A segmentation network for farmland ridge based on encoder-decoder architecture in combined with strip pooling module and ASPP.

In order to effectively support wheat breeding, farmland ridge segmentation can be used to visualize the size and spacing of a wheat field. At the same time, accurate ridge information collecting can deliver useful data support for farmland management. However, in the farming ridge segmentation scenarios based on remote sensing photos, the commonly used semantic segmentation methods tend to overlook the ridge edges and ridge strip features, which impair the segmentation effect. In order to efficiently collect ridge information, this paper proposes a segmentation method based on encoder-decoder of network with strip pooling module and ASPP module. First, in order to extract context information for multi-scale features, ASPP module are integrated in the deepest feature map. Second, the remote dependence of the ridge features is improved in both horizontal and vertical directions by using the strip pooling module. The final segmentation map is generated by fusing the boundary features and semantic features using an encoder and decoder architecture. As a result, the accuracy of the proposed method in the validation set is 98.0% and mIoU is 94.6%. The results of the experiments demonstrate that the method suggested in this paper can precisely segment the ridge information, as well as its value in obtaining data on the distribution of farmland and its potential for practical application.

Targeted Protein Degradation Mediated by Genetically Engineered Lysosome-Targeting Exosomes.

Protein-degrading chimeras are superior drug modalities compared to traditional protein inhibitors because of their effective therapeutic performance. So far, various targeted protein degradation strategies, including proteolysis-targeting chimeras and lysosome-targeting chimeras, have emerged as essential technologies for tackling diseases caused by abnormal protein expression. Here, we report the development and application of lysosome-targeting exosomes (LYTEXs) for the selective degradation of membrane protein targets. LYTEXs are genetically engineered exosomes expressing multivalent single-chain fragment variables, simultaneously recognizing cell-surface lysosome-targeting and to-be-degraded protein. We show that by targeting the lysosome-directing asialoglycoprotein receptor, bispecific LYTEXs can induce lysosomal degradation of membrane-associated therapeutic targets. This strategy provides a generalizable, easy-to-prepare platform for modulating surface protein expression, with the advantage of therapeutic delivery.

Selective Proteolysis of Activated Transcriptional Factor by NIR-Responsive Palindromic DNA Thalidomide Conjugate Inhibits the Canonical Smad Pathway.

Dysfunctional transcription factors that activate abnormal expressions of specific proteins are often associated with the progression of various diseases. Despite being attractive drug targets, the lack of druggable sites has dramatically hindered their drug development. The emergence of proteolysis targeting chimeras (PROTACs) has revitalized the drug development of many conventional hard-to-drug protein targets. Here, the use of a palindromic double-strand DNA thalidomide conjugate (PASTE) to selectively bind and induce proteolysis of targeted activated transcription factor (PROTAF) is reported. The selective proteolysis of the dimerized phosphorylated receptor-regulated Smad2/3 and inhibition of the canonical Smad pathway validates PASTE-mediated PROTAF. Further aptamer-guided active delivery of PASTE and near-infrared light-triggered PROTAF are demonstrated. Great potential in using PASTE for the selective degradation of the activated transcription factor is seen, providing a powerful tool for studying signaling pathways and developing precision medicines.

Lampshade web spider Ectatosticta davidi chromosome-level genome assembly provides evidence for its phylogenetic position.

The spider of Ectatosticta davidi, belonging to the lamp-shade web spider family, Hypochilidae, which is closely related to Hypochilidae and Filistatidae and recovered as sister of the rest Araneomorphs spiders. Here we show the final assembled genome of E. davidi with 2.16 Gb in 15 chromosomes. Then we confirm the evolutionary position of Hypochilidae. Moreover, we find that the GMC gene family exhibit high conservation throughout the evolution of true spiders. We also find that the MaSp genes of E. davidi may represent an early stage of MaSp and MiSp genes in other true spiders, while CrSp shares a common origin with AgSp and PySp but differ from MaSp. Altogether, this study contributes to addressing the limited availability of genomic sequences from Hypochilidae spiders, and provides a valuable resource for investigating the genomic evolution of spiders.

MdZAT5 regulates drought tolerance via mediating accumulation of drought-responsive miRNAs and mRNAs in apple.

Drought limits apple yield and fruit quality. However, the molecular mechanism of apple in response to drought is not well known. Here, we report a Cys2/His2 (C2H2)-type zinc-finger protein, MdZAT5, that positively regulates apple drought tolerance by regulating drought-responsive RNAs and microRNAs (miRNAs). DNA affinity purification and sequencing and yeast-one hybrid analysis identified the binding motifs of MdZAT5, T/ACACT/AC/A/G. Chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) and electrophoretic mobility shift assays (EMSAs) showed that MdZAT5 directly binds to the promoters of the drought-responsive genes including MdRHA2a, MdLEA14, MdTPX1, and MdCAT3, and activates their expression under drought stress. MdZAT5 interacts with and directly targets HYPONASTIC LEAVES1 (MdHYL1). MdZAT5 may facilitate the interaction of MdHYL1 with pri-miRNAs or MdDCL1 by activating MdHYL1 expression, thereby regulating the biogenesis of drought-responsive miRNAs. Genetic dissection showed that MdHYL1 is essential for MdZAT5-mediated drought tolerance and miRNA biogenesis. In addition, ChIP-qPCR and EMSA revealed that MdZAT5 binds directly to the promoters of some MIR genes including Mdm-miR171i and Mdm-miR172c, and modulates their transcription. Taken together, our findings improve our understanding of the molecular mechanisms of drought response in apple and provide a candidate gene for the breeding of drought-tolerant cultivars.

Nanostructured Cyclodextrin-Mediated Surface for Capacitive Determination of Cortisol in Multiple Biofluids.

The aim of this work is to develop a reusable polypropylene glycol (PPG):ß-cyclodextrin (ßCD) biosensor for cortisol detection. To achieve the most stable support for ßCD, we developed two PPG surfaces. The first surface is based on a gold surface modified with SAM of 3-mercaptopropionic acid (3MPA), and the second surface is based on a glassy carbon surface grafted with 4-carboxyphenyl diazonium salt. We characterized both surfaces by EIS, XPS, and ATR-FTIR and evaluated the stability and reusability of each surface. We found the GC-carboxyphenyl-PPG:ßCD is stable for at least 1 month. We have also demonstrated the reusability of the surface up to 10 times. In detecting cortisol, we used a nonfaradaic electrochemical impedance capacitive model to interpret the surface confirmation changes. We achieved sensitive detection of cortisol in PBS buffer, urine, and saliva with limit of detection of 2.13, 1.29, and 1.33 nM, respectively.

Metabolomics analysis of the potential toxicological mechanisms of diquat dibromide herbicide in adult zebrafish (Danio rerio) liver.

Although diquat is a widely used water-soluble herbicide in the world, its sublethal adverse effects to fish have not been well characterised. In this study, histopathological examination and biochemical assays were applied to assess hepatotoxicity and combined with gas chromatography-mass spectrometry (GC-MS)-based metabolomics analysis to reveal overall metabolic mechanisms in the liver of zebrafish (Danio rerio) after diquat exposure at concentrations of 0.34 and 1.69 mg·L-1 for 21 days. Results indicated that 1.69 mg·L-1 diquat exposure caused cellular vacuolisation and degeneration with nuclear abnormality and led to the disturbance of antioxidative system and dysfunction in the liver. No evident pathological injury was detected, and changes in liver biochemistry were not obvious in the fish exposed to 0.34 mg·L-1 diquat. Multivariate statistical analysis revealed differences between profiles obtained by GC-MS spectrometry from control and two treatment groups. A total of 17 and 22 metabolites belonging to different classes were identified following exposure to 0.34 and 1.69 mg·L-1 diquat, respectively. The metabolic changes in the liver of zebrafish are mainly manifested as inhibition of energy metabolism, disorders of amino acid metabolism and reduction of antioxidant capacity caused by 1.69 mg·L-1 diquat exposure. The energy metabolism of zebrafish exposed to 0.34 mg·L-1 diquat was more inclined to rely on anaerobic glycolysis than that of normal zebrafish, and interference effects on lipid metabolism were observed. The metabolomics approach provided an innovative perspective to explore possible hepatic damages on fish induced by diquat as a basis for further research.

Silica covered stannic oxide nanoparticles-an easily prepared robust substrate for optical sensors.

This paper describes a facile way to prepare a photophysically inert sensor substrate. Stannic oxide encapsulated silica nanoparticles with average diameters between 30 and 70 nm have been prepared by one-pot reverse-phase emulsion methodology. The constituents and core/shell morphology of the nanoparticles were demonstrated by electron microscopic technology, energy-dispersive x-ray spectroscopy, and x-ray photoelectron spectroscopy. X-ray diffraction was employed to provide additional constitutional and structural information. It has been shown that nanoparticles prepared by this method are optically clear in suspension. After anchoring optical indicators, this nanoparticle can be utilized as a sensor module both in biology and other analytical areas.

Bioinformatic and experimental analyses of key biomarkers in pancreatic cancer.

The present study aimed to screen the key genes in pancreatic cancer and to explore the pathogenesis of pancreatic cancer. A total of three expression profiling datasets (GSE28735, GSE16515 and GSE15471) associated with pancreatic cancer were retrieved from the public gene chip database. The differentially expressed genes (DEGs) were screened by GEO2R and subjected to Gene Ontology (GO) and signaling pathway enrichment analysis. Furthermore, a protein interaction network was constructed. The GEPIA online database was used to screen for genes that affect the prognosis of pancreatic cancer. Finally, cell functional experiments were performed on the selected key genes. A total of 72 DEGs were identified, including 52 upregulated and 20 downregulated genes. Enrichment analysis revealed roles of the DEGs in endodermal cell differentiation, cell adhesion, extracellular matrix-receptor interaction and PI3K-Akt signaling pathway. In total, 10 key nodal genes were identified, including integrin subunit α 2 (ITGA2), ITGB6 and collagen α 1 chain 1. Through survival analysis, two genes with an impact on the prognosis of pancreatic cancer were identified, namely ITGA2 and ITGB6. Silencing of ITGB6 in a pancreatic cancer cell line significantly suppressed cell proliferation and induced cell cycle arrest at G2/M phase. The identified key genes and signaling pathways may help to deepen the understanding of the molecular mechanisms involved in pancreatic cancer and provide a theoretical basis to develop novel therapies.

Hydrolytic Modification of SiO2 Microspheres with Na2SiO3 and the Performance of Supported Nano-TiO2 Composite Photocatalyst.

Modified microspheres (SiO2-M) were obtained by the hydrolytic modification of silicon dioxide (SiO2) microspheres with Na2SiO3, and then, SiO2-M was used as a carrier to prepare a composite photocatalyst (SiO2-M/TiO2) using the sol-gel method; i.e., nano-TiO2 was loaded on the surface of SiO2-M. The structure, morphology, and photocatalytic properties of SiO2-M/TiO2 were investigated. Besides, the mechanism of the effect of SiO2-M was also explored. The results show that the hydrolytic modification of Na2SiO3 coated the surface of SiO2 microspheres with an amorphous SiO2 shell layer and increased the quantity of hydroxyl groups. The photocatalytic performance of the composite photocatalyst was slightly better than that of pure nano-TiO2 and significantly better than that of the composite photocatalyst supported by unmodified SiO2. Thus, increasing the loading capacity of nano-TiO2, improving the dispersion of TiO2, and increasing the active surface sites are essential factors for improving the functional efficiency of nano-TiO2. This work provides a new concept for the design of composite photocatalysts by optimizing the performance of the carrier.

Molecular Recognition: Perspective and a New Approach.

This perspective presents an overview of approaches to the preparation of molecular recognition agents for chemical sensing. These approaches include chemical synthesis, using catalysts from biological systems, partitioning, aptamers, antibodies and molecularly imprinted polymers. The latter three approaches are general in that they can be applied with a large number of analytes, both proteins and smaller molecules like drugs and hormones. Aptamers and antibodies bind analytes rapidly while molecularly imprinted polymers bind much more slowly. Most molecularly imprinted polymers, formed by polymerizing in the presence of a template, contain a high level of covalent crosslinker that causes the polymer to form a separate phase. This results in a material that is rigid with low affinity for analyte and slow binding kinetics. Our approach to templating is to use predominantly or exclusively noncovalent crosslinks. This results in soluble templated polymers that bind analyte rapidly with high affinity. The biggest challenge of this approach is that the chains are tangled when the templated polymer is dissolved in water, blocking access to binding sites.

Low-carbon technology collaborative innovation in industrial cluster with social exclusion: An evolutionary game theory perspective.

As governments implement low-carbon economy widely, boosting low-carbon transformation in industrial clusters has become a challenge. This study establishes an evolutionary game model of low-carbon technology collaborative innovation based on spatial public goods game to solve the free-riding problem effectively in research and development. By introducing a social exclusion mechanism, we explore the requirements for the emergence of cooperation between enterprises, and we consider the heterogeneity and scale-free characteristics of industrial clusters comprehensively. Simulation results confirm that social exclusion can significantly promote cooperation as a form of cooperation with additional cost. When exclusion cost decreases and probability increases, an excluder can survive in a lower enhancement factor, which guarantees a stable exclusion mechanism. Furthermore, this mechanism is key to forming and maintaining cooperative behavior. When a cluster follows a scale-free distribution, the sparse network structure can avoid cooperation collapse. Moreover, heterogeneous investment is a robust alternative in the face of invading defectors. This study provides a new understanding to promote the collaborative innovation of enterprises in industrial clusters.

Application of Voltage in Dynamic Light Scattering Particle Size Analysis.

Dynamic light scattering (DLS) is a common method for characterizing the size distribution of polymers, proteins, and other nano- and microparticles. Modern instrumentation permits measurement of particle size as a function of time and/or temperature, but currently there is no simple method for performing DLS particle size distribution measurements in the presence of applied voltage. The ability to perform such measurements would be useful in the development of electroactive, stimuli-responsive polymers for applications such as sensing, soft robotics, and energy storage. Here, a technique using applied voltage coupled with DLS and a temperature ramp to observe changes in aggregation and particle size in thermoresponsive polymers with and without electroactive monomers is presented. The changes in aggregation behavior observed in these experiments were only possible through the combined application of voltage and temperature control. To obtain these results, a potentiostat was connected to a modified cuvette in order to apply voltage to a solution. Changes in polymer particle size were monitored using DLS in the presence of constant voltage. Simultaneously, current data were produced, which could be compared with particle size data, to understand the relationship between current and particle behavior. The polymer poly(N-isopropylacrylamide) (pNIPAM) served as a test polymer for this technique, as pNIPAM's response to temperature is well-studied. Changes in the lower-critical solution temperature (LCST) aggregation behavior of pNIPAM and poly(N-isopropylacrylamide)-block-poly(ferrocenylmethyl methacrylate), an electrochemically active block-copolymer, in the presence of applied voltage are observed. Understanding the mechanisms behind such changes will be important when trying to achieve reversible polymer structures in the presence of applied voltage.

Insights on the Lower Critical Solution Temperature Behavior of pNIPAM in an Applied Electric Field.

Poly(N-isopropylacrylamide), or pNIPAM, is a free-radical polymer that is commonly studied for uses in surface coatings, tissue engineering, energy storage, biosensing, and more, due to its temperature responsiveness. pNIPAM is known to solubilize at temperatures below its lower critical solution temperature (LCST) and agglomerate above its LCST. This behavior has been shown to be reproducible and reversible. We confirmed this reversibility and the value of the LCST by performing dynamic light scattering (DLS) with a temperature sweep (increase and decrease). However, performing the same experiment under an applied voltage from copper electrodes, we observed a decrease in the LCST of pNIPAM and irreversible aggregation. Here we present preliminary data comparing the LCST behavior of pNIPAM in the presence of applied voltage using copper, aluminum, and carbon electrodes. We present data in support of the hypothesis that a phenomenon is occurring specifically with the use of copper electrodes that is altering pNIPAM LCST behavior.

A Single-chain Templated Polymer-based Target Receptor as a New Platform for Label-free Selective Electrochemical Sensing.

We report a novel single-chain polymer-based chemical receptor that can be used for the label-free electrochemical detection of an analyte with high selectivity. The polymer was developed using poly-N-isopropylacrylamide (pNIPAM) as a backbone structure in addition to other functional monomers that are used to imprint the template molecule 4-nitrophenol. The polymer also contains a redox reporting monomers (ferrocene) which create a change in the electrochemical signal upon molecular recognition. We hypothesize that the analyte binding to the receptor causes the polymer conformation change from the extended to the collapsed phase. After anchoring the polymer-based receptors onto the surfaces of the gold electrode, when exposed to the analyte, the changes in the electrochemical signals were observed which confirmed the selective target binding as well as the polymer conformation change as a result.

Intradermal delivery of a fractional dose of influenza H7N9 split vaccine elicits protective immunity in mice and rats.

Vaccination is the most effective method of preventing the spread of the influenza virus. However, the traditional intramuscular (IM) immunization causes fear, pain, and cross infection. In contrast, needle-free (NF) immunization is quick and easy for medical personnel and painless and safe for patients. In this study, we assessed the safety and protective efficacy of NF intradermal (ID) immunization with the influenza H7N9 split vaccine (Anhui H7N9/PR8). A preliminary safety evaluation showed that ID immunization with 15 µg of the H7N9 influenza vaccine was not toxic in rats. Moreover, the antigen was metabolized more rapidly after ID than after IM immunization, as determined by in vivo imaging, and ID immunization accelerated the generation of a specific immune response. Additionally, ID immunization with a 20% dose of the H7N9 split vaccine Anhui H7N9/PR8 offered complete protection against lethal challenge by the live H7N9 virus. Taken together, our findings suggest that NF ID immunization with the H7N9 influenza vaccine induces effective protection, has a good safety profile, requires little antigen, and elicits an immune response more rapidly than does IM immunization. This approach may be used to improve the control of influenza H7N9 outbreaks.

Immunogenicity of an influenza virus-vectored vaccine carrying the hepatitis C virus protein epitopes in mice.

Hepatitis C virus (HCV) has a devastating impact on human health, and infections can progress into liver fibrosis, cirrhosis, and hepatocellular carcinoma. There is no effective HCV vaccine. In this study, we rescued a recombinant PR8 influenza viral vector, called rgFLU-HCVCE1E2, carrying the core and envelope glycoprotein (C/E1/E2) epitopes of HCV inserted into the influenza nonstructural protein 1 gene. The morphological characteristics of rgFLU-HCVCE1E2 and the expression of the C/E1/E2 epitopes of HCV were examined. rgFLU-HCVCE1E2 replicated in various cell lines, including MDCK, A549, and Huh7.5 cells. More importantly, in BALB/c mice immunized intranasally twice at a 21-day interval with 104, 105, or 106 TCID50 rgFLU-HCVCE1E2, the viral vector induced a robust antibody response to influenza and HCV and potent IFN-γ and IL-4 secretion in response to HCV antigens in a dose-dependent manner. The rgFLU-HCVCE1E2 virus also stimulated IFN-γ production by virus-specific peripheral blood mononuclear cells in patients with chronic HCV infection. The study demonstrated that rgFLU-HCVCE1E2 carrying HCV antigens is immunogenic in vivo and has potential for the development of a HCV vaccine.

Intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar protective immunity to intramuscular inoculation of a full dose of an Al(OH)3-adjuvanted vaccine.

Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the two major causative agents of hand, foot and mouth disease (HFMD), which erupts in the Asia-Pacific regions. A bivalent vaccine against both EV71 and CVA16 is highly desirable. In the present study, on the bases that an experimental bivalent vaccine comprising of inactivated EV71 and CVA16 induces a balanced protective immunity against both EV71 and CVA16, we compare the immunogenicity and reactogenicity of one fourth of a full dose of an intradermal vaccine administered by needle-free liquid jet injector with a full dose of an intramuscular vaccine administered by needle-syringe in monkeys. The results suggest that intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar immunogenicity and reactogenicity to intramuscular inoculation of a full dose of an Al(OH)3-adjuvanted vaccine, regardless of whether monovalent or bivalent vaccines were used. Our results support the use of an intradermal bivalent vaccine strategy for HFMD vaccination in order to satisfy the requirements and reduce the costs.