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A FMCW LiDAR system of both the distributed feedback laser and external cavity laser is established in baseband beat notes, rather than up-conversion to an intermediate frequency to exclude flicker noise. Meanwhile, utilizing fast-scanning MEMS mirrors, high-quality real-time (1 fps) 4-D images of the slow-moving object (10 mm/s) can be directly constructed at the baseband with a central frequency as low as 100 kHz and a small Doppler shift. The proposed LiDAR architecture based on such a low-frequency baseband significantly improves the optical power budget on the transmitter side and eliminates the costly high-speed sampling circuits on the receiver side.
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This paper proposes a passive optical brightening element design, a non-axisymmetric freeform lens (NAFL), arranged and assembled on a traditional traffic sign. NAFL is the first optical design which can effectively solve the traffic problem that direct sunlight affects the driver's inability to look directly at the traffic sign. The NAFL can converge the sunlight behind the traffic sign and diverge forward to 150 meters away. In this way, the NAFL array combinations on the traffic sign can directly rely on sunlight as image information pixels. According to the simulation, the optical efficiency of the NAFL can be as high as 81.5%. Besides, the angular tolerance is also analyzed to evaluate the working hours of the NAFL. Finally, we made the prototype and proved that such passive brightening components could effectively improve the traffic sign's visibility in harsh sunlight.
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BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer and poses a threat to the health and survival of humans. Mitochondrial ribosomal protein L48 (MRPL48) belongs to the mitochondrial ribosomal protein family, which participates in energy production. Studies have shown that MRPL48 can predict osteosarcoma incidence and prognosis, as well as promotes colorectal cancer progression. However, the role of MRPL48 in HCC remains unknown. METHODS: TCGA, GEO, HCCDB, CPTAC, SMART, UALCAN, Kaplan-Meier plotter, cBioPortal, and MethSurv were performed for bioinformatics purposes. Quantitative RT-PCR, immunoblotting, and functional studies were conducted to validate the methodology in vitro. RESULTS: MRPL48 was greatly overexpressed in HCC tissues, compared with healthy tissue, which was subsequently demonstrated in vitro as well. The survival and regression analyses showed that MRPL48 expression is of significant clinical prognostic value in HCC. The ROC curve and nomogram analysis indicated that MRPL48 is a powerful predictor of HCC. MRPL48 methylation was adversely associated with the expression of MRPL48, and patients with a low level of methylation had poorer overall survival than those with a high level of methylation. GSEA showed that the expression of the MRPL48 was correlated with Resolution of Sister Chromatid Cohesion, Mitotic Prometaphase, Retinoblastoma Gene in Cancer, RHO Gtpases Activate Formins, Mitotic Metaphase and Anaphase, and Cell Cycle Checkpoints. An analysis of immune cell infiltration showed a significant association between MRPL48 and immune cell infiltration subsets, which impacted the survival of HCC patients. Additionally, MRPL48 knockdown reduced HCC cell proliferation, migration, and invasion in vitro. CONCLUSIONS: We demonstrated that MRPL48 expression may be associated with HCC development and prognosis. These findings may open up new research directions and opportunities for the development of HCC treatments.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Prognosis , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Biomarkers , Ribosomal ProteinsABSTRACT
OBJECTIVE: To observe the clinical efficacy of Tiaohe Yinyang acupotomy (acupotomy for regulating and harmonizing yin and yang) for knee osteoarthritis (KOA). METHODS: A total of 88 patients with KOA were randomized into a acupotomy group and a sham-acupotomy group, 44 cases in each group. In the acupotomy group, acupotomy was applied at yin side (4-5 high stress points i.e. pes anserinus and terminal of popliteus) and yang side (1-2 high stress points i.e. stimulation point of infrapatellar ligament and suprapatellar bursa) of knee joint. In the sham-acupotomy group, sham-acupotomy was applied at the same points as the acupotomy group. The treatment was given once a week for 2 weeks in the two groups. Before and after treatment, the Western Ontario and McMaster Universities arthritis index (WOMAC) score, visual analogue scale (VAS) score, thickness of medial and lateral collateral ligaments of knee joint, motion range of knee joint and plantar pressure distribution were observed in the two groups. In the follow-up of 3 months after treatment, the WOMAC and VAS scores were recorded in the acupotomy group. RESULTS: After treatment, the sub item scores (pain, stiffness and function) and total scores of WOMAC and VAS scores were decreased in the both groups (P<0.05), pain score, function score and total score of WOMAC and VAS score in the acupotomy group were lower than those in the sham-acupotomy group (P<0.05). Before and after treatment, there were no statistical differences in thickness of medial and lateral collateral ligaments of knee joint and motion range of knee joint between the two groups (P>0.05). After treatment, the plantar medial pressure was increased while the plantar lateral pressure was decreased (P<0.05), and the plantar force line moved medially in the acupotomy group. In the follow-up, the sub item scores and total score of WOMAC and VAS score were lower than those before and after treatment in the acupotomy group (P<0.05). CONCLUSION: Tiaohe Yinyang acupotomy can improve the clinical symptoms of knee joint in patients with KOA by changing the local biological stress.
Subject(s)
Pain , HumansABSTRACT
Our previous study has confirmed that astrocytes overexpressing neurogenic differentiation factor 1 (NEUROD1) in the spinal cord can be reprogrammed into neurons under in vivo conditions. However, whether they can also be reprogrammed into neurons under in vitro conditions remains unclear, and the mechanisms of programmed conversion from astrocytes to neurons have not yet been clarified. In the present study, we prepared reactive astrocytes from newborn rat spinal cord astrocytes using the scratch method and infected them with lentivirus carrying NEUROD1. The results showed that NEUROD1 overexpression reprogrammed the cultured reactive astrocytes into neurons in vitro with an efficiency of 13.4%. Using proteomic and bioinformatic analyses, 1952 proteins were identified, of which 92 were differentially expressed. Among these proteins, 11 were identified as candidate proteins in the process of reprogramming based on their biological functions and fold-changes in the bioinformatic analysis. Furthermore, western blot assay revealed that casein kinase II subunit alpha (CSNK2A2) and pinin (PNN) expression in NEUROD1-overexpressing reactive astrocytes was significantly increased, suggesting that NEUROD1 can directly reprogram spinal cord-derived reactive astrocytes into neurons in vitro, and that the NEUROD1-CSNK2A2-PNN pathway is involved in this process. This study was approved by the Animal Ethics Committee of Fujian Medical University, China (approval No. 2016-05) on April 18, 2016.
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Bidens pilosa is an annual invasive and Cd-hyperaccumulator herb. The complete chloroplast genome sequence of the B. pilosa is 150,542 bp in length, which is composed of a large single-copy region of 83,542 bp, a small single-copy region of 17,624 bp and a pair of inverted repeat regions of 24,688 bp. It encodes a set of 114 genes, consisting of 80 protein coding, 30 tRNA and 4 rRNA genes. Among all of these genes, 2 genes possess double introns, and 16 genes have a single intron. Phylogenetic analysis showed that B. pilosa clustered together with Marshallia obovata.
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BACKGROUND: Survival in elderly patients undergoing sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) has not been specifically analyzed. This study aimed to explore the association between different types of axillary lymph node (ALN) evaluations and survival of elderly breast cancer patients. METHODS: A retrospective cohort study was conducted of invasive ductal breast cancer patients 70 years and older in the Surveillance, Epidemiology, and End Results database (2004-2016). Analyses were performed to compare the characteristics and survival outcomes of patients who received surgical lymph node dissection and those who did not. Breast cancer specific survival (BCSS) and overall survival were compared by using Cox proportional hazards regression analysis and propensity score matching (PSM) methods to account for selection bias from covariate imbalance. RESULTS: Of the 75,950 patients analyzed, patients without ALN evaluation had a significantly worse prognosis, while there was no significant difference for BCSS between using a sentinel lymph node biopsy (SLNB) and an axillary lymph node dissection (ALND) after adjustment for known covariates [adjusted hazard ratio (HR) = 0.991, 95% confidence interval (CI) = 0.925-1.062, p = 0.800]. In the stratification analyses after PSM, the ALND did not show a significant BCSS advantage compared with SLNB in any subgroups except for the pN1 stage or above. Furthermore, after PSM of the pN1 stage patients, SLNB was associated with a significantly worse BCSS in hormone receptor negative (HR-) patients (HR = 1.536, 95%CI = 1.213-1.946, p < 0.001), but not in the hormone receptor positive (HR+) group (HR = 1.150, 95%CI = 0.986-1.340, p = 0.075). CONCLUSION: In our study, ALND does not yield superior survival compared with SLNB for elderly patients with pN1 stage HR+ breast cancer. Although our findings are limited by the bias associated with retrospective study design, we believe that in the absence of results from randomized clinical trials, our findings should be considered when recommending the omission of ALND for elderly breast cancer patients.
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Purpose: The aim of our study was to evaluate the different clinicopathological characteristics and prognostic factors for occult and non-occult breast cancer. Methods: 572 OBC cases and 117,217 non-OBC patients between 2004 and 2015 was selected from Surveillance, Epidemiology, and End Results (SEER) database. We analyzed the clinicopathological characteristics and survival outcomes between OBC and non-OBC patients. Furthermore, the propensity score matching method was utilized to reduce the influences of baseline differences in demographic and clinical characteristics on outcome differences. Univariable and multivariable analyses were used to evaluate the prognostic factors of OBC patients. Results: Compared with non-OBC patients, OBC patients in this study presented a higher proportion of older age, American Joint Committee on Cancer (AJCC) N3 stage, estrogen receptor (ER)-negative status, progesterone receptor (PR)-negative status, and human epidermal growth factor receptor-2 (HER-2)-positive status, and underwent more chemotherapy. Multivariate analysis revealed a better survival in overall patients with OBC patients according to breast cancer-specific survival (BCSS) and overall survival (OS). Propensity score analysis also achieved a similar result for OBC patients. Stratified analyses by nodal status and molecular subtypes indicated that these survival advantage were mainly presented in patients with AJCC N2/N3 stage or hormone receptor (HR)-positive tumors. In addition, nodal status, HER-2 status, and radiation status were demonstrated to be three independent prognostic factors for OBC patients. Conclusion: Patients with OBC retained exclusive clinical characteristics and were shown to have a better outcome compared with non-OBC patients, especially for those with N2/N3 stage or HR-positive tumors.
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PURPOSE: Receptor-interacting protein kinase 1 (RIPK1) is an important upstream regulator of multiple cell signaling pathways including inflammatory signals. RIPK1 is reported to be closely associated with the prognostic implications of cancer, especially epithelial tumors. But its role in proliferation and lymphangiogenesis in cholangiocarcinoma (CCA) remains unclear and requires further investigation. PATIENTS AND METHODS: Expression of RIPK1 in human CCA tissues and CCA cell lines (QBC939, HUH28 and CCPL-1) was measured using qPCR, immunoblotting and immunohistochemistry. Silencing of RIPK1 was achieved by transduction of CCA cells via lentiviral plasmids (LV3-H1/GFP&Puro) encapsulating RIPK1 shRNA (LV-shRIPK1) or negative control shRNA (LV-shNC), and puromycin was used to select stable colonies. Proliferation and lymphangiogenesis were assessed in vitro by CCK-8 and matrigel-based tube formation assays, respectively. Activity of the activation protein-1 (AP-1) was evaluated by double-luciferase reporter gene assay. Protein expression of JNK, P38MAPK, ERK1/2, AP-1, P-AP-1, E-cadherin, N-cadherin and vascular endothelial growth factor-C (VEGF-C) was measured by immunoblotting or ELISA. An orthotopic CCA model in null mice was generated by transplanting QBC939 LV-shRIPK1, LV-shNC and control cells to further evaluate the role of RIPK1 on lymphangiogenesis in vivo. Immunohistochemistry was utilized to evaluate the expression of RIPK1 and VEGF-C, and tumor lymphatic vessels in the CCA model mice. RESULTS: Upregulated expression of RIPK1 in CCA tissues was closely related to tumor size, lymph node metastasis and poor prognosis. RIPK1 promoted proliferation and lymphangiogenesis in CCA cells, and regulated the activation of JNK and P38MAPK-mediated AP-1/VEGF-C pathway. Finally, in vivo animal experiments in the orthotopic CCA mouse model further confirmed the function of RIPK1 in lymphangiogenesis. CONCLUSION: This is the first report demonstrating the role of RIPK1 in proliferation and lymphangiogenesis through the MAPK (JNK and P38MAPK)- AP-1 pathway in CCA.
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Focused ultrasound (FUS) can be used to locally and temporally enhance vascular permeability, improving the efficiency of drug delivery from the blood vessels into the surrounding tissue. However, it is difficult to evaluate in real time the effect induced by FUS and to noninvasively observe the permeability enhancement. In this study, speckle-variance optical coherence tomography (SVOCT) was implemented for the investigation of temporal effects on vessels induced by FUS treatment. With OCT scanning, the dynamic change in vessels during FUS exposure can be observed and studied. Moreover, the vascular effects induced by FUS treatment with and without the presence of microbubbles were investigated and quantitatively compared. Additionally, 2D and 3D speckle-variance images were used for quantitative observation of blood leakage from vessels due to the permeability enhancement caused by FUS, which could be an indicator that can be used to determine the influence of FUS power exposure. In conclusion, SVOCT can be a useful tool for monitoring FUS treatment in real time, facilitating the dynamic observation of temporal effects and helping to determine the optimal FUS power.
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Focused ultrasound (FUS) is a recently discovered noninvasive technique for local and temporal enhancement of vascular permeability, which facilitates drug delivery from the vessels into the surrounding tissue. However, exposure to FUS at a high intensity may cause permanent damage. To investigate the effects of the FUS treatment on blood vessels, we propose to use fluorescein angiography (FA) and optical coherence tomography (OCT) for real-time observation of the diffusion of fluorescence dye from blood vessels and to evaluate the morphological changes of the vessels in vivo. With time-resolved FA imaging, the relationship between the exposed power and the improved permeability of the vessels can be assessed according to the enhancement of the fluorescent intensity due to the dye leakage. Furthermore, the variation of the time-resolved fluorescent intensities can be used to identify the occurrence of dye leakage. In contrast, OCT can be implemented for the reconstruction of tissue microstructures. To quantitatively evaluate the morphological changes of the vessels after the FUS exposure with OCT, a new algorithm was proposed to estimate the vessel area based on the comparison of backscattering properties resulting from the tissue and vascular structures. Results showed that the vessel area increased as the exposed power increased, and the area became significantly larger at a higher FUS exposure power of 10 W. In conclusion, integrated FA and OCT observation can be potentially effective for monitoring the outcome and investigating the effects of FUS treatment.
Subject(s)
Blood Vessels/diagnostic imaging , Blood Vessels/radiation effects , Fluorescein Angiography/methods , Tomography, Optical Coherence/methods , Ultrasonic Therapy/methods , Algorithms , Animals , Ear/blood supply , Image Processing, Computer-Assisted , Male , Mice , UltrasonographyABSTRACT
MicroRNAs (miRNAs) are posttranscriptional modulators of gene expression and play an important role in many developmental processes. Recent studies suggest roles of miRNAs in carcinogenesis. Fragile histidine triad (FHIT) gene deletion, methylation, and reduced Fhit protein expression occur in about 70% of human epithelial tumors and are clearly associated with tumor progression. Although it has been previously reported that Fhit(-/-)cells exhibit more resistance to multi-DNA damage inducers, including ionizing radiation, it remains unclear how miRNAs targeting FHIT in DNA damage response play the role. This study reports that miR-143 directly targets FHIT and that overexpression of miR-143 results in significant G2-phase arrest and protects cells from DNA damage-induced killing. These results indicate an association of FHIT gene inactivation with increased survival after DNA damage and also provide useful information for miRNA-based drug development in two directions: protect cells from DNA damage-induced killing and sensitize cells to radiation therapy.
Subject(s)
Acid Anhydride Hydrolases/genetics , DNA Damage , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , Neoplasm Proteins/genetics , Skin Neoplasms/metabolism , 3' Untranslated Regions , Cell Line, Tumor , Cell Survival , DNA Repair , G2 Phase , Humans , MicroRNAs/pharmacology , Recombination, Genetic , TransfectionABSTRACT
OBJECTIVE: To investigate the effect of Porphyromonas gingivalis (Pg) with different fimA genotypes on vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) production by human umbilical vein endothelial cells (HUVEC). METHODS: In the present study, PgATCC33277 (type I fimA genotype), WCSP 115 (type II fimA genotype), W83 (type IV fimA genotype), and Escherichia coli-lipopolysaccharide (Ec-LPS) were designed as experimental group 1, 2, 3, and positive control group, respectively, to stimulate HUVEC, and the un-stimulated HUVEC were analyzed as negative control group. The three strains of Pg were cultured anaerobically in standard condition, and then the Pg cells and Ec-LPS were co-cultured with HUVEC for 2, 6, and 24 h, respectively. The amount of ICAM-1 and VCAM-1 produced by HUVEC was detected with flow cytometry (FCM). The expression of ICAM-1 and VCAM-1 by HUVEC were assayed with confocal laser scanning microscope (CLSM). RESULTS: The expression of ICAM-1 on the surface of HUVEC were intensified after infected by Pg with I, II, and IV fimA genotypes (P < 0.05). The amounts of ICAM-1 were 60.27 ± 5.43, 80.81 ± 1.44, and 85.94 ± 2.56 for Pg with type I fimA genotype, 86.69 ± 8.81, 90.19 ± 0.00, and 96.18 ± 0.48 for Pg with type II fimA genotype, 59.66 ± 0.40, 85.79 ± 4.86, and 96.04 ± 2.07 for Pg with type IV fimA genotype at 2, 6 and 24 h after infection, respectively. The up-regulation effects caused by Pg with type II and IV fimA genotypes were stronger than those caused by Pg with type I fimA genotype at different time points except at 2 h (P < 0.05). Under the present experimental condition, infected by Pg with type I, II and IV fimA genotypes stimulated low expression of VCAM-1 by HUVEC, it showed no significant differences among all the groups (P > 0.05). Expression of ICAM-1 and VCAM-1 in Pg infected HUVEC were confirmed by CLSM. Infection of HUVEC with Pg resulted in more fluorescence staining of ICAM-1 and VCAM-1 compared with that in uninfected HUVEC cultures. CONCLUSIONS: The virulence and pathogenicity of Pg is associated with its fimA genotypes, Pg with type II and IV fimA genes possess stronger ability to stimulate HUVEC to up-regulate the expression of cell adhesion molecules, which may lead to disorders in vascular endothelial function.