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Abstract Molecule alterations are important to explore the pathological mechanism of ischemic stroke (IS). Ferroptosis, a newly recognized type of regulated cell death, is related to IS. Identification of the interactions between circular RNA (circRNA), microRNA (miRNA) and ferroptosis related mRNA may be useful to understand the molecular mechanism of IS. The circRNA, miRNA and mRNA transcriptome data in IS, downloaded from the Gene Expression Omnibus (GEO) database, was used for differential expression analysis. Ferroptosis related mRNAs were identified from the FerrDb database, followed by construction of circRNA-miRNA-ferroptosis related mRNA network. Enrichment and protein–protein interaction analysis of mRNAs in circRNA-miRNA-mRNA network was performed, followed by expression validation by reverse transcriptase polymerase chain reaction and online dataset. A total of 694, 41 and 104 differentially expressed circRNAs, miRNAs and mRNAs were respectively identified in IS. Among which, dual specificity phosphatase 1 (DUSP1), nuclear receptor coactivator 4 (NCOA4) and solute carrier family 2 member 3 (SLC2A3) were the only three up-regulated ferroptosis related mRNAs. Moreover, DUSP1, NCOA4 and SLC2A3 were significantly up-regulated in IS after 3, 5 and 24 h of the attack. Based on these three ferroptosis related mRNAs, 4 circRNA-miRNA-ferroptosis related mRNA regulatory relationship pairs were identified in IS, including hsa_circ_0071036/hsa_circ_0039365/hsa_circ_0079347/hsa_circ_0008857-hsa-miR-122-5p-DUSP1, hsa_circ_0067717/hsa_circ_0003956/hsa_circ_0013729-hsa-miR-4446-3p-SLC2A3, hsa_circ_0059347/hsa_circ_0001414/hsa_circ_0049637-hsa-miR-885-3p-SLC2A3, and hsa_circ_0005633/hsa_circ_0004479-hsa-miR-4435-NCOA4. In addition, DUSP1 is involved in the signaling pathway of fluid shear stress and atherosclerosis. Relationship of regulatory action between circRNAs, miRNAs and ferroptosis related mRNAs may be associated with the development of IS.

Abstract Following the relaxation of control measures for COVID-19 in China in December 2022, there was a resurgence of influenza A among children in Linyi. This research aims to analyze the epidemiology and genetic characteristics of influenza A viruses circulating among children in Linyi from April 2022 to March 2024. Throat swab specimens were collected from children with influenza-like illness (ILI), and the types of influenza were identified. The hemagglutinin (HA) genes of influenza A viruses were amplified using reverse transcription-polymerase chain reaction (RT-PCR) and then sequenced. Subsequently, the gene characteristics and phylogenetics of these sequences were analyzed. A total of 6258 cases of influenza A were tested from 54,926 children with ILI over two years, showing three epidemic waves: one in summer 2022 and two in spring and winter 2023. The epidemic waves in summer 2022 and winter 2023 were caused by influenza A(H3N2) viruses. In spring 2023, influenza A(H1N1)pdm09 viruses accounted for 77.1% and A(H3N2) viruses accounted for 22.9%, respectively. The influenza A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.2a, while the influenza A(H3N2) viruses evolved from clade 3C.2a1b.2a.1a to 3C.2a1b.2a.2a.3a.1. Compared with the vaccine strain of the Northern Hemisphere of the current year, multiple amino acid substitutions and glycosylation sites changes were observed in the HA protein that most likely resulted in antigenic drift. The influenza A viruses have been circulating and evolving persistently in Linyi from 2022 to 2024. Continuous surveillance is essential for comprehending the dynamics of influenza in the post-COVID-19 era.

Abstract Fibromyalgia (FM) and ankylosing spondylitis (AS) are both rheumatic diseases characterized by significant musculoskeletal pain. In this study, we investigated the differences of the resting-state network (RSN) connectivity and gray matter volume (GMV) between FM, AS and healthy controls (HCs). We recruited 38 FM patients, 82 AS patients and 61 HCs in this study. All the participants underwent resting-state functional MRI (rs-fMRI) scans in a GE 3.0T MR system. Independent component analysis (ICA) was conducted on the rs-fMRI data, and group differences of the rsFC between different resting-state networks were calculated using dual regression. We also conducted voxel-based morphometry (VBM) analysis to investigate the differences of the GMV in FM, AS and HCs. The rsFC between the dorsal default mode network (DDMN) and the body of left caudate nucleus was significantly decreased in FM patients in comparison to AS patients (87 voxels, p = 0.025). VBM analysis showed that the GMV of the left posterior lobe of cerebellum was significantly increased in FM patients compared with AS patients (88 voxels, p = 0.036). Neither ICA nor VBM analysis revealed significant differences of RSN connectivity or GMV between FM patients and HCs. The altered rsFC between DMN and the caudate nucleus suggested an aberrant cortico-striato-thalamo-cortical circuit in FM patients, indicating aberrant reward processing, with potential association with mood, motivation and cognitive functions. The increased GMV in the left posterior lobe of cerebellum indicated the participation of cerebellum in the abnormal pain processing in FM patients.

Abstract In this paper, we examined the elevation-dependent warming (EDW) patterns of MODIS LST across different seasons in the Qinling-Daba Mountains, further investigate the connections between the EDW patterns of Land surface temperature (LST) and land surface albedo (ALB) as well as aerosol optical depth (AOD). The key findings include: (1) Our study reveals a robust correlation between LST and air temperature in the Qinling-Daba Mountains, suggesting the feasibility of using MODIS LST to predict the temperature trends (2) During the period from 2001 to 2010, MODIS LST shows a significant EDW trend, primarily in the spring season. In contrast, a negative EDW is observed in the period during 2011–2021, which is contrary to the earlier decade, particularly during the autumn and winter seasons. (3) EDW of MODIS LST is affected by the combination of ALB and AOD. The former has a negative influence on the change of LST, particularly above 2500 m in elevation. However, the latter is negatively correlated with the trend of MODIS LST, primarily at lower and middle altitudes (0–2500 m). This study gives a comprehensive explanation for the EDW of the temporal variations of LST in the Qinling-Daba Mountains to improve our understanding of the complex interactions and potential future climate scenarios in the region.

Abstract The early diagnosis of esophageal cancer (EC) is extremely challenging due to a lack of effective diagnostic methods. The study presented herein aims to assess whether serum volatile organic compounds (VOCs) could be utilised as emerging diagnostic biomarkers for EC. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in the serum samples of 55 patients with EC, with samples from 84 healthy controls (HCs) patients analysed as a comparison. All machine learning analyses were based on data from serum VOCs obtained by GC-IMS. A total of 33 substance peak heights were detected in all patient serum samples. The ROC analysis revealed that four machine learning models were effective in facilitating the diagnosis of EC. In addition, the random forests model for 5 VOCs had an AUC of 0.951, with sensitivities and specificities of 94.1 and 96.0%, respectively.

Abstract Monitoring and preventing coal-rock dynamic disasters are vital for safe mining. To investigate the time–frequency features of induced charge signals with coal damage and failure of roadways, the generation mechanism of free charge in loaded coal is analyzed and the induced charge monitoring test is conducted. According to the stress-induced charge-time curves, the time-domain features of charge signals at each loading stage are obtained. The wavelet threshold denoising approach and generalized Morse wavelet transform method are applied to denoise the raw signals and study the frequency-domain features. Further, the quantitative relationship between the de-noised induced charge signals and the degree of coal damage is established. The results show that the event number, amplitude and fluctuation degree of available induced charge signals are all at a low level in the compaction and elastic stages of the coal, which are mainly generated by the piezoelectric effect and predominantly represent discreteness. When entering the plastic and failure stages, the available signals are primarily produced by the crack propagation and triboelectric effects, with a significant increase in the event number, amplitude, and fluctuation degree. Then the induced charge signals gradually transit from discrete to continuous. Generally, the dominant frequency of the available induced charge signals during the coal damage process is concentrated at 0 ~ 11 Hz. The available induced charge is positively correlated with the degree of coal damage, which can perform the damage degree of coal mass, providing a new approach to evaluate the stability of roadway surrounding rocks.

Abstract S-palmitoylases and S-depalmitoylases are differentially expressed in various cancers and several malignant tumors and show a strong prognostic ability. Notwithstanding, the potential clinical impact of S-palmitoylases and S-depalmitoylases, particularly in the prognosis and progression of lung adenocarcinoma (LUAD), has not been clarified. Expression levels of S-palmitoylases and S-depalmitoylases in LUAD were investigated using TCGA. GEPIA was used to evaluate the mRNA levels of S-palmitoylases and S-depalmitoylases at different pathological stages. Metascape was used to investigate the biological significance of S-palmitoylases and S-depalmitoylases. The Kaplan–Meier plotter was used to analyze the prognostic value of S-palmitoylases and S-depalmitoylases. CBioportal was used to analyze gene alterations in S-palmitoylases and S-depalmitoylases. UALCAN was used to examine DNA promoter methylation levels of S-palmitoylases and S-depalmitoylases. Finally, we investigated the relationship between S-palmitoylases, S-depalmitoylases, and tumor-infiltrating immune cells using TIMER. Correlations with immune checkpoint-related genes were determined using the R packages reshape2, ggpubr, ggplot2, and corrplot. PCR was also performed to assess the degree of ZDHHC4/12/18/24 and APT2 transcript expression in lung adenocarcinoma and adjacent normal lung tissues. HPA was utilized to investigate protein levels of S-palmitoylases and S-depalmitoylases in LUAD and normal lung tissue. Our study found that ZDHHC2/3/4/5/6/7/9/12/13/16/18/20/21/23/24, APT1/2, PPT1, LYPLAL1, ABHD4/10/11/12/13 and ABHD17C mRNA expression was significantly upregulated in LUAD, whereas ZDHHC1/8/11/11B/14/15/17/19/22, ABHD6/16A and ABHD17A mRNA expression was significantly downregulated. The functions of the differentially expressed S-palmitoylases and S-depalmitoylases were mainly associated with protein-cysteine S-palmitoyltransferase and protein-cysteine S-acyltransferase activities. Patients with high expression of ZDHHC4/12/18/24, APT2, ABHD4, ABHD11 and ABHD12 had a shorter overall survival. Infiltration of six immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) was closely associated with the expression of ZDHHC4/12/18/24 and APT2. ZDHHC4/12/18/24 and APT2 positively correlated with the immune checkpoint-related gene CD276. We assessed the mRNA levels of ZDHHC4/12/18/24 and APT2 using qRT-PCR and found increased expression of ZDHHC4/12/18/24 in LUAD compared with healty control lung tissues. ZDHHC4/12/18/24, and APT2 are potential prognostic biomarkers of LUAD. Their expression levels could be related to the tumor microenvironment in LUAD.

Abstract Anti‐virulence therapy that interferes with bacterial communication, known as “quorum sensing (QS)”, is a promising strategy for circumventing bacterial resistance. Using nanomaterials to regulate bacterial QS in anti‐virulence therapy has attracted much attention, which is mainly attributed to unique physicochemical properties and excellent designability of nanomaterials. However, bacterial QS is a dynamic and multistep process, and there are significant differences in the specific regulatory mechanisms and related influencing factors of nanomaterials in different steps of the QS process. An in‐depth understanding of the specific regulatory mechanisms and related influencing factors of nanomaterials in each step can significantly optimize QS regulatory activity and enhance the development of novel nanomaterials with better comprehensive performance. Therefore, this review focuses on the mechanisms by which nanomaterials regulate bacterial QS in the signal supply (including signal synthesis, secretion, and accumulation) and signal transduction cascade (including signal perception and response) processes. Moreover, based on the two key influencing factors (i.e., the nanomaterial itself and the environment), optimization strategies to enhance the QS regulatory activity are comprehensively summarized. Collectively, applying nanomaterials to regulate bacterial QS is a promising strategy for anti‐virulence therapy. This review provides reference and inspiration for further research on the anti‐virulence application of nanomaterials.

Abstract The current staging method is inadequate to identify high-risk recurrence patients with stage II colon cancer (CC). Using a systematic and comprehensive-biomarker discovery and validation method, we aimed to construct a lncRNA-based signature to improve the prognostic prediction of stage II CC. We identified 1,377 differently expressed lncRNAs by analyzing 16 paired stage II CC tumor tissue and adjacent normal mucosal tissue from the TCGA dataset. Subsequently, using a univariable and step multivariable Cox regression model, we trained an 11-lncRNA signature in the training cohort (n = 141), which could divide patients into high-risk and low-risk groups (AUC at 3 years = 0.801, 95% CI: 0.724–0.877; AUC at 5 years = 0.801, 95% CI: 0.718–0.885). Significantly, patients in the high-risk group had poorer recurrence-free survival (RFS) compared with the low-risk group (log-rank test, P

Extrusion bioprinting can be used to produce living materials but controlling cell microenvironments is challenging. Here, the authors use a type of core-shell microgel ink that decouples cell culture from material processing to produce functional materials with a range of potential applications.

Summary: Fusobacterium nucleatum (Fn) infection and microRNAs (miRNAs) are closely associated with colorectal cancer (CRC) development, but the mechanism by which Fn regulates tumor-suppressive miRNAs via exosomes and facilitates CRC metastasis remains unclear. Here, we identified that Fn infection significantly increased exosomal miR-122-5p levels in the serum of CRC patients and CRC cell culture supernatants through two miRNA panels of high-throughput sequencing and RT-qPCR analysis. In Fn-infected patients, the serum exosomal levels of miR-122-5p were negatively associated with their expression levels of tissues. Downregulated miR-122-5p was demonstrated to enhance the migration, invasion, and metastasis abilities of CRC cells in vivo and in vitro. Secretion of miR-122-5p into exosomes is mediated by hnRNPA2B1. Mechanistically, Fn activated the TGF-β1/Smads signaling pathway to promote EMT by regulation of the miR-122-5p/FUT8 axis. In conclusion, Fn infection may stimulate CRC cells to excrete exosome-wrapped miR-122-5p, and activate the FUT8/TGF-β1/Smads axis to promote metastasis.

Snow cover is a sensitive indicator of global climate change, and optical images are an important means for monitoring its spatiotemporal changes. Due to the high reflectivity, rapid change, and intense spatial heterogeneity of mountainous snow cover, Sentinel-2 (S2) and Landsat 8 (L8) satellite imagery with both high spatial resolution and spectral resolution have become major data sources. However, optical sensors are more susceptible to cloud cover, and the two satellite images have significant spectral differences, making it challenging to obtain snow cover beneath clouds and cloud shadows (CCSs). Based on our previously published approach for snow reconstruction on S2 images using the Google Earth Engine (GEE), this study introduces two main innovations to reconstruct snow cover: (1) combining S2 and L8 images and choosing different CCS detection methods, and (2) improving the cloud shadow detection algorithm by considering land cover types, thus further improving the mountainous-snow-monitoring ability. The Babao River Basin of the Qilian Mountains in China is chosen as the study area; 399 scenes of S2 and 35 scenes of L8 are selected to analyze the spatiotemporal variations of snow cover from September 2019 to August 2022 in GEE. The results indicate that the snow reconstruction accuracies of both images are relatively high, and the overall accuracies for S2 and L8 are 80.74% and 88.81%, respectively. According to the time-series analysis of three hydrological years, it is found that there is a marked difference in the spatial distribution of snow cover in different hydrological years within the basin, with fluctuations observed overall.

The optical and biological properties of functionalized gold nanoparticles (GNPs) have been widely used in sensing applications. GNPs have a strong binding ability to thiol groups. Furthermore, thiols are used to bind functional molecules, which can then be used, for example, to detect metal ions in solution. Herein, we describe 13 nm GNPs functionalized by glutathione (GSH) and conjugated with a rhodamine 6G derivative (Rh6G2), which can be used to detect Hg(II) in cells. The detection of Hg2+ ions is based on an ion-catalyzed hydrolysis of the spirolactam ring of Rh6G2, leading to a significant change in the fluorescence of GNPs-GSH-Rh6G2 from an “OFF” to an “ON” state. This strategy is an effective tool to detect Hg2+ ions. In cytotoxicity experiments, GNPs-GSH-Rh6G2 could penetrate living cells and detect mercury ions through the fluorescent “ON” form.

F1Fo-ATP synthase is a key enzyme for energy production in fungi. Here, the authors show that the δ subunit of the enzyme is required for Candida albicans lethal infection and represents a potential therapeutic target.

Abstract This study aimed to observe the safety and clinical efficacy of early application of ruxolitinib to prevent acute graft-versus-host disease (aGVHD) after alternative donor transplantation in acute leukemia. There were 57 patients undergoing allo-HSCT at the Affiliated Cancer Hospital of Zhengzhou University from July 2017 to October 2019. They were divided into control(16 patients) and ruxolitinib (41 patients) groups. For aGVHD prophylaxis, the control group received post-transplantation cyclophosphamide, antithymocyte globulin-Fresenius, cyclosporine A, and mycophenolate mofetil, while in the ruxolitinib group, ruxolitinib 5 mg/d in adults or 0.07–0.1 mg/(kg d) in children was administered from the day of neutrophil engraftment to 100 days post-transplantation based on control group. We found 55 patients had successful reconstitution of hematopoiesis; No significant difference was found in cGVHD, hemorrhagic cystitis, pulmonary infection, intestinal infection, Epstein-Barr virus infection, cytomegalovirus infection, relapse, death, and nonrelapse mortality. The incidences of aGVHD (50 vs. 22%, P = 0.046) and grade II–IV aGVHD (42.9 vs. 12.2%, P = 0.013) were significantly higher in the control group than in the ruxolitinib group. No significant differences were observed in overall survival (P = 0.514), disease-free survival (P = 0.691), and cumulative platelet transfusion within 100 days post-transplantation between two groups. This suggests early application of ruxolitinib can reduce the incidence and severity of aGVHD and patients are well tolerated.

We studied the use of self-attention mechanism networks (SAN) and convolutional neural networks (CNNs) for forest tree species classification using unmanned aerial vehicle (UAV) remote sensing imagery in Dongtai Forest Farm, Jiangsu Province, China. We trained and validated representative CNN models, such as ResNet and ConvNeXt, as well as the SAN model, which incorporates Transformer models such as Swin Transformer and Vision Transformer (ViT). Our goal was to compare and evaluate the performance and accuracy of these networks when used in parallel. Due to various factors, such as noise, motion blur, and atmospheric scattering, the quality of low-altitude aerial images may be compromised, resulting in indistinct tree crown edges and deficient texture. To address these issues, we adopted Real-ESRGAN technology for image super-resolution reconstruction. Our results showed that the image dataset after reconstruction improved classification accuracy for both the CNN and Transformer models. The final classification accuracies, validated by ResNet, ConvNeXt, ViT, and Swin Transformer, were 96.71%, 98.70%, 97.88%, and 98.59%, respectively, with corresponding improvements of 1.39%, 1.53%, 0.47%, and 1.18%. Our study highlights the potential benefits of Transformer and CNN for forest tree species classification and the importance of addressing the image quality degradation issues in low-altitude aerial images.

Abstract Posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in MSD-HSCT cohort and 25 mg/kg for 22 patients in haplo-HSCT cohort, on days + 3, + 4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for severe aplastic anemia (SAA). In MSD-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control cohort (P

Summary: Fusobacterium nucleatum (Fn) is primarily colonized in the oral cavity. Recently, Fn has been closely associated with the tumorigenesis of colorectal cancer (CRC). Here, we showed that the relative level of Fn DNA was increased in the saliva of the CRC group compared with the normal colonoscopy, hyperplastic polyp, and adenoma groups. Receiver operating characteristic curve analysis illustrated that Fn DNA was superior to carcinoembryonic antigen and carbohydrate antigen 19-9 in CRC diagnosis. Moreover, levels of Fn DNA were associated with the overall survival and disease-free survival of CRC patients, which was an independent factor for prognostic prediction. Transcriptome sequencing identified 1,287 differentially expressed mRNAs in tumor tissues between CRC patients with high-Fn and low-Fn infection. Kyoto encyclopedia of genes and genomes analysis showed that ECM-receptor interaction and focal adhesion were the top two significant pathways. Overall, salivary Fn DNA may be a noninvasive diagnostic and prognostic biomarker for CRC patients.

The ISTTWN algorithm overcame the defect of separating the production process of skeleton points and skeleton lines in tree branch point cloud skeleton extraction and improved the accuracy of the extracted initial skeletons, but the skeletons need further optimization. In the existing skeleton optimization, it is difficult to see the stump adjustment, and most of the bifurcation optimization and skeleton smoothness adopt fitting. Based on the characteristics of the initial skeletons extracted by the ISTTWN algorithm, this research optimizes the skeleton from four aspects. An algorithm for the stump adjustment for reconstructing the stump based on the layer and hierarchical relationship and an algorithm for the bifurcation optimization based on the local branch point cloud and cosine correlation are proposed, and an existing pruning method and a skeleton smoothing method are used. The results show that the skeleton optimization method proposed or used in this research has a high computational efficiency in general and can ultimately retain the necessary skeleton lines. In a visual analysis, the optimized skeleton is obviously much more natural and more in line with the actual topology of trees. In the quantitative analysis, the completeness, accuracy and effectiveness reached 97.82%, 95.72% and 89.47%, respectively. In this study, in addition to the existing tree parameters extracted by the skeleton or generalized cylinder model, the generated skeleton is used to extract the branch attributes. The R2 of the deflection angle of the branch tip, distance from branch tip and branch length are about 0.897, 0.986 and 0.988, respectively, which illustrates that their models are very good. This research can further expand the application of the skeleton.

Enterprises acquire heterogeneous knowledge through external knowledge search and adapt to the change of external environment, which is of great significance to enterprise breakthrough innovation. This paper takes the innovation ecosystem as the boundary of the research paradigm. Based on innovation ecosystem theory, knowledge management theory and enterprise innovation theory, this paper constructs a moderated mediation model of the enterprise knowledge search, knowledge integration and breakthrough innovation under the characteristics of innovation ecosystem network. This model is tested on the survey data of 344 technology enterprise and manufacturing industries including R&D departments in the Beijing-Tianjin-Hebei region. The research results show that: knowledge integration plays part of the intermediary role between knowledge search and enterprise breakthrough innovation; the larger the network scale, the stronger the network connection, the stronger the intermediary role of knowledge integration on the relationship between knowledge search and enterprise breakthrough innovation. The research results reveal the important role of the innovation ecosystem in enterprise breakthrough innovation. At the same time, the research on knowledge search and enterprise breakthrough innovation should consider the network characteristics of innovation ecosystem and the ability of enterprise knowledge integration.

The downward surface shortwave radiation (DSSR) received by an inclined surface can be estimated accurately based on the mountain radiation transfer model by using the digital elevation model (DEM) and high-resolution optical remote sensing images. However, it is still challenging to obtain the high-resolution daily average DSSR affected by the atmosphere and local topography in mountain areas. In this study, the spatial downscaling and temporal extrapolation methods were explored separately to estimate the high-resolution daily average DSSR under clear-sky conditions based on Himawari-8, Sentinel-2 satellite radiation products and DEM data. The upper and middle reaches of the Heihe River Basin (UM-HRB) and the Laohugou area of Qilian Mountain (LGH) were used as the study areas because there are many ground observation stations in the UM-HRB that are convenient for DSSR spatial downscaling studies and the high-resolution instantaneous DSSR datasets published for the LHG are helpful for DSSR temporal extrapolation studies. The verification results show that both methods of spatial downscaling and temporal extrapolation can effectively estimate the daily average DSSR. A total of 3002 measurements from six observation sites showed that the 50 m downscaled results of the Himawari-8 10-min 5 km radiation products had quite a high correlation with the ground-based measurements from the UM-HRB. The coefficient of determination (R2) exceeded 0.96. The mean bias error (MBE) and the root-mean-squared error (RMSE) were about 41.57 W/m2 (or 8.22%) and 49.25 W/m2 (or 9.73%), respectively. The fifty-two measurements from two stations in the LHG indicated that the temporal extrapolated results of the Sentinel-2 10 m instantaneous DSSR datasets published previously performed well, giving R2, MBE, and RMSE values of 0.65, 41.06 W/m2 (or 7.89%) and 88.90 W/m2 (or 17.07%), respectively. By comparing the estimation results of the two methods in the LHG, it was found that although the temporal extrapolation method of instantaneous high-resolution radiation products can more finely describe the spatial heterogeneity of solar radiation in complex terrain areas, the overall accuracy is lower than that achieved with the spatial downscaling approach.

Tuberculosis (TB) remains a serious global public health problem in the present. TB also affects other sites (extrapulmonary tuberculosis, EPTB), and accounts for a significant proportion of tuberculosis cases worldwide. In order to comprehensively understand epidemiology of EBTB in China, and improve early diagnosis and treatment, we conducted a large-scale multi-center observational study to assess the demographic data and the prevalence of common EPTB inpatients, and further evaluate the prevalence of EPTB concurrent with Pulmonary tuberculosis (PTB) and the associations between multiple EPTB types and gender-age group in China. All consecutive age≥15yr inpatients with a confirmed diagnosis of EPTB during the period from January 2011 to December 2017 were included in the study. The descriptive statistical analysis included median and quartile measurements for continuous variables, and frequencies and proportions with 95% confidence intervals (CIs) for categorical variables. Multinomial logistic regression analysis was used to compare the association of multiple EPTB types between age group and gender. The results showed that the proportion of 15-24 years and 25-34 years in EPTB inpatients were the most and the ratio of male: female was 1.51. Approximately 70% of EPTB inpatients were concurrent with PTB or other types of EPTB. The most common of EPTB was tuberculous pleurisy (50.15%), followed by bronchial tuberculosis (14.96%), tuberculous lymphadenitis of the neck (7.24%), tuberculous meningitis (7.23%), etc. It was found that many EPTB inpatients concurrent with PTB. The highest prevalence of EPTB concurrent with PTB was pharyngeal/laryngeal tuberculosis (91.31%), followed by bronchial tuberculosis (89.52%), tuberculosis of hilar lymph nodes (79.52%), tuberculosis of mediastinal lymph nodes (79.13%), intestinal tuberculosis (72.04%), tuberculous pleurisy (65.31%) and tuberculous meningitis (62.64%), etc. The results from EPTB concurrent with PTB suggested that females EPTB inpatients were less likely to be at higher risk of concurrent PTB (aOR = 0.819, 95%CI:0.803-0.835) after adjusted by age. As age increasing, the trend risk of concurrent PTB decreased (aOR = 0.994, 95%CI: 0.989-0.999) after adjusted by gender. Our study demonstrated that the common EPTB were tuberculous pleurisy, bronchial tuberculosis, tuberculous lymphadenitis of the neck, tuberculous meningitis, etc. A majority of patients with pharyngeal/laryngeal tuberculosis, bronchial tuberculosis, tuberculosis of hilar/mediastinal lymph nodes, intestinal tuberculosis, tuberculous pleurisy, tuberculous meningitis, etc. were concurrent with PTB. Female EPTB inpatients were less likely to be at higher risk of concurrent PTB, and as age increasing, the trend risk of concurrent PTB decreased. The clinicians should be alert to the presence of concurrent tuberculosis in EPTB, and all suspected cases of EPTB should be assessed for concomitant PTB to determine whether the case is infectious and to help for early diagnosis and treatment.

UTX is a tumor suppressor gene located on the X-chromosome so it could potentially contribute to the cancer gender bias. Here the authors, using a mouse model of B cell lymphoma, show that UTX is a dosage sensitive tumor suppressor and may be responsible for some of the increased incidence and possibly aggressiveness of male cancers that harbour UTX mutations.

Abstract The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and IL-4, and decreased Treg cells and IFN-γ. In patients experiencing asthma, mTOR activation was positively correlated with the loss of Th17/Treg and Th1/Th2 balance. The role of mTOR in asthma was further confirmed using an ovalbumin-induced asthmatic mouse model. The mTOR pathway was activated in asthmatic mice, demonstrated by elevated levels of p-PI3K, p-Akt, p-mTOR, and p-p70S6k, and this activation was significantly reduced by treatment with budenoside or mTOR pathway inhibitors. Moreover, mTOR pathway inhibitor treatment reduced asthmatic markers and reversed the Th17/Treg and Th1/Th2 imbalances in asthmatic mice. Finally, different mTOR pathway inhibitor treatments have different inhibitory effects on signaling molecules in asthmatic mice. In summary, mTOR is activated during asthma onset and suppressed during asthma remission, and inhibiting the mTOR pathway in asthmatic mice alleviates asthmatic markers and restores the balances of Th17/Treg and Th1/Th2 cytokines. These data strongly suggest a critical requirement for mTOR pathway activation in asthma onset, suggesting potential targets for asthma treatments.

Abstract Spermatogenesis can be affected by nutrition, which operates through normal physiological processes by changing the testicular mass and hormone levels profoundly. However, little is known regarding how testis development is regulated by long noncoding RNA (lncRNA). In this study, we investigated the effects of high-grain (HG) feeding on testis development during sexual maturation mediated by lncRNA. The HG diet group showed an increase in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and testosterone (T) levels, and in the number of sperm in the seminiferous tubules compared with the hay-fed group (p

Titanium dioxide nanoparticles (TiO2 NPs) possess unique characteristics and are widely used in many fields. Numerous in vivo studies, exposing experimental animals to these NPs through systematic administration, have suggested that TiO2 NPs can accumulate in the brain and induce brain dysfunction. Nevertheless, the exact mechanisms underlying the neurotoxicity of TiO2 NPs remain unclear. However, we have concluded from previous studies that these mechanisms mainly consist of oxidative stress (OS), apoptosis, inflammatory response, genotoxicity, and direct impairment of cell components. Meanwhile, other factors such as disturbed distributions of trace elements, disrupted signaling pathways, dysregulated neurotransmitters and synaptic plasticity have also been shown to contribute to neurotoxicity of TiO2 NPs. Recently, studies on autophagy and DNA methylation have shed some light on possible mechanisms of nanotoxicity. Therefore, we offer a new perspective that autophagy and DNA methylation could contribute to neurotoxicity of TiO2 NPs. Undoubtedly, more studies are needed to test this idea in the future. In short, to fully understand the health threats posed by TiO2 NPs and to improve the bio-safety of TiO2 NPs-based products, the neurotoxicity of TiO2 NPs must be investigated comprehensively through studying every possible molecular mechanism.

Downward surface shortwave radiation (DSSR) is the main energy source for most glacial melting, and Moderate Resolution Imaging Spectroradiometer (MODIS) and Landsat Thematic Mapper (TM) data have been used extensively in the inversion of input parameters for estimating DSSR. However, for valley glaciers under complex climatic conditions, the values of MODIS atmospheric products, especially aerosol products, are often invalid, and TM images are always saturated with snow. Furthermore, an estimation model based on optical satellite images must simultaneously consider terrain and atmospheric effects and the transient nature of ice/snow albedo. Based on a high-resolution (12 m) digital elevation model (DEM), the newly launched Sentinel-2 satellites, rather than MODIS and TM, were used to provide input data for our published mountain radiation scheme in a valley glacier. Considering Laohugou Glacier No. 12 as the study area, 62 typical Sentinel-2 scenes were selected and spatiotemporal DSSR variations on the glacier surface were obtained with a 10 m spatial resolution during a mass-balance year from September 2017 to August 2018. Ground-based measurements on 52 clear-sky days were used for validation and the mean bias error (MBE = −16.0 W/m2) and root-mean-square difference (RMSD = 73.6 W/m2) were relatively low. The results confirm that DSSR is affected mainly by the solar zenith angle and atmospheric attenuation in flat areas of valley glaciers, while in areas with complex terrain, the DSSR received by the glacier surface is affected primarily by the terrain and ice/snow albedo, which exhibits very high spatial heterogeneity.

n -Alkanes and fatty acids are important molecular markers for the source apportionment of organic matter in the atmosphere. Traditional approaches to date have mostly relied upon the source-specific differences in their molecular distributions and carbon preference index. Alternatively, we demonstrate here the use of stable carbon and radiocarbon isotopic composition ( δ ^13 C and Δ ^14 C, respectively) of n -alkanes and n -fatty acids in aerosols from two urban receptor sites (Beijing and Tianjin) in Northeast China to assess their sources in autumn. The Δ ^14 C _n _-alkanes of C _19 –C _24 and C _26 –C _32 even-carbon homologs (−851 to −708‰) indicate their dominance from fossil fuel combustion. In contrast, the Δ ^14 C of most abundant palmitic acid (C _16:0 ) and stearic acid (C _18:0 ) suggest a larger contribution from nonfossil sources (∼91%–94%), mainly due to inputs from cooking, biomass burning and microorganisms. Compared with lower Δ ^14 C of C _27 and C _31 n -alkanes (−449‰), C _29 n -alkane (−241‰) and C _20 –C _30 n -fatty acids (−263‰) showed more contemporary likely due to significant contribution from plant litter and biomass burning that contain more fresh biogenic material. Fossil character of C _27 –C _31 n -alkanes (40%) and C _20 –C _30 n -fatty acids (30%) could be from soil resuspension and/or loess deposits in upwind regions through long-range atmospheric transport.

In rugged terrain, the accuracy of surface reflectance estimations is compromised by atmospheric and topographic effects. We propose a new method to simultaneously eliminate atmospheric and terrain effects in Landsat Thematic Mapper (TM) images based on a 30 m digital elevation model (DEM) and Moderate Resolution Imaging Spectroradiometer (MODIS) atmospheric products. Moreover, we define a normalized factor of a Bidirectional Reflectance Distribution Function (BRDF) to convert the sloping pixel reflectance into a flat pixel reflectance by using the Ross Thick-Li Sparse BRDF model (Ambrals algorithm) and MODIS BRDF/albedo kernel coefficient products. Sole atmospheric correction and topographic normalization were performed for TM images in the upper stream of the Heihe River Basin. The results show that using MODIS atmospheric products can effectively remove atmospheric effects compared with the Fast Line-of-Sight Atmospheric Analysis of Spectral Hypercubes (FLAASH) model and the Landsat Climate Data Record (CDR). Moreover, superior topographic effect removal can be achieved by considering the surface BRDF when compared with the surface Lambertian assumption of topographic normalization.

Goat's milk, considered a substitute for cow's milk, has a high nutritional value. However, goat's milk contains various allergens, predominantly β-lactoglobulin (BLG). In this study, we employed the CRISPR/Cas9 system to target the BLG locus in goat fibroblasts for sgRNA optimization and generate BLG knock-out goats through co-injection of Cas9 mRNA and small guide RNAs (sgRNAs) into goat embryos at the one-cell stage. We firstly tested sgRNA editing efficiencies in goat fibroblast cells, and approximately 8.00%-9.09% of the cells were modified in single sgRNA-guided targeting experiment. Among the kids, the genome-targeting efficiencies of single sgRNA were 12.5% (10 ng/μL sg1) and 0% (10 ng/μL sg2) and efficiencies of dual sgRNAs were 25.0% (25 ng/μL sg2+sg3 group) and 28.6% (50 ng/μL sg2+sg3 group). Relative expression of BLG in BLG knock-out goat mammary glands significantly (p < 0.01) decreased as well as other milk protein coding genes, such as CSN1S1, CSN1S2, CSN2, CSN3 and LALBA (p < 0.05). As expected, BLG protein had been abolished in the milk of the BLG knock-out goat. In addition, most of the targeted kids were chimeric (3/4), and their various body tissues were edited simultaneously. Our study thus provides a basis for optimizing the quality of goat milk, which can be applied to biomedical and agricultural research.

To screen susceptibility loci for ankylosing spondylitis (AS) using an affected-only linkage analysis based on high-density single nucleotide polymorphisms (SNPs) in a genome-wide manner.AS patients from ten families with Cantonese origin of China were enrolled in the study. Blood samples were genotyped using genomic DNA derived from peripheral blood leukocytes by Illumina HumanHap 610-Quad SNP Chip. Genotype data were generated using the Illumina BeadStudio 3.2 software. PLINK package was used to remove non-autosomal SNPs and to further eliminate markers of typing errors. An affected-only linkage analysis was carried out using both non-parametric and parametric linkage analyses, as implemented in MERLIN.Seventy-eight AS patients (48 males and 30 females, mean age: 39±16 years) were enrolled in the study. The mean age of onset was 23±10 years and mean duration of disease was 16.7±12.2 years. Iritis (2/76, 2.86%), dactylitis (5/78, 6.41%), hip joint involvement (9/78, 11.54%), peripheral arthritis (22/78, 28.21%), inflammatory back pain (IBP) (69/78, 88.46%) and HLA-B27 positivity (70/78, 89.74%) were observed in these patients. Using non-parameter linkage analysis, we found one susceptibility locus for AS, IBP and HLA-B27 in 6p21 respectively, spanning about 13.5Mb, 20.9Mb and 21.2Mb, respectively No significant results were found in the other clinical trait groups including dactylitis, hip involved and arthritis. The identical susceptibility locus region spanning above 9.44Mb was detected in AS IBP and HLA-B27 by the parametric linkage analysis.Our genome-wide SNP linkage analysis in ten families with ankylosing spondylitis suggests a susceptibility locus on 6p21 in AS, which is a risk locus for IBP in AS patients.

Resistance to cisplatin-based chemotherapy is a major cause of treatment failure in advanced bladder cancer (BC) patients. There is increasing evidence that microRNAs are involved in the development and progression of BC. However, little is known about the function of microRNAs in predicting the effect of adjuvant chemotherapy on BC survival and regulating response to cisplatin. To address this issue, we employed RT-qPCR to evaluate the clinical significance of miR-203 expression in 108 tissues of BC patients receiving cisplatin-based adjuvant chemotherapy, and performed in vitro studies to explore chemotherapeutic sensitivity to cisplatin in miR-203 overexpressing BC cells. We found miR-203 levels were significantly lower in BC progression group than non-progression group (P

To present a new and effective method of producing titanium surfaces modified with strontium and to investigate the surface characteristics and in vitro biocompatibility of titanium (Ti) surfaces modified with strontium (Sr) for bone implant applications.Sr-modified Ti surfaces were produced by sequential treatments with NaOH, strontium acetate, heat and water. The surface characteristics and the concentration of the Sr ions released from the samples were examined. Cell adhesion, morphology and growth were investigated using osteoblasts isolated from the calvaria of neonatal Sprague-Dawley rats. Expression of osteogenesis-related genes and proteins was examined to assess the effect of the Sr-modified Ti surfaces on osteoblasts.The modified titanium surface had a mesh structure with significantly greater porosity, and approximately5.37±0.35at.% of Sr was incorporated into the surface. The hydrophilicity was enhanced by the incorporation of Sr ions and water treatment. The average amounts of Sr released from the Sr-modified plates subjected to water treatment were slight higher than the plates without water treatment. Sr promoted cellular adhesion, spreading and growth compared with untreated Ti surfaces. The Sr-modified Ti plates also promoted expression of osteogenesis-related genes,and expression of OPN and COL-І by osteoblasts. Ti plates heat treated at 700°C showed increased bioactivity in comparison with those treated at 600°C. Water treatment upregulated the expression of osteogenesis-related genes.These results show that Sr-modification of Ti surfaces may improve bioactivity in vitro. Water treatment has enhanced the response of osteoblasts. The Sr-modified Ti heat-treated at 700°C exhibited better bioactivity compared with that heated at 600°C.

Myostatin functions as a negative regulator of skeletal muscle growth by suppressing proliferation and differentiation of myoblasts. Dysfunction of the myostatin gene, either due to natural mutation or genetic manipulations such as knockout or knockdown, has been reported to increase muscle mass in mammalian species. RNA interference (RNAi) mediated by microRNAs (miRNAs) is a promising method for gene knockdown studies. In the present study, transient and stable silencing of the myostatin gene in caprine fetal fibroblasts (CFF) was evaluated using the two most effective constructs selected from four different miRNA expression constructs screened in 293FT cells. Using these two miRNA constructs, we achieved up to 84% silencing of myostatin mRNA in transiently transfected CFF cells and up to 31% silencing in stably transfected CFF cells. Moreover, off-target effects due to induction of interferon (IFN) response genes, such as interferon beta (IFN-β) and 2'-5'-oligoadenylate synthetase 2 (OAS2), were markedly fewer in stably transfected CFF cells than in transiently transfected cells. Stable expression of anti-myostatin miRNA with minimal induction of interferon shows great promise for increasing muscle mass in transgenic goats.

BACKGROUND: Somatic cell nuclear transfer (SCNT) is a promising technique to produce transgenic cloned mammalian, including transgenic goats which may produce Human Lactoferrin (hLF). However, success percentage of SCNT is low, because of gestational and neonatal failure of transgenic embryos. According to the studies on cattle and mice, DNA methylation of some imprinted genes, which plays a vital role in the reprogramming of embryo in NT maybe an underlying mechanism. METHODOLOGY/PRINCIPAL FINDINGS: Fibroblast cells were derived from the ear of a two-month-old goat. The vector expressing hLF was constructed and transfected into fibroblasts. G418 selection, EGFP expression, PCR, and cell cycle distribution were applied sequentially to select transgenic cells clones. After NT and embryo transfer, five transgenic cloned goats were obtained from 240 cloned transgenic embryos. These transgenic goats were identified by 8 microsatellites genotyping and southern blot. Of the five transgenic goats, 3 were lived after birth, while 2 were dead during gestation. We compared differential methylation regions (DMR) pattern of two paternally imprinted genes (H19 and IGF2R) of the ear tissues from the lived transgenic goats, dead transgenic goats, and control goats from natural reproduction. Hyper-methylation pattern appeared in cloned aborted goats, while methylation status was relatively normal in cloned lived goats compared with normal goats. CONCLUSIONS/SIGNIFICANCE: In this study, we generated five hLF transgenic cloned goats by SCNT. This is the first time the DNA methylation of lived and dead transgenic cloned goats was compared. The results demonstrated that the methylation status of DMRs of H19 and IGF2R were different in lived and dead transgenic goats and therefore this may be potentially used to assess the reprogramming status of transgenic cloned goats. Understanding the pattern of gene imprinting may be useful to improve cloning techniques in future.

BACKGROUND: The 2009 influenza pandemic affected people in almost all countries in the world, especially in younger age groups. During this time, the debate over whether to use corticosteroid treatment in severe influenza H1N1 infections patients resurfaced and was disputed by clinicians. There is an urgent need for a susceptible animal model of 2009 H1N1 infection that can be used to evaluate the pathogenesis and the therapeutic effect of corticosteroid treatment during infection. METHODOLOGY/PRINCIPAL FINDINGS: We intranasally inoculated two groups of C57BL/6 and BALB/c mice (using 4- or 6-to 8-week-old mice) to compare the pathogenesis of several different H1N1 strains in mice of different ages. Based on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501 strain of 2009 H1N1 virus infection was established, showing significantly elevated lung edema and cytokine levels compared to controls. Using our established animal model, the cytokine production profile and lung histology were assessed at different times post-infection, revealing increased lung lesions in a time-dependent manner. In additional,the mice were also treated with dexamethasone, which significantly improved survival rate and lung lesions in infected mice compared to those in control mice. Our data showed that corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1 virus in mice and suggested that corticosteroids are valid drugs for treating 2009 A/H1N1 infection. CONCLUSIONS/SIGNIFICANCE: Using the established, very susceptible 2009 Pandemic Influenza A (H1N1) mouse model, our studies indicate that corticosteroids are a potential therapeutic remedy that may address the increasing concerns over future 2009 A/H1N1 pandemics.

Ammonia (NH _3 ) is the primary alkaline gas in the atmosphere that contributes to formation of secondary particles. Emission of NH _3 from vehicles, particularly gasoline powered light duty vehicles equipped with three-way catalysts, is regarded as an important source apart from emissions from animal wastes and soils, yet measured emission factors for motor vehicles are still not available in China, where traffic-related emission has become an increasingly important source of air pollutants in urban areas. Here we present our tunnel tests for NH _3 from motor vehicles under ‘real world conditions’ in an urban roadway tunnel in Guangzhou, a central city in the Pearl River Delta (PRD) region in south China. By attributing all NH _3 emissions in the tunnel to light-duty gasoline vehicles, we obtained a fuel-based emission rate of 2.92 ± 0.18 g L ^−1 and a mileage-based emission factor of 229.5 ± 14.1 mg km ^−1 . These emission factors were much higher than those measured in the United States while measured NO _x emission factors (7.17 ± 0.60 g L ^−1 or 0.56 ± 0.05 g km ^−1 ) were contrastingly near or lower than those previously estimated by MOBILE/PART5 or COPERT IV models. Based on the NH _3 emission factors from this study, on-road vehicles accounted for 8.1% of NH _3 emissions in the PRD region in 2006 instead of 2.5% as estimated in a previous study using emission factors taken from the Emission Inventory Improvement Program (EIIP) in the United States.