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1.
Exp Eye Res ; 238: 109715, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37951338

RESUMO

This study aimed to examine the intraocular tolerability of the epidermal growth factor receptor antibody cetuximab, when applied intravitreally, and its effect on axial elongation. Guinea pigs aged 2-3 weeks were subjected to bilateral plano glasses and bilateral lens-induced myopization (LIM) as a single procedure for group I (n = 8) and group II (n = 8), respectively. In the animals of group III (n = 8), group IV (n = 8), and group V (n = 8), the right eyes of the animals, in addition to LIM, received four weekly intravitreal injections of cetuximab (Erbitux®) in doses of 6.25 µg, 12.5 µg, and 25 µg, respectively. As controls, the left eyes, in addition to LIM, received corresponding intraocular injections of phosphate-buffered saline. The animals underwent regular ophthalmoscopic examinations and biometry for axial length measurements. With increasing doses of cetuximab, the inter-eye difference in axial elongation (at study end, left eyes minus right eyes) were significantly the smallest in group I (0.00 ± 0.02 mm) and group II (-0.01 ± 0.02 mm), they were larger in group III (0.04 ± 0.04 mm) and group IV (0.10 ± 0.03 mm), and they were the largest in group V (0.11 ± 0.01 mm). The inter-eye difference in axial elongation enlarged (P < 0.001) with the number of injections applied. Retinal thickness at the posterior pole (right eyes) was significantly thicker in group V than in group II (P < 0.01). The density of apoptotic cells (visualized by TUNEL-staining) did not vary significantly between any of the groups (all P > 0.05). The results suggest that intravitreal injections of cetuximab in young guinea pigs with LIM resulted in a reduction in axial elongation in a dose-dependent and number of treatment-dependent manner. Intraocular toxic effects, such as intraocular inflammation, retinal thinning, or an increased density of apoptotic cells in the retina, were not observed in association with the intravitreally applied cetuximab.


Assuntos
Cristalino , Miopia , Cobaias , Animais , Miopia/metabolismo , Cetuximab/toxicidade , Cetuximab/metabolismo , Retina/metabolismo , Cristalino/metabolismo , Injeções Intraoculares , Modelos Animais de Doenças
2.
BMC Ophthalmol ; 24(1): 6, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172796

RESUMO

BACKGROUND: To investigate the relationship between body weight and Axial length in guinea pigs. METHODS: Forty pigmented guinea pigs were randomly divided into two groups, namely control group and negative lens-induced myopization (LIM) group. After measuring the baseline axial length and body weight (BW), guinea pigs of LIM group received bilateral negative lens-induced myopization using - 10.0 diopters lenses. One week later, the lenses were removed and biometric and ophthalmoscopic examinations were repeated. RESULTS: Two groups of guinea pigs showed no statistical difference in initial body weight and eye axis length. Compared to the control group, the lens-induced group had a lower weight (P = 0.02) and a longer axial length (P < 0.01) at the end of study Neither at baseline nor at week 1 did AL correlate with BW in both groups (Control Baseline: r = 0.306, P = 0.19; Control Week1: r = 0.333, P = 0.15; LIM Baseline: r=-0.142, P = 0.55; LIM Week 1: r = 0.189, P = 0.42). Lens-induction had a significant effect on axial elongation (P < 0.01) while body weight had no impact on such aspect (P > 0.05). CONCLUSION: In guinea pigs of the same age, axial length was not correlated with body weight. Also, baseline body weight had no impact on natural axial length growth or lens-induced myopia. Lens-induction caused a significant reduction in body weight gain.


Assuntos
Cristalino , Miopia , Animais , Cobaias , Miopia/etiologia , Comprimento Axial do Olho , Biometria , Modelos Animais de Doenças
3.
Br J Cancer ; 129(3): 466-474, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37344582

RESUMO

BACKGROUND: Retinoblastoma is the most common intraocular malignancy in childhood. With the advanced management strategy, the globe salvage and overall survival have significantly improved, which proposes subsequent challenges regarding long-term surveillance and offspring screening. This study aimed to apply a deep learning algorithm to reduce the burden of follow-up and offspring screening. METHODS: This cohort study includes retinoblastoma patients who visited Beijing Tongren Hospital from March 2018 to January 2022 for deep learning algorism development. Clinical-suspected and treated retinoblastoma patients from February 2022 to June 2022 were prospectively collected for prospective validation. Images from the posterior pole and peripheral retina were collected, and reference standards were made according to the consensus of the multidisciplinary management team. A deep learning algorithm was trained to identify "normal fundus", "stable retinoblastoma" in which specific treatment is not required, and "active retinoblastoma" in which specific treatment is required. The performance of each classifier included sensitivity, specificity, accuracy, and cost-utility. RESULTS: A total of 36,623 images were included for developing the Deep Learning Assistant for Retinoblastoma Monitoring (DLA-RB) algorithm. In internal fivefold cross-validation, DLA-RB achieved an area under curve (AUC) of 0.998 (95% confidence interval [CI] 0.986-1.000) in distinguishing normal fundus and active retinoblastoma, and 0.940 (95% CI 0.851-0.996) in distinguishing stable and active retinoblastoma. From February 2022 to June 2022, 139 eyes of 103 patients were prospectively collected. In identifying active retinoblastoma tumours from all clinical-suspected patients and active retinoblastoma from all treated retinoblastoma patients, the AUC of DLA-RB reached 0.991 (95% CI 0.970-1.000), and 0.962 (95% CI 0.915-1.000), respectively. The combination between ophthalmologists and DLA-RB significantly improved the accuracy of competent ophthalmologists and residents regarding both binary tasks. Cost-utility analysis revealed DLA-RB-based diagnosis mode is cost-effective in both retinoblastoma diagnosis and active retinoblastoma identification. CONCLUSIONS: DLA-RB achieved high accuracy and sensitivity in identifying active retinoblastoma from the normal and stable retinoblastoma fundus. It can be used to surveil the activity of retinoblastoma during follow-up and screen high-risk offspring. Compared with referral procedures to ophthalmologic centres, DLA-RB-based screening and surveillance is cost-effective and can be incorporated within telemedicine programs. CLINICAL TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT05308043).


Assuntos
Aprendizado Profundo , Neoplasias da Retina , Retinoblastoma , Humanos , Retinoblastoma/diagnóstico , Estudos de Coortes , Algoritmos , Estudos Retrospectivos , Neoplasias da Retina/diagnóstico
4.
BMC Ophthalmol ; 23(1): 176, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095443

RESUMO

BACKGROUND: To evaluate the prevalence and associated health and lifestyle factors of myopic maculopathy (MM) in a northern Chinese industrial city. METHODS: The cross-sectional Kailuan Eye Study included subjects who participated in the longitudinal Kailuan Study in 2016. Ophthalmologic and general examinations were performed on all the participants. MM was graded based on fundus photographs using the International Photographic Classification and Grading System. The prevalence of MM was evaluated. Univariate and multiple logistic regression were adopted to evaluated risk factors of MM. RESULTS: The study included 8330 participants with gradable fundus photographs for MM and ocular biometry data. The prevalence of MM was 1.11% (93/8330; 95% confidence interval [CI] 0.89-1.33%). Diffuse chorioretinal atrophy, patchy chorioretinal atrophy, macular atrophy, and plus lesions were observed in 72 (0.9%), 15 (0.2%), 6 (0.007%), and 32 eyes (0.4%), respectively. MM was more common in eyes with longer axial length (OR 4.517; 95%CI 3.273 to 6.235) and in participants with hypertension (OR 3.460; 95%CI 1.152 to 10.391), and older age (OR 1.084; 95%CI 1.036 to 1.134). CONCLUSIONS: The MM was present in 1.11% of the northern Chinese individuals 21 years or older and the associate factors include longer axial length, older age, and hypertension.


Assuntos
Degeneração Macular , Miopia Degenerativa , Degeneração Retiniana , Doenças Retinianas , Humanos , Acuidade Visual , Prevalência , Estudos Transversais , China/epidemiologia , Estilo de Vida , Atrofia
5.
Phys Chem Chem Phys ; 24(9): 5738-5747, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35191433

RESUMO

Two stable high-pressure phases (C2/m-MnN4 and P1̄-MnN4) and four metastable phases (P4/mmm-MnN4, P1̄-MnN5, C2/m-MnN6 and P1̄-MnN8) are proposed by using ab initio evolutionary simulations. Besides the reported quasi-diatomic molecule N2, the armchair chain and S-like chain, the N4 ring and N22 ring are firstly reported in the P4/mmm-MnN4 and P1̄-MnN5 phases. A detailed study is performed on the energetic properties, mechanical properties and stability of these polynitrogen structures. Ab initio molecular dynamics simulations show that P1̄-MnN4 and P1̄-MnN5 can be quenched down to ambient conditions, and large decomposition energy barriers result in the high decomposition temperatures of P1̄-MnN4 (2000 K) and P1̄-MnN5 (3000 K). Interestingly, P4/mmm-MnN4 with the N4 ring exhibits outstanding mechanical properties, including high incompressibility, high hardness, uniform strength in the 2-D direction and excellent ductility. Strong N-N covalent bond and weak Mn-N ionic bond interactions are observed in the predicted Mn-N compounds, and the charge transfer between the Mn and N atoms provides an important contribution to the stabilization of polymeric N-structures. All the proposed structures are metallic phases. Our results provide a deep understanding of the chemistry of transition metal polynitrides under pressure and encourage experimental synthesis of these new manganese polynitrides in future.

6.
BMC Ophthalmol ; 22(1): 193, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477375

RESUMO

BACKGROUND: To examine an effect of intravitreally applied antibodies against epidermal growth factor family members, namely epiregulin, epigen and betacellulin, on ocular axial elongation. METHODS: The experimental study included 30 guinea pigs (age:3-4 weeks) which underwent bilateral lens-induced myopization and received three intraocular injections of 20 µg of epiregulin antibody, epigen antibody and betacellulin antibody in weekly intervals into their right eyes, and of phosphate-buffered saline into their left eyes. Seven days after the last injection, the animals were sacrificed. Axial length was measured by sonographic biometry. RESULTS: At baseline, right eyes and left eyes did not differ (all P > 0.10) in axial length in neither group, nor did the interocular difference in axial length vary between the groups (P = 0.19). During the study period, right and left eyes elongated (P < 0.001) from 8.08 ± 0.07 mm to 8.59 ± 0.06 mm and from 8.08 ± 0.07 mm to 8.66 ± 0.07 mm, respectively. The interocular difference (left eye minus right eye) in axial elongation increased significantly in all three groups (epiregulin-antibody:from 0.03 ± 0.06 mm at one week after baseline to 0.16 ± 0.08 mm at three weeks after baseline;P = 0.001); epigen-antibody group:from -0.01 ± 0.06 mm to 0.06 ± 0.08 mm;P = 0.02; betacellulin antibody group:from -0.05 ± 0.05 mm to 0.02 ± 0.04 mm;P = 0.004). Correspondingly, interocular difference in axial length increased from -0.02 ± 0.04 mm to 0.13 ± 0.06 mm in the epiregulin-antibody group (P < 0.001), and from 0.01 ± 0.05 mm to 0.07 ± 0.05 mm in the epigen-antibody group (P = 0.045). In the betacellulin-antibody group the increase (0.01 ± 0.04 mm to 0.03 ± 0.03 mm) was not significant (P = 0.24). CONCLUSIONS: The EGF family members epiregulin, epigen and betacellulin may be associated with axial elongation in young guinea pigs, with the effect decreasing from epiregulin to epigen and to betacellulin.


Assuntos
Cristalino , Animais , Betacelulina , Epigen , Epirregulina , Olho , Cobaias , Humanos
7.
Inorg Chem ; 60(9): 6772-6781, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33858137

RESUMO

A systematic high-pressure study of the CdNx (x = 2, 3, 4, 5, and 6) system is performed by using the first-principles calculation method in combination with the particle swarm optimization algorithm. We proposed four stable high-pressure phases (P4mbm-CdN2, Cmmm-CdN4, I4̅2d-CdN4, and C2/c-CdN5) and one metastable high-pressure phase (C2/m-CdN6), for which the structural frames are composed of a diatomic quasi-molecule N2, standard armchair N-chain, S-type bent armchair N-chain, zigzag-antizigzag N-chain, and N14 network structure. Among them, the novel zigzag-antizigzag N-chain and N14 network structure are reported for the first time. More importantly, Cmmm-CdN4 and C2/m-CdN6 possess high stability under ambient conditions, which may be quenched to ambient conditions once they are synthesized at high-pressure conditions. The high decomposition energy barrier (1.14 eV) results in a high decomposition temperature (2500 K) of Cmmm-CdN4, while a low decomposition energy barrier (0.19 eV) results in a mild decomposition temperature (500 K) of C2/m-CdN6. The high energy density and outstanding explosive performance make Cmmm-CdN4, I4̅2d-CdN4, C2/c-CdN5, and C2/m-CdN6 potential high-energy materials. The electronic structure analyses show that these predicted high-pressure structures are all metallic phases, and the N-N and Cd-N bonds are the strong covalent and ionic bond interactions, respectively. The charge transfer from the Cd atom plays an important role in the stability of the proposed structures.

8.
Inorg Chem ; 60(18): 14022-14030, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34459583

RESUMO

The high-pressure phase diagram of Co-N compounds is enriched by proposing five stable phases (Pnnm-Co2N, Pmn21-Co2N, Pmna-CoN, Pnnm-CoN2, and P1̅-CoN4) and two metastable phases (P3̅1c-CoN8 and P1̅-CoN10). A systematic study has been performed for revealing the novel polymeric nitrogen structure and the outstanding properties of predicted polynitrides, such as structural characterization, energy analysis, stability analysis, and electronic analysis. P3̅1c-CoN8 with the novel layer-shaped N-structure and P1̅-CoN10 with the novel band-shaped N-structure are first reported in this work. Moreover, P3̅1c-CoN8 (6.14 kJ/g) and P1̅-CoN10 (5.18 kJ/g) with high energy density can be quenched down to ambient conditions. The proposed seven high-pressure phases are all metallic phases. A weak ionic bond interaction is observed between the Co and N atoms, while a strong N-N covalent bond interaction is observed in the Pnnm-CoN2, P1̅-CoN4, P3̅1c-CoN8, and P1̅-CoN10 phases. The N atoms in the polynitrides hybridize in the sp2 state, for which the hybrid orbitals are constructed by the σ bond or lone electronic pair. The charge transfer between the Co and N atoms plays an important role to the structural stability. Moreover, the vibrational analysis of P3̅1c-CoN8 and P1̅-CoN10 phases is performed to guide the future experimental study.

9.
Eye (Lond) ; 38(7): 1246-1251, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38238576

RESUMO

BACKGROUND: Analyzing fundus images with deep learning techniques is promising for screening systematic diseases. However, the quality of the rapidly increasing number of studies was variable and lacked systematic evaluation. OBJECTIVE: To systematically review all the articles that aimed to predict systemic parameters and conditions using fundus image and deep learning, assessing their performance, and providing suggestions that would enable translation into clinical practice. METHODS: Two major electronic databases (MEDLINE and EMBASE) were searched until August 22, 2023, with keywords 'deep learning' and 'fundus'. Studies using deep learning and fundus images to predict systematic parameters were included, and assessed in four aspects: study characteristics, transparent reporting, risk of bias, and clinical availability. Transparent reporting was assessed by the TRIPOD statement, while the risk of bias was assessed by PROBAST. RESULTS: 4969 articles were identified through systematic research. Thirty-one articles were included in the review. A variety of vascular and non-vascular diseases can be predicted by fundus images, including diabetes and related diseases (19%), sex (22%) and age (19%). Most of the studies focused on developed countries. The models' reporting was insufficient in determining sample size and missing data treatment according to the TRIPOD. Full access to datasets and code was also under-reported. 1/31(3.2%) study was classified as having a low risk of bias overall, whereas 30/31(96.8%) were classified as having a high risk of bias according to the PROBAST. 5/31(16.1%) of studies used prospective external validation cohorts. Only two (6.4%) described the study's calibration. The number of publications by year increased significantly from 2018 to 2023. However, only two models (6.5%) were applied to the device, and no model has been applied in clinical. CONCLUSION: Deep learning fundus images have shown great potential in predicting systematic conditions in clinical situations. Further work needs to be done to improve the methodology and clinical application.


Assuntos
Aprendizado Profundo , Fundo de Olho , Humanos , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/diagnóstico
10.
Transl Vis Sci Technol ; 13(4): 28, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38648051

RESUMO

Purpose: Retinal and optic nerve diseases have become the primary cause of irreversible vision loss and blindness. However, there is still a lack of thorough evaluation regarding their prevalence in China. Methods: This artificial intelligence-based national screening study applied a previously developed deep learning algorithm, named the Retinal Artificial Intelligence Diagnosis System (RAIDS). De-identified personal medical records from January 2019 to December 2021 were extracted from 65 examination centers in 19 provinces of China. Crude prevalence and age-sex-adjusted prevalence were calculated by mapping to the standard population in the seventh national census. Results: In 2021, adjusted referral possible glaucoma (63.29, 95% confidence interval [CI] = 57.12-68.90 cases per 1000), epiretinal macular membrane (21.84, 95% CI = 15.64-29.22), age-related macular degeneration (13.93, 95% CI = 11.09-17.17), and diabetic retinopathy (11.33, 95% CI = 8.89-13.77) ranked the highest among 10 diseases. Female participants had significantly higher adjusted prevalence of pathologic myopia, yet a lower adjusted prevalence of diabetic retinopathy, referral possible glaucoma, and hypertensive retinopathy than male participants. From 2019 to 2021, the adjusted prevalence of retinal vein occlusion (0.99, 95% CI = 0.73-1.26 to 1.88, 95% CI = 1.42-2.44), macular hole (0.59, 95% CI = 0.41-0.82 to 1.12, 95% CI = 0.76-1.51), and hypertensive retinopathy (0.53, 95% CI = 0.40-0.67 to 0.77, 95% CI = 0.60-0.95) significantly increased. The prevalence of diabetic retinopathy in participants under 50 years old significant increased. Conclusions: Retinal and optic nerve diseases are an important public health concern in China. Further well-conceived epidemiological studies are required to validate the observed increased prevalence of diabetic retinopathy, hypertensive retinopathy, retinal vein occlusion, and macular hole nationwide. Translational Relevance: This artificial intelligence system can be a potential tool to monitor the prevalence of major retinal and optic nerve diseases over a wide geographic area.


Assuntos
Inteligência Artificial , Doenças do Nervo Óptico , Doenças Retinianas , Humanos , China/epidemiologia , Prevalência , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Doenças Retinianas/epidemiologia , Doenças Retinianas/diagnóstico , Doenças do Nervo Óptico/epidemiologia , Doenças do Nervo Óptico/diagnóstico , Adulto Jovem , Adolescente , Programas de Rastreamento/métodos , Idoso de 80 Anos ou mais
11.
Heliyon ; 10(17): e36588, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39263185

RESUMO

Purpose: Primary surgery failure of macular holes causes poor visual acuity outcomes. Several studies indicate that small-medium idiopathic full-thickness macular holes (iFTMH) have consistent and high anatomical closure rates after vitrectomy and internal limiting membrane (ILM) peeling, regardless of iFTMH diameters. However, there is no systematic analysis examining the relationship between iFTMH diameters and anatomical closure rates. Methods: In this systematic review and meta-regression, we searched PubMed, Embase, and Web of Science databases on October 24th, 2022. We included studies regarding iFTMH, with ILM peeling/inverted flap technique, long-lasting gas tamponade, and face-down position after surgery. Univariable meta-regression with a restricted cubic spline model and component-plus-residual plot after covariables adjustment were used to explore non-linear association. Results: A total of 7257 participants from 19 randomized controlled trials and 49 observational studies were included in this meta-analysis. In ILM peeling group, every 100-µm increment in diameter was associated with a 3.8 % (95 % confidence interval [CI], 1.8%-5.7 %, P < 0.001) relatively lower anatomical closure rate. Yet, among studies using the inverted flap technique, baseline iFTMH diameter was not associated with a lower anatomical closure rate (0.2 %, 95%CI, -4.2 %-4.5 %, P > 0.9). The restricted cubic spline model and component-plus-residual plot controlling for age, sex, and symptom duration prior to surgery showed no evident non-linearity in both surgical techniques. Conclusions: The iFTMH diameter is linear and inversely associated with the anatomical closure rate after the ILM peeling technique, but not with the inverted flap technique. The present study supports the use of advanced techniques, e.g., inverted flap technique, in small-medium iFTMH to improve anatomical closure rates.

12.
Invest Ophthalmol Vis Sci ; 64(10): 24, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37466949

RESUMO

Purpose: The mechanism underlying axial elongation during myopia progression remains unknown. Epidermal growth factor receptor (EGFR) signaling is associated with axial elongation. We explored whether mammalian target of rapamycin complex 1 (mTORC1) signaling acts as the downstream pathway of EGFR and participates in negative lens-induced axial elongation (NLIAE). Methods: Three-week-old male pigmented guinea pigs underwent binocular NLIAE. (1) To investigate whether EGFR is the upstream regulator of mTORC1, an EGFR inhibitor (20 µg erlotinib) was intravitreally injected once a week for three weeks. (2) To assess the effect of mTORC1 inhibition on NLIAE, an mTORC1 inhibitor (2 µg, 10 µg, and 20 µg everolimus) was intravitreally injected once a week for three weeks. (3) To explore the long-term effect of mTORC1 overactivation on axial elongation, an mTORC1 agonist (4 µg MHY1485) was intravitreally injected once a week for three months. Biometric measurements included axial length and choroidal thickness were performed. Results: Compared with the guinea pigs without NLIAE, NLIAE was associated with activation of mTORC1 signaling, which was suppressed by intravitreal erlotinib injection. Intravitreally injected everolimus suppressed NLIAE-induced axial elongation, mTORC1 activation, choroidal thinning, and hypoxia-inducible factor-1α expression in the sclera. Immunofluorescence revealed that the retinal pigment epithelium was the primary location of mTORC1 activation during NLIAE. Combining NLIAE and MHY1485 intravitreal injections significantly promoted axial elongation, choroidal thinning, and peripapillary choroidal atrophy. Conclusions: The mTORC1 signaling is associated with increased axial elongation, as in NLIAE, raising the possibility of inhibiting mTORC1 as a novel treatment for slowing myopia progression.


Assuntos
Everolimo , Miopia , Masculino , Animais , Cobaias , Cloridrato de Erlotinib/uso terapêutico , Everolimo/farmacologia , Everolimo/uso terapêutico , Miopia/tratamento farmacológico , Injeções Intravítreas , Receptores ErbB , Mamíferos
13.
Invest Ophthalmol Vis Sci ; 64(4): 11, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37040096

RESUMO

Background: Epidermal growth factor (EGF) and its family members have been reported to be involved in myopic axial elongation. We examined whether short hairpin RNA attenuated adeno-associated virus (shRNA-AAV)-induced knockdown of amphiregulin, an EGF family member, has an influence on axial elongation. Methods: Three-week-old pigmented guinea pigs underwent lens-induced myopization (LIM) without additional intervention (LIM group; n = 10 animals) or additionally received into their right eyes at baseline an intravitreal injection of scramble shRNA-AAV (5 × 1010 vector genome [vg]) (LIM + Scr-shRNA group; n = 10) or of amphiregulin (AR)-shRNA-AAV (5 × 1010 vg/5 µL) (LIM + AR-shRNA-AAV group; n = 10), or they received an injection of AR-shRNA-AAV at baseline and three weekly amphiregulin injections (20 ng/5 µL) (LIM + AR-shRNA-AAV + AR group; n = 10). The left eyes received equivalent intravitreal injections of phosphate-buffered saline. Four weeks after baseline, the animals were sacrificed. Results: At study end, interocular axial length difference was higher (P < 0.001), choroid and retina were thicker (P < 0.05), and relative expression of amphiregulin and p-PI3K, p-p70S6K, and p-ERK1/2 was lower (P < 0.05) in the LIM + AR-shRNA-AAV group than in any other group. The other groups did not differ significantly when compared with each other. In the LIM + AR-shRNA-AAV group, the interocular axial length difference increased with longer study duration. TUNEL assay did not reveal significant differences among all groups in retinal apoptotic cell density. In vitro retinal pigment epithelium cell proliferation and migration were the lowest (P < 0.05) in the LIM + AR-shRNA-AAV group, followed by the LIM + AR-shRNA-AAV + AR group. Conclusions: shRNA-AAV-induced knockdown of amphiregulin expression, in association with suppression of epidermal growth factor receptor signaling, attenuated axial elongation in guinea pigs with LIM. The finding supports the notion of EGF playing a role in axial elongation.


Assuntos
Dependovirus , Miopia , Animais , Cobaias , Dependovirus/genética , Anfirregulina/metabolismo , Fator de Crescimento Epidérmico , RNA Interferente Pequeno/genética , Miopia/metabolismo , Retina/metabolismo
14.
Front Oncol ; 12: 854253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433428

RESUMO

For uveal melanoma (UM) patients, it is significant to establish diagnosis and prognosis evaluation systems through imaging techniques. However, imaging examinations are short of quantitative biomarkers and it is difficult to finish early diagnosis of UM. In order to discover new molecular biomarkers for the diagnosis and prognostic evaluation of UM, six circulating miRNAs (mir-132-3p, mir-21-5p, mir-34a-5p, mir-126-3p, mir-199a-3p, mir-214-3p) were chosen as candidates for independent validation. Validation of these miRNAs was performed in a cohort of 20 patients, including 10 spindle-shaped melanoma and 10 epithelioid cell melanoma, and 10 healthy donors. Then 5 patients with metastatic UM were included to validate the performance of miRNAs in advanced UM. Serum levels of miRNAs were determined using quantitative real-time PCR. We confirmed significantly higher levels of three miRNAs in serum of UM patients in comparison to healthy controls, and miR-199a-3p had the best performance (p < 0.0001; AUC = 0.985). MiR-214-3p and miR-21-5p were significantly upregulated in serum of epithelioid cell melanoma patients compared to spindle-shaped melanoma patients and miR-132-3p and, conversely, were significantly downregulated in serum of epithelioid cell melanoma patients. MiR-21-5p shows their best performance (p < 0.0001; AUC = 0.980). Both miR-199a-3p and miR-21-5p showed great performance in advanced UM. Significantly higher levels of miR-21-5p (p < 0.001) were found in serum of metastatic UM patients compared to patients with localized spindle-shaped melanoma, and significantly higher levels of miR-199a-3p (p < 0.001) were detected in serum of metastatic UM patients compared to healthy controls. Our preliminary data indicate promising diagnostic utility of circulating miR-199a-3p and promising prognostic utility of circulating miR-21-5p in both early and advanced UM patients.

15.
RSC Adv ; 9(51): 29987-29992, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-35531505

RESUMO

A new hybrid material comprising of armchair shaped polymeric nitrogen chains (N8) encapsulated in h-BN matrix is proposed and studied through ab initio calculations. Interestingly, the theoretical results demonstrate that N8 chains, confined in h-BN matrix, are effectively stabilized at ambient pressure and room temperature. Moreover, N8 chains can dissociate and release energy at a much milder temperature of 600 K. The confined polymer N8 unit needs to absorb 0.68 eV energy to span the decomposition energy barrier before decomposing. Further research shows that the charge transfer between N8 chain and h-BN layer is the stabilizing mechanism of this new hybrid material. And the low dissociation temperature is due to a much smaller amount of charge transfer compared to other confined systems in previous reports. The IR and Raman vibrational analyses suggest that host-guest interactions in the hybrid material influence the vibration modes of both the confined N8 chain and h-BN layer.

16.
RSC Adv ; 8(54): 30912-30918, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35548752

RESUMO

Polymeric nitrogen, as a potential high-energy-density material (HEDM), has many applications, such as in energy storage systems, explosives and propellants. Nowadays it is very urgent to find a suitable method to stabilize polymeric nitrogen at ambient conditions. Herein, we present a new hybrid structure where polymeric nitrogen sheets are sandwiched between graphene sheets in the form of a three-dimensional crystal. According to ab initio molecular dynamics (AIMD) calculations and phonon spectrum calculations, it is demonstrated that polymeric nitrogen sheets are stable at ambient pressure and temperature. The hybrid material has a higher nitrogen content (the weight ratio of nitrogen is up to 53.84%), and the corresponding energy density is 5.2 kJ g-1. The hybrid material (A7@graphene system) has a satisfactory energy density, detonation velocity and detonation pressure. Importantly, the hybrid material can be preserved up to 450 K, and above this temperature, the polymeric nitrogen sheets break up into polymeric nitrogen chains or nitrogen gases and release tremendous energy. Further calculations reveal that small charge transfer between the polymeric nitrogen sheets and graphene sheets creates a weak electrostatic attraction compared with other hybrid materials, which is just good for the stabilization of the polymeric nitrogen sheets at ambient conditions, and favors energy release in a gentle way. The proposed confinement hybrid material which has a high energy density and a gentle energy release temperature, provides a highly promising method for the capture and application of polymeric nitrogen in a controllable way.

17.
Sci Rep ; 8(1): 13758, 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30213961

RESUMO

Polymeric nitrogen, as a potential high-energy-density material (HEDM), has attracted many theoretical calculations and predictions for its potential applications, such as energy storage, propellants and explosives. Searching for an effective method to stabilize polymeric nitrogen in ambient conditions of temperature and pressure has become a hot topic. Herein, we propose a new hybrid material where polymeric nitrogen layers are intercalated in a multilayer BN matrix forming a three-dimensional structure, by means of ab initio density functional theory. It is demonstrated polymeric nitrogen layers can be stable at ambient conditions and can release tremendous energy just above 500 K, more gentle and controllable. Further calculations reveal the new hybrid material exhibits a much smaller charge transfer than that of previous reports, which not only stabilizes polymeric nitrogen layer at ambient conditions, but also favours energy releasing at milder conditions. It is also very exciting that, the weight ratio of polymeric nitrogen in new material is up to 53.84%, approximately three times higher than previous one-dimensional hybrid materials. The energy density (5.4 KJ/g) also indicates it is a promising HEDMs candidate. Our findings provide a new insight into nitrogen-based HEDMs capture and storage.

18.
Sci Rep ; 7(1): 2404, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28546586

RESUMO

Two-dimensional (2D) crystals exhibit unique and exceptional properties and show promise for various applications. In this work, we systematically studied the structures of a 2D boronphosphide (BP) monolayer with different stoichiometric ratios (BPx, x = 1, 2, 3, 4, 5, 6 and 7) and observed that each compound had a stable 2D structure with metallic or semiconducting electronic properties. Surprisingly, for the BP5 compounds, we discovered a rare penta-graphene-like 2D structure with a tetragonal lattice. This monolayer was a semiconductor with a quasi-direct band gap of 2.68 eV. More importantly, investigation of the strain effect revealed that small uniaxial strain can trigger the band gap of the penta-BP5 monolayer to transition from a quasi-direct to direct band gap, whereas moderate biaxial strain can cause the penta-BP5 to transform from a semiconductor into a metal, indicating the great potential of this material for nanoelectronic device applications based on strain-engineering techniques. The wide and tuneable band gap of monolayer penta-BP5 makes it more advantageous for high-frequency-response optoelectronic materials than the currently popular 2D systems, such as transition metal dichalcogenides and black phosphorus. These unique structural and electronic properties of 2D BP sheets make them promising for many potential applications in future nanodevices.

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