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1.
Mol Syst Biol ; 19(12): e11801, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37984409

RESUMO

The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases (NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi-layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK-3ß), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell-based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long-term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.


Assuntos
Doença de Alzheimer , Doença de Huntington , Deficiências na Proteostase , Animais , Humanos , Camundongos , Doença de Alzheimer/genética , Glicogênio Sintase Quinase 3 beta , Doença de Huntington/genética , Transdução de Sinais
2.
J Neuroeng Rehabil ; 21(1): 58, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627779

RESUMO

BACKGROUND: Identification of cortical loci for lower limb movements for stroke rehabilitation is crucial for better rehabilitation outcomes via noninvasive brain stimulation by targeting the fine-grained cortical loci of the movements. However, identification of the cortical loci for lower limb movements using functional MRI (fMRI) is challenging due to head motion and difficulty in isolating different types of movement. Therefore, we developed a custom-made MR-compatible footplate and leg cushion to identify the cortical loci for lower limb movements and conducted multivariate analysis on the fMRI data. We evaluated the validity of the identified loci using both fMRI and behavioral data, obtained from healthy participants as well as individuals after stroke. METHODS: We recruited 33 healthy participants who performed four different lower limb movements (ankle dorsiflexion, ankle rotation, knee extension, and toe flexion) using our custom-built equipment while fMRI data were acquired. A subgroup of these participants (Dataset 1; n = 21) was used to identify the cortical loci associated with each lower limb movement in the paracentral lobule (PCL) using multivoxel pattern analysis and representational similarity analysis. The identified cortical loci were then evaluated using the remaining healthy participants (Dataset 2; n = 11), for whom the laterality index (LI) was calculated for each lower limb movement using the cortical loci identified for the left and right lower limbs. In addition, we acquired a dataset from 15 individuals with chronic stroke for regression analysis using the LI and the Fugl-Meyer Assessment (FMA) scale. RESULTS: The cortical loci associated with the lower limb movements were hierarchically organized in the medial wall of the PCL following the cortical homunculus. The LI was clearer using the identified cortical loci than using the PCL. The healthy participants (mean ± standard deviation: 0.12 ± 0.30; range: - 0.63 to 0.91) exhibited a higher contralateral LI than the individuals after stroke (0.07 ± 0.47; - 0.83 to 0.97). The corresponding LI scores for individuals after stroke showed a significant positive correlation with the FMA scale for paretic side movement in ankle dorsiflexion (R2 = 0.33, p = 0.025) and toe flexion (R2 = 0.37, p = 0.016). CONCLUSIONS: The cortical loci associated with lower limb movements in the PCL identified in healthy participants were validated using independent groups of healthy participants and individuals after stroke. Our findings suggest that these cortical loci may be beneficial for the neurorehabilitation of lower limb movement in individuals after stroke, such as in developing effective rehabilitation interventions guided by the LI scores obtained for neuronal activations calculated from the identified cortical loci across the paretic and non-paretic sides of the brain.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Movimento/fisiologia , Extremidade Inferior , Imageamento por Ressonância Magnética
3.
FASEB J ; 34(5): 6449-6465, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32196731

RESUMO

The steroid hormone ecdysone is the central regulator of insect metamorphosis, during which a growing, immature larva is remodeled, through pupal stages, to a reproductive adult. However, the underlying mechanisms of ecdysone-mediated metamorphosis remain to be fully elucidated. Here, we identified metamorphosis-associated microRNAs (miRNAs) and their potential targets by cross-linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 protein in Drosophila. Interestingly, miR-8-3p targeted five Vha genes encoding distinct subunits of vacuolar H+ -ATPase (V-ATPase), which has a vital role in the organellar acidification. The expression of ecdysone-responsive miR-8-3p is normally downregulated during Drosophila metamorphosis, but temporary overexpression of miR-8-3p in the whole body at the end of larval development led to defects in metamorphosis and survival, hallmarks of aberrant ecdysone signaling. In addition, miR-8-3p was expressed in the prothoracic gland (PG), which produces and releases ecdysone in response to prothoracicotropic hormone (PTTH). Notably, overexpression of miR-8-3p or knockdown of its Vha targets in the PG resulted in larger than normal, ecdysone-deficient larvae that failed to develop into the pupal stage but could be rescued by ecdysone feeding. Moreover, these animals showed defective PTTH signaling with a concomitant decrease in the expression of ecdysone biosynthetic genes. We also demonstrated that the regulatory network between the conserved miR-8-3p/miR-200 family and V-ATPase was functional in human cells. Consequently, our data indicate that the coordinated regulation of V-ATPase subunits by miR-8-3p is involved in Drosophila metamorphosis by controlling the ecdysone biosynthesis.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Ecdisona/biossíntese , Metamorfose Biológica , MicroRNAs/genética , ATPases Vacuolares Próton-Translocadoras/metabolismo , Animais , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Proteínas de Drosophila/genética , ATPases Vacuolares Próton-Translocadoras/genética
4.
J Appl Toxicol ; 40(2): 300-312, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31680285

RESUMO

Ethical issues in animal toxicity testing have led to the search for alternative methods to determine the skin sensitization potential of cosmetic products. The emergence of ethical testing issues has led to the development of many alternative methods that can reliably estimate skin sensitization potentials. However, a single alternative method may not be able to achieve high predictivity due to the complexity of the skin sensitization mechanism. Therefore, several prediction assays, including both in chemico and in vitro test methods, were investigated and integrated based on the skin sensitization adverse outcome pathway. In this study, we evaluated three different integrated approaches to predict a human skin sensitization hazard using data from in vitro assays (KeratinoSens™ and human cell line activation test [h-CLAT]), and a newly developed in chemico assay (spectrophotometric direct peptide reactivity assay [Spectro-DPRA]). When the results of the in chemico and in vitro assays were combined, the predictivity of human data increased compared with that of a single assay. The highest predictivity was obtained for the approach in which sensitization potential was determined by Spectro-DPRA followed by final determination using the result of KeratinoSens™ and h-CLAT assays (96.3% sensitivity, 87.1% specificity, 86.7% positive predictive value, 96.4% negative predictive value and 91.4% accuracy compared with human data). While further optimization is needed, we believe this integrated approach may provide useful predictive data when determining the human skin sensitization potential of chemicals.


Assuntos
Células Cultivadas/efeitos dos fármacos , Cosméticos/toxicidade , Dermatite Alérgica de Contato/diagnóstico , Espectrofotometria Atômica/métodos , Testes de Toxicidade/métodos , Alternativas aos Testes com Animais , Humanos , Medição de Risco
5.
FASEB J ; 32(8): 4519-4533, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29543534

RESUMO

The steroid hormone ecdysone has a central role in the developmental transitions of insects through its control of responsive protein-coding and microRNA (miRNA) gene expression. However, the complete regulatory network controlling the expression of these genes remains to be elucidated. In this study, we performed cross-linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 (Ago1) protein, the core effector of the miRNA pathway, in Drosophila S2 cells. We found that regulatory interactions between miRNAs and their cognate targets were substantially altered by Ago1 in response to ecdysone signaling. Additionally, during the larva-to-adult metamorphosis, miR-252-5p was up-regulated via the canonical ecdysone-signaling pathway. Moreover, we provide evidence that miR-252-5p targets Abelson interacting protein ( Abi) to decrease the protein levels of cyclins A and B, controlling the cell cycle. Overall, our data suggest a potential role for the ecdysone/miR-252-5p/Abi regulatory axis partly in cell-cycle control during metamorphosis in Drosophila.-Lim, D.-H., Lee, S., Han, J. Y., Choi, M.-S., Hong, J.-S., Seong, Y., Kwon, Y.-S., Lee, Y. S. Ecdysone-responsive microR-252-5p controls the cell cycle by targeting Abi in Drosophila.


Assuntos
Proteínas de Transporte/metabolismo , Ciclo Celular/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Ecdisona/metabolismo , MicroRNAs/metabolismo , Animais , Proteínas Argonautas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Larva/metabolismo , Transporte Proteico/fisiologia , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo
6.
BMC Nephrol ; 20(1): 39, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717699

RESUMO

BACKGROUND: The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). METHODS: Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. RESULTS: The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. CONCLUSIONS: The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.


Assuntos
Injúria Renal Aguda/patologia , Função Retardada do Enxerto/etiologia , Seleção do Doador/normas , Transplante de Rim , Doadores de Tecidos , Transplantados , Transplantes/patologia , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Cadáver , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/fisiopatologia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Transplantes/fisiopatologia , Resultado do Tratamento
7.
Nanotechnology ; 29(27): 275709, 2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-29658891

RESUMO

The manipulation of local ionic behavior via external stimuli in oxide systems is of great interest because it can help in directly tuning material properties. Among external stimuli, mechanical force has attracted intriguing attention as novel stimulus for ionic modulation. Even though effectiveness of mechanical force on local ionic modulation has been validated in terms of static effect, its real-time i.e., dynamic, behavior under an application of the force is barely investigated in spite of its crucial impact on device performance such as force or pressure sensors. In this study, we explore dynamic ionic behavior modulated by mechanical force in NiO thin films using electrochemical strain microscopy (ESM). Ionically mediated ESM hysteresis loops were significantly varied under an application of mechanical force. Based on these results, we were able to investigate relative relationship between the force and voltage effects on ionic motion and, further, control effectively ionic behavior through combination of mechanical and electrical stimuli. Our results can provide comprehensive information on the effect of mechanical forces on ionic dynamics in ionic systems.

8.
J Acoust Soc Am ; 143(1): EL37, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29390776

RESUMO

In this letter, a generic search grid generation algorithm for far-field source localization (SL) is proposed. Since conventional uniform regular grid structures only consider the resolution of the distribution, it is difficult to control the number of grid points to be distributed. The proposed algorithm generates a search grid by distributing a desired number of points evenly, depending on the target criterion, in either direction of arrival or time difference of arrival domain. The experimental results show that the proposed algorithm provides optimally distributed grid points given the number of desired points and the corresponding domain for SL processing.

9.
Nat Mater ; 15(10): 1113-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27400385

RESUMO

Hydrogen, the smallest and the lightest atomic element, is reversibly incorporated into interstitial sites in vanadium dioxide (VO2), a correlated oxide with a 3d(1) electronic configuration, and induces electronic phase modulation. It is widely reported that low hydrogen concentrations stabilize the metallic phase, but the understanding of hydrogen in the high doping regime is limited. Here, we demonstrate that as many as two hydrogen atoms can be incorporated into each VO2 unit cell, and that hydrogen is reversibly absorbed into, and released from, VO2 without destroying its lattice framework. This hydrogenation process allows us to elucidate electronic phase modulation of vanadium oxyhydride, demonstrating two-step insulator (VO2)-metal (HxVO2)-insulator (HVO2) phase modulation during inter-integer d-band filling. Our finding suggests the possibility of reversible and dynamic control of topotactic phase modulation in VO2 and opens up the potential application in proton-based Mottronics and novel hydrogen storage.

10.
Nano Lett ; 15(6): 4129-34, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-26000901

RESUMO

Atomic-scale defects strongly influence the electrical and optical properties of materials, and their impact can be more pronounced in localized dimensions. Here, we directly demonstrate that strain triggers the formation of oxygen vacancies in complex oxides by examining the tilt boundary of SrTiO3 bicrystals. Through transmission electron microscopy and electron energy loss spectroscopy, we identify strains along the tilt boundary and oxygen vacancies in the strain-imposed regions between dislocation cores. First-principles calculations support that strains, irrespective of their type or sign, lower the formation energy of oxygen vacancies, thereby enhancing vacancy formation. Finally, current-voltage measurements confirm that such oxygen vacancies at the strained boundary result in a decrease of the nonlinearity of the I-V curve as well as the resistivity. Our results strongly indicate that oxygen vacancies are preferentially formed and are segregated at the regions where strains accumulate, such as heterogeneous interfaces and grain boundaries.

11.
Nanotechnology ; 26(21): 215603, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-25944839

RESUMO

Al-based composites incorporating multilayered graphene sheets were developed via a facile approach. The multilayered graphene sheets were fabricated from the expanded graphite via a simple mechanical exfoliation process. The facile extrusion molding process with Al powder and graphene sheets exfoliated from expended graphite afforded Al-based graphene composite rods. These composites showed enhanced thermal conductivity compared to the pristine Al rods. Moreover, the Al-based multilayered graphene sheet composites exhibited lower interfacial contact resistance between graphene-based electrodes than the pristine Al. With increasing degrees of dispersion, the number of exposed graphene sheets increases, thereby significantly decreasing the interfacial contact resistance between the composite and external graphite electrode.

12.
Small Methods ; : e2301224, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38193264

RESUMO

Colloidal quantum dots (QDs) are widely regarded as advanced emissive materials with significant potential for display applications owing to their excellent optical properties such as high color purity, near-unity photoluminescence quantum yield, and size-tunable emission color. Building upon these attractive attributes, QDs have successfully garnered attention in the display market as down-conversion luminophores and now venturing into the realm of self-emissive displays, exemplified by QD light-emitting diodes (QD-LEDs). However, despite these advancements, there remains a relatively limited body of research on QD patterning technologies, which are crucial prerequisites for the successful commercialization of QD-LEDs. Thus, in this review, an overview of the current status and prospects of QD patterning technologies to accelerate the commercialization of QD-LEDs is provided. Within this review, a comprehensive investigation of three prevailing patterning methods: optical lithography, transfer printing, and inkjet printing are conducted. Furthermore, several exploratory QD patterning techniques that offer distinct advantages are introduced. This study not only paves the way for successful commercialization but also extends the potential application of QD-LEDs into uncharted frontiers.

13.
Am J Vet Res ; 85(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38531156

RESUMO

OBJECTIVE: To evaluate the relationships between the severity of myxomatous mitral valve disease (MMVD) and pulmonary hypertension (PH) and serum angiopoietin (Ang)-1 and Ang-2 concentrations in dogs with MMVD. ANIMALS: 74 dogs (control, n = 12; MMVD, n = 62) were included. METHODS: Serum Ang-1 and Ang-2 concentrations were estimated using the canine-specific ELISA kit. The concentrations were compared between dogs with MMVD and healthy dogs, and they were analyzed according to the severity of MMVD and PH. RESULTS: The median serum Ang-1 concentration did not differ among the study groups. The median serum Ang-2 concentration was higher in dogs with stage B2 MMVD (P = .041) and acute congestive heart failure (P = .002) than in control dogs. In addition, the median serum Ang-2 concentration was higher in MMVD dogs with PH than in those without PH (P = .031). Serum Ang-2 concentration was correlated with vertebral heart score (rs = 0.36, P = .004) and vertebral left atrial score (r = 0.50, P < .001) in dogs with MMVD, and correlated with vertebral heart score (r = 0.63, P = .01), maximum E wave amplitude of the diastolic transmitral flow (rs = 0.61, P = .018), ejection fraction (rs = -0.77, P < .001) and fractional shortening (rs = -0.56, P = .032) in dogs with acute congestive heart failure. CLINICAL RELEVANCE: Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.


Assuntos
Angiopoietina-2 , Doenças do Cão , Hipertensão Pulmonar , Animais , Cães , Doenças do Cão/sangue , Hipertensão Pulmonar/veterinária , Hipertensão Pulmonar/sangue , Angiopoietina-2/sangue , Masculino , Feminino , Insuficiência da Valva Mitral/veterinária , Insuficiência da Valva Mitral/sangue , Angiopoietina-1/sangue , Estudos de Casos e Controles , Doenças das Valvas Cardíacas/veterinária , Doenças das Valvas Cardíacas/sangue
14.
J Clin Med ; 13(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38731257

RESUMO

Background/Objectives: Lumbar lordotic curvature (LLC), closely associated with low back pain (LBP) when decreased, is infrequently assessed in clinical settings due to the spatiotemporal limitations of radiographic methods. To overcome these constraints, this study used an inertial measurement system to compare the magnitude and maintenance of LLC across various sitting conditions, categorized into three aspects: verbal instructions, chair type, and desk task types. Methods: Twenty-nine healthy participants were instructed to sit for 3 min with two wireless sensors placed on the 12th thoracic vertebra and the 2nd sacral vertebra. The lumbar lordotic angle (LLA) was measured using relative angles for the mediolateral axis and comparisons were made within each sitting category. Results: The maintenance of LLA (LLAdev) was significantly smaller when participants were instructed to sit upright (-3.7 ± 3.9°) compared to that of their habitual sitting posture (-1.2 ± 2.4°) (p = 0.001), while the magnitude of LLA (LLAavg) was significantly larger with an upright sitting posture (p = 0.001). LLAdev was significantly larger when using an office chair (-0.4 ± 1.1°) than when using a stool (-3.2 ± 7.1°) (p = 0.033), and LLAavg was also significantly larger with the office chair (p < 0.001). Among the desk tasks, LLAavg was largest during keyboard tasks (p < 0.001), followed by mouse and writing tasks; LLAdev showed a similar trend without statistical significance (keyboard, -1.2 ± 3.0°; mouse, -1.8 ± 2.2°; writing, -2.9 ± 3.1°) (p = 0.067). Conclusions: Our findings suggest that strategies including the use of an office chair and preference for computer work may help preserve LLC, whereas in the case of cueing, repetition may be necessary.

15.
Environ Sci Pollut Res Int ; 31(13): 20521-20533, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38376780

RESUMO

To determine the sources and pathways of lead (Pb) and zinc (Zn) in river sediments contaminated with metals from mining and smelting activities, metal concentrations and Pb and Zn isotope ratios were measured in river water and sediment, and potential metal contaminant samples (imported Zn concentrates, smelting wastes, soils around the smelter, mine ores, and riverside tailings). Zn and cadmium (Cd) concentrations in river water and sediment samples were 30- and 11-25-fold higher, respectively, near the smelter than upstream, while a 6-fold increase in sediment Pb concentrations was detected over the same region. Sediment samples near the smelter (207Pb/206Pb = 0.8638 and 208Pb/206Pb = 2.0960) were observed to have a different Pb isotopic composition from upstream of the smelter (207Pb/206Pb = 0.8322 and 208Pb/206Pb = 2.0502), with δ66Zn values increasing from -0.01 to 0.82‰. Analysis of Pb and Zn isotopes and concentrations revealed that dust-contaminated soils were a major Pb source, and baseline sediments were found to be contaminated by regional mining tailings. For Zn in sediments, the main Zn sources were groundwater-derived Zn (δ66Zn = 1.02 ± 0.43‰, n = 4), dust-contaminated soils (δ66Zn = -0.18 ± 0.08‰, n = 3), and tailings-contaminated sediments (δ66Zn = 0.01 ± 0.07‰, n = 10). Endmember mixing model results showed that dust-contaminated soils contributed 78% and 64% of sediment Pb and Zn, respectively, within 2 km of the Zn smelter, decreasing to negligible levels after 47.1 km downstream. Downstream of the smelter, groundwater-derived Zn contributed 54% of sediment Zn, whereas tailings contaminated sediments contributed 70% and 25% of Pb and Zn, respectively.


Assuntos
Metais Pesados , Metais Pesados/análise , Chumbo/análise , Isótopos de Zinco/análise , Zinco/análise , Solo , Poeira/análise , Água/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Isótopos/análise
16.
Insect Sci ; 30(5): 1431-1444, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36847222

RESUMO

The Notch signaling pathway plays a central role in the development of various organisms. However, dysregulation of microRNAs (miRNAs), which are crucial regulators of gene expression, can disrupt signaling pathways at all stages of development. Although Notch signaling is involved in wing development in Drosophila, the mechanism underlying miRNA-based regulation of the Notch signaling pathway is unclear. Here, we report that loss of Drosophila miR-252 increases the size of adult wings, whereas the overexpression of miR-252 in specific compartments of larval wing discs leads to patterning defects in the adult wings. The miR-252 overexpression-induced wing phenotypes were caused by aberrant Notch signaling with intracellular accumulation of the full-length Notch receptor during development, which could be due to defects in intracellular Notch trafficking associated with its recycling to the plasma membrane and autophagy-mediated degradation. Moreover, we identified Rab6 as a direct target of miR-252-5p; Rab6 encodes a small Ras-like GTPase that regulates endosomal trafficking pathways. Consistent with this finding, RNAi-mediated downregulation of Rab6 led to similar defects in both wing patterning and Notch signaling. Notably, co-overexpression of Rab6 completely rescued the wing phenotype associated with miR-252 overexpression, further supporting that Rab6 is a biologically relevant target of miR-252-5p in the context of wing development. Thus, our data indicate that the miR-252-5p-Rab6 regulatory axis is involved in Drosophila wing development by controlling the Notch signaling pathway.

17.
Toxicol Res ; 39(1): 15-24, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36726825

RESUMO

Cosmetics, especially rinse-off personal care products (PCPs), such as shampoo, facial cleanser, and body wash, are composed of various chemicals and are one of the sources of chemicals released into aquatic ecosystems. Therefore, the cosmetic industry strives to reduce the impact of their products on the aquatic environment. In this study, we proposed an algorithm based on persistence, bioaccumulation potential, and toxicity (PBT) for the environmental risk assessment of cosmetics. PBT features are generally used in the evaluation of the environmental impact of chemicals. Based on the PBT assessment, it is possible to predict the short- and long-term effects of chemicals on the environment. Our algorithm derives substance and product scores from PBT features, allowing for the risk assessment of each ingredient in the product. Furthermore, we proposed a criterion for the environmental impact grade through which each component can be classified. We intend to use this grade and factors determined through the algorithm to manufacture products with low environmental impact.

18.
J Vet Intern Med ; 37(1): 92-100, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36461714

RESUMO

BACKGROUND: Serum microRNAs have emerged as biomarkers of various diseases. Overexpression of serum miR-216a and miR-375 occurs in dogs with experimentally induced acute pancreatitis (AP). OBJECTIVES: To identify the possibility of using serum miR-216a and miR-375 as biomarkers for the diagnosis and evaluation of treatment response in dogs with naturally occurring AP. ANIMALS: Twenty-one dogs with AP and 20 healthy dogs. METHODS: Cross-sectional study. The relative expression of serum hsa-miR-216a-5p, cfa-miR-216a, and cfa-miR-375 were analyzed using reverse transcription and real-time PCR. RESULTS: A significant difference in the serum expression of cfa-miR-375 was found between dogs with AP (median [interquartile range] 3.59 [1.55-24.52]-fold) and healthy dogs (0.81 [0.54-2.21]-fold, P < .001), and no significant differences were observed in hsa-miR-216a-5p and cfa-miR-216a (P > .05). The area under the receiver operating characteristic curve of serum cfa-miR-375 for differentiating between AP dogs and healthy dogs was 0.84 (95% confidence interval [CI]: 0.71-0.96). The expressions of hsa-miR-216a-5p and cfa-miR-375 were positively correlated with the concentrations of serum C-reactive protein (rs  = .46, rs  = .48, respectively), but not with the serum specific canine pancreatic lipase. The expression of cfa-miR-375 was significantly less after treatment in dogs with AP (P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum cfa-miR-375 could be a potential biomarker for the diagnosis and evaluation of treatment response of AP in dogs. In addition, miR-216a and miR-375 could be associated with inflammatory processes in dogs with AP.


Assuntos
Doenças do Cão , MicroRNAs , Pancreatite , Cães , Animais , Pancreatite/diagnóstico , Pancreatite/veterinária , Doença Aguda , Estudos Transversais , MicroRNAs/genética , Biomarcadores , Doenças do Cão/diagnóstico
19.
Vet Med Sci ; 9(4): 1483-1487, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37224266

RESUMO

A 3-year-old, 3.5 kg, female spayed Pomeranian was referred due to persistent vomiting, anorexia, polyuria and polydipsia, 7 days after receiving general anaesthetic for a medial patellar luxation correction. Physical examination revealed lethargy, tachypnoea and 7% dehydration. Complete blood count and serum chemistry results were unremarkable, and venous blood gas analysis revealed hypokalaemia and hyperchloraemic metabolic acidosis with a normal anion gap. Urinalysis revealed a urine specific gravity (USG) of 1.005, pH of 7.0 and proteinuria, and the bacterial culture was negative. Based on these results, the dog was diagnosed with distal renal tubular acidosis, and potassium citrate was prescribed to correct metabolic acidosis. In addition, concurrent diabetes insipidus (DI) was suspected because the dog showed persistent polyuria, polydipsia and a USG below 1.006 despite dehydration. After 3 days of initial treatment, acidosis was corrected, and vomiting resolved. Desmopressin acetate and hydrochlorothiazide were also prescribed for DI, but the USG was not normalized. Based on the insignificant therapeutic response, nephrogenic DI was highly suspected. DI was resolved after 24 days. This case report describes the concomitant presence of RTA and DI in a dog after general anaesthesia.


Assuntos
Acidose Tubular Renal , Acidose , Diabetes Insípido Nefrogênico , Diabetes Mellitus , Doenças do Cão , Cães , Feminino , Animais , Acidose Tubular Renal/diagnóstico , Acidose Tubular Renal/etiologia , Acidose Tubular Renal/veterinária , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/veterinária , Diabetes Insípido Nefrogênico/complicações , Poliúria/complicações , Poliúria/veterinária , Desidratação/complicações , Desidratação/veterinária , Acidose/complicações , Acidose/veterinária , Polidipsia/complicações , Polidipsia/veterinária , Anestesia Geral/efeitos adversos , Anestesia Geral/veterinária , Vômito/veterinária , Diabetes Mellitus/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/etiologia
20.
Light Sci Appl ; 12(1): 152, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37339970

RESUMO

Metasurfaces have been continuously garnering attention in both scientific and industrial fields, owing to their unprecedented wavefront manipulation capabilities using arranged subwavelength artificial structures. To date, research has mainly focused on the full control of electromagnetic characteristics, including polarization, phase, amplitude, and even frequencies. Consequently, versatile possibilities of electromagnetic wave control have been achieved, yielding practical optical components such as metalenses, beam-steerers, metaholograms, and sensors. Current research is now focused on integrating the aforementioned metasurfaces with other standard optical components (e.g., light-emitting diodes, charged-coupled devices, micro-electro-mechanical systems, liquid crystals, heaters, refractive optical elements, planar waveguides, optical fibers, etc.) for commercialization with miniaturization trends of optical devices. Herein, this review describes and classifies metasurface-integrated optical components, and subsequently discusses their promising applications with metasurface-integrated optical platforms including those of augmented/virtual reality, light detection and ranging, and sensors. In conclusion, this review presents several challenges and prospects that are prevalent in the field in order to accelerate the commercialization of metasurfaces-integrated optical platforms.

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