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Additional file 2: Figure S1. The frequency distribution of allele number and polymorphic information content (PIC) with 75 molecular markers. (A) Allele number per locus ranges from 3 to 37 with an average of 12.7. (B) PIC ranges from 0.18 to 0.95 with an average of 0.72. Figure S2. (a) Structure simulation analysis to determine best K. (A) LnP(D), the log likelihood for each K, was calculated by 100,000 permutations and mean LnP(D) value was taken from 10 replications. ∆K, an ad hoc quantity, is transferred by mean LnP(D) value and ∆K of 148 accessions. (B) LnP(D) value and ΔK of 86 indica accessions. (C) LnP(D) value and ΔK of 86 japonica accessions. Figure S3. Population structure analysis of 148 accessions. Each individual is indicated by a vertical bar. (A) For K = 2, pop2–1 and pop2–2, indicated by red and green, are composed of japonica and indica rice, respectively. (B) For K = 5, pop5–1, pop5–2, pop5–3, pop5–4 and pop5–5, indicated by red, green, blue, yellow and magenta, are composed of indica cultivar, japonica landrace, japonica cultivar, indica landraces and wild rices, respectively. The numbers of accessions in each subpopulation are indicated in brackets (). Figure S4. Three-dimensional plot from principle coordinate analysis of 148 rice accessions. Japonica and indica are separated on opposite sides. Japonica and indica cultivars are marked with circles.

Additional file 1: Table S1. Name, type, subspecies/species and origin of 148 rice accessions used in this study. Table S2. Chromosomal position, locus name and PIC value of 75 SSR marker used for this study.

Constructing a porous architecture is a considerable strategy to enhance the catalytic activity of metal oxides catalysts for CO oxidation. In this work, we have developed porous sponge-like Fe2O3 microspheres by employing a facile aerosol spray pyrolysis. The NaNO3 salt in the spray solution plays a crucial role as a fluxing sacrifice template in the formation of the sponge-like structure, in which a high surface area of 216.2 m2 g−1 and an average pore size of 4 nm are obtained. This novel Fe2O3 catalyst exhibits an improved catalytic activity compared to usual iron oxides catalysts. Nearly 50% CO conversion at a relatively low temperature of 200 °C and 100% CO conversion at 300 °C at a space velocity of 60 000 ml h−1 g−1 are achieved. Furthermore, it displays an outstanding catalytic stability without distinct decay for 1000 min in a continuous stream at 300 °C. In addition to the effect of plentiful adsorption sites for the gas reactant, the promoted catalytic performance is also attributed to the function of abundant OH groups rooted in the large surface of the sponge-like structure, which induces faster reaction rate of CO oxidation via a bicarbonate route.

To compare the renal parenchyma attenuation of virtual noncontrast (VNC) images derived from multiphase renal dual-energy computed tomography (DECT) with standard noncontrast (SNC) images, and to determine the optimum phase for VNC images.Twenty-nine men and 16 women (mean age, 61 ± 13 years; range, 37-89 years) underwent dynamic renal DECT (100/Sn140 kVp) were included in this institutional review board-approved retrospective study. There were four phases of the scan, which included noncontrast, corticomedullary (CMP), nephrographic (NP), and excretory phases (EP). The VNC images was generated from CMP, NP and EP. CT numbers of SNC images and VNC images of each phases were measured in the renal cortex and medulla. Mean standard deviation of subcutaneous fat was measured as image noise on SNC and VNC images. Radiation dose was recorded and potential radiation dose reduction was estimated. Results were tested for statistical significance using the unpaired t-test and agreement using Bland-Altman plot analysis.The difference in mean attenuation between SNC and each phase of VNC images were ≤4 HU. The mean attenuation of renal cortex and medulla was 33.2 ± 4.4 HU, and 34.2 ± 4.8 HU in SNC, 33.6 ± 7.6 HU and 31.1 ± 8.3 HU in VNC of CMP, 34.8 ± 8.6 HU and 35.6 ± 8.5 HU in VNC of NP, 31.5 ± 7.6 HU and 32.4 ± 7.5 HU in VNC of EP. In VNC of CMP, the attenuation of the cortex was higher than the medulla (p 0.05), and the attenuation of medulla was significant lower than that of SNC (p 0.01). In VNC of NP, the attenuation of renal cortex was higher than SNC (p 0.05). In VNC of EP, the attenuation of cortex and medulla were lower than SNC (p 0.05), and inadequate iodine subtraction in collecting system was noted. Image noise was significantly greater in SNC (p 0.001). Mean radiation dose reduction achievable by removing the SNC was 12.3% ± 0.9%.VNC images from multiphase renal DECT were similar to SNC images. Using the nephrographic phase can gives more comparable VNC images to SNC images in renal parenchyma than other phases.

Evidence has shown that leukocyte telomere length (LTL) at birth is related to the susceptibility to various diseases in later life and the setting of newborn LTL is influenced by the intrauterine environment. Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a kind of persistent organic pollutants, are commonly used in commercial and domestic applications and are capable of crossing the maternal-fetal barrier during pregnancy. We hypothesized that intrauterine exposure to PFASs may affect fetal LTL by increasing oxidative stress. To verify this hypothesis, LTL, concentrations of PFASs and reactive oxygen species (ROS) were measured in umbilical cord blood of 581 newborns from a prospective cohort. Our results showed that there were interactions between PFOS/PFDA and sex on LTL and ROS. The LTL was significantly shorter (0.926 ± 0.053 vs 0.945 ± 0.054, P = .023 for PFOS; 0.919 ± 0.063 vs 0.940 ± 0.059, P = .011 for PFDA) and the ROS levels were extremely higher (252.9 ± 60.5 [M] vs 233.5 ± 53.6 [M], P = .031 for PFOS; 255.2 ± 62.9 [M] vs 232.9 ± 58.3 [M], P = .011 for PFDA) in the female newborns whose PFOS or PFDA concentrations fell in the upmost quartile compared with those in the lowest quartile after adjusting for potential confounders. ROS levels were inversely associated with LTL in female newborns (β = -1.42 × 10-4, P = .022). 13% of the effect of PFOS on female LTL was mediated through ROS approximately by the mediation analyses. However, in male newborns, no relationships among PFASs, ROS and LTL were observed. Our findings suggest a "programming" role of PFASs on fetal telomere biology system in females in intrauterine stage.

Superior electrochemical performance of LiMn2O4 is considered to be one of the most important properties for lithium-ion batteries (LIBs). This paper presents an extremely high performance cathode material, multi-shelled LiMn1.95Co0.05O4 cages, which are created using a sucrose template. A small amount of Co substitution uniformly in a bulk material not only tunes Mn3+ in the minority with bulk stability improving, but can also accommodate specific capacity. In addition, the unique caged structure enhances Li+ diffusion and electrolyte penetration, leading to an outstanding rate capability. The as-synthesized cathode material exhibits a very high capacity of 154.4 mA h g−1, and retains a high value of 136.7 mA h g−1 after 500 cycles. The present work investigated the combined effect of a tunable average Mn oxidation state and unique multi-shelled cages in a controllable aerosol process.

The global concerns to the environmental pollution and health risks by microplastics (MPs) urgently require action to develop effective and sustainable processes to deal with this problem. Coagulation removal and photocatalytic degradation, considered as cost- and energy-effective techniques, have attracted growing attention to remove MPs from urban waters. However, its removal behavior and degradation mechanism have not been systematically summarized. Therefore, the recent progress on coagulation and photocatalysis for MPs removal was comprehensively reviewed in this study. Particularly, the effects of parameters (e.g., type and dosage of coagulant, environmental conditions, characteristics of MPs and catalyst type, etc) and removal mechanisms were commendably discussed. Moreover, the challenges of current techniques application process and the potential coping strategies were also put forward. This review will not only help to deeply understand the detailed processes and mechanisms for removing MPs by coagulation and photocatalysis but also provide constructive information and useful data for future researches relevant to the enhanced removal of MPs from urban waters.

Summary Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/β-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs). Activation of β-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, β-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted β-catenin-HIF-1α interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1α activities distinguished proliferative and inflammatory AMs in vivo. This β-catenin-HIF-1α axis was conserved in human AMs and enhanced HIF-1α expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by β-catenin-HIF-1α signaling, with implications for the treatment of severe respiratory diseases.

IFN regulatory factor 4 (IRF4) is a key transcription factor that promotes effector CD8+ T cell differentiation and expansion. The roles of IRF4 in regulating the CD8+ T cell response to cytokines have not been explored. In this article, we show that IL-2 and IL-15 signaling and STAT5 activation regulate IRF4 expression in CD8+ T cells. Gene-expression profile analysis has also revealed that IRF4 is required for expression of the receptors of IL-2 family cytokines CD122 and CD127. We found that IRF4 binds directly to CD122 and CD127 gene loci, indicating that it may directly promote CD122 and CD127 gene transcription. As a consequence, IRF4-deficient CD8+ T cells show diminished sensitivity to IL-2, IL-15, and IL-7 treatment in vitro. Furthermore, we found that IRF4-deficient CD8+ T cells had lower expression of CD122 and CD127 in vivo during influenza virus infection. These data suggest that IRF4 regulates the sensitivity of CD8+ T cells to IL-2 family cytokines, which correlates with the diminished effector and memory CD8+ T cell responses in IRF4-deficient CD8+ T cells.

A series of novel selenochroman-4-one derivatives bearing semicarbazone or nitrogen heterocycle was designed, synthesized, tested antifungal activity and characterized via 1H-NMR, 13C-NMR, and HRMS. The design of the compounds is based on the principle of molecule hybrid and bioisosterism. We aimed at attaching semicarbazones or nitrogen heterocycle to the selenochroman-4-one for enhancing antifungal activity. The antifungal activity of target compounds was evaluated using the microdilution broth method in vitro test. Bioassay results indicated that some of the derivatives displayed good fungistatic activity on Candida zeylanoides, Candida albicans, Cryptococcus neoformans, resistant to fluconazole strain 103 (Candida albicans), resistant to fluconazole strain 100 (Candida albicans) and strain SC5314 (Candida albicans). All the compounds exhibit antifungal activities against the tested funguses in different levels, among them, 7 compounds of antifungal activity against several funguses is better than that of the control drug fluconazole. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation.

In this work, Au neuronal-like nanostructures (Au NNs) were synthesized by a facile N-methylimidazole-assisted aqueous method, using ascorbic acid as the reducing agent. The as-prepared Au nanocrystals exhibited improved electrocatalytic performances for the reduction of azathioprine, which was further explored to construct an azathioprine sensor with low detection limit of 0.033 μM (S/N = 3), wide linear range from 0.5 to 2300 μM, good reproducibility, and long-term stability. The as-synthesized Au architectures provide more potential applications in the fabrication of (bio) sensors.

Organometallic perovskite solar cells have gained immense attention due to their rapid increase in efficiency and compatibility with low-cost fabrication methods. However, the material's instability in humid ambient conditions has remained a key challenge for the large-scale fabrication and application of such cells. In this paper, we present devices fabricated under 50% humidity with significantly improved long-term stability through three parallel approaches. First, the small molecule hole transport material, 2,2′,7,7′-Tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9′-spirobifluorene (spiro-MeOTAD) is replaced by a polymeric material Poly(3-hexylthiophene) (P3HT). Second, the device stability is further enhanced by increasing the thickness of the mesoporous titania scaffold. Finally, tetraethyl orthosilicate (TEOS) is used as a processing additive in the perovskite precursor solution to form an in situ protective layer. On our optimized device, a remarkable long-term device stability of more than 1200 h is achieved. X-ray diffraction patterns suggest more than 2500 h of material stability.

Ternary bismuth iodides (A3Bi2I9, where A is a monovalent cation) have been recently suggested as less toxic alternatives to lead halide perovskites for photovoltaic applications. Using density functional theory based calculations, we predict that the band gap in these compounds is insensitive to chemical pressure applied by changing the size of A-site cations, which is confirmed experimentally. We further show that the band gap in A3Bi2I9 compounds increases (or decreases) by stretching (or compressing) Bi2I9 bioctahedra, and the observed band gap insensitivity is a direct result of the counteractive interplay of three factors: the size of the A-site cations, the presence of H-bonds with organic A-site cations, and spin–orbit coupling (SOC) effects. Our study demonstrates that the layered structure of A3Bi2I9 compounds intrinsically limits any significant modification of their band gap and highlights the need for three-dimensional connectivity of BiI6 octahedra in order to achieve high efficiency Bi-base...

Elemental Ag

CD8+ tissue-resident memory T (TRM) cells provide frontline immunity in mucosal tissues. The mechanisms regulating CD8+ TRM maintenance, heterogeneity, and protective and pathological functions are largely elusive. Here, we identify a population of CD8+ TRM cells that is maintained by major histocompatibility complex class I (MHC-I) signaling, and CD80 and CD86 costimulation after acute influenza infection. These TRM cells have both exhausted-like phenotypes and memory features and provide heterologous immunity against secondary infection. PD-L1 blockade after the resolution of primary infection promotes the rejuvenation of these exhausted-like TRM cells, restoring protective immunity at the cost of promoting postinfection inflammatory and fibrotic sequelae. Thus, PD-1 serves to limit the pathogenic capacity of exhausted-like TRM cells at the memory phase. Our data indicate that TRM cell exhaustion is the result of a tissue-specific cellular adaptation that balances fibrotic sequelae with protective immunity.

Computed Tomography Coronary Angiography (CTCA) is an effective imaging technique used for diagnosis and surgical planning. Segmentation of the aorta from the CTCA can be used clinically for interpretation, aortic valve measurement for intervention and identification of coronary structures. The process of segmentation done manually is tedious and time consuming. In this paper we propose an approach to automatic aorta segmentation from cardiac CTCA scans using deep learning. A dataset of 20 pairs of CT and mask is used, with the manually segmented masks as ground truth. The dataset is split into a training set of 10 pairs, validation set of 3 pairs and test set of 7 pairs. The proposed framework uses two different U-Net models trained for location and refined segmentation tasks. The U-Net architecture and multiple variants of the U-Net are adopted, and their performances are compared. The paper also explores different types of data preprocessing and augmentation that can be performed to improve the performance of the deep learning model. The results show that 3D Inception U-Net performs the best in localization and segmentation tasks. The Localization test DSC is 0.77 and Segmentation test DSC is 0.81. Qualitative testing shows that predicted masks are quite similar to the original.

Automatic segmentation of medical images, such as computed tomography (CT) or magnetic resonance imaging (MRI), plays an essential role in efficient clinical diagnosis. While deep learning have gained popularity in academia and industry, more works have to be done to improve the performance for clinical practice. U-Net architecture, along with Dice coefficient optimization, has shown its effectiveness in medical image segmentation. Although it is an efficient measurement of the difference between the ground truth and the network's output, the Dice loss struggles to train with samples that do not contain targeted objects. While the situation is unusual in standard datasets, it is commonly seen in clinical data, where many training data available without the anomalies shown in the images, such as lesions and anatomic structures in some CTs/regions. In this paper, we propose a novel loss function - Stochastic Aggregated Dice Coefficient (SA Dice) and a modification of the network structure to improve its performance. Experimentally, in our own heart aorta CT dataset, our models beats the baseline by 4% in cross-validation Dice scores. In BRATS 2017 brain tumor segmentation challenge, the models also perform better than the state-of-the-art by approximately 2%.

Obesity is an independent risk factor for severe influenza infection. However, the underlying cellular and molecular mechanisms are still incompletely understood. In this study, we have utilized a murine influenza infection model in genetic-induced obese (db/db) mice to explore the mechanisms by which obesity increases host susceptibility to influenza infection. We find that db/db mice have enhanced viral replication, exaggerated inflammatory responses, and dysregulated lung repair process after influenza infection, and consequently increased host mortality. Furthermore, we demonstrate that the transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ), an important inflammation regulator, was downregulated in the lung macrophages of db/db mice after influenza infection. Strikingly, the treatment of 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2), a PPAR-γ agonist, largely rescued the survival of db/db mice after influenza infection. Interestingly, macrophage PPAR-γ-deficient mice exhibited enhanced mortality after influenza infection and 15d-PGJ2 fails to rescue host mortality in macrophage PPAR-γ-deficient mice, suggesting that PPAR-γ expression in macrophages is critical for the action of 15d-PGJ2. These data indicate that obesity attenuates lung antiviral immunity and hampers host recovery through the modulation of macrophage PPAR-γ expression. Furthermore, modalities targeting macrophage PPAR-γ expression and/or function may serve as promising therapeutics to treat severe influenza infection in obese patients.

Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-γ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-γ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-γ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-γ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-γ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-γ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-γ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-γ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections. IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.

Influenza virus causes a heterogeneous respiratory infectious disease ranging from self-limiting symptoms to non-resolving pathology in the lungs. Worldwide, seasonal influenza infections claim ~500,000 lives annually. Recent reports describe pathologic pulmonary sequelae that result in remodeling the architecture of lung parenchyma following respiratory infections. These dysfunctional recovery processes that disproportionately impact the elderly have been understudied. Macrophages are involved in tissue remodeling and are critical for survival of severe influenza infection. Here, we found intrinsic deficiency of the nuclear receptor PPAR-γ in myeloid cells delayed the resolution of pulmonary inflammation following influenza infection. Mice with myeloid cell-specific PPAR-γ deficiency subsequently presented with increased influenza-induced deposition of pulmonary collagen compared to control mice. This dysfunctional lung remodeling was progressive and sustained for at least 3 months following infection of mice with myeloid PPAR-γ deficiency. These progressive changes were accompanied by a pro-fibrotic gene signature from lung macrophages and preceded by deficiencies in activation of genes involved with damage repair. Importantly similar aberrant gene expression patterns were also found in a secondary analysis of a study where macrophages were isolated from patients with fibrotic interstitial lung disease. Quite unexpectedly, mice with PPAR-γ deficient macrophages were more resistant to bleomycin-induced weight loss whereas extracellular matrix deposition was unaffected compared to controls. Therefore PPAR-γ expression in macrophages may be a pathogen-specific limiter of organ recovery rather than a ubiquitous effector pathway in response to generic damage.

This retrospective study was aimed to evaluate the reduced iodine load on image quality and diagnostic performance in multiphasic hepatic CT using a novel monoenergetic reconstruction algorithm (nMERA) in assessment of local tumor progression after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). Ninety patients who underwent CT 1 month after RFA of HCC. Forty-five patients had multiphasic hepatic dual-energy CT with a half-reduced contrast medium (HRCM) of 277.5 mg I/kg. The nMERA (40-70-keV) images were reconstructed in each phase. Another 45 patients received a standard contrast medium (SCM) of 555 mg I/kg, and the images were reconstructed as a simulated 120-kVp images. Primary outcome was accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) in assessment of local tumor progression. Additional advanced assessments included the image noise, attenuation value, contrast-to-noise ratio (CNR), and subjective image quality between the groups. The accuracy, sensitivity and specificity of nMERA HRCM images were 95.7%, 100% and 93.9% for 40 keV, 95.7%, 85.7% and 100% for 50 keV, 83.0%, 42.8% and 100% for 60 keV, and 83.0%, 42.9% and 100% for 70 keV. The AUROC was 0.99, 0.99, 0.94, and 0.93 for 40-70 keV nMERA HRCM images, respectively. Compared with simulated 120-kVp SCM images, nMERA HRCM images demonstrated comparable noise at 70-keV (P < 0.05), and comparable CNR at 40- and 50-keV (P < 0.05). nMERA DECT enables the contrast medium to be reduced to up to 50% in multiphasic hepatic CT while preserving diagnostic accuracy.

The treatment and disposal of waste activated sludge (WAS) has become one of the major challenges for the wastewater treatment plants (WWTPs) due to large output, high treatment costs and enriched substantial emerging contaminants (ECs). Therefore, reducing sludge volume, recovering energy and resource from WAS, and removing ECs and decreasing environmental risk have gained increasing attentions. Calcium peroxide (CaO2), a versatile and safe peroxide, has been widely applied in terms of WAS treatment including sludge dewatering, anaerobic sludge digestion and anaerobic sludge fermentation due to its specific properties such as generating free radicals and alkali, etc., providing supports for sludge reduction, recycling, and risk mitigation. This review outlines comprehensively the recent progresses and breakthroughs of CaO2 in the fields of sludge treatment. In particular, the relevant mechanisms of CaO2 enhancing WAS dewaterability, methane production from anaerobic digestion, short-chain fatty acids (SCFA) and hydrogen production from anaerobic fermentation, and the removal of ECs in WAS and role of experiment parameters are systematically elucidated and discussed, respectively. Finally, the knowledge gaps and opportunities in CaO2-based sludge treatment technologies that need to be focused in the future are prospected. The review presented can supply a theoretical basis and technical reference for the application of CaO2 for improving the treatment of WAS.

Recent evidence has suggested that IL-10-producing effector CD8+ T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL-10-producing effector CD8+ T cells are not completely defined. Here, we show that type I interferons (IFNs) are required for the development of IL-10-producing effector CD8+ T cells during influenza virus infection in mice. We find that type I IFNs can enhance IL-27 production by lung APCs, thereby facilitating IL-10-producing CD8+ T-cell development through a CD8+ T-cell-nonautonomous way. Surprisingly, we also demonstrate that direct type I IFN signaling in CD8+ T cells is required for the maximal generation of IL-10-producing CD8+ T cells. Type I IFN signaling in CD8+ T cells, in cooperation with IL-27 and IL-2 signaling, promotes and sustains the expression of IFN regulatory factor 4 (IRF4) and B-lymphocyte-induced maturation protein-1 (Blimp-1), two transcription factors required for the production of IL-10 by effector CD8+ T cells. Our data reveal a critical role of the innate antiviral effector cytokines in regulating the production of a regulatory cytokine by effector CD8+ T cells during respiratory virus infection.

Objective: To explore the users’ insights that contributes to behaviour change in prediabetics and the user requirements for a self-care application from the prediabetics’ perspective. Methods/Statistical Analysis: We conducted Focus Group Discussions (FGD) on four distinct groups of diabetics and prediabetics at a Diabetes Resource Centre and among the public through advertisement. Open-ended questions were asked to stimulate the discussions. Transcripts of each discussion session were read several times, coded, categorised and analysed thoroughly by identifying the themes. The facial expressions during the discussion were also observed and taken into consideration. Findings: Results indicated that diabetes can be prevented through proper lifestyle changes, if and only if the person is willing to change his/her behaviour. The idea of a self-care application was well accepted by the participants and the components to be included were identified. The identified components are such as self-monitoring, diet, exercise, activity planning, goal setting, forum, social support and reminders. As for diabetics, taking medication has second highest priority where else it holds lesser priority among prediabetics. About 20% of the participants showed less interest in a self-care application either because they are not technology savvy or because of their advanced age status. Application/Improvements: A framework for designing prediabetes self-care application will be formulated, which integrates behavioural change theories.

Bimetallic gold-copper nanochain networks (AuCu NCNs) were prepared by a single-step wet-chemical approach using metformin as a growth-directing agent. The formation mechanism was investigated in detail, and the AuCu NCNs were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The nanocrystals were deposited on glassy carbon electrode and this resulted in a highly sensitive sensor for nitrite. Features include a low working potential (best at 0.684 V vs. SCE), fair sensitivity (17.55 μA mM−1), a wide linear range (0.01 to 4.0 mM), a low detection limit (0.2 μM, S/N = 3), and superior selectivity as compared to other sensors.

1. Purpose Solid-state lithium-ion batteries (SSLIBs) have attracted extensive attentions because of their potentials to improve safety and to achieve higher power and energy densities compared with the conventional lithium-ion batteries. In composite electrodes for SSLIBs, particles of active material (AM) and solid electrolyte (SE) are three-dimensionally distributed and form complicated Li-ion and electron pathways. Then, especially during high rate charging/discharging, the inhomogeneous reaction distribution may be formed in the electrode. The reaction distribution can substantially deteriorate the battery performances of SSLIBs such as capacity, power output, rate capability, and cyclability. Therefore, understanding how the reaction distribution affects the battery performances is crucial for the development of high-performance SSLIBs. In this study, we performed operando three-dimensional (3D) observation of reaction distributions in composite electrodes for SSLIBs using CT-XAFS1 to elucidate the influence of reaction distributions on the battery performances of SSLIBs. 2. Experimental An SSLIB cell with a configuration of Li x CoO2 (LCO)-Li2.2C0.8B0.2O3 (LCBO) composite electrode|LCBO electrolyte|poly (ethylene oxide) (PEO)-based polymer electrolyte|Li metal electrode was fabricated based on the literature2. The composite electrode comprised 8 mg of LCO and 2 mg of LCBO. The SSLIB cell was charged to 4.5V and discharged to 2.0 V with a current of 240 μA (0.3 C) for 3 cycles at 100 °C. The reaction distribution in the composite electrode was observed every 40 minutes during charging and discharging using operando CT-XAFS. The CT-XAFS measurements were carried out in the energy range between 7725.5-7730 eV with an energy step of 0.1 eV under an exposure time of 20 ms per energy and projection angle from -65 to 65° with an angle step of 0.1°. The observation area was 517 × 517 × 49 μm. The spatial and time resolutions were 3.1 μm and 40 min., respectively. 3. Results and Discussion Figure 1(a) shows the charge-discharge curves of the SSLIB cell. The SSLIB cell exhibited the initial charge and discharge capacities of 84 and 46 mAh·g−1, respectively. Those degraded to 24 and 13 mAh·g−1 in the 2nd cycle, and 12 and 12 mAh·g−1 in the 3rd cycle, respectively. Figure 1(b) shows the 3D charging state (Li content) maps of the composite electrode and the representative 2D cross-sectional charging state maps in the in-plane direction at the end of 1st, 2nd, and 3rd charge. Colored/uncolored areas stand for the regions where the AMs exist or not, respectively. The red/blue areas stand for the charged (x = 0.6) /discharged (x = 1.0) AMs, respectively. After the 1st charge, the AMs generally showed a high charging state (red). However, the regions with high charging state significantly decreased after the 2nd charge, and most of the AMs showed a charging state corresponding to x = 0.7 ~ 0.8 (green). The regions with high charging state further decreased after the 3rd charge, and AMs with a low charging state were increased (blue). To more precisely investigate where the less-charged AMs existed after the 2nd and 3rd charge, we subtracted the charging state map after the 1st discharge from that after the 2nd charge, and also the charging state map after the 2nd discharge from that after the 3rd charge (Fig. 1(c)). The 2D maps in Fig. 1(c) thus indicate to what extent the charge reaction progressed during the 2nd or 3rd charge compared with the end of the 1st or 2nd discharge, respectively. The red/blue areas in Fig. 1(c) represent the AM regions where the reaction progressed (Δx = 0.4) or not (Δx = 0) from the end of the 1st or 2nd discharge, respectively. As shown in the left map in Fig. 1(c), the inner parts of the aggregated AMs were significantly less charged compared to the regions near AM/SE interfaces during the 2nd charge. Similarly to the 2nd charge, the charge reaction preferentially progressed near the AM/SE interfaces, while the reaction insufficiently progressed at the inner parts of the aggregated AMs during the 3rd charge. Such a variation in the charging state distribution during cycling could be explained by considering the microstructural change due to the expansion/shrinkage of AM particles. The above results suggest that the expansion/shrinkage of AM particles reduced the connections between AM particles but did not reduce the AM/SE interfaces. We further discuss the mechanism of the capacity degradation during cycling in the presentation. References: (1) H. Matsui et al., Angew. Chem. Int. Ed., 56, 9371 (2017). (2) T. Okumura et al., Solid State Ionics, 288, 248 (2016). Acknowledgement: This work was supported by JST ALCA-SPRING (JPMJAL1301). Figure 1

MicroRNAs (miRs) play important roles in the protection against and development of congenital heart disease (CHD). However, the role and potential mechanisms of miR-219-5p in cyanotic CHD remains unclear. Reverse transcription-quantitative PCR (RT-qPCR) was used to measure miR-219-5p levels in cyanotic CHD and hypoxia-induced H9C2 cells. Dual luciferase reporter gene assay was used to confirm whether liver receptor homolog-1 (LRH-1) was a direct target of miR-219-5p. miR-219-5p inhibitor and LRH-1-small interfering RNA were transfected into H9C2 cells under hypoxic conditions to investigate the role of miR-219-5p in hypoxia-induced H9C2 cells. Subsequently, cell viability was detected using an MTT assay and cell apoptosis was detected using flow cytometry. In addition, RT-qPCR and western blotting assays were performed to detect the mRNA and protein expression of LRH-1, cyclin D1 and β-catenin, respectively. The data showed that miR-219-5p expression was higher in patients with cyanotic CHD compared with patients with acyanotic CHD gradually increased in H9C2 cells with prolonged hypoxia time. Dual luciferase reporter assay results showed that LRH-1 was a direct target gene of miR-219-5p. Inhibition of miR-219-5p reversed hypoxia-induced cell viability reduction and attenuated hypoxia-induced cell apoptosis. In addition, hypoxia induction inhibited the expression of LRH-1, cyclin D1 and β-catenin, which was reversed by miR-219-5p inhibitor. However, LRH-1 downregulation reversed the miR-219-5p inhibitor enhanced cell viability, decreased cell apoptosis and increased expression of LRH-1, cyclin D1 and β-catenin in hypoxia-treated cardiomyocytes. The present results demonstrated that downregulation of miR-219-5p promoted the expression of the LRH-1/Wnt/β-catenin signaling pathway-associated components, reduced cardiomyocyte apoptosis and increased cell growth under hypoxic conditions. miR-219-5p may be a potential therapeutic target for cyanotic CHD therapy.

The negative effects of ubiquitous microplastics on wastewater treatment have attracted increasing attention. However, the potential impacts of microplastics on anaerobic granular sludge (AGS) remain unknown. To fill this knowledge gap, this paper investigated the response of AGS to the exposure of model microplastics (polyethylene terephthalate (PET-MPs)) and provided insights into the mechanisms involved. The 84 days’ long-term exposure experiments demonstrated that PET-MPs, at relatively low level (15 MP L−1) did not affect AGS performance during anaerobic wastewater treatment, while 75–300 MP L−1 of PET-MPs caused the decreases of COD removal efficiency and methane yields by 17.4–30.4% and 17.2–28.4%, accompanied with the 119.4–227.8% increase in short-chain fatty acid (SCFA) accumulation and particle breakage. Extracellular polymeric substances (EPS) analysis showed that dosage-dependent tolerance of AGS to PET-MPs was attributed to the induced EPS producing protection role, but PET-MPs at higher concentrations (75–300 MP L−1) suppressed EPS generation. Correspondingly, microbial community analysis revealed that the populations of key acidogens (e.g., Levilinea sp.) and methanogens (e.g., Methanosaeta sp.) decreased after long-term exposure to PET-MPs. Assessment of the toxicity of PET-MPs revealed that the leached di-n-butyl phthalate (DBP) and the induced reactive oxygen species (ROS) by PET-MPs were causing toxicity towards AGS, confirmed by the increases in cell mortality and lactate dehydrogenase (LDH) release. These results provide novel insights into the ecological risk assessment of microplastics in anaerobic wastewater treatment system.

The paper is aimed to detect atrial fibrillation (AF) based on convolutional neural network (CNN) in artificial intelligence environment and to analyze its cause location. The feature extraction of body surface ECG (Electrocardiograph) data is acted as CNN and the core of AF, the accuracy of recognition is improved by comprehensive features and the relationship between pneumonia infection and AF in the elderly are studied. In addition, the postoperative vagal reflex problems in patients after AF radiofrequency ablation is analyzed in experiment. The results showed that in the automatic detection of AF, the sensitivity, specificity and accuracy of the mixed feature method combined with the CNN are better than those of the other two methods, and the detection effect of F wave spectrum analysis method is relatively poor compared to R-R interval analysis. Regression tests showed that infection is an independent risk factor for AF, with a RR value of 31.54, 95% CI (1.602,620.78) (P

The common coexistence of heavy metal ions (HMIs) and toxic organic matters (OMs) arouses public concerns for their combined toxicity and carcinogenicity. The magnetic poly[aniline(AN)-co-5-sulfo-2-anisidine(SA)] (AN-SA/Fe3O4) was synthesized by an oxidative copolymerization method for the highly-effectively simultaneous removal of Cr(VI) and 2,4-dichlorophenol (2,4-DCP) from aqueous solution. The novel adsorbent exhibited ultra-strong adsorption capacities for sole Cr(VI) and sole 2,4-DCP. The mechanism studies revealed that Cr(VI) species (HCrO4− and Cr2O72− in solution pH as 5) were reduced to Cr(III) by the –NH–/–NH2 groups after attaching to the protonated binding sites of AN-SA/Fe3O4 through electrostatic attraction. By contrast, multiple reactions involving the n-π electron donor-acceptor (EDA) interaction, π-π stacking and hydrogen bond contributed to the elimination of 2,4-DCP. In binary system, the coexistent Cr(VI) and 2,4-DCP elevated mutual adsorption capacities by 88.1% and 102.1%, respectively. Specially, 2,4-DCP can form bridge interactions with both Cr(VI) and Cr(III) due to conjugate effect. This property enabled Cr(VI) to additionally link to the hydrophobic sites, except for the hydrophilic sites, via 2,4-DCP bridges. Moreover, the produced Cr(III) can forcefully captured 2,4-DCP with the electron-rich groups (i.e., NH , N , SO3H, OCH3) on AN-SA/Fe3O4 to form the multi-components complexes. The bridge interactions (i.e., n-π EDA interaction, complexation) created the newly available sites for Cr(VI) and 2,4-DCP, resulting in enlarged adsorbance and synchronous removal on AN-SA/Fe3O4 in coexisting system. In addition, the high proportion of N groups generated by Cr(VI) oxidation also devoted to the uptake enhancement due to its strong affinity for 2,4-DCP. Overall, the high-performance and synergistic removal qualified AN-SA/Fe3O4 as a multifunctional adsorbent for the integrated treatment of HIMs-OMs hybrid pollutants.

Fetal-derived tissue-resident macrophages exhibit stem cell-like features of self-renewal in adulthood to maintain macrophage population during homeostasis and/or various insults. However, little is known about the cellular and molecular mechanisms modulating proliferative and inflammatory fate decisions of tissue-resident macrophages in vivo. Here, we show that WNT-β-catenin signaling inhibited lung-resident alveolar macrophage (AM) self-renewal, while simultaneously promoted AM inflammatory activities in vitro and in vivo during influenza virus infection. Mechanistically, WNT engagement facilitated the binding of β-catenin with HIF-1α over its conventional binding partner TCF-4. Such a binding choice led to the elevated macrophage inflammation in a glycolysis-dependent manner, while inhibited AM self-renewal by causing mitochondrial damage and impairing oxidative phosphorylation. Thus, AM self-renewal and inflammatory activity are uncoupled by WNT-β-catenin signaling through HIF-1α-mediated cellular metabolic choice. Importantly, we showed that AM with high HIF-1α activity had limited proliferative capacity and produced inflammatory cytokines, while AM with low HIF-1α activity were highly proliferative and expressed genes associated with tissue repair function in vivo during influenza virus infection. In accordance, we demonstrated that AM proliferation and repopulation were needed for optimal lung repair following the clearance of influenza virus in the respiratory tract. Our results have revealed key mechanisms modulating macrophage fate choice between progeny production versus inflammatory effector activity, and subsequent effects on tissue inflammation and repair.

CD8(+) tissue-resident memory T (T(RM)) cells provide frontline immunity in mucosal tissues. The mechanisms regulating CD8(+) T(RM) maintenance, heterogeneity, and protective and pathological functions are largely elusive. Here, we identify a population of CD8(+) T(RM) cells that is maintained by major histocompatibility complex class I (MHC-I) signaling, and CD80 and CD86 costimulation after acute influenza infection. These T(RM) cells have both exhausted-like phenotypes and memory features and provide heterologous immunity against secondary infection. PD-L1 blockade after the resolution of primary infection promotes the rejuvenation of these exhausted-like T(RM) cells, restoring protective immunity at the cost of promoting postinfection inflammatory and fibrotic sequelae. Thus, PD-1 serves to limit the pathogenic capacity of exhausted-like T(RM) cells at the memory phase. Our data indicate that T(RM) cell exhaustion is the result of a tissue-specific cellular adaptation that balances fibrotic sequelae with protective immunity.

This paper presents a new medical image segmentation method by using wavelet frame energy distribution, which is the sum of squares of the wavelet frame coefficients at each pixel. This work shows that the wavelet frame energy distribution contains the fine texture information extracted from images with low intensity contrast and complex structures using wavelet frame transform. Thus it is employed to enhance the segmentation quality under some challenge conditions such as low intensity contrast, weak/ambiguous boundaries, intensity inhomogeneity and heavy noise. Furthermore, this paper adopts convex relaxation approach to solve the corresponding optimization problem instead of classical level-set method, so the leading numerical computation is efficient and robust to initialization values. Experimental results also illustrate the efficiency of the proposed segmentation method for biomedical images under these extreme imaging conditions.

Coronary artery lumen delineation, to localize and grade stenosis, is an important but tedious and challenging task for coronary heart disease evaluation. Deep learning has recently been successful applied to many applications, including medical imaging. However for small imaged objects such as coronary arteries and their segmentation, it remains a challenge. This paper investigates coronary artery lumen segmentation using 3D U-net convolutional neural networks, and tests its utility with multiple datasets on two settings. We adapted the computed tomography coronary angiography (CTCA) volumes into small patches for the networks and tuned the kernels, layers and the batch size for machine learning. Our experiment involves additional efforts to select and test various data transform, so as to reduce the problem of overfitting. Compared with traditional normalization of data, we showed that subject-specific normalization of dataset was superior to patch based normalization. The results also showed that the proposed deep learning approach outperformed other methods, evaluated by the Dice coefficients.

IFN regulatory factor 4 (IRF4) is a key transcription factor that promotes effector CD8+ T cell differentiation and expansion. The roles of IRF4 in regulating the CD8+ T cell response to cytokines have not been explored. In this article, we show that IL-2 and IL-15 signaling and STAT5 activation regulate IRF4 expression in CD8+ T cells. Gene-expression profile analysis has also revealed that IRF4 is required for expression of the receptors of IL-2 family cytokines CD122 and CD127. We found that IRF4 binds directly to CD122 and CD127 gene loci, indicating that it may directly promote CD122 and CD127 gene transcription. As a consequence, IRF4-deficient CD8+ T cells show diminished sensitivity to IL-2, IL-15, and IL-7 treatment in vitro. Furthermore, we found that IRF4-deficient CD8+ T cells had lower expression of CD122 and CD127 in vivo during influenza virus infection. These data suggest that IRF4 regulates the sensitivity of CD8+ T cells to IL-2 family cytokines, which correlates with the diminished effector and memory CD8+ T cell responses in IRF4-deficient CD8+ T cells.