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1.
Opt Lett ; 45(5): 1124-1127, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32108786

RESUMO

Here, we report $ {\chi ^{(3)}} $χ(3)-based optical parametric oscillation (OPO) with widely separated signal-idler frequencies from crystalline aluminum nitride microrings pumped at $ 2\,\,\unicode{x00B5}{\rm m} $2µm. By tailoring the width of the microring, OPO reaching toward the telecom and mid-infrared bands with a frequency separation of 64.2 THz is achieved. While dispersion engineering through changing the microring width is capable of shifting the OPO sideband by $ \gt {9}\;{\rm THz}$>9THz, the OPO frequency can also be agilely tuned in the ranges of 1 and 0.1 THz, respectively, by shifting the pump wavelength and controlling the chip's temperature. At high pump powers, the OPO sidebands further evolve into localized frequency comb lines. Such large-frequency-shift OPO with flexible wavelength tunability will lead to enhanced chip-scale light sources.

2.
Sci Rep ; 9(1): 15596, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666602

RESUMO

Notch signaling is involved in the early onset of osteoarthritis. The aim of this study was to investigate the role of Notch signaling changes during proliferation and differentiation of chondrocyte, and to testify the mechanism of MMP-13 regulation by Notch and Runx2 expression changes during osteoarthritis. In this study, Chondrocytes were isolated from rat knee cartilages. Notch signaling was activated/inhibited by Jagged-1/DAPT. Proliferative capacity of Chondrocytes was analyzed by CCK-8 staining and EdU labeling. ColX, Runx2 and MMP-13 expressions were analyzed as cell differentiation makers. Then, Runx2 gene expression was interfered using lentivirus transfection (RNAi) and was over-expressed by plasmids transfected siRNA in chondrocytes, and MMP-13 expression was analyzed after Jagged-1/DAPT treatment. In vivo, an intra-articular injection of shRunx2 lentivirus followed with Jagged1/DAPT treatments was performed in rats. MMP-13 expression in articular cartilage was detected by immunohistochemistry. Finally, MMP-13 expression changes were analyzed in chondrocytes under IL-1ß stimulation. Our findings showed that, CCK-8 staining and EdU labeling revealed suppression of cell proliferation by Notch signaling activation after Jagged-1 treatment in chondrocytes. Promoted differentiation was also observed, characterized by increased expressions of Col X, MMP-13 and Runx2. Meanwhile, Sox9, aggrecan and Col II expressions were down-regulated. The opposite results were observed in Notch signaling inhibited cells by DAPT treatment. In addition, Runx2 RNAi significantly attenuated the 'regulatory sensitivity' of Notch signaling on MMP-13 expression both in vitro and in vivo. However, we found there wasn't significant changes of this 'regulatory sensitivity' of Notch signaling after Runx2 over-expression. Under IL-1ß circumstance, MMP-13 expression could be reduced by both DAPT treatment and Runx2 RNAi, while Runx2 interference also attenuated the 'regulatory sensitivity' of Notch in MMP-13 under IL-1ß stimulation. In conclusion, Notch signaling is an important regulator on rat chondrocyte proliferation and differentiation, and this regulatory effect was partially mediated by proper Runx2 expression under both normal and IL-1ß circumstances. In the meanwhile, DAPT treatment could effectively suppress expression of MMP-13 stimulated by IL-1 ß.

3.
Opt Express ; 27(16): 22246-22253, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510521

RESUMO

In optical microresonators, stimulated Raman scattering (SRS) competes with four-wave mixing process and impact Kerr comb generation. Here, we demonstrate Raman frequency combs in poly-crystalline aluminum nitride (AlN) microring resonators. The Raman shifts at transverse-electric (TE) and transverse-magnetic (TM) polarizations are characterized from AlN straight waveguides using backscattering geometries. In poly-crystalline AlN microring resonators, the frequency matching of cavity resonances with broad Raman gain enhances the SRS and leads to Raman-assisted frequency combs. As a result, comb lines near Raman scattering regions of AlN are generated.

4.
Nat Commun ; 10(1): 2971, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278261

RESUMO

Ultraviolet frequency combs enable applications ranging from precision spectroscopy to atomic clocks by addressing electronic transitions of atoms and molecules. Access to ultraviolet light via integrated nonlinear optics is usually hampered by the strong material dispersion and large waveguide attention in ultraviolet regions. Here we demonstrate a simple route to chip-scale ultraviolet comb generators, simultaneously showing a gap-free frequency span of 128 terahertz and high conversion efficiency. This process relies on adiabatic quadratic frequency translation of a near-visible supercontinuum sourced by an ultrafast fiber laser. The simultaneous cubic and quadratic nonlinear processes are implemented in single-crystalline aluminum nitride thin films, where chirp-modulated taper waveguides are patterned to ensure a broad phase matching. The heterodyne characterization suggests that both the near-visible and ultraviolet supercontinuum combs maintain high coherence. Our approach is also adaptable to other non-centrosymmetric photonic platforms for ultrafast nonlinear optics with scalable bandwidth.

5.
Opt Lett ; 44(12): 3182-3185, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31199411

RESUMO

Chip-based soliton frequency combs have been demonstrated on various material platforms, offering broadband, mutually coherent, and equally spaced frequency lines desired for many applications. Lithium niobate (LN), possessing both second- and third-order optical nonlinearities, as well as integrability on insulating substrates, has emerged as a novel source for microcomb generation and controlling. Here we demonstrate mode-locked soliton microcombs generated around 2 µm in a high-Q z-cut LN microring resonator. The intracavity photorefractive effect is found to be still dominant over the thermal effect in the 2 µm region, which facilitates direct accessing soliton states in the red-detuned regime, as reported in the telecom band. We also find that intracavity stimulated Raman scattering is greatly suppressed when moving the pump wavelength from the telecom band to 2 µm, thus alleviating Raman-Kerr comb competition. This Letter expands mode-locked LN microcombs to 2 µm, and could enable a variety of potential applications based on LN nanophotonic platform.

6.
Opt Lett ; 44(6): 1492-1495, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30874684

RESUMO

We demonstrate octave-spanning supercontinuum generation in unpoled lithium niobate waveguides, which are engineered to possess anomalous dispersion and pumped by a turn-key femtosecond laser centered at 1560 nm. Tunable dispersive waves and strong phase-matched second-harmonic generation are both observed by controlling the widths of the waveguides. The major features of the experimental spectra are reproduced by numerical modeling of the generalized nonlinear Schrödinger equation, which can be used to guide waveguide designs for tailoring the supercontinuum spectrum. Our results identify a path to a simple and integrable supercontinuum source in lithium niobate nanophotonic platform and will enable new capabilities in precision frequency metrology.

7.
Opt Lett ; 43(18): 4366-4369, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30211865

RESUMO

Chip-scale mode-locked dissipative Kerr solitons have been realized on various materials platforms, making it possible to achieve a miniature, highly coherent frequency comb source with high repetition rates. Aluminum nitride (AlN), an appealing nonlinear optical material having both Kerr (χ3), and Pockels (χ2) effects, has immerse potential for comb self-referencing without the need for external harmonic generators. However, cavity soliton states have not yet been achieved in AlN microresonators. Here, we demonstrate mode-locked Kerr cavity soliton generation in a crystalline AlN microring resonator. By utilizing ultrafast tuning of the pump frequency through single-sideband modulation, in combination with an optimized wavelength scan and pump power-ramp patterns, we can deterministically elongate a ∼400 ns short-lived soliton to a time span as long as we wish to hold it.

8.
J Craniofac Surg ; 28(6): 1620-1625, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28692512

RESUMO

BACKGROUND: The mutations in a Notch signaling ligand, jagged 1, are associated with unilateral coronal craniosynostosis in humans. However, the underlying mechanisms of Notch signaling in cranial suture biology still remain unclear. METHODS: The temporal and spatial patterns of Notch signaling expression were examined in the posterofrontal and sagittal sutures of Sprague-Dawley rats by real-time quantitative reverse-transcription polymerase chain reaction at postnatal ages of 2, 15, and 25 days. The role of Notch signaling in the proliferation and differentiation of osteoblasts isolated from calvarial was examined in vitro by EdU incorporation assays and real-time quantitative reverse-transcription polymerase chain reaction after activating and inhibiting Notch signaling. RESULTS: The mRNA levels of Notch family members (including Jagged 1, Delta 1, 3, 4, Notch 1-4, Hes 1, and Hes 5) decreased during the posterofrontal cranial suture fusion in rat. However, in the patent sagittal sutures, the mRNA levels of Notch family members (Jagged 2, Delta 1, Notch 1, Notch 3, Hes 5, and Hey 1) increased during suture development. The EdU incorporation assays revealed that the induction of Notch signaling in calvaria osteobalsts using Jagged 1 promoted the proliferation rates in those cells in vitro. Further studies showed that activation of Notch signaling calvaria osteobalsts using Jagged 1 led to the suppression of late osteogenetic markers such as type I collagen and osteocalcin. CONCLUSIONS: The regulation of Notch signaling is of crucial importance during the physiological patterning of posterofrontal and sagittal cranial sutures. Thus, targeting this pathway may prove significant for the development of future therapeutic applications in craniosynostosis.


Assuntos
Suturas Cranianas , Osteoblastos , Receptores Notch , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Suturas Cranianas/citologia , Suturas Cranianas/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Receptores Notch/análise , Receptores Notch/genética , Receptores Notch/metabolismo , Transdução de Sinais/fisiologia
9.
Exp Ther Med ; 13(2): 461-466, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28352316

RESUMO

Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days. In addition, anti-MCP-1 antibodies were intrathecally injected to rats in various groups in order to investigate the association of MCP-1 with mechanical and heat hyperalgesia using the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) tests, respectively. Furthermore, MCP-1 and CCR2 expression levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, and CCR2 expression levels were measured using RT-qPCR. The results indicated that MCP-1 and CCR2 expression levels were significantly increased in the spinal cord of MTBP rats. Intrathecal administration of anti-MCP-1 neutralizing antibodies was observed to attenuate the mechanical and thermal allodynia in MTBP rats. Therefore, the upregulation of spinal MCP-1 and CCR2 expression levels may contribute to the development of mechanical allodynia in MTBP rats. In conclusion, MCP-1/CCR2 signaling may serve a crucial role in morphine tolerance development in rats suffering from cancer-induced bone pain.

10.
Opt Express ; 25(2): 587-594, 2017 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-28157948

RESUMO

We demonstrate aluminum nitride (AlN) on sapphire as a novel platform for integrated optics. High-confinement AlN microring resonators are realized by adopting a partially etched (pedestal) waveguide to relax the required etching selectivity for exact pattern transfer. A wide taper is employed at the chip end facets to ensure a low fiber-to-chip coupling loss of ~2.8 dB/facet for both transverse-electric (TE) and transverse-magnetic (TM) modes. Furthermore, the intrinsic quality factors (Qint) recorded with a high-resolution linewidth measurement are up to ~2.5 and 1.9 million at telecom band for fundamental TE00 and TM00 modes, corresponding to a low intracavity propagation loss of ~0.14 and 0.2 dB/cm as well as high resonant buildup of 473 and 327, respectively. Such high-Q AlN-on-sapphire microresonators are believed to be very promising for on-chip nonlinear optics.

11.
Opt Lett ; 41(15): 3599-602, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27472628

RESUMO

An all-optically tunable microwave photonic phase shifter is demonstrated based on an epitaxial aluminum nitride (AlN) microring with an intrinsic quality factor of 3.2×106. The microring adopts a pedestal structure, which allows overcoupling with 700 nm gap size and facilitates the fabrication process. A phase shift for broadband signals from 4 to 25 GHz is demonstrated by employing the thermo-optic effect and the separate carrier tuning technique. A phase tuning range of 0°-332° is recorded with a 3 dB radio frequency (RF) power variation and 48 mW optical power consumption. In addition, AlN exhibits intrinsic second-order optical nonlinearity. Thus, our work presents a novel platform with a low propagation loss and the capability of electro-optic modulation for applications in integrated microwave photonics.

12.
Nat Med ; 20(11): 1279-88, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25306233

RESUMO

The WNT16 locus is a major determinant of cortical bone thickness and nonvertebral fracture risk in humans. The disability, mortality and costs caused by osteoporosis-induced nonvertebral fractures are enormous. We demonstrate here that Wnt16-deficient mice develop spontaneous fractures as a result of low cortical thickness and high cortical porosity. In contrast, trabecular bone volume is not altered in these mice. Mechanistic studies revealed that WNT16 is osteoblast derived and inhibits human and mouse osteoclastogenesis both directly by acting on osteoclast progenitors and indirectly by increasing expression of osteoprotegerin (Opg) in osteoblasts. The signaling pathway activated by WNT16 in osteoclast progenitors is noncanonical, whereas the pathway activated in osteoblasts is both canonical and noncanonical. Conditional Wnt16 inactivation revealed that osteoblast-lineage cells are the principal source of WNT16, and its targeted deletion in osteoblasts increases fracture susceptibility. Thus, osteoblast-derived WNT16 is a previously unreported key regulator of osteoclastogenesis and fracture susceptibility. These findings open new avenues for the specific prevention or treatment of nonvertebral fractures, a substantial unmet medical need.


Assuntos
Fraturas Ósseas/metabolismo , Fraturas Ósseas/prevenção & controle , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Envelhecimento/patologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular , Linhagem da Célula/efeitos dos fármacos , Células Cultivadas , Suscetibilidade a Doenças , Fraturas Ósseas/genética , Fraturas Ósseas/patologia , Deleção de Genes , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/genética , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Osteócitos/patologia , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteoprotegerina/metabolismo , Ligante RANK/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Crânio/patologia , Proteínas Wnt/deficiência
13.
Cell Transplant ; 23(6): 715-27, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24763260

RESUMO

In cartilage tissue engineering using stem cells, it is important to stimulate proliferation and control the differentiation of stem cells to specific lineages. Here we reported a combined technique for articular cartilage repair, consisting of bone marrow mesenchymal stem cells (BMMSCs) transfected with connective tissue growth factor (CTGF) gene and NaOH-treated poly(lactic-co-glycolic) acid (PLGA) scaffolds. In the present study, BMMSCs or CTGF-modified BMMSCs seeded on PLGA or NaOH-treated PLGA scaffolds were incubated in vitro and NaOH-treated PLGA significantly stimulated proliferation of BMMSCs, while CTGF gene transfer promoted chondrogenic differentiation. The effects of the composite on the repair of cartilage defects were evaluated in rabbit knee joints in vivo. Full-thickness cartilage defects (diameter: 5 mm; depth: 3 mm) were created unilaterally in the patellar groove. Defects were either left empty (n = 18) or implanted with BMMSCs/PLGA (n = 18), BMMSCs/NaOH-treated PLGA (n = 18), or CTGF-modified BMMSCs/NaOH-treated PLGA (n = 18). The defect area was examined grossly, histologically, and mechanically at 6, 12, and 24 weeks postoperatively. Implanted cells were tracked using adeno-LacZ labeling at 6 weeks after implantation. Overall, the CTGF-modified BMMSCs/NaOH-treated PLGA group showed successful hyaline-like cartilage regeneration similar to normal cartilage, which was superior to the other groups using gross examination, qualitative and quantitative histology, and mechanical assessment. The in vivo viability of the implanted cells was demonstrated by their retention for 6 weeks after implantation. These findings suggested that a combination of CTGF-modified BMMSCs and NaOH-treated PLGA may be an alternative treatment for large osteochondral defects in high-loading sites.


Assuntos
Doenças das Cartilagens/terapia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Ácido Láctico/química , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Ácido Poliglicólico/química , Animais , Materiais Biocompatíveis/química , Células da Medula Óssea/citologia , Doenças das Cartilagens/metabolismo , Doenças das Cartilagens/patologia , Células Cultivadas , Condrogênese , Colágeno/análise , Fator de Crescimento do Tecido Conjuntivo/genética , DNA/análise , Módulo de Elasticidade , Glicosaminoglicanos/análise , Articulação do Joelho/patologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Hidróxido de Sódio/química , Engenharia Tecidual , Tecidos Suporte
14.
Artigo em Inglês | MEDLINE | ID: mdl-24332326

RESUMO

OBJECTIVE: The purpose of this systematic review is to evaluate the efficacy of a new modified alar base cinch suture by comparing it with the commonly used classic alar base suture after LeFort I osteotomy. STUDY DESIGN: A comprehensive search strategy was performed to include interventional studies involving the comparisons of alar base suturing methods after LeFort I osteotomy. Data analyses were conducted using the random-effects model. RESULTS: Three studies with 146 participants undergoing LeFort I maxillary osteotomy were included in this review. The results showed that, compared with the classic method, both modified transseptal alar base suture and modified reinsertion sutures significantly decreased postoperative alar and alar base widening. CONCLUSIONS: The modified alar base cinch suture was more effective than the classic alar base suture in maintaining preoperative alar and alar base width after LeFort I osteotomy.


Assuntos
Maxila/cirurgia , Cartilagens Nasais/cirurgia , Osteotomia de Le Fort/métodos , Técnicas de Sutura , Humanos , Resultado do Tratamento
15.
Exp Ther Med ; 5(4): 1063-1066, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23596472

RESUMO

The aim of this study was to observe the changes in mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in a rat model of incisional pain with nicotine dependence and withdrawal. Twelve Wistar rats were randomly divided into a control and a withdrawal group, with 6 rats per group. In the control group, the rats were raised in normal conditions for 7 days without any treatment. A model of plantar incisional pain was established in the right lower extremity and changes in the plantar MWT and TWL of the healthy and operative sides were observed for 7 successive days. In the withdrawal group, the rats were raised in normal conditions and treated with a subcutaneous injection of pure nicotine (3 mg/kg), 3 times each day for 7 days. The model of plantar incisional pain in the right lower extremity was established, and changes in bilateral plantar MWT and TWL were observed for 7 days. The operative side plantar MWT and TWL in the withdrawal group were significantly lower than those in the control group on postoperative days 1-7, respectively (P<0.05). Compared with the healthy side in the control group, the healthy plantar MWT was significantly reduced on postoperative days 1-7 (P<0.05) and TWL was significantly decreased in postoperative days 1-6 (P<0.05) in the withdrawal group. The pain sensitivity to mechanical and thermal stimulation significantly increased in the rat model of incisional pain with nicotine dependence and withdrawal. This is consistent with the clinical increase of postoperative pain observed in patients after quitting smoking.

16.
Artigo em Inglês | MEDLINE | ID: mdl-20163971

RESUMO

OBJECTIVE: This study investigated the effect of locally immobilized bisphosphonates and systemic estrogen replacement therapy on fixation of hydroxyapatite-coated screws in ovariectomized rats. STUDY DESIGN: Twelve weeks after being ovariectomized, each of the 20 rats received 2 hydroxyapatite-coated screws in the proximal tibia, with or without immobilized bisphosphonates. Half of the animals also received subcutaneous injections of 17beta-estradiol. Thus, there were 4 groups: control, estrogen, bisphosphonates, and estrogen plus bisphosphonates. Tibiae with screws were measured by microscopic computerized tomography and push-out test 12 weeks after implantation. RESULTS: Combined treatment had the strongest effects, with the bone volume ratio around screws and the percentage of osteointegration significantly increased by 2.3-fold and 1.9-fold and the push-out force by 3.3-fold compared with untreated control samples. Monotherapy also enhanced the fixation of screws, although less. CONCLUSIONS: Systemic estrogen replacement therapy and locally immobilized bisphosphonates had additive effects on fixation of hydroxyapatite-coated screws in ovariectomized rats.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Parafusos Ósseos , Materiais Revestidos Biocompatíveis/química , Ligas Dentárias/química , Difosfonatos/uso terapêutico , Durapatita/química , Terapia de Reposição de Estrogênios , Osseointegração/efeitos dos fármacos , Ovariectomia , Titânio/química , Animais , Fenômenos Biomecânicos , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Feminino , Imidazóis/uso terapêutico , Injeções Subcutâneas , Ratos , Ratos Sprague-Dawley , Resistência ao Cisalhamento , Estresse Mecânico , Tíbia/cirurgia , Fatores de Tempo , Microtomografia por Raio-X , Ácido Zoledrônico
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