RESUMO
An asymmetrical Fabry-Perot interferometric (AFPI) force sensor is fabricated based on a narrowband reflection of low-reflectivity fiber Bragg grating (LR-FBG) and a broadband Fresnel reflection of the cleaved fiber end. The AFPI sensor includes a section of microfiber made by tapering and it achieves a force sensitivity of 0.221 pm/µN with a tapered microfiber of 40 mm length and 6.1 µm waist diameter. Compared with similar AFPI structure in 125 µm-diameter single mode fiber, the force sensitivity of the microfiber AFPI structure is greatly enhanced due to its smaller diameter and can be optimized for different force scales by controlling the diameter. The fabrication process of the AFPI sensor is simple and cost-effective. The AFPI sensor has better multiplexing capacity than conventional extrinsic fiber-optic Fabry-Perot sensors, while it also release the requirement on the wavelength matching of the FBG-pair-based FPI.
Assuntos
Tecnologia de Fibra Óptica/instrumentação , Interferometria/instrumentação , Refratometria/instrumentação , Transdutores de Pressão , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização , Estresse MecânicoRESUMO
OBJECTIVE: To observe the effects and mechanism of Xiaoyao Powder extract on the content of melanin in co-culture model of melanoma cells and keratinocytes. METHODS: Eluting components of Xiaoyao Powder was collected by AB-8 macroporous resin column. Different concentration extracts of Xiaoyao Powder were added into the co-culture model of A375 melanoma cells and HaCat ke- ratinocytes. Hunt method was used to detected the content of melanin. RT-PCR assay was used to detect the effects of the extract of Xi- aoyao Powder on the TYR,TRP-1 and TRP-2 mRNA expression in A375 melanoma cells. RESULTS: Compared with the control group,the extract of Xiaoyao Powder down-regulated content of melanin and mRNA expression of TYR,TRP-1 and TRP-2 in A375 melanoma cells by 82.23% ,93. 01% and 29. 11% ,23.78% ,20. 05% ;25. 13% ,15.02% ,11.64% ,respectively(P < 0. 01). CONCLUSION: The extract of Xiaoyao Powder can decrease the melanogenesis by down-regulating the mRNA expression of tyrosinase and its related protein.
Assuntos
Medicamentos de Ervas Chinesas/química , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Melanoma/enzimologia , Monofenol Mono-Oxigenase/metabolismo , Oxirredutases/metabolismo , Técnicas de Cocultura , Interferon Tipo I , Oxirredutases Intramoleculares , Melaninas , Pós , Proteínas da GravidezRESUMO
BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Assuntos
Anticorpos Antivirais , Vacina contra Varicela , Varicela , Vacinas Atenuadas , Humanos , Vacina contra Varicela/imunologia , Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/efeitos adversos , Método Duplo-Cego , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Masculino , Feminino , Pré-Escolar , Criança , Anticorpos Antivirais/sangue , Varicela/prevenção & controle , Varicela/imunologia , China , Herpesvirus Humano 3/imunologia , Imunogenicidade da Vacina , Vacinação/métodosRESUMO
BACKGROUND: An Escherichia coli-produced human papillomavirus (HPV) 16 and 18 bivalent vaccine (Cecolin) was prequalified by WHO in 2021. This study aimed to compare the immunogenicity of the E coli-produced HPV 9-valent vaccine Cecolin 9 (against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) with Gardasil 9. METHODS: This was a randomised, single-blind trial conducted in China. Healthy non-pregnant women aged 18-26 years, who were not breastfeeding and with no HPV vaccination history, were enrolled in the Ganyu Centre for Disease Control and Prevention (Lianyungang City, Jiangsu Province, China). Women were stratified by age (18-22 years and 23-26 years) and randomly assigned (1:1) using a permutated block size of eight to receive three doses of Cecolin 9 or Gardasil 9 at day 0, day 45, and month 6. All participants, as well as study personnel without access to the vaccines, were masked. Neutralising antibodies were measured by a triple-colour pseudovirion-based neutralisation assay. The primary outcomes, seroconversion rates and geometric mean concentrations (GMCs) at month 7, were analysed in the per-protocol set for immunogenicity (PPS-I). Non-inferiority was identified for the lower limit of the 95% CI of the GMC ratio (Cecolin 9 vs Gardasil 9) at a margin of 0·5 and a seroconversion rate difference (Cecolin 9-Gardasil 9) at a margin of -5%. This study was registered at ClinicalTrials.gov (NCT04782895) and is completed. FINDINGS: From March 14 to 18, 2021, a total of 553 potential participants were screened, of which 244 received at least one dose of Cecolin 9 and 243 received at least one dose of Gardasil 9. The seroconversion rates for all HPV types in both groups were 100% in the PPS-I, with the values of the lower limits of 95% CIs for seroconversion rate differences ranging between -1·8% and -1·7%. The GMC ratios of five types were higher than 1·0, with the highest ratio, for HPV 58, at 1·65 (95% CI 1·38-1·97), and those of four types were lower than 1·0, with the lowest ratio, for HPV 11, at 0·79 (0·68-0·93). The incidence of adverse reactions in both groups was similar (43% [104/244] vs 47% [115/243]). INTERPRETATION: Cecolin 9 induced non-inferior HPV type-specific immune responses compared with Gardasil 9 and is a potential candidate to accelerate the elimination of cervical cancer by allowing for global accessibility to 9-valent HPV vaccinations, especially in low-income and middle-income countries. FUNDING: National Natural Science Foundation, Fujian Provincial Natural Science Foundation, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Feminino , Escherichia coli , Papillomavirus Humano , Infecções por Papillomavirus/epidemiologia , Método Simples-Cego , China , Imunogenicidade da Vacina , Anticorpos Antivirais , Método Duplo-CegoRESUMO
Purpose: The present study was performed to detect the prevalence of myopia among primary-school students in Xi'an, north-western of China. Methods: The present study was a school-based study with students aged from 6 to 13 years old. All the individuals underwent ophthalmological examination and spherical equivalent (SE) of refractive error were measured with non-cycloplegic refraction. Myopia was defined as a SE of ≤ -0.5 diopters (D), and further divided into three stratified groups based on SE: low myopia (≤ -0.5 to >-3.0 D), moderate myopia (≤ -3.0 to >-6.0 D), and high myopia (≤ -6.0 D). Relative risk factors, including age, sex, grade and ethnicity were investigated using questionnaire. Results: A total of 4,680 individuals were eligible for this survey and 4,654 (99.4% participation rate) were finally included (51.2% boys). The mean age of participants was 8.756 ± 1.727 years. The whole city-level prevalence of total myopia was 57.1% (95% CI: 55.7-58.6%). Additionally, the prevalence of low, moderate, and high myopia was 45.0% (95% CI: 43.5-46.4%), 11.1% (95% CI: 10.2-12.0%), and 1.0% (95% CI: 0.7-1.3%), respectively. Moreover, grade (education level) instead of age, sex and ethnicity was the most essential risk factor for prevalence of overall myopia (OR = 1.844, 95% CI: 1.605-2.119), and an increase of prevalence by 84.4% per grade was seen. Furthermore, similar associations of grade were significant with low myopia (OR = 1.613, 95% CI: 1.385-1.877) and moderate myopia (OR = 2.186, 95% CI: 1.693-2.823), meanwhile, prevalence of low myopia and moderate myopia demonstrated an increase of prevalence by 61.3 and 118.6% per grade, respectively. None of the factors included in the present study was significant risk factor for high myopia. Conclusions: The present study investigated a non-negligible high prevalence of myopia among primary-school students in Xi'an, north-western of China, and a gradual increasing in proportion with education level.
Assuntos
Miopia , Masculino , Humanos , Criança , Adolescente , Feminino , Prevalência , Miopia/epidemiologia , Estudantes , China/epidemiologia , EscolaridadeRESUMO
The function and mechanism of sodium cantharidininate (SC) underlying its suppression of human osteosarcoma (OS) MG63 cells were investigated for the first time in the present study. MG63 cell proliferation was determined by WST1 assay post SC treatment at 0, 12, 24, 48 and 72 h. The results showed that SC effectively inhibited MG63 cell proliferation and induced cell cycle arrest at the G0/G1 phase in a dosedependent manner. Western blotting revealed that SC induced MG63 cell cycle arrest at the G0/G1 phase by means of inhibition of cyclin D1, CDK4 and CDK6 expression. The expression of MAPK and AKT were evaluated using western blotting and FACS experiments to determine whether such signaling pathways are involved in the antiproliferative action of SC on MG63 cells. SC significantly inhibited the phosphorylation of AKT, but not mTOR, JNK or P38. PI3K/AKT stimulator, IGF1, reversed the SCinduced cell cycle arrest in the MG63 cells. Collectively, our data indicate that the phosphorylation of AKT was inhibited by SC, consequently decreasing the expression of cyclin D1, CDK4 and CDK6 and inducing MG63 cell G0/G1 phase arrest. SC has potential as a treatment agent for human osteosarcoma.
RESUMO
Osteosarcoma is a serious malignancy in pediatric patients, which comprises 2.4% of fatal cancer in children and achieves 20% of all primary bone cancers. In the present study, we employed three human osteosarcoma cell lines MG63, HOS and U2OS for susceptibility to cytolytic activity of freshly isolated healthy donor NK cells. Cells were lysed by NK cells in a dose dependent manner. MG63 cells exhibited less susceptibility to NK cells than HOS and U2OS cells at all cell ratios. The specific mechanism underlying the effects of NK cells on osteosarcoma cells was determined by antibody blockage experiments. The results revealed that granzyme B was the key factor in the NK cellinduced cytotoxicity of human osteosarcoma cells. To the best of our knowledge, the present study is the first to investigate the expression of PDL1 in MG63, HOS and U2OS cells. The relative expression of the PDL1 gene and protein in MG63 cell was greater than HOS and U2OS cells. The specific lysis of human osteosarcoma cells induced by NK cells was enhanced when PDL1/PD1 was blocked by the PDL1 antibody. The present study proposed that the PDL1/PD1 axis serves an important role in NK cellinduced cytotoxicity in osteosarcoma via granzyme B secretion. Our findings may contribute to the development of precise treatments for osteosarcoma based on the expression profile of PDL1 in patients with this disease.
Assuntos
Antígeno B7-H1/genética , Neoplasias Ósseas/imunologia , Granzimas/metabolismo , Células Matadoras Naturais/citologia , Osteossarcoma/imunologia , Receptor de Morte Celular Programada 1/genética , Adulto , Apoptose , Antígeno B7-H1/metabolismo , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Relação Dose-Resposta a Droga , Humanos , Células Matadoras Naturais/imunologia , Masculino , Osteossarcoma/genética , Osteossarcoma/terapia , Receptor de Morte Celular Programada 1/metabolismo , Adulto JovemRESUMO
Engineering novel scaffolds that can mimic the functional extracellular matrix (ECM) would be a great achievement in bone tissue engineering. This paper reports the fabrication of novel collagen/chitosan/ß-tricalcium phosphate (CCTP) based tissue engineering scaffold. In order to improve the regeneration ability of scaffold, we have embedded raloxifene (RLX)-loaded PLGA microsphere in the CCTP scaffold. The average pore of scaffold was in the range of 150-200µm with ideal mechanical strength and swelling/degradation characteristics. The release rate of RLX from the microsphere (MS) embedded scaffold was gradual and controlled. Also a significantly enhanced cell proliferation was observed in RLX-MS exposed cell group suggesting that microsphere/scaffold could be an ideal biomaterial for bone tissue engineering. Specifically, RLX-MS showed a significantly higher Alizarin red staining indicating the higher mineralization capacity of this group. Furthermore, a high alkaline phosphatase (ALP) activity for RLX-MS exposed group after 15days incubation indicates the bone regeneration capacity of MC3T3-E1 cells. Overall, present study showed that RLX-loaded microsphere embedded scaffold has the promising potential for bone tissue engineering applications.