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1.
J Transl Med ; 21(1): 279, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37101210

RESUMO

BACKGROUND: Auditory neuropathy is an unusual type of hearing loss. At least 40% of patients with this disease have underlying genetic causes. However, in many hereditary auditory neuropathy cases, etiology remains undetermined. METHODS: We collected data and blood samples from a four-generation Chinese family. After excluding relevant variants in known deafness-related genes, exome sequencing was conducted. Candidate genes were verified by pedigree segregation, transcript/protein expression in the mouse cochlea, and plasmid expression studies in HEK 293T cells. Moreover, a mutant mouse model was generated and underwent hearing evaluations; protein localization in the inner ear was also assessed. RESULTS: The clinical features of the family were diagnosed as auditory neuropathy. A novel variant c.710G > A (p.W237X) in apoptosis-related gene XKR8 was identified. Genotyping of 16 family members confirmed the segregation of this variant with the deafness phenotype. Both XKR8 mRNA and XKR8 protein were expressed in the mouse inner ear, predominantly in regions of spiral ganglion neurons; Moreover, this nonsense variant impaired the surface localization of XKR8 in cells. Transgenic mutant mice exhibited late-onset auditory neuropathy, and their altered XKR8 protein localization in the inner ear confirmed the damaging effects of this variant. CONCLUSIONS: We identified a variant in the XKR8 gene that is relevant to auditory neuropathy. The essential role of XKR8 in inner ear development and neural homeostasis should be explored.


Assuntos
Surdez , Perda Auditiva Central , Perda Auditiva , Camundongos , Animais , Perda Auditiva Central/genética , Perda Auditiva/genética , Linhagem , Surdez/genética , Surdez/metabolismo , Apoptose/genética , Proteínas de Membrana/genética , Proteínas Reguladoras de Apoptose/genética
2.
Ophthalmology ; 130(5): 542-550, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36642334

RESUMO

PURPOSE: Defocus incorporated multiple segments (DIMS) spectacle lenses were reported to slow myopia progression significantly in a randomized controlled trial (RCT). The study evaluated their effectiveness in clinical settings. DESIGN: Retrospective study. PARTICIPANTS: Patient records involving use of DIMS and single-vision (SV) spectacle lenses were collected from subsidiary hospitals of Aier Eye Hospital Group. METHODS: The spherical equivalent (SE), determined by subjective refraction, was adopted to assess the myopia progression. The strategy of propensity score matching (PSM) was applied to match the confounding baseline characteristics between the 2 groups. The effectiveness was calculated based on the difference of myopia progression of these 2 approaches. MAIN OUTCOME MEASURES: Change in SE. RESULTS: Three thousand six hundred thirty-nine patients with DIMS and 6838 patients with SV spectacles were included. The age of the patients was 6 to 16 years (mean ± standard deviation: 11.02 ± 2.53 years). The baseline SE was between 0.00 and -10.00 diopters (D) (mean ± standard deviation: -2.78 ± 1.74 D). After the PSM, data on 2240 pairs with 1-year follow-up and on 735 pairs with 2-year follow-up were obtained. Significantly slower progression was seen in the DIMS group at both the 1-year (DIMS, -0.50 ± 0.43 D; SV, -0.77 ± 0.58 D; P < 0.001) and 2-year (DIMS, -0.88 ± 0.62 D; SV, -1.23 ± 0.76 D; P < 0.001) subdataset. In the 1-year subdataset, 40% and 19% showed myopia progression of no more than 0.25 D for the DIMS and SV groups, respectively (chi-square, 223.43; P < 0.001), whereas 9% and 22% showed myopia progression of more than 1.00 D for the DIMS and SV groups, respectively (chi-square, 163.38; P < 0.001). In the 2-year subdataset, 33% and 20% showed myopia progression of no more than 0.50 D for the DIMS and SV groups, respectively (chi-square, 31.15; P < 0.001), whereas 12% and 29% showed myopia progression of more than 1.50 D for the DIMS and SV groups (chi-square, 65.60; P < 0.001). CONCLUSIONS: Although the magnitude was lower than that reported in the previous RCT, this large-scale study with diversity of the data sources confirmed the effectiveness of DIMS spectacles to slow myopia progression in clinical practice. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.


Assuntos
Miopia , Humanos , Criança , Adolescente , Miopia/terapia , Refração Ocular , Óculos , Progressão da Doença , Face
3.
Int Arch Allergy Immunol ; 184(10): 1056-1070, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37343537

RESUMO

INTRODUCTION: Circular RNAs (circRNAs) are essential in the progression of allergic rhinitis (AR). The purpose of this research was to examine the role of circRNA ADP-ribosylation factor 3 (circARF3) in the pathogenesis of AR. METHODS: To generate an animal model of AR, mice were treated with house dust mite (HDM), and mice nasal epithelial cells (NEpCs) were treated with IL-4/IL-13 to imitate the inflammatory damage of AR in vitro. Sanger sequencing, qRT-PCR, and RNAse R digestion assays all validated the circularization structure of circARF3. The levels of circARF3, miR-205-5p, and sirtuin 5 (SIRT5) were determined by qRT-PCR or Western blotting. Luciferase reporter, RNA immunoprecipitation, and pull-down experiments were used to investigate the regulatory network. Flow cytometry was used to investigate the rate of cell apoptosis, and Western blotting was used to determine the levels of apoptotic-related proteins (cleaved caspase 3, cleaved polyadenosine-diphosphate-ribose polymerase) and HMGB1, TLR4, and MyD88. Enzyme-linked immunosorbent assay was used to assess the inflammatory response. Hematoxylin-eosin staining and TUNEL were used to detect the histology of injury and apoptosis of nasal mucosa tissues. RESULTS: CircARF3 and SIRT5 levels were reduced in HDM-treated animals and IL-4/IL-13-treated NEpCs, while miR-205-5p expression was increased. CircARF3 was generated by back-splicing exons 3-5 with a stable circular shape. CircARF3 overexpression mitigated IL-4/IL-13-induced apoptosis in NEpCs by inhibiting miR-205-5p. SIRT5 upregulation attenuated IL-4/IL-13-induced inflammatory injury in NEpCs, and SIRT5 knockdown induced opposite effects. miR-205-5p silencing reversed the effects of SIRT5 knockdown on IL-4/IL-13-induced inflammatory injury. Furthermore, circARF3 overexpression alleviated histological abnormalities, apoptosis, inflammatory response, and HMGB1/TLR4 signaling activation in HDM-treated animals. CONCLUSION: CircARF3 inhibited cell apoptosis and inflammation via the miR-205-5p/SIRT5 axis in IL-4/IL-13-treated NEpCs and HDM-treated mice.


Assuntos
Proteína HMGB1 , MicroRNAs , Rinite Alérgica , Sirtuínas , Animais , Camundongos , Interleucina-13 , Interleucina-4 , Receptor 4 Toll-Like/genética , Rinite Alérgica/genética , MicroRNAs/genética , Mucosa Nasal , Dermatophagoides pteronyssinus , Pyroglyphidae , Apoptose/genética , Sirtuínas/genética
4.
Cell Commun Signal ; 21(1): 363, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38115126

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM) is a devastating disease that lacks effective drugs for targeted therapy. Previously, we found that the third-generation epidermal growth factor receptor (EGFR) inhibitor AZD-9291 persistently blocked the activation of the ERK pathway but had no inhibitory effect on the phosphoinositide 3-kinase (PI3K)/Akt pathway. Given that the PI3K inhibitor GDC-0084 is being evaluated in phase I/II clinical trials of GBM treatment, we hypothesized that combined inhibition of the EGFR/ERK and PI3K/Akt pathways may have a synergistic effect in the treatment of GBM. METHODS: The synergistic effects of cotreatment with AZD-9291 and GDC-0084 were validated using cell viability assays in GBM and primary GBM cell lines. Moreover, the underlying inhibitory mechanisms were assessed through colony formation, EdU proliferation, and cell cycle assays, as well as RNA-seq analyses and western blot. The therapeutic effects of the drug combination on tumor growth and survival were investigated in mice bearing tumors using subcutaneously or intracranially injected LN229 xenografts. RESULTS: Combined treatment with AZD-9291 and GDC-0084 synergistically inhibited the proliferation and clonogenic survival, as well as induced cell cycle arrest of GBM cells and primary GBM cells, compared to monotherapy. Moreover, AZD-9291 plus GDC-0084 combination therapy significantly inhibited the growth of subcutaneous tumors and orthotopic brain tumor xenografts, thus prolonging the survival of tumor-bearing mice. More importantly, the combination of AZD-9291 and GDC-0084 simultaneously blocked the activation of the EGFR/MEK/ERK and PI3K/AKT/mTOR signaling pathways, thereby exerting significant antitumor activity. CONCLUSION: Our findings demonstrate that the combined blockade of the EGFR/MEK/ERK and PI3K/AKT/mTOR pathways is more effective against GBM than inhibition of each pathway alone, both in vitro and in vivo. Our results suggest that AZD-9291 combined with GDC-0084 may be considered as a potential treatment strategy in future clinical trials. Video Abstract.


Assuntos
Glioblastoma , Humanos , Animais , Camundongos , Glioblastoma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Receptores ErbB/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Linhagem Celular Tumoral , Proliferação de Células
5.
Ann Hum Biol ; 50(1): 1-8, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37401376

RESUMO

BACKGROUND: Schizophrenia spectrum disorder (SSD) is a common mental disorder causing severe and chronic disability. Epigenetic changes in genes related to the hypothalamic-pituitary-adrenal (HPA) axis are believed to play an important role in SSD pathogenesis. The methylation status of the corticotropin-releasing hormone (CRH) gene, which is central to the HPA axis, has not been investigated in patients with SSD. AIM: We investigated the methylation status of the coding region of the CRH gene (hereafter, CRH methylation) using peripheral blood samples from patients with SSD. SUBJECTS AND METHODS: We used sodium bisulphite and MethylTarget to determine CRH methylation after collecting peripheral blood samples from 70 patients with SSD who had positive symptoms and 68 healthy controls. RESULTS: CRH methylation was significantly increased in patients with SSD, especially in male patients. CONCLUSIONS: Differences in CRH methylation were detectable in the peripheral blood of patients with SSD. Epigenetic abnormalities in the CRH gene were closely related to positive symptoms of SSD, suggesting that epigenetic processes may mediate the pathophysiology of SSD.


Assuntos
Metilação de DNA , Esquizofrenia , Humanos , Masculino , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Esquizofrenia/genética , Sistema Hipófise-Suprarrenal/metabolismo
6.
Mikrochim Acta ; 190(8): 295, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37458810

RESUMO

The development and performance of a DNA probe adsorbing Mn2+-modified black phosphorus (BP@Mn2+/DNA) hybrid nanosensor is reported that enables rapid detection of cancer-derived exosomal microRNAs (miRNAs) and exosomes. This two-dimensional (2D) nanosensor can spontaneously penetrate the lipid bilayer of exosome membranes owing to its ultra-thin geometry. Subsequently, the adsorbed probe specifically hybridizes with the target miRNA and then dissociates from the nanosensor surface, generating fluorescent signals. Therefore, the BP@Mn2+/DNA nanosensor can differentiate between colorectal cancer (CRC) cell-derived exosomes and those derived from intestinal epithelial cells through sensing of exosomal miRNAs. Furthermore, when the epithelial cell adhesion molecule (EpCAM) aptamer is adsorbed onto BP@Mn2+ instead of the miRNA probe, the nanosensor is able to distinguish exosomes derived from the plasma of CRC patients from those of healthy controls by the recognition ability of the EpCAM aptamer. By utilizing this nanosensor, we were able to effectively differentiate cancer-derived exosomes through the direct detection of miRNA-21 within the exosomes, as well as the identification of specific exosomal membrane proteins. This nanosensor design paves the way for the development of rapid and efficient cancer-derived exosomal miRNA and exosome biosensing nanoplatforms.


Assuntos
Exossomos , MicroRNAs , Neoplasias , Humanos , Exossomos/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Neoplasias/metabolismo , Oligonucleotídeos/metabolismo
7.
Cancer Sci ; 113(5): 1652-1668, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35293097

RESUMO

Nasopharyngeal carcinoma (NPC) is prevalent in East Asia and causes increased health burden. Elucidating the regulatory mechanism of NPC progression is important for understanding the pathogenesis of NPC and developing novel therapeutic strategies. Nasopharyngeal carcinoma and normal tissues were collected. Nasopharyngeal carcinoma cell proliferation, migration, and invasion were evaluated using CCK-8, colony formation, wound healing, and transwell assays, respectively. A xenograft mouse model of NPC was established to analyze NPC cell growth and metastasis in vivo. The expression of miR-106a-5p, FBXW7, TRIM24, and SRGN was determined with RT-qPCR and Western blot. MiR-106a-5p, TRIM24, and SRGN were upregulated, and FBXW7 was downregulated in NPC tissues and cells. Exosomal miR-106a-5p could enter NPC cells, and its overexpression promoted the proliferation, migration, invasion, and metastasis of NPC cells, which were suppressed by knockdown of exosomal miR-106a-5p. MiR-106a-5p targeted FBXW7 to regulate FBXW7-mediated degradation of TRIM24. Furthermore, TRIM24 regulated SRGN expression by binding to its promoter in NPC cells. Suppression of exosomal miR-106a-5p attenuated NPC growth and metastasis through the FBXW7-TRIM24-SRGN axis in vivo. Exosomal miR-106a-5p accelerated the progression of NPC through the FBXW7-TRIM24-SRGN axis. Our study elucidates novel regulatory mechanisms of NPC progression and provides potential exosome-based therapeutic strategies for NPC.


Assuntos
MicroRNAs , Neoplasias Nasofaríngeas , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteína 7 com Repetições F-Box-WD/genética , Proteína 7 com Repetições F-Box-WD/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia
8.
Bull Math Biol ; 83(10): 109, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524555

RESUMO

We study the evolution of dispersal in advective three-patch models with distinct network topologies. Organisms can move between connected patches freely and they are also subject to the passive, directed drift. The carrying capacity is assumed to be the same in all patches, while the drift rates could vary. We first show that if all drift rates are the same, the faster dispersal rate is selected for all three models. For general drift rates, we show that the infinite diffusion rate is a local Convergence Stable Strategy (CvSS) for all three models. However, there are notable differences for three models: For Model I, the faster dispersal is always favored, irrespective of the drift rates, and thus the infinity dispersal rate is a global CvSS. In contrast, for Models II and III a singular strategy will exist for some ranges of drift rates and bi-stability phenomenon happens, i.e., both infinity and zero diffusion rates are local CvSSs. Furthermore, for both Models II and III, it is possible for two competing populations to coexist by varying drift and diffusion rates. Some predictions on the dynamics of n-patch models in advective environments are given along with some numerical evidence.


Assuntos
Evolução Biológica , Ecossistema , Conceitos Matemáticos , Modelos Biológicos , Dinâmica Populacional
9.
J Chem Phys ; 155(3): 034702, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34293879

RESUMO

We report inelastic differential scattering experiments for energetic H and D atoms colliding at a Pt(111) surface with and without adsorbed O atoms. Dramatically, more energy loss is seen for scattering from the Pt(111) surface compared to p(2 × 2) O on Pt(111), indicating that O adsorption reduces the probability of electron-hole pair (EHP) excitation. We produced a new full-dimensional potential energy surface for H interaction with O/Pt that reproduces density functional theory energies accurately. We then attempted to model the EHP excitation in H/D scattering with molecular dynamics simulations employing the electronic density information from the Pt(111) to calculate electronic friction at the level of the local density friction approximation (LDFA). This approach, which assumes that O atoms simply block the Pt atom from the approaching H atom, fails to reproduce experiment due to the fact that the effective collision cross section of the O atom is only 10% of the area of the surface unit cell. An empirical adiabatic sphere model that reduces electronic nonadiabaticity within an O-Pt bonding length scale of 2.8 Å reproduces experiment well, suggesting that the electronic structure changes induced by chemisorption of O atoms nearly remove the H atom's ability to excite EHPs in the Pt. Alternatives to LDFA friction are needed to account for this adsorbate effect.

10.
Skin Res Technol ; 27(2): 272-276, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33174647

RESUMO

BACKGROUND: In clinical, common facial papule dermatosis such as seborrheic keratosis (SK), verruca plana (VP), syringoma and lichen nitidus (LN) is often misdiagnosed. Summarizing in vivo reflectance confocal microscopy (RCM) features of the facial papule dermatosis is helpful in the diagnosis of ambiguous lesions. The purpose of this study was to evaluate the features of SK, VP, syringoma, and LN in RCM. METHODS: We recruited 144 patients referred for unequivocal facial papule dermatosis including 60 patients with SK, 60 patients with VP, 10 patients with syringoma, and 14 patients with LN. The RCM images were evaluated at the epidermis, the dermoepidermal junction, and the dermis from both papule lesions and normal skin. RESULTS: In the epidermis, the cerebriform shape was the main RCM characteristic of SK and the "petal-like" structure was the main RCM characteristic of VP. In the dermoepidermal junction, the RCM features we found were as follows: For SK, the bright dermal papillary rings, the abnormal dermal papilla and the looped vessels were also observed at the abnormal dermal papilla. For VP, the bright dermal papillary rings and the point-like blood vessels were also observed at the round dermal papills. For LN, the round, enlarged, well-circumscribed dermal papillae and the enlarged dermal papillaes were heavily laden with individual highly refractive cells. In the dermis, RCM examination revealed brightly refractile teratogenous sweat tube, designing variably visible bright "moon" structures in all syringoma patients. CONCLUSION: Considering our results, RCM may be useful to non-invasively discriminate SK, VP, syringoma and LN in vivo.


Assuntos
Ceratose Seborreica , Líquen Nítido , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Siringoma , Verrugas , Humanos , Ceratose Seborreica/diagnóstico por imagem , Microscopia Confocal , Neoplasias das Glândulas Sudoríparas/diagnóstico por imagem , Verrugas/diagnóstico por imagem
11.
Proc Natl Acad Sci U S A ; 115(4): 680-684, 2018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29311297

RESUMO

The Born-Oppenheimer approximation (BOA) provides the foundation for virtually all computational studies of chemical binding and reactivity, and it is the justification for the widely used "balls and springs" picture of molecules. The BOA assumes that nuclei effectively stand still on the timescale of electronic motion, due to their large masses relative to electrons. This implies electrons never change their energy quantum state. When molecules react, atoms must move, meaning that electrons may become excited in violation of the BOA. Such electronic excitation is clearly seen for: (i) Schottky diodes where H adsorption at Ag surfaces produces electrical "chemicurrent;" (ii) Au-based metal-insulator-metal (MIM) devices, where chemicurrents arise from H-H surface recombination; and (iii) Inelastic energy transfer, where H collisions with Au surfaces show H-atom translation excites the metal's electrons. As part of this work, we report isotopically selective hydrogen/deuterium (H/D) translational inelasticity measurements in collisions with Ag and Au. Together, these experiments provide an opportunity to test new theories that simultaneously describe both nuclear and electronic motion, a standing challenge to the field. Here, we show results of a recently developed first-principles theory that quantitatively explains both inelastic scattering experiments that probe nuclear motion and chemicurrent experiments that probe electronic excitation. The theory explains the magnitude of chemicurrents on Ag Schottky diodes and resolves an apparent paradox--chemicurrents exhibit a much larger isotope effect than does H/D inelastic scattering. It also explains why, unlike Ag-based Schottky diodes, Au-based MIM devices are insensitive to H adsorption.

12.
Lasers Med Sci ; 36(4): 783-790, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32651700

RESUMO

The optical properties of hemoglobin could indicate the degree of hemolysis. We aimed to utilize this to develop a real-time blood damage monitoring device for cardiopulmonary bypass (CPB) systems. The real-time blood damage monitoring device comprised a near-infrared spectroscopy optical module with a fiber spectrometer and monitoring platform and computer software developed using LabVIEW 2017. The fiber spectrometer operated at wavelengths of 545, 660, and 940 nm and contained a detector fiber bundle (source-detector distance = 1.0-2.5 cm). CPB operation was simulated using an artificial heart-lung machine with a flow rate of 3, 4, or 5 L/min. Four hundred milliliter of anticoagulated porcine blood was continuously rotated for 4 h. The transmittance, reflectivity, and absorbance of the blood were measured using the optical device at a frequency of 25 Hz and then digitally averaged into 1-s interval. Samples of damaged blood were collected at regular intervals for in vitro hemolysis tests to calculate the normalized index of hemolysis (NIH). All experiments were repeated three times. We prepared 28 blood bags containing 400 ml of anticoagulant. Paired t test was used to examine the test-retest reliability of the differences between the three methods and control samples. Statistical tests revealed significant differences in the mean values between the test and control groups over time (P < 0.01). Relationship was established between the real-time monitoring results and the NIH values. An effective blood damage detection method that combined in vitro hemolysis tests and near-infrared spectroscopy was achieved. The results demonstrate the clinical potential of a real-time, low-cost, and reliable blood damage monitoring device to improve the safety of CPB operation.


Assuntos
Ponte Cardiopulmonar/instrumentação , Espectroscopia de Luz Próxima ao Infravermelho , Máquina Coração-Pulmão , Hemoglobinas/metabolismo , Hemólise , Humanos , Reprodutibilidade dos Testes
13.
J Insect Sci ; 21(4)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34280294

RESUMO

Euproctis pseudoconspersa is a major pest of tea plants, and also causes a skin rash on workers in tea plantations. Research on virus could provide fundamental insights for classification, genetic diversity, evolution, and host-virus interaction mechanisms. Here, we identified a novel RNA virus, Euproctis pseudoconspersa bunyavirus (Phenuiviridae), and found that it is widely distributed in field populations of E. pseudoconspersa. The replication of virus in E. pseudoconspersa was indicated by Tag-PCR. These results contribute to the classification of bunyaviruses and provide insight into the diversity of commensal E. pseudoconspersa bunyavirus and the host.


Assuntos
Mariposas/virologia , Orthobunyavirus/genética , Animais , Produtos Agrícolas , Interações entre Hospedeiro e Microrganismos , Controle Biológico de Vetores , Filogenia , Prevalência , RNA Viral , Chá
14.
Immunol Invest ; 49(5): 555-570, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31957545

RESUMO

BACKGROUND: MiR-146a has been shown to negatively regulate innate immune, inflammatory response and antiviral pathway, however, its role in the tolerogenic responses remains largely unknown. This study aimed to investigate the role of miR-146a in the OVA-induced allergic inflammation of dendritic cells (DCs). METHODS: Bone marrow-derived DCs (BMDCs) were treated with OVA (100 µg/ml) for 24 h. MiR-146a expressions were assessed by quantitative RT-PCR. BMDCs were transfected with miR-146a mimics or inhibitor. Cell surface markers were analyzed by flow cytometry. Cytokine levels were determined by ELISA assay. Mixed lymphocyte culture assay was adopted to assess CD4 + T-cell differentiation. The 3' UTR luciferase reporter assay was utilized to determine the miRNA target sequence. RESULTS: OVA treatment significantly up-regulated miR-146a in BMDCs in a dose- and time-dependent manner. In the OVA-treated DCs, overexpression of miR-146a (mimics transfection) down-regulated the surface markers (CD80, CD86) and increased production of anti-inflammatory cytokines TGF-ß1 and IL-10 but decreased pro-inflammatory cytokine IL-12. MiR-146a overexpression promoted immature DC to induce regulatory T cells (Treg) differentiation. By contrast, transfection of miR-146a inhibitor into DC exhibited the opposite trends. Notch1 was a direct target of miR-146a, and Notch1 knock-down induced similar effects as miR-146a mimics transfection in BMDCs. Moreover, the effect of miR-146a inhibitor on OVA-induced DC was attenuated by Notch1 knock-down. CONCLUSION: miRNA-146a promoted tolerogenic properties of DCs, at least partially, through targeting Notch1 signaling.


Assuntos
Células Dendríticas/imunologia , Hipersensibilidade/imunologia , Inflamação/imunologia , MicroRNAs/genética , Receptor Notch1/metabolismo , Linfócitos T Reguladores/imunologia , Alérgenos/imunologia , Animais , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Humanos , Tolerância Imunológica , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , RNA Interferente Pequeno/genética , Receptor Notch1/genética , Transdução de Sinais
15.
Phys Chem Chem Phys ; 22(45): 26113-26120, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-32915176

RESUMO

We present a first principles-quality potential energy surface (PES) describing the inter-atomic forces for hydrogen atoms interacting with free-standing graphene. The PES is a high-dimensional neural network potential that has been parameterized to 75 945 data points computed with density-functional theory employing the PBE-D2 functional. Improving over a previously published PES [Jiang et al., Science, 2019, 364, 379], this neural network exhibits a realistic physisorption well and achieves a 10-fold reduction in the RMS fitting error, which is 0.6 meV per atom. The chemisorption barrier is 172 meV, which is lower than that of the REBO-EMFT PES (260 meV). We used this PES to calculate about 1.5 million classical trajectories with carefully selected initial conditions to allow for direct comparison to results of H- and D-atom scattering experiments performed at incidence translational energy of 1.9 eV and a surface temperature of 300 K. The theoretically predicted scattering angular and energy loss distributions are in good agreement with experiment, despite the fact that the experiments employed graphene grown on Pt(111). Compared to previous calculations, the agreement with experiments is improved. The remaining discrepancies between experiment and theory are likely due to the influence of the Pt substrate only present in the experiment.

16.
Bull Math Biol ; 82(10): 131, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025293

RESUMO

We study the dynamics of two competing species in three-patch models and illustrate how the topology of directed river network modules may affect the evolution of dispersal. Each model assumes that patch 1 is at the upstream end, patch 3 is at the downstream end, but patch 2 could be upstream, or middle stream, or downstream, depending on the specific topology of the modules. We posit that individuals are subject to both unbiased dispersal between patches and passive drift from one patch to another, depending upon the connectivity of patches. When the drift rate is small, we show that for all models, the mutant species can invade when rare if and only if it is the slower disperser. However, when the drift rate is large, most models predict that the faster disperser wins, while some predict that there exists one evolutionarily singular strategy. The intermediate range of drift is much more complex: most models predict the existence of one singular strategy, but it may or may not be evolutionarily stable, again depending upon the topology of modules, while one model even predicts that for some intermediate drift rate, singular strategy does not exist and the faster disperser wins the competition.


Assuntos
Evolução Biológica , Ecologia , Modelos Biológicos , Dinâmica Populacional , Rios , Ecologia/métodos , Ecossistema , Conceitos Matemáticos , Mutação
17.
Sensors (Basel) ; 20(12)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32549316

RESUMO

In this paper, low-density parity-check (LDPC)-coded carrierless amplitude and phase (CAP) modulation with spatial diversity is proposed to mitigate turbulence-induced fading in an underwater visible-light communication (UVLC) channel. Generalized-gamma (GG) distribution was used to model the fading, as this model is valid for weak- and strong-turbulence regimes. On the basis of the characteristic function (CHF) of GG random variables, we derived an approximated bit-error rate (BER) for the CAP modulation scheme with spatial diversity and equal-gain combining (EGC). Furthermore, we simulated the performance of the CAP system with diversity and LDPC for various turbulence conditions and validated the analysis. Obtained results showed that the combination of LDPC and spatial diversity is effective in mitigating turbulence-induced fading, especially when turbulence strength is strong.

18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(6): 495-498, 2020 Dec 08.
Artigo em Zh | MEDLINE | ID: mdl-33314856

RESUMO

A rehabilitation equipment is developed by mechanical and electronic engineering principle based on the need of rehabilitation training for patients with paraplegia. The device can prevent complications such as palsy bedsores and deep venous thrombosis. The device effectively reduces the labor intensity of the rehabilitation staff or family members to carry the patient's body, and promotes the physical and psychological rehabilitation progress of patients with lower limb paralysis.


Assuntos
Posição Ortostática , Reabilitação do Acidente Vascular Cerebral/instrumentação , Caminhada , Humanos , Extremidade Inferior
19.
Phys Rev Lett ; 123(15): 156101, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31702291

RESUMO

Previous measurements of vibrational relaxation lifetimes for molecules adsorbed at metal surfaces yielded values of 1-3 ps; however, only chemisorbed molecules have been studied. We report the first measurements of the vibrational relaxation lifetime of a molecule physisorbed to a metal surface. For CO(v=1) adsorbed on Au(111) at 35 K the vibrational lifetime of the excited stretching mode is 49±3 ps. The long lifetime seen here is likely to be a general feature of physisorption, which involves weaker electronic coupling between the adsorbate and the solid due to bonding at larger distances.

20.
J Chem Phys ; 150(18): 184704, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091898

RESUMO

Efficient transfer of translational energy to electron-hole pair excitation involving multiple collisions dominates H atom collisions with metal surfaces. For this reason, H atom interaction with metal surfaces cannot be modeled within the commonly used Born-Oppenheimer approximation (BOA). This fact makes H atom scattering from metal surfaces an ideal model system for dynamics that go beyond the BOA. We chose the H/Au(111) system as a model system to obtain a detailed dataset that can serve as a benchmark for theoretical models developed for describing electronically nonadiabatic processes at metal surfaces. Therefore, we investigate the influence of various experimental parameters on the energy loss in detail including isotopic variant, incidence translational energy, incidence polar and azimuthal angles, and outgoing scattering angles.

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