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ObjectivesWe developed and tested a deep learning (DL) framework applicable to color Doppler echocardiography for automatic detection and quantification of atrial septal defects (ASDs).BackgroundColor Doppler echocardiography is the most commonly used non-invasive imaging tool for detection of ASDs. While prior studies have used DL to detect the presence of ASDs from standard 2D echocardiographic views, no study has yet reported automatic interpretation of color Doppler videos for detection and quantification of ASD.MethodsA total of 821 examinations from two tertiary care hospitals were collected as the training and external testing dataset. We developed DL models to automatically process color Doppler echocardiograms, including view selection, ASD detection and identification of the endpoints of the atrial septum and of the defect to quantify the size of defect and the residual rim.ResultsThe view selection model achieved an average accuracy of 99% in identifying four standard views required for evaluating ASD. In the external testing dataset, the ASD detection model achieved an area under the curve (AUC) of 0.92 with 88% sensitivity and 89% specificity. The final model automatically measured the size of defect and residual rim, with the mean biases of 1.9 mm and 2.2 mm, respectively.ConclusionWe demonstrated the feasibility of using a deep learning model for automated detection and quantification of ASD from color Doppler echocardiography. This model has the potential to improve the accuracy and efficiency of using color Doppler in clinical practice for screening and quantification of ASDs, that are required for clinical decision making.

BackgroundThe APLAID syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the PLCG2 gene. We present a 7-year-old APLAID patient who has recurrent blistering skin lesions, skin infections in the perineum, a rectal perineal fistula, and inflammatory bowel disease.MethodsTo determine the genetic cause of our patient, WES and bioinformatics analysis were performed. Flow cytometry was used for phenotyping immune cell populations in peripheral blood. Cytokines released into plasma were analyzed using protein chip technology. The PBMCs of patient and a healthy child were subjected to single-cell RNA-sequencing analysis.ResultsThe patient carried a novel de novo missense mutation c.2534T>C in exon 24 of the PLCG2 gene that causes a leucine to serine amino acid substitution (p.Leu845Ser). Bioinformatics analysis revealed that this mutation had a negative impact on the structure of the PLCγ2 protein, which is highly conserved in many other species. Immunophenotyping by flow cytometry revealed that in addition to the typical decrease in circulating memory B cells, the levels of myeloid dendritic cells (mDCs) in the children’s peripheral blood were significantly lower, as were the CD4+ effector T cells induced by their activation. Single-cell sequencing revealed that the proportion of different types of cells in the peripheral blood of the APLAID patient changed.ConclusionsWe present the first case of APLAID with severely reduced myeloid dendritic cells carrying a novel PLCG2 mutation, and conducted a comprehensive analysis of immunological features in the ALPAID patient, which has not been mentioned in previous reports. This study expands the spectrum of APLAID-associated immunophenotype and genotype. The detailed immune analyses in this patient may provide a basis for the development of targeted therapies for this severe autoinflammatory disease.

Competition-based approach to controlling the false discovery rate (FDR) recently rose to prominence when, generalizing it to sequential hypothesis testing, Barber and Cand\`es used it as part of their knockoff-filter. Control of the FDR implies that the, arguably more important, false discovery proportion is only controlled in an average sense. We present TDC-SB and TDC-UB that provide upper prediction bounds on the FDP in the list of discoveries generated when controlling the FDR using competition. Using simulated and real data we show that, overall, our new procedures offer significantly tighter upper bounds than ones obtained using the recently published approach of Katsevich and Ramdas, even when the latter is further improved using the interpolation concept of Goeman et al., Comment: The original version of this paper appeared as arxiv:2011.11939v1. That version was split into two: one branch continuing as v2 & v3 of that original submission, and the other branch is now added here as a new submission

Geometric rectification of images of distorted documents finds wide applications in document digitization and Optical Character Recognition (OCR). Although smoothly curved deformations have been widely investigated by many works, the most challenging distortions, e.g. complex creases and large foldings, have not been studied in particular. The performance of existing approaches, when applied to largely creased or folded documents, is far from satisfying, leaving substantial room for improvement. To tackle this task, knowledge about document rectification should be incorporated into the computation, among which the developability of 3D document models and particular textural features in the images, such as straight lines, are the most essential ones. For this purpose, we propose a general framework of document image rectification in which a computational isometric mapping model is utilized for expressing a 3D document model and its flattening in the plane. Based on this framework, both model developability and textural features are considered in the computation. The experiments and comparisons to the state-of-the-art approaches demonstrated the effectiveness and outstanding performance of the proposed method. Our method is also flexible in that the rectification results can be enhanced by any other methods that extract high-quality feature lines in the images., 23 pages,17 figures

This study aimed to develop and validate a biochemical signature for predicting the prognosis of patients with nasopharyngeal carcinoma (NPC) and explore roles of the constructed signature for screening optimal candidates for induction chemotherapy (IC). The biochemical signature was constructed based on a retrospective cohort of 3742 patients from January 2008 to December 2010; 2078 patients from prospective studies from January 2011 to December 2012 and 2153 patients from January 2013 to December 2016 served as validation cohort A and validation cohort B. Overall survival (OS) was the primary endpoint. The least absolute shrinkage and selection operator coefficients on the Cox regression model were calculated to construct the prediction model with the data of 33 biochemical indicators. A total of six prognostic indicators, including sodium, alkaline phosphatase, lactate dehydrogenase, albumin, indirect bilirubin, and cystatin-C, were screened for constructing the biochemical signature. The patients were divided into low-risk and high-risk groups using an optimal cut-off value of 0.823. The patients in high-risk group had significantly lower OS and distant metastasis-free survival (DMFS) compared with patients in low-risk group in three cohorts (P < 0.05). Furthermore, among patients with high-risk scores in the combined cohort, the addition of IC to CCRT further improved their OS and DMFS, whereas patients with low-risk scores did not benefit from IC. Our study developed and validated a clinically useful biochemical signature that could predict the survival outcomes in NPC patients. This signature can help clinicians design personalized treatment strategies.

Objective This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II–IVa nasopharyngeal carcinoma (NPC) based on Epstein–Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax‐N) of [18F]‐fluorodeoxyglucose positron emission tomography. Patients and materials A total of 679 patients diagnosed with stage II–IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log‐rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. Results Both high levels of EBV DNA (>1500 copies/mL) and SUVmax‐N (>12.3) indicated worse survival conditions. All patients were divided into low‐ and high‐risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression‐free survival (PFS), and distant metastasis‐free survival (DMFS) (all p‐values, Our study has demonstrated that EBV DNA and SUVmax‐N could serve as biomarkers to stratify NPC patients and guide physicians to select those who benefit from IC. Our findings provide important information for personalizing NPC treatment. Prospective clinical trials are warranted to evaluate the results of this study.

Supplemental material, sj-pdf-1-eji-10.1177_1721727X221091532 for Daxx ameliorates abdominal aortic aneurysm through inhibiting the TGF-β1-mediated PI3K/AKT/ID2 signaling pathway by Jie Chen, Guo-zuo Xiong, Dong-yang Luo, Qing-qing Zou, Yang-yi-jing Wnag and Guo-shan Bi in European Journal of Inflammation

Supplemental material, sj-pdf-1-eji-10.1177_1721727X221091532 for Daxx ameliorates abdominal aortic aneurysm through inhibiting the TGF-β1-mediated PI3K/AKT/ID2 signaling pathway by Jie Chen, Guo-zuo Xiong, Dong-yang Luo, Qing-qing Zou, Yang-yi-jing Wnag and Guo-shan Bi in European Journal of Inflammation

Additional file 2: Fig. S1. Identification of the DEGs in five development stages: S2 vs. S1 (A); S3 vs. S1 (B). S4 vs. S1 (C) and S5 vs. S1 (D). Fig. S2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in: S2 vs. S1 (A); S3 vs. S1 (B). S4 vs. S1 (C) and S5 vs. S1 (D). The left Y-axis indicates the KEGG pathway. The X-axis indicates the gene ratio. High padj values are indicated in purple, and low padj values are indicated in red.

Background Pancreatic cancer is one of the most common malignant diseases in the world. Gemcitabine chemotherapy remains the most important clinical treatment. However, research found that pancreatic cancer cells have chemoresistance to gemcitabine and the effect is not satisfactory. Therefore, it is urgent to find an effective early diagnosis and treatment strategy. Circular RNA is one of the most popular prognostic biomarkers in GEM-resistant PC. Materials and methods The present study was designed to evaluate the role of circHIPK3 in PC. The expression of circHIPK3 in PC tissues and cells and its effect on proliferation, migration, invasion, EMT, and apoptosis were investigated in vitro; its effect on tumor xenografts was assessed in vivo. Used bioinformation analysis to predict which miRNAs could potentially interact with circHIPK3, mRNA, and miR-330-5p. Results RT-PCR showed that the level of circHIPK3 was increased in PC tumor tissues; moreover, circHIPK3 was also increased in GEM-resistant PC tumors tissues and GEM-resistant PC cells. Sh-circHIPK3 could knockdown circHIPK3 in PANC-1-GEM and SW-1990-GEM and could significantly inhibit cell proliferation, invasion, migration, EMT and enhance cell apoptosis, compare with control group, the tumor xenografts of circHIPK3 knockdown group were significantly smaller. CircHIPK3 served as a sponge for miR-330-5p, and miR-330-5p directly bound to the 3' UTR of RASSF1 were revealed by dual luciferase assay and RIP in PC cells. CircHIPK3 knockdown of RASSF1 expression could neutralize the cytological function of PC cells by miR-330-5p inhibitor mediated GEM-resistance. Conclusion CircHIPK3 promotes gemcitabine (GEM) resistance in pancreatic cancer cells by targeting RASSF1 via miR-330-5p and regulates proliferation, invasive, migration, EMT, and apoptosis. Our research revealed that circHIPK3 may be a novel biomarker in GEM-resistant PC and could be used as a prognostic target.

Background Gemcitabine (GEM) is one of the most widely chemotherapy drugs in PC. However, the chemotherapy resistance always occurs after a period of treatment indicating poor prognosis. lncRNA may play an essential role in PC and serve as a prognosis biomarkers in PC with GEM-resistance. In our study, we aim to investigate the role of lncRNA HCP5 in PC. Materials and methods QRT-PCR detected the expression of lncRNA HCP5. The effects of knockdown lncRNA HCP5 on the proliferation, migration, invasion, cell apoptosis and autophagy were investigated in GEM-resistance PC cells. Bioinformatic analysis, luciferase reporter assay and RNA immunoprecipitation assay were performed to predict for potential miRNAs that can interact with lncRNA HCP5 and mRNAs that can interact with miR-214-3p. Results Our study revealed that lncRNA HCP5 expression was upregulated in PC tissues, especially increased expression in GEM-resistant PC tissues and GEM-resistant PC cells. Wound healing, Transwell assays, flow cytometry, Western blot, luciferase reporter assay and RNA immunoprecipitation (RIP) results demonstrated lncRNA HCP5 acted as a ceRNA to regulate GEM-resistance PC cells' proliferation, invasion, migration, cell apoptosis and autophagy by targeting HDGF via miR-214-3p. Conclusion Our results revealed that lncRNA HCP5 is highly expressed in HCC, and development of GEM-resistance PC cells involving the processes of proliferation, invasive, migration, cell apoptosis and autophagy through the miR-214-3p/HDGF axis. Targeting lncRNA HCP5 may improve gemcitabine-based therapeutic efficacy.

Key Points Question Does nedaplatin-based concurrent chemoradiotherapy (CCRT) have comparable efficacy to cisplatin-based CCRT in stage II to IVB nasopharyngeal carcinoma? Findings In this 5-year follow-up secondary analysis of a randomized clinical trial of 402 eligible patients, nedaplatin-based CCRT achieved 5-year progression-free survival rates comparable to those in the cisplatin-based CCRT group. Patients in the nedaplatin group also experienced fewer late toxic effects. Meaning These results confirm that nedaplatin-based CCRT can be regarded as an alternative to cisplatin-based CCRT in stage II to IVB nasopharyngeal carcinoma., Importance Nedaplatin-based concurrent chemoradiotherapy (CCRT) regimen at 2 years was noninferior to cisplatin-based regimen in patients with locoregional, stage II to IVB nasopharyngeal carcinoma (NPC) and was associated with fewer late adverse events, but longer-term outcomes and toxicity are unclear. Objective To evaluate the 5-year outcomes and late toxicity profile of nedaplatin-based CCRT in patients with locoregional, stage II to IVB NPC. Design, Settings, and Participants This 5-year follow-up secondary analysis of an open-label, noninferiority, multicenter randomized clinical trial enrolled patients with nonkeratinizing stage II to IVB NPC between January 16, 2012, and July 16, 2014, with a median follow-up duration of 78 months (IQR, 3-99 months). Data analysis was conducted from November 10, 2020, to July 8, 2021. Interventions Patients were randomly assigned (1:1) to receive nedaplatin (100 mg/m2)– or cisplatin (100 mg/m2)–based chemotherapy every 3 weeks for 3 cycles concurrently with intensity-modulated radiotherapy. Main Outcomes and Measures The primary end point was progression-free survival (PFS). Secondary end points were overall survival, distant metastasis–free survival, and locoregional relapse–free survival. Results A total of 402 eligible participants were enrolled (median [IQR] age, 45 [18-65] years; 302 [75.1%] male). Patients were randomly assigned to receive nedaplatin- or cisplatin-based CCRT (n = 201 for each): 196 patients (97.5%) started nedaplatin-based CCRT and 197 patients (98.0%) started cisplatin-based CCRT. Intention-to-treat analysis demonstrated a 5-year progression-free survival rate of 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for nedaplatin group, with a difference of 1.6% (95% CI, −6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs 88.8%, P = .63), distant metastasis–free survival (85.9% vs 90.4%, P = .17), and locoregional relapse–free survival (92.6% vs 89.6%, P = .17) rates. The cisplatin group had a higher incidence of grade 3 and 4 auditory toxic effects than the nedaplatin group (35 [17.7%] vs 21 [10.5%], P = .04). Conclusions and Relevance In this secondary analysis of a randomized clinical trial, long-term analysis confirmed that nedaplatin-based CCRT could be regarded as an alternative doublet treatment strategy to cisplatin-based CCRT in stage II to IVB NPC. Trial Registration ClinicalTrials.gov Identifier: NCT01540136, This 5-year follow-up secondary analysis of a randomized clinical trial analyzed survival outcomes and late toxic effects to assess the efficacy of nedaplatin-based concurrent chemoradiotherapy in the treatment of stage II to IVB nasopharyngeal carcinoma.

The rapid development of the economy and society in China has led to a series of environmental pollution problems. Exploring the interaction and coupling effects within the Economy–Society–Environment (ESE) system in urban agglomeration areas is conducive to promoting high-quality sustainable urban development. Based on systems theory, we constructed an ESE system with multiple elements, information and interaction flows. Taking the Yangtze River Delta Urban Agglomeration (YRDUA) in the period from 2010 to 2018 as a research sample, we used the Entropy Method (EM) and the Coupling Coordination Degree Model (CCDM) to synthetically evaluate the coupling coordination degree of the ESE system. The Back-Propagation Artificial Neural Network (BPANN) was applied to explore the influencing factors of the ESE system’s coupling coordination degree considering the nonlinear relationship between the various indicators and the ESE system’s coupling coordination degree. The main results can be summarized as follows. (1) The coupling coordination degree of the ESE system and the comprehensive quality of its subsystems in the YRDUA showed trends of growth during 2010–2018. There were obvious spatial differences: Shanghai had the highest quality scores, Jiangsu and Zhejiang had medium values, and Anhui had the lowest scores. However, these disparities continued to decrease during the study period. The overall coupling coordination degree distribution presents a normal distribution shape, most of cities concentrated in the moderate coordination grade. (2) At present, the coupling coordination of the society-environment binary system makes a great contribution to the ESE ternary system. (3) The comprehensive quality of the economy provides strong support for sustainable social and environmental development. (4) Factors such as the urbanization rate, proportion of tertiary industry in GDP, per-capita retail sales of consumer goods are critical to the coordinated development of the ESE system.

Prostate-Specific Membrane Antigen (PSMA) targeted radiosensitizers are developed for prostate cancer CT imaging and radiotherapy based on gold nanoparticles and a high-affinity targeting peptide, PSMA-1, revealing a size-dependent pattern., Since the introduction of PSA testing, significantly more men have been diagnosed and treated for prostate cancer. Localized prostate cancer typically is treated with prostatectomy, however there is still a high risk of recurrence after surgery, and adjuvant radiation has been shown to mitigate disease progression. X-ray therapy is frequently used as an adjuvant to treat prostate cancer, but is an imperfect tool. In this report we describe the development of a targeted-radiosensitizing nanoparticle that significantly improves X-ray therapy. Taking advantage of the demonstrated radiosensitizing activity of gold nanoparticles (AuNPs) we developed targeted AuNPs and varied both surface ligand density and AuNP size to develop an optimized AuNP for X-ray radiotherapy. We conjugated a prostate-specific membrane antigen (PSMA) targeting ligand, PSMA-1, to AuNPs and found that the targeting ligand dramatically improved gold uptake by PSMA-expressing PC3pip cells compared with PC3flu cells lacking the PSMA receptors. Further, enhancement of radiotherapy was significantly more pronounced by internalization of smaller PSMA targeted-AuNPs. Our studies provide a foundation for design of size-selected AuNPs for targeted radiotherapy and, for the first time, systematically investigate both the effect of ligand and AuNP size on the cell uptake, tumor targeting and radiotherapy efficacy.

Abundant tight oil resources have been found in the Qingxi depression of the Jiuquan basin. However, the accumulation characteristics of the tight oil in the basin remain unclear, as well as the resources potential, which restricts tight oil exploration and development in the basin. In this article, reservoir characteristics analysis result, based on the study of the Xiagou formation in the Qingxi depression, Jiuquan Basin, shows that the distribution of tight oil is consistent to the distribution of source rocks and faults in the area, besides, high hydrocarbon output intervals are characterized by high TOC content and well developed faults system. It is indicated from the source and reservoir assemblage characteristics that both source–reservoir coexistence and sandwich type are favorable for tight oil enrichment. Tight oil reserves of three formations, K1g3、 K1g2、K1g1, have been calculated by facet volume calculation method and the calculated results of the three layers are 42.257×106t、56.326×106t、106.324×106t, respectively. The overall reserves are supposed to be 204.897×106t and the favorable target for tight oil has thus been predicted. The assessment would effectively further guide tight oil exploration and development in the area.

Wind turbines are one of the key systems in wind energy development. The wind tower supporting the whole wind turbine is a towering structure, which has been affected by installation, transportation, environment, and other factors. Furthermore, it is prone to experience other quality problems that would be difficult to detect for wind turbine towers. Therefore, the key to maintain the wind tower structure and to ensure the normal operation of a wind turbine is to carry out comprehensive and detailed detection and monitoring studies during its service stage. This paper sorted out several common quality problems including structural damage, deformation, flange bolts loosening, and corrosion of wind tower and relevant research on the detection and monitoring of these quality problems. In addition, some nondestructive testing technologies are introduced, including the ultrasonic phased array, time of flight diffraction, magnetic memory, acoustic emission, fiber Bragg grating and piezoelectric impedance, and applications in wind turbine towers.

Recently, Barber and Cand\`es laid the theoretical foundation for a general framework for false discovery rate (FDR) control based on the notion of "knockoffs." A closely related FDR control methodology has long been employed in the analysis of mass spectrometry data, referred to there as "target-decoy competition" (TDC). However, any approach that aims to control the FDR, which is defined as the expected value of the false discovery proportion (FDP), suffers from a problem. Specifically, even when successfully controlling the FDR at level $\alpha$, the FDP in the list of discoveries can significantly exceed $\alpha$. We offer FDP-SD, a new procedure that rigorously controls the FDP in the competition (knockoff / TDC) setup by guaranteeing that the FDP is bounded by $\alpha$ at any desired confidence level. Compared with the just-published general framework of Katsevich and Ramdas, FDP-SD generally delivers more power and often substantially so in simulated as well as real data., Comment: This revision focuses only on FDP-SD described in the original submission. A later submission will further develop the procedures for simultaneous bounds on the FDP

Additional file 1: Supplementary Table 1. Description of drinking behaviors and association with self-harm frequency by gender.

Additional file 2: Supplementary Table 2. Results of Log-binomial regression (Reasons for drinking).

Additional file 3: Supplementary Table 3. AORs for students in different school types by gender.

Background Pancreatic cancer is one of the most common malignant diseases in the world. Gemcitabine chemotherapy remains the most important clinical treatment. However, research found that pancreatic cancer cells have chemoresistance to gemcitabine and the effect is not satisfactory. Therefore, it is urgent to find an effective early diagnosis and treatment strategy. Circular RNA is one of the most popular prognostic biomarkers in GEM-resistant PC. Materials and Methods The present study was designed to evaluate the role of circHIPK3 in PC. The expression of circHIPK3 in PC tissues and cells and its effect on proliferation, migration, invasion, EMT, and apoptosis were investigated in vitro; its effect on tumor xenografts was assessed in vivo. Used bioinformation analysis to predict which miRNAs could potentially interact with circHIPK3, mRNA, and miR-330-5p. Results RT-PCR showed that the level of circHIPK3 was increased in PC tumor tissues; moreover, circHIPK3 was also increased in GEM-resistant PC tumors tissues and GEM-resistant PC cells. Sh-circHIPK3 could knockdown circHIPK3 in PANC-1-GEM and SW-1990-GEM and could significantly inhibit cell proliferation, invasion, migration, EMT and enhance cell apoptosis, compare with control group, the tumor xenografts of circHIPK3 knockdown group were significantly smaller. CircHIPK3 served as a sponge for miR-330-5p, and miR-330-5p directly bound to the 3′ UTR of RASSF1 were revealed by dual luciferase assay and RIP in PC cells. CircHIPK3 knockdown of RASSF1 expression could neutralize the cytological function of PC cells by miR-330-5p inhibitor mediated GEM-resistance. Conclusion CircHIPK3 promotes gemcitabine (GEM) resistance in pancreatic cancer cells by targeting RASSF1 via miR-330-5p and regulates proliferation, invasive, migration, EMT, and apoptosis. Our research revealed that circHIPK3 may be a novel biomarker in GEM-resistant PC and could be used as a prognostic target.

Controlled drug delivery and gene expression is required for a large variety of applications including cancer therapy, wound healing, cell migration, cell modification, cell-analysis, reproductive and regenerative medicine. Controlled delivery of precise amounts of drugs to a single cell is especially interesting for cell and tissue engineering as well as therapeutics and has until now required the application of micro-pipettes, precisely placed dispersed drug delivery vehicles, or injections close to or into the cell. Here we present surface bound micro-chamber arrays able to store small hydrophilic molecules for prolonged times in subaqueous conditions supporting spatiotemporal near infrared laser mediated release. The micro-chambers (MCs) are composed of biocompatible and biodegradable polylactic acid (PLA). Biocompatible gold nanoparticles are employed as light harvesting agents to facilitate photothermal MC opening. The degree of photothermal heating is determined by numerical simulations utilizing optical properties of the MC, and confirmed by Brownian motion measurements of laser-irradiated micro-particles exhibiting similar optical properties like the MCs. The amount of bioactive small molecular cargo (doxycycline) from local release is determined by fluorescence spectroscopy and gene expression in isolated C2C12 cells via enhanced green fluorescent protein (EGFP) biosynthesis.

The luminous efficiency of radiation (LER) and colour rendering indices (CRIs) are two key technological parameters for white light-emission diodes (WLEDs), but there is always a trade-off between them, especially between LER and R9 (the 9th CRI for red colour). It is therefore necessary to find ways to solve this problem by choosing appropriate red phosphors as well as the phosphor blend. In this work, we attempted to apply both a narrow-band (K2SiF6:Mn4+,KSF) and a broad-band ((Sr,Ca)AlSiN3:Eu2+, SCASN) red phosphors together with a green phosphor (Lu3Al5O12:Ce3+, LuAG) to minimize the trade-off. For a warm white LED with the correlated colour temperature of 3000 K, the combination of a single red phosphor (either KSF or SCASN) and LuAG led to high LERs (92.4 lm W−1 for KSF and 95 lm W−1 for SCASN) but low Ra (average of the first eight CRIs) and R9 (Ra = 60.9 and R9 = −28.2 for KSF; Ra = 83.7 and R9 = 16.6 for SCASN). On the other hand, by using dual red phosphors instead of one, CRIs and even LERs are significantly increased, which is dominantly ascribed to the narrow emission band and the absence of re-absorption of green light of KSF. A superior WLED with LER = 115.4 lm W−1, Ra = 96.9 and R9 = 95.8 was attained when pumping the phosphor blend of (KSF:SCASN:LuAG = 6 : 0.75 : 5.1 in weight ratio) by a blue InGaN LED, which enables it to be used broadly for high quality solid state lighting.

In this paper, magnetic Fe 3 O 4 hollow spheres based magnetic-fluorescent nanoparticles, hollow structured Fe 3 O 4 @Gd 2 O 3 :Eu 3+ , were synthesized through a homogeneous precipitation method. The microstructure, luminescence, and magnetic properties of the samples were investigated and discussed with the help of various analytic techniques including X-ray diffraction, scanning electron microscope, energy dispersive spectrometer, cathodelumincence mapping, photoluminescence spectra and vibrating sample magnetometer. The hollow spheres nanoparticles, emitting at 612 nm dominantly under the 254 nm excitation, exhibited the photoluminescence intensity 2.45 times higher than the solid sphere samples, due to the. hollow spheres structure. The hollow Fe 3 O 4 @Gd 2 O 3 :Eu 3+ nanoparticles were spherical, and had a particle size of about 1400 nm in diameter. They also showed a saturation magnetization of 1.33 emu/g, a coercivity Hc of 160 Oe and a remanence of 0.05 emu/g at room temperature, the saturation magnetization of hollow spheres nanoparticles is higher than the solid sphere samples. The enhanced photoluminescence and magnetic properties of the hollow structured nanoparticles allow them to be used in biomedical applications.

Supplemental material, PUL888428 Supplementary material2 for Prediction value of pulmonary hypertension in newly identified left ventricular dysfunction among adult patients after patent ductus arteriosus closure by Peng-yuan Chen, Dong-ling Luo, He-zhi Li, Hong-wen Fei, Tao Huang, Yi-gao Huang, Ji-mei Chen, Jian Zhuang, Peng-cheng He and Cao-jin Zhang in Pulmonary Circulation

Figure S1. Investigation of the characteristics of NaCl and mannitol stress resistance in alfalfa seedlings. Figure S2. Iso-Seq sequencing, assembly, and annotation of alfalfa. Figure S3. The quality of the BGISEQ-500 RNA-Seq data. Figure S4. An overview of continuous dynamic changes in DEG expression levels. Figure S5. Heatmap plot of the expression levels of the osmotic stress-related DEGs co-regulated by NaCl and mannitol. (PDF 875 kb)

As a mining industry which is vital to the national economy, the oil and gas industry is faced with various uncertainties from the exploration and development at the upstream, refining and production at the midstream to the transportation and sale at the downstream. With the implementation of the “Go Global” strategy of the oil and gas industry and the steady progress of the Belt and Road Initiative, a more comprehensive and accurate identification, classification and quantification of the uncertain factors facing the oil and gas industry is required by the “14th Five-Year Plan”. This paper first identifies and classifies the uncertain factors of the oil and gas industry and then analyzes the difference between those uncertain factors from the domestic and overseas perspectives. Different methods of quantifying the uncertainties are also designed from the three dimensions of resource, technology and economy. Based on the development trend of various factors during the “14th Five-Year Plan” period, this paper predicts the quantitative results of uncertainties in the following 10 years.

In this paper, the Gd 3+ codoped bifunctional coreshell nanoparticles, Fe 3 O 4 @(Y 1-x Gd x ) 2 O 3 :Eu 3+ , were synthesized through a Urea Homogeneous Preci-pitation method. The microstructure, luminescence, and magnetic properties of the codoped samples were investigated and discussed with the help of various analytic techniques including X-ray diffraction, scanning electron microscope, photo-luminescence spectra, cathodelumincence mapping and vibrating sample magnetometer. The co-doped sample (x = 0.3), emitting at 612 nm dominantly under the 254 nm excitation, exhibited the photoluminescence intensity 2.7 times higher than the undoped one (x = 0), due to the efficient energy transfer between Gd 3+ and Eu 3+ . The Fe 3 O 4 @(Y 1-x Gd x ) 2 O 3 :Eu 3+ core–shell nanoparticles were spherical and uniform, and had a particle size of about 180 nm in diameter. They also showed a saturation magnetization of 1.09 emu/g, a coercivity of 20 Oe and a remanence of 0.01emu/g. The enhanced photoluminescence and good magnetic properties of the title core–shell nanocomposites allow them to be used in biomedical applications.

In this paper, bifunctional Fe 3 O 4 @Gd 2 O 3 :Eu 3+ core-shell nanoparticles with both magnetic and fluorescent properties were synthesized through a urea homogeneous precipitation (UHP) method. Particular emphasis was placed on investigating the influence of the solution pH value on the photoluminescence of the core-shell nanocomposites. It showed that the samples treated at the solution of pH=3.0 had the highest luminescence due to the enhanced crystallinity and size uniformity of nanoparticles. The Fe 3 O 4 @Gd 2 O 3 :Eu 3+ nanocomposites exhibited an almost spherical shape with a mean diameter of 60 nm, and had strong red emissions of Eu 3+ at 612 nm as well as good magnetization with the saturation magnetization of 1.29 emu/g. It thus indicated that the core-shell nanocomposites investigated has great potential in biomedical applications.

Background: Sainfoin (Onobrychis viciifolia) is a highly nutritious, tannin-containing, and tetraploid forage legume. Due to the lack of detailed transcriptomic and genomic information on this species, genetic and breeding projects for sainfoin improvement have been significantly hindered. Methods: In this study, a total of 24,630,711 clean reads were generated from 14 different sainfoin tissues using Illumina paired-end sequencing technology and deposited in the NCBI SRA database (SRX3763386). From these clean reads, 77,764 unigene sequences were obtained and 6,752 EST-SSRs were identified using denovo assembly. A total of 2,469 primer pairs were designed, and 200 primer pairs were randomly selected to analyze the polymorphism in five sainfoin wild accessions. Results: Further analysis of 40 sainfoin individuals from the five wild populations using 61 EST-SSR loci showed that the number of alleles per locus ranged from 4 to 15, and the expected heterozygosity varied from 0.55 to 0.91. Additionally, by counting the EST-SSR band number and sequencing the three or four bands in one sainfoin individual, sainfoin was confirmed to be autotetraploid. This finding provides a high level of information about this plant. Discussion: Through this study, 61 EST-SSR markers were successfully developed and shown to be useful for genetic studies and investigations of population genetic structures and variabilities among different sainfoin accessions.

Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10–20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments.

With the era of globalisation, China has become one of the most important video game markets in the world. To enter the Chinese market, culture adjustments are often made to video games in order to meet the needs and expectations of Chinese gamers. After briefly describing the characteristics of the Chinese game market, this article will focus on the process of cultural adaptation that games undergo when they are localised into Chinese, focusing on game-related aspects such as number format, food-related terminology, myths and legends, songs, the use of colours, character design, and game mechanics, as well as sociocultural, economic and political issues such as gaming habits and censorship. A number of examples are provided to illustrate how the above-mentioned aspects may affect the success of a foreign game in the Chinese market. The article concludes by highlighting the importance of cultural adaptation in game localisation into Chinese and outlining future research avenues

Knockdown of CLCA2 promotes the growth in NPC cells in vitro. (PDF 464Â kb)

Overexpressing CLCA2 impairs NPC cell migration and silencing CLCA2 promotes NPC cell migration ability in vitro. (PDF 492Â kb)

Hu, Ben, Zeng, Lei-Ping, Yang, Xing-Lou, Ge, Xing-Yi, Zhang, Wei, Li, Bei, Shen, Xu-Rui, Zhang, Yun-Zhi, Wang, Ning, Luo, Dong-Sheng, Zheng, Xiao- Shuang, Wang, Mei-Niang, Daszak, Peter, Wang, Lin-Fa, Cui, Jie, Shi, Zheng- Li (2017): Discovery of a rich gene pool of bat SARSrelated coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathogens 13 (11), No. 1006698: 1-27, DOI: 10.1371/journal.ppat.1006698

This paper proposes a new gate driver circuit integrated by IZO-thin film transistors(TFTs),which employs a new driving method called input block multiplex structure.One input blockdriving several output blocks is used in this method,which can reduce the number of TFTs and save the area of the circuit dramatically,satisfying the design of the high resolution and narrow bezel displays.The working time of the input block is ntimes as the output block,where the parameter‘n'is the quantity of output blocks driven by one input block.Therefore the frequency of the driving clock of the proposed circuit is 1/nof the traditional circuits,in which one input block is used to drive one output block.We have successfully fabricated 20 stages of the circuit.The structure is one input block driving two output blocks and the dimension is 730μm width and 164μm height,which can realize the narrow bezel easily.The experimental results show the circuit can work well and be suitable for 300 PPI displays of AMLCD or AMOLEDs.

Objective: This study aims to examine the effects of low intensity pulsed ultrasound (LIPUS) on leukopenia induced by cyclophosphamide in a rabbit model. Methods: The leukopenia model in New Zealand rabbit was established by injecting cyclophosphamide into the ear vein. Forty leukopenia model rabbits were randomly allocated to control group (n = 20) and LIPUS group (n = 20). LIPUS group underwent 20 minutes of daily ultrasound treatment at femoral metaphysis for 7 days while control group received sham treatment. Diarrhea rate, mortality and blood cell count were calculated. IgA, IgG and IgM levels were measured by ELISA. Flow cytometry was used to detect CD44, CD49d, and PU.1. HE staining was performed to analyze bone marrow hyperplasia and changes of skin and muscle. Results: LIPUS treatment significantly promoted the proliferation of bone marrow nucleated cells, increased the number of WBC, IgA, IgG and IgM in the peripheral blood, and reduced the diarrhea rate and mortality. The irradiated skin and muscle tissues showed no obvious damages. LIPUS treatment promoted the migration of hematopoietic cells to peripheral blood by decreasing the expression of CD49d and CD44 on the surface of CD34 positive cells. It also promoted the differentiation of hematopoietic stem cells into granulocytes and lymphocytes by decreasing the expression of PU.1. Conclusion: LIPUS can be used as a safe and effective clinical treatment for cyclophosphamide induced leukopenia.

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Background: Though as a heavy metal, mercury has a long history in the culture of traditional Chinese medicine (TCM). Also until now, we can still find evidence of mercury in some Chinese folk prescriptions (CFP)s in China. Case: We report a case of a 35-year-old rural woman, who took almost 35 g of Hg2O orally to treat her itchy skin followed a folk prescription of an unlicensed practitioners engaging in quackery (UPEQ), which lead to dark red bloody stool and mucus, nausea, and numbness. She sought help from some general hospitals, which brought her only misdiagnosis. Only after a mercury level test conducted by Chongqing Prevention and Treatment Center for Occupational Diseases (CPOD) confirmed her mercury intoxication, she was treated with chelation therapy with sodium dimercaptosulphonat and showed significant improvements. Conclusion: Confused by differences between TCM and CFP, people might take dangerous remedies without realizing the consequences; not only could it exacerbate their primary disease, but it could lead to unexpected and disastrous results.

According to the 2030 Agenda for Sustainable Development, the sustainable development goal 11 is to “make cities and human settlement inclusive, safe, resilient and sustainable”. China has been making great effort in this respect. With the advancement in science and technology, the concepts of green development, environmental friendliness, and fair development are gradually moving from theories to practices, guiding the construction and development of sustainable cities in China. Over the past 40 years of reform and opening up, the overall process of China’s construction of sustainable cities and development can be divided into three stages: the initial practice stage (1986–2000), the stage focusing on transformation (2001–2012), and the stage emphasizing coordinated development and social fairness (2012 to present). During the process, China has proposed and carried out a series of pilot demonstrations of sustainable cities, eco-cities, garden cities, low-carbon cities, livable cities, resilient cities, sanitary cities, sponge cities, and circular economy cities. It has achieved remarkable results with valuable experience; meanwhile, it still faces many challenges considering the current practices. With the integration of planning for the national economy and social development, rural and urban development, land use, and other aspects, as well as the implementation of the 2030 Agenda for Sustainable Development, sustainable urban practices in China will receive more policy support and effective administrative support. As the largest developing country in the world, China’s practice in sustainable urban development undoubtedly has a broad demonstration effect and can contribute to global sustainable development.

The tyrosine kinase Janus kinase 3 (JAK3) contributes to signaling regulating the proliferation and apoptosis of lymphocytes and tumor cells. Replacement of lysine by alanine in the catalytic subunit yields the inactive (K851A)JAK3 mutant that underlies severe combined immune deficiency. The gain-of-function mutation (A572V)JAK3 is found in acute megakaryoplastic leukemia and T cell lymphoma. The excessive nutrient demand of tumor cells requires upregulation of transporters in the cell membrane including peptide transporters PEPT1 and PEPT2. The carriers further accomplish intestinal peptide transport. Little is known about signaling regulating peptide transport. The present study explored whether PEPT1 and PEPT2 are upregulated by JAK3. PEPT1 or PEPT2 was expressed in Xenopus oocytes with or without additional expression of JAK3, and electrogenic peptide (glycine-glycine) transport was determined by dual-electrode voltage clamp. PEPT2-HA membrane protein abundance was analyzed by chemiluminescence. Intestinal electrogenic peptide transport was estimated from peptide-induced current in Ussing chamber experiments. In PEPT1- and PEPT2-expressing oocytes, but not in water-injected oocytes, the dipeptide gly-gly generated an inward current, which was significantly increased following coexpression of JAK3. The effect of JAK3 on PEPT1 was mimicked by (A568V)JAK3 but not by (K851A)JAK3. JAK3 increased maximal peptide-induced current in PEPT1-expressing oocytes but rather decreased apparent affinity of the carrier. Coexpression of JAK3 enhanced the PEPT2-HA protein abundance in the cell membrane. In JAK3- and PEPT1-expressing oocytes, peptide-induced current was blunted by the JAK3 inhibitor WHI-P154, 4-[(3'-bromo-4'-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline (22 μM). In intestinal segments gly-gly generated a current which was significantly smaller in JAK3-deficient mice (jak3⁻/⁻) than in wild-type mice (jak3⁺/⁺). In conclusion, JAK3 is a powerful regulator of peptide transporters PEPT1 and PEPT2.

We report the findings of three randomized, double-blind, placebo-controlled Phase I studies undertaken to support licensure of the liquid formulation of the human G1P[8] rotavirus (RV) vaccine (RIX4414; GlaxoSmithKline Biologicals SA) in China. Healthy adults aged 18–45 y (n = 48) and children aged 2–6 y (n = 50) received a single dose of the human RV vaccine or placebo. Healthy infants (n = 50) aged 6–16 weeks at the time of first vaccination received two oral doses of the human RV vaccine or placebo according to a 0, 1 mo schedule. In infants, blood samples were collected prior to vaccination and one month post-dose 2 to assess anti-RV IgA antibody concentrations using ELISA. Stool samples were collected from all infants on the day of each vaccination, at 7 and 15 d after each vaccination and one month post-dose 2. Stool samples were analyzed by ELISA for detection of RV antigen to assess RV antigen excretion. The reactogenicity profile of the human RV vaccine was found to be comparable to that of placebo in all age groups studied. The anti-RV IgA antibody seroconversion rate in infants after two vaccine doses was 86.7% (95% CI: 59.5–98.3). Vaccine take in infants who received the liquid human RV vaccine was 86.7% (95% CI: 59.5–98.3). A Phase III efficacy study of the human RV vaccine in the infant population in China has now been completed (ROTA-075/NCT01171963).

Background/Aims: Janus-activated kinase-2 JAK2 participates in the signaling of several hormones including growth hormone, fosters tumor growth and modifies the activity of several Na+ coupled nutrient transporters. Peptide uptake into intestinal and tumor cells is accomplished by electrogenic peptide transporters PEPT1 and PEPT2. The present study thus explored whether JAK2 contributes to the regulation of PEPT1 and PEPT2 activity. Methods: cRNA encoding either PEPT1 or PEPT2 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild type JAK2, constitutively active V617FJAK2 or inactive K882EJAK2. The current created by the dipeptide glycine-glycine (Igly-gly) was determined by dual electrode voltage clamp and taken as measure for electrogenic peptide transport. Results: No appreciable Igly-gly was observed in water injected oocytes. In PEPT1 or PEPT2 expressing oocytes Igly-gly was significantly increased by additional coexpression of JAK2. As shown in PEPT1 expressing oocytes, Igly-gly without significantly modifying the concentration required for halfmaximal Igly-gly (KM). Following disruption of carrier insertion with brefeldin A (5 µM) Igly-gly declined similarly fast in Xenopus oocytes expressing PEPT1 with JAK2 and in Xenopus oocytes expressing PEPT1 alone. In oocytes expressing both, PEPT1 and V617FJAK2, Igly-gly was gradually decreased by JAK2 inhibitor AG490 (40 µM). According to Ussing chamber experiments pharmacological JAK2 inhibition similarly decreased Igly-gly in mouse intestine. Conclusion: Regulation of the peptide transporters PEPT and PEPT2 does involve the Janus-activated kinase-2 JAK2.