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Background Genetic correlations, causalities and pathways between large-scale complex exposures and ovarian and breast cancers need systematic exploration. Methods Mendelian randomisation (MR) and genetic correlation (GC) were used to identify causal biomarkers from 95 cancer-related exposures for risk of breast cancer [BC: oestrogen receptor-positive (ER + BC) and oestrogen receptor-negative (ER - BC) subtypes] and ovarian cancer [OC: high-grade serous (HGSOC), low-grade serous, invasive mucinous (IMOC), endometrioid (EOC) and clear cell (CCOC) subtypes]. Results Of 31 identified robust risk factors, 16 were new causal biomarkers for BC and OC. Body mass index (BMI), body fat mass (BFM), comparative body size at age 10 (CBS-10), waist circumference (WC) and education attainment were shared risk factors for overall BC and OC. Childhood obesity, BMI, CBS-10, WC, schizophrenia and age at menopause were significantly associated with ER + BC and ER - BC. Omega-6:omega-3 fatty acids, body fat-free mass and basal metabolic rate were positively associated with CCOC and EOC; BFM, linoleic acid, omega-6 fatty acids, CBS-10 and birth weight were significantly associated with IMOC; and body fat percentage, BFM and adiponectin were significantly associated with HGSOC. Both GC and MR identified 13 shared factors. Factors were stratified into five priority levels, and visual causal networks were constructed for future interventions. Conclusions With analysis of large-scale exposures for breast and ovarian cancers, causalities, genetic correlations, shared or specific factors, risk factor priority and causal pathways and networks were identified.

The self-tapping screw connectors are widely used in Cold-formed Steel (CFS) construction due to their rapid fastening with automatic power driving and ease of installation via a self-drilling process. However, there is a lack of a robust numerical method for the modelling of behaviours of screw fasteners bearing against steel sheets, where the connections can undergo different failure modes including fracture, bearing, tilting, pull-out and shear failure, particularly for CFS thin plates. A nonlinear explicit dynamic finite element (FE) model is developed in this paper to address this issue by validating the modelled load-deformation relationships and failure modes with available tests in literature. The proposed numerical model is improved in two aspects comparing to available research: firstly, a ductile fracture criterion was proposed that could address the fracture of ply metals subjected to complex stress state with less trial-and-error process. Secondly, the threads in the screw fasteners and ply sheets were carefully modelled where the inter-locking capacity between the screws and steel sheets were better taken into account, eliminating the need for an artificial friction factor. The FE modelled results were compared against the test results and showed good agreement in terms of connection strength and failure modes, including fracture, bearing, tilting, pull-out and shear failure. Finally, parametric studies were carried out to investigate the influence of steel sheet thickness and the screw outer diameter on the force–displacement relationships of the steel lap joints.

CD8+ cytotoxic T-lymphocytes are essential components of the anti-tumor immunity. To better understand the expansion of CD8+ T-cells we used multiplex fluorescence immunohistochemistry to study Ki67+CD8+ cells in normal lymphoid tissues, selected inflammatory diseases and cancers in 41 large sections/ microenvironment tissue microarrays (TMAs) as well as 765 samples in a conventional TMA format. The evaluation of more than 20 different compartments of normal lymphoid tissues revealed that the percentage of proliferating (ki67+) CD8+ cells did commonly not exceed 3%. In inflammations, the percentage of Ki67+CD8+ cells was more variable and higher compared to normal tissues. In cancers, the percentage of Ki67+CD8+ cells was higher in the tumor center than at the invasive margin. In the tumor center of 765 colorectal cancers, the density of Ki67+CD8+ cells and the percentage of proliferating CD8+ cytotoxic T-cells was significantly associated with microsatellite instability (p

Purpose Expansion of CD8+ cytotoxic Tlymphocytes is a prerequisite for anti-cancer immune activity and has gained interest in the era of immune checkpoint therapy. Methods To understand the CD8+ T cell dynamics in the tumor microenvironment, we used multiplex fluorescence immunohistochemistry to quantitate CD8+ proliferation (Ki67 co-expression) in tissue microarrays from 1107 colorectal, 642 renal cell, 1066 breast, 375 ovarian, 451 pancreatic and 347 gastric cancer samples. Results The density and the percentage of proliferating (Ki67+) CD8+ T cells were both highly variable between tumor types as well as between patients with the same tumor type. Elevated density and percentage of proliferating CD8+ cytotoxic T cells were significantly associated with favorable tumor parameters such as low tumor stage, negative nodal stage (p ≤ 0.0041 each), prolonged overall survival (p ≤ 0.0028 each) and an inflamed immune phenotype (p = 0.0025) in colorectal cancer and, in contrast, linked to high tumor stage, advanced ISUP/Fuhrman/Thoenes grading (each p ≤ 0.003), shorter overall survival (p ≤ 0.0330 each) and an immune inflamed phenotype (p = 0.0094) in renal cell cancer. In breast, ovarian, pancreatic and gastric cancer the role of (Ki67+)CD8+ Tcells was not linked to clinicopathological data. Conclusion Our data demonstrate a tumor type dependent prognostic impact of proliferating (Ki67+)CD8+ Tcells and an inverse impact in colorectal and renal cell cancer.

Type 2 diabetes (T2D) is affected by a combination of genetic and environmental factors. However, the comprehensive genomic risk scores (GRSs) for T2D prediction have not been evaluated. Using a meta-scoring approach, we developed a metaGRS for T2D; T2D-related traits consist of 1,692 genetic variants in the UK Biobank training set (n = 40,423 + 7,558 events) and evaluate this score in the validation set (n = 303,053). The hazard ratio (HR) for T2D was 1.32 (95% confidence interval [CI]: 1.29–1.35) per standard deviation of metaGRS and was larger than previously published T2D-GRS. Individuals, in the top 25% of metaGRS, have an HR of 2.08 (95%CI: 1.93–2.23) compared with those in the bottom 25%. The addition of metaGRS to all conventional risk factors significantly increased the AUC (P

Background: Lupus nephritis (LN) is the most severe organ manifestations of systemic lupus erythematosus (SLE). Although increased knowledge of the disease pathogenesis has improved treatment options, outcomes have plateaued as current immunosuppressive therapies have failed to prevent disease relapse in more than half of treated patients. Thus, there is still an urgent need for novel therapy. Mesenchymal stem cells (MSCs) possess a potently immunosuppressive regulation on immune responses, and intravenous transplantation of MSCs ameliorates disease symptoms and has emerged as a potential beneficial therapy for LN. The objective of this review is to discuss the defective functions of MSCs in LN patients and the application of MSCs in the treatment of both LN animal models and patients. Summary: Bone marrow MSCs from SLE patients exhibit impaired capabilities of migration, differentiation, and immune regulation and display senescent phenotype. Allogeneic MSCs suppress autoimmunity and restore renal function in mouse models and patients with LN by inducing regulatory immune cells and suppressing Th1, Th17, T follicular helper cell, and B-cell responses. In addition, MSCs can home to the kidney and integrate into tubular cells and differentiate into mesangial cells. Key Messages: The efficacy of MSCs in the LN treatment remains to be confirmed, and future advances from stem cell science can be expected to pinpoint significant MSC subpopulations, as well as specific mechanisms of action, leading the way to the use of more potent stimulated or primed pretreated MSCs to treat LN.

Forward-looking imaging and target detection are highly desirable in many military and civilian fields, such as search and rescue, sea surface surveillance, airport surveillance, and guidance. However, there is a blind zone of forward-looking imaging for conventional Doppler beam sharpening and synthetic aperture radar. Scanning radar can be utilized to obtain a real beam image of a forward-looking area and implement target detection, while its azimuth resolution is poor due to the limitation of antenna size. Besides, during the processing procedure, imaging and target detection are usually regarded as two independent parts, which means that the imaging result will directly affect the detection performance. In this article, an integrated algorithm of super-resolution imaging and target detection for forward-looking scanning radar is proposed. In this algorithm, first of all, low-rank and sparse constraints as regularization norms are incorporated into the forward-looking scanning radar imaging and the objective function is established. Subsequently, the convex theory is utilized to solve the objective function and transform the problem of simultaneous super-resolution imaging and target detection into an optimization problem. Lastly, the super-resolution imaging and the target detection results are obtained simultaneously by solving the optimization problem using the alternating direction method of multipliers. In addition, simulation and experiment results are given to verify the effectiveness of the proposed algorithm.

Real-aperture radar can be utilized to realize forward-looking imaging by antenna scanning the imaging region. However, low azimuth resolution seriously affects its practical application. Although traditional super-resolution methods could enhance azimuth resolution to a certain extent, effective preservation of contour information for important targets still remains to be a problem. In this article, a method of total variation-sparse (TV-sparse) multiconstraint deconvolution is proposed to improve azimuth resolution of forward-looking imaging as well as preserve contour information of important targets. Since our interested targets usually appear to be sparse, the sparse constraint of the target is introduced first to achieve high resolution of forward-looking images, which may cause the loss of target contour information in the meantime. Second, total variation (TV) constraint is introduced based on the sparse constraint, converting traditional single-constraint super-resolution problem to a multiconstraint problem. We then use the split Bregman algorithm (SBA) to solve the multiconstraint problem, whose solution is the super-resolution image of radar forward-looking region. Compared with traditional super-resolution methods, the proposed method can improve the azimuth resolution of radar forward-looking imaging as well as better restore target contour information by adjusting respective weights of sparse constraint and TV constraint. Finally, the performance of the proposed method is validated with the simulation and measured data.

Purpose Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8+ lymphocytes in a wide range of different cancer types and subtypes. Methods The density of CD8+ lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides. Results We found that the median CD8+ lymphocyte counts ranged from 6 cells/mm2 in pleomorphic adenoma up to 1573 cells/mm2 in Hodgkin’s lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin’s lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm2) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved. Conclusion These data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors.

Background: Zinc finger protein of cerebellum 2 (ZIC2) is a transcriptional activator or repressor that is important for the organogenesis of the central nervous system. Previous studies have reported that ZIC2 is widely upregulated in a variety of tumors. Methods: Oncomine database was used to evaluate the expression levels of ZIC2 in hepatocellular carcinoma (HCC) and normal liver tissues. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to validate the results from the database. Cox regression analysis and survival curves were performed to assess the survival effect of ZIC2 in HCC. Results: Increased expression of ZIC2 was detected in HCC tissues compared with normal liver tissues. In addition, patients with high ZIC2 levels had a poor prognosis. Multivariate analysis showed that clinical stage (T or M classification) and ZIC2 levels were independent prognostic factors for overall survival. Moreover, a subgroup analysis revealed that patients with moderate or poor grade tumors, T1–2 tumors, N0 tumors, early American Joint Committee on Cancer (AJCC) stage, and old age were more likely to present with overexpression of ZIC2. To conclude, ZIC2 is upregulated in HCC and associated with the histology and survival of HCC patients. Conclusions: The expression status of ZIC2 may serve as an independent prognostic marker of HCC. Keywords: Zinc finger protein of cerebellum 2 (ZIC2), Prognosis, Hepatocellular carcinoma (HCC), Liver, Biomarker

Background Microsatellite instability (MSI) has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in pancreatic cancer, but data on the possible extent of intratumoral heterogeneity are lacking. Methods To study MSI heterogeneity in pancreatic cancer, a tissue microarray (TMA) comprising 597 tumors was screened by immunohistochemistry with antibodies for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. Results In six suspicious cases, large section immunohistochemistry and microsatellite analysis (Bethesda panel) resulted in the identification of 4 (0.8%) validated MSI cases out of 480 interpretable pancreatic ductal adenocarcinomas. MSI was absent in 55 adenocarcinomas of the ampulla of Vater and 7 acinar cell carcinomas. MMR deficiency always involved MSH6 loss, in three cases with additional loss of MSH2 expression. Three cancers were MSI-high and one case with isolated MSH6 loss was MSS in PCR analysis. The analysis of 44 cancer-containing tumor blocks revealed that the loss of MMR protein expression was always homogeneous in affected tumors. Automated digital image analysis of CD8 immunostaining demonstrated markedly higher CD8 + tumor infiltrating lymphocytes in tumors with (mean = 685, median = 626) than without (mean = 227; median = 124) MMR deficiency (p Conclusions Our data suggest that MSI occurs early in a small subset of ductal adenocarcinomas of the pancreas and that immunohistochemical MMR analysis on limited biopsy or cytology material may be sufficient to estimate MMR status of the entire cancer mass.

Background and purpose Previous studies have found ischemic stroke is associated with atrial fibrillation. However, the causal association between ischemic stroke and atrial fibrillation is not clear. Furthermore, the network relationship among ischemic stroke, atrial fibrillation and its risk factors need further attention. This study aims to examine the potential causal association between ischemic stroke and atrial fibrillation and further to explore potential mediators in the causal pathway from ischemic stroke to atrial fibrillation. Methods Summary statistics from the ISGC (case = 10,307 and control = 19,326) were used as ischemic stroke genetic instruments, AFGen Consortium data (case = 65,446 and control = 522,744) were used for atrial fibrillation, and other consortia data were used for potential mediators (fasting insulin, white blood cell count, procalcitonin, systolic and diastolic blood pressure, body mass index, waist circumference, and height). Under the framework of network Mendelian randomization, two-sample Mendelian randomization study was performed using summary statistics from several genome-wide association studies. Inverse-variance weighted method was performed to estimate causal effect. Results Blood pressure mediates the causal pathways from ischemic stroke to atrial fibrillation. The total odds ratio of ischemic stroke on atrial fibrillation was 1.05 (95% confidence interval [CI], 1.02 to 1.07; P = 1.3 × 10−5). One-unit increase of genetically determined ischemic stroke was associated with 0.02 (DBP: 95% CI, 0.001 to 0.034, P = 0.029; SBP: 95% CI, 0.006 to 0.034, P = 0.003) upper systolic and diastolic blood pressure levels. Higher genetically determined systolic and diastolic blood pressure levels were associated with higher atrial fibrillation risk (DBP: RR, 1.18; 95% CI, 1.03 to 1.35; P = 0.012. SBP: RR, 1.18; 95% CI, 1.01 to 1.38; P = 0.04). Specially, we also found the bidirectional causality between blood pressure and ischemic stroke. Conclusions Our study provided a strong evidence that raised blood pressure in stroke patients increases the risk of atrial fibrillation and active acute blood pressure lowering can improve the outcome in ischemic stroke patients.

An experimental program investigating the flexural behavior of an innovative dovetail ultra-high performance concrete joint for connecting precast ultra-high performance concrete slabs in composite bridges is reported in this study. Test parameters included interface treatment method, joint material, reinforcing bar overlapping form, and prestressing level. Specifically, a new steel wire mesh interface treatment was proposed, which could generate an additional fiber-bridging mechanism in the joint surface. An enhancement of 17.4%, 20.1%, and 50% on flexural cracking strength, ultimate strength, and ductility were obtained by using the steel wire mesh. Joint material showed no significant influence, while prestressing had obvious influence on the flexural behavior of ultra-high performance concrete joints. The post-cracking behavior, ductility performance, and stiffness degradation of the tested specimens were analyzed. Good deformability was obtained for the jointed ultra-high performance concrete slabs as the ratio of deflection to span was about 1/50 at failure. The post-cracking stiffness was retained at about 90% of the initial stiffness, while the ultimate stiffness was retained at about 10% of the initial stiffness. The research findings are useful in popularizing and applying the proposed innovative dovetail ultra-high performance concrete joints in composite bridges.

Rationale: Although mesenchymal stem cell (MSC) transplantation has been proved to be an effective therapeutic approach to treat experimental Sjogren's syndrome (SS), the detailed underlying mechanisms remains unknown. IL-27 has diverse influences on the regulation of T cell differentiation and was involved in SS through modulating immune response. Here we aimed to explore whether IL-27-mediated regulation of immune cells was responsible for the beneficial effects of MSC transplantation on SS. Methods: The SS-like symptoms were evaluated in IL-27 deficient and recombinant IL-27-treated NOD mice. The MSCs were infused into NOD mice via the tail vein. The histological features of submandibular glands, saliva flow rate and serum IL-27 were examined. The effects of MSCs on the IL-27 production and Th17/Treg cell in SS patients and mice in vitro and in vivo were determined for the mechanistic study. Results: This study showed that SS patients had decreased IL-27 level and increased ratio of Th17/Treg cells. Consistently, exacerbated SS-like symptoms were observed in IL-27 deficient NOD mice, along with increased ratio of Th17/Treg cells. Importantly, MSC transplantation alleviated SS-like symptoms by elevating the level of IL-27 to restore Th17/Treg balance in NOD mice. Mechanistically, MSC-secreted interferon-β (IFN-β) promote dendritic cells to produce IL-27. Conclusions: Thus, we have revealed a previously unrecognized function of MSC-mediated IL-27 production by DCs in suppressing SS-like syndrome, which provided evidences for clinical application of MSC in patients with SS.

Introduction Chronic eosinophilic pneumonia (CEP) is a rare disease with unknown etiology. Due to lack of specificity of CEP symptoms, clinicians are not experienced in establishing its diagnosis. Objectives To summarize the clinical data of CEP patients to improve the understanding of CEP and reduce misdiagnosis. Methods Data of patients pathologically diagnosed with CEP in the PLA General Hospital between May 2013 and May 2019 were collected, and clinical manifestations, imaging characteristics, pathological features, and treatment were retrospectively analyzed. Results Twenty patients, including 6 males and 14 females, were diagnosed with CEP. The average age was 47.0 ± 10.2 years. The main clinical manifestations were cough and dyspnea. The average duration of CEP was 15.5 ± 11.5 months. The average proportion of eosinophils in the peripheral blood was 18.9 ± 17.8%, and the average proportion of eosinophils in the bronchoalveolar lavage fluid was 41.5 ± 19.4%. The main imaging features were patchy shadows and consolidation shadows. The most common manifestations on bronchoscopic examination were congestion and edema of the bronchial mucosa. Two patients had granular protrusions of the endotracheal membrane. Histological examination indicated infiltration of numerous eosinophils. All patients improved after prednisone therapy. Conclusion CEP onset is insidious, and clinical manifestations lack specificity. Typical imaging features are peripheral and subpleural distribution of lung infiltrates. Some patients have a normal proportion of eosinophils in the peripheral blood, but most have an increased number of eosinophils in the BALF, which contributes to CEP diagnosis. A biopsy is necessary when differential diagnosis is difficult. A systemic glucocorticoid is effective.

ObjectivesBetter understanding of the dynamics of the COVID-19 (2019 novel coronavirus disease) pandemic to curb its spread is now a global imperative. While travel restrictions and control measures have been shown to limit the spread of the disease, the effectiveness of the enforcement of those measures should depend on the strength of the government. Whether, and how, the government plays a role in fighting the disease, however, has not been investigated. Here, we show that government management capacities are critical to the containment of the disease.SettingWe conducted a statistical analysis based on cross-city comparisons within China. China has undergone almost the entire cycle of the anticoronavirus campaign, which allows us to trace the full dynamics of the outbreak, with homogeneity in standards for statistics recording.Primary and secondary outcome measuresOutcome measures include city-specific COVID-19 case incidence and recoveries in China.ResultsThe containment of COVID-19 depends on the effectiveness of the enforcement of control measures, which in turn depends on the local government’s management capacities. Specifically, government efficiency, capacity for law enforcement, and the transparency of laws and policies significantly reduce COVID-19 prevalence and increase the likelihood of recoveries. The organisation size of the government, which is not closely related to its capacity for management, has a limited role.

Infection is a common cause of hospitalization and mortality in patients with systemic lupus erythematosus (SLE). How the underlying immune dysfunctions affect the antimicrobial immunity remains largely unknown. In the present study, employing the pulmonary infection model, we determined the antimicrobial defence of lupus-prone mice. After infecting with opportunistic bacterium Haemophilus influenzae (Hi), lupus-prone mice (B6/lpr) exhibited inefficient bacterial elimination and recovered slowly. They generated severer inflammation at the early stage of infection, as excessive accumulation of neutrophils and enhanced production of proinflammatory cytokines were observed in the lung. In addition, a large number of apoptotic cells were detected in the lungs of B6/lpr mice. For adaptive immune responses, B6/lpr mice were capable to generate enough protective Hi-specific Th17 cells. They evoked stronger Hi-specific γδ T17 response in both lungs and spleens. Unexpectedly, both CD4 and γδ T cells from lupus-prone mice showed deficiency in IFN-γ production. For humoral immune responses, compared with those of WT mice, the concentrations of Hi-specific IgA, IgM, and IgG, especially IgG, were significantly higher in the B6/lpr mice. Our findings suggest that lupus mice are capable to generate antibacterial immune responses; however, the overwhelming inflammation and overactivated immune responses increase the severity of infection.

In the age of information explosion, image classification is the key technology of dealing with and organizing a large number of image data. Currently, the classical image classification algorithms are mostly based on RGB images or grayscale images, and fail to make good use of the depth information about objects or scenes. The depth information in the images has a strong complementary effect, which can enhance the classification accuracy significantly. In this paper, we propose an image classification technology using principal component analysis based on multi-view depth characters. In detail, firstly, the depth image of the original image is estimated; secondly, depth characters are extracted from the RGB views and the depth view separately, and then the reducing dimension operation through the PCA is implemented. Eventually, the SVM is applied to image classification. The experimental results show that the method has good performance.

In this study, a novel hybrid surface plasmon waveguide structure based on CdS nanowires and metal ridges was designed. The waveguide structure was simulated and analysed at a working wavelength of 490 nm based on the finite element method. The electric field distribution, mode characteristics, transmission length and quality factor of the waveguide were studied with geometric parameters. Results show that the comprehensive performance of the waveguide can be significantly optimised by appropriately adjusting the geometric parameters of the structure. Through the optimal parameter design, the effective mode field area reaches 0.008 λ 2 , the transmission length is 21,289 nm, and the quality factor is 702.12. This waveguide structure has great potential in the fields of optoelectronic communication and optical sensing technology.

Background Defective clearance of apoptotic cells (ACs) has been suggested to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) exhibit promising therapeutic effects on SLE, but whether MSCs phagocytose ACs and contributes to the underlying mechanism in the treatment of SLE remain unknown. Methods Human umbilical cord (UC) MSCs were co-cultured with ACs, and the engulfment of ACs by MSCs was either detected by flow cytometry or observed under confocal laser scanning microscope. Peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) were cultured in MSC conditioned medium (MCM) or MSC exposed to ACs (AC-MSC) conditioned medium (ACMCM), and then CD4+ T cell proliferation was detected. Soluble factors including prostaglandin (PG)E2 in the supernatants of MSCs and AC-MSCs, as well as in the mouse peritoneal lavage fluids (PLF) were determined by enzyme-linked immunosorbent assay (ELISA). Cyclooxygenase (COX)2 inhibitors and siRNA transfection were utilized to determine the function of COX2/PGE2 in AC-MSC-mediated immunosuppression. PGE2 metabolites (PGEM) in the plasma of SLE patients were measured before and 24 h after MSC transplantation respectively. Findings Human UC MSCs possessed the ability to engulf ACs. AC-MSCs increased MSC-mediated suppression of CD4+ T cell proliferation compared to MSCs alone. Mechanistically, ACs stimulated MSCs to express COX2 and consequently produced PGE2 that inhibited T cell responses. NF-κB signalling pathway mediated the activation of COX2/PGE2 in AC-MSCs. Importantly, in patients with SLE, the plasma PGEM levels increased significantly in those with reduced apoptotic mononuclear cells in peripheral blood after MSC transplantation. Interpretation Clearance of ACs by MSCs contributes to immunosuppressive function via increasing PGE2 production. These findings reveal a previously unrecognized role of MSC-mediated phagocytosis of ACs in MSC-based immunotherapy. Fund This study was supported by grants from the Chinese Major International (Regional) Joint Research Project (No. 81720108020), the Jiangsu Province Major Research and Development Program (No. BE2015602) and the Jiangsu Province 333 Talent Grant (BRA2016001). WJ. Chen was supported by the Intramural Research Program of NIH, NIDCR.

This study presents an experimental and numerical investigation on the static behavior of headed stud shear connectors in ultra-high performance concrete (UHPC) of composite bridges. Four push-out specimens were tested. It was found that no cracking, crushing or splitting was observed on the concrete slab, indicating that UHPC slab exhibited good performance and could resist the high force transferred from the headed studs. The numerical and experimental results indicated that the shear capacity is supposed to be composed of two parts stud shank shear contribution and concrete wedge block shear contribution. The stiffness increment of a stud in UHPC was at least 60% higher than that in normal strength concrete. Even if the stud height was reduced from 6d to 2d, there was no reduction in the shear strength of a stud. Short stud shear connectors with an aspect ratio as small as 2 could develop full strength in UHPC slabs. An empirical load-slip equation taking into account stud diameter was proposed to predict the load-slip response of a stud. The reliability and accuracy of the proposed load-slip equation was verified by the experimental and numerical load-slip curves.

Fifth generation mobile networks (5G) is coming into our life and it will not only provide an increase of 1000 times in Internet traffic in the next decade but will also offer “smarter” user experience. With the commercial uses of 5G, online social networks and smart phones will spring up again. Then cross-modality data will play a more important role in the daily information dissemination. As an effective way of content analysis, topic detection has attracted much research interest, but conventional topic analysis is undergoing the limitations from the cross-modality heterogenous data. This paper proposes a sentimental image dominant graph topic model, that can detect the topic from the heterogenous data and mine the sentiment of each topic. In details, we design a topic model to transfer both the low-level visual modality and the high-level text modality into a semantic manifold, and improve the discriminative power of CNN feature by jointly optimizing the output of both convolutional layer and fully-connected layer. Furthermore, since the sentimental impact is very significant for understanding the intrinsic meaning of topics, we introduce a semantic score of subjective sentences to calculate the sentiment on the base of the contextual sentence structure. The comparison experiments on the public cross-modality benchmark show the promising performance of our model. So our method using AI technology will facilitate the intellectualization of 5G.

In this paper, the electromagnetically induced transparency (EIT) effect of graphene nanostructures was studied by numerical methods. Numerous branch structures were added to the sides of the graphene/medium/graphene waveguide, and the Fabry-Perot resonators were formed between adjacent branches due to the phase coupling effect. The back and forth oscillation of electromagnetic waves in the cavity significantly enhanced the transmitted light in a narrow band. Thus, an output spectrum similar to the EIT effect was produced. The output spectrum can be further adjusted by the gate voltage with the unique electrically adjustable properties of graphene. The surface of plasmon exhibited stronger locality in graphene nanostructures than metals. Thus, graphene-based electro-optical devices were more compact and integrated in the deep sub-wavelength scale. The proposed graphene nanostructures facilitated the implementation of a variety of high performance electro-optical devices, including multi-channel selective filters, sensors, and modulators.

The convenience of the cloud-assisted Internet of Things has led to the need for improved protections for the large volumes of data collected from devices around the world and stored on cloud-based servers. Proxy re-encryption (PRE) has been presented as a suitable mechanism for secure transmission and sharing of files within the cloud. However, existing PRE schemes do not support unidirectional data transformation, fine-grained controls, multiple hops, and identity-based encryption simultaneously. To solve these problems, we propose a unidirectional multi-hop identity based-conditional PRE scheme that meets all of the above requirements. Our proposal has the additional benefits of a constant ciphertext size, non-interactivity, and collusion resistance. We also prove that our scheme is secure against adaptive identity chosen-ciphertext attacks in the standard model.

As a novel network architecture, information-centric networking (ICN) has a good performance in facilitating content sharing among users. Although in-network cache used in ICN can effectively solve the problem of network congestion. Meanwhile, it also brings a lot of challenges such as security and privacy issues during data transformation. Some of the current solutions are based on the traditional encryption technology, but these solutions introduce significant overhead in the client side and have a high requirement to the memory and computing power of end user. In this paper, we use an efficient proxy re-encryption (PRE) scheme in ICN framework to help reduce the overhead on the user-side while guaranteeing flexible data sharing between subscribers and even their cooperator. Our proposal has the additional benefits of a non-interactivity and collusion resistance. We also prove that our scheme is secure against adaptive replayable adaptive chosen ciphertext attack (RCCA) in re-encryption and chosen ciphertext attack (CCA) secure in complete ICN encryption. Our analysis of this program also shows that the scheme has a relatively good performance in computation cost and communication complexity aspects.

We proposed an electro-optic modulator with two-bus one-ring (TBOR) structure to improve the extinction ratio and reduce insert loss. It has a dual output compared with one-bus one-ring structure. In addition, double-layer graphene makes it possible for the modulation in the visible to mid-infrared wavelength range. It shows that this new electro-optic modulator can present two switching states well with low insertion loss, high absorption and high extinction ratio. At λ = 1550 nm , when the switching states are based on the chemical potential, μ c = 0.38 eV and μ c = 0.4 eV , the insertion losses of both output ports are less than 2 dB, the absorption of the output port coupled via a micro-ring reaches 45 dB and the extinction ratio reaches 14 dB. When the refractive index of the dielectric material is 4.2, the applied voltage will be less than 1.2 V, thus can be used in low-voltage CMOS technology.

Aim Cardiovascular complications related to atherosclerosis are major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, the underlying mechanisms are not fully understood. Endothelial dysfunction has been identified as having involvement in pathogenesis of cardiovascular diseases and SLE. This study aims to evaluate endothelial cell injury in mice with the combination of lupus and atherosclerosis. Methods The mouse model of accelerated atherosclerosis in lupus (gld.apoE- / - mouse) was generated from apolipoprotein E-deficient (apoE- / - ) and Faslgld C57BL/6 mice. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. The endothelial cell injury was determined. Results The results showed that the double-mutant gld.apoE- / - mice were generated. Spleens from 5-month-old gld.apoE- / - mice were significantly enlarged compared with wild-type mice (WT mice). The gld.apoE- / - mice produced high levels of total immunoglobulin G (IgG) and IgM and showed marked increase of IgG and C3 deposits in the glomeruli. The gld.apoE- / - mice displayed a pattern of glomerulonephritis typically found in SLE. The gld.apoE- / - mice have high levels of serum creatinine. The total cholesterol, low-density lipoprotein cholesterol and triglycerides were significantly increased, while high-density lipoprotein cholesterol decreased in the double-mutant mice. The circulating endothelial progenitor cells were significantly decreased. The serum levels of thrombomodulin and vascular cell adhesion molecule-1 were significantly elevated in gld.apoE- / - mice. The gld.apoE- / - mice simultaneously exhibited SLE and atherosclerosis characteristics. Conclusion Our findings indicated that endothelial cell injury might be a biomarker for evaluating risks of cardiovascular disease in SLE and targeting endothelial cell dysfunction might prevent and treat atherosclerosis in SLE.

An in-fiber integrated sensor array with the embedded weakly reflective joint surface is proposed and demonstrated. The weak reflector is formed of a single-mode fiber (SMF) and a double-cladding fiber (DCF), whose cores have different refractive index. A sensor array based on this structure is sensitive to strain and temperature, and it has the ability to achieve quasi-distributed measurements. Therefore, it can be used for structural health monitoring. Besides that, without any connector, the sensors were integrated in a fiber. Consequently, they are more suitable for a harsh test environment (space limitation or high temperature).

A novel perovskite hybrid surface plasmon waveguide structure is designed. Established its physical model and introduced its theoretical basis in detail. Based on the finite element method, the mode characteristics, quality factor, and gain threshold of the waveguide structure are analyzed with geometric parameters. The results show that the optical field constraint of the waveguide can reach a good deep sub-wavelength level under the optimal operating wavelength of 1550nm. By adjusting the waveguide design parameters, the high quality factor, low energy loss, low threshold limit and ultra small effective mode field area are obtained. Compared with the hybrid waveguide structure proposed in the current research results, this structure has stronger optical field limiting ability and microcavity binding ability. The waveguide structure can provide theoretical and technical support for the development of new efficient nano laser devices, and has a good application prospect.

Background Although observational studies have shown an association between sex hormone-binding globulin (SHBG), testosterone (T) and cardiovascular diseases (CVD), controversy remains. In this study, we aim to explore the causal effects of SHBG and T on Coronary heart disease (CHD). Methods We used univariable, network and multivariable mendelian randomization (MR) analysis to investigate the causal effect of SHBG and T on CHD. We performed inverse variance weighted (IVW) MR as the primary analysis, with the robustness of this approach further tested by other methods in sensitivity analysis. The SHBG and T were collected from the UK Biobank data, about 180,000 men aged 40 to 69 years. CHD was collected from CARDIoGRAMplusC4D 1000 Genomes-based GWAS, which was a meta-analysis including 48 studies and involving 60,801 CHD cases and 123,504 controls. Results Using univariable MR-IVW, the results suggested that a one standard deviation (SD) increase in SHBG, the risk of CHD decreased by approximately 14% (OR (95% CI): 0.86(0.76,0.97)), and that a SD increase in total testosterone (TT), the risk also decreased, approximately 8% (OR (95% CI): 0.92(0.85,0.99)). Multivariable MR showed that both SHBG and TT had no direct causal effect with CHD (a SD increase in SHBG: OR (95% CI):0.75(0.57,1.00), P = 0.053; a SD increase in TT: OR (95% CI): 1.05(0.90,1.22), P = 0.53). In the network MR analysis, the results suggested that TT might act as mediator in the causal pathway from SHBG to CHD and account for 93% of the total effect of SHBG on CHD, and that SHBG might be a mediator in the causal pathway from TT to CHD and account for 67% of the total effect of TT on CHD. Conclusions Genetically predicted SHBG and TT were negatively correlated with CHD in both univariable and network MR, which may provide a causal explanation behind the observed conclusion. In addition, TT and SHBG had a bidirectional causal effect. Further work is required to disentangle the downstream effects of SHBG/TT on CHD and the molecular pathways involved, as the simultaneous regulation of SHBG and TT may make it a viable strategy for the prevention or treatment of CHD.

Absolute localization of a flying UAV on its own in a global-navigation-satellite-system (GNSS)-denied environment is always a challenge. In this paper, we present a landmark-based approach where a UAV is automatically locked into the landmark scene shown in a georeferenced image via a feedback control loop, which is driven by the output of an aerial image registration. To pursue a real-time application, we design and implement a speeded-up-robust-features (SURF)-based image registration algorithm that focuses efficiency and robustness under a 2D geometric transformation. A linear UAV controller with signals of four degrees of freedom is derived from the estimated transformation matrix. The approach is validated in a virtual simulation environment, with experimental results demonstrating the effectiveness and robustness of the proposed UAV self-localization system.

This paper considers the two-dimensional (2D) anchorless localization problem for sensor networks in global positioning system (GPS)-denied environments. We present an efficient method, based on the multidimensional scaling (MDS) algorithm, in order to estimate the positions of the nodes in the network using measurements of the inter-node distances. The proposed method takes advantage of the mobility of the nodes to address the location ambiguity problem, i.e., rotation and flip ambiguity, which arises in the anchorless MDS algorithm. Knowledge of the displacement of the moving node is used to produce an analytical solution for the noise-free case. Subsequently, a least squares estimator is presented for the noisy scenario and the associated closed-form solution derived. The simulations show that the proposed algorithm accurately and efficiently estimates the locations of nodes, outperforming alternative methods.

Background: The causal evidence of the triglyceride–glucose (TyG) index, as well as the joint exposure of higher glucose and triglyceride on the risk of cardio-cerebrovascular diseases (CVD), was lacking.Methods: A comprehensive factorial Mendelian randomization (MR) was performed in the UK Biobank cohort involving 273,368 individuals with European ancestry to assess and quantify these effects. The factorial MR, MR-PRESSO, MR-Egger, meta-regression, sensitivity analysis, positive control, and external verification were utilized. Outcomes include major outcomes [overall CVD, ischemic heart diseases (IHD), and cerebrovascular diseases (CED)] and minor outcomes [angina pectoris (AP), acute myocardial infarction (AMI), chronic IHD (CIHD), heart failure (HF), hemorrhagic stroke (HS), and ischemic stroke (IS)].Results: The TyG index significantly increased the risk of overall CVD [OR (95% CI): 1.20 (1.14–1.25)], IHD [OR (95% CI): 1.22 (1.15–1.29)], CED [OR (95% CI): 1.14 (1.05–1.23)], AP [OR (95% CI): 1.29 (1.20–1.39)], AMI [OR (95% CI): 1.27 (1.16–1.39)], CIHD [OR (95% CI): 1.21 (1.13–1.29)], and IS [OR (95% CI): 1.22 (1.06–1.40)]. Joint exposure to genetically higher GLU and TG was significantly associated with a higher risk of overall CVD [OR (95% CI): 1.17 (1.12–1.23)] and IHD [OR (95% CI): 1.22 (1.16–1.29)], but not with CED. The effect of GLU and TG was independent of each other genetically and presented dose–response effects in bivariate meta-regression analysis.Conclusions: Lifelong genetic exposure to higher GLU and TG was jointly associated with higher cardiac metabolic risk while the TyG index additionally associated with several cerebrovascular diseases. The TyG index could serve as a more sensitive pre-diagnostic indicator for CVD while the joint GLU and TG could offer a quantitative risk for cardiac metabolic outcomes.

Causal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD.Two-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed.Apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were still important risk factors for CHD and myocardial infarction (MI) but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The odds ratios (ORs) of total TG on CHD and MI were 1.25 (95% confidence interval [CI], 1.13-1.38) and 1.24 (95% CI, 1.11-1.38), respectively. A one standard deviation difference increased TG in medium very-low-density lipoproteins (M.VLDL.TG), TG in small VLDL (S.VLDL.TG), TG in very small VLDL (XS.VLDL.TG), TG in intermediate-density lipoproteins (IDL.TG), TG in very large HDL (XL.HDL.TG), and TG in small HDL (S.HDL.TG) particles also robustly increased the risk of CHD and MI by 9-28% and 9-27%, respectively. TG in very/extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable TSMR), and negatively associated with IS as well.The remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.

A tunable Fano resonance based on a microring resonator is proposed. The double microring is nested in parallel in the U-shaped feedback waveguide with the graphene embedded in part of the waveguide as the active modulation region of Fano resonance. When different voltages are applied to the graphene in the feedback waveguide or microrings, the Fano resonance exhibits different and asymmetrical shapes and has a larger extinction ratio than the traditional Lorentz shape. The maximum extinction ratio of the proposed device is up to 71.50 dB. The proposed structure will have a wide application in sensors, switches, and integrated optoelectronic devices.

The inhalation of dust containing certain nickel compounds has been associated with an increased risk of lung and nasal cancers in occupational studies of workers who process or refine sulfidic nickel ores and are exposed to relatively high levels of mixtures of water-soluble, sulfidic, oxidic, and/or metallic forms of nickel. We conducted a systematic review of the potential carcinogenicity of metallic nickel, focusing on cancers of the respiratory tract. We evaluated the quality and risk of bias (RoB) of the relevant epidemiology, experimental animal, and in vitro mechanistic studies using the National Toxicology Program's Office of Health Assessment and Translation (OHAT) RoB Rating Tool. We then used a systematic review protocol based on the OHAT approach to critically assess whether metallic nickel should be considered a human respiratory carcinogen. Our evaluation of the epidemiology studies indicates that there is no substantive evidence of increased respiratory cancer risk in workers exposed predominantly to metallic nickel. Animal evidence indicates that metallic nickel does not increase the incidence of respiratory tumors in rodents exposed by inhalation. The in vitro studies are limited in value, as they bypass normal clearance mechanisms. Nevertheless, the mechanistic evidence indicates that metallic nickel is not mutagenic but can induce DNA strand breaks under certain conditions. Based on a standard framework for assessing causality, we conclude that the evidence does not support a causal relationship between metallic nickel exposure and respiratory cancer in humans.

Background In epidemiology studies, ambient measurements of PM2.5 are often used as surrogates for personal exposures. However, it is unclear the degree to which ambient PM2.5 reflects personal exposures. Objective In order to examine potential sources of bias in epidemiology studies, we conducted a review and meta-analysis of studies to determine the extent to which short-term measurements of ambient PM2.5 levels are related to short-term measurements of personal PM2.5 levels. Methods We conducted a literature search of studies reporting both personal and ambient measurements of PM2.5 published in the last 10 years (2009–2019) and incorporated studies published prior to 2009 from reviews. Results Seventy-one studies were identified. Based on 17 studies reporting slopes, a meta-analysis revealed an overall slope of 0.56 μg/m3 (95% CI: [0.39, 0.73]) personal PM2.5 per μg/m3 increase in ambient PM2.5. Slopes for summer months were higher (slope = 0.73, 95% CI: [0.64, 0.81]) than for winter (slope = 0.46, 95% CI: [0.36, 0.57]). Based on 44 studies reporting correlations, we calculated an overall personal-ambient PM2.5 correlation of 0.63 (95% CI: [0.55, 0.71]). Correlations were stronger in studies conducted in Canada (r = 0.86, 95% CI: [0.67, 0.94]) compared to the USA (r = 0.60, 95% CI: [0.49, 0.70]) and China (r = 0.60, 95% CI: [0.46, 0.71]). Correlations also were stronger in urban areas (r = 0.53, 95% CI: [0.43, 0.62]) vs. suburban areas (r = 0.36, 95% CI: [0.21, 0.49]). Significance Our results suggest a large degree of variability in the personal-ambient PM2.5 association and the potential for exposure misclassification and measurement error in PM2.5 epidemiology studies.

Total variation (TV) method has been utilized to realize super-resolution and preserve contour information of target in radar forward-looking imaging. However, its real-time ability is restricted to matrix inversion. In this paper, a fast TV (FTV) superresolution method is proposed to improve the real-time superresolution ability of traditional TV method. The proposed FTV method utilizes the low displacement rank features of Toplitz matrix and realizes fast matrix inversion by Gohberg-Semencul (GS) representation. It not only effectively improves the azimuth resolution and preserve the contour information of target, but also reduced the computational complexity of traditional TV method to improve its real-time superresolution ability. The superior performance of the proposed FTV method is verified by simulation and measured data processing.

Animated visualization is becoming increasingly popular as a compelling way to illustrate changes in time series data. However, maintaining the viewer’s focus throughout the entire animation is difficult because of its time-consuming nature. Viewers are likely to become bored and distracted during the ever-changing animated visualization. Informed by the role of foreshadowing that builds the expectation in film and literature, we introduce visual foreshadowing to improve the engagement of animated visualizations. In specific, we propose designs of visual foreshadowing that engage the audience while watching the animation. To demonstrate our approach, we built a proof-of-concept animated visualization authoring tool that incorporates visual foreshadowing techniques with various styles. Our user study indicates the effectiveness of our foreshadowing techniques on improving engagement for animated visualization.

To predict epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma using MR-based radiomics signature of brain metastasis and explore the optimal MR sequence for prediction. Data from 52 patients with brain metastasis from lung adenocarcinoma (28 with mutant EGFR, 24 with wild-type EGFR) were retrospectively reviewed. Contrast-enhanced T1-weighted imaging (T1-CE), T2 fluid-attenuated inversion recovery (T2-FLAIR), T2WI, and DWI sequences were selected for radiomics features extraction. A total of 438 radiomics features were extracted from each MR sequence. All sequences were randomly divided into training and validation cohorts. The least absolute shrinkage selection operator was used to select informative features, a radiomics signature was built with the logistic regression model of the training cohort, and the radiomics signature performance was evaluated using the validation cohort and an independent testing data set. The radiomics signature built on 9 selected features showed good discrimination in both the training and validation cohorts for T2-FLAIR. The radiomics signature of T2-FLAIR yielded an AUC of 0.987, a classification accuracy of 0.991, sensitivity of 1.000, and specificity of 0.980 in the validation cohort. The AUC was 0.871 in the independent testing data set. The AUCs of our radiomics signature to differentiate exon 19 and exon 21 mutations were 0.529, 0.580, 0.645, and 0.406 for T1-CE, T2-FLAIR, T2WI, and DWI, respectively. We developed a T2-FLAIR radiomics signature that can be used as a noninvasive auxiliary tool for predicting EGFR mutation status in lung adenocarcinoma, which is helpful to guide therapeutic strategies. • MR-based radiomics signature of brain metastasis may help predict EGFR mutation status in lung adenocarcinoma, especially using T2-FLAIR. • Nine radiomics features extracted from T2-FLAIR sequence strongly correlate with EGFR mutation status. • Radiomics features reflect tumor heterogeneity through potential changes in tissue morphology caused by EGFR mutation.

BACKGROUND: Lipocalin-2 (LCN2) is an indicator of the severity of lupus nephritis (LN) and plays a pivotal role in immune responses, but it is not known if its effect on LN pathogenesis derives from regulating the immune imbalance of T lymphocyte subsets. METHODS: The expression of LCN2 in T cells and kidneys was assessed in renal biopsies from patients with LN. We investigated the relationship between LCN2 levels and development of LN and systemic illness by injecting anti-LCN2 antibodies into MRL/lpr mice and analyzing pristane-treated LCN2(−/−) mice. RESULTS: LCN2 is highly expressed in CD4(+) T cells and in renal tissues, and is associated with severe renal damage in patients with LN and in mice with experimental lupus. LCN2 promotes IFN-γ overexpression in CD4(+) T cells through the IL-12/STAT4 pathway in an autocrine or paracrine manner. Both neutralization of LCN2 in MRL/lpr mice and genetic depletion of LCN2 in pristane-induced lupus mice greatly ameliorate nephritis. The frequency and number of splenic and renal Th1 cells decrease in proportion to LN disease activity. Conversely, administration of LCN2 exacerbates the disease with significantly higher renal activity scores and increased numbers of Th1 cells. CONCLUSIONS: LCN2 plays a crucial role in Th1 cell differentiation, and may present a potential therapeutic target for LN.

We present TrojDRL, a tool for exploring and evaluating backdoor attacks on deep reinforcement learning agents. TrojDRL exploits the sequential nature of deep reinforcement learning (DRL) and considers different gradations of threat models. We show that untargeted attacks on state-of-the-art actor-critic algorithms can circumvent existing defenses built on the assumption of backdoors being targeted. We evaluated TrojDRL on a broad set of DRL benchmarks and showed that the attacks require only poisoning as little as 0.025% of the training data. Compared with existing works of backdoor attacks on classification models, TrojDRL provides a first step towards understanding the vulnerability of DRL agents.

Background Available data about the effects of circulating polyunsaturated fatty acids (PUFAs) on ischemic stroke (IS) and its main risk factors remains limited and conflicting. Therefore, we conducted Mendelian randomization (MR) to assess whether genetically predicted PUFA affected IS, lipids and blood pressure (BP). Methods Genetic instruments associated with IS were derived from ISGC Consortium (n = 29,633), with lipids were derived from GLGC(n = 188,577), with BP were derived from Neale Lab(n = 337,000). The inverse-variance weighted method was the main analysis to estimate the effect of exposure on outcome. Sensitivity analyses included principal components analysis, MR-Egger, weighted median, and weighted mode. Results Per SD increases in serum α-linolenic acid (ALA) were associated with lower IS risk, with odd ratio (OR) of 0.867(0.782,0.961), arachidonic acid (AA) were associated with higher IS risk (OR: 1.053(1.014,1.094)). Likewise, Per SD increases in ALA were associated with the lower-level low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) (β:-0.122(− 0.144, − 0.101), − 0.159(− 0.182, − 0.135), − 0.148(− 0.171, − 0.126), respectively), AA were associated with the higher-level of LDL-C, HDL-C and TC (β:0.045(0.034,0.056), 0.059(0.050,0.067), 0.055(0.046,0.063), respectively). Linoleic acid (LA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) had little or no association with IS, lipids or BP at Bonferroni-corrected significance. Different analytic methods supported these findings. The intercept test of MR-Egger implied no pleiotropy. Conclusions High-level plasma ALA was protective for IS but AA was the opposite. LA, EPA, DHA, and DPA had no effects on IS.

Recent successes of wireless networked systems in advancing industrial automation and in spawning the Internet of Things paradigm motivate the adoption of wireless networked systems in current and future safety-critical applications. As reliability is key in safety-critical applications, in this work we present NetDAG, a scheduler design and implementation suitable for real-time applications in the wireless setting. NetDAG is built upon the Low-Power Wireless Bus, a high-performant communication abstraction for wireless networked systems, and enables system designers to directly schedule applications under specified task-level real-time constraints. Access to real-time primitives in the scheduler permits efficient design exploration of tradeoffs between power consumption and latency. Furthermore, NetDAG provides support for weakly hard real-time applications with deterministic guarantees, in addition to heretofore considered soft real-time applications with probabilistic guarantees. We propose novel abstraction techniques for reasoning about conjunctions of weakly hard constraints and show how such abstractions can be used to handle the significant scheduling difficulties brought on by networked components with weakly hard behaviors.

The logistics industry is a derivative industry of manufacturing services extraposition. A variety of strategies to develop the manufacturing industry are important programs of action for China's manufacturing strategic power, and it is of great significance to promote the high-quality development of the logistics industry. This paper takes strong manufacturing provinces with the development of the logistics industry as the research object and applies network DEA measuring the production efficiency and service efficiency of the logistics industry from 2004 to 2017. This paper adopts the "Made in China 2025" strategy as a natural experiment and uses double difference to study the impact of manufacturing policies on the high-quality development of the logistics industry. The empirical results show that compared with the Reference group, the impact of the "Made in China 2025" strategy led to a significant increase in the production efficiency and service efficiency of the experimental group. The group-based test based on innovation type shows that independent innovation has a significant positive effect on the high-quality development of the logistics industry, which shows that from the perspective of technological innovation, independent innovation is the main path of the "Made in China 2025" strategy to promote the high-quality development of the logistics industry. This paper not only identifies the causal relationship between the "Made in China 2025" strategy and the high-quality development of the logistics industry but also helps clarify the mechanism of how manufacturing policies improve the high-quality development of the logistics industry, which has important implications for further promoting the combined development between manufacturing and logistics.

Objectives Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases (ADs). Unlike the traditional immunosuppressants, which inadvertently impair patients' antimicrobial immunity, MSCs reduce the incidence and duration of respiratory infection. However, the underlying mechanisms are unknown. Methods To investigate how MSCs regulate the lung immunity and improve the defence against respiratory infection, we infected MSC‐treated wild‐type and lupus‐prone mice with Haemophilus influenzae intranasally and determined the clearance of bacteria. Tissue damage and inflammatory cytokines were measured by H&E staining and ELISA separately. Immune cell subsets in the tissues were analysed by flow cytometry. Results MSC pretreatment prevented overwhelming inflammation and accelerated bacterial clearance in both wild‐type and lupus‐prone mice. Tregs increased dramatically in the lung after MSC treatment. Adoptive transfer of Tregs isolated from MSC‐treated mice offered similar protection, while deletion of Tregs abrogated the protective effects of MSCs. The majority of the intravenously injected MSCs were engulfed by lung phagocytes, which in turn produced CXCL9 and CXCL10 and recruited tremendous CXCR3+ Tregs into the lung. Compared with their CXCR3− counterparts, CXCR3+ Tregs displayed enhanced proliferation and stronger inhibitory functions. Neutralisation of CXCL9 and CXCL10 significantly downregulated the migration of CXCR3+ Tregs and eliminated the benefits of MSC pretreatment. Conclusion Here, we showed that by recruiting CXCR3+ Tregs, MSC treatment restricted the overactivation of inflammatory responses and prevented severe symptoms caused by infection. By discovering this novel property of MSCs, our study sheds light on optimising long‐term immunosuppressive regimen for autoimmune diseases and other immune disorders.

Background. Immunosuppressants such as cyclophosphamide (CTX) have been employed to treat a wide array of autoimmune diseases. The most unfavourable side effects of these drugs are their suppression on the antimicrobial immunity and increasing the risk of infection. As a promising substitution/adjunct, mesenchymal stem cells (MSCs) are currently being tested in several clinical trials. However, their influence on the recipients’ antimicrobial immunity remains unclear.Methods. In this study, C57BL/6 mice were treated with either CTX or MSCs, and then both the innate and adaptive immunity of the lung were determined. To investigate the influence of CTX and MSCs on the immune defence against infection, the treated mice were intranasally infected with opportunistic pathogenHaemophilus influenzae(Hi).Bacterial clearance and antibacterial immune responses were analysed.Results. Our data showed that CTX strongly inhibited the proliferation of lung immune cells, including alveolar macrophages (AMs) and T cells, whereas MSCs increased the numbers of these cells. CTX suppressed the phagocytic activity of AMs; on the contrary, MSCs enhanced it. Notably, infusion of MSCs led to a remarkable increase of regulatory T cells and Th1 cells in the lung. When infected by Hi, CTX did not significantly impair the elimination of invaded bacteria. However, MSC-treated mice exhibited accelerated bacterial clearance and moderate inflammation and tissue damage.Conclusion. Our study reported that unlike traditional immunosuppressants, modulation of MSCs on the recipient’s immune response is more elegant. It could preserve and even enhance the antimicrobial defence, suggesting that MSCs are better choice for patients with high risk of infection or those who need long-term immunosuppressive regimen.