizing a stable transgenic zebrafish that expresses the human TAUP301L mutant in a neuron-specific manner, we found that accumulating Tau protein was efficiently cleared via an enhanced autophagy activity despite constant Tau mRNA expression; apparent tauopathy-like phenotypes were revealed only when the autophagy was genetically or chemically inhibited. We performed RNA-seq analysis, genetic knockdown, and rescue experiments with clinically relevant point mutations of valosin-containing protein (VCP), and showed that induced expression of VCP, an essential cytosolic chaperone for the protein quality system, was a key factor for Tau degradation via its facilitation of the autophagy flux. This novel function of VCP in Tau clearance was further confirmed in a tauopathy mouse model where VCP overexpression significantly decreased the level of phosphorylated and oligomeric/aggregate Tau and rescued Tau-induced cognitive behavioral phenotypes, which were reversed when the autophagy was blocked. Importantly, VCP expression in the brains of human Alzheimer's disease patients was severely downregulated, consistent with its proposed role in Tau clearance. Taken together, these results suggest that enhancing the expression and activity of VCP in a spatiotemporal manner to facilitate the autophagy pathway is a potential therapeutic approach for treating tauopathy.

6.
Cerebrovasc Dis ; 53(1): 69-78, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37399789

RESUMO

INTRODUCTION: Patients with atrial fibrillation-related stroke (AF-stroke) are prone to developing rapid ventricular response (RVR). We investigated whether RVR is associated with initial stroke severity, early neurological deterioration (END) and poor outcome at 3 months. METHODS: We reviewed patients who had AF-stroke between January 2017 and March 2022. RVR was defined as having heart rate >100 beats per minute on initial electrocardiogram. Neurological deficit was evaluated with National Institutes of Health Stroke Scale (NIHSS) score at admission. END was defined as increase of ≥2 in total NIHSS score or ≥1 in motor NIHSS score within first 72 h. Functional outcome was score on modified Rankin Scale at 3 months. Mediation analysis was performed to examine potential causal chain in which initial stroke severity may mediate relationship between RVR and functional outcome. RESULTS: We studied 568 AF-stroke patients, among whom 86 (15.1%) had RVR. Patients with RVR had higher initial NIHSS score (p < 0.001) and poor outcome at 3 months (p = 0.004) than those without RVR. The presence of RVR [adjusted odds ratio (aOR) = 2.13; p = 0.013] was associated with initial stroke severity, but not with END and functional outcome. Otherwise, initial stroke severity [aOR = 1.27; p = <0.001] was significantly associated with functional outcome. Initial stroke severity as a mediator explained 58% of relationship between RVR and poor outcome at 3 months. CONCLUSION: In patients with AF-stroke, RVR was independently associated with initial stroke severity but not with END and functional outcome. Initial stroke severity mediated considerable proportion of association between RVR and functional outcome.


Assuntos
Fibrilação Atrial , AVC Embólico , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapia
7.
Nucleic Acids Res ; 50(20): 11738-11754, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36321646

RESUMO

We describe a purified biochemical system to produce monoclonal antibodies (Abs) in vitro using activation-induced deoxycytidine deaminase (AID) and DNA polymerase η (Polη) to diversify immunoglobulin variable gene (IgV) libraries within a phage display format. AID and Polη function during B-cell affinity maturation by catalyzing somatic hypermutation (SHM) of immunoglobulin variable genes (IgV) to generate high-affinity Abs. The IgV mutational motif specificities observed in vivo are conserved in vitro. IgV mutations occurred in antibody complementary determining regions (CDRs) and less frequently in framework (FW) regions. A unique feature of our system is the use of AID and Polη to perform repetitive affinity maturation on libraries reconstructed from a preceding selection step. We have obtained scFv Abs against human glucagon-like peptide-1 receptor (GLP-1R), a target in the treatment of type 2 diabetes, and VHH nanobodies targeting Fatty Acid Amide Hydrolase (FAAH), involved in chronic pain, and artemin, a neurotropic factor that regulates cold pain. A round of in vitro affinity maturation typically resulted in a 2- to 4-fold enhancement in Ab-Ag binding, demonstrating the utility of the system. We tested one of the affinity matured nanobodies and found that it reduced injury-induced cold pain in a mouse model.


Assuntos
Anticorpos de Cadeia Única , Anticorpos de Domínio Único , Hipermutação Somática de Imunoglobulina , Animais , Humanos , Camundongos , Afinidade de Anticorpos/genética , Citidina Desaminase/metabolismo , Diabetes Mellitus Tipo 2 , Região Variável de Imunoglobulina/genética , Dor , Anticorpos de Domínio Único/genética , Anticorpos de Cadeia Única/genética
8.
BMC Musculoskelet Disord ; 25(1): 147, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365755

RESUMO

BACKGROUND: This study aimed to investigate work-related musculoskeletal disorders (WMSDs), occupational stress, and health-related quality of life (HRQoL); identify the factors that affect HRQoL; and investigate the moderating effects of WMSDs on occupational stress and HRQoL. METHODS: The participants were construction workers who had worked in the construction industry for over three months. A total of 178 construction workers voluntarily participated and anonymously completed the musculoskeletal symptoms questionnaire, the Korean Occupational Stress Scale, short-form 36. The moderation effect of WMSDs on occupational stress and HRQoL were analyzed by Haye's Process Macro Model. RESULTS: The results of the study showed that 96 subjects (53.9%) had WMSDs, and the most common pain site was the lower back (33.3%). The group with WMSDs had higher occupational stress than did the group without WMSDs (p < 0.01). Compared with the group without WMSDs, the group with WMSDs displayed significant differences in HRQoL (p < 0.001). Furthermore, the factor affecting HRQoL was WMSDs (p < 0.001). In the impact of occupational stress on HRQoL, WMSDs had a significant moderating effect (p < 0.001). CONCLUSION: The results of this study indicate that construction workers' WMSDs significantly impact occupational stress and HRQoL, and WMSDs have a significant moderating effect on the relationship between occupational stress and HRQoL. Therefore, to improve the HRQoL of workers in the construction industry, it is necessary to develop methods to reduce occupational stress and prevent and treat WMSDs.


Assuntos
Indústria da Construção , Doenças Musculoesqueléticas , Doenças Profissionais , Estresse Ocupacional , Humanos , Doenças Profissionais/diagnóstico , Doenças Profissionais/epidemiologia , Qualidade de Vida , Estudos Transversais , Fatores de Risco , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/epidemiologia , Inquéritos e Questionários , Estresse Ocupacional/epidemiologia , Prevalência
9.
Drug Chem Toxicol ; : 1-11, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034857

RESUMO

The increasing prevalence of particulate matter (PM) has raised significant concerns about its adverse effects on human health. This study investigates the potential of fermented blueberry and black rice (FBBR) in mitigating the effects of PM2.5 in SH-SY5Y cells and mice. Various assays, including MTT, NO, western blot, ELISA, and behavioral studies were conducted. Results showed that PM2.5 induced considerable cytotoxicity and elevated NO production at a concentration of 100 µg/mL of PM2.5 in SH-SY5Y cells. FBBR administration attenuated PM2.5-exposed cytotoxicity and suppressed NO production in SH-SY5Y cells. In an intranasally-exposed mice model, 10 mg/kg body weight (BW) of PM2.5 resulted in cognitive impairments. However, FBBR treatment ameliorated these impairments in both the Y-maze and MWM tests in PM2.5-exposed mice. Additionally, FBBR administration increased the expression of BDNF and reduced inflammatory markers in the brains of PM2.5-exposed SH-SY5Y cells. These findings highlight the detrimental effects of PM2.5 on the nervous system and suggest the potential of FBBR as a nutraceutical agent for mitigating these effects. Importantly, the results emphasize the urgency of addressing the harmful impact of PM2.5 on the nervous system and underscore the promising role of FBBR as a protective intervention against the adverse effects associated with PM2.5 exposure.

10.
Plant Dis ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160128

RESUMO

Visual detection of stromata (brown-black, elevated fungal fruiting bodies) is a primary method for quantifying tar spot early in the season, as these structures are definitive signs of the disease and essential for effective disease monitoring and management. Here, we present Stromata Contour Detection Algorithm version 2 (SCDA v2), which addresses the limitations of the previously developed SCDA version 1 (SCDA v1) without the need for empirical search of the optimal Decision Making Input Parameters (DMIPs), while achieving higher and consistent accuracy in tar spot stromata detection. SCDA v2 operates in two components: (i) SCDA v1 producing tar-spot-like region proposals for a given input corn leaf Red-Green-Blue (RGB) image, and (ii) a pre-trained Convolutional Neural Network (CNN) classifier identifying true tar spot stromata from the region proposals. To demonstrate the enhanced performance of the SCDA v2, we utilized datasets of RGB images of corn leaves from field (low, middle, and upper canopies) and glasshouse conditions under variable environments, exhibiting different tar spot severities at various corn developmental stages. Various accuracy analyses (F1-score, linear regression, and Lin's concordance correlation), showed that SCDA v2 had a greater agreement with the reference data (human visual annotation) than SCDA v1. SCDA v2 achievd 73.7% mean Dice values (overall accuracy), compared to 30.8% for SCDA v1. The enhanced F1-score primarily resulted from eliminating overestimation cases using the CNN classifier. Our findings indicate the promising potential of SCDA v2 for glasshouse and field-scale applications, including tar spot phenotyping and surveillance projects.

11.
Prep Biochem Biotechnol ; 54(2): 218-225, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37222635

RESUMO

Activin A, a member of the TGF-ß superfamily, is a homodimer of the inhibin ßΑ subunit that plays a diversity of roles in biological processes. Because of its multiple functions, significant efforts have been made to produce activin A, however, unsatisfactory results were obtained due to its low level of expression. In this study, a stable CHO cell line exhibiting high expression of rhActivin A was isolated and production of rhActivin A was achieved using the cell line from 11-day fed-batch cultures in a 7.5 L bioreactor. The production rate was 0.22 g/L, substantially higher than those reported in previous studies. The culture supernatant of the bioreactor was used to purify rhActivin A (purity: >99%, recovery rate: 47%). The purified rhActivin A exhibited biological activity, with an EC50 of 3.893 ng/mL and a specific activity of 1.38 × 103 IU/mg. The control of process-related impurities in the purified rhActivin A was successful and met the USP recommendations for use in cell therapy. Thus, our production and purification methods were appropriate for large-scale GMP-grade rhActivin A production, which can be used for various purposes including cell therapy.


Assuntos
Ativinas , Reatores Biológicos , Cricetinae , Animais , Humanos , Cricetulus , Células CHO , Proteínas Recombinantes/genética
12.
Nanotechnology ; 35(11)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38091622

RESUMO

We demonstrate an InGaZnO (IGZO)-based synaptic transistor with a TiO2buffer layer. The structure of the synaptic transistor with TiO2inserted between the Ti metal electrode and an IGZO semiconductor channel O2trapping layer produces a large hysteresis window, which is crucial for achieving synaptic functionality. The Ti/TiO2/IGZO synaptic transistor exhibits reliable synaptic plasticity features such as excitatory post-synaptic current, paired-pulse facilitation, and potentiation and depression, originating from the reversible charge trapping and detrapping in the TiO2layer. Finally, the pattern recognition accuracy of Modified National Institute of Standards and Technology handwritten digit images was modeled using CrossSim simulation software. The simulation results present a high image recognition accuracy of ∼89%. Therefore, this simple approach using an oxide buffer layer can aid the implementation of high-performance synaptic devices for neuromorphic computing systems.

13.
Int Urogynecol J ; 34(11): 2719-2724, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37401960

RESUMO

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the incidence and risk factors for premalignant and malignant pathology in patients receiving vaginal hysterectomy (VH) and pelvic floor repair (PFR) for pelvic organ prolapse (POP). METHODS: We performed a retrospective cohort study of pathological results after VH and PFR of 569 women at our institution from January 2011 through December 2020. Age, body mass index (BMI), POP-Q stage, and preoperative ultrasound results were evaluated as risk factors for occult malignancy. RESULTS: Six of the 569 patients (1.1%) had unanticipated premalignant uterine pathology and 2 (0.4%) had unanticipated malignant uterine pathology (endometrial cancer). There was no significant difference in the incidence of premalignant or malignant uterine pathology according to age, BMI, and POP-Q stage. However, if endometrial pathology is confirmed on preoperative ultrasonography, the probability of confirming malignant pathology increases (OR 4.63; 95% CI 1.84-51.4; p=0.016). CONCLUSION: The incidence of occult malignancy during VH for POP was significantly lower than that found in hysterectomy owing to benign disease. In the case of POP patients, for whom uterine-conserving surgery is not absolutely contraindicated, it can be performed. However, if endometrial pathology is confirmed by preoperative ultrasonography, uterine-conserving surgery is not recommended.


Assuntos
Neoplasias do Endométrio , Histerectomia Vaginal , Prolapso de Órgão Pélvico , Feminino , Humanos , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/cirurgia , Histerectomia Vaginal/efeitos adversos , Incidência , Prolapso de Órgão Pélvico/epidemiologia , Prolapso de Órgão Pélvico/etiologia , Prolapso de Órgão Pélvico/cirurgia , Estudos Retrospectivos , Fatores de Risco
14.
J Korean Med Sci ; 38(34): e264, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37644680

RESUMO

BACKGROUND: Recently, active surveillance (AS) has been introduced as an alternative to early surgery (ES) for the management of papillary thyroid microcarcinoma (PTMC), because of its indolent features and low mortality. However, its cost effects have not been determined and the findings of current studies differ, according to each country's medical system. METHODS: A Markov model was constructed to compare the cost-effectiveness of AS and ES, based on a reference case of a 40-year-old patient diagnosed with PTMC. Costs and transition probabilities were derived from previous clinical studies in Korean populations, and the incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were calculated. The willingness-to-pay (WTP) threshold was set at USD 100,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address the uncertainties in the model's variables. RESULTS: From the base scenario, the cumulative costs and effectiveness were both higher in ES than AS. The ICER for ES, compared with AS, was USD 6,619.86/QALY, lower than the set WTP. The NMB difference between AS and ES increased across the stages (USD 5,980 at the first stage and USD 159,667 at the last stage). The ICER increased along with decreasing age and increasing cost of surgery. The higher the ES utility score and the lower that of AS, the more cost-effective ES, with WTP set at USD 30,000. CONCLUSION: In the current Korean medical system, ES is more cost-effective than AS. ES is more cost-effective as it is diagnosed at young age and followed-up for a long time.


Assuntos
Neoplasias da Glândula Tireoide , Conduta Expectante , Humanos , Adulto , Câncer Papilífero da Tireoide/cirurgia , Estudos Retrospectivos , Análise Custo-Benefício , Neoplasias da Glândula Tireoide/cirurgia , República da Coreia
15.
Am J Otolaryngol ; 44(3): 103820, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36893530

RESUMO

BACKGROUND: Voice change after thyroidectomy is an important issue in thyroid surgery. However, little is known about long-term voice outcomes after thyroidectomy. This study investigates the long-term voice outcomes of thyroidectomy up to two years after surgery. Also, we analyzed the pattern of recovery through acoustic tests over time. METHODS: We reviewed data from 168 patients who underwent thyroidectomy between January 2020 and August 2020 at a single institution. The Thyroidectomy-related Voice and Symptom Questionnaire (TVSQ) score and acoustic voice analysis results were examined preoperatively and postoperative one, three, and six months, and one and two years after surgery. We divided patients into two groups based on the TVSQ score (≥15 or <15) at two years postoperatively. We investigated the difference of acoustic characteristics between the two groups and analyzed correlations between acoustic parameters and various clinical and surgical factors. RESULTS: Voice parameters tended to recover, but some parameters and TVSQ scores exhibited deterioration two years after surgery. In the subgroups, among the many clinicopathologic factors examined, voice abuse history including professional voice users (p = 0.014), greater extent of thyroidectomy and neck dissection (p = 0.019, p = 0.029), and high pitch voice (F0; p = 0.005, SFF; p = 0.016) were associated with high TVSQ score at two years. CONCLUSIONS: Patients frequently experience voice discomfort after thyroidectomy. After surgery, voice abuse history including professional voice users, greater extent of surgery, and higher pitch voice are associated with worse voice quality and increased risk of persistent voice symptoms over the long-term.


Assuntos
Disfonia , Distúrbios da Voz , Voz , Humanos , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Distúrbios da Voz/diagnóstico , Distúrbios da Voz/etiologia , Glândula Tireoide , Qualidade da Voz , Disfonia/etiologia
16.
Nano Lett ; 22(18): 7415-7422, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36069378

RESUMO

Regulation of genetic activity in single cells and tissues is pivotal to determine key cellular functions in current biomedicine, yet the conventional biochemical activators lack spatiotemporal precision due to the diffusion-mediated slow kinetics and nonselectivity. Here, we describe a magnetogenetic method for target-specific activation of a clustered regularly interspaced short palindromic repeats (CRISPR) system for the regulation of intracellular proteins. We used magnetomechanical force generated by the magnetic nanostructure to activate pre-encoded Piezo1, the mechanosensitive ion channel, on the target cell. The activated Piezo1 further triggers the intracellular Ca2+ signaling pathway, inducing the pre-encoded genes to express genes of interest (GOIs), which is Cas9 protein for the CRISPR regulation of the target proteins. We demonstrated that this magnetogenetic CRISPR system successfully edits the target genome for both in vitro and pseudo-in vivo environments, providing a versatile magnetic platform for remote gene editing of animals with various size scales.


Assuntos
Proteína 9 Associada à CRISPR , Edição de Genes , Animais , Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Canais Iônicos/genética
17.
J Stroke Cerebrovasc Dis ; 32(4): 106999, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36689795

RESUMO

BACKGROUND: Propensity for lesion lateralization in atrial fibrillation-related cardiac embolic stroke (AF-stroke) remains controversial. In this study, we compared the hemispheric differences among patients with AF-stroke and identified factors associated with lesion laterality. METHODS: We retrospectively reviewed patients with acute AF-stroke admitted from January, 2017 to March, 2022. Patients were grouped based on whether lesions were right or left hemispheric in the anterior circulation territory, based on diffusion-weighted imaging. Factors associated with right-side propensity were analyzed. RESULTS: Among 385 patients, the mean age was 74±11 years and 52.5 % were male. Right and left hemispheric lesions were observed in 189 (49.1 %) and 196 (50.9%) patients, respectively. In the multivariate analysis, enlarged left atrium (LA) (adjusted odds ratio [aOR]=1.03, 95% confidential interval [CI], 1.007-1.061; p=0.013) and single confluent lesion pattern (aOR= 1.55, 95% CI, 1.012-2.381; p=0.044) were associated with right hemispheric lesions. CONCLUSIONS: Enlarged LA and single confluent lesion pattern were strongly related to right-sided propensity in patients with AF-stroke.


Assuntos
Fibrilação Atrial , AVC Embólico , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , AVC Embólico/etiologia , AVC Embólico/complicações , Estudos Retrospectivos , Átrios do Coração/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/diagnóstico por imagem , Fatores de Risco
18.
Clin Otolaryngol ; 48(1): 39-49, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36268608

RESUMO

OBJECTIVES: Voice change after uncomplicated thyroidectomy has been an important issue in the field of thyroid surgery. The aim of this study was to promote understanding of voice change after uncomplicated thyroidectomy by analysing the results for a large number of patients from a single institute. DESIGN: We retrospectively reviewed the medical records of 2879 consecutive patients who underwent thyroidectomy and voice evaluation between January 2014 and December 2019 in a single institute. All the patients had their vocal status assessed using videostroboscopy, acoustic voice analyses, aerodynamic study, and Thyroidectomy-related Voice and Symptom Questionnaire (TVSQ) scores preoperatively and at 1, 3, and 6 months postoperatively. We analysed the pattern of voice changes over time and differences in voice parameters based on clinical factors. To confirm the usefulness of the TVSQ, the correlation between TVSQ scores and objective parameters was analysed. Lastly, predictive factors for persistent voice symptoms were analysed. SETTING: Tertiary referral hospital. RESULTS: The frequency ranges and TVSQ scores exhibited significant deterioration until 6 months following surgery. Among clinical factors, the extents of thyroidectomy and neck dissection were associated with worse voice parameters. The TVSQ score was significantly correlated with objective voice parameters. The extents of thyroidectomy and neck dissection were predictive of persistent voice symptoms at 6 months after thyroidectomy. CONCLUSION: After uncomplicated thyroidectomy, most voice parameters tended to recover, but some parameters remained aggravated even at 6 months after surgery. With more extensive surgery, worse voice quality and the higher risk of persistent voice symptoms may be anticipated.


Assuntos
Disfonia , Distúrbios da Voz , Humanos , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Distúrbios da Voz/diagnóstico , Distúrbios da Voz/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Qualidade da Voz
19.
Medicina (Kaunas) ; 59(5)2023 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-37241228

RESUMO

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.


Assuntos
Neoplasias do Endométrio , Transição Epitelial-Mesenquimal , Feminino , Humanos , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Proliferação de Células , Movimento Celular , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo
20.
Biochem Biophys Res Commun ; 587: 92-98, 2022 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-34872004

RESUMO

Aminoacyl tRNA synthetases (ARSs) are a group of proteins, acting as transporters to transfer and attach the appropriate amino acids onto their cognate tRNAs for translation. So far, 18 out of 20 cytoplasmic ARSs are reported to be connected to different neuropathy disorders with multi-organ defects that are often accompanied with developmental delays. Thus, it is important to understand functions and impacts of ARSs at the whole organism level. Here, we systematically analyzed the spatiotemporal expression of 14 ars and 2 aimp genes during development in zebrafish that have not be previously reported. Not only in the brain, their dynamic expression patterns in several tissues such as in the muscles, liver and intestine suggest diverse roles in a wide range of development processes in addition to neuronal function, which is consistent with potential involvement in multiple syndrome diseases associated with ARS mutations. In particular, hinted by its robust expression pattern in the brain, we confirmed that aimp1 is required for the formation of cerebrovasculature by a loss-of-function approach. Overall, our systematic profiling data provides a useful basis for studying roles of ARSs during development and understanding their potential functions in the etiology of related diseases.


Assuntos
Aminoacil-tRNA Sintetases/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/genética , RNA de Transferência/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Aminoacil-tRNA Sintetases/classificação , Aminoacil-tRNA Sintetases/metabolismo , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Embrião não Mamífero , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Intestinos/crescimento & desenvolvimento , Intestinos/metabolismo , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Anotação de Sequência Molecular , Morfolinos/administração & dosagem , Morfolinos/genética , Morfolinos/metabolismo , Músculos/metabolismo , Proteínas do Tecido Nervoso/classificação , Proteínas do Tecido Nervoso/metabolismo , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/patologia , RNA Mensageiro/metabolismo , RNA de Transferência/metabolismo , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/classificação , Proteínas de Peixe-Zebra/metabolismo
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