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Antibodies targeting non-structural protein 1 (NS1) confer protection against Zika virus (ZIKV). Although monoclonal antibodies (MAbs) 3G2 and 4B8 are more potent than MAb 4F10 in suppressing ZIKV infection in neonatal mice models, the epitopes are unclear. Herein, we determined the Cryo-electron microscopy (Cryo-EM) structures of ZIKV NS1 in complex with five human antibodies at 2.6–2.9 Å resolution. Group I antibodies (3G2 and 4B8) recognize the previously unreported epitopes on the outer surface of the NS1 dimer. The unique binding mode of Group I antibodies led to a stronger recognition of the cell surface form of NS1 and completely inhibited secreted form non-structural protein 1 (sNS1)-induced endothelial permeability via their immunoglobulin G (IgG) and Fab. Group II antibodies (4F10, 2E11, and 14G5) recognize common epitopes in the distal end of the β-ladder domain, with a blockade efficiency that may be related to their affinity for the sNS1 protein and the presence of full-length IgG. These findings elucidate the correlation between epitope recognition and protective efficacy of anti-NS1 antibodies and highlight the diagnostic and therapeutic potential of 3G2 and 4B8.

Abstract The subcortical maternal complex (SCMC) is essential for safeguarding female fertility in mammals. Assembled in oocytes, the SCMC maintains the cleavage of early embryos, but the underlying mechanism remains unclear. Here, we report that 14-3-3, a multifunctional protein, is a component of the SCMC. By resolving the structure of the 14-3-3-containing SCMC, we discover that phosphorylation of TLE6 contributes to the recruitment of 14-3-3. Mechanistically, during maternal-to-embryo transition, the SCMC stabilizes 14-3-3 protein and contributes to the proper control of CDC25B, thus ensuring the activation of the maturation-promoting factor and mitotic entry in mouse zygotes. Notably, the SCMC establishes a conserved molecular link with 14-3-3 and CDC25B in human oocytes/embryos. This study discloses the molecular mechanism through which the SCMC regulates the cell cycle in early embryos and elucidates the function of the SCMC in mammalian early embryogenesis.

Existing self-supervised models for monocular depth estimation suffer from issues such as discontinuity, blurred edges, and unclear contours, particularly for small objects. We propose a self-supervised monocular depth estimation network with multi-scale selective Transformer feature fusion. To preserve more detailed features, this paper constructs a multi-scale encoder to extract features and leverages the self-attention mechanism of Transformer to capture global contextual information, enabling better depth prediction for small objects. Additionally, the multi-scale selective fusion module (MSSF) is also proposed, which can make full use of multi-scale feature information in the decoding part and perform selective fusion step by step, which can effectively eliminate noise and retain local detail features to obtain a clear depth map with clear edges. Experimental evaluations on the KITTI dataset demonstrate that the proposed algorithm achieves an absolute relative error (Abs Rel) of 0.098 and an accuracy rate (δ) of 0.983. The results indicate that the proposed algorithm not only estimates depth values with high accuracy but also predicts the continuous depth map with clear edges.

Three-dimensional (3D) printing ceramics based on vat photopolymerization (VPP) have attracted increasing interest in recent years because of their intrinsic properties and a wide range of potential applications. To overcome the drawbacks of traditional printing slurries, such as weak interlayer bonding and high viscosity, a series of organosilicon-grafted silica nanoparticles with a core/shell structure were prepared. These grafted nanoparticles possess small size (around 20 nm), good dispersion in photoactive diluents, and excellent photoactivity. Based on them, organic/inorganic hybrid materials with uniform microstructure and excellent mechanical performance (compressive stress 235.4 ± 33.2 MPa) were obtained by the vat photopolymerization technique. Further, oxide ceramics and carbide/oxide ceramic composites (compressive stress around 15 MPa) were prepared by calcination in air and argon, respectively. This study demonstrates the synthesis of organic/inorganic hybrid silica nanoparticles with good photoactivity, and their promising application as 3D-printable raw materials.

Yellow fever virus (YFV) infections can cause severe diseases in humans, resulting in mass casualties in Africa and the Americas each year. Secretory NS1 (sNS1) is thought to be used as a diagnostic marker of flavivirus infections, playing an essential role in the flavivirus life cycle, but little is known about the composition and structure of YFV sNS1. Here, we present that the recombinant YFV sNS1 exists in a heterogeneous mixture of oligomerizations, predominantly in the tetrameric form. The cryoEM structures show that the YFV tetramer of sNS1 is stacked by the hydrophobic interaction between β-roll domains and greasy fingers. According to the 3D variability analysis, the tetramer is in a semi-stable state that may contain multiple conformations with dynamic changes. We believe that our study provides critical insights into the oligomerization of NS1 and will aid the development of NS1-based diagnoses and therapies.

Detection of invading bacteria is key to immunity. Here, the authors report cryo-electron microscopy structures of agonist-bound formyl peptide receptor 1 (FPR1), that reveal structural basis for recognition of bacteria-derived formyl peptides.

Mas-related G-protein-coupled receptors X1-X4 (MRGPRX1-X4) are 4 primate-specific receptors that are recently reported to be responsible for many biological processes, including itch sensation, pain transmission, and inflammatory reactions. MRGPRX1 is the first identified human MRGPR, and its expression is restricted to primary sensory neurons. Due to its dual roles in itch and pain signaling pathways, MRGPRX1 has been regarded as a promising target for itch remission and pain inhibition. Here, we reported a cryo-electron microscopy (cryo-EM) structure of Gq-coupled MRGPRX1 in complex with a synthetic agonist compound 16 in an active conformation at an overall resolution of 3.0 Å via a NanoBiT tethering strategy. Compound 16 is a new pain-relieving compound with high potency and selectivity to MRGPRX1 over other MRGPRXs and opioid receptor. MRGPRX1 was revealed to share common structural features of the Gq-mediated receptor activation mechanism of MRGPRX family members, but the variable residues in orthosteric pocket of MRGPRX1 exhibit the unique agonist recognition pattern, potentially facilitating to design MRGPRX1-specific modulators. Together with receptor activation and itch behavior evaluation assays, our study provides a structural snapshot to modify therapeutic molecules for itch relieving and analgesia targeting MRGPRX1.

In recent decades, the sol-gel process accompanied with phase separation has been employed to fabricate porous monolithic ceramic materials. However, it is challenging to obtain crack-free samples by using this method, due to the fragile nature of porous ceramic materials and the large internal stress generated from drying and calcination process. In this work, tough monolithic titania (TiO2) materials were fabricated by the sol-gel process accompanied with phase separation in solutions of silicon carbide (SiC) nanofibers and preceramic polymers. It was found that polyethylene oxide (PEO) and ethylenediamine (EDA) can promote phase separation and sol-gel process respectively, and the micro-morphology of porous monolithic TiO2 materials can be flexibly tuned by adjusting the contents of PEO and EDA. The addition of SiC nanofibers effectively enhanced the mechanical performance and photocatalytic activity of porous TiO2 materials without altering their bicontinuous micro-morphology. Taking TiO2 materials as an example, this work demonstrates a novel methodology to fabricate ceramic nanofibers reinforced porous monolithic ceramic materials.

Considering the dynamic uncertainty, input saturation, and the discrete characteristics of digital control, a practical path following method is proposed for unmanned surface vessels (USV). Online identification for the heading model with uncertainty is presented based on a data-driven technique. Further, a constrained full-order terminal sliding manifold is constructed based on an auxiliary system to solve the input saturation. A full-order sliding mode heading controller is designed for USV in discrete-time form and the stability analysis is provided. Additionally, integral line of sight (ILOS) guidance law is introduced to generate the desired signal for the path following of USV. Simulations and experiments show that the proposed method is effective to realize tracking the desired path and has better performance than the existing popular method.

Study objectivePostoperative pulmonary complications (PPCs) are common and associated with adverse outcomes impairing long-term survival and quality of recovery. This single-centered retrospective study aimed to examine factors associated with PPCs in patients receiving elective colorectal surgery aged ≥60 years.MethodsBetween January 2019 and December 2019, 638 patients at the Shanghai Changhai Hospital who had received elective surgery for colorectal cancer were enrolled in this study. Patients were divided into the PPC group (n=38) and non-PPC group (n=600). Neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), red blood cell distribution width (RDW), and systemic inflammatory index (SII) were selected and caculated to indicate preoperative and postoperative inflammatory status. Receiver operating characteristic curve and bivariate correlation analyses were performed to evaluate the identified risk factors.Main resultsThe overall incidence of PPCs was approximately 5.96%. Multivariate regression analysis identified age (OR = 1.094, 95%CI 1.038–1.153, P = 0.001), preoperative RDW (OR = 1.159, 95%CI 1.025–1.309, P = 0.018), and preoperative SII (OR = 1.001, 95%CI 1.000–1.003, P = 0.035) as independent risk factors for PPCs. The cut-off values of age, preoperative RDW, and preoperative SII for predicting PPCs were 69.5 (sensitivity 0.658, specificity 0.653), 13.2 (sensitivity 0.789, specificity 0.552) and 556.1 (sensitivity 0.579, specificity 0.672), respectively.ConclusionsAge, preoperative RDW, and preoperative SII were identified as independent risk factors for PPC occurrence in elderly patients receiving elective colorectal surgery. Further studies are warranted to evaluate whether normalization of preoperative RDW and SII, as modifiable risk factors, are associated with improved surgical outcomes.

Ascochyta versabilis is the fungal pathogen that causes the severe leaf spot disease of Pseudostellaria heterophylla (Miq.) Pax, a vital Chinese herbal plant. Here, we deployed PacBio single-molecule real-time long-read sequencing technology to generate a near-complete genome assembly for the A. versabilis KC1 strain and obtained a total of 9.80 Gb raw reads. These reads were processed into a 41.05 Mb genome assembly containing 95 contigs with N50 of 1.70 Mb and a maximum length of 3.93 Mb. A total of 10,457 gene models, of which 1,004 encode putatively secreted proteins, were identified in the genome. This high-quality genome assembly and gene annotation resource will facilitate the institution of functional genetic studies aimed at providing a better insight into the infection mechanisms of A. versabilis to support the development of effective control strategies for leaf spot disease of P. heterophylla.

This paper presents a sectional water fraction measurement method using electrical capacitance tomography (ECT) image. To achieve a desired measurement accuracy, an optimal threshold-search method based on fast simulated annealing (FSA) algorithm is applied for image binarization; and to guarantee the imaging time consumption, fast fixed point continuation (FFPC) iterative algorithm cooperating with the compressed sensing (CS) theory was applied to the image reconstruction. In this study, the imaging time consumption and the measurement accuracy of water fraction are used to compare the proposed method and other methods. A numerical model is established with COMSOL Multiphysics to conduct the simulative validation of the proposed method firstly and physical experiments are conducted then. The experiment results show the average relative error of water fraction is lower than 15%, where the even as low as 3.68%.

The sexual morph Leptosphaeria taiwanensis Yen and Chi and its asexual morph Stagonospora tainanensis W. H. Hsieh is an important necrotrophic fungal phytopathogen, which causes sugarcane leaf blight, resulting in loss of cane tonnage and sucrose in susceptible sugarcane varieties. Decoding the genome and understanding of the basis of virulence is vitally important for devising effective disease control strategies. Here, we present a 38.25-Mb high-quality genome assembly of S. tainanensis strain StFZ01, denovo assembled with 10.19 Gb Nanopore sequencing long reads (~267×) and 3.82 Gb Illumina short reads (~100×). The genome assembly consists of 12 contigs with N50 of 2.86 Mb of which 5 belong to the telomere to telomere (T2T) chromosome. It contains 13.20% repeat sequences, 12,543 proteins, and 12,206 protein-coding genes with the BUSCO completeness 99.18% at fungi (n = 758) and 99.87% at ascomycota (n = 1706), indicating the high accuracy and completeness of our gene annotations. The virulence analysis in silico revealed the presence of 2379 PHIs, 599 CAZys, 248 membrane transport proteins, 191 cytochrome P450 enzymes, 609 putative secreted proteins, and 333 effectors in the StFZ01 genome. The genomic resources presented here will not only be helpful for development of specific molecular marker and diagnosis technique, population genetics, molecular taxonomy, and disease managements, it can also provide a significant precise genomic reference for investigating the ascomycetous genome, the necrotrophic lifestyle, and pathogenicity in the future.

To realize the non-contact measurement of the rotational shaft centerline orbit, a shaft centerline orbit reconstruction method using a specifically designed electrostatic sensor in conjunction with the neural network approximator is proposed in this paper. The sensing principle of the designed electrostatic sensor is based on the partial capacitance theory. The proposed sensor consists of one electrostatic field excitation electrode, two sensing electrodes, and a cylindrical metal shield covering the three electrodes. It directly establishes the map from the sensor output (voltages between sensing electrodes and shield) to shaft center position through the neural network approximator so that the shaft centerline orbit can be reconstructed. The CAE software COMSOL Multiphysics is used for sensor modeling and simulation analysis. The simulation reconstruction experiment is carried out to test the performance of the proposed sensor and to obtain training data for the neural network. The experiment result shows that the RMS error of the proposed sensor is within 0.4 μm, which has proved the feasibility of the novel sensor combined with the neural network fitting algorithm for industrial applications.

Abstract Background A number of Pyricularia species are known to infect different grass species. In the case of Pyricularia oryzae (syn. Magnaporthe oryzae), distinct populations are known to be adapted to a wide variety of grass hosts, including rice, wheat and many other grasses. The genome sizes of Pyricularia species are typical for filamentous ascomycete fungi [~ 40 Mbp for P. oryzae, and ~ 45 Mbp for P. grisea]. Genome plasticity, mediated in part by deletions promoted by recombination between repetitive elements [Genome Res 26:1091-1100, 2016, Nat Rev Microbiol 10:417-430,2012] and transposable elements [Annu Rev Phytopathol 55:483-503,2017] contributes to host adaptation. Therefore, comparisons of genome structure of individual species will provide insight into the evolution of host specificity. However, except for the P. oryzae subgroup, little is known about the gene content or genome organization of other Pyricularia species, such as those infecting Pennisetum grasses. Results Here, we report the genome sequence of P. penniseti strain P1609 isolated from a Pennisetum grass (JUJUNCAO) using PacBio SMRT sequencing technology. Phylogenomic analysis of 28 Magnaporthales species and 5 non-Magnaporthales species indicated that P1609 belongs to a Pyricularia subclade, which is genetically distant from P. oryzae. Comparative genomic analysis revealed that the pathogenicity-related gene repertoires had diverged between P1609 and the P. oryzae strain 70–15, including the known avirulence genes, other putative secreted proteins, as well as some other predicted Pathogen-Host Interaction (PHI) genes. Genomic sequence comparison also identified many genomic rearrangements relative to P. oryzae. Conclusion Our results suggested that the genomic sequence of the P. penniseti P1609 could be a useful resource for the genetic study of the Pennisetum-infecting Pyricularia species and provide new insight into evolution of pathogen genomes during host adaptation.

The determination of high resolution structures of G protein coupled receptors (GPCRs) in complex with heterotrimeric G proteins is challenging. Here authors develop an antibody fragment, mAB16, which stabilizes GPCR/G-protein complexes and facilitates the application of high resolution cryo-EM.

In industrial production processes, rotational speed is a key parameter for equipment condition monitoring and fault diagnosis. To achieve rotational speed measurement of rotational equipment under a condition of high temperature and heavy dust, this article proposes a digital approach using an electrostatic sensor. The proposed method utilizes a strip of a predetermined material stuck on the rotational shaft which will accumulate a charge because of the relative motion with the air. Then an electrostatic sensor mounted near the strip is employed to obtain the fluctuating signal related to the rotation of the charged strip. Via a signal conversion circuit, a square wave, the frequency of which equals that of the rotation shaft can be obtained. Having the square wave, the M/T method and T method are adopted to work out the rotational speed. Experiments were conducted on a laboratory-scale test rig to compare the proposed method with the auto-correlation method. The largest relative errors of the auto-correlation method with the sampling rate of 2 ksps, 5 ksps are 3.2% and 1.3%, respectively. The relative errors using digital approaches are both within ±4‰. The linearity of the digital approach combined with the M/T method or T method is also superior to that of the auto-correlation method. The performance of the standard deviations and response speed was also compared and analyzed to show the priority of the digital approach.

Rabbit muscle vesicles derived from sarcoplasmic reticulum were used as a material in studying networks of ryanodine receptors by cryo electron tomography. Three-dimensional analysis reveals the dynamical features of these networks. It was found that the connection angles were rotated along the transmembrane axis of ryanodine receptors. Majority of the connections was observed at domains 6/6 of ryanodine receptors while a small group of connections were showed at domains 9/10. The flexible rotation and connection shift seem to facilitate the extension of an annular network on the wall of the sarcoplasmic reticulum in a triad.

Recently, 3D image fusion reconstruction using a FDK algorithm along threeorthogonal circular isocentric orbits has been proposed. On the other hand, we know that 3D image reconstruction based on three-orthogonal circular isocentric orbits is sufficient in the sense of Tuy data sufficiency condition. Therefore the datum obtained from three-orthogonal circular isocentric orbits can derive an exact reconstruction algorithm. In this paper, an exact weighted-FBP algorithm with three-orthogonal circular isocentric orbits is derived by means of Katsevich’s equations of filtering lines based on a circle trajectory and a modified weighted form of Tuy’s reconstruction scheme.

Electrical capacitance tomography (ECT) is a promising imaging technology of permittivity distributions in multiphase flow. To reduce the effect of charging phenomenon on ECT measurement, an improved extreme learning machine method combined with adaptive soft-thresholding (AST-ELM) is presented and studied for image reconstruction. This method can provide a nonlinear mapping model between the capacitance values and medium distributions by using machine learning but not an electromagnetic-sensitive mechanism. Both simulation and experimental tests are carried out to validate the performance of the presented method, and reconstructed images are evaluated by relative error and correlation coefficient. The results have illustrated that the image reconstruction accuracy by the proposed AST-ELM method has greatly improved than that by the conventional methods under the condition with charging object.

BackgroundChemokines are well-known for playing an essential role in the development of cancer. However, the association between SNPs in the CCL2 and CXCL12 genes and the susceptibility to breast cancer remains unclear.MethodsA case-control study was conducted in southeast China, including 1855 breast cancer patients and 1838 cancer-free controls. The association between single nucleotide polymorphisms (SNPs) in the CCL2 and CXCL12 genes and the susceptibility to breast cancer was investigated using logistic regression models. The association between plasma CCL2 and CXCL12 with breast cancer was further examined in 72 patients and 75 controls.ResultsThe CXCL12 SNP rs3740085 was associated with breast cancer in the additive model (OR=1.15, 95%CI=1.01-1.32), particularly in postmenopausal women. The association between rs1024611 in CCL2 and breast cancer was only found in women with a BMI of ≥24kg/m2. SNPs in the CCL2 gene were mainly associated with PR-positive breast cancer, whereas rs1144471 in CXCL12 was associated with ER-negative (OR=0.43, 95% CI=0.23-0.84), PR-negative (OR=0.38, 95% CI=0.19-0.74), and HER-2-positive (OR=1.27, 95% CI=1.03-1.56) breast cancer. The interaction between rs1801157 and rs3740085 in CXCL12 SNPs was statistically significant, and rs3740085 was also associated with breast cancer survival. Additionally, we found a strong association between plasma CXCL12 and breast cancer.ConclusionCCL2 and CXCL12 SNPs are associated with breast cancer susceptibility in overweight and postmenopausal women, and the effect varies according to subtypes. The interaction of SNPs within CXCL12 gene and the association with breast cancer survival further suggest potential targets for improved risk assessment and treatment strategies.