Serious toxicity for organisms from pesticide glyphosate (Gly) residues to the ecosystem and human health has become a consensus. Rapid and selective detection of glyphosate, especially using a ...simple and portable instrument, is highly desired. In this work, we develop a novel enzyme-free rapid and visual ratiometric fluorescence sensor for selectively quantitative detecting glyphosate by integrating the designed blue carbon nanodots (CDs) and gold nanoclusters (Au NCs). The fluorescence of CDs can be quickly quenched via aggregation-caused quenching (ACQ) within 2 s after introducing glyphosate, resulting from the formation of CDs-Gly-CDs complex aggregation. While the Au NCs serve as the reference signal without any change, therefore leading to obvious and instant ratiometric fluorescence variation from blue to pink to orange. The broad linear range was obtained from 0 to 180 nM with a satisfactory detection limit of 4.19 nM. Furthermore, this approach was successfully applied to detect glyphosate in real samples and a portable smartphone platform integrated paper sensor was developed for in-site visual quantitative glyphosate detection, offering a promising strategy for the construction of enzyme-free trace hazard detection system.
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•An enzyme-free ratiometric fluorescence sensor based on aggregation-caused quenching was designed.•The sensor was prepared by utilizing environmentally friendly nanomaterials.•The sensor exhibited visual and rapid detection to glyphosate residues.•Portable smartphone platform achieved on-site quantitative pesticides detection.
Host cells possess the metabolic assets required for viral infection. Recent studies indicate that control of the host's metabolic resources is a core host–pathogen interaction. Viruses have evolved ...mechanisms to usurp the host's metabolic resources, funneling them towards the production of virion components as well as the organization of specialized compartments for replication, maturation, and dissemination. Consequently, hosts have developed a variety of metabolic countermeasures to sense and resist these viral changes. The complex interplay between virus and host over metabolic control has only just begun to be deconvoluted. However, it is clear that virally induced metabolic reprogramming can substantially impact infectious outcomes, highlighting the promise of targeting these processes for antiviral therapeutic development.
Traditional GCNs have limitations due to fixed convolutional kernels with a narrow receptive field, which prevent them from adequately learning the local fine-grained features between the points and ...frequently employ a max pooling function to eliminate noise (redundant information), exacerbating a substantial loss of global information during the sampling process. To address these issues, we propose a novel multi-level feature pyramid graph convolutional neural network that combines multi-scale adaptive atrous graph convolution (MSAGConv) and learnable graph pooling (LGP) techniques. With an adaptive atrous kernel in a multi-scale architecture, MSAGConv can mine more deeply into the local fine-grained features of the points, enhance the flexibility of the point convolution kernel, extend its perception field, and capture more rich semantic information between points across scales. Next, LGP aims to eliminate noise by maximizing practical global information retention. Our approach outperforms state-of-the-art shape classification and part segmentation techniques on the ModelNet40, ScanObjectNN, and ShapeNetPart datasets in comprehensive qualitative and quantitative evaluations.
Fast, simple, and low-cost on-site visualized detection of inorganic phosphate (Pi) is in great demand since phosphate is the major reason of eutrophication. In this work, a ratiometric fluorescent ...probe composed by green carbon dots (GCDs) and red carbon dots (RCDs) has been established for high-sensitivity and selective sensing of Pi. A trend of color change from red to green is observed for the detection of Pi under ultraviolet light and the detection limit is 0.09 μM in the range of 0 to 55 μM. Fluorescent test paper prepared from the probe solution was successfully applied to semi-quantitative visual detection of Pi in real-world water and soil samples, which shows great real-world application potentials.
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The emergence of edge computing provides a new solution to big data processing in the Internet of Things (IoT) environment. By combining edge computing with deep neural network, it can make better ...use of the advantages of multi-layer architecture of the network. However, the current task offloading and scheduling frameworks for edge computing are not well applicable to neural network training tasks. In this paper, we propose a task model offloading algorithm by considering how to optimally deploy neural network model into the edge nodes. An adaptive task scheduling algorithm is also designed to adaptively optimize the task assignment by using the improved ant colony algorithm. Based on them, a collaborative cloud-edge computing framework is proposed, which can be used in the distributed neural network. Moreover, this framework sets up some mechanisms so that the cloud can collaborate with edge computing in the work. The simulation results show that the framework can reduce time delay and energy consumption, and improve task accuracy.
Ischemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI). The role of N
methyladenosine (m6A) modification in AKI remains unclear. Here, we characterize the role of AlkB ...homolog 5 (ALKBH5) and m6A modification in an I/R-induced renal injury model in male mice. Alkbh5-knockout mice exhibit milder pathological damage and better renal function than wild-type mice post-IRI, whereas Alkbh5-knockin mice show contrary results. Also conditional knockout of Alkbh5 in the tubular epithelial cells alleviates I/R-induced AKI and fibrosis. CCL28 is identified as a target of ALKBH5. Furthermore, Ccl28 mRNA stability increases with Alkbh5 deficiency, mediating by the binding of insulin-like growth factor 2 binding protein 2. Treg recruitment is upregulated and inflammatory cells are inhibited by the increased CCL28 level in IRI-Alkbh5
Ksp
mice. The ALKBH5 inhibitor IOX1 exhibits protective effects against I/R-induced AKI. In summary, inhibition of ALKBH5 promotes the m6A modifications of Ccl28 mRNA, enhancing its stability, and regulating the Treg/inflammatory cell axis. ALKBH5 and this axis is a potential AKI treatment target.
Immunotherapy has revolutionized cancer treatment, yet most patients do not respond. Here, we investigated mechanisms of response by profiling the proteome of clinical samples from advanced stage ...melanoma patients undergoing either tumor infiltrating lymphocyte (TIL)-based or anti- programmed death 1 (PD1) immunotherapy. Using high-resolution mass spectrometry, we quantified over 10,300 proteins in total and ∼4,500 proteins across most samples in each dataset. Statistical analyses revealed higher oxidative phosphorylation and lipid metabolism in responders than in non-responders in both treatments. To elucidate the effects of the metabolic state on the immune response, we examined melanoma cells upon metabolic perturbations or CRISPR-Cas9 knockouts. These experiments indicated lipid metabolism as a regulatory mechanism that increases melanoma immunogenicity by elevating antigen presentation, thereby increasing sensitivity to T cell mediated killing both in vitro and in vivo. Altogether, our proteomic analyses revealed association between the melanoma metabolic state and the response to immunotherapy, which can be the basis for future improvement of therapeutic response.
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•Proteomics of 116 melanoma tumors shows the landscapes of response to immunotherapy•Immunotherapy response was associated with enriched mitochondrial lipid metabolism•High mitochondrial metabolism led to higher antigen presentation and IFN signaling•Knockout of beta-oxidation genes reduced melanoma sensitivity to T cell killing
Proteomic profiling of melanomas from patients undergoing immunotherapy reveals key mediators of tumor immunogenicity.
Sensors-based and radio frequency (RF)-based indoor localization technology is one of the keys in location-based services. The IEEE 802.11-2016 introduced the Wi-Fi fine timing measurement (FTM) ...protocol, which provides a new approach for Wi-Fi-based indoor localization. However, Wi-Fi signals are susceptible to complex indoor environments. To improve the positioning accuracy and stability, an enhanced particle filter (PF) with two different state update strategies, a new criterion for divergence monitoring and rapid re-initialization is proposed to integrate the advantages of pedestrian dead reckoning (PDR) and Wi-Fi FTM. In addition, an adaptive tilt compensation is proposed to improve real-time heading estimation of conventional PDR, and the Wi-Fi FTM outliers are detected by displacement estimation of the PDR. The experimental results show that the proposed PF has better localization performance than the single source positioning methods in a typical indoor scenario. The accuracy of final localization is within 1 m in 86.7% of the dynamic cases and the average calculation time is less than 0.5 s when the number of particles is 2000.
In contrast to many viruses, human cytomegalovirus (HCMV) is unable to productively infect most cancer-derived cell lines. The mechanisms of this restriction are unclear. To explore this issue, we ...tested whether defined oncogenic alleles, including the simian virus 40 (SV40) T antigen (TAg) and oncogenic H-Ras, inhibit HCMV infection. We found that expression of SV40 TAg blocks HCMV infection in human fibroblasts, whereas the replication of a related herpesvirus, herpes simplex virus 1 (HSV-1), was not impacted. The earliest restriction of HCMV infection involves a block of viral entry, as TAg expression prevented the nuclear delivery of viral DNA and pp65. Subsequently, we found that TAg expression reduces the abundance of platelet-derived growth factor receptor α (PDGFRα), a host protein important for HCMV entry. Viral entry into TAg-immortalized fibroblasts could largely be rescued by PDGFRα overexpression. Similarly, PDGFRα overexpression in HeLa cells markedly increased the levels of HCMV gene expression and DNA replication. However, the robust production of viral progeny was not restored by PDGFRα overexpression in either HeLa cells or TAg-immortalized fibroblasts, suggesting additional restrictions associated with transformation and TAg expression. In TAg-expressing fibroblasts, expression of the immediate early 2 (IE2) protein was not rescued to the same extent as that of the immediate early 1 (IE1) protein, suggesting that TAg expression impacts the accumulation of major immediate early (MIE) transcripts. Transduction of IE2 largely rescued HCMV gene expression in TAg-expressing fibroblasts but did not rescue the production of infectious virions. Collectively, our data indicate that oncogenic alleles induce multiple restrictions to HCMV replication.
HCMV cannot replicate in most cancerous cells, yet the causes of this restriction are not clear. The mechanisms that restrict viral replication in cancerous cells represent viral vulnerabilities that can potentially be exploited therapeutically in other contexts. Here we found that SV40 T antigen-mediated transformation inhibits HCMV infection at multiple points in the viral life cycle, including through inhibition of proper viral entry, normal expression of immediate early genes, and viral DNA replication. Our results suggest that the SV40 T antigen could be a valuable tool to dissect cellular activities that are important for successful infection, thereby potentially informing novel antiviral development strategies. This is an important consideration, given that HCMV is a leading cause of birth defects and causes severe infection in immunocompromised individuals.
Hepatocellular carcinoma (HCC) is an aggressive malignancy with increasing mortality in China. Angiogenesis is crucial for tumor formation, development and metastasis in HCC. Previous studies ...indicated that high expression levels of elongation factor 2 kinase (eEF2K), a protein kinase that negatively regulates the elongation stage of translation, were associated with poor prognosis of HCC. Here, we show that pharmacological inhibition or knockdown of eEF2K in highly metastatic liver cancer cells inhibits their colony forming and migratory capacities, as well as reducing their invasiveness. Importantly, knocking down eEF2K by lentiviral directed shRNA prevented tumor growth and angiogenesis of HCC in mice. Silencing of eEF2K in endothelial cells (HUVECs) led to a reduction in vascularization, evidenced by a decrease in capillary‐like structures in the matrigel. Notably, knocking down eEF2K reduced the expression of angiogenesis‐related growth factors in liver cancer cells and the expression of growth factor receptors on HUVECs, and thus restricted signaling crosstalk that promotes angiogenesis between HCC cells and endothelial cells. We also showed that silencing of eEF2K effectively reduced protein levels of SP1/KLF5 transcription factors and hence decreased the levels of bound SP1/KLF5 to the VEGF promoter, resulted in a decrease in VEGF mRNA expression. Knocking down eEF2K also led to a striking decrease in the phosphorylation of PI3K/Akt and STAT3, indicating inactivation of these tumorigenic pathways. Taken together, our data suggest that eEF2K contributes to angiogenesis and tumor progression in HCC via SP1/KLF5‐mediated VEGF expression, as well as the subsequent stimulation of PI3K/Akt and STAT3 signaling.
What's new?
Eukaryotic elongation factor 2 kinase (eEF2K) represses protein synthesis by preventing ribosomes from moving along the mRNA strand. Recent work has associated eEF2K with tumor cell migration and invasion. These authors show how eEF2K promotes angiogenesis and tumor progression in hepatocellular cancer (HCC). Knocking down eEF2K in metastatic liver cancer cells reduced the cells’ invasiveness. Cells without eEF2K had less SP1/KLF5 transcription factors, which reduced the amount of VEGF mRNA in the cell. The cells also showed less activity in the PI3K/Akt and STAT pathways. Reducing eEF2K expression in mice, they found, prevented HCC tumor growth and angiogenesis.
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