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DC circuit breakers (DCCBs) play a significant role in obtaining the reliability and stability of DC power systems. Selective and fast isolating of faults minimizes the power supply outages to end electricity users and protects the power converters implemented in the DC system. During the last decades, DCCBs have been deeply investigated in industry and academia. There has been impressive progress in terms of efficiency, response time, power-density, lifetime, and electrical operating ratings. Introducing wide bandgap (WBG) devices further has motivated researchers to propose more efficient and novel topologies. This paper provides a point of reference and a background review for DCCBs from novel aspects, fulfilling absent parts in the literature. The elaborated subjects include current commutation circuitry, DCCBs trip-curves developments, newly added functions to DCCBs, as well as marketing analysis. The advancements of DCCBs are surveyed and development needs are recognized. This paper aims to identify the future research needs of DCCBs for emerging DC power systems.

Objective: Summarize the experience of transporting patients in the pre-hospital emergency center of our hospital from January 20, 2020 to May 2020 during the outbreak of novel coronavirus pneumonia in Zhuzhou City, and formulate a series of transport strategies. Methods: During the novel coronavirus pneumonia epidemic, review the relevant experience of the medical staff and drivers in the pre-hospital emergency center of Zhuzhou Central Hospital to improve the procedures for the transfer of patients during the epidemic. Results: As of the time when patients with novel coronavirus pneumonia in our city are cleared, none of the medical staff in the pre-hospital emergency center of Zhuzhou Central Hospital has been infected, and the city's patients in need of pre-hospital emergency treatment have been treated in an orderly manner. In conjunction with our hospital's epidemic prevention and control expert team, combined with the actual situation in the region, we jointly formulated a series of transfer procedures for Zhuzhou Central Hospital to comply with the region during the epidemic. Conclusion: During the novel coronavirus pneumonia epidemic, all patients received by the pre-hospital emergency center of our hospital were transferred in a timely and safe manner, and a series of transfer procedures were developed.

This paper introduces a 4kV/120A solid-state DC circuit breaker (DCCB) based on discrete SiC MOSFETs. The DCCB is designed in a 5-layer tower structure. Each layer consists of a circular main conduction branch and an attached gate driver. There are two primary benefits in the proposed DCCB. First, it reduces conduction loss with multiple devices in parallel. Second, it achieves an ultrafast response speed with SiC MOSFETs. Moreover, the gate drivers of the DCCB are powered by a domino inductive power transfer (IPT) system. It achieves the load-independent constant-voltage output characteristics, which means the outputs are immune to load variations. An IPT system prototype is implemented to test the power transfer performance. At 500kHz frequency, the total output power reaches 15.73W that is sufficient to power on 5 gate drivers, with a peak transfer efficiency of 75.4%. The IPT system is tested to power a 4kV/120A DCCB prototype. It validates that the DCCB is effective to turn off 120A current within 3.5s.

The high operating temperature of dielectric capacitors applied in electric vehicles, aerospace and underground exploration require dielectric materials with high temperature resistance and high energy density. Polyimide (PI) turns out to be a potential dielectric material for capacitors applications at high temperature. In this review, the key parameters related to high temperature resistance and energy storage characteristics were introduced and recent developments in all-organic PI dielectrics and PI-matrix dielectric nanocomposites were discussed. Synthetic strategies of new functional PI via modification at the molecular level together with the design engineering of nanofillers and multilayer structures of PIs were also analysed. Finally, a systematic summary of the current challenges and future developments for capacitor materials used at high temperatures were presented.

Background The role of different types and quantities of macronutrients on human health has been controversial, and the individual response to dietary macronutrient intake needs more investigation. Objectives We aimed to use an 'n-of-1' study design to investigate the individual variability in postprandial glycemic response when eating diets with different macronutrient distributions among apparently healthy adults. Methods Thirty apparently healthy young Chinese adults (women, 68%) aged between 22 and 34 y, with BMI between 17.2 and 31.9 kg/m2, were provided with high-fat, low-carbohydrate (HF-LC, 60-70% fat, 15-25% carbohydrate, 15% protein, of total energy) and low-fat, high-carbohydrate (LF-HC, 10-20% fat, 65-75% carbohydrate, 15% protein) diets, for 6 d wearing continuous glucose monitoring systems, respectively, in a randomized sequence, interspersed by a 6-d wash-out period. Three cycles were conducted. The primary outcomes were the differences of maximum postprandial glucose (MPG), mean amplitude of glycemic excursions (MAGE), and AUC24 between intervention periods of LF-HC and HF-LC diets. A Bayesian model was used to predict responders with the posterior probability of any 1 of the 3 outcomes reaching a clinically meaningful difference. Results Twenty-eight participants were included in the analysis. Posterior probability of reaching a clinically meaningful difference of MPG (0.167 mmol/L), MAGE (0.072 mmol/L), and AUC24 (13.889 mmol/L·h) between LF-HC and HF-LC diets varied among participants, and those with posterior probability >80% were identified as high-carbohydrate responders (n = 9) or high-fat responders (n = 6). Analyses of the Bayesian-aggregated n-of-1 trials among all participants showed a relatively low posterior probability of reaching a clinically meaningful difference of the 3 outcomes between LF-HC and HF-LC diets. Conclusions N-of-1 trials are feasible to characterize personal response to dietary intervention in young Chinese adults.

The frequency and distribution of chromosomal abnormalities and the impact of parental chromosomal aberration on the pregnancy outcomes of couples with recurrent pregnancy loss remains controversial. 3235 RPL couples who experienced two or more miscarriages before 20 weeks were diagnosed in our tertiary referral hospital during 2008–2018 and included in the single-center retrospective cohort study covering a 10-year period. Chromosome aberration was detected in 121 (3.74%) among 3235 RPL couples which included 75 female and 46 male cases at an individual level. 101 cases were structural aberrations including balanced translocations in 46(38.0%) cases, Robertsonian translocations in 13(10.7%) cases, inversions in 42(34.7%) cases and 20(16.5%) cases were numerical aberrations. 121 carriers and 428 non-carriers were followed up for two years, 55 carriers and 229 non-carriers were subsequent pregnant after diagnosis by natural conception or intrauterine insemination. The frequency of carriers to have a health newborn was not significantly different with non-carriers (72.7% vs. 71.2%, adjusted P = 0.968). This study described the majority of carriers were balanced translocations and chromosome aberrations had a limited influence on live birth rate from the present data. The results of the study also remind us that natural conception may be also a good alternative rather than PGD (Pre-implantation Genetic Diagnosis) which is common in many other reproductive centers for such patients.

This article presents six groups of dynamic temperature-sensitive electrical parameters (TSEPs) for the medium-voltage silicon carbide (SiC) and silicon (Si) devices. The physical mechanisms of the temperature dependence of these parameters are analyzed with the difference between SiC and Si devices highlighted. A test platform is developed that enables implementation of the temperature relevant dynamic characterization. The investigated TSEPs are summarized in terms of their relationship with junction temperature, load current, dc voltage, and external gate resistance. The impact of the parasitic parameters on the evaluation results is analyzed. The comparison between 3.3-kV 5-A SiC MOSFETs and 3-kV 12-A Si insulated-gate bipolar transistors (IGBTs) is conducted. The results verify that for the medium-voltage SiC MOSFETs, the turn-off drain–source voltage switching rate, the turn-off gate current peak value, and the turn-on gate current plateau achieve better thermal sensitivity, in comparison with the Si IGBTs. The turn-off and turn-on delay time exhibit better thermal linearity compared with other investigated TSEPs.

Sleep deprivation (SD) leads to cognitive impairment due to neuroinflammation associated with impaired hippocampal neuronal plasticity and memory processes. Liver X receptors (LXRs), including LXRα and LXRβ isoforms, are crucial for synaptic plasticity as well as anti-inflammation. However, the potential roles of LXRs in the pathogenesis of cognitive impairment induced by SD remain unclear. We revealed that SD resulted in LXRβ reduction in hippocampus, which was associated with upregulated expression of high mobility group box1 (HMGB1)/toll-like receptor 4 (TLR4)/NF-κB p65, and knockdown of hippocampal LXRβ by shRNA (shLXRβ) led to cognitive impairment. GW3965, a dual agonist for both LXRα and LXRβ, ameliorated SD-induced cognitive impairment by inhibiting microglia activation, suppressing HMGB1/TLR4/NF-κB p65 pathway, and ultimately affecting the hippocampal expression of inflammatory cytokines in SD mice. LXRβ knockdown by shLXRβ, abrogated GW3965-mediated the inhibition of HMGB1/TLR4/NF-κB p65 pathway, therefore abolished the cognitive improvement. Moreover, inhibition of HMGB1 by glycyrrhizin (GLY) synergistic promoted GW3965-mediated anti-inflammation in activated microglia after LPS/ATP stimulation and facilitated the cognitive improvement after GW administration by activating LXRβ. All the data suggested that GW3965 ameliorated impaired cognition in SD mice by suppressing HMGB1/TLR4/NF-κB p65 pathway followed LXRβ activation. This study correlates a deficit of LXRβ in cognitive dysfunction in SD associated with HMGB1 inflammatory pathway in hippocampus, and LXRs may serve as a potential therapeutic target for cognitive impairment with anti-inflammation.

This article proposes an S-CLC compensation network to achieve a relay system to power multiple gate drivers of series modules. There are three major contributions. First, it achieves the constant voltage (CV) and load-independent property, meaning the induced voltage on each receiver is immune to load variations. Second, the S-CLC circuit topology is compact to be constructed, and an integrated coil structure is proposed to limit the system size. Third, the efficiency of the power relay system is analyzed, including parasitic resistances of resonant components and coils, which reveal the load regulation phenomenon in practical applications. In order to validate the proposed topology, the parameter design methodology to achieve the highest efficiency is proposed, and a single-input-four-output prototype is implemented. The coil size is 180 mm × 175 mm, the transfer distance between receivers is 50 mm, and the switching frequency is 200 kHz. When the input dc voltage is 18 V, the induced voltage of each receiver is around 15 V, and the voltage difference between receivers is within 2 V. When the load resistances vary in a wide range from 15 to 100 Ω, the output voltage regulation rate is within 17.01%. The maximum power of the receiver can reach 13.53 W, and the maximum efficiency can reach 89.79%, showing that the proposed system can be used in practical applications. Besides, the prototype is exploited to power gate drivers with a total power consumption of 2.75 W, further verifying the practical application value.

Partial discharge (PD) is a common phenomenon in high voltage (HV) equipment, which will radiate light signals outward in the process of discharge, by detecting this optical signal, we can judge whether the HV equipment have PDs or not, the conventional detection methods under impulse voltage are very complex due to the interference of electromagnetic (EM) wave, but optical method does not have this problem. Fluorescent optical fiber is not affected by numerical aperture problem, so the sensitivity of fluorescent optical fiber sensor is much higher than that of traditional quartz optical fiber sensor. In this work, the fluorescent optical fiber sensor was manufactured and applied to the PD detection in gas insulated switch (GIS) and transformer, fluorescent optical fiber was used as a probe, which was connected with the transmission optical fiber by coupler, and the photomultiplier tube was used to convert the optical signal into electrical signal for displaying by oscilloscope. The discharge signal can be detected by the sensor when the impulse voltage was applied to the GIS and transformer, and it was less affected by the interference of EM wave signals. As the PD source at different positions in GIS, we found that the optical signal attenuates greatly when the optical was blocked by some internal structures, and the attenuation was increase with the increase of distance between PD source and the sensor. The optical signals of PDs can also be detected by the sensor in the transformer, but the attenuation of the optical signal in the transformer was greater than that in GIS, it was greatly affected by the blocking of windings. The two experiments were verified in the TracePro simulation software, and the average deviations between results of experiments and simulations were less than 10%.

Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

Background Distant metastasis (DM) is relatively rare in superficial gastric cancer (SGC), especially in patients without lymph node metastasis. This study aimed to explore the main clinical risk factors for DM in patients with superficial gastric cancer‐no lymph node metastasis (SGC‐NLNM) and the prognostic factors for patients with DM. Methods Records of patients with SGC‐NLNM between 2004 and 2015 were collected from the public Surveillance, Epidemiology, and End Results (SEER) database. Both univariate and multivariate logistic regressions were performed to analyze the clinical risk factors for DM. The Kaplan–Meier method and Cox regression model were used to identify prognostic factors for patients with DM. A nomogram was built based on multivariate logistic regression and evaluated by the C‐index, the calibration, and the area under the receiver operating characteristic curve (AUC). Results We developed and validated a nomogram to predict DM in patients with SGC‐NLNM, showing that race, age, primary site, depth, size, and grade were independent risk factors. The built nomogram had a good discriminatory performance, with a C‐index of 0.836 (95% confidence interval [CI]: 0.813–0.859). Calibration plots showed that the predicted DM probability was identical to the actual observations in both the training and validation sets. AUC was 0.846 (95% CI: 0.820–0.871) and 0.801 (95% CI: 0.751–0.850) in the training and validation sets, respectively. The results of the survival analysis revealed that surgery (hazard ratio [HR] = 0.249; 95% CI, 0.125–0.495), chemotherapy (HR = 0.473; 95% CI, 0.353–0.633), and grade (HR = 1.374; 95% CI, 1.018–1.854) were independent prognostic factors associated with cancer‐specific survival (CSS), but radiotherapy was not (log‐rank test, p = 0.676). Conclusions We constructed a sensitive and discriminative nomogram to identify high‐risk patients with SGC‐NLNM who may harbor dissemination at initial diagnosis. The tumor size and primary site were the largest contributors to DM prediction. Compared with radiotherapy, aggressive surgery, and chemotherapy may be better options for patients with DM., We identified the main clinical risk factors for distant metastasis (DM) in superficial gastric cancer‐no lymph node metastasis patients and the prognostic factors for the metastatic patients. Besides, a clinical tool was built for the DM prediction.

Keeping a vehicle in its current lane without veering into adjacent lanes is important in hard-braking manoeuvres on split- μ roads. Whether the emergency braking is initiated by a human driver or ...

OBJECTIVE Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10−8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.

Distant metastasis is the major cause of short survival in ccRCC patients. However, the development of effective therapies for metastatic ccRCC is limited. Herein, we reported that ETV4 was selected from among 150 relevant genes with in vivo evidence of promoting metastasis. In this study, we identified that ETV4 promoted ccRCC cell migration and metastasis in vitro and in vivo, and a positive correlation between ETV4 and FOSL1 expression was found in ccRCC tissues and cell lines. Further investigation suggested that ETV4 increase FOSL1 expression through direct binding with the FOSL1 promoter. Furthermore, ETV4/FOSL1 was proved as a novel upstream and downstream causal relationship in ccRCC in an AKT dependent manner. In addition, both ETV4 and FOSL1 serve as an independent, unfavorable ccRCC prognostic indicator, and the accumulation of the ETV4 and FOSL1 in ccRCC patients result in a worse survival outcome in ccRCC patients. Taken together, our results suggest that the ETV4/FOSL1 axis acts as a prognostic biomarker and ETV4 directly up-regulates FOSL1 by binding with its promoter in a PI3K-AKT dependent manner, leading to metastasis and disease progression of ccRCC.

Background. The catheter-tissue contact force (CF) is one of the significant determinants of lesion size and thus has a considerable impact on the effectiveness of ablation procedures. This study aimed to evaluate the impact of CF on the lesion size during right ventricular outflow tract (RVOT) ablation in a swine model. Methods. Twelve Guangxi Bama miniature male pigs weighing 40 to 50 kg were studied. After general anesthesia, a ThermoCool SmartTouch contact-sensing ablation catheter was introduced to the RVOT via the femoral vein under the guidance of the CARTO 3 system. The local ventricular voltage amplitude and impedance were measured using different CF levels. We randomly divided the animals into the following four groups according to the different CF levels: group A (3–9 g); group B (10–19 g); group C (20–29 g); and group D (30–39 g). Radiofrequency ablations were performed at three points in the free wall and septum of the RVOT in power control mode at 30 W for 30 s while maintaining the saline irrigation rate at 17 mL/min. At the end of the procedures, the maximum depth, surface diameter, and lesion volume were measured and recorded. A linear regression analysis was performed to determine the relationship between continuous variables. Results. A total of 72 ablation lesions were created in the RVOT of the 12 Bama pigs. The maximum depth, surface diameter, and volume of the lesions measured were well correlated with the CF (free wall: β = 0.105, β = 0.162, β = 3.355, respectively, P

Aim We conducted a two-sample Mendelian randomization (MR) study to assess the associations of genetically predicted circulating vitamin C levels with cardiovascular diseases (CVDs). Methods and results Ten lead single-nucleotide polymorphisms associated with plasma vitamin C levels at the genome-wide significance level were used as instrumental variables. Summary-level data for 15 CVDs were obtained from corresponding genetic consortia, the UK Biobank study, and the FinnGen consortium. The inverse-variance-weighted method was the primary analysis method, supplemented by the weighted median and MR-Egger methods. Estimates for each CVD from different sources were combined. Genetically predicted vitamin C levels were not associated with any CVD after accounting for multiple testing. However, there were suggestive associations of higher genetically predicted vitamin C levels (per 1 standard deviation increase) with lower risk of cardioembolic stroke [odds ratio, 0.79; 95% confidence interval (CI), 0.64, 0.99; P = 0.038] and higher risk of atrial fibrillation (odds ratio, 1.09; 95% CI, 1.00, 1.18; P = 0.049) in the inverse-variance-weighted method and with lower risk of peripheral artery disease (odds ratio, 0.76, 95% CI, 0.62, 0.93; P = 0.009) in the weighted median method. Conclusion We found limited evidence with MR techniques for an overall protective role of vitamin C in the primary prevention of CVD. The associations of vitamin C levels with cardioembolic stroke, atrial fibrillation, and peripheral artery disease need further study.

Automatically recognizing and tracking dynamic targets on the sea is an important task for intelligent navigation, which is the prerequisite and foundation of the realization of autonomous ships. Nowadays, the radar is a typical perception system which is used to detect targets, but the radar echo cannot depict the target’s shape and appearance, which affects the decision-making ability of the ship collision avoidance. Therefore, visual perception system based on camera video is very useful for further supporting the autonomous ship navigational system. However, ship’s recognition and tracking has been a challenge task in the navigational application field due to the long distance detection and the ship itself motion. An effective and stable approach is required to resolve this problem. In this paper, a novel ship recognition and tracking system is proposed by using the deep learning framework. In this framework, the deep residual network and cross-layer jump connection policy are employed to extract the advanced ship features which help enhance the classification accuracy, thus improves the performance of the object recognition. Experimentally, the superiority of the proposed ship recognition and tracking system was confirmed by comparing it with state of-the-art algorithms on a large number of ship video datasets.

EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270; MR/L003120/1), British Heart Foundation (BHF) (SP/09/002; RG13/13/30194; RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_ 2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France); German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany); Associazione Italiana per la Ricerca sul Cancro--AIRC--Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands); Health Research Fund-Instituto de Salud Carlos III, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_ 00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215--20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R. Z.-R. thanks the "Miguel Servet" program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund--European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart).R.C.was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. The funders of the study had no role in study design, data collection, analysis, data interpretation, or writing of the article, or in the decision to submit for publication. M.S. had full access to all the data in the study, and M.S. and N.G.F. had final responsibility for the decision to submit for publication., BACKGROUND: There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. METHODS AND RESULTS: We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88–0.99]), cheese (HR, 0.98 [95% CI, 0.96–1.00]), and fish (HR, 0.87 [95% CI, 0.75–1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02–1.12]) and butter (HR, 1.02 [95% CI, 1.00–1.04]). CONCLUSIONS: This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix., European Commission Framework Programme 7 HEALTH-F2-2012-279233, European Research Council (ERC), European Commission 268834, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) G0800270 MR/L003120/1, British Heart Foundation SP/09/002 RG13/13/30194 RG/18/13/33946, National Institute for Health Research (NIHR) BRC-1215-20014, European Commission LSHM_CT_ 2006_037197, Medical Research Council UK (MRC) MC_UU_ 00006/1 MC_UU_00006/3, International Agency for Research on Cancer, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam, Rehbruecke, Federal Ministry of Education and Research (Germany), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund International (WCRF), Netherlands Government, Instituto de Salud Carlos III, Junta de Andalucia, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Catalan Institute of Oncology (Spain), Swedish Cancer Society, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, Medical Research Council UK (MRC) 1000143 MR/M012190/1, Hellenic Health Foundation (Greece), NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme IS-BRC-1215-20014, British Heart Foundation, Institute of Health Carlos III (European Social Fund-European Social Fund Investing in Your Future) CP15/00100, BHF-Turing Cardiovascular Data Science Award, European Commission-Innovative Medicines Initiative (BigData@Heart), MRC-Newton project grant MR/P013880/1, United Kingdom Research and Innovation-Global Challenges Research Fund, NIHR Senior Investigator Award

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Purpose: To qualitatively and quantitatively compare the image quality and diagnostic performance of turbo gradient and spin echo PROPELLER diffusion-weighted imaging (TGSE-PROPELLER-DWI) vs. readout-segmented echo-planar imaging (rs-EPI) in the evaluation of orbital tumors.Materials and Methods: A total of 43 patients with suspected orbital tumors were enrolled to perform the two DWIs with comparable spatial resolution on 3T. The overall image qualities, geometric distortions, susceptibility artifacts, and lesion conspicuities were scored by using a four-point scale (1, poor; 4, excellent). Quantitative measurements, including contrast-to-noise ratios (CNRs), apparent diffusion coefficients (ADCs), geometric distortion rates (GDRs), and lesion sizes, were calculated and compared. The two ADCs for differentiating malignant from benign orbital tumors were evaluated. Wilcoxon signed-rank test, Kappa statistic, and receiver operating characteristics (ROC) curves were used.Results: TGSE-PROPELLER-DWI performed superior in all subjective scores and quantitative GDR evaluation than rs-EPI (p < 0.001), and excellent interobserver agreement was obtained for Kappa value ranging from 0.876 to 1.000. ADClesion of TGSE-PROPELLER-DWI was significantly higher than those of rs-EPI (p < 0.001). Mean ADC of malignant tumors was significantly lower than that of benign tumors both in two DWIs. However, the AUC for differentiating malignant and benign tumors showed no significant difference in the two DWIs (0.860 vs. 0.854, p = 0.7448). Sensitivity and specificity could achieve 92.86% and 72.73% for TGSE-PROPELLER-DWI with a cutoff value of 1.23 × 10–3 mm2/s, and 85.71% and 81.82% for rs-EPI with a cutoff value of 0.99 × 10–3 mm2/s.Conclusion: Compared with rs-EPI, TGSE-PROPELLER-DWI showed minimized geometric distortion and susceptibility artifacts significantly improved the image quality for orbital tumors and achieved comparable diagnostic performance in differentiating malignant and benign orbital tumors.

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-dysfunction-associated fatty liver disease (MAFLD), affects a quarter of the worldwide population. Natural products have been extensively utilized in treating NAFLD because of their distinctive advantages over chemotherapeutic drugs, despite the fact that there are no approved drugs for therapy. Notably, the limitations of many natural products, such as poor water solubility, low bioavailabilityiin vivo/i, low hepatic distribution, and lack of targeted effects, have severely restricted their clinical application. These issues could be resolvedivia/ihepatic targeted drug delivery systems (HTDDS) that boost clinical efficacy in treating NAFLD and decrease the adverse effects on other organs. Herein an overview of natural products comprising formulas, single medicinal plants, and their crude extracts has been presented to treat NAFLD. Also, the clinical efficacy and molecular mechanism of active monomer compounds against NAFLD are systematically discussed. The targeted delivery of natural productsivia/iHTDDS has been explored to provide a different nanotechnology-based NAFLD treatment strategy and to make suggestions for natural-product-based targeted nanocarrier design. Finally, the challenges and opportunities put forth by the nomenclature update of NAFLD are outlined along with insights into how to improve the NAFLD therapy and how to design more rigorous nanocarriers for the HTDDS. In brief, we summarize the up-to-date developments of the NAFLD-HTDDS based on natural products and provide viewpoints for the establishment of more stringent anti-NAFLD natural-product-targeted nanoformulations.

Background and objective Sympathetic activity plays an important role in the proliferation and differentiation of stem cells, and it changes over time, thereby exerting differential effects on various stem cell types. Aging causes sympathetic hyperactivity in aged tissues and blunts sympathetic nerves regulation, and sympathetic abnormalities play a role in aging-related diseases. Currently, the effect of sympathetic activity on skeletal muscle stem cells, namely satellite cells (SCs), is unclear. This study aimed to investigate the effects of skeletal muscle sympathetic activity on SC aging and skeletal muscle repair. Materials and methods To evaluate skeletal muscle and fibrotic areas, numbers of SCs and myonuclei per muscle fiber, β2-adrenoceptor (β2-ADR) expression, muscle repair, and sympathetic innervation in skeletal muscle, aged mice, young mice that underwent chemical sympathectomy (CS) were utilized. Mice with a tibialis anterior muscle injury were treated by barium chloride (BaCl2) and clenbuterol (CLB) in vivo. SCs or C2C12 cells were differentiated into myotubes and treated with or without CLB. Immunofluorescence, western blot, sirius red, and hematoxylin–eosin were used to evaluate SCs, myogenic repair and differentiation. Results The number of SCs, sympathetic activity, and reparability of muscle injury in aged mice were significantly decreased, compared with those in young mice. The above characteristics of young mice that underwent CS were similar to those of aged mice. While CLB promoted the repair of muscle injury in aged and CS mice and ameliorated the reduction in the SC number and sympathetic activity, the effects of CLB on the SCs and sympathetic nerves in young mice were not significant. CLB inhibited the myogenic differentiation of C2C12 cells in vitro. We further found that NF-κB and ERK1/2 signaling pathways were activated during myogenic differentiation, and this process could be inhibited by CLB. Conclusion Normal sympathetic activity promoted the stemness of SCs to thereby maintain a steady state. It also could maintain total and self-renewing number of SCs and maintain a quiescent state, which was correlated with skeletal SCs via β2-ADR. Normal sympathetic activity was also beneficial for the myogenic repair of injured skeletal muscle.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complicated maternally inherited disorder lacking of sensitive and specific biomarkers. The objective of this study was to investigate the serum neurofilament light chain (NfL) as a novel biomarker of neurological dysfunction in MELAS. Patients with different status of MELAS were enrolled in this study. The Mini-Mental State Examination (MMSE) was given to the participants to evaluate cognition status. Multiple functional MRI was performed on the participants. Blood samples were collected and the serum NfL concentrations were determined by the single-molecule array technology (Simoa). This study enrolled 23 patients with MELAS, 15 people in the acute attack phase of MELAS and 10 people in the remission phase, including 2 patients in both acute attack and remission phase. Sixteen healthy controls (HCs) were also enrolled. Serum NfL level increased significantly in patients with MELAS. Serum NfL level in the acute attack group (146.73 [120.91-411.31] pg/ml, median [IQR]) was higher than in the remission group (40.31 [19.54-151.05] pg/ml, median [IQR]) and HCs group (7.70 [6.13-9.78] pg/ml, median [IQR]) (p 0.05). The level of NfL in the remission phase group was higher than in HCs group (p 0.05). A negative correlation was found between the serum NfL level and MMSE (p = 0.006, r = -0.650). The NfL concentration correlated positively with stroke-like lesion volume in the brain (r = 0.740, p 0.001). Serum NfL may serve as a novel biomarker for the neurological dysfunction in MELAS patients.

In recent years, Industrial Internet of Things (IIoT) has been at a high-speed development stage. However, the diversity of services and technical standards in the Industrial Internet of Things and vertical industries makes it impossible for the existing communication technologies to use the same physical network to meet different needs of services. To tackle this problem, Network Slicing (NS) is proposed and has become the key enabling technology of the fifth generation mobile communication (5G) network. Network Slicing is a logical network running on the physical or virtual infrastructure, which can divide the network into multiple logical networks with different configurations according to different requirements. Each slice is isolated from each other and does not affect each other, which can meet the needs of different application scenarios in IIoT. In this paper, a delay optimization oriented Service Function Chain (SFC) deployment model is proposed and a two-stage collaborative deployment algorithm called DSFC is designed. Simulations validate that the proposed method can reduce the delay while ensuring the reliability of SFC deployment.

Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) have regulatory functions in hepatocellular carcinoma (HCC). The link between lincSCRG1 and HCC remains unclear.To explore the lincSCRG1 regulation axis, bioinformatics, RIP and luciferase reporter assay were performed. The expressions of lincSCRG1-miR26a-SKP2 were detected in HCC tissues and cell lines through qPCR and western blot. The functions of HCC cells were investigated through in vitro assays (MTT, colony formation, transwell and flow cytometry) and the inner effect of lincSCRG1-miR26a in vivo was evaluated by xenografts and liver metatstatic nude mice models.LincSCRG1 was found to be strongly elevated in human HCC tissues and cell lines. MiR26a and S phase kinase-related protein 2 (SKP2) were predicted as the target miRNA for lincSCRG1 and the target gene for miR26a with direct binding sites, respectively. LincSCRG1 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR26a and derepression of SKP2 in HCC cells. Both overexpression of lincSCRG1 (ov-lincSCRG1) and inhibition of miR26a (in-miR26a) obviously stimulated cellular viability, colony formation, migration and proliferation of S phase cells and also significantly increased the protein levels of cyclinD1, CDK4, MMP2/3/9, Vimentin, and N-cadherin or inhibited the protein level of E-cadherin of HCC cells, while knockdown of lincSCRG1 (sh-lincSCRG1) and upregulation of miR26a (mi-miR26a) had the opposite effects on HCC cells. Cotransfection of in-miR26a or overexpression of SKP2 (ov-SKP2) with sh-lincSCRG1 could rescue the anticancer functions of sh-lincSCRG1, including suppressing proliferation and migration of HCC cells. Additionally, sh-lincSCRG1 could effectively inhibit the growth of subcutaneous xenograft tumours and lung metastasis, while the anticancer effect of sh-lincSCRG1 could be reversed by cotransfection of in-miR26a.LincSCRG1 acts as a ceRNA of miR26a to restrict its ability to derepress SKP2, thereby inducing the proliferation and migration of HCC cells in vitro and in vivo. Depletion of lincSCRG1 could be used as a potential therapeutic approach in HCC.

Summary The pathophysiological influence of gene‐lifestyle interactions on the risk to develop type 2 diabetes (T2D) is currently under intensive research. This systematic review summarizes the evidence for gene‐lifestyle interactions regarding T2D incidence. MEDLINE, EMBASE, and Web of Science were systematically searched until 31 January 2019 to identify publication with (a) prospective study design; (b) T2D incidence; (c) gene‐diet, gene‐physical activity, and gene‐weight loss intervention interaction; and (d) population who are healthy or prediabetic. Of 66 eligible publications, 28 reported significant interactions. A variety of different genetic variants and dietary factors were studied. Variants at TCF7L2 were most frequently investigated and showed interactions with fiber and whole grain on T2D incidence. Further gene‐diet interactions were reported for, eg, a western dietary pattern with a T2D‐GRS, fat and carbohydrate with IRS1 rs2943641, and heme iron with variants of HFE. Physical activity showed interaction with HNF1B, IRS1, PPARγ, ADRA2B, SLC2A2, and ABCC8 variants and weight loss interventions with ENPP1, PPARγ, ADIPOR2, ADRA2B, TNFα, and LIPC variants. However, most findings represent single study findings obtained in European ethnicities. Although some interactions have been reported, their conclusiveness is still low, as most findings were not yet replicated across multiple study populations.

Quantitative magnetic resonance image (MRI) in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy (DMD). The purpose of this study was to measure T2 relaxation time of thigh muscles in children with DMD and healthy boys, and to correlate the T2 relaxation time of muscles with the fat fraction (FF) at quantitative magnetic resonance and results of clinical assessment. Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI. Age, body mass index (BMI), muscle strength assessment, timed functional tests (time to walk or run 10 metres, rise from the floor and ascend four stairs), and the North Star Ambulatory Assessment (NSAA) were evaluated. Spearman's correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time. The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group (P

Purpose/Objective(s) To clarify the efficacy of FLASH radiotherapy (FLASH-RT) in inhibiting mammary tumorigenesis and normal tissue sparing. Materials/Methods We used a spontaneous mammary tumor model of MMTV-PyMT mice for the study. Prior to the formation of mammary tumor, MMTV-PyMT mice (3–6-week-old) were treated with a single fraction dose of 9-16 Gy FLASH-RT or conventional radiotherapy (CONV-RT) using a mice-applicator designed targeting five pair of mammary glands. Tumor growth was detected by thorough palpation of all 10 mammary glands twice a week. Liver function, HE however, IFN-g and IL-6 also significantly increased in FLASH compared with control, while IL-10 significantly decreased in CONV compared with control. Serum IL-6, IFN-g and TNF-a levels in FLASH did not markedly change on D6, D18 and D31 post-IR compared with control. Serum IL-6, IFN-g and TNF-a levels were elevated on D6 and continuously increased on D18 and D31 in CONV, but began to increase on D6, and then recovered to the control level on D18 or D31 in FLASH. Serum IL-10 levels decreased at D6, D18 and D31 in CONV, but began to decrease at D6, and then recovered to the control level at D18 or D31 in FLASH. FLASH induced reactive oxygen species (ROS) accumulation in the tumor tissue but not in normal tissue; while absence of ROS accumulation in either tumor or normal tissue under CONV. Notably, the ROS level of normal liver tissue did not differ under CONV or FLASH. Conclusion We found that mammary tumorigenesis was inhibited by FLASH without significant liver injury compared with CONV-RT. The alteration of serum and liver inflammatory cytokines induced by CONV-RT was mildly altered by FLASH. This unique benefit can by partially explained by the accumulatio of ROS in tumor tissue after FLASH.

Background The muramyl dipeptide compound adjuvant, CVC1303, was one new resigned adjuvant to PEDV inactivated vaccine. Exploring the effects of CVC1303 on the immune induction to PEDV vaccine was of vital importance to the clinical application. Objectives Here we explored the functions of CVC1303 on the humoral, cellular and mucosal immune response to PEDV vaccine in mice immunization. Methods Mice were twice subcutaneously injected with PEDV vaccine including high, medium and low dosages CVC1303, respectively. On 30th day after the second immunization, sera samples were collected from the immunized mice to measure PEDV-specific IgG and IgG subclasses levels, and lymphocytes were isolated to detect T cell subtype and intracellular IL-4 and IL-6 cytokine productions, and the expressions of co-stimulatory molecule on dendritic cells in the immunized mice. Small intestinal and lung washings were collected on 30th and 47th day after the second immunization to measure PEDV-specific IgA levels, and SP immunohistochemical method staining was employed to analyze the deviations of IgA+ positive cells in the small intestinal of the immunized mice. Results Our investigation proved the strong regulatory roles of CVC1303 on PEDV-specific IgG and IgG1 antibody and cytokines productions, and the significant increased CD3+CD4+T cells subpopulation and expressions of co-stimulatory molecules on dendritic cells in the immunized mice. Moreover, our findings verified the significantly enhanced PEDV-specific IgA antibody titers in small intestinal and lung in the mice immunized with PEDV vaccine and CVC1303. Conclusion Compound adjuvant CVC1303 could effectively improve the PEDV-specific immune responses and mucosal immune, which provided an experimental basis for the further clinical application of new adjuvant CVC1303 and the development of improvement on the mucosal immune response.

Higher levels of fatty acids (FAs) in the de novo lipogenesis (DNL) pathway might be associated with higher levels of fat mass (FM), while limited evidence is available from the general population. We aimed to examine the associations between DNL-FAs and body fat and fat distribution in a general population of Chinese adults. This community-based prospective cohort study included 3,075 participants (68% women) aged 40–75 years in urban Guangzhou, China. We measured erythrocyte DNL-FAs composition (including C16:0, C16:1n-7, C18:0, and C18:1n-9) at baseline and %FM over the total body (TB), trunk, limbs, android (A) and gynoid (G) regions after 3.2 years and 6.3 years of follow-up, respectively. Generally, higher proportions of individual erythrocyte DNL-FAs and their combined index were positively associated with adipose indices in the multivariable cross-sectional and longitudinal analyses. The cross-sectional percentage mean differences in quartile 4 (vs. 1) of the DNL index were 3.43% (TB), 4.56% (trunk), and 2.67% (A/G ratio) (all P trends

Zizhen Zhang,1– 3,* Fangyu Ju,1– 3,* Fei Chen,1– 3 Haoyue Wu,4 Jingyu Chen,1– 3 Jing Zhong,1– 3 Liming Shao,1– 3 Sheng Zheng,1– 3 Liangjing Wang,1– 3 Meng Xue1– 3 1Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310020, People’s Republic of China; 2Institution of Gastroenterology, Zhejiang University, Hangzhou, 310000, People’s Republic of China; 3Zhejiang University Cancer Center, Hangzhou, 310000, People’s Republic of China; 4Institute of Genetics and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, 310012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meng Xue; Liangjing Wang Email xuemeng@zju.edu.cn; wangljzju@zju.edu.cnAim: Chemoresistance to 5-fluorouracil (5-Fu) is common in colorectal cancer (CRC). Programmed necrosis (necroptosis) is an alternative form of programmed cell death regulated by receptor-interacting protein kinase (RIPK) 1 and 3, assumed as a novel target of cancer therapy. In this study, we aimed to explore whether a novel small molecular agent GDC-0326 could facilitate the effect of 5-Fu through necroptosis.Main Methods: Cell Counting Kit-8 (CCK-8) assay and colony formation were performed to confirm the function of GDC-0326 in CRC cells. Western blot and immunofluorescence were conducted to measure the altered expressions of RIPK1/RIPK3 induced by GDC-0326. Subcutaneous tumor models were used to evaluate the chemotherapeutic effects and concomitant side effects of GDC-0326 in vivo.Key Findings: We found that GDC-0326 effectively suppressed the growth of CRC cells in a dose-dependent manner. The induction of necroptosis by GDC-0326 was correlated with the modulation of RIPK1 and RIPK3. Necrostatin-1 and GSK-872, inhibitors of RIPK1 and RIPK3, respectively, could rescue the cell death induced by GDC-0326. In addition, in vitro and in vivo studies showed that 5-Fu plus GDC-0326 evinced a better antitumor efficacy by suppressing tumor growth and increasing tumor necrosis with no increased toxicity.Significance: This study demonstrates that GDC-0326 plus 5-Fu has augmented antitumor efficacy and acceptable safety, which might be a promising therapeutic strategy for CRC patients in the future.Keywords: GDC-0326, 5-fluorouracil, colorectal cancer, combination therapy

Polyimide (PI) film is considered to be an ideal packaging material due to its excellent comprehensive properties. However, the traditional PI has a relatively high dielectric permittivity ( $k=3.0\sim 3.4$ ), which cannot meet the current requirements in the field of microelectronic packaging ( $k ). In this work, Tris(4-aminophenyl) amine (TPA) was used the cross-linking agent to combine with biphenyl-3,3′,4,4′-tetracarboxylic dianhydride (BPDA) and 1,4-Bis(4-amino-2-trifluoromethylphenoxy) benzene (6FAPB) by in-situ polymerization for the purpose of obtaining cross-linked low-dielectric polyimide. And the influences of cross-linking agent ratio on the comprehensive properties of PI were studied. The results showed that under a certain loading of TPA, the dielectric permittivity of the PI gradually decreased with the incremental crosslinking agent content. When the molar ratios of amino groups in TPA and 6FAPB was 1:9, the dielectric properties of the cross-linked PI can be minimized, with the lowest value of 1.86 (107 Hz). In addition, the obtained cross-linked polyimide had good thermal stability. It has broad development prospects in the field of microelectronic packaging and integrated circuits in the future.

Studying solar filaments can help in understanding the distribution of large-scale field in the solar atmosphere and provide useful insights into the nature of the solar magnetic field. Recently, the National Astronomical Observatory of the Chinese Academy of Sciences has collected huge volumes of data about solar filaments from several international observing stations for nearly 100 years. Designing a database, as well as establishing a networked tool for making the best of it, are necessary to provide efficient and convenient access to the data for researchers. In this study, we introduce a solar filament database, involving digital image data of nearly 45 terabytes, based on MySQL and a data management platform named database management system of hundred years of solar filament archives ( http://faste.ctgu.edu.cn ) that adopts Browser/Server mode and is written in the Java programming language. From this data system, users can realise multi-property query on the basis of demands, download data under multiple conditions, perform visual query for information on one single filament, view long-term data statistics of filament properties, and implement extensions and management of the database.

Background Circulating vitamin C concentrations have been associated with several cancers in observational studies, but little is known about the causal direction of the associations. This study aims to explore the potential causal relationship between circulating vitamin C and risk of five most common cancers in Europe. Methods We used summary-level data for genetic variants associated with plasma vitamin C in a large vitamin C genome-wide association study (GWAS) meta-analysis on 52,018 Europeans, and the corresponding associations with lung, breast, prostate, colon, and rectal cancer from GWAS consortia including up to 870,984 participants of European ancestry. We performed two-sample, bi-directional Mendelian randomization (MR) analyses using inverse-variance-weighted method as the primary approach, while using 6 additional methods (e.g., MR-Egger, weighted median-based, and mode-based methods) as sensitivity analysis to detect and adjust for pleiotropy. We also conducted a meta-analysis of prospective cohort studies and randomized controlled trials to examine the association of vitamin C intakes with cancer outcomes. Results The MR analysis showed no evidence of a causal association of circulating vitamin C concentration with any examined cancer. Although the odds ratio (OR) per one standard deviation increase in genetically predicted circulating vitamin C concentration was 1.34 (95% confidence interval 1.14 to 1.57) for breast cancer in the UK Biobank, this association could not be replicated in the Breast Cancer Association Consortium with an OR of 1.05 (0.94 to 1.17). Smoking initiation, as a positive control for our reverse MR analysis, showed a negative association with circulating vitamin C concentration. However, there was no strong evidence of a causal association of any examined cancer with circulating vitamin C. Sensitivity analysis using 6 different analytical approaches yielded similar results. Moreover, our MR results were consistent with the null findings from the meta-analysis exploring prospective associations of dietary or supplemental vitamin C intakes with cancer risk, except that higher dietary vitamin C intake, but not vitamin C supplement, was associated with a lower risk of lung cancer (risk ratio: 0.84, 95% confidence interval 0.71 to 0.99). Conclusions These findings provide no evidence to support that physiological-level circulating vitamin C has a large effect on risk of the five most common cancers in European populations, but we cannot rule out very small effect sizes.

Background: There is growing evidence even amongst those with chronic aphasia that transcranial direct current stimulation (tDCS) combined with behavioral speech therapy could boost language. However, current findings do not allow making strong recommendations for using tDCS in order to improve language in post-stroke aphasia. The efficacy of tDCS therefore still needs to be established using double-blind controlled randomized trials in large samples. Intervention: In this ongoing double-blind randomized placebo controlled trial study, participants were randomly assigned either to the tDCS group or to the sham group. Both groups had five consecutive days of 20 minutes session, using a FDA approved tDCS device (soterixmedical.com). Behavioral and neuroimaging data were performed the week before/after tDCS/sham intervention and again 3 months following treatment. Participants: 42 post-stroke patients with chronic aphasia (32 males; age: 61±11y; 0.9-18years post-injury; 32 ischemic stroke; 19 non-fluent aphasia). Eighteen patients were in the tDCS group. Main Outcome Measures: The Western Aphasia Battery-Revised (WAB-R), Communication Outcomes after Stroke, patient and family report (COAST). MRI Diffusion Tensor Imaging data (64 dir) were also collected. Statistical Analyses: Anova with repeated measures was used on the behavioral outcome measures with aphasia severity, age and time since injury as covariates in SPSS. The average fractional anisotropy (FA) and mean diffusivity (MD) were extracted per ROI from each participant and timepoint. Main Results: a) Behavioral. Groups differed, pre/post intervention, on the WAB-R total score, for the Auditory-Verbal Comprehension and Repetition subscores; b) Neuroimaging. Change in Spontaneous Speech and Auditory Verbal Comprehension negatively correlated with change in mean MD and FA, respectively, in Superior Cerebellar Peduncle for tDCS, but not sham. Conclusion: Our preliminary findings show a higher improvement in language functions (for both receptive and expressive language skills) in response to treatment (vs. sham). Neuroplasticity was observed in superior cerebellar peduncle in response to tDCS mediated language improvement.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complicated maternally inherited disorder lacking of sensitive and specific biomarkers. The objective of this study was to investigate the serum neurofilament light chain (NfL) as a novel biomarker of neurological dysfunction in MELAS. Patients with different status of MELAS were enrolled in this study. The Mini-Mental State Examination (MMSE) was given to the participants to evaluate cognition status. Multiple functional MRI was performed on the participants. Blood samples were collected and the serum NfL concentrations were determined by the single-molecule array technology (Simoa). This study enrolled 23 patients with MELAS, 15 people in the acute attack phase of MELAS and 10 people in the remission phase, including 2 patients in both acute attack and remission phase. Sixteen healthy controls (HCs) were also enrolled. Serum NfL level increased significantly in patients with MELAS. Serum NfL level in the acute attack group (146.73 [120.91–411.31] pg/ml, median [IQR]) was higher than in the remission group (40.31 [19.54–151.05] pg/ml, median [IQR]) and HCs group (7.70 [6.13–9.78] pg/ml, median [IQR]) (p

The study of water resources carrying capacity (WRCC) has vital significance for coordination of water and society, economy along with ecology. The purpose of this paper was to analyze current concept and methods of evaluation on WRCC, then carry out the assessment and obtain the carrying status. Based on the review of research on WRCC, considering water quantity, quality and social economy factors, a comprehensive evaluation model was established by application of AHP-PCA method. Both subjective and objective conditions were taken into consideration simultaneously in this method. Binzhou City was taken as a case study to assessment the carrying status of its water resources. Calculating by the AHP-PCA Synthetic Evaluation model based on data from 2010 to 2017, it is considered that the WRCC of Binzhou was mainly affected by total population, total water supply and per capita water consumption. And the result showed that the evaluation values fluctuate between 2.10 and 2.75 in recent years, which indicated the WRCC was at the level of mild overload in this city. From the above conclusion, we learned that the sustainable development of Binzhou had been limited by the level of its WRCC. Therefore, some practical policies were provided.

The solar chromosphere data products of the New Vacuum Solar Telescope (NVST) have been affected by the interference fringes since its first operation. These fringes have a serious impact on the quality of NVST high-resolution data, which are reconstructed by short-exposure data. In order to improve the quality of NVST high-resolution data, this article proposes a method based on “Fringes Flat Field” to remove the interference fringes in NVST short-exposure data. We made the “Fringes Flat Field” using Adaptive Wavelet Transform (AWT) and Butterworth low-pass filter. The results of the experiments are satisfactory, and the method cannot only remove the fringes effectively, but keep the solar structures from being lost.

Binzhou, Shandong is located in the hinterland of the lower Yellow River Delta with the typical sub-humid warm temperate monsoon climate. The average per capita water resources in Binzhou (265 m3 per person) is considerably lower than the national standards (2100 m3 per person). To study the current situation of water resources utilization and supply pressure in Binzhou city, the grey system prediction model and quota prediction method were used to predict the near and long-term water demand. The results showed that the shortage of water resources in Binzhou would be more serious in the foreseeable future, with an estimated water shortage of 3.91 × 108 m3 in 2025 and 2.90 × 108 m3 in 2035. In the future, agricultural water consumption would still be the largest portion in Binzhou, but its increment would be rather small, and industrial water consumption would increase obviously, compared with 2018, the growth rates in 2025 and 2035 are 109.9% and 192.7%. The demand for domestic water and ecological water would rise due to the development of urbanization. Based on the prediction results of water supply-demand balance, over 3 × 108 m3 shortfall in water supply, Binzhou needs to improve the water supply capacity to meet the water demand of production and living.

In order to introduce the grid power flow model to intelligently monitor the network security situation, a model based on grid power flow is established. In the construction of the network security situation intelligent monitoring system, the hierarchical database is protected and managed, the attacks brought by the network security situation are changed, and the network security situation level protection system is improved and improved. On this basis, the network trend correction factor is introduced, and the network security situation is normalized according to the network security situation value. The network information flow is processed uniformly, and the intelligent monitoring model of network security situation based on power flow is built. Compared with the traditional network security situation intelligent monitoring model, the application of network security situation intelligent monitoring model can effectively solve the uncertainty and fuzziness of information provided by various network security devices.

BACKGROUND To investigate the value of D-dimer combined with red blood cell distribution width (RDW) in evaluating the disease activity of systemic lupus erythematosus (SLE). METHODS A total of 105 SLE patients confirmed in our hospital from July 2018 to September 2020 were collected as the SLE group, and 60 healthy persons matched in age and gender during the same period were collected as the control group. According to the SLEDAI score, SLE patients were divided into SLE active group and SLE inactive group, and RDW and D-Dimer levels were detected. RESULTS The level of RDW in the SLE active group [14.8 (13.4, 16.8)] was significantly higher than that in the SLE inactive group [13.4 (12.6, 14.37)] and control group [12.3 (12, 12.7)], with statistically significant differences (p < 0.05). The D-dimer level in the SLE active group was 1.36 (0.9, 2.25) mg/L, which was significantly higher than that in SLE inactive group [0.34 (0.22, 0.52)] mg/L and control group [0.15 (0.08, 0.19)] mg/L, with statistically significant differences (p < 0.05). Both RDW and D-dimer were positively correlated with the SLEDAI score (r = 0.393, p = 0.000), (r = 0.483, p = 0.000). The results of receiver operating characteristic curve showed that the area under the curve of RDW and D-Dimer alone was 0.875 and 0.954, respectively, while the area under the curve of RDW combined with D-Dimer was the largest, 0.984. CONCLUSIONS The levels of RDW and D-dimer are closely related to the disease activity of SLE patients, and RDW combined with D-dimer is more valuable in assessing the disease activity of SLE patients.

Background: The extracellular matrix (ECM) component serglycin promotes the epithelial-to-mesenchymal transition (EMT) and metastasis in an autocrine manner. However, the detailed mechanism underlying the roles of serglycin in Hepatocellular carcinoma (HCC) metastasis progression remains to be clarified.Methods: Analyzing 123 patients’ serum by ELISA to investigate the association between serglycin expression and HCC metastasis and prognosis. Serglycin, CRISPLD2, and YAP were overexpressed or knocked down with vector or RNAi. The RNA - sequence was used to screen serglycin downstream effectors, followed by bioinformatics, ChIP-PCR, luciferase, and promoter site mutation to identify novel target genes. The metastatic abilities of serglycin were demonstrated by a series of in vitro and in vivo experiments. Immunofluorescence, flow cytometry, and western blotting were carried out to demonstrate the potential mechanisms of serglycin.Results: We observed that serglycin was overexpressed in HCC tissues and serum, and its level was associated with metastasis and poor prognosis. By gain- and loss-of-function approaches, we found serglycin affects migratory motility and metastatic capacity in vitro and in vivo, and it's significantly associated with the stemness-like properties. Interestingly, serglycin activated the effector YAP of Hippo pathway, and further study verified the crucial role of serglycin/YAP in tumorigenesis by the DEN-induced HCC mouse model. Furthermore, the CRISPLD2 was selectively upregulated by serglycin, the axis of serglycin / YAP / CRISPLD2 regulated metastatic capacity in HCC cells, it revealed CRISPLD2 was the direct target gene of serglycin-mediated YAP/TEAD1 complex. Besides, serglycin-mediated YAP pathway enhanced cell sorafenib resistance, sorafenib combined with verteporfin reversed serglycin-mediated cellular insensitivity to sorafenib therapy.Conclusions: Autocrine ECM serglycin plays a crucial role in the process of stemness maintenance, tumorigenesis, and metastasis via selective reactivation of the novel YAP/CRISPLD2 developmental axis promotes metastasis and sorafenib resistance in Hepatocellular carcinoma, YAP-TEAD1 inhibitor verteporfin reversed serglycin-mediated cellular sorafenib resistance.

High-voltage direct current (HVDC) transmission plays an important role in the development of sustainable transmission networks and the conversion of energy systems. As an important medium in the transmission system, HVDC cables have become a hot research topic. Flexible DC transmission using HVDC plastic cables is the mainstream direction advocated by the international power grid. Therefore, the demand for high-performance HVDC plastic cables is increasing. Aiming at the development process of thermoplastic environmental polypropylene insulation materials for HVDC cables, the development status and technical bottlenecks of HVDC cable insulation materials were summarized. This chapter discussed the research progress of polypropylene insulation materials from the perspective of the basic structure of polypropylene, intrinsic modification, and its nanocomposite, etc. The necessity and urgency of research and development of insulation materials for HVDC cables were clarified. Finally, the future development direction of HVDC cables was summarized and prospected.

OBJECTIVE To identify the core gut microbial features associated with type 2 diabetes risk and potential demographic, adiposity, and dietary factors associated with these features. RESEARCH DESIGN AND METHODS We used an interpretable machine learning framework to identify the type 2 diabetes–related gut microbiome features in the cross-sectional analyses of three Chinese cohorts: one discovery cohort (n = 1,832, 270 cases of type 2 diabetes) and two validation cohorts (cohort 1: n = 203, 48 cases; cohort 2: n = 7,009, 608 cases). We constructed a microbiome risk score (MRS) with the identified features. We examined the prospective association of the MRS with glucose increment in 249 participants without type 2 diabetes and assessed the correlation between the MRS and host blood metabolites (n = 1,016). We transferred human fecal samples with different MRS levels to germ-free mice to confirm the MRS–type 2 diabetes relationship. We then examined the prospective association of demographic, adiposity, and dietary factors with the MRS (n = 1,832). RESULTS The MRS (including 14 microbial features) consistently associated with type 2 diabetes, with risk ratio for per 1-unit change in MRS 1.28 (95% CI 1.23–1.33), 1.23 (1.13–1.34), and 1.12 (1.06–1.18) across three cohorts. The MRS was positively associated with future glucose increment (P < 0.05) and was correlated with a variety of gut microbiota–derived blood metabolites. Animal study further confirmed the MRS–type 2 diabetes relationship. Body fat distribution was found to be a key factor modulating the gut microbiome–type 2 diabetes relationship. CONCLUSIONS Our results reveal a core set of gut microbiome features associated with type 2 diabetes risk and future glucose increment.

Background Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk. Methods This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008–2013). Fecal samples were collected at follow-up (2015–2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants. Results In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake (p p = 0.003) and the FMI-T2D association (OR 0.90, 95%CI 0.84–0.97) were both successfully replicated in the independent cohort. The FMI-positive associated metabolite sebacic acid was inversely associated with T2D risk (OR 0.67, 95%CI 0.51–0.86). The FMI-negative associated metabolites cholic acid (OR 1.35, 95%CI 1.13–1.62), 3-dehydrocholic acid (OR 1.30, 95%CI 1.09–1.54), oleylcarnitine (OR 1.77, 95%CI 1.45–2.20), linoleylcarnitine (OR 1.66, 95%CI 1.37–2.05), palmitoylcarnitine (OR 1.62, 95%CI 1.33–2.02), and 2-hydroglutaric acid (OR 1.47, 95%CI 1.25–1.72) were positively associated with T2D risk. Conclusions Higher fruit intake-associated gut microbiota and metabolic alteration were associated with a lower risk of T2D, supporting the public dietary recommendation of adopting high fruit intake for the T2D prevention.

Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D., Using both observational and genetic analyses, Ju-Sheng Zheng and colleagues investigate the relationship between vitamin D metabolites and type 2 diabetes among European individuals., Author summary Why was this study done? There is ongoing uncertainty on whether the body’s vitamin D status indicated by blood 25-hydroxyvitamin D (25(OH)D) is relevant to the prevention of type 2 diabetes. There are conflicting findings from observational studies and a limited number of randomised controlled trials. Prior research did not distinguish between different metabolites of total 25(OH)D, including 25(OH)D3 and C3-epi-25(OH)D3, an isomer of 25(OH)D3. It is not clear whether the associations of 25(OH)D metabolites with type 2 diabetes are causal, with conflicting findings from prior Mendelian randomisation studies of total 25(OH)D and no previous Mendelian randomisation studies appraising 25(OH)D metabolites. What did the researchers do and find? The current research compared observational estimates of the association between 25(OH)D metabolites and incident type 2 diabetes with Mendelian randomisation estimates based on genetic instruments. Using multiple data sources, we performed genome-wide association studies among 120,618 individuals for total 25(OH)D, and among 40,562 individuals for the other vitamin D metabolites. Among participants of European descent, 10 genetic loci were identified for total 25(OH)D, 7 loci for 25(OH)D3 and 3 loci for C3-epi-25(OH)D3. In meta-analysis of observational studies, we found that each 1–standard deviation higher level of total 25(OH)D was associated with 20% lower risk of type 2 diabetes. The result was similar for 25(OH)D3, but for C3-epi-25(OH)D3, a positive association with type 2 diabetes was found. With up to 80,983 type 2 diabetes cases and 842,909 controls, we assessed the association of genetically predicted differences in total 25(OH)D and its metabolites with type 2 diabetes. Neither genetically predicted higher total 25(OH)D level nor genetically predicted higher levels of 25(OH)D metabolites were significantly associated with type 2 diabetes. What do these findings mean? There were conflicting findings for a link with type 2 diabetes for the observational analysis of biochemically measured 25(OH)D metabolites versus the genetically predicted levels of these metabolites. The null findings based on Mendelian randomisation analysis indicate that blood levels of 25(OH)D or its metabolites are not likely to be causal factors for the development of type 2 diabetes. The current findings together with other evidence from randomised controlled trials do not support the use of vitamin D supplementation for the prevention of type 2 diabetes.