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Lanthanide-doped colloidal nanoparticles capable of photon upconversion (UC) offer long luminescence lifetimes, narrowband absorption and emission spectra, and efficient anti-Stokes emission. These features are highly advantageous for Förster Resonance Energy Transfer (FRET) based detection. Upconverting nanoparticles (UCNPs) as donors may solve the existing problems of molecular FRET systems, such as photobleaching and limitations in quantitative analysis, but these new labels also bring new challenges. Here we have studied the impact of the core-shell compositional architecture of upconverting nanoparticle donors and the mode of photoexcitation on the performance of UC-FRET from UCNPs to Rose Bengal (RB) molecular acceptor. We have quantitatively compared luminescence rise and decay kinetics of Er3+ emission using core-only NaYF4 20% Yb, 2% Er and core-shell NaYF4 20% Yb @ NaYF4 20% Yb, 5% Er donor UCNPs under three photoexcitation schemes (1) direct short-pulse photoexcitation of Er3+ at 520 nm; indirect photoexcitation of Er3+ through Yb3+ sensitizer with (2) 980 nm short (5-7 ns) or (3) 980 nm long (4 ms) laser pulses. The donor luminescence kinetics and steady-state emission spectra differed between the UCNP architectures and excitation schemes. Aiming for highly sensitive kinetic upconversion FRET-based biomolecular assays, the experimental results underline the complexity of the excitation and energy-migration mechanisms affecting the Er3+ donor responses and suggest ways to optimize the photoexcitation scheme and the architecture of the UCNPs used as luminescent donors.As the water source for the middle route of the South-to-North Water Transfer Project, the Han River in China plays a role of the world's largest inter-basin water transfer project. However, this human-interfered area has suffered from over-standard pollution emission and water blooms in recent years, which necessitates urgent awareness at both national and provincial scales. To perform a comprehensive analysis of the water quality condition of this study area, we apply both the water quality index (WQI) and minimal WQI (WQImin) methods to investigate the spatiotemporal variation characteristics of water quality. The results show that 8 parameters consisting of permanganate index (PI), chemical oxygen demand (COD), total phosphorus (TP), fluoride (F-), arsenic (As), plumbum (Pb), copper (Cu), and zinc (Zn) have significant discrepancy in spatial scales, and the study basin also has a seasonal variation pattern with the lowest WQI values in summer and autumn. Moreover, compared to the traditional WQI, the WQImin model, with the assistance of stepwise linear regression analysis, could exhibit more accurate explanation with the coefficient of determination (R2) and percentage error (PE) values being 0.895 and 5.515%, respectively. The proposed framework is of great importance to improve the spatiotemporal recognition of water quality patterns and further helps develop efficient water management strategies at a reduced cost.Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world's population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δcdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3 vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4+ and CD8+ T-lymphocytes. The high level of Toxoplasma-specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δcdpk3 were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δcdpk3 inoculation induced effective cellular and humoral immune responses against acute and chronic Toxoplasma infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis.How animals rewire cellular programs to survive cold is a fascinating problem with potential biomedical implications, ranging from emergency medicine to space travel. Studying a hibernation-like response in the free-living nematode Caenorhabditis elegans, we uncovered a regulatory axis that enhances the natural resistance of nematodes to severe cold. This axis involves conserved transcription factors, DAF-16/FoxO and PQM-1, which jointly promote cold survival by upregulating FTN-1, a protein related to mammalian ferritin heavy chain (FTH1). Moreover, we show that inducing expression of FTH1 also promotes cold survival of mammalian neurons, a cell type particularly sensitive to deterioration in hypothermia. Our findings in both animals and cells suggest that FTN-1/FTH1 facilitates cold survival by detoxifying ROS-generating iron species. We finally show that mimicking the effects of FTN-1/FTH1 with drugs protects neurons from cold-induced degeneration, opening a potential avenue to improved treatments of hypothermia.Segmentation of abdominal Computed Tomography (CT) scan is essential for analyzing, diagnosing, and treating visceral organ diseases (e.g., hepatocellular carcinoma). This paper proposes a novel neural network (Res-PAC-UNet) that employs a fixed-width residual UNet backbone and Pyramid Atrous Convolutions, providing a low disk utilization method for precise liver CT segmentation. The proposed network is trained on medical segmentation decathlon dataset using a modified surface loss function. Additionally, we evaluate its quantitative and qualitative performance; the Res16-PAC-UNet achieves a Dice coefficient of 0.950 ± 0.019 with less than half a million parameters. click here Alternatively, the Res32-PAC-UNet obtains a Dice coefficient of 0.958 ± 0.015 with an acceptable parameter count of approximately 1.2 million.The perceived and real threat of shark bites have significant direct health and indirect economic impacts. Here we assess the changing odds of surviving an unprovoked shark bite using 200 years of Australian records. Bite survivability rates for bull (Carcharhinus leucas), tiger (Galeocerdo cuvier) and white (Carcharodon carcharias) sharks were assessed relative to environmental and anthropogenic factors. Survivability of unprovoked bull, tiger and white shark bites were 62, 75 and 53% respectively. Bull shark survivability increased over time between 1807 and 2018. Survivability decreased for both tiger and white sharks when the person was doing an in water activity, such as swimming or diving. Not unsurprisingly, a watercraft for protection/floatation increased survivability to 92% from 30%, and 88% from 45%, for tiger and white sharks respectively. We speculate that survival may be related to time between injury and treatment, indicating the importance of rapid and appropriate medical care. Understanding the predictors of unprovoked bites, as well as survivability (year and water activity), may be useful for developing strategies that reduce the number of serious or fatal human-shark interactions without impacting sharks and other marine wildlife.Tumors invade the surrounding tissues to progress, but the heterogeneity of cell types at the tumor-stroma interface and the complexity of their potential interactions hampered mechanistic insight required for efficient therapeutic targeting. Here, combining single-cell and spatial transcriptomics on human basal cell carcinomas, we define the cellular contributors of tumor progression. In the invasive niche, tumor cells exhibit a collective migration phenotype, characterized by the expression of cell-cell junction complexes. In physical proximity, we identify cancer-associated fibroblasts with extracellular matrix-remodeling features. Tumor cells strongly express the cytokine Activin A, and increased Activin A-induced gene signature is found in adjacent cancer-associated fibroblast subpopulations. Altogether, our data identify the cell populations and their transcriptional reprogramming contributing to the spatial organization of the basal cell carcinoma invasive niche. They also demonstrate the power of integrated spatial and single-cell multi-omics to decipher cancer-specific invasive properties and develop targeted therapies.China has a huge population with respiratory diseases, these diseases should be managed well in primary care, however, primary care physicians' knowledge level of these diseases were unknown. The aim of the study was to assess primary care physicians' knowledge of asthma, CAP, COPD, and influenza in China. An e-questionnaire was distributed to attendees of respiratory diseases academic conferences in China from July, 2017 to December, 2018. 7391 questionnaires were returned and 4815 valid questionnaires were analyzed, 3802 (79.0%) from community health service centers and 1013 (21.0%) from township hospitals. The average score of the questionnaire was 83.3 (±20.397) and 72.1 (±20.898) in township and community hospitals, respectively (P  less then  0.05). 61.4%, 48.7%, and 42.5% of the primary care physicians were aware of clinical manifestations of COPD, asthma, and simple influenza. 85.7%, 8.1%, 16.1%, and 1.0% knew how to diagnose COPD, asthma, CAP and influenza, respectively. 94.4% of the physicians lacked the knowledge of treating COPD with bronchodilators; 53.7% knew non-pharmacological treatments for COPD. 73.6% were unable to deal with asthma attacks. 65.1% did not know what the most essential and important treatment for influenza was. 92% of physicians did not know the management for stable COPD; 3.0% knew all prevention and management measures for asthma. 37.9% knew all the preventive measures for CAP. 44.9% did not know the important role of influenza vaccine in preventing influenza and its complications. Primary care physicians in China had a poor knowledge of CAP, asthma, Influenza, COPD. There is a need for improved training of common respiratory diseases.Tumor-associated exosomes play essential roles in intercellular communication and the foundation of cancer microenvironment in glioma. Many mRNAs, microRNAs (miRNAs) and proteins contained in tumor-associated exosomes can be transferred to recipient cells and contribute to the progression of tumor. Nevertheless, the cellular communication between malignant cells with different heterogeneities or characteristics and resultant tumor progression are still unclear in glioma. Here, we show that exosomes released from glioma stem-like cells (GSCs) contain a significant increasing level of miR-155-5p and could be horizontally transferred to surrounding glioma cells. High expression of miR-155-5p in plasma exosomes from patients was associated with glioma diagnosis and grading. Mechanically, we found that miR-155-5p markedly reduced the expression of acetyl-CoA thioesterase 12 (ACOT12), which played as a tumor suppressor in glioma. Furthermore, mesenchymal transition was significantly promoted in glioma cells treated with GSCs-derived exosomes.click here