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GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14. The structure of AA-14-GPR101-Gs provides direct evidence of the AA-14 binding at the side pocket. Functionally, AA-14 partially restores the functions of GH/IGF-1 axis and exhibits several rejuvenating effects in wild-type mice, which are abrogated in Gpr101-deficient mice. In summary, we provide a structural basis for the constitutive activity of GPR101. The structure-facilitated identification of GPR101 agonists and functional analysis suggest that targeting this orphan receptor has rejuvenating potential.
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Receptores Acoplados a Proteínas G , Camundongos , Animais , Microscopia Crioeletrônica , Receptores Acoplados a Proteínas G/metabolismo , LigantesRESUMO
A switchable and tunable dual-function absorber/polarization converter is presented in this work. The constitution of the structure, which incorporates patterned graphene and photosensitive silicon (Si), can minimize undesired optical losses. Simulated results show that when the Si is metallic, the structure behaves as a broadband absorption of more than 90% in the range of 1.45-3.36 THz. Its peak absorption can be tuned from 22% to 99.8% by changing the Fermi energy of graphene. Furthermore, the interference theory analyzes the physical mechanism for broadband absorption. When the Si is in the dielectric state, the structure has a transmission polarization conversion function, which realizes the conversion from linear to cross-polarized waves. The polarization conversion ratio (PCR) is greater than 90% in the 3.82-4.43 THz range. Meanwhile, the cross-polarization transmission can be dynamically tuned from 28% to 97%, and the PCR can also be tuned from 17% to 99.9% by adjusting the conductivity of the Si. The reason for realizing polarization conversion is explained by the polarization decomposition method. This study provides a design opinion of high-performance multifunctional tunable terahertz devices.
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OBJECTIVE: To investigate the role of the lncRNA MEG3 (MEG3) in opposing the biochemical processes thought to be involved in the development of atherosclerosis (AS). METHODS: Thirty patients with AS and thirty healthy control subjects were enrolled in this study. The expression of MEG3, miR-200b-3p and ABCA1 was analyzed by RT-qPCR in the individuals and the macrophages-derived foam cells. Lipid accumulation was detected by oil red O staining. Cholesterol efflux was measured by ELISA assay in the foam cells. Expression of miR-200b-3p was identified by sequencing. Targeting relationships were determined by dual luciferase assay between MEG3 and miR-200b-3p, miR-200b-3p and ABCA1. RESULTS: In the patients with AS, MEG3 and ABCA1 expression were decreased and miR-200b-3p expression was upregulated. Foam cells transfected with an expression vector (pcDNA3.1) containing MEG3 (pcDNA3.1-MEG3) induced decrease of lipid accumulation and increase of cholesterol efflux compared to cells transfected with control plasmid alone. Foam cells transfected by pcDNA3.1-MEG3 also showed decreased miR-200b-3p and increased ABCA1 expression. Interestingly, co-expression of miR-200b-3p partially prevented these effects of MEG3 expression. CONCLUSION: Expression of MEG3 is downregulated in the patients with AS and foam cells. Overexpressed MEG3 may act as an anti-atherosclerotic factor by reducing lipid accumulation and accelerating cholesterol efflux through the miR-200b-3p/ABCA1 axis.
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Aterosclerose , MicroRNAs , Humanos , Aterosclerose/genética , Bioensaio , Colesterol , Lipídeos , MicroRNAs/genéticaRESUMO
BACKGROUND: Whether slim the face or not after removed third molars is the concern of some orthodontic treatment candidates. The aim of this article is to explore the volume changes of facial soft and hard tissues after third molars extraction, as well as develop a reproducible clinical protocol to precisely assess facial soft tissue volume change. METHODS: A non-randomized, non-blind, self-controlled pilot study was conducted. 24 adults aged 18-30 had ipsilateral third molars extracted. The body weight change was controlled within 2 kg. Structured light scans were taken under a standardized procedure pre-extraction (T0), three (T1), and six (T2) months post-extraction; CBCTs were taken at T0 and T2. The projection method was proposed to measure the soft tissue volume (STV) and the soft tissue volume change (STVC) by the Geomagic software. The hard tissue volume change (HTVC) was measured in the Dragonfly software. RESULTS: The final sample size is 23, including 5 males (age 26.6 ± 2.5 years) and 18 females (age 27.3 ± 2.5 years). The HTVC was - 2.33 ± 0.46ml on the extraction side. On the extraction side, the STV decreased by 1.396 (95% CI: 0.323-2.470) ml (P < 0.05) at T1, and increased by 1.753 (95% CI: -0.01-3.507) ml (P = 0.05) at T2. T2 and T0 had no difference (P > 0.05). The inter and intra-raters ICC of the projection method was 0.959 and 0.974. There was no correlation between the STVC and HTVC (P > 0.05). CONCLUSIONS: After ipsilateral wisdom teeth extraction, the volume of hard tissue on the extraction side reduces, and the volume of facial soft tissue does not change evidently. However, further research with large sample size is still needed. The STV measurement has excellent repeatability. It can be extended to other interested areas, including forehead, nose, paranasal, upper lip, lower lip and chin, which is meaningful in the field of orthodontics and orthopedics. TRIAL REGISTRATION: ChiCTR, ChiCTR1800018305 (11/09/2018), http://www.chictr.org.cn/showproj.aspx?proj=28868 .
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Assistência Odontológica , Feminino , Humanos , Masculino , Queixo , Lábio , Projetos Piloto , AdultoRESUMO
In this study, the integrated three-in-one (temperature, humidity, and wind speed) microsensor was made through the technology of the Micro-electro-mechanical Systems (MEMS) to measure three important physical quantities of the internal environment of the cold air pipe of the Heating, Ventilation and Air Conditioning (HVAC) in the factory, plan the installation positions of the integrated three-in-one microsensor and commercially available wind speed sensor required by the internal environment of the cold air pipe, and conduct the actual 310-h long term test and comparison. In the experiment, it was also observed that the self-made micro wind speed sensor had higher stability compared to the commercially available wind speed sensor (FS7.0.1L.195). The self-made micro wind speed sensor has a variation range of ±200 mm/s, while the commercially available wind speed sensor a variation range of ±1000 mm/s. The commercially available wind speed sensor (FS7.0.1L.195) can only measure the wind speed; however, the self-made integrated three-in-one microsensor can conduct real-time measurements of temperature and humidity according to the environment at that time, and use different calibration curves to know the wind speed. As a result, it is more accurate and less costly than commercially available wind speed sensors. The material cost of self-made integrated three-in-one microsensor includes chemicals, equipment usage fees, and wires. In the future, factories may install a large number of self-made integrated three-in-one microsensors in place of commercially available wind speed sensors. Through real-time wireless measurements, the self-made integrated three-in-one microsensors can achieve the control optimization of the HVAC cold air pipe's internal environment to improve the quality of manufactured materials.
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OBJECTIVE: To compare clinical efficacy of platelet-rich plasma (PRP) and extracorporeal shock wave in treating chronic insertional Achilles tendinopathy. METHODS: From February 2019 to August 2021, 42 patients with chronic insertional Achilles tendinopathy were selected and divided into PRP group(20 patients, 28 feet) and shock wave group (22 patients, 29 feet). In PRP group, there were 12 males and 8 females, aged 47.00(28.00, 50.75) years old, and the courses of disease ranged 7.00(6.00, 7.00) months;PRP injection was performed in the Achilles tendon stop area of the affected side. In shock wave group, there were 16 males and 6 females, aged 42.00(35.75, 47.25) years old;and the courses of disease was 7.00(6.00, 8.00) months;shock wave was performed in Achilles tendon stop area of the affected side and triceps surae area. Visual analogue scale (VAS) and Victorian Institute of Sport Assessment-Achilles (VISA-A) were applied to evaluate clnical effect before treatment, 1, 3 and 6 months after treatment, and satisfaction of patients was investigated. RESULTS: VAS and VISA-A score in both groups were significantly improved at 1, 3 and 6 months after treatment than before treatment (P<0.05), VAS and VISA-A score in PRP group at 6 months after treatment were significantly higher than those at 1 and 3 months after treatment, and VAS and VISA-A score in shock wave group were lower than those at 1 and 3 months after treatment (P<0.05). There was no significant difference in VAS and VISA-A score between two groups before treatment, 1 and 3 months after treatment(P>0.05), while VAS and VISA-A score in PRP group were better than those in shock wave group at 6 months after treatment(P<0.05), and the satisfaction survey in PRP group was better than that in shock wave group(P<0.05). CONCLUSION: PRP injection has a good clinical effect on chronic insertional Achilles tendinopathy with high patient satisfaction, and medium-and long-term effect of PRP injection for the treatment of chronic insertional Achilles tendinopathy is better than that of extracorporeal divergent shock wave.
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Tendão do Calcâneo , Plasma Rico em Plaquetas , Tendinopatia , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Tendinopatia/terapia , Resultado do Tratamento , Terapia por ExercícioRESUMO
A wireless flexible air velocity microsensor was developed by using micro-electro-mechanical systems (MEMS) technology. Polyimide (PI) material was selected for the waterproof and oilproof requirements of the cold air duct environment of heating, ventilation, and air conditioning (HVAC) systems, and then a wireless flexible micro air velocity sensor was completed. To obtain real-time wireless measurements of the air velocity inside the cold air ducts of an HVAC system, and to create a measurements database, the deployment locations and quantity of micro air velocity sensors for the internal environment of the cold air ducts were planned. A field domain verification was performed to optimize the internal environment control of the cold air ducts of ventilation and air conditioning systems and to enhance the quality and reliability of process materials. This study realized real-time monitoring of velocity in the HVAC ducts of a chemical-fiber plant. A commercial velocity sensor (FS7.0.1L.195) was purchased and a micro-electro-mechanical systems (MEMS) approach was also used to develop a home-built micro air velocity sensor, to optimize the provision of the commercial sensors and our home-built micro air velocity sensor. Comparing the specifications of the two commercially available sensors with our home-built micro air velocity sensor, the results show that the home-built micro air velocity sensor has the advantages of fast response time, simultaneous sensing of three important physical quantities, and low cost.
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OBJECTIVE: To explore clinical effect of rotational Scarf osteotomy in treating hallux valgus (HV) with rotation of the first metatarsal bone. METHODS: From January 2018 to October 2019, 35 patients (40 feet) with HV and rotation deformity of the first metatarsal were treated with rotational Scarf osteotomy, including 5 males and 30 females;aged from 25 to 76 years old with an average of (40.32±5.43) years old. Hallux valgus angle(HVA), intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), the first metatarsal length (FML) were observed and compared, American Orthopedic Foot and Ankle Society(AOFAS) of hallux metatarsophalangeal interphalangeal joint score and visual analogue scale (VAS) were used to evaluate functional evaluation. RESULTS: Thirty-five patients(40 feet) were followed up from 12 to 36 months with an average of (14.35±3.62) months. HVA, IMA and DMAA were corrected from (36.32±4.51) °, (14.21±3.22) ° and (28.35±4.32) ° before operation to (14.32±5.71) °, (5.83±3.97) ° and (7.32±2.14) ° after operation respectively (P<0.05). There was no satistical difference in FML before and after operation (P>0.05). AOFAS score and VAS improved from (57.00±4.31) and (6.00±1.21) before operation to (90.31±3.28) and (1.42±0.83) after operation, respectively, and had significant difference(P<0.05);according to AOFAS score, 23 feet got excellent results, 15 feet good and 2 feet fair. CONCLUSION: Rotational Scarf osteotomy with strong correction and high dimension could effectively correct HV combined with rotation deformity of the first metatarsal bone, improve function of the forefoot, and obtain good clinical results.
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Joanete , Hallux Valgus , Ossos do Metatarso , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Hallux Valgus/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Fluormetolona , Rotação , Resultado do Tratamento , Radiografia , Osteotomia/métodosRESUMO
Chronic low back pain (CLBP) is a common symptom of lumbar degenerative disease. Degeneration of the lumbar paravertebral muscles causes a loss of muscle mass and strength, which is a vital factor causing CLBP and often accompanied by lipid infiltration. Tandem mass spectrometry (TMT) was used to identify differentially expressed proteins in lipid-infiltrated and normal muscles. The results show that fatty acid binding protein 4 (FABP4) participated in the peroxisome proliferator-activated receptor-γ (PPAR γ) signaling pathway as an up-regulated protein, which is related to lipogenesis in diverse cells. In addition, chronic inflammation is believed to be involved in lumbar muscle degeneration and lipogenesis, with interleukin-4 (IL-4) considered as the predominant contributor. In present study, we investigate the effect of FABP4 on lipogenesis in human skeletal muscle cells (HSMCs) stimulated by Interleukin-4 (IL-4) and explore the mechanistic basis. We found expression level of FABP4 in lipid-infiltrated muscles was significantly higher than that in normal muscles. Lipogenesis in HSMCs could be increased by IL-4 treatment, as well as by FABP4 overexpression. FABP4 inhibition suppressed IL-4-mediated lipogenesis in HSMCs, whereas the PPAR γ inhibitor alleviated lipogenesis in both IL-4-treated and FABP4-overexpressed HSMCs. Collectively, the results indicate that FABP4 induces lipogenesis in HSMCs stimulated with IL-4 via activating the PPAR γ signaling pathway. Our study offers a detailed perspective on the pathogenesis of muscle lipid infiltration and provides a potential target for the clinical treatment strategy of muscle lipid infiltration and CLBP.
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Interleucina-4 , PPAR gama , Proteínas de Ligação a Ácido Graxo/genética , Humanos , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Lipídeos , Lipogênese , Músculo Esquelético/metabolismo , PPAR gama/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: To evaluate lumbar mobility in various positions using upright left and right bending radiographs in patients with degenerative lumbar spondylolisthesis (DLS), as well as to assess the impact of lateral instability on patient-reported outcomes. METHODS: This study retrospectively reviewed a consecutive series of patients with DLS between January 2019 and October 2020. The enrolled patients were divided into two groups: the lateral instability group (group L) and non-lateral instability group (group NL). Translational and angular motion in both sagittal and coronal planes and patient-reported outcomes were compared between the two groups. RESULTS: There were 104 (59.8%) patients in group L and 70 (40.2%) patients in group NL, with an average age of 60.6 ± 7.8 years. Patients with a right bending posture in group L had a higher slip percentage (14.2 ± 7.4% vs 9.2 ± 3.2%, p = 0.01) and slip angle (6.3 ± 1.5° vs 2.2 ± 0.8°, p = 0.021). Compared with group NL, group L demonstrated significantly larger angular motion in the coronal plane (2.4 ± 1.3° vs 1.0 ± 0.7°, p = 0.008). Patients with lateral instability had worse preoperative back pain (6.1 ± 1.6 vs 2.7 ± 1.9, p = 0.01) and Oswestry Disability Index (ODI) scores (37.7 ± 5.5 vs 25.6 ± 2.6, p = 0.002). In terms of pain characteristics, group L was characterized by pain when getting out of a car, when rising from a chair, and when climbing stairs (all p values < 0.05). CONCLUSION: Lumbar lateral instability, that is, increased mobility in the coronal plane on lateral bending radiographs, translational and/or angular, correlates to more pronounced patient related symptoms in degenerative L4-5 spondylolisthesis. The existence of lumbar lateral instability leads to worse impacts on patient-reported outcomes when patients change their positions including getting out of a car, rising from a chair, and climbing stairs.
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Degeneração do Disco Intervertebral , Espondilolistese , Idoso , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral , Pessoa de Meia-Idade , Estudos Retrospectivos , Espondilolistese/diagnóstico por imagemRESUMO
INTRODUCTION: A standardized procedure was proposed to control involuntary motion and other factors during the capture of structural light scanning that could influence the morphology of 3-dimensional facial models; interoperator reproducibility was evaluated. METHODS: Twenty subjects volunteered for facial scanning. Three researchers scanned each volunteer 3 times on the same day using the FaceScan structural light scanning system (Isravision, Darmstadt, Germany) and after the proposed procedure. Captures were done at 5-minute intervals. The 3 facial scans acquired by the same researcher were compared by reverse engineering software (Geomagic; 3D Systems, Rock Hill, SC). Six facial regions, including forehead, nose, paranasal, upper lip, lower lip and chin, and cheek, were divided. With the first scan as a reference, the other 2 scans were registered, and surface-to-surface distance maps were acquired to calculate the mean, standard deviation, and root mean squares (RMS) between 2 surfaces. The reproducibility between 3 researchers was then evaluated by a 1-way analysis of variance. RESULTS: The mean of 6 facial regions was close to 0. The RMS of lip regions were largest (0.48-0.53 mm), the forehead was smallest (0.21 mm), and the others ranged 0.37 mm to 0.42 mm. The standard deviation was slightly smaller than RMS and had the same trend of change. There was no significant difference in RMS among the 3 researchers (P >0.05). CONCLUSIONS: With the constraint of the standardized procedure, the morphologic reproducibility of facial models in 6 regions was satisfying.
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Face , Imageamento Tridimensional , Face/anatomia & histologia , Face/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Lábio/anatomia & histologia , Nariz/anatomia & histologia , Nariz/diagnóstico por imagem , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Ankylosing spondylitis (AS) is a systematic and rheumatic disease, which causes multiple symptoms. However, dysphagia due to the formation of a giant anterior cervical osteophyte is rare in patients with AS. CASE SUMMARY: We present the case of a 65-year-old male patient who was diagnosed with AS and visited the hospital with a complaint of progressive dysphagia. The appropriate imaging examinations indicated that a giant anterior cervical osteo-phyte at C3-4 caused esophageal compression, which led to dysphagia. An operation for resection was performed without complications. CONCLUSION: This case demonstrates that a large cervical osteophyte may be the cause of dysphagia in patients with AS, and early accurate diagnosis and surgical treat-ment are very important for the improvement of symptoms. Anterior cervical discectomy and fusion are extremely effective and should be taken into consideration.
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OBJECTIVE: To report the radiological and clinical outcomes of the modified scarf osteotomy for the treatment of hallux valgus deformity in adolescents. METHODS: This retrospective study analyzed 21 patients (31 feet) who underwent a modified scarf osteotomy for correcting juvenile hallux valgus deformity between March 2015 and January 2017. There were 3 male (3 feet) and 18 female (28 feet) patients. The average age at the time of surgery was 28.6 years (range, 20-35). Patients were postoperatively followed up in the outpatient department for 12-18 months. Clinical and radiological assessments were performed preoperatively and postoperatively at 1 year. Moreover, postoperative complications were recorded. Statistical analyses for differences between preoperative and postoperative values were performed. RESULTS: All the 21 patients were postoperatively followed up for 12-18 months, with an average of 13.2 ± 2.5 months. Clinical assessment showed that the American Orthopaedic Foot and Ankle Society score was increased from preoperative 58.0 ± 5.8 to postoperative 94.2 ± 6.6 points, respectively, and the visual analog scale score was remarkably decreased from preoperative 6.0 ± 2.0 to postoperative 1.5 ± 2.0 points at 1 year follow-up. Further radiological assessment showed that the hallux valgus angle was 37.5° ± 9.2°, 14.1° ± 6.5°, and 14.5° ± 6.5° before surgery, half a year after surgery, and 1 year after surgery, respectively; the intermetatarsal angle was 14.1° ± 4.4°, 4.8° ± 3.2°, and 5.5° ± 4.9°, respectively; and the distal metatarsal articular angle was 31.0° ± 3.5°, 7.2° ± 2.3°, and 7.5° ± 2.1°, respectively. They were significantly improved at half a year after surgery and 1 year after surgery compared to those before surgery. Complications occurred in two patients (9.5%) who had numbness on the skin of the edge of the medial incision, and the symptoms were relieved after 10 months. There was no clinical recurrence in all patients. One of the 31 feet had hallux varus, which was corrected in a second operation. Notably, a postoperative radiograph of a typical case whose both feet had hallux valgus deformity and underwent modified scarf osteotomy and additional Akin osteotomy showed adequate correction of the hallux valgus angle (HVA, 11°), intermetatarsal angle (IMA, 6°), and distal metatarsal articular angle (DMAA, 8°) on left foot compared to preoperative HVA (28°), IMA (13°), and DMAA (35°). CONCLUSION: The modified scarf osteotomy can effectively correct the adolescent hallux valgus deformity, which is worth popularizing.
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Hallux Valgus/cirurgia , Ossos do Metatarso/cirurgia , Osteotomia/métodos , Adulto , Avaliação da Deficiência , Feminino , Hallux Valgus/diagnóstico por imagem , Humanos , Masculino , Ossos do Metatarso/diagnóstico por imagem , Medição da Dor , Radiografia , Estudos Retrospectivos , Adulto JovemRESUMO
Osteosarcoma (OS) is the most common primary malignant bone tumor. Numerous studies have strongly implicated the ectopic expression of microRNAs (miRNAs/miRs), including miR-885-5p, which is aberrantly expressed in several cancer types, in multiple cancer-related processes. However, the role of miR-885-5p in OS remains unknown. In the present study, it was found that the expression of miR-885-5p was markedly upregulated in OS cell lines and clinical tissues. Moreover, high expression of miR-885-5p was significantly associated with the development of OS. The human OS MG-63 cell line was transfected with recombinant lentivirus to regulate miR-885-5p expression. Overexpressed miR-885-5p significantly promoted the proliferation and migration of MG-63 cells in vitro, while downregulating miR-885-5p expression reversed these effects. Furthermore, bioinformatic analysis was used to predict the potential target genes of miR-885-5p, and cell division cycle protein 73 homolog (CDC73) was identified as a novel and direct target of miR-885-5p. This interaction was further confirmed using reverse transcription-quantitative polymerase chain reaction, western blotting and luciferase activity assays. These findings suggest that miR-885-5p serves a critical role in facilitating OS proliferation and migration, and can regulate CDC73 expression in OS cells and tissues. Thus, miR-885-5p could be a promising novel therapeutic biomarker for OS.
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In the practical application of quantum entanglement, entangled particles usually need to be distributed to many distant parties or stored in different quantum memories. In these processes, entangled particles unavoidably interact with their surrounding environments, respectively. We here systematically investigate the entanglement-decay laws of cat-like states under independent Pauli noises with unbalanced probability distribution of three kinds of errors. We show that the robustness of cat-like entangled states is not only related to the overall noise strength and error distribution parameters, but also to the basis of qubits. Moreover, we find that whether a multi-qubit state is more robust in the computational basis or transversal basis depends on the initial entanglement and number of qubits of the state as well as the overall noise strength and error distribution parameters of the environment. However, which qubit basis is conductive to enhancing the robustness of two-qubit states is only dependent on the error distribution parameters. These results imply that one could improve the intrinsic robustness of entangled states by simply transforming the qubit basis at the right moment. This robustness-improving method does not introduce extra particles and works in a deterministic manner.
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The prognosis of patients with metastatic osteosarcoma is poor and has shown no significant improvement in nearly 20 years. The human epidermal growth factor (EGF) receptor (HER) family is frequently overexpressed in the majority of human carcinomas, and is involved in promoting the proliferation and survival of cancer cells. However, the role of EGFR and HER-2 expression in osteosarcoma survival remains controversial and no previous study has simultaneously investigated the association of the expression of all the four HER family members with the prognostic significance of osteosarcoma. Therefore, the present study investigated the expression levels of the complete members of the HER family in osteosarcoma specimens, as well as their associations with the clinicopathological parameters, progression-free survival (PFS) and overall survival (OS) time of patients with osteosarcoma. The expression of HER family members was detected in osteosarcoma tumor specimens from 60 patients using immunohistochemistry. The association of the expression of HER receptors in osteosarcoma with clinicopathological parameters was analyzed using χ2 test and Fishers exact test. Survival analyses were evaluated by Kaplan-Meier method and Cox proportional hazards regression model. Overall, 18 (30%), 13 (22%), 23 (38%) and 19 (32%) patients presented with high expression of EGFR, HER-2, HER-3 and HER-4, respectively, and the co-expression of 2, 3 and all 4 members of the HER family was observed. High expression of EGFR and HER-4 was associated with distant metastasis. High HER-3 expression was significantly associated with an advanced Enneking stage and distant metastasis. Multivariate analysis demonstrated that the expression of EGFR, HER-3, HER-4, EGFR/HER-3, EGFR/HER-4 and HER-3/HER-4 was an independent predictor of poor PFS and OS time in osteosarcoma patients with stage I-IIB disease. In patients with stage IIB osteosarcoma, the expression of HER-4 and EGFR/HER-4 demonstrated a more significant effect on PFS and OS time. In conclusion, therapies targeting EGFR, HER-3 and HER-4 may provide promising strategies for primary osteosarcoma.
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AIMS: We aim to investigate the role of microRNA-133a (miR-133a) in intervertebral disc destruction by targeting MMP9 in spinal tuberculosis (TB). MAIN METHODS: Rabbit models with spinal TB were established and assigned to the blank, miR-133a mimic, miR-133a inhibitor and negative control (NC) groups. Primary notochordal cells were extracted and separately transfected with miR-133a mimics, miR-133a inhibitor, miR-nonsense sequence control (NC), si-NC and si-MMP9. QRT-PCR and Western blot assay were used to detect the expression of MMP-9, Collagen I, Collagen II and Collagen-X. Gelatin Zymography was performed to detect MMP9 activity. Immunohistochemistry was used to detect the expression of Collagen I, Collagen II and Collagen-X proteins. Osteoclast morphology and the number of osteoclast cells were observed after Tartrate resistant acid phosphatase staining. KEY FINDINGS: MMP9, Collagen-X and Collagen I expression and MMP9 activity were higher while the expression of Collagen II was lower in the miR-133a mimic group than the miR-NC group. MMP9, Collagen-X Collagen I and MMP9 activities were lower and Collagen II expression was higher in the miR-133a inhibitor group than the miR-NC group. Compared with the si-NC group, the si-MMP9 group showed increased Collagen II expression but decreased expression of MMP9, Collagen-X and Collagen I and MMP9 activity. A reduced amount of osteoclast cells exhibited in the miR-133a mimic group while an increased number was seen in the miR-133a inhibitor group compared to the blank group. SIGNIFICANCE: MiR-133a could inhibit Collagen degradation by down-regulating MMP-9 expression to attenuate the destructive effects of spinal TB on intervertebral disc.
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Regulação para Baixo , Regulação Enzimológica da Expressão Gênica , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , MicroRNAs/genética , Animais , Contagem de Células , Colágeno/biossíntese , Feminino , Disco Intervertebral/enzimologia , Masculino , Inibidores de Metaloproteinases de Matriz , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Osteoclastos/patologia , Osteoclastos/fisiologia , RNA Interferente Pequeno/agonistas , RNA Interferente Pequeno/antagonistas & inibidores , RNA Interferente Pequeno/genética , Coelhos , Tuberculose da Coluna Vertebral/metabolismo , Tuberculose da Coluna Vertebral/patologiaRESUMO
BACKGROUND: Regenerative techniques help promote the formation of new attachment and bone filling in periodontal defects. However, the dimensions of intraosseous defects are a key determinant of periodontal regeneration outcomes. In this study, we evaluated the efficacy of use of anorganic bovine bone (ABB) graft in combination with collagen membrane (CM), to facilitate healing of noncontained (1-wall) and contained (3-wall) critical size periodontal defects. METHODS: The study began on March 2013, and was completed on May 2014. One-wall (7 mm × 4 mm) and 3-wall (5 mm × 4 mm) intrabony periodontal defects were surgically created bilaterally in the mandibular third premolars and first molars in eight beagles. The defects were treated with ABB in combination with CM (ABB + CM group) or open flap debridement (OFD group). The animals were euthanized at 8-week postsurgery for histological analysis. Two independent Student's t-tests (1-wall [ABB + CM] vs. 1-wall [OFD] and 3-wall [ABB + CM] vs. 3-wall [OFD]) were used to assess between-group differences. RESULTS: The mean new bone height in both 1- and 3-wall intrabony defects in the ABB + CM group was significantly greater than that in the OFD group (1-wall: 4.99 ± 0.70 mm vs. 3.01 ± 0.37 mm, P < 0.05; 3-wall: 3.11 ± 0.59 mm vs. 2.08 ± 0.24 mm, P < 0.05). The mean new cementum in 1-wall intrabony defects in the ABB + CM group was significantly greater than that in their counterparts in the OFD group (5.08 ± 0.68 mm vs. 1.16 ± 0.38 mm; P < 0.05). Likewise, only the 1-wall intrabony defect model showed a significant difference with respect to junctional epithelium between ABB + CM and OFD groups (0.67 ± 0.23 mm vs. 1.12 ± 0.28 mm, P < 0.05). CONCLUSIONS: One-wall intrabony defects treated with ABB and CM did not show less periodontal regeneration than that in 3-wall intrabony defect. The noncontained 1-wall intrabony defect might be a more discriminative defect model for further research into periodontal regeneration.