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Parrots have enormous vocal imitation capacities and produce individually unique vocal signatures. Like songbirds, parrots have a nucleated neural song system, but because the two sister groups diverged over 50 million years ago it remains unknown if the song systems operate according to similar principles. Here we established a neuroscience-compatible call-and-response behavioral paradigm to elicit learned contact calls in budgerigars (Melopsittacus undulatus). Using variational autoencoder-based machine learning methods, we show that contact calls within affiliated groups converge but that individuals maintain unique acoustic features, or vocal signatures, even after call convergence. Next, we transiently and reversibly inactivated the outputs of the anterior forebrain pathway (AFP) as animals engaged in call-and-response interactions. Contact call pitch modulation, stereotypy and acoustic structure were dramatically degraded, resulting in the loss of individually unique features of the vocal signature. These results are in stark contrast to results from songbirds, where AFP inactivations with identical methods have the opposite result of increasing the stereotypy of learned vocalizations and retaining acoustic structure. Together, our results show that the anterior pathways of parrots and songbirds have different functional organization and that parrot frontal cortical circuits are necessary for individually unique features of vocal communication.

Flesh-reddening usually occurs in the amber-fleshed plum (Prunus salicina Lindl.) fruit during cold storage but not during ambient storage direct after harvest. It is not clear how postharvest cold signal is mediated to regulate the anthocyanin biosynthesis in the forming of flesh-reddening yet. In this study, anthocyanins dramatically accumulated and ethylene produced in the ‘Friar’ plums during cold storage, in comparison with plums directly stored at ambient temperature. Expression of genes associated with anthocyanin biosynthesis, as well as transcription factors of PsMYB10.1, PsbHLH3, and PsERF1B were strongly stimulated to upregulated in the plums in the period of cold storage. Suppression of ethylene act with 1-methylcyclopropene greatly suppressed flesh-reddening and downregulated the expression of these genes. Transient overexpression and virus-induced gene silencing assays in plum flesh indicated that PsMYB10.1 encodes a positive regulator of anthocyanin accumulation. The transient overexpression of PsERF1B, coupled with PsMYB10.1 and PsbHLH3, could further prompt the anthocyanin biosynthesis in a tobacco leaf system. Results from yeast two-hybrid and luciferase complementation assays verified that PsERF1B directly interacts with PsMYB10.1. PsERF1B and PsMYB10.1 enhanced the activity of the promoter of PsUFGT individually, and the enhancement was prompted by the co-action of PsERF1B and PsMYB10.1. Overall, the stimulation of the PsERF1B-PsMYB10.1-PsbHLH3 module mediated cold signal in the transcriptomic supervision of the anthocyanin biosynthesis in the ‘Friar’ plums. The results thereby revealed the underlying mechanism of the postharvest alteration of the flesh phenotype of ‘Friar’ plums subjected to low temperature.

Understanding the neural basis of mosquito behavior is critical for designing effective vector control strategies and can potentially shed new light on basic nervous system function. Because mosquitoes are a non-model species, however, functional studies of mosquito nervous systems have long been restricted to electrophysiological recording from peripheral sensory organs such as the antenna. This is now changing with the advent of CRISPR-Cas9 gene editing and the development of other powerful new genetic tools. Transgenic mosquitoes that carry genetically encoded calcium sensors, for example, open the door to optical recording of neural activity with two-photon calcium imaging. Compared with electrophysiology, calcium imaging permits continuous monitoring of neural activity from large populations of neurons, even deep in the brain. When combined with selective neural drivers, it also allows targeted recording from specific neuronal types. Here, we describe a calcium imaging protocol we use in our laboratory to study neural activity in the brain of

Mosquitoes spread dengue, Zika, malaria, and other pathogens to hundreds of millions of people every year. A better understanding of mosquito behavior and its underlying neural mechanisms may lead to new control strategies, but such an understanding requires the development of tools and approaches for exploring the nervous system of key vector species. For example, we can now image neural activity in mosquito brains using genetically encoded calcium sensors like GCaMP. Compared with other types of neural recording, GCaMP imaging has the advantage of allowing one to record from many neurons simultaneously and/or to record from specific neuronal types. Successful implementation requires careful consideration of many factors, including the choice of microscope and how to make the brains of experimental animals visible and stable while minimizing damage. Here, we elaborate on these points and provide a concise introduction to GCaMP imaging in the mosquito central nervous system.

Hot compression deformation behavior of the Cu-0.45Cr-1.0Ni-0.28Si-0.14Co alloy was studied by a thermal-mechanical simulator at strain rates of 0.001–1 s−1 and deformation temperatures of 700–900°C. The microstructure and texture of the copper alloy after the hot compression deformation were investigated. The results showed that the flow behavior of the Cu-Cr-Ni-Si-Co alloy was significantly affected by the deformation temperature and strain rate. The typical dynamic recrystallization (DRX) occurred at high temperatures and low strain rates, while the typical dynamic recovery (DRV) appeared at low temperatures and high strain rates. When the deformation temperature increased from 700°C to 900°C, a transition from copper and S texture to gross texture was found. The value of hot deformation activation energy (Q) was calculated as 330.87 kJ/mol. The optimized hot deformation parameters for the Cu-Cr-Ni-Si-Co alloy were 800–850°C/0.01–0.1 s−1.

Based on the near-infrared hyperspectral imaging technology (NIR-HSI) (950-1700 nm), a rapid identification method was proposed for Ziziphi Spinosae Semen (Suanzaoren, SZR) and its three kinds of counterfeits, i.e. Ziziphus mauritiana lam (Lizaoren, LZR), Hovenia dulcis Thunb. (Zhijuzi, ZJZ) and Lens culinaris (Bingdou, BD). According to the proportion of 2:1, by randomly dividing the sample set, 480 samples are taken as the training set and 240 samples are taken as the test set. Five preprocessing methods were used to process the extracted raw spectra from region of interest, and the optimal preprocessing method was selected. The full spectral models were established by using the Grey Wolf Optimizer (GWO-SVM), partial least square discrimination analysis (PLS-DA) and soft independent modeling class analog (SIMCA) algorithms. The best classification results of the full spectrum-based PLS-DA, GWO-SVM and SIMCA models were 0.95, 0.99 and 0.97, respectively. Selecting characteristic wavelength by combining spectral data with Competitive adaptive reweighted sampling (CARS) and Successful projects algorithm (SPA) algorithms. The comparison results showed that the recognition rate of SPA-GWO-SVM and SPA-SIMCA were 0.97. The optimal model was SPA-NON-SIMCA. Finally, according to prediction results of the optimal model, the samples were marked with different colours to obtain the visualization map of SZR with different fake products.

Platelet factor 4 (PF4) or the CXC chemokine CXCL4 is the most abundant protein within the α-granules of platelets. Previous studies found that PF4 regulates infections of several viruses, including HIV-1, H1N1, hepatitis C virus (HCV), and dengue virus. Here, we show that PF4 is an inhibitor of enterovirus A71 (EV71) and coxsackievirus A16 (CA16) infections. The secreted form of PF4 from transfected cells or soluble purified PF4 from Escherichia coli, even lacking signal peptide affected secretion, obviously inhibited the propagation of EV71 and CA16. Mechanistically, we demonstrated that PF4 blocked the entry of the virus into the host cells by interactions with VP3 proteins of EV71/CA16 and the interaction with SCARB2 receptor-mediated EV71 and CA16 endocytosis. As expected, the incubation of anti-PF4 antibody with PF4 blocked PF4 inhibition on EV71 and CA16 infections further supported the above conclusion. Importantly, pretreatment of EV71 viruses with PF4 significantly protected the neonatal mice from EV71 lethal challenge and promoted the survival rate of infected mice. PF4 derived from natural platelets by EV71/CA16 activation also presented strong inhibition on EV71 and CA16. In summary, our study identified a new host factor against EV71 and CA16 infections, providing a novel strategy for EV71 and CA16 treatment. IMPORTANCE The virus's life cycle starts with binding to cell surface receptors, resulting in receptor-mediated endocytosis. Targeting the entry of the virus into target cells is an effective strategy to develop a novel drug. EV71 and CA16 are the major pathogens that cause hand, foot, and mouth disease (HFMD) outbreaks worldwide since 2008. However, the treatment of EV71 and CA16 infections is mainly symptomatic because there is no approved drug. Therefore, the underlying pathogenesis of EV71/CA16 and the interaction between host-EV71/CA16 need to be further investigated to develop an inhibitor. Here, we identified PF4 as a potent entry inhibitor of EV71 and CA16 via binding to VP3 proteins of EV71 and CA16 or binding to receptor SCARB2. In the EV71 infection model, PF4 protected mice from EV71 lethal challenge and promoted the survival rate of EV71-infected mice. Our study suggests that PF4 represents a potential candidate host factor for anti-EV71 and CA16 infections.

A globally invasive form of the mosquito Aedes aegypti specializes in biting humans, making it an efficient disease vector(1). Host-seeking females strongly prefer human odour over the odour of non-human animals(2,3), but exactly how they distinguish the two is not known. Vertebrate odours are complex blends of volatile chemicals with many shared components(4–7), making discrimination an interesting sensory coding challenge. Here we show that human and animal odour blends evoke activity in distinct combinations of olfactory glomeruli within the Aedes aegypti antennal lobe. One glomerulus in particular is strongly activated by human odour but responds weakly, or not at all, to animal odour. This ‘human-sensitive’ glomerulus is selectively tuned to the long-chain aldehydes decanal and undecanal, which we show are consistently enriched in human odour and which likely originate from unique human skin lipids. Using synthetic blends, we further demonstrate that signalling in the human-sensitive glomerulus significantly enhances long-range host-seeking behaviour in a wind tunnel, recapitulating preference for human over animal odour. Our work suggests that animal brains may distill complex odour stimuli of innate biological relevance into simple neural codes and reveals novel targets for the design of next-generation mosquito-control strategies.

Accurate segmentation of ground-glass opacity (GGO) is an important premise for doctors to judge COVID-19. Aiming at the problem of mis-segmentation for GGO segmentation methods, especially the problem of adhesive GGO connected with chest wall or blood vessel, this paper proposes an accurate segmentation of GGO based on fuzzy c-means (FCM) clustering and improved random walk algorithm. The innovation of this paper is to construct a Markov random field (MRF) with adaptive spatial information by using the spatial gravity Model and the spatial structural characteristics, which is introduced into the FCM model to automatically balance the insensitivity to noise and preserve the effectiveness of image edge details to improve the clustering accuracy of image. Then, the coordinate values of nodes and seed points in the image are combined with the spatial distance, and the geodesic distance is added to redefine the weight. According to the edge density of the image, the weight of the grayscale and the spatial feature in the weight function is adaptively calculated. In order to reduce the influence of edge noise on GGO segmentation, an adaptive snowfall model is proposed to preprocess the image, which can suppress the noise without losing the edge information. In this paper, CT images of different types of COVID-19 are selected for segmentation experiments, and the experimental results are compared with the traditional segmentation methods and several SOTA methods. The results suggest that the paper method can be used for the auxiliary diagnosis of COVID-19, so as to improve the work efficiency of doctors.

BACKGROUND: Red raspberry (Rubus idaeus L.), known as “golden fruit”, has excellent potential for immune-regulation, anti-inflammation and anti-cancer due to its health-promoting secondary metabolites. The lack of genetic information in public databases has been a constraint for the genetic improvement of red raspberry. OBJECTIVE: The primary aim of the work was to find the key genes relating with the secondary metabolite pathways. METHODS: De novo assembly transcriptome sequencing of red raspberry (‘Heritage’ variety) fruit in different development stages was performed using an Illumina Hiseq platform. Transcriptome was obtained by the de novo assembly through Trinity assembler. Coding sequences were successfully characterized using databases including non-redundant protein (NR), euKaryotic Ortholog Groups of proteins (KOG), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Fragments Per Kilobase of transcript sequence per Million base pairs sequenced (FPKM) method was used to calculate the differentially expressed unigenes. RESULTS: In total, 205,880 unigenes with an average length of 1120 bp and an N50 of 2005 bp were obtained, of which 182,443 unigenes were annotated. Non redundant (NR) annotation showed that a majority of the best hits (58.6%) are wild strawberry (Fragaria vesca). Additionally, the unigenes were also annotated in euKaryotic Ortholog Groups of proteins database and Gene ontology database, and mapped the KEGG pathways. We predicted that 8331 TFs from the unigenes database and these TFs were classified into 94 different common families. The major families were associated with the C2H2 (9.19%), followed by the C3H (4.60%), MYB-related group (4.23%), bZIP (4.13%) and B3 (4.03%). These results were considered to be involved in the regulation of metabolic and secondary metabolic biosynthesis. Totally, 3,369, 3,461 and 441 differentially expressed genes (DEGs) were found in period 2 vs period 1, period 3 vs period 2 and period 4 vs period 3 paired comparisons, respectively. These DEGs were analyzed based on BLASTx, which were mapped to 22 KEGG pathways associating with secondary metabolites during red raspberry fruit ripening, involving anthocyanin biosynthesis, flavonoid biosynthesis, sesquiterpenoid and triterpenoid biosynthesis, etc. To validate the high-throughput sequencing results, six target genes involved in secondary metabolite pathways of red raspberry fruit were tested by qRT-PCR. The results of qRT-PCR assay were generally consistent with the results of RNA sequencing. CONCLUSION: The transcriptome sequencing of the red raspberry fruit at different development stage in this study enriched the genetic information resources of this variety, and will discover the genes relating with secondary metabolic pathways, benefiting to engineer high-quality plants with enhanced active ingredients.

The host restriction factor APOBEC3G (A3G) inhibits an extensive variety of viruses, including retroviruses, DNA viruses, and RNA viruses. Our study shows that A3G inhibits enterovirus 71 (EV71) and coxsackievirus A16 (CA16) via competitively binding the 5′ untranslated region (UTR) with the host protein poly(C)-binding protein 1 (PCBP1), which is required for the replication of multiple EVs. However, whether A3G inhibits other EVs in addition to EV71 and CA16 has not been investigated. Here, we demonstrate that A3G could inhibit the replication of EVD68, which requires PCBP1 for its replication, but not CA6, which does not require PCBP1 for replication. Further investigation revealed that the nucleic-acid-binding activity of A3G is required for EVD68 restriction, similar to the mechanism presented for EV71 restriction. Mechanistically, A3G competitively binds to the cloverleaf (1 to 123 nucleotides [nt]) and the stem-loop IV (234 to 446 nt) domains of the EVD68 5′ UTR with PCBP1, thereby inhibiting the 5′ UTR activity of EVD68; by contrast, A3G does not interact with CA6 5′ UTR, resulting in no effect on CA6 replication. Moreover, the nonstructural protein 2C, encoded by EVD68, overcomes A3G suppression by inducing A3G degradation via the autophagy-lysosome pathway. Our findings revealed that A3G might have broad-spectrum antiviral activity against multiple EVs through this general mechanism, and they might provide important information for the development of an anti-EV strategy. IMPORTANCE As the two major pathogens causing hand, foot, and mouth disease (HFMD), enterovirus 71 (EV71) and coxsackievirus A16 (CA16) attract a lot of attention for the study of their pathogenesis, their involvement with cellular proteins, and so on. However, other EVs such as CA6 and EVD68 constantly occur sporadically or have spread worldwide in recent years. Therefore, more information related to these EVs is needed in order to develop a broad-spectrum anti-EV inhibitor. In this study, we first reveal that the protein poly(C)-binding protein 1 (PCBP1), involved in PV- and EV71 virus replication, is also required for the replication of EVD68, but not for the replication of CA6. Next, we found that the host-restriction factor A3G specifically inhibits the replication of EVD68, but not the replication of CA6, by competitively binding to the 5′ UTR of EVD68 along with PCBP1. Our findings broaden knowledge related to EV replication and the interplay between EVs and host factors.

Recent years have seen an explosion of interest in the evolution of neural circuits. Comparison of animals from different families, orders, and phyla reveals fascinating variation in brain morphology, circuit structure, and neural cell types. However, it can be difficult to connect the complex changes that occur across long evolutionary distances to behavior. Luckily, these changes accumulate through processes that should also be observable in recent time, making more tractable comparisons of closely related species relevant and complementary. Here, we review several decades of research on the evolution of insect olfactory circuits across short evolutionary time scales. We describe two well-studied systems,Drosophila sechelliaflies andHeliothismoths, in detailed case studies. We then move through key types of circuit evolution, cataloging examples from other insects and looking for general patterns. The literature is dominated by changes in sensory neuron number and tuning at the periphery—often enhancing neural response to odorants with new ecological or social relevance. However, changes in the way olfactory information is processed by central circuits is clearly important in a few cases, and we suspect the development of genetic tools in non-model species will reveal a broad role for central circuit evolution. Moving forward, such tools should also be used to rigorously test causal links between brain evolution and behavior.

Blended vegetable oil is a vital product in the vegetable oil market, and quantifying high-value vegetable oil is of great significance to protect the rights and interests of consumers. In this study, we established a one-dimensional convolutional neural network (1D CNN) quantitative identification model based on Raman spectra to identify the amount of olive oil in a corn-olive oil blend. The results show that the 1D CNN model based on 315 extended average Raman spectra can quantitatively identify the content of olive oil, with R

Sterile alpha motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) possesses multiple biological activities such as virus restriction, innate immunity regulation, and autoimmunity. Our previous study demonstrated that SAMHD1 potently inhibits the replication of enterovirus 71 (EV71). In this study, we observed that SAMHD1 also restricts multiple enteroviruses (EVs), including coxsackievirus A16 (CA16) and enterovirus D68 (EVD68), but not coxsackievirus A6 (CA6). Mechanistically, SAMHD1 competitively interacted with the same domain in VP1 that binds to VP2 of EV71 and EVD68, thereby interfering with the interaction between VP1 and VP2 , and therefore viral assembly. Moreover, we showed that the SAMHD1 T592A mutant maintained the EV71 inhibitory effect by attenuating the interaction between VP1 and VP2, whereas the T592D mutant failed to. We also demonstrated that SAMHD1 could not inhibit CA6 because a different binding site is required for the SAMHD1 and VP1 interaction. Our findings reveal the mechanism of SAMHD1 inhibition of multiple EVs, and this could potentially be important for developing drugs against a broad range of EVs. IMPORTANCE Enterovirus causes a wide variety of diseases, such as hand, foot, and mouth disease (HFMD), which is a severe public problem threatening children under 5 years. Therefore, identifying essential genes which restrict EV infection and exploring the underlying mechanisms are necessary to develop an effective strategy to inhibit EV infection. In this study, we report that host restrictive factor SAMHD1 has broad-spectrum antiviral activity against EV71, CA16, and EVD68 independent of its well-known deoxynucleoside triphosphate triphosphohydrolase (dNTPase) or RNase activity. Mechanistically, SAMHD1 restricts EVs by competitively interacting with the same domain in VP1 that binds to VP2 of EVs, thereby interfering with the interaction between VP1 and VP2, and therefore viral assembly. In contrast, we also demonstrated that SAMHD1 could not inhibit CA6 because a different binding site is required for the SAMHD1 and CA6 VP1 interaction. Our study reveals a novel mechanism for the SAMHD1 anti-EV replication activity.

A novel Cu-1.01%Ni-0.28%Si-0.14%Co-0.45%Cr (mass percent) alloy with high strength and high conductivity was fabricated. Microstructure, mechanical and electrical properties of the alloy after multi-stage thermo-mechanical treatment were investigated in detail. The alloy has excellent comprehensive properties, with a tensile strength of 810 MPa, yield strength of 777 MPa, elongation of 3.4%, and electrical conductivity of 57.5%IACS (International Annealing Copper Standard). Three kinds of precipitates, (Cr,Co)2Si, (Ni,Co)2Si and Cr, form during aging treatment. Addition of Co element promotes the precipitation of Cr, Ni and Si solute elements from the matrix, while inhibits the growth of the (Cr,Co)2Si. The high strength of the alloy treated by multi-stage thermo-mechanical process is attributed to the dispersion strengthening, sub-structure strengthening, and work-hardening. The multi-aging process and addition of Co effectively improve the electrical conductivity of the studied alloy. The high strength and high conductivity of studied alloy make it as a potential candidate for lead frame materials in electrical and electronics industry.

A globally invasive form of the mosquito Aedes aegypti specializes in biting humans, making it an efficient vector of dengue, yellow fever, Zika, and chikungunya viruses. Host-seeking females strongly prefer human odour over the odour of non-human animals, but exactly how they distinguish the two is not known. Vertebrate odours are complex blends of volatile chemicals with many shared components, making discrimination an interesting sensory coding challenge. Here we show that human and animal odour blends evoke activity in unique combinations of olfactory glomeruli within the Aedes aegypti antennal lobe. Human blends consistently activate a ‘universal’ glomerulus, which is equally responsive to diverse animal and nectar-related blends, and a more selective ‘human-sensitive’ glomerulus. This dual signal robustly distinguishes humans from animals across concentrations, individual humans, and diverse animal species. Remarkably, the human-sensitive glomerulus is narrowly tuned to the long-chain aldehydes decanal and undecanal, which we show are consistently enriched in (though not specific to) human odour and which likely originate from unique human skin lipids. We propose a model of host-odour coding wherein normalization of activity in the human-sensitive glomerulus by that in the broadly-tuned universal glomerulus generates a robust discriminatory signal of the relative concentration of long-chain aldehydes in a host odour blend. Our work demonstrates how animal brains may distil complex odour stimuli of innate biological relevance into simple neural codes and reveals novel targets for the design of next-generation mosquito-control strategies.

Purpose: Increased volume ratio of Biologic Effective Dose (BED) was associated with higher local control rate in a setting of large (greater than 5 cm) non-small cell lung cancer (NSCLC) via photon partial stereotactic ablative boost radiotherapy (P-SABR). Taking advantage of unique physics characteristic of the Bragg peak, we exploit the potential dosimetric and clinical benefit of using proton P-SABR.Methods: Thirty patients’ CT structure set with large NSCLC previously treated with photon P-SABR were re-planned with three different treatment modalities: intensity modulated proton therapy (Proton-IMPT), proton volumetric modulated arc therapy (Proton-Arc) and photon volumetric modulated arc therapy (Photon-VMAT). Proton-Arc was mimicked with 8 to 14 beams (10 to 20 degree apart). Dosimetric metrics were compared among all of three treatment modalities in which tumor and organ at risks (OARs) doses were compared in volumes receiving >50% and ≤50% of the prescription dose, representing high- and low-dose regions, respectively. Normal Tissue Complication Probability (NTCP) of lungs and esophagus were compared as well.Results: In the high-dose region, mean doses of PTVs were 72.64 GyE, 80.42 GyE and 82.22 GyE and B90 (the ratio of BED>90GyE to the in-field tumor) were 71.17%, 86.59% and 87.32% for Photon-VMAT, Proton-IMPT and Proton-Arc plans, respectively (photon versus proton, p50 of esophageal were comparable for the three treatment modalities (p>0.05). In the low-dose region, doses of OARs were reduced dramatically in proton plans compared with Photon-VMAT plans (pConclusion: Higher BED inside the target could be achieved by using proton beam therapy with similar OARs dose sparing in high-dose region and significantly better OARs low dose sparing compared with photon techniques. Proton techniques has a potential role in the management of large NSCLC to increase the local control rate while reducing the side effect.

Blood-feeding mosquitoes survive by feeding on nectar for metabolic energy but require a blood meal to develop eggs. Aedes aegypti females must accurately discriminate blood and nectar because each meal promotes mutually exclusive feeding programs with distinct sensory appendages, meal sizes, digestive tract targets, and metabolic fates. We investigated the syringe-like blood-feeding appendage, the stylet, and discovered that sexually dimorphic stylet neurons taste blood. Using pan-neuronal calcium imaging, we found that blood is detected by four functionally distinct stylet neuron classes, each tuned to specific blood components associated with diverse taste qualities. Stylet neurons are insensitive to nectar-specific sugars and respond to glucose only in the presence of additional blood components. The distinction between blood and nectar is therefore encoded in specialized neurons at the very first level of sensory detection in mosquitoes. This innate ability to recognize blood is the basis of vector-borne disease transmission to millions of people worldwide.