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Abstract Oocyte aging is a key constraint on oocyte quality, leading to fertilization failure and abnormal embryonic development. In addition, it is likely to generate unfavorable assisted reproductive technology (ART) outcomes. SCM-198, a synthetic form of leonurine, was found to rescue the rate of oocyte fragmentation caused by postovulatory aging. Therefore, the aim of this study was to conduct a more in-depth investigation of SCM-198 by exploring its relationship with aged oocytes after ovulation or maternal aging and clarifying whether it affects cell quality. The results indicate that, compared to the postovulatory aged group, the 50 µM SCM-198 group significantly improved sperm-egg binding and increased fertilization of aged oocytes, restoring the spindle apparatus/chromosome structure, cortical granule distribution, and ovastacin and Juno protein distribution. The 50 µM SCM-198 group showed significantly normal mitochondrial distribution, low levels of reactive oxygen species (ROS), and a small quantity of early oocyte apoptosis compared to the postovulatory aged group. Above all, in vivo supplementation with SCM-198 effectively eliminated excess ROS and reduced the spindle/chromosome structural defects in aged mouse oocytes. In summary, these findings indicate that SCM-198 inhibits excessive oxidative stress in oocytes and alters oocyte quality both in vitro and in vivo. Graphical Abstract

Objective: To investigate the relative effectiveness of various Non-Invasive Treatment Techniques (NITs) in chronic tinnitus management. Methods: We searched PubMed, Embase and Cochrane Library databases from the time of data construction to December 31, 2022. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, NITs were evaluated, including Aacceptance and commitment therapy (A), Cognitive behavioral therapy (C), Sound therapy (S), Transcranial magnetic stimulation (T), Electrical stimulation therapy (E), Virtual reality therapy (V), tinnitus Retraining therapy (R), general psychotherapy (D), and Placebo (P). The outcome indicators included the Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), Hospital Anxiety and Depression Scale-anxiety-Depression (HADS-D), Insomnia Severity Index (ISI), Visual Analogue Scales-Loudness (VAS-L), and Visual Analogue Scales-Distress (VAS-D). Statistical analysis was performed using Stata 14.0 for NMA. Results: This systematic review and meta-analysis included 22 randomized controlled trials comprising 2,354 patients. The treatment effects varied on each scale. For THI, S (86.9%) was the most effective, whereas P (6.5%) was the worst. For TQ, C (89.5%) was the most effective, whereas D (25.4%) was the worst. For HADS-D, A (82.4%) was the most effective, whereas D (9.47%) was the worst. For ISI, A (83.2%) was the most effective, whereas R (20.6%) was the worst. For VAS-L, S (73.5%) was the most effective, whereas E (18.9%) was the worst. For VAS-D, C (84.7%) was the most effective, whereas P (18.1%) was the worst. Conclusions: The combination of acoustics and cognitive behavioral therapy may be an effectively treat patients with chronic tinnitus. Level of evidence: How common is the problem? Level 2.Is this diagnostic or monitoring test accurate? (Diagnosis) Level 1.What will happen if we do not add a therapy? (Prognosis) Level 1.Does this intervention help? (Treatment Benefits) Level 1.What are the COMMON harms? (Treatment Harms) Level 1.What are the RARE harms? (Treatment Harms) Level 1.Is this (early detection) test worthwhile? (Screening) Level 1I.

Abstract Human papillomavirus (HPV) status strongly predicts positive clinical outcomes in patients with head and neck squamous cell cancer (HNSCC); however, the potential reasons have not been fully elucidated. Here, we characterized the immune context in HPV+ and HPV− HNSCC by integrating scRNA-seq and bulk RNA-seq data. In scRNA-seq data, HPV + HNSCC displayed increased B cells, plasma cells, CD4+ effector T cells, and decreased macrophages and mast cells. This finding was validated using bulk-cell data. Plasma cells predicted improved survival, and macrophages were associated with survival disadvantage. 1403 upregulated and 1877 downregulated differential expressed genes (DEGs) were obtained. Gene Ontology and KEGG enrichment analysis showed these DEGs focused on cytokine-related activity. Transcriptional analysis of B and plasma cells revealed associations between B-cell surface marker FCER2 and improved survival. In vitro assays confirmed the ability of FCER2 to suppress cellular proliferation and migration of HPV + tumors. In conclusion, our analysis revealed a heterogeneous tumor immune environment (TME) for HPV+ and HPV− HNSCC. Further, FCER2+ B cells contribute to antitumor immunity.

Abstract Under high ambient pressure (5 MPa) and different injection pressures (90, 120, and 150 MPa), a high‐speed imaging technique was carried out to comparatively investigate the macroscopic spray characteristics of diesel with three different types of blended fuel in a constant volume chamber. The oxygenated fuels were n‐butanol (B), pine oil (P), and 2,5‐dimethylfuran (DMF). All their blending ratio with diesel were 20%. Results showed that less viscosity could be improved the spray characteristics of the fuel in the range of experimental conditions. Then, the tested fuels had a longer penetration and a greater spray area with increasing the injection pressure from 90 to 150 MPa. On the other hand, the percentage increases in the mean spray cone angle of D100, B20, P20, and DMF20 were 3%, 4.4%, 2.4%, and 2.9%, respectively. At the same experimental condition, the spray penetrations of DMF20 and P20 were larger than that of D100, but the spray penetration of B20 was basically similar to D100. Besides, the performance of the spray cone angle and spray area were D100

Abstract Background Nutritional status influences the growth and development of the eyes. However, there are few studies on the association between diet, especially whole grains (WG) consumption, and myopia. The study aimed to evaluate the association between WG intake and myopia prevalence among primary school-age children in China. Methods This cross-sectional epidemiological study conducted between November 2019 and December 2019 included 586 children, aged 6–12 years, attending primary school in Binhai district, Tianjin, China. Ophthalmologic examinations and optometric cycloplegic refraction measurements were conducted. Information was collected on known risks and protective factors for myopia and the consumption of WGs, vegetables, and fruits. This association between the probability of myopia and the proportion of WG consumption (WG proportion was calculated as the mean intake from WG sources divided by total grain intake), adjusted for protective and risk factors, was analysed using crude and multivariable logistic regression. Results Among the study participants, 226/586 (38.57%) children had myopia in at least one eye. WG intake was inversely correlated with the prevalence of myopia. Furthermore, in the multivariate analysis, WG intake of > 50% was identified as a protective factor against myopia after subsequent adjustment for children’s age, sex, parental myopia, near-work activity, screen time, reading and writing habits, visual fatigue, outdoor time, and classroom light environment (all P 50%) was an independent protective factor against myopia. Modifying the form of grains consumed (whole versus refined) could be one of the targets of future public health measures.

Fengyun-4B (FY-4B) is the latest Chinese next-generation geostationary meteorological satellite. The Advanced Geostationary Radiation Imager (AGRI) aboard FY-4B is equipped with 15 spectral bands, from visible to infrared, suitable for aerosol optical depth (AOD) retrieval. In this study, an overland AOD retrieval algorithm was developed for the FY-4B AGRI. Considering the large directional variation in the FY-4B AGRI reflectances, a bidirectional reflectance distribution function (BRDF) database was built, through which to estimate land surface reflectance/albedo. Seasonal aerosol models, based on four geographical regions in China, were developed between 2016 and 2022 using AERONET aerosol products, to improve their applicability to regional distribution differences and seasonal variations in aerosol types. AGRI AODs were retrieved using this new method over China from September 2022 to August 2023 and validated against ground-based measurements. The AGRI, Advanced Himawari Imager (AHI), and Moderate-Resolution Imaging Spectroradiometer (MODIS) official land aerosol products were also evaluated for comparison purposes. The results showed that the AGRI AOD retrievals were highly consistent with the AERONET AOD measurements, with a correlation coefficient (R) of 0.88, root mean square error (RMSE) of 0.14, and proportion that met an expected error (EE) of 65.04%. Intercomparisons between the AGRI AOD and other operational AOD products showed that the AGRI AOD retrievals achieved better performance results than the AGRI, AHI, and MODIS official AOD products. Moreover, the AGRI AOD retrievals showed high spatial integrity and stable performance at different times and regions, as well as under different aerosol loadings and characteristics. These results demonstrate the robustness of the new aerosol retrieval method and the potential of FY-4B AGRI measurements for the monitoring of aerosols with high accuracy and temporal resolutions.

The research motivation of this paper is to utilize the large amount of energy wasted during the LNG (liquefied natural gas) gasification process, and proposes a synergistic liquefied hydrogen (LH2) production and storage process scheme for LNG receiving station and methane reforming hydrogen production process - SMR-LNG combined liquefied hydrogen production system, which uses the cold energy from LNG to pre-cool the hydrogen and subsequently uses an expander to complete the liquefaction of hydrogen. The proposed process is modeled and simulated by Aspen HYSYS software, and its efficiency is evaluated and sensitivity analysis is carried out. The simulation results show that the system can produce liquefied hydrogen with a flow rate of 5.89 t/h with 99.99% purity when the LNG supply rate is 50 t/h. The power consumption of liquefied hydrogen is 46.6 kWh/kg LH2; meanwhile, the energy consumption of the HL subsystem is 15.9 kWh/kg LH2, lower than traditional value of 17∼19 kWh/kg LH2. The efficiency of the hydrogen production subsystem was 16.9%; the efficiency of the hydrogen liquefaction (HL) subsystem was 29.61%, which was significantly higher than the conventional industrial value of 21%; the overall energy efficiency (EE1) of the system was 56.52% with the exergy efficiency (EE2) of 22.2%, reflecting a relatively good thermodynamic perfection. The energy consumption of liquefied hydrogen per unit product is 98.71 GJ/kg LH2.

PurposeTo predict the need for cycloplegic assessment, as well as refractive state under cycloplegia, based on non-cycloplegic ocular parameters in school-age children.DesignRandom cluster sampling.MethodsThe cross-sectional study was conducted from December 2018 to January 2019. Random cluster sampling was used to select 2,467 students aged 6–18 years. All participants were from primary school, middle school and high school. Visual acuity, optical biometry, intraocular pressure, accommodation lag, gaze deviation in primary position, non-cycloplegic and cycloplegic autorefraction were conducted. A binary classification model and a three-way classification model were established to predict the necessity of cycloplegia and the refractive status, respectively. A regression model was also developed to predict the refractive error using machine learning algorithms.ResultsThe accuracy of the model recognizing requirement of cycloplegia was 68.5–77.0% and the AUC was 0.762–0.833. The model for prediction of SE had performances of R^2 0.889–0.927, MSE 0.250–0.380, MAE 0.372–0.436 and r 0.943–0.963. As the prediction of refractive error status, the accuracy and F1 score was 80.3–81.7% and 0.757–0.775, respectively. There was no statistical difference between the distribution of refractive status predicted by the machine learning models and the one obtained under cycloplegic conditions in school-age students.ConclusionBased on big data acquisition and machine learning techniques, the difference before and after cycloplegia can be effectively predicted in school-age children. This study provides a theoretical basis and supporting evidence for the epidemiological study of myopia and the accurate analysis of vision screening data and optometry services.

Abstract Background The increase in the prevalence of myopia has become a matter of serious public health concern, and few studies to date have examined the ocular biometric parameters of myopia in young Chinese adults. This study aimed to investigate the longitudinal ocular biometric and refractive development of first-year university students and the influence of near work. Methods This study included 526 first-year university students from Tianjin Medical University (mean age, 18.34 years; 313 females and 213 males). From 2016 to 2018, participants underwent ocular biometry measurements and subjective refraction annually. Near-work activities such as the use of electronic devices, online games, reading, and writing as well as demographic data were recorded by questionnaires. Results The prevalence of myopia in this population from 2016 to 2018 was 92.40%, 92.59%, and 92.97%, respectively. Importantly, the prevalence of high myopia increased significantly from 20.91% to 28.33% (P

The Medium Resolution Spectral Imager-II (MERSI-II) onboard the recently launched Chinese Fengyun-3D (FY-3D) satellite has great capability in detecting global aerosols as it includes aerosol bands similar to Moderate Resolution Imaging Spectroradiometer (MODIS). However, to date, aerosol retrieval based on MERSI-II is still limited to dark target regions and there is no official aerosol products for the MERSI-II. This study focuses on developing a high-precision algorithm to retrieve aerosol optical depth (AOD) suitable for entire land areas (except snow/ice and inland waters) based on MERSI-II measurements. Considering both the accuracy and retrieval efficiency, a new cost function is constructed based on (1) the fact that the AOD (550 nm) retrieved independently from different bands should be the same with the correct aerosol model, and (2) the assumption that the aerosol types are the same in the 5 × 5 km spatial range. The retrieval method based on the new cost function is nearly 50 times faster than most current methods using iterative calculations. To extend the application adaption of the FY-3D MERSI-II AOD retrieval and avoid the errors caused by the surface Lambertian hypothesis, a bidirectional reflectance distribution function (BRDF) database is built using MODIS products. Eight candidate aerosol models in different natural zones of China are constructed based on AERONET aerosol products from 2010 − 2021. The new method is applied to MERSI-II images over China and validated against ground-based measurements at 14 stations from 2020 to 2021. MODIS aerosol products from three operational algorithms are also used for comparison purposes. The results show that MERSI-II AOD retrievals agree well with the ground-based measurements with correlation coefficient (R), root mean square error (RMSE), and relative mean bias (RMB) of 0.913, 0.123, and 0.955, respectively. In addition, 72.19 % of AOD matchups fall within the expected error (EE) envelopes. The MERSI-II retrievals show higher accuracy than that of MODIS dark target (DT) and deep blue (DB) products and comparable accuracy of the MODIS Multi-Angle Implementation of Atmospheric Correction (MAIAC) product. MERSI-II AOD also shows higher stability in terms of spatial and temporal and better performance under heavy aerosol loading conditions than MODIS products. A good AOD agreement with R from 0.777 to 0.863 between MERSI-II and MODIS products is found over the land of China. The new method showing high retrieval efficiency and accuracy has great potential to be operationally applied on AOD retrieval for MERSI-II.

Abstract A metal–organic framework (MOF) formed between Zn and p‐hydroxybenzoic acid (PHBA) is synthesized using a solvothermal method. These Zn‐PHBA nanorods, which are inexpensive and suitable for mass production, are added as a flame‐retardant into vinyl resin (430 LV, a material used in marine composites). Data from cone calorimetric test demonstrates that adding the Zn‐PHBA nanorods to 430 LV significantly improves flame retardation and smoke suppression. At a high Zn‐PHBA content of 10.0 wt%, the limiting oxygen index of 430 LV increases from 19.5% to 28.5%, and the material reaches the V‐0 rating in vertical burning tests (UL‐94). Moreover, the tensile and impact strengths of 430 LV containing 10 wt% Zn‐PHBA as flame‐retardant do not deteriorate and are even slightly improved. This work demonstrates that this MOF synthesized by a simple and efficient method may be used to produce nanocomposites with excellent flame retardation and mechanical properties, while keeping the material cost sufficiently low for marine applications.

Lipid metabolism disorder is the basis of atherosclerotic lesions, in which cholesterol and low-density lipoprotein (LDL) is the main factor involved with the atherosclerotic development. A high-fat and high-cholesterol diet can lead to this disorder in the human body, thus accelerating the process of disease. The development of single-cell RNA sequencing in recent years has opened the possibility to unbiasedly map cellular heterogeneity with high throughput and high resolution; alterations mediated by a high-fat and high-cholesterol diet at the single-cell transcriptomic level can be explored with this mean afterward. We assessed the aortic arch of 16-week old Apoe−/− mice of two control groups (12 weeks of chow diet) and two HFD groups (12 weeks of high fat, high cholesterol diet) to process single-cell suspension and use single-cell RNA sequencing to anatomize the transcripts of 5,416 cells from the control group and 2,739 from the HFD group. Through unsupervised clustering, 14 cell types were divided and defined. Among these cells, the cellular heterogeneity exhibited in endothelial cells and immune cells is the most prominent. Subsequent screening delineated ten endothelial cell subsets with various function based on gene expression profiling. The distribution of endothelial cells and immune cells differs significantly between the control group versus the HFD one. The existence of pathways that inhibit atherosclerosis was found in both dysfunctional endothelial cells and foam cells. Our data provide a comprehensive transcriptional landscape of aortic arch cells and unravel the cellular heterogeneity brought by a high-fat and high-cholesterol diet. All these findings open new perspectives at the transcriptomic level to studying the pathology of atherosclerosis.

Numerical methods, such as finite element or finite difference, have been widely used in the past decades for modeling solid mechanics problems by solving partial differential equations (PDEs). Differently from the traditional computational paradigm employed in numerical methods, physics-informed deep learning approximates the physics domains using a neural network and embeds physics laws to regularize the network. In this work, a physics-informed neural network (PINN) is extended for application to linear elasticity problems that arise in modeling non-uniform deformation for a typical open-holed plate specimen. The main focus will be on investigating the performance of a conventional PINN approach to modeling non-uniform deformation with high stress concentration in relation to solid mechanics involving forward and inverse problems. Compared to the conventional finite element method, our results show the promise of using PINN in modeling the non-uniform deformation of materials with the occurrence of both forward and inverse problems.

As a useful tool, artificial intelligence has surpassed human beings in many fields. Artificial intelligence-based automated radiotherapy planning strategies have been proposed in lots of cancer sites and are the future of treatment planning. Postmastectomy radiotherapy (PMRT) decreases local recurrence probability and improves overall survival, and volumetric modulated arc therapy (VMAT) has gradually become the mainstream technique of radiotherapy. However, there are few customized effective automated treatment planning schemes for postmastectomy VMAT so far. This study investigated an artificial intelligence based automated planning using the MD Anderson Cancer Center AutoPlan (MDAP) system and Pinnacle treatment planning system (TPS), to effectively generate high-quality postmastectomy VMAT plans. In this study, 20 patients treated with PMRT were retrospectively investigated, including 10 left- and 10 right-sided postmastectomy patients. Chest wall and the supraclavicular, subclavicular, and internal mammary regions were delineated as target volume by radiation oncologists, and 50 Gy in 25 fractions was prescribed. Organs at risk including heart, spinal cord, left lung, right lung, and lungs were also contoured. All patients were planned with VMAT using 2 arcs. An optimization objective template was summarized based on the dose of clinical plans and requirements from oncologists. Several treatment planning parameters were investigated using an artificial intelligence algorithm, including collimation angle, jaw collimator mode, gantry spacing resolution (GSR), and number of start optimization times. The treatment planning parameters with the best performance or that were most preferred were applied to the automated treatment planning method. Dosimetric indexes of automated treatment plans (autoplans) and manual clinical plans were compared by the paired t-test. The jaw tracking mode, 2-degree GSR, and 3 rounds of optimization were selected in all the PMRT autoplans. Additionally, the 350- and 10-degree collimation angles were selected in the left- and right-sided PMRT autoplans, respectively. The uniformity index and conformity index of the planning target volume, mean heart dose, spinal cord D0.03cc, mean lung dose, and V5Gy and V20Gy of the lung of autoplans were significantly better compared with the manual clinical plans. An artificial intelligence-based automated treatment planning method for postmastectomy VMAT has been developed to ensure plan quality and improve clinical efficiency.

Purpose: To investigate the characteristics of macular structures and microcirculation of posterior staphyloma (PS) and explored factors related to PS in eyes with high myopia.Methods: There were 114 eyes of 82 patients in this study. Using 1:1 matching of the axial length of myopic eyes, patients were divided into no PS (NPS) and PS groups. Comprehensive ophthalmic examinations were performed on all patients. Structural parameters were acquired using swept source optical coherence tomography (SS-OCT). OCT angiography (OCTA) was used to measure the microcirculation parameters. Generalized estimated equation and linear correlation analysis were used for the statistical analysis.Results: Patients with PS had a thinner retinal thickness (RT) and choroid thickness (CT) (all p < 0.05) in the measurement areas and a significantly lower subfoveal scleral thickness (SFST) (p < 0.001) than those without PS. Retinal deep vascular complex density (DVD) (all p < 0.05) and choriocapillaris perfusion area (CCPA) (all p < 0.001) were significantly lower in the measurement areas of the PS group than in those of the NPS group. There was no significant difference in the retinal superficial vascular density between the two groups. Generalized estimating equation indicated that SFST (B = 0.079, p = 0.001), parafoveal RT (B = −0.162, p = 0.041), foveal CT (B = 0.292, p = 0.013), parafoveal CT (B = −0.157, p = 0.023), foveal CCPA (B = 0.691, p = 0.003) and parafoveal CCPA (B = −0.026, p = 0.004) were significantly correlated with PS. Age (r = −0.323, p = 0.001), spherical equivalent refraction (SER) (r = 0.289, p = 0.004), subfoveal CT (r = 0.398, p < 0.001), foveal DVD (r = 0.346, p < 0.001), foveal CT (r = 0.429, p < 0.001), and foveal CCPA (r = 0.387, p < 0.001) were strongly correlated with SFST.Conclusions: The macular structures and microcirculation in the PS group were different from those in the NPS group. SFST, CT, and CCPA were significantly correlated with PS. Lower SFST in PS was correlated with abnormalities of CT and microcirculation.

Osteosarcoma is the most common primary malignant bone tumor in adolescents. While chemotherapy combined with surgery can improve the prognosis of some patients, chemo-resistance is still a huge obstacle in osteosarcoma treatment. Accumulating evidence demonstrates that circular RNAs (circRNAs) are involved in cancer progression and metastasis, but their specific role in osteosarcoma remains mostly undescribed. In this study, we performed circRNA deep sequencing and identified 88 distinct circRNAs from a human osteosarcoma cell lines group (143B, HOS, SJSA, and U2OS) and the human osteoblast hFOB 1.19 (control). We found that circCAMSAP1, also named hsa_circ_0004338, is significantly upregulated in human osteosarcoma tissues and cell lines, and it is positively correlated with osteosarcoma development. Silencing of circCAMSAP1 effectively suppresses osteosarcoma cell growth, apoptosis, migration, and invasion. Furthermore, we validated that circCAMSAP1 functions in osteosarcoma tumorigenesis through a circCAMSAP1/miR-145-5p/friend leukemia virus integration 1 (FLI1) pathway. FLI1 promotes osteosarcoma tumorigenesis and miR-145-5p suppresses FLI translation. circCAMSAP1 directly sequesters miR-145-5p in the cytoplasm and inhibits its activity to suppress osteosarcoma tumorigenesis. Moreover, the regulatory role of circCAMSAP1 upregulation was examined and validated in rats. In summary, our findings provide evidence that circCAMSAP1 act as a “microRNA sponge” and suggest a new therapeutic target of human osteosarcoma.

To enhance the damping properties of nitrile butadiene rubber (NBR), the elastomer used was blended with chlorinated paraffin 52 (CP52) to prepare NBR/CP52 composites. The results showed that CP52 could significantly enhance the damping properties of NBR and shift the glass transition temperature (Tg) to lower temperatures. Molecular dynamics models of the CP52/NBR system were established, and the damping properties of the CP52-reinforced NBR were investigated using molecular dynamics (MD) simulations. Through the combination of MD simulations and the experimental results, the essential mechanism of the enhanced damping properties of the NBR was methodically expatiated and was ascribed to the Cl-CP-H····NC-NBR (type I) and CP-Cl····H-NBR-CN (type II) analogous hydrogen bonds formed between NBR and CP52. The higher the CP52 content, the higher the analogous hydrogen bond concentration, and the better the damping properties of the CP52/NBR composites. The experimental results were very consistent with the MD simulation results, meaning that the combination method can provide a new means to optimize the design of damping materials and broaden the application range of small polar molecules in the damping modification of polar rubber materials.

Purpose: The aim of this study is to develop a practicable automatic clinical target volume (CTV) delineation method for radiotherapy of breast cancer after modified radical mastectomy.Methods: Unlike breast conserving surgery, the radiotherapy CTV for modified radical mastectomy involves several regions, including CTV in the chest wall (CTVcw), supra- and infra-clavicular region (CTVsc), and internal mammary lymphatic region (CTVim). For accurate and efficient segmentation of the CTVs in radiotherapy of breast cancer after modified radical mastectomy, a multi-scale convolutional neural network with an orientation attention mechanism is proposed to capture the corresponding features in different perception fields. A channel-specific local Dice loss, alongside several data augmentation methods, is also designed specifically to stabilize the model training and improve the generalization performance of the model. The segmentation performance is quantitatively evaluated by statistical metrics and qualitatively evaluated by clinicians in terms of consistency and time efficiency.Results: The proposed method is trained and evaluated on the self-collected dataset, which contains 110 computed tomography scans from patients with breast cancer who underwent modified mastectomy. The experimental results show that the proposed segmentation method achieved superior performance in terms of Dice similarity coefficient (DSC), Hausdorff distance (HD) and Average symmetric surface distance (ASSD) compared with baseline approaches.Conclusion: Both quantitative and qualitative evaluation results demonstrated that the specifically designed method is practical and effective in automatic contouring of CTVs for radiotherapy of breast cancer after modified radical mastectomy. Clinicians can significantly save time on manual delineation while obtaining contouring results with high consistency by employing this method.

Purpose: A novel deep learning model, Siamese Ensemble Boundary Network (SEB-Net) was developed to improve the accuracy of automatic organs-at-risk (OARs) segmentation in CT images for head and neck (HaN) as well as small organs, which was verified for use in radiation oncology practice and is therefore proposed.Methods: SEB-Net was designed to transfer CT slices into probability maps for the HaN OARs segmentation purpose. Dual key contributions were made to the network design to improve the accuracy and reliability of automatic segmentation toward the specific organs (e.g., relatively tiny or irregularly shaped) without sacrificing the field of view. The first implements an ensemble of learning strategies with shared weights that aggregates the pixel-probability transfer at three orthogonal CT planes to ameliorate 3D information integrity; the second exploits the boundary loss that takes the form of a distance metric on the space of contours to mitigate the challenges of conventional region-based regularization, when applied to highly unbalanced segmentation scenarios. By combining the two techniques, enhanced segmentation could be expected by comprehensively maximizing inter- and intra-CT slice information. In total, 188 patients with HaN cancer were included in the study, of which 133 patients were randomly selected for training and 55 for validation. An additional 50 untreated cases were used for clinical evaluation.Results: With the proposed method, the average volumetric Dice similarity coefficient (DSC) of HaN OARs (and small organs) was 0.871 (0.900), which was significantly higher than the results from Ua-Net, Anatomy-Net, and SRM by 4.94% (26.05%), 7.80% (24.65%), and 12.97% (40.19%), respectively. By contrast, the average 95% Hausdorff distance (95% HD) of HaN OARs (and small organs) was 2.87 mm (0.81 mm), which improves the other three methods by 50.94% (75.45%), 88.41% (79.07%), and 5.59% (67.98%), respectively. After delineation by SEB-Net, 81.92% of all organs in 50 HaN cancer untreated cases did not require modification for clinical evaluation.Conclusions: In comparison to several cutting-edge methods, including Ua-Net, Anatomy-Net, and SRM, the proposed method is capable of substantially improving segmentation accuracy for HaN and small organs from CT imaging in terms of efficiency, feasibility, and applicability.

Abstract Gut microbiota have been implicated in the development of many human diseases, including both digestive diseases and non-digestive diseases. In this study, we investigated whether the gut bacteria differed in cervical cancer (CCa) patients compared with healthy controls by 16S rRNA sequencing analysis. Subjects including eight CCa and five healthy controls were included. Microbiota profiles in fecal DNA were characterized by PCR amplification of the 16S rRNA V4 variable region and deep sequencing using the Illumina HiSeq platform. The CCa-associated gut microbiota had an increasing trend in alpha diversity, although statistical significance was not reached. Inter-group variability in community structure by beta diversity analysis showed a clear separation between cancer patients and healthy controls. Gut microbiota profiles were different between patients and controls; namely, the proportions of Proteobacteria phylum was notably higher in patients with CCa (ρ = 0.012). Seven genera differentiated significantly in relative abundance between CCa and controls (all ρ

Recombinant adeno-associated virus (rAAV) vectors are considered ideal vehicles for human gene therapy. Meanwhile, non-viral strategies, such as transfection agents (TAs), have also shown promise to deliver genetic materials, such as siRNA. Transduction with the rAAV vector is performed concurrently with transfection with plasmid DNA or RNA. In the present study, we report that various TAs inhibited rAAV-mediated transgene expression at diverse levels. Overall, cationic polymers and dendrimers dramatically blocked rAAV transduction, while lipid-based liposomes displayed the least effect. The inhibitory effect was dependent on the dose of TAs and the timing of infection, suggesting that the early stages of viral infection were involved. In addition, the present results indicate that the transgene expression of rAAV vectors was significantly increased by liposome-mediated transfection with adenoviral helper genes. At the same time, this was dramatically inhibited by liposome-mediated transfection with the trichosanthin gene encoding a type I ribosome-inactivating protein isolated from traditional Chinese medicine. Furthermore, liposomes also have little effect on rAAV-mediated transgene expression in vivo. Taken together, these findings suggest liposome as the best choice of TAs, which should be used in combination with rAAV-mediated gene therapy. Keywords: liposome lipid-based formulation, rAAV, transduction, transfection agents, trichosanthin

Recent studies have shown that the high-resolution satellite Landsat-8 has the capability to retrieve aerosol optical depth (AOD) over urban areas at a 30 m spatial resolution. However, its long revisiting time and narrow swath limit the coverage and frequency of the high resolution AOD observations. With the increasing number of Earth observation satellites launched in recent years, combining the observations of multiple satellites can provide higher temporal-spatial coverage. In this study, a fusing retrieval algorithm is developed to retrieve high-resolution (30 m) aerosols over urban areas from Landsat-8 and Sentinel-2 A/B satellite measurements. The new fusing algorithm was tested and evaluated over Beijing city and its surrounding area in China. The validation results show that the retrieved AODs show a high level of agreement with the local urban ground-based Aerosol Robotic Network (AERONET) AOD measurements, with an overall high coefficient of determination (R2) of 0.905 and small root mean square error (RMSE) of 0.119. Compared with the operational AOD products processed by the Landsat-8 Surface Reflectance Code (LaSRC-AOD), Sentinel Radiative Transfer Atmospheric Correction code (SEN2COR-AOD), and MODIS Collection 6 AOD (MOD04) products, the AOD retrieved from the new fusing algorithm based on the Landsat-8 and Sentinel-2 A/B observations exhibits an overall higher accuracy and better performance in spatial continuity over the complex urban area. Moreover, the temporal resolution of the high spatial resolution AOD observations was greatly improved (from 16/10/10 days to about two to four days over globe land in theory under cloud-free conditions) and the daily spatial coverage was increased by two to three times compared to the coverage gained using a single sensor.

The geostationary satellite Himawari-8, possessing the Advanced Himawari Imager (AHI), which features 16 spectral bands from the visible to infrared range, is suitable for aerosol observations. In this study, a new algorithm is introduced to retrieve aerosol optical depth (AOD) over land at a resolution of 2 km from the AHI level 1 data. Considering the anisotropic effects of complex surface structures over land, Moderate Resolution Imaging Spectroradiometer (MODIS) bidirectional reflectance distribution function (BRDF) model parameters product (MCD19A3) is used to calculate the surface reflectance for Himawari-8’s view angle and band. In addition, daily BRDF model parameters are calculated in areas with dense vegetation, considering the rapid variation of surface reflectance caused by vegetation growth. Moreover, aerosol models are constructed based on long duration Aerosol Robotic Network (AERONET) single scattering albedo (SSA) values to stand for aerosol types in the retrieval algorithm. The new algorithm is applied to AHI images over Bohai Rim region from 2018 and is evaluated using the newest AERONET version 3 AOD measurements and the latest MODIS collection 6.1 AOD products. The AOD retrievals from the new algorithm show good agreement with the AERONET AOD measurements, with a correlation coefficient of 0.93 and root mean square error (RMSE) of 0.12. In addition, the new algorithm increases AOD retrievals and retrieval accuracy compared to the Japan Aerospace Exploration Agency (JAXA) aerosol products. The algorithm shows stable performance during different seasons and times, which makes it possible for use in climate or diurnal aerosol variation studies.

Accurately estimating fine ambient particulate matter (PM2.5) is important to assess air quality and to support epidemiological studies. To analyze the spatiotemporal variation of PM2.5 concentrations, previous studies used different methodologies, such as statistical models or neural networks, to estimate PM2.5. However, there is little research on full-coverage PM2.5 estimation using a combination of ground-measured, satellite-estimated, and atmospheric chemical model data. In this study, the linear mixed effect (LME) model, which used the aerosol optical depth (AOD) from the Moderate Resolution Imaging Spectroradiometer (MODIS), meteorological data, normalized difference vegetation index (NDVI), and elevation data as predictors, was fitted for 2017 over Beijing–Tianjin–Hebei (BTH). The LME model was used to calibrate the PM2.5 concentration using the nested air-quality prediction modeling system (NAQPMS) simulated with ground measurements. The inverse variance weighting (IVW) method was used to fuse satellite-estimated and model-calibrated PM2.5. The results showed a strong agreement with ground measurements, with an overall coefficient (R2) of 0.78 and a root-mean-square error (RMSE) of 26.44 μg/m3 in cross-validation (CV). The seasonal R2 values were 0.75, 0.62, 0.80, and 0.78 in the spring, summer, autumn, and winter, respectively. The fusion results supplement the lack of satellite estimates and can capture more detailed information than the NAQPMS model. Therefore, the results will be helpful for pollution process analyses and health-related studies.

Land surface reflectance (LSR) and aerosol types are the two main factors that affect aerosol inversions over land. According to LSR determination methods, Moderate resolution Imaging Spectroradiometer (MODIS) aerosol products are produced using the Deep Blue (DB) and Dark Target (DT) algorithms. Five aerosol types that are determined from Aerosol Robotic Network (AERONET) ground measurements are used to describe the global distribution of aerosol types in each algorithm. To assess the influence of LSR and the method used to determine aerosol type from aerosol retrievals, 10-km global aerosol products that cover 2013 are selected for validation using Level 2.0 aerosol observations from 175 AERONET sites. The variations in the retrieval accuracy of the DB and DT algorithms for different LSR values are analyzed by combining them with a global 10-km LSR database. Meanwhile, the adaptability of the MODIS products over areas covered with different aerosols is also explored. The results are as follows. (1) Compared with DT retrievals, the DB algorithm yields lower root mean squared error (RMSE) and mean absolut error (MAE) values, and a greater number of appropriate sample points fall within the expected error (EE). The DB algorithm shows higher overall reliability; (2) The aerosol retrieval accuracy of the DB and DT algorithms decline irregularly as the surface reflectance increases; the DB algorithm displays relatively high accuracy; (3) Both algorithms have a high retrieval accuracy over areas covered by weak absorbing aerosols, whereas dust aerosols and continental aerosols produce a low retrieval accuracy. The DB algorithm shows good retrieval results for most aerosols, but a lower accuracy for strong absorbing aerosols.

Folliculogenesis is tightly controlled by a series of hormones, growth factors and cytokines, many of which are secreted as proproteins and require processing by proteases before becoming functional. Furin is a member of the subtilisin-like proteases that activate large numbers of proprotein substrates and is ubiquitously expressed and implicated in many physiological and pathological processes. However, the precise role of furin during folliculogenesis has not been thoroughly investigated. The goal of the present work is to identify the role of furin in the development of granulosa cells during folliculogenesis, using immunohistochemistry, RT-PCR, Western blot and functional studies in primary cultured rat granulosa cells. Our results demonstrate that furin is highly expressed in granulosa cells and oocytes of the ovary with very limited expression in other ovarian cells such as the epithelial, stromal or theca cells. Furin siRNA significantly increases apoptosis of the granulosa cells from large antral/preovulatory follicles, in part via downregulation of the anti-apoptotic proteins, XIAP and p-AKT. On the contrary, furin siRNA markedly decreases proliferation of granulosa cells based on the downregulation of proliferation cell nuclear antigen (PCNA). Taken together, these data suggest that furin may play an important role in regulating apoptosis and proliferation of granulosa cells.

Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa_circ_0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa_circ_0000566 is regulated by hypoxia-inducible factor-1a (HIF-1a) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1a is impeded. Furthermore, Hsa_circ_0000566 contributes to OS progression by binding to HIF-1a (while competing with VHL) and by confers protection against HIF-1a against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1a and Hsa_circ_0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa_circ_0000566 in the Warburg effect and suggest that Hsa_circ_0000566 could be a potential therapeutic target to combat OS progression. [ABSTRACT FROM AUTHOR]