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The construction of a high-quality wheat genome variation map is important to wheat genetic studies and breeding. In this study, we developed the second-generation whole-genome genetic variation map of wheat (VMap 2.0) by integrating whole-genome sequencing data of 1,062 diverse wheat accessions from 20 species/subspecies. VMap 2.0 contains 195.96 million single nucleotide polymorphisms (SNPs), 2.22 million insertions, and 4.72 million deletions, achieving a high density of variation map in which one variant exists in every 73 base pairs on average. By systematically analyzing the phylogenetic relationships and genetic diversity of tetraploid wheat, hexaploid wheat, and diploid goatgrass (Aegilops tauschii), we found that the genetic diversity of wild emmer wheat was 2.4 times higher than that of common wheat. In contrast, the genetic diversity of diploid goatgrass is 7.8 times higher than the D subgenome of hexaploid wheat. With the high-density genetic variations, VMap 2.0 is anticipated to facilitate high-resolution trait dissection and expedite prediction-based breeding of wheat.

Aberrant post-translational modification (PTM) is a key molecular event inciting p53 tumor suppressor function loss or transformation. Here, we report that p53 acetylation, independent of the overall level of p53 expression, predicts improved survival in glioblastoma (GBM). It revealed that acetylation at the C-terminal domain (CTD) reversed tumorigenic gain of function (GOF) of p53 mutants in GBM. An important finding was that acetylation not only strengthened the tumor suppression of wild-type p53, but also reinforced the chemosensitivity of GBM cells with missense mutant p53, as evidenced by attenuated DNA damage repair. Mechanical exploration revealed that the acetylation of p53 in GBM was negatively regulated by Smad1. Smad1 served as an oncoprotein in GBM by promoting tumorigenesis and chemoresistance in a BMP or TGF-β independent manner. It formed a ternary complex with p53 through the MH1 domain and with p300 through the MH2 domain, inhibiting p300-mediated p53 acetylation via competitively binding of the C-terminus of p300. Acetylated Smad1 was identified by p300 at the lysine site 373 (K373). Smad1 acetylation was indispensable due to its transcriptional activity and onco-functions. Collectively, this study highlights that acetylation is critical for p53 and Smad1 functions, and that Smad1 acts as an oncoprotein partially by impairing p53 acetylation in GBM.

Bread wheat expanded its habitat from a core area of the Fertile Crescent to global environments within ~10,000 years. The genetic mechanisms of this remarkable evolutionary success are not well understood. By whole-genome sequencing of populations from 25 subspecies within the genera Triticum and Aegilops, we identified composite introgression from wild populations contributing to a substantial portion (4-32%) of the bread wheat genome, which increased the genetic diversity of bread wheat and allowed its divergent adaptation. Meanwhile, convergent adaptation to human selection showed 2- to 16-fold enrichment relative to random expectation-a certain set of genes were repeatedly selected in Triticum species despite their drastic differences in ploidy levels and growing zones, indicating the important role of evolutionary constraints in shaping the adaptive landscape of bread wheat. These results showed the genetic necessities of wheat as a global crop and provided new perspectives on transferring adaptive success across species for crop improvement.

Intestinal epithelial dysfunction is the foundation of various intestinal and extra-intestinal diseases, while the effects and mechanism of uric acid on the intestinal barrier are little known. TSPO has been shown to be related to the generation of ROS and is involved in regulating inflammation, whether uric acid drives intestinal epithelial dysfunction through TSPO-mediated NLRP3 inflammasome activation is unknown. UOX gene knockout mouse (UOX-/-) were used for models of hyperuricemia. Fluorescein isothiocyanate (FITC)-labeled dextran was used to assess in vivo intestinal permeability. Serum lipopolysaccharide (LPS) and culture supernatants IL-1β were measured using ELISA Kit. IEC-6 exposed to different concentrations of uric acid was used for in vitro experiment. Protein content and mRNA were assessed using Western blotting and Q-PCR, respectively. Intracellular ROS was determined using flow cytometry and fluorescence microscope. Mitochondrial membrane potential was detected on an immunofluorescence. Small interfering RNA transfection was used to assess the interaction between translocator protein (TSPO) and NLRP3 inflammasome. N-acetyl-L-cysteine (NAC) was used as ROS scavenger. Our results showed that hyperuricemia mice were characteristic by increased intestinal permeability. Hyperuricemia upregulated TSPO, increased production of ROS and activated NLRP3 inflammasome, which resulted in lower expression of occludin and claudin-1. In vitro, we showed that soluble uric acid alone increased the expression of TSPO, depolarized mitochondrial membrane potential, increased ROS release and activated NLRP3 inflammasome, which further reduced the expression of occludin and claudin-1. Silencing TSPO suppressed NLRP3 inflammasome activation and increased expression of claudin-1 and occludin, which was accompanied by lower levels of ROS. Scavenging ROS also significantly inhibited NLRP3 inflammasome activation without change of TSPO, indicating that TSPO-mediated NLRP3 inflammasome activation was dependent on ROS. In conclusion, uric acid drives intestinal barrier dysfunction through TSPO-mediated NLRP3 inflammasome.

This paper studies the distributed dimensionality reduction fusion estimation problem for cyber-physical systems with limited bandwidth in presence of eavesdroppers. Since wireless communication is implemented by broadcasting, the eavesdroppers can collude to collect the data through anther communication networks. To protect data privacy, based on the physical processes and local estimation error covariance (EEC) matrix, an insertion method of artificial noise (AN) is developed such that only eavesdroppers’ fusion EEC becomes worse. Meanwhile, the fusion center needs to decode the received signal due to the noise interference, while the successful decoding probability varies with signal to noise ratio. Subsequently, some criteria for the selection probabilities and the successful decoding probabilities are given to guarantee the effectiveness of the AN insertion strategy. Moreover, a sufficient condition of the designed AN power is derived to guarantee the confidentiality. Simulation examples are given to show the effectiveness of the proposed methods.

Deep knowledge of crop biodiversity is essential to improve global food security. Despite bread wheat serving as a keystone crop worldwide, the population history of bread wheat and its wild relatives (a.k.a. wheats) remains elusive. By analyzing whole-genome sequences of 795 wheats, we found that bread wheat originated southwest of the Caspian Sea ∼11,700 years ago and underwent a slow speciation process, lasting ∼3,300 years due to persistent gene flow from wild relatives. Soon after, bread wheat spread across Eurasia and reached Europe, South Asia, and East Asia ∼7,000 to ∼5,000 years ago, shaping a diversified but occasionally convergent adaptive landscape of bread wheat in novel environments. Opposite to cultivated wheat, wild wheat populations have declined by ∼82% in the past ∼2,000 years due to the food choice shift of humans, and likely continue to drop because of the changing climate. These findings will guide future efforts in protecting and utilizing wheat biodiversity to improve global food security.

The molecular mechanism underlying hyperuricemia-induced lipid metabolism disorders is not clear. The purpose of the current study was to investigate the mechanism of lipid disturbances in a hyperuricemia mice model. RNA-Seq showed that differentially expressed genes (DEGs) in the fatty acid synthesis signaling pathway were mainly enriched and CXCL-13 was significantly enriched in protein-protein interaction networks. Western blotting, Q-PCR, and immunofluorescence results further showed that hyperuricemia upregulated CXCL-13 and disturbed lipid metabolism in vivo and in vitro. Furthermore, CXCL-13 alone also promoted the accumulation of lipid droplets and upregulated the expression of FAS and SREBP1, blocking AMPK signaling and activating the PKC and P38 signaling pathways. Silencing CXCL-13 reversed uric-acid-induced lipid droplet accumulation, which further downregulated FAS and SREBP1 expression, inhibited the p38 and PKC signaling, and activated AMPK signaling. In conclusion, hyperuricemia induces lipid metabolism disorders via the CXCL-13 pathway, making CXCL-13 a key regulatory factor linking hyperuricemia and lipid metabolism disorders. These results may provide novel insights for the treatment of hyperuricemia.

BackgroundStructural variations (SVs) pervade the genome and contribute substantially to the phenotypic diversity of species. However, most SVs were ineffectively assayed because of the complexity of plant genomes and the limitations of sequencing technologies. Recent advancement of third-generation sequencing technologies, particularly the PacBio high-fidelity (HiFi) sequencing, which generates both long and highly accurate reads, offers an unprecedented opportunity to characterize SVs and reveal their functionality. Since HiFi sequencing is new, it is crucial to evaluate HiFi reads in SV detection before applying the technology at scale.ResultsWe sequenced wheat genomes using HiFi, then conducted a comprehensive evaluation of SV detection using mainstream long-read aligners and SV callers. The results showed the accuracy of SV discovery depends more on aligners rather than callers. For aligners, pbmm2 and NGMLR provided the most accurate results while detecting deletion and insertion, respectively. Likewise, cuteSV and SVIM achieved the best performance across all SV callers. We demonstrated that the combination of the aligners and callers mentioned above is optimal for SV detection. Furthermore, we evaluated the impact of sequencing depth on the accuracy of SV detection. The results showed that low-coverage HiFi sequencing is capable of generating high-quality SV genotyping.ConclusionsThis study provides a robust benchmark of SV discovery with HiFi reads, showing the remarkable potential of long-read sequencing to investigate structural variations in plant genomes. The high accuracy SV discovery from low-coverage HiFi sequencing indicates that skim HiFi sequencing is an ideal approach to study structural variations at the population level.

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, characterized by diffuse infiltration, dysplasia, and resistance to therapy. Metabolic remodeling and immunosuppression are typical events which contribute to GBM progression, but the molecular link between these two events remains largely undetermined. Studies have shown that high levels of transforming growth factor-β (TGF-β) and its receptors are associated with glioma malignancy and a poor prognosis. TGF-β plays an important role in cell metabolism and immunity. During tumorigenesis, TGF-β induces a shift in cell metabolism from oxidative phosphorylation to aerobic glycolysis, providing a favorable environment for tumor growth. Locally, TGF-β creates an immunosuppressive microenvironment and promotes the malignant phenotype of GBM. In this review, we aim to link GBM aerobic glycolysis and immunosuppression through TGF-β to provide new ideas for the study of GBM.

The stems of cereal crops provide both mechanical support for lodging resistance and a nutrient supply for reproductive organs. Elongation, which is considered a critical phase for yield determination in winter wheat (Triticum aestivum L.), begins from the first node detectable to anthesis. Previously, we characterized a heavy ion beam triggered wheat mutant qd, which exhibited an altered stem elongation pattern without affecting mature plant height. In this study, we further analyzed mutant stem developmental characteristics by using transcriptome data. More than 40.87 Mb of clean reads including at least 36.61 Mb of unique mapped reads were obtained for each biological sample in this project. We utilized our transcriptome data to identify 124,971 genes. Among these genes, 4,340 differentially expressed genes (DEG) were identified between the qd and wild-type (WT) plants. Compared to their WT counterparts, qd plants expressed 2,462 DEGs with downregulated expression levels and 1878 DEGs with upregulated expression levels. Using DEXSeq, we identified 2,391 counting bins corresponding to 1,148 genes, and 289 of them were also found in the DEG analysis, demonstrating differences between qd and WT. The 5,199 differentially expressed genes between qd and WT were employed for GO and KEGG analyses. Biological processes, including protein-DNA complex subunit organization, protein-DNA complex assembly, nucleosome organization, nucleosome assembly, and chromatin assembly, were significantly enriched by GO analysis. However, only benzoxazinoid biosynthesis pathway-associated genes were enriched by KEGG analysis. Genes encoding the benzoxazinoid biosynthesis enzymes Bx1, Bx3, Bx4, Bx5, and Bx8_9 were confirmed to be differentially expressed between qd and WT. Our results suggest that benzoxazinoids could play critical roles in regulating the stem elongation phenotype of qd.

Vehicle state, including location and motion information, plays an essential role on the Internet of Vehicles (IoV). Accurately obtaining the system state information is the premise of realizing precise control. However, the statistics of system process noise are often unknown due to the complex physical process. It is challenging to estimate the system state when the process noise statistics are unknown. This paper proposes a new adaptive high-degree unscented Kalman filter based on the improved Sage–Husa algorithm. First, the traditional Sage–Husa algorithm is improved using a high-degree unscented transform. A noise estimator suitable for the high-degree unscented Kalman filter is obtained to estimate the statistics of the unknown process noise. Then, an adaptive high-degree unscented Kalman filter is designed to improve the accuracy and stability of the state estimation system. Finally, the target tracking simulation results verify the proposed algorithm’s effectiveness.

With the development of the industry, the physical model of controlled object tends to be complicated and unknown. It is particularly important to estimate the state variables of a nonlinear system when the model is unknown. This paper proposes a state estimation method based on adaptive fusion of multiple kernel functions to improve the accuracy of system state estimation. First, a dynamic neural network is used to build the system state model, where the kernel function node is constructed by a weighted linear combination of multiple local kernel functions and global kernel functions. Then, the state of the system and the weight of the kernel functions are put together to form an augmented state vector, which can be estimated in real time by using high-degree cubature Kalman filter. The high-degree cubature Kalman filter performs adaptive fusion of the kernel function weights according to specific samples, which makes the neural network function approximate the real system model, and the state estimate follows the real value. Finally, the simulation results verify the feasibility and effectiveness of the proposed algorithm.

Intestinal epithelial dysfunction is the foundation of various intestinal and extra-intestinal diseases, while the effects and mechanism of uric acid on the intestinal barrier are little known. TSPO has been shown to be related to the generation of ROS and is involved in regulating inflammation, whether uric acid drives intestinal epithelial dysfunction through TSPO-mediated NLRP3 inflammasome activation is unknown.UOX gene knockout mouse (UOX-/-) were used for models of hyperuricemia. Fluorescein isothiocyanate (FITC)-labeled dextran was used to assess in vivo intestinal permeability. Serum lipopolysaccharide (LPS) and culture supernatants IL-1β were measured using ELISA Kit. IEC-6 exposed to different concentrations of uric acid was used for in vitro experiment. Protein content and mRNA were assessed using Western blotting and Q-PCR, respectively. Intracellular ROS was determined using flow cytometry and fluorescence microscope. Mitochondrial membrane potential was detected on an immunofluorescence. Small interfering RNA transfection was used to assess the interaction between translocator protein (TSPO) and NLRP3 inflammasome. N-acetyl-L-cysteine (NAC) was used as ROS scavenger.Our results showed that hyperuricemia mice were characteristic by increased intestinal permeability. Hyperuricemia upregulated TSPO, increased production of ROS and activated NLRP3 inflammasome, which resulted in lower expression of occludin and claudin-1. In vitro, we showed that soluble uric acid alone increased the expression of TSPO, depolarized mitochondrial membrane potential, increased ROS release and activated NLRP3 inflammasome, which further reduced the expression of occludin and claudin-1. Silencing TSPO suppressed NLRP3 inflammasome activation and increased expression of claudin-1 and occludin, which was accompanied by lower levels of ROS. Scavenging ROS also significantly inhibited NLRP3 inflammasome activation without change of TSPO, indicating that TSPO-mediated NLRP3 inflammasome activation was dependent on ROS.In conclusion, uric acid drives intestinal barrier dysfunction through TSPO-mediated NLRP3 inflammasome.

Some studies on the hyperuricemia (HUA) have focused on intestinal bacteria. To better understand the correlation between gut microbiota and HUA, we established a HUA rat model with high-purine diet, and used 16S rRNA genes sequencing to analyze gut microbiota changes in HUA rats. To analyze the potential role played by gut microbiota in HUA, we altered the gut microbiota of HUA rats with antibiotics, and compared the degree of uric acid elevation between HUA and antibiotic-fed HUA rats (Ab+HUA). Finally, we established a recipient rat model, in which we transplanted fecal microbiota of HUA and normal rats into recipient rats. Three weeks later, we compared the uric acid content of recipient rats. As a result, the diversity and abundance of the gut microbiota had changed in HUA rats. The Ab-fed HUA rats had significantly lower uric acid content compared to the HUA rats, and gut microbiota from HUA rats increased uric acid content of recipient rats. The genera Vallitalea, Christensenella and Insolitispirillum may associate with HUA. Our findings highlight the association between gut microbiota and HUA, and the potential role played by gut microbiota in HUA. We hope that this finding will promote the isolation and culture of HUA-related bacteria and orient HUA-related studies from being correlational to mechanistic. These steps will therefore make it possible for us to treat HUA using gut microbiota as the target.

This paper is concerned with remote state estimation problem with bandwidth and energy constrained wireless sensor networks(WSNs). To improve the estimation quality under these constrains in addressed system, measurement quantization and event-triggered communication strategies are adopted in WSN. Specifically, quantization strategy and event-triggering mechanism are introduced to describe the set region of original measurements, and a closest ellipsoid approximation of measurement sets method is presented. Subsequently, set-valued Kalman filter based on quantization and event is designed by utilizing the quantizer and trigger information. Finally, an illustrative example is employed to demonstrate the advantages and effectiveness of the proposed methods.

A filter based on characteristic functions is developed in this paper, to fit to a class of non-Gaussian dynamical systems, which state models and measurement models are all nonlinear and multi-dimensional. The new filter overcomes limitations and expands the application of this kind of filter, which is proved to just fit to one special kind of systems with multi-dimensional linear state models and one-dimensional nonlinear measurement models. Firstly, the filter using characteristic function is introduced and its limitation is analysed. Then, we design the new filter to fit to nonlinear states and multi-dimensional measurements. Thirdly, the matrix format of performance index is presented to match to the new filter gain, and the weighting function vector is given to ensure the uniform boundedness of such a performance index. Finally, the new filter gain can be obtained by minimizing this performance index, and the process of filtering design is accomplished. Simulation examples are given to illustrate the effectiveness of the proposed filter design scheme.

This paper designs a novel filter based on characteristic function for multidimensional observation systems, essentially extending the proposed filter, which just fitted to one-dimensional observations. For the dynamic model from grinding process cylindrical workpieces, this filter could result in enhanced and incremental productivity and quality control in manufacturing processes. In the processing of the filter design, a new form of filter will be given to adapt to the multidimensional observations, the matrix format of performance index will be designed to fit to matrix format of filter gain, the selecting range of the weighting function vector will be given to ensure the uniform boundedness of the designed performance index, and the filter gain can be obtained by minimizing the performance index. Finally, we illustrate the effectiveness of the proposed method by simulation examples in the field of the target tracking and the grinding process cylindrical workpieces.

Neural network is an important tool to solve the problem of nonlinear system prediction and control. It has been widely concerned by scholars. However, the existing neural network cannot adaptively allocate the weight of mixed kernel function according to the sample characteristics when it is applied to electric load forecasting. Aiming at this problem, short-term load forecasting algorithm based on adaptive fusion of mixed kernel function is proposed. Firstly, kernel functions are selected from the standard local kernel function and the global kernel function library to form a mixed kernel function. The weight variables and parameters of the kernel function are combined to form a new parameter state vector. Then a nonlinear parameter estimation model is established. Based on this model, the high-order cubature Kalman filter is used to estimate the parameter state, so that the local kernel function and the global kernel function can be adaptively fused. Moreover, the trained neural network is used to predict the load. Finally, the experimental analysis is given based on the actual grid data, and the effectiveness of the adaptive fusion of mixed function algorithm is proved.

Hyperuricemia is associated with many metabolic diseases. However, the underlying mechanism remains unknown. The gut microbiota has been demonstrated to play significant roles in the immunity and metabolism of the host. In the present study, we constructed a hyperuricemic mouse model to investigate whether the metabolic disorder caused by hyperuricemia is related to intestinal dysbiosis. A significantly increased intestinal permeability was detected in hyperuricemic mice. The difference in microflora between wild-type and hyperuricemic mice accompanies the translocation of gut microbiota to the extraintestinal tissues. Such a process is followed by an increase in innate immune system activation. We observed increased LPS and TNF-α levels in the hyperuricemic mice, indicating that hyperuricemic mice were in a state of low-grade systemic inflammation. In addition, hyperuricemic mice presented early injury of parenteral tissue and disordered lipid metabolism. These findings suggest that intestinal dysbiosis due to an impaired intestinal barrier may be the key cause of metabolic disorders in hyperuricemic mice. Our findings should aid in paving a new way of preventing and treating hyperuricemia and its complications. NEW & NOTEWORTHY Hyperuricemia is associated with many metabolic diseases. However, the underlying mechanism remains unknown. We constructed a hyperuricemic mouse model to explore the relationship between intestinal dysbiosis and metabolic disorder caused by hyperuricemia.