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Introduction: Gliadins are the major components of gluten proteins with vital roles on properties of end-use wheat product and health-relate quality of wheat. However, the function and regulation mechanisms of γ-gliadin genes remain unclear. Objectives: Dissect the effect of DNA methylation in the promoter of γ-gliadin gene on its expression level and gluten strength of wheat. Methods: The prokaryotic expression and reduction–oxidation reactions were performed to identify the effect of TaGli-γ-2.1 on dough strength. Bisulfite analysis and 5-Aza-2′-deoxycytidine treatment were used to verify the regulation of TaGli-γ-2.1 expression by pTaGli-γ-2.1 methylation. The content of gluten proteins composition was measured by RP-HPLC, and the gluten strength was measured by Gluten Index and Farinograph. Results: TaGli-γ-2.1 was classified into a subgroup of γ-gliadin multigene family and was preferentially expressed in the later period of grain filling. Addition of TaGli-γ-2.1 protein fragment into strong gluten wheat flour significantly decreased the stability time. Hypermethylation of three CG loci of pTaGli-γ-2.1 conferred to lower TaGli-γ-2.1 expression. Treatment with 5-Aza-2′-deoxycytidine in seeds of strong gluten wheat varieties increased the expression levels of TaGli-γ-2.1. Furthermore, the accumulations of gliadin and γ-gliadin were significantly decreased in hypermethylated wheat varieties, corresponding with the increasing of gluten index and dough stability time. Conclusion: Epigenetic modification of pTaGli-γ-2.1 affected gluten strength by modulating the proportion of gluten proteins. Hypermethylation of pTaGli-γ-2.1 is a novel genetic resource for enhancing gluten strength in wheat quality breeding.

Primary angle-closure glaucoma(PACG)is an irreversible disease-causing blindness, the damage of optic nerve is caused by elevated intraocular pressure(IOP)as a result of angle-closure. Angle-closure is a fundamental pathologic process in PACG. In addition, PACG is characterized by elevated IOP as a result of mechanical obstruction of the trabecular meshwork by either apposition of the peripheral iris to the trabecular meshwork or by a synechial closed angle. In recent years, with the development of ophthalmic imaging technology, the iris has been recognized as necessary to complement anatomical risk factors in assessing the risk of PACG. In this review, we intend to describe the potential role of the iris in the pathogenesis of PACG, so as to provide new ideas and directions for prevention and treatment of such disease.

ABSTRACT Chromosome evolution drives species evolution, speciation, and adaptive radiation. Accurate genome assembly is crucial to understanding chromosome evolution of species, such as dikaryotic fungi. Rust fungi (Pucciniales) in dikaryons represent the largest group of plant pathogens, but the evolutionary process of adaptive radiation in Pucciniales remains poorly understood. Here, we report a gapless genome for the wheat leaf rust fungus Puccinia triticina determined using PacBio high-fidelity (HiFi) sequencing. This gapless assembly contains two sets of chromosomes, showing that one contig represents one chromosome. Comparisons of homologous chromosomes between the phased haplotypes revealed that highly frequent small-scale sequence divergence shapes haplotypic variation. Genome analyses of Puccinia triticina along with other rusts revealed that recent transposable element bursts and extensive segmental gene duplications synergistically highlight the evolution of chromosome structures. Comparative analysis of chromosomes indicated that frequent chromosomal rearrangements may act as a major contributor to rapid radiation of Pucciniales. This study presents the first gapless, phased assembly for a dikaryotic rust fungus and provides insights into adaptive evolution and species radiation in Pucciniales. IMPORTANCE Rust fungi (Pucciniales) are the largest group of plant pathogens. Adaptive radiation is a predominant feature in Pucciniales evolution. Chromosome evolution plays an important role in adaptive evolution. Accurate chromosome-scale assembly is required to understand the role of chromosome evolution in Pucciniales. We took advantage of HiFi sequencing to construct a gapless, phased genome for Puccinia triticina. Further analyses revealed that the evolution of chromosome structures in rust lineage is shaped by the combination of transposable element bursts and segmental gene duplications. Chromosome comparisons of Puccinia triticina and other rusts suggested that frequent chromosomal arrangements may make remarkable contributions to high species diversity of rust fungi. Our results present the first gapless genome for Pucciniales and shed light on the feature of chromosome evolution in Pucciniales.

This paper reports a numerical research on MEMS (microelectromechanical system) micronozzles through multiphysics coupling simulation along with design optimization based on simulation results. The micronozzle, which is a core component of the electrothermal microthruster, features a micron-scale geometry, a 2-dimensional (2D) Laval configuration, a rectangular cross section, and a highly thermal conductive silicon wall due to MEMS fabrication. As a result, viscous loss in the flow field and heat transfer to the nozzle wall can strongly influence nozzle performance, namely, thrust force and specific impulse. To accurately understand the flow field inside the micronozzle and how the highly thermal conductive silicon wall interacts with gas flow, a numerical simulation that couples fluid dynamics field and solid heat transfer field is employed in the research. The influence of different structural parameters on micronozzle performance is then investigated to set a basis for design optimization. The optimum design of the linear expander micronozzle is obtained through constrained optimization by linear approximation. To further improve micronozzle performance, the bell-shaped expander is adapted. The optimization result shows that the bell-shaped expander is not suitable for micronozzle featuring 2D Laval configuration, and the reason behind the phenomenon is thoroughly discussed.

Normal microsporogenesis is determined by both nuclear and mitochondrial genes. In maize C-type cytoplasmic male sterility, it is unclear how the development of meiocytes and microspores is affected by the mitochondrial sterility gene and the nuclear restorer gene. In this study, we sequenced the transcriptomes of single meiocytes (tetrad stage) and early mononucleate microspores from sterile and restorer lines. The numbers of expressed genes varied in individual cells and fewer than half of the expressed genes were common to the same cell types. Four comparisons revealed 3379 differentially expressed genes (DEGs), with 277 putatively associated with mitochondria, 226 encoding transcription factors, and 467 possibly targeted by RF4. KEGG analysis indicated that the DEGs in the two lines at the tetrad stage were involved predominantly in carbon metabolism and in amino acid biosynthesis and metabolism, whereas the DEGs during the transition from the tetrad stage to the early mononucleate stage were associated mostly with regulation of protein metabolism, fatty acid metabolism, and anatomical structure morphogenesis. Thus, meiocyte and microspore development was affected by the surrounding cells and the restorer gene, and the restorer gene helped restore the redox homeostasis of microspores and the normal cellular reconstruction during the transition.

Abstract Background Esterase D (ESD) is a nonspecific esterase that detoxifies formaldehyde. Many reports have stated that ESD activity is associated with a variety of physiological and pathological processes. However, the detailed signaling pathway of ESD remains poorly understood. Methods Considering the advantages of the small chemical molecule, our recent work demonstrated that 4-chloro-2-(5-phenyl-1-(pyridin-2-yl)-4,5-dihydro-1H-pyrazol-3-yl) phenol (FPD5) activates ESD, and will be a good tool for studying ESD further. Firstly, we determined the interaction between ESD and FK506 binding protein 25 (FKBP25) by yeast two-hybrid assay and co-immunoprecipitation (CO-IP) and analyzed the phosphorylation levels of mTORC1, P70S6K and 4EBP1 by western blot. Furthermore, we used the sulforhodamine B (SRB) and chick chorioallantoic membrane (CAM) assay to analyze cell viability in vitro and in vivo after treatment with ESD activator FPD5. Results We screened FKBP25 as a candidate protein to interact with ESD by yeast two-hybrid assay. Then we verified the interaction between ESD and endogenous FKBP25 or ectopically expressed GFP-FKBP25 by CO-IP. Moreover, the N-terminus (1–90 aa) domain of FKBP25 served as the crucial element for their interaction. More importantly, ESD reduced the K48-linked poly-ubiquitin chains of FKBP25 and thus stabilized cytoplasmic FKBP25. ESD also promoted FKBP25 to bind more mTORC1, suppressing the activity of mTORC1. In addition, ESD suppressed tumor cell growth in vitro and in vivo through autophagy. Conclusions These findings provide novel evidence for elucidating the molecular mechanism of ESD and ubiquitination of FKBP25 to regulate autophagy and cancer cell growth. The ESD/FKBP25/mTORC1 signaling pathway is involved in inhibiting tumor cell growth via regulating autophagy.

IntroductionTo investigate whether rescue in vitro maturation (R-IVM) improves the reproductive outcomes among women undergoing intracytoplasmic sperm injection (ICSI) after one oocyte retrieved cycle.MethodsBetween January 2019 and December 2020, 2602 women who underwent ICSI in the Reproductive Medicine Center of Tongji Hospital, Wuhan, China, were included in our retrospective cohort study. There were 2112 women undergoing only ICSI and 490 women with R-IVM followed by ICSI. The intermediate reproductive outcomes and pregnancy outcomes were assessed, including the number of normally fertilized embryos, number of cleaved embryos, number of good-quality embryos, number of day-3 available embryos, number of embryos cultured past day-3, number of blastocysts, number of available blastocysts, biochemical pregnancy, miscarriage, clinical pregnancy and live birth. The perinatal outcomes were also assessed, including preterm birth and birth weight. The abovementioned outcomes were also calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group.Result(s)Compared with the women who underwent only ICSI, those who underwent ICSI with R-IVM had higher numbers of MII oocytes, normally fertilized embryos, cleaved embryos, day-3 available embryos, embryos cultured past day-3, and higher oocyte maturation rate, available embryo rate than women undergoing only ICSI. Additionally, we found that women undergoing ICSI with R-IVM had an increased chance of clinical pregnancy (adjusted OR=1.50, 95% CI: 1.17–1.93) and cumulative live birth (adjusted OR=1.35, 95% CI: 1.07–1.71). After propensity score matching (PSM), the cumulative live birth rate was 60.1% for women undergoing ICSI with R-IVM versus 54.9% for women undergoing only ICSI (OR=1.24, 95% CI: 0.94–1.63). The reproductive outcomes were also significantly different when calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. All live births from R-IVM embryos were healthy and without malformations or complications.ConclusionR-IVM may improve the reproductive outcomes of women undergoing ICSI. It may also provide a reference for the safety of R-IVM. This study maybe support a routine application of R-IVM among patients who intend to undergo ICSI.

Summary As global warming intensifies, emerging evidence has demonstrated high ambient temperature during pregnancy negatively affects maternal physiology with compromised pregnant outcomes; however, little is known about the roles of gut microbiota and its underlying mechanisms in this process. Here, for the first time, we explored the potential mechanisms of gut microbiota involved in the disrupted glycolipid metabolism via hepatic mitochondrial function. Our results indicate heat stress (HS) reduces fat and protein contents and serum levels of insulin and triglyceride (TG), while increases that of non‐esterified fatty acid (NEFA), β‐hydroxybutyric acid (B‐HBA), creatinine and blood urea nitrogen (BUN) (P

Ischemia/reperfusion (I/R) injury is a common pathological mechanism involved in many ocular diseases. I/R is characterized by microvascular dysfunction and neurodegeneration. However, the mechanisms of neurodegeneration induced by I/R remain largely unknown. This study showed that the expression of long non-coding RNA-CRNDE was significantly upregulated after retinal ischemia-reperfusion (RIR). LncRNA-CRNDE knockdown alleviated retinal neurodegeneration induced by RIR injury, as shown by decreased reactive gliosis and reduced retinal cells loss. Furthermore, lncRNA-CRNDE knockdown directly regulated Müller cell function and indirectly affected RGC function in vitro. In addition, lncRNA-CRNDE knockdown led to a significant reduction in the release of several cytokines after RIR. This study suggests that lncRNA-CRNDE is a promising therapeutic target for RIR.

Highly robust networks can resist attacks, as when some UAVs fail, the remaining UAVs can still transmit data to each other. In order to improve the robustness of a multi-UAV network, most methods construct the network by adjusting the positions of the UAVs and adding a large number of links. However, having a large number of links greatly consumes communication resources and increases serious signal interference. Therefore, it is necessary to study a method that can improve robustness and reduce the number of links. In this paper, we propose a method that consists of combining formation control and link selection, which can work in a distributed manner. For formation control, our method keeps the UAVs compact in the obstacle environment through an improved artificial potential field. The compact formation enables UAVs to have a large number of neighbors. For link selection, reinforcement learning is used to improve the robustness of the network and reduce the number of network edges. In the simulation of the 3D urban environment, three failure modes are used to verify the robustness of the network. The experimental results show that even if the number of links is reduced by 20%, the networks designed by our method still have strong robustness.

The light environment regulates animal physiology and behaviour. As widely used supplementary heat sources in creep areas, the effect of visible light radiated by infrared heat lamps on pigs is worth investigating. To investigate the effects of light from heat lamps on the behaviour of sows and piglets and possible endocrine mechanisms, 24 primiparous sows were randomly assigned to three supplementary heat source treatments: (1) 250 W non-luminous ceramic heat lamps (CE, n = 8), (2) 175 W red heat lamps (RL, n = 8), and (3) 175 W transparent heat lamps (TL, n = 8). All heat lamps were turned off on Day 15 postpartum. Piglets were weighed on days 3 and 21 postpartum. The number and duration of suckling within 24 h were analysed via video recordings on days 4, 8, and 16 postpartum. Sow posture changes during the day and night were detected using the YOLOv4 target detection network model. One marked piglet from six litters randomly selected from each treatment was used for saliva collection. Saliva samples were collected at 0800, 1400, 2000, and 0200 (+1 d) on days 10 and 20 postpartum. The results showed that the mean postural change frequency of TL sows was higher than that of CE sows (P

Efficient exploration is a critical issue in swarm UAVs with substantial research interest due to its applications in search and rescue missions. In this study, we propose a cooperative exploration approach that uses multiple unmanned aerial vehicles (UAVs). Our approach allows UAVs to explore separate areas dynamically, resulting in increased efficiency and decreased redundancy. We use a novel dynamic centroid-based method to partition the 3D working area for each UAV, with each UAV generating new targets in its partitioned area only using the onboard computational resource. To ensure the cooperation and exploration of the unknown, we use a next-best-view (NBV) method based on rapidly-exploring random tree (RRT), which generates a tree in the partitioned area until a threshold is reached. We compare this approach with three classical methods using Gazebo simulation, including a Voronoi-based area partition method, a coordination method for reducing scanning repetition between UAVs, and a greedy method that works according to its exploration planner without any interaction. We also conduct practical experiments to verify the effectiveness of our proposed method.

Objective Vanin1 (VNN1) is a pantetheinase that can catalyze the hydrolysis of pantetheine to produce pantothenic acid and cysteamine. Our previous studies showed that VNN1 is specifically expressed in chicken liver. In this study, we aimed to investigate the roles of peroxisome proliferators activated receptor α (PPARα) and miRNA-181a-5p in regulating VNN1 gene expression in chicken liver. Methods 5′-RACE was performed to identify the transcription start site of chicken VNN1. JASPAR and TFSEARCH were used to analyze the potential transcription factor binding sites in the promoter region of chicken VNN1 and miRanda was used to search miRNA binding sites in 3′ untranslated region (3′UTR) of chicken VNN1. We used a knock-down strategy to manipulate PPARα (or miRNA-181a-5p) expression levels in vitro to further investigate its effect on VNN1 gene transcription. Luciferase reporter assays were used to explore the specific regions of VNN1 targeted by PPARα and miRNA-181a-5p. Results Sequence analysis of the VNN1 promoter region revealed several transcription factor-binding sites, including hepatocyte nuclear factor 1α (HNF1α), PPARα, and CCAAT/enhancer binding protein α. GW7647 (a specific agonist of PPARα) increased the expression level of VNN1 mRNA in chicken primary hepatocytes, whereas knockdown of PPARα with siRNA increased VNN1 mRNA expression. Moreover, the predicted PPARα-binding site was confirmed to be necessary for PPARα regulation of VNN1 gene expression. In addition, the VNN1 3′UTR contains a sequence that is completely complementary to nucleotides 1 to 7 of miRNA-181a-5p. Overexpression of miR-181a-5p significantly decreased the expression level of VNN1 mRNA. Conclusion This study demonstrates that PPARα is an important transcriptional activator of VNN1 gene expression and that miRNA-181a-5p acts as a negative regulator of VNN1 expression in chicken hepatocytes.

BackgroundWhile chimeric antigen receptor (CAR)-T cell therapy is becoming widely used in hematological malignancies with remarkable remission rate, their high recurrence remains an obstacle to overcome. The role of consolidative transplantation following CAR-T cell-mediated remission remains controversial. We conducted a retrospective study to explore whether bridging to unrelated cord blood transplantation (UCBT) could improve the prognosis of patients entering remission after CAR-T therapy with different characteristics through subgroup analyses.MethodsWe reviewed 53 patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) successfully infused with CD19 CAR-T cells and achieved complete remission (CR). In this study, 25 patients received consolidative UCBT (UCBT group) and 28 patients did not accept any intervention until relapse (non-UCBT group). Subgroup analysis on prognosis was then performed according to gender, age, number of previous relapses, tumor burden, presence of poor prognostic markers, and structure of CAR.ResultsCompared with the non-UCBT group, patients who underwent consolidative UCBT had better median event-free survival (EFS; 12.3 months vs. 6.2 months; P = 0.035) and relapse-free survival (RFS; 22.3 months vs. 7.2 months; P = 0.046), while no significant difference was found in overall survival (OS; 30.8 months vs. 15.3 months; P = 0.118). Subsequent multivariate analysis revealed that bridging to UCBT was a protective factor for RFS (P = 0.048) but had no significant effect on EFS (P = 0.205) or OS (P = 0.541). In the subgroup analysis, UCBT has an added benefit in patients with specific characteristics. Patients who experienced ≥2 relapses or with sustained non-remission (NR) showed better RFS (P = 0.025) after UCBT. Better EFS was seen in patients with poor prognostic markers (P = 0.027). In the subgroup with pre-infusion minimal residual disease (MRD) ≥5% or with extramedullary disease (EMD), UCBT significantly prolonged EFS (P = 0.009), RFS (P = 0.017), and OS (P = 0.026). Patients with occurrence of acute graft-versus-host disease (aGVHD) appeared to have a longer duration of remission (P = 0.007).ConclusionConsolidative UCBT can, to some extent, improve clinical outcomes of patients with R/R B-ALL entering remission following CD19 CAR-T therapy, especially in patients with more recurrences before treatment, patients with poor prognostic markers, and patients with a higher tumor burden. The occurrence of aGVHD after UCBT was associated with better RFS.

The placenta is critical for the regulation of fetal innate immune function. Maternal heat stress (HS) impairs the immune function and the intestinal barrier in the offspring. However, the effects of maternal HS on the placental immune response and the development of the fetal intestine and its innate immune system remain unclear. Fetal mice were divided into the utero control (IUTN) and heat stress (IUHS) groups according to the maternal ambient temperature. Transcriptome analysis revealed that the expressions of placental immune response–related genes such as macrophage antigen CD68 and Fc gamma receptors 1 and 3 (fcgγ1 and fcgγ3) were increased, but the mRNA expression and protein levels of colony-stimulating factor-1 (Csf1) were decreased in the HS group compared with the TN group (p < 0.05). Furthermore, there was no significant difference in the intestinal length normalized to pup weight between the IUTN and IUHS groups. The expression of genes (such as alpi and ttr) involved in fetal duodenum and jejunum development was downregulated by maternal HS, whereas the expression of genes enriched in the cell cycle was increased. The mRNA expression and protein levels of cell division cycle 6 (Cdc6) in the fetal duodenum and jejunum were much higher in the IUHS group than in the IUTN group (p < 0.05). Maternal HS also down-regulated the expression of genes enriched in the innate immune system in the fetal duodenum and jejunum. The mRNA expression and protein levels of interleukin 1 alpha (IL1a) were reduced in the IUHS group compared with the IUTN group (p < 0.05). Taken together, these data demonstrated that maternal HS modulated the expression of genes in the placenta related to the immune response and inhibited the development of the fetal intestine and its innate immune system.

Summary: Background: Diabetic retinopathy (DR) is a leading cause of blindness in the working-age population, which is characterized by retinal neurodegeneration and vascular dysfunction. Long non-coding RNAs (LncRNAs) have emerged as critical regulators in several biological processes and disease progression. Here we investigated the role of lncRNA AQP4-AS1 in retinal neurovascular dysfunction induced by diabetes. Methods: Quantitative RT-PCR was used to detect the AQP4-AS1 expression pattern upon diabetes mellitus-related stresses. Visual electrophysiology examination, TUNEL staining, Evans blue staining, retinal trypsin digestion and immunofluorescent staining were conducted to detect the role of AQP4-AS1 in retinal neurovascular dysfunction in vivo. MTT assays, TUNEL staining, PI/Calcein-AM staining, EdU incorporation assay transwell assay and tube formation were conducted to detect the role of AQP4-AS1 in retinal cells function in vitro. qRT-PCR, western blot and in vivo studies were conducted to reveal the mechanism of AQP4-AS1-mediated retinal neurovascular dysfunction. Findings: AQP4-AS1 was significantly increased in the clinical samples of diabetic retinopathy patients, high glucose-treated Müller cells, and diabetic retinas of a murine model. AQP4-AS1 silencing in vivo alleviated retinal neurodegeneration and vascular dysfunction as shown by improved retinal capillary degeneration, decreased reactive gliosis, and reduced RGC loss. AQP4-AS1 directly regulated Müller cell function and indirectly affected endothelial cell and RGC function in vitro. Mechanistically, AQP4-AS1 regulated retinal neurovascular dysfunction through affecting AQP4 levels. Interpretation: This study reveals AQP4-AS1 is involved in retinal neurovascular dysfunction and expected to become a promising target for the treatment of neurovascular dysfunction in DR. Funding: This work was generously supported by the grants from the National Natural Science Foundation of China (Grant No. 81800858, 82070983, 81870679 and 81970823), grants from the Medical Science and Technology Development Project Fund of Nanjing (Grant No ZKX17053 and YKK19158), grants from Innovation Team Project Fund of Jiangsu Province (No. CXTDB2017010), and the Science and Technology Development Plan Project Fund of Nanjing (Grant No 201716007, 201805007 and 201803058).

Gliadin is a group of grain storage proteins that confers extensibility/viscosity to the dough and are vital to end-use quality in wheat. Moreover, gliadins are one of the important components for nutritional quality because they contain the nutritional unprofitable epitopes that cause chronic immune-mediated intestinal disorder in genetically susceptible individuals designated celiac disease (CD). The main genetic loci encoding the gliadins were revealed by previous studies; however, the genes related to the content of gliadins and their fractions were less elucidated. To illustrate the genetic basis of the content of gliadins and their fractions comprehensively, a recombinant inbred line (RIL) population that consisted of 196 lines was constructed from the two parents, Luozhen No.1 and Zhengyumai 9987. Quantitative trait loci (QTL) controlling the content of total gliadins and their fractions (ω-, α-, and γ-gliadin) were screened genome-widely under four environments across 2 years. Totally, thirty QTL which explained 1.97–12.83% of the phenotypic variation were detected to be distributed on 17 chromosomes and they were gathered into 12 clusters. One hundred and one pairs of epistatic QTL (E-QTL) were revealed, among which five were involved with the total gliadins and its fractions content QTL located on chromosome 1AS, 1DS, 4DS, 1DL, and 6AS. Three Kompetitive Allele-Specific PCR (KASP) markers were developed from three major QTL clusters located on chromosomes 6A, 6D, and 7D, respectively. The present research not only dissects the genetic loci for improving the content of gliadins and their three fractions, but may also contribute to marker-assisted selection of varieties with appropriate gliadin fractions content for end-use quality and health benefit at the early developmental stages and early breeding generations.

Abstract In the present study, the complete mitogenome of Clavaria fumosa, was sequenced, assembled, and compared. The complete mitogenome of C. fumosa is 256,807 bp in length and is the largest mitogenomes among all Basidiomycota mitogenomes reported. Comparative mitogenomic analysis indicated that the C. fumosa mitogenome contained the most introns and intronic ORFs among all fungal mitogenomes. Large intergenic regions, intronic regions, accumulation of repeat sequences and plasmid-derived genes together promoted the size expansion of the C. fumosa mitogenome. In addition, the rps3 gene was found subjected to positive selection between some Agaricales species. We found frequent intron gain/loss events in Agaricales mitogenomes, and four novel intron classes were detected in the C. fumosa mitogenome. Large-scale gene rearrangements were found occurred in Agaricales species and the C. fumosa mitogenome had a unique gene arrangement which differed from other Agaricales species. Phylogenetic analysis for 76 Basidiomycetes based on combined mitochondrial gene sets indicated that mitochondrial genes could be used as effective molecular markers for reconstructing evolution of Basidiomycota. The study served as the first report on the mitogenomes of the family Clavariaceae, which will promote the understanding of the genetics, evolution and taxonomy of C. fumosa and related species.

Fusarium ear rot (FER) caused by Fusarium verticillioides is one of the most common diseases affecting maize production worldwide. FER results in severe yield losses and grain contamination with health-threatening mycotoxins. Although most studies to date have focused on comprehensive analysis of gene regulation in maize during defense responses against F. verticillioides infection, less is known about the role of microRNAs (miRNAs) in this process. We used deep sequencing to compare small RNA libraries from the maize kernels of susceptible (N6) or resistant (BT-1) inbred lines from uninfected plants and upon F. verticillioides infection. We found that pathogen exposure was accompanied by dynamic alterations in expression levels of multiple miRNAs, including new members of previously annotated miRNA families. A combination of transcriptomic, degradomic, and bioinformatics analyses revealed that F. verticillioides-responsive miRNAs and their potential target genes displayed opposite expression patterns in the susceptible and resistant genotypes. Functional category analysis uncovered preferential enrichment of the pathogen-responsive miRNAs and their targets in the phenylpropanoid metabolic processes, plant–pathogen interactions, and plant phytohormone signal transduction pathways. Furthermore, transgenic maize plants overexpressing miR408b exhibited reduced resistance to F. verticillioides infection in a susceptible maize line. These findings provide new insights into the regulatory roles of miRNAs in maize immunity against FER and new resources for breeding disease resistance into maize.

Abstract Background Next generation sequencing (NGS) has been widely used in biological research, due to its rapid decrease in cost and increasing ability to generate data. However, while the sequence generation step has seen many improvements over time, the library preparation step has not, resulting in low-efficiency library preparation methods, especially for the most time-consuming and labor-intensive steps: size-selection and quantification. Consequently, there can be bottlenecks in projects with large sample cohorts. Results We have described the all-in-one sequencing (AIO-seq) method, where instead of performing size-selection and quantification for samples individually, one sample one tube, up to 116 samples are pooled and analyzed in a single tube, ‘All-In-One’. The AIO-seq method pools libraries based on the samples’ expected data yields and the calculated concentrations of the size selected regions (target region), which can easily be obtained with the Agilent 2100 Bioanalyzer and Qubit Fluorometer. AIO-seq was applied to whole genome sequencing and RNA-seq libraries successfully, and it is envisaged that it could be applied to any type of NGS library, such as chromatin immunoprecipitation coupled with massively parallel sequencing, assays for transposase-accessible chromatin with high-throughput sequencing, and high-throughput chromosome conformation capture. We also demonstrated that for genetic population samples with low coverage sequences, like recombinant inbred lines (RIL), AIO-seq could be further simplified, by mixing the libraries immediately after PCR, without calculating the target region concentrations. Conclusions The AIO-seq method is thus labor saving and cost effective, and suitable for projects with large sample cohorts, like those used in plant breeding or population genetics research.

The coastal retreat is one of the most common problems taking place at littoral zones, and it will only become an issue if the area is overwhelmed with commercial developments and anthropogenic activities. The coastal erosion experienced by the shoreline of Teluk Nipah, which is located at the west of Pangkor Island in Malaysia, has triggered some levels of attention among the local authorities and community. The root cause of the erosion and shoreline retreat rates remain uncertain, is due to the unavailability of records studies on beach morphodynamics in the past. Hence, this study aims to assess the decadal shoreline changes of Teluk Nipah by using remote sensing technology. Landsat satellite imageries, which ranges from 1990 to 2018, have been acquired for quantification of the shoreline change rate at Teluk Nipah using a GIS software - ArcGIS. The analysis results indicated that the shoreline is dynamic and unstable between the 1990s to 2010s. The most populated area of the shoreline experienced critical erosion that requires immediate attention by the stakeholders.

We previously conducted a QTL analysis of small RNA (sRNA) abundance in flag leaves of an immortalized rice F2 (IMF2) population by aligning sRNA reads to the reference genome to quantify the expression levels of sRNAs. However, this approach missed about half of the sRNAs as only 50% of all sRNA reads could be uniquely aligned to the reference genome. Here, we quantified the expression levels of sRNAs and sRNA clusters without the use of a reference genome. QTL analysis of the expression levels of sRNAs and sRNA clusters confirmed the feasibility of this approach. sRNAs and sRNA clusters with identified QTLs were then aligned to the high-quality parental genomes of the IMF2 population to resolve the identified QTLs into local vs. distant regulation mode. We were able to detect new QTL hotspots by considering sRNAs aligned to multiple positions of the parental genomes and sRNAs unaligned to the parental genomes. We found that several local-QTL hotspots were caused by sequence variations in long inverted repeats, which probably function as precursors of sRNAs, between the two parental genomes. The expression levels of these sRNAs were significantly associated with the presence/absence of the long inverted repeats in the IMF2 population. Moreover, we found that the variations in whole-genome sRNA species composition among different IMF2s were attributed to sRNA biogenesis genes including OsDCL2b and OsRDR2. Our results highlight that genetic dissection of sRNA expression is a promising approach to disclose new components functioning in sRNA biogenesis and new mechanisms of sRNA biogenesis.

The lightning research group of the Chinese Academy of Meteorological Sciences has carried out observations and experiments with artificially triggered lightning for more than ten years, and it accumulated thousands of examples of channel base current data on the return stroke of artificially triggered lightning prior to 2020. Based on the current data, this paper explores ways of improving the constructed function of a long time-series (400 μs) return stroke and the parametric reconstruction of the current waveform. The long time-series current can be divided into three components: the breakdown pulse current, corona current and quasi-uniform current. The corona current and quasi-uniform current are constructed by a Heidler function, while the breakdown pulse current is determined by the waveform characteristics of the current peak, which can be divided into the Heidler type and high-order exponential type. According to the three-component model of the return-stroke current, a two-step parametric reconstruction method for the long time-series lightning return-stroke current based on the particle swarm optimization (PSO) algorithm is proposed. In this paper, the results of the parameterized reconstruction of 14 return strokes are given, and the results of the multidimensional error analysis of 13 long time-series return strokes are given to illustrate the accuracy of the improved parameterized model of the return-stroke current and the effectiveness of the two-step reconstruction method based on the PSO algorithm.

Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells from UCB are naïve T cells, which have not yet been exposed to antigens and therefore do not contain T cells with specific immune functions against viruses. Cytomegalovirus (CMV) infections occur in more than 80% of patients after UCBT compared to other types of transplantation. Anti-CMV medications are currently restricted, with ganciclovir, foscarnet, and valganciclovir being the most common in China; however, with limited efficacy and considerable side effects, all these drugs are susceptible to viral resistance. In recent years, cytomegalovirus-specific T cells (CMVST) have advanced the treatment of viral infections in immunodeficient patients. CMVST usually uses the same donor as hematopoietic stem cell transplantation. CMVST should be administered to UCBT patients because of the absence of donors after UCBT. In China, there is no report on the use of CMVST to treat CMV infection after UCBT, and foreign reports are also limited. This paper reported a 20-year-old male patient with acute myeloid leukemia who developed cytomegalovirus retinitis (CMVR) after umbilical cord blood transplantation. After ineffective viral treatment, he was treated with a third-party donor CMVST and was successfully transformed into CMV nucleic acid negative.

In the satellite overall design phase, it is a crucial step to perform satellite layout design to guarantee that the aggregation of electronic components can operate normally and stably in an appropriate temperature environment. In order to handle the satellite payload placement problem of the DongFangHong 4 (DFH-4) platform, the heat pipe-constrained component layout optimization (HCLO) problem is proposed with the HCLO model formulated. Through careful investigation, it can be divided into two optimization subproblems that can be solved subsequently. Based on the divide-and-conquer strategy, an integer linear programming- (ILP-) assisted two-stage layout optimization method is proposed. In stage one, component-heat pipe distribution optimization is performed using the ILP technique so that specific heat pipes occupied by each component can be determined and the horizontal movement range of components can be reduced. In stage two, the detailed component layout optimization is investigated to obtain the final positions of components. First, the sequence layout sampling (SeqLS) method is used to generate one nonoverlap initial layout. Next, swap operation between components is incorporated to reduce the centroid deviation. Finally, sequential quadratic programming (SQP) search is conducted based on the generated promising initial layout solutions. Therefore, the SeqLS-based heuristic layout search algorithm is proposed in the second stage. Two layout test cases, including 15 components and 90 components, respectively, are investigated to demonstrate the validity and efficacy of the proposed layout design method. Experimental results show that it is promising to apply such a two-stage approach for satellite payload placement in engineering.

Over nearly three rainy seasons of lightning activity in North China, numerical prediction experiments were carried out using the Weather Research and Forecasting model coupled with electrification and discharge schemes (WRF-Electric). The numerical forecast results were evaluated using the neighborhood-based equitable threat score (ETS) and fraction skill score (FSS) verification methods based on nationwide observational lightning data. An algorithm was used to generate the coverage of the total flash (intracloud and cloud-to-ground flashes) by fitting the cloud-to-ground flash data. The numerical results showed that the region of lightning activity could be well predicted by the mesoscale WRF-Electric model, particularly during a 6–12-hour forecasting period. The average ETS score of the 6–12-hour forecasting period was 0.34 for a 20 km neighborhood radius. The predictive skill of the model varied not only monthly but also diurnally. The model showed better forecasting skills during the main rainy season (June–July–August) and at 14 : 00–20 : 00 local time. The predictability of the model was enhanced with increasing thunderstorm scale. On the other hand, the coverage of predicted lightning activity was relatively concentrated, and the lightning flash density was higher than the observations. The main discrepancies in the model prediction were related to the design of the discharge parameterization. Thus, in discharge parameterization, the initial threshold for lightning should be modified according to the model resolution, while the magnitude of the neutralization charge in a single discharge should be referenced to the observational results.

Sow farrowing is an important part of pig breeding. The accurate and effective early warning of sow behaviors in farrowing helps breeders determine whether it is necessary to intervene with the farrowing process in a timely manner and is thus essential for increasing the survival rate of piglets and the profits of pig farms. For large pig farms, human resources and costs are important considerations in farrowing supervision. The existing method, which uses cloud computing-based deep learning to supervise sow farrowing, has a high equipment cost and requires uploading all data to a cloud data center, requiring a large network bandwidth. Thus, this paper proposes an approach for the early warning and supervision of farrowing behaviors based on the embedded artificial-intelligence computing platform (NVIDIA Jetson Nano). This lightweight deep learning method allows the rapid processing of sow farrowing video data at edge nodes, reducing the bandwidth requirement and ensuring data security in the network transmission. Experiments indicated that after the model was migrated to the Jetson Nano, its precision of sow postures and newborn piglets detection was 93.5%, with a recall rate of 92.2%, and the detection speed was increased by a factor larger than 8. The early warning of 18 approaching farrowing (5 h) sows were tested. The mean error of warning was 1.02 h.

High ambient temperature-induced heat stress (HS) during pregnancy may affect the placental function and fetal development. Late gestation is a critical period of the developing fetal brain and intestine. The study aimed to investigate the effects of HS during late pregnancy on the function of placenta, fetal brain and intestine in a mouse model. We found that the number of stillborn fetal mice were increased due to maternal HS. Transcriptome analysis revealed that the expression of genes enriched in nutrients transport and metabolism of HS group were up-regulated in the placenta, but down-regulated in the fetal duodenum and jejunum. Interestingly, the concentration of triglyceride (TG) in the HS group was raised in the placenta, but reduced both in the fetal duodenum and jejunum compared with the thermal-neutral (TN) group. Additionally, maternal HS also reduced total cholesterol (TC) contents in the fetal duodenum. The mRNA expression and protein levels of placental fatty acid binding protein 2 and 4 (fabp2 and fabp4) were not affected by maternal HS, but the mRNA expression and protein levels of cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase-2 (Dgat2) were decreased in the fetal intestine. Furthermore, maternal HS reduced the mRNA expression and protein levels of the placental 11beta-hydroxysteroid dehydrogenase type 2 (Hsd11b2) and 5-hydroxytryptamine receptor 1D (Htr1d). The concentrations of corticosterone and the expression of heat shock protein 90 beta family member 1 (hsp90b1), hypoxia up-regulated 1 (hyou1) and corticotropin releasing hormone receptor 1 (crhr1) enriched in response to glucocorticoids in the fetal brain were increased by maternal HS. Taken together, our findings demonstrated that maternal HS disrupted the placental glucocorticoid barrier and serotonin system associated with the raised corticosterone levels in the fetal brain, which might contribute to the decreased capacity of nutrients transport and metabolism in the fetal intestine.

Background: Oxidized low-density lipoprotein (oxLDL) induces vascular endothelial cell (VEC) injury and atherosclerosis through activating endoplasmic reticulum stress. Expression of glucose-regulated protein 94 (Grp94) is induced by endoplasmic reticulum stress and Grp94 is involved in cardiovascular diseases. This study aimed to determine the role of Grp94 in oxLDL-induced vascular endothelial cell injury and atherosclerosis.Methods and Results: An inhibitor of Grp94, HCP1, was used to investigate the role of Grp94 in oxLDL-induced VEC injury in human umbilical vein endothelial cells and atherosclerosis in apolipoprotein E−/− mice. Results showed that HCP1 inhibited autophagy and apoptosis induced by oxLDL in VECs. And we found that Grp94 might interact with adenosine monophosphate-activated protein kinase (AMPK) and activate its activity. HCP1 inhibited AMPK activity and overexpression of Grp94 blocked the effect of HCP1. Besides, HCP1 activated the activity of mechanistic target of rapamycin complex 1 (mTORC1), co-treatment with AMPK activator acadesine eliminated the effect of HCP1 on mTORC1 activity as well as autophagy. In apolipoprotein E−/− mice, HCP1 suppressed autophagy and apoptosis of atherosclerotic plaque endothelium. In addition, HCP1 increased the content of collagen, smooth muscle cells, and anti-inflammatory macrophages while reducing the activity of MMP-2/9 and pro-inflammatory macrophages in the atherosclerotic lesion.Conclusion: HCP1 inhibited oxLDL-induced VEC injury and promoted the stabilization of atherosclerotic plaque in apoE−/− mice. Grp94 might be a potential therapeutic target in the clinical treatment of atherosclerosis.

Traditional LiDAR odometry (LO) systems mainly leverage geometric information obtained from the traversed surroundings to register lazer scans and estimate LiDAR ego-motion, while they may be unreliable in dynamic or degraded environments. This paper proposes InTEn-LOAM, a low-drift and robust LiDAR odometry and mapping method that fully exploits implicit information of lazer sweeps (i.e., geometric, intensity and temporal characteristics). The specific content of this work includes method innovation and experimental verification. With respect to method innovation, we propose the cylindrical-image-based feature extraction scheme, which makes use of the characteristic of uniform spatial distribution of lazer points to boost the adaptive extraction of various types of features, i.e., ground, beam, facade and reflector. We propose a novel intensity-based point registration algorithm and incorporate it into the LiDAR odometry, enabling the LO system to jointly estimate the LiDAR ego-motion using both geometric and intensity feature points. To eliminate the interference of dynamic objects, we propose a temporal-based dynamic object removal approach to filter them out in the resulting points map. Moreover, the local map is organized and downsampled using a temporal-related voxel grid filter to maintain the similarity between the current scan and the static local map. With respect to experimental verification, extensive tests are conducted on both simulated and real-world datasets. The results show that the proposed method achieves similar or better accuracy with respect to the state-of-the-art in normal driving scenarios and outperforms geometric-based LO in unstructured environments.

Deoxynivalenol (DON) is a prevalent Fusarium mycotoxin, occurs predominantly in the global environment, especially in cereals, animal feed and food commodities. The widespread contamination causes a serious risk to human and animal health. DON usually impairs weight gain, which is presumably from its capacity to reduce feed intake by interfering with intestinal motility. To clarify the role of smooth muscle cells (SMCs) contractility in intestinal motility and growth inhibition caused by DON, twelve weaned piglets were firstly divided into two groups to feed control or Fusarium mycotoxin-contaminated (MC) diet. Results showed that the final body weight, average daily gain and average daily feed intake were significantly reduced in piglets fed the MC diet. Exposure to the MC diet also significantly decreased the thickness of smooth muscle layer and SMCs contractile markers expression (myosin heavy chain 11, smooth muscle actin gamma 2, transgelin, calponin 1) in jejunum and ileum of piglets. Furthermore, oral DON supplementation (3 mg/kg body weight) to mice in six consecutive days could significantly inhibit the upper intestinal transit, impede normal defecation and downregulate SMCs contractile markers expression in small intestine. Finally, we generated a porcine enteric smooth muscle cell line (PISMC), and found that DON could depress its contractility by decreasing PISMC proliferation, migration and contractile markers expression. In conclusion, these findings in vivo and in vitro suggest that DON, as a common environmental toxin, can not only reduce proliferative and motile phenotype, but also decrease contractile apparatus components (contractile markers expression) in SMCs, which in turn influences SMCs contractility and then interferes with intestinal motility and growth performance.

Resistant starch (RS) is a special group of starches which are slowly degraded and rarely digested in the gastrointestinal tract. It was recognized as a new type of dietary fiber that improved cardiovascular, cerebrovascular, and intestinal health. Breeding high-RS-content wheat is one of the most efficient and convenient approaches for providing an adequate amount of RS for a healthy diet. However, studies which aim to genetically illustrate RS content in wheat are still rare. In the present study, a panel of 207 wheat varieties were collected world-wide and planted under three locations. The RS content of each variety was measured, and 14 additive genetic loci were found to stably exist under more than two environments. Meanwhile, four genes were recognized as the putative candidates with annotated functions of β-amylase, α-1,4 glucan phosphorylase, sucrose transporter, and NAC domain protein. A kompetitive allele-specific PCR (KASP) marker was developed from the SNP AX-94546744, representing the genetic locus of β-amylase located. The AX-94546744-T allele can significantly increase the RS content compared to the AX-94546744-C allele. The genetic loci and KASP marker associated with RS content may be useful for wheat germplasm cultivation and variety breeding with a high RS content, further helping to improve the nutritional quality in wheat.

Exploration is an important aspect of autonomous robotics, whether it is for target searching, rescue missions, or reconnaissance in an unknown environment. In this paper, we propose a solution to efficiently explore the unknown environment by unmanned aerial vehicles (UAV). Innovatively, a topological road map is incrementally built based on Rapidly-exploring Random Tree (RRT) and maintained along with the whole exploration process. The topological structure can provide a set of waypoints for searching an optimal informative path. To evaluate the path, we consider the information measurement based on prior map uncertainty and the distance cost of the path, and formulate a normalized utility to describe information-richness along the path. The informative path is determined in every period by a local planner, and the robot executes the planned path to collect measurements of the unknown environment and restructure a map. The proposed framework and its composed modules are verified in two 3-D environments, which exhibit better performance in improving the exploration efficiency than other methods.

In this study, dustfall samples were systematically collected in various regions of Shanghai before and after the occurrence of COVID-19 in December 2019 and December 2020. The magnetic response, content and pollution status of relevant heavy metal elements in the samples were analyzed using environmental magnetism, geochemistry, scanning electron microscopy (SEM) and the enrichment factor (EF) method. The results show that the magnetic particles in the dustfall samples are mainly pseudo-single-domain (PSD) and multi-domain (MD) ferrimagnetic minerals, and Fe, Zn, Cr, and Cu are mainly concentrated in the districts with intensive human activities. Due to restrictions on human activities following the COVID-19 epidemic, both the values of magnetic parameters and the heavy metal pollution level in 2019 are more significant than those in 2020, which is consistent with the Air Quality Index (AQI) results. In addition, magnetic susceptibility (χlf), non-hysteresis remanence (χARM) and saturation isothermal remanence (SIRM) have different degrees of correlation with heavy metal elements, and the correlations with Fe, Pb, Cr and Zn are extremely prominent. The magnetic parameters can effectively and quickly reflect the level of particulate matter pollution, making them a useful tool for monitoring urban air quality.

The rapid analysis of thermal stress and deformation plays a pivotal role in the thermal control measures and optimization of the structural design of satellites. For achieving real-time thermal stress and thermal deformation analysis of satellite motherboards, this paper proposes a novel Multi-Task Attention UNet (MTA-UNet) neural network which combines the advantages of both Multi-Task Learning (MTL) and U-Net with an attention mechanism. Furthermore, a physics-informed strategy is used in the training process, where partial differential equations (PDEs) are integrated into the loss functions as residual terms. Finally, an uncertainty-based loss balancing approach is applied to weight different loss functions of multiple training tasks. Experimental results show that the proposed MTA-UNet effectively improves the prediction accuracy of multiple physics tasks compared with Single-Task Learning (STL) models. In addition, the physics-informed method brings less error in the prediction of each task, especially on small data sets.

In plants, the cell fates of a vegetative cell (VC) and generative cell (GC) are determined after the asymmetric division of the haploid microspore. The VC exits the cell cycle and grows a pollen tube, while the GC undergoes further mitosis to produce two sperm cells for double fertilization. However, our understanding of the mechanisms underlying their fate differentiation remains limited. One major advantage of the nuclear proteome analysis is that it is the only method currently able to uncover the systemic differences between VC and GC due to GC being engulfed within the cytoplasm of VC, limiting the use of transcriptome. Here, we obtained pure preparations of the vegetative cell nuclei (VNs) and generative cell nuclei (GNs) from germinating lily pollens. Utilizing these high-purity VNs and GNs, we compared the differential nucleoproteins between them using state-of-the-art quantitative proteomic techniques. We identified 720 different amount proteins (DAPs) and grouped the results in 11 fate differentiation categories. Among them, we identified 29 transcription factors (TFs) and 10 cell fate determinants. Significant differences were found in the molecular activities of vegetative and reproductive nuclei. The TFs in VN mainly participate in pollen tube development. In comparison, the TFs in GN are mainly involved in cell differentiation and male gametogenesis. The identified novel TFs may play an important role in cell fate differentiation. Our data also indicate differences in nuclear pore complexes and epigenetic modifications: more nucleoporins synthesized in VN; more histone variants and chaperones; and structural maintenance of chromosome (SMC) proteins, chromatin remodelers, and DNA methylation-related proteins expressed in GN. The VC has active macromolecular metabolism and mRNA processing, while GC has active nucleic acid metabolism and translation. Moreover, the members of unfolded protein response (UPR) and programmed cell death accumulate in VN, and DNA damage repair is active in GN. Differences in the stress response of DAPs in VN vs. GN were also found. This study provides a further understanding of pollen cell differentiation mechanisms and also a sound basis for future studies of the molecular mechanisms behind cell fate differentiation.

Abstract Background Heat stress (HS) jeopardizes intestinal barrier functions and augments intestinal permeability in pigs. However, whether HS-induced maternal microbial and metabolic changes in primiparous sows during late gestation remains elusive. We present here, a study investigating the fecal microbial and metabolic responses in late gestational primiparous sows when exposed to HS. Methods Twelve first-parity Landrace × Large White F1 sows were randomly assigned into two environmental treatments including the thermoneutral (TN) (18–22 °C; n = 6) and HS (28–32 °C; n = 6) conditions. Both treatments were applied from 85 d of gestation to farrowing. The serum and feces samples were collected on d 107 of gestation, for analyses including intestinal integrity biomarkers, high-throughput sequencing metagenomics, short-chain fatty acid (SCFA) profiles and nontargeted metabolomics. Results Our results show that HS group has higher serum Heat shock protein 70 (HSP70), lipopolysaccharide (LPS) and lipopolysaccharide-binding protein (LBP) levels. The gut microbial community can be altered upon HS by using β-diversity and taxon-based analysis. In particular, the relative abundance of genera and operational taxonomic units (OTUs) related to Clostridiales and Halomonas are higher in HS group, the relative abundance of genera and OTUs related to Bacteroidales and Streptococcus, however, are lower in HS group. Results of metabolic analysis reveal that HS lowers the concentrations of propionate, butyrate, total SCFA, succinate, fumarate, malate, lactate, aspartate, ethanolamine, β-alanine and niacin, whereas that of fructose and azelaic acid are higher in HS group. These metabolites mainly affect propanoate metabolism, alanine, aspartate and glutamate metabolism, phenylalanine metabolism, β-alanine metabolism, pantothenate and CoA biosynthesis, tricarboxylic acid cycle (TCA) and nicotinate and nicotinamide metabolism. Additionally, correlation analysis between significant microbes and metabolites indicated that the HS-induced microbiota shift is likely the cause of changes of intestinal metabolism. Conclusions Taken together, we reveal characteristic structural and metabolic changes in maternal gut microbiota as a result of late gestational HS, which could potentially provide the basis for further study on offspring gut microbiota and immune programming.

Abstract Backgrounds The aberrant activation of complement system is critically involved in lupus nephropathy. Recent study showed complement C3 inhibitor was effective in the treatment of lupus nephropathy. In this study, we investigate the effect of a novel complement C3 inhibitor, CRIg/FH, in the treatment of lupus nephropathy in MRL/lpr lupus mice. Methods We treated MRL/lpr female mice with a dose escalation of CRIg/FH (10, 5 and 2 mg/kg) by intraperitoneal injection twice weekly since 12 weeks age. In addition, MRL/lpr mice treated with intraperitoneal injection of normal saline or oral prednisone, along with C57BL/6 J healthy mice were maintained to serve as controls. We started 8-h urine collection weekly to screen proteinuria by measuring the levels of urine urea/creatinine. Serum samples was collected at week 16 and 20 to measure levels of urea nitrogen, creatinine, and immunological markers (C3, C4, A-ds-DNA) before the mice were sacrificed at 20 weeks age to collect kidneys for histopathological examinations. Results Overt skin lesions were observed in MRL/lpr mice treated with normal saline, while skin lesion was not observed in CRIg/FH treated MRL/lpr mice. There was no overt proteinuria observed in MRL/lpr mice treated with CRIg/FH. Serum creatinine and BUN levels in MRL/lpr mice was maintained in highest CRIg/FH dose (10 mg/kg twice a week) to be significantly lower than that in prednisone treated MRL/lpr mice at 20 weeks age. In addition, CRIg/FH treatment in MRL/lpr mice results in a significantly elevated serum C3 and C4 levels when compared to prednisone treatment at both 16 and 20 weeks. Furthermore, our study identified that serum level of A-ds-DNA was also significantly lower in CRIg/FH treatment than that in predisone treated MRL/lpr mice. Renal pathology confirmed that kidneys from CRIg/FH treated MRL/lpr mice suffered less from nephritis and complement disposition. Conclusion Our results showed that the complement inhibitor CRIg/FH can protect MRL/lpr mice from lupus nephropathy by preserving renal function and glomerulus complement activation. Our findings support the positive effect of complement inhibitors in the treatment of lupus nephropathy.

Non-circular plots of whole genomes are natural representations of genomic data aligned along all chromosomes. Currently, there is no specialized graphical user interface (GUI) designed to produce non-circular whole genome diagrams, and the use of existing tools requires considerable coding effort from users. Moreover, such tools also require improvement, including the addition of new functionalities. To address these issues, we developed a new R/Shiny application, named shinyChromosome, as a GUI for the interactive creation of non-circular whole genome diagrams. shinyChromosome can be easily installed on personal computers for own use as well as on local or public servers for community use. Publication-quality images can be readily generated and annotated from user input using diverse widgets. shinyChromosome is deployed at http://150.109.59.144:3838/shinyChromosome/, http://shinyChromosome.ncpgr.cn, and https://yimingyu.shinyapps.io/shinyChromosome for online use. The source code and manual of shinyChromosome are freely available at https://github.com/venyao/shinyChromosome. Keywords: Genomic data visualization, Non-circular whole genome plot, Shiny application, Graphical user interface, shinyChromosome

Abstract Background Following the intake of Fusarium mycotoxin-contaminated feed, small intestines may be exposed to high levels of toxic substances that can potentially damage intestinal functions in livestock. It is well known that Fusarium mycotoxins will lead a breakdown of the normally impeccable epithelial barrier, resulting in the development of a “leaky” gut. H2 administration with different methods has been proved definitely potentials to prevent serious intestinal diseases. The goal of this study is to investigate the roles of lactulose (LAC) and hydrogen-rich water (HRW) in preventing intestinal dysfunction in piglets fed Fusarium mycotoxin-contaminated feed. Methods A total of 24 female piglets were evenly assigned to 4 groups: negative control (NC) group, mycotoxin-contaminated (MC) feed group, MC feed with LAC treatment (MC + LAC), and MC feed with HRW treatment (MC + HRW), respectively. Piglets in the NC group were fed uncontaminated control diet, while remaining piglets were fed Fusarium mycotoxin-contaminated diet. For the NC and MC groups, 10 mL/kg body weight (BW) of hydrogen-free water (HFW) was orally administrated to piglets twice daily; while in the MC + LAC and MC + HRW groups, piglets were treated with the same dose of LAC solution (500 mg/kg BW) and HRW twice daily, respectively. On d 25, serum was collected and used for biochemical analysis. Intestinal tissues were sampled for morphological examination as well as relative genes and protein expression analysis. Results Our data showed that Fusarium mycotoxins induced higher serum diamine oxidase (DAO) activities (P

Accurate lightning forecast is significant for disaster prevention and reduction. However, the mainstream lightning forecast methods, which mainly rely on numerical simulations and parameterizations, can hardly cope with the spatiotemporal deviations. Meanwhile, the rapid and complex evolution of lightning regions go beyond the traditional extrapolation-based forecast methods. In this work, we propose a data-driven neural network model for hourly lightning forecast, which exploits both the numerical simulations and the recent historical lightning observations. The two kinds of data complement each other and play different roles at different stages of the forecast. The use of dual-source data greatly increases the amount of information available to improve the forecasting performance. To handle the variability of deviation patterns in numerical simulations, we introduce a channel-wise attention mechanism, which adaptively adjusts the proportion of each simulated parameter to maximize the useful information. The attention mechanism also enables the model to reveal the contribution of each simulated parameter for the forecast. Experimental results on a real-world dataset show that the proposed method outperforms several baseline methods. Ablation studies further demonstrate the effectiveness of our data fusion approach and attention module.

In the satellite lifetime optimization, reliability is a critical issue. For the complex satellite system, Bayesian network (BN) is an important method for reliability modeling and inference. As the number of system's components increases dramatically, the memory storage requirements of the system's node probability table (NPT) will exceed the computer's random access memory (RAM). To solve this challenge, compression methods have been proposed to reduce the memory storage requirements of NPT. However, for the complex satellite system with extreme large number of components and the explosion of probable state combination, the existing methods still face big challenge in compression efficiency. Therefore, an improved encoding compression algorithm is proposed to further enhance the NPT compression effect in this paper. For the hierarchical complex satellite system that has multiple subsystems which are further composed of multiple components, the multilevel BN reliability model is first constructed based on the proposed encoding compression algorithm. By the variable elimination algorithm, a multilevel BN reliability inference algorithm is proposed to perform the inference of the multilevel BN reliability model. Based on the basis of the reliability model above, further considering system mass, power and cost requirement, the satellite lifetime is properly designed by optimizing the system component configuration, including component model/type selection and number determination for redundancy. Finally, two cases are studied to demonstrate and validate the proposed algorithms.

With the rapid decreasing of sequencing cost, large volume of genotype data has been generated in many organisms based on high-throughput sequencing, which was utilized in various fields of biological studies in the post-genome era. The raw sequencing data were usually deposited in the NCBI SRA database. Construction of the database to store and analyze the processed genotype data is an essential step for the utilization of the genotype data by the community. Up to now, a comprehensive genotype database is still missing from maize, which is an important crop of the world. We report the construction of the MaizeSNPDB database using genotype data of 1210 maize line across 35,370,939 SNP sites refined from a large set of genomic variations reported by the maize HapMap 3 project. We further implemented several genetic analysis programs as graphical interfaces in the MaizeSNPDB database. SNPs in user-specified genomic regions could be easily extracted and analyzed in MaizeSNPDB. The whole dataset and code of MaizeSNPDB is available at https://github.com/venyao/MaizeSNPDB. MaizeSNPDB is deployed at http://150.109.59.144:3838/MaizeSNPDB/ for online use. The MaizeSNPDB database is of great value to future maize functional genomic studies, which can also facilitate marker-assisted breeding in maize. Keywords: Maize, SNP, Database, Genomic variation, Genotype, Graphical interface

In reliability-based design optimization (RBDO) for the satellite system, reliability modeling is a very important issue. However, due to the limited failure information and small scale production in space engineering, it remains challenging as how to properly construct the reliability model especially in the early conceptual design phase for a new satellite. Actually, there is multi-source lifetime (or failure) information of satellite subsystems or systems from the past missions or designer experiences. How to fully integrate the multi-source information so as to enhance the reliability model with more knowledge is an open problem to be solved. To address this problem, in this paper, it is proposed to use the Bayesian Melding Method (BMM) to merge the multi-source lifetime information from the multi-level structure of satellite system and subsystems, based on which the lifetime distributions can be updated and the satellite reliability model can be properly constructed. With the enhanced reliability model, the satellite RBDO is further studied to optimize the satellite design with budget constraints on mass, cost, and reliability. Finally, two case studies are utilized to demonstrate and verify the proposed method.

A triggered lightning flash (TLF) provides a unique perspective on the relationship between spatiotemporal proximity flashes, owing to its determined location and time, convenient direction measurement, and explicit association with the charge region. In this study, 3-D lightning location, current measurement, and atmospheric average electric field (AAEF) data were used to investigate the spatiotemporal relationship of TLFs (68 samples in South China) with adjacent natural lightning flashes (NLFs). The TLF-related negative charge regions had an average core height of 5.2 km and ambient temperature of approximately −1.7 °C. The effective negative charge region (the charge density that was high enough for the occurrence of lightning discharge) can be approximately equivalent to a circle with an average diameter of 10.3 km. For approximately 93% of (all) the TLFs, no NLF channel (initiation) was located within 5 km of the flash-triggered position, within 5 s before and after their occurrence. In situations where spatiotemporally adjacent NLFs and TLFs occurred, they were either associated with different charge layers or the same charge layer but different charge positions. Most NLFs that caused significantly sharp AAEF changes just before or after the TLFs were not associated with the TLF-related negative charge. Therefore, the recovery of the AAEF, which has usually been referenced as the timing choice of the triggering operation, was not directly associated with the TLF-related charge region. The average interval between the TLFs and NLFs that occurred within 10 min before and after the TLFs and neutralized the TLF-related negative charge was approximately 145 s.

Thunderstorm activity over the Qinghai–Tibet Plateau (QTP) has important climatic effects and disaster impacts. Using the thunderstorm feature dataset (TFD) established based on the black body temperature (TBB) and cloud classification (CLC) products of the Fengyun-2E (FY-2E) geostationary satellite, as well as the lightning data of the World Wide Lightning Location Network (WWLLN), the temporal and spatial distributions and some cloud properties of the thunderstorms over the QTP were analyzed. Approximately 93.9% and 82.7% of thunderstorms over the QTP occur from May to September and from 12 to 21 o’clock local time, and the corresponding peaks are in August and at 14:00, respectively. There are three centers featuring frequent thunderstorms in the southeast, south-central, and southwest regions of the QTP. The average thunderstorm cloud area (the region with TBB ≤ −32 °C) is 1.8 × 104 km2. Approximately 32.9% of thunderstorms have strong convective cells (SCCs) composed of areas with TBB ≤ −52 °C. The average number and area ratio of SCCs are 3.6 and 25.4%, respectively, and their spatial distribution is given. The average cloud area and the number and area ratio of SCCs of extreme-lightning thunderstorms (thunderstorms with the top 10% of lightning numbers) are approximately 30.0, 3.9, and 1.5 times those of normal thunderstorms. The spatial distribution of the thunderstorm activity is quite different from that of lightning activity given by the Lightning Imaging Sensor (LIS) and Optical Transient Detector (OTD) over the northeastern and southwestern QTP, which may mean that the convection intensity, cloud structure, and charge structure of the thunderstorms over the QTP are different between different regions and seasons.

Abstract Background Bloodstream infection (BSI) is one of the major causes of morbidity and mortality for patients undergoing hematopoietic stem cell transplantation (HSCT). The unrelated cord blood transplantation (UCBT) can provided opportunities for patients without suitable donors for bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT), while few studies have addressed BSI after UCBT. The aim of this study was to analyse the incidence and risk factors of BSI, causative organisms, microbial resistance, and its impact on the clinical outcomes and survival of patients. Methods There are 336 patients, were divided into two groups depending on whether developing BSI. Demographic characteristics, laboratory data, and clinical outcome were compared between different groups. The risk factors of BSI was examined using logistic regression and the survival was examined using the Kaplan-Meier method and log-rank test. Results Ninety-two patients (27.4%) developed early BSI with 101 pathogenic bacteria isolated, and the median day of developing initial BSI was 4.5 d. Gram-negative bacteria were the most common isolate (60, 59.4%), followed by Gram-positive bacteria (40, 39.6%) and fungi (1, 1.0%). Thirty-seven (36.6%) isolates were documented as having multiple drug resistance (MDR). Myeloid malignancies, conditioning regimens including total body irradiation (TBI), and prolonged neutropenia were identified as the independent risk factors for early BSI. The 3-year OS was 59.9% versus 69.2% in the BSI group and no-BSI group (P = 0.0574), respectively. The 3-year OS of the MDR group was significantly lower than that of the non-BSI group (51.1% versus 69.2%, p = 0.013). Conclusions Our data indicate that the incidence of early BSI after UCBT was high, especially in patients with myeloid disease and a conditioning regimen including TBI and prolonged neutropenia. Early BSI with MDR after UCBT had a negative impact on long-term survival.