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Summary Cultivated jute, which comprises the two species Corchorus capsularis and C. olitorius, is the second most important natural fibre source after cotton. Here we describe chromosome‐level assemblies of the genomes of both cultivated species. The C. capsularis and C. olitorius assemblies are each comprised of seven pseudo‐chromosomes, with the C. capsularis assembly consisting of 336 Mb with 25,874 genes and the C. olitorius assembly containing 361 Mb with 28 479 genes. Although the two Corchorus genomes exhibit collinearity, the genome of C. olitorius contains 25 Mb of additional sequences than that of C. capsularis with 13 putative inversions, which might give a hint to the difference of phenotypic variants between the two cultivated jute species. Analysis of gene expression in isolated fibre tissues reveals candidate genes involved in fibre development. Our analysis of the population structures of 242 cultivars from C. capsularis and 57 cultivars from C. olitorius by whole‐genome resequencing resulted in post‐domestication bottlenecks occurred ~2000 years ago in these species. We identified hundreds of putative significant marker‐trait associations (MTAs) controlling fibre fineness, cellulose content and lignin content of fibre by integrating data from genome‐wide association studies (GWAS) with data from analyses of selective sweeps due to natural and artificial selection in these two jute species. Among them, we further validated that CcCOBRA1 and CcC4H1 regulate fibre quality in transgenic plants via improving the biosynthesis of the secondary cell wall. Our results yielded important new resources for functional genomics research and genetic improvement in jute and allied fibre crops.

Ferroptosis is a newly recognised type of regulated cell death (RCD) characterised by iron-dependent accumulation of lipid peroxidation. It is significantly distinct from other RCDs at the morphological, biochemical, and genetic levels. Recent reports have implicated ferroptosis in multiple diseases, including neurological disorders, kidney injury, liver diseases, and cancer. Ferroptotic cell death has also been associated with dysfunction of the intestinal epithelium, which contributes to several intestinal diseases. Research on ferroptosis may provide a new understanding of intestinal disease pathogenesis that benefits clinical treatment. In this review, we provide an overview of ferroptosis and its underlying mechanisms, then describe its emerging role in intestinal diseases, including intestinal ischaemia/reperfusion (I/R) injury, inflammatory bowel disease (IBD), and colorectal cancer (CRC).

Establishing saturated mutagenesis in a specific gene through gene editing is an efficient approach for identifying the relationships between mutations and the corresponding phenotypes. CRISPR/Cas9-based sgRNA library screening often creates indel mutations with multiple nucleotides. Single base editors and dual deaminase-mediated base editors can achieve only one and two types of base substitutions, respectively. A new glycosylase base editor (CGBE) system, in which the uracil glycosylase inhibitor (UGI) is replaced with uracil-DNA glycosylase (UNG), was recently reported to efficiently induce multiple base conversions, including C-to-G, C-to-T and C-to-A. In this study, we fused a CGBE with ABE to develop a new type of dual deaminase-mediated base editing system, the AGBE system, that can simultaneously introduce 4 types of base conversions (C-to-G, C-to-T, C-to-A and A-to-G) as well as indels with a single sgRNA in mammalian cells. AGBEs can be used to establish saturated mutant populations for verification of the functions and consequences of multiple gene mutation patterns, including single-nucleotide variants (SNVs) and indels, through high-throughput screening.

Lihui Lin,1,* Ying Li,1,2,* Gaoshi Zhou,1 Ying Wang,1 Li Li,1 Jing Han,1 Minhu Chen,1 Yao He,1 Shenghong Zhang1 1Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Division of Gastroenterology, The Seventh Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shenghong Zhang; Yao He, Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China, Email zhshh3@mail.sysu.edu.cn; heyao@mail.sysu.edu.cnBackground: Western-style diet (WSD) is associated with inflammatory bowel disease (IBD) prevalence. However, the impact of WSD on IBD development and its underlying mechanism remain unclear. Transcriptomics and metabolomics could be beneficial for identifying key factors in WSD-related experimental IBD susceptibility. However, no such study has been conducted yet. We aimed to analyze the implications of WSD for experimental colitis susceptibility in mice and its underlying mechanism using these high-throughput technologies.Methods: We fed experimental mice a WSD and a control diet from weaning. After 9 weeks, the mice were treated with 2,4,6 trinitrobenzene sulfonic acid to induce colitis, and the control group was treated with 50% ethanol (commonly used IBD animal model). Genome-wide microarray and liquid chromatography-tandem mass spectrometry were used to identify the differential transcripts and metabolites of experimental colitis with and without pre-illness WSD.Results: WSD induced more severe inflammation in experimental colitis than the control diet. We found 2540 up-regulated genes and 2737 down-regulated genes in experimental colitis with WSD compared with those for the control diet. In addition, levels of 41 colonic tissue metabolites and 56 serum metabolites showed significant differences. Integrating transcriptomic and metabolomic data, we found major co-expression networks through which WSD promoted experimental IBD susceptibility, including enzymes of biotransformation, glycan synthesis and metabolism, steroid hormone metabolites.Conclusion: Pre-illness WSD increased experimental colitis susceptibility. Our results could provide important evidences for the potential mechanisms and assist dietary recommendations to better manage IBD.Keywords: Western-style diet, susceptibility, experimental colitis, inflammatory bowel disease, transcriptomics, metabolomics

The majority of acute myeloid leukemia (AML) patients will respond to standard chemotherapy, however, resistance is a prevalent problem contributing to incomplete responses, refractory disease, and ultimately patient death. Therefore, choosing more sensitive and effective chemotherapy regimens is of key clinical importance. In order to explore this issue, we investigated and optimized PharmaFlow, an automated flow cytometry method for evaluating the sensitivity of leukemia cells to multiple chemotherapeutic drugs ex vivo. We examined bone marrow samples from 38 Chinese AML patients and incubated them for 48 or 72 h with a panel of 7 single drugs and 6 combinations with cytarabine at different concentrations. Leukemic cell depletion was assessed by PharmaFlow and drug response parameter, called PharmaFlow score, was estimated using population pharmacodynamic models. We identified that most chemotherapeutic drugs and combinations could effectively eliminate pathological cells ex vivo. Estimated drug activities strongly correlated with the patients’ duration to achieve clinical remission and PharmaFlow chemosensitivity measured ex vivo was highly predictive of the clinical outcome after chemotherapy. Applying a classification model, we determined a PharmaFlow score of 89.4 as the threshold to predict response to chemotherapy. Using this threshold, we found that in 84.2% of cases patient's cell response ex vivo predicted the observed clinical response and performed similarly or better than prognostic subgroups determined by cytogenetic characteristics. PharmaFlow has the potential to predict chemosensitivity for de novo, secondary and relapsed AML patients prior to treatment and may guide clinicians to tailor treatments and improve patient outcome.

Summary Kenaf is an annual crop that is widely cultivated as a source of bast (phloem) fibres, the phytoremediation of heavy metal‐contaminated farmlands and textile‐relevant compounds. Leaf shape played a unique role in kenaf improvement, due to the inheritance as a single locus and the association with fibre development in typical lobed‐leaf varieties. Here we report a high‐quality genome assembly and annotation for var. ‘Fuhong 952’ with 1078 Mbp genome and 66 004 protein‐coding genes integrating single‐molecule real‐time sequencing, a high‐density genetic map and high‐throughput chromosome conformation capture techniques. Gene mapping assists the identification of a homeobox transcription factor LATE MERISTEM IDENTITY 1 (HcLMI1) gene controlling lobed‐leaf. Virus‐induced gene silencing (VIGS) of HcLMI1 in a lobed‐leaf variety was critical to induce round (entire)‐like leaf formation. Candidate genes involved in cell wall formation were found in quantitative trait loci (QTL) for fibre yield and quality‐related traits. Comparative genomic and transcriptome analyses revealed key genes involved in bast fibre formation, among which there are twice as many cellulose synthase A (CesA) genes due to a recent whole‐genome duplication after divergence from Gossypium. Population genomic analysis showed two recent population bottlenecks in kenaf, suggesting domestication and improvement process have led to an increase in fibre biogenesis and yield. This chromosome‐scale genome provides an important framework and toolkit for sequence‐directed genetic improvement of fibre crops.

Pregnancy-induced hypertension is a common complication in obstetrics and an important cause of maternal death. We explored the correlations among stress, family function and coping mode in women with pregnancy-induced hypertension syndrome.A total of 58 pregnant women with pregnancy-induced hypertension syndrome were included in the study. The perceived stress scale (PSS), family assessment device (FAD), and medical coping modes questionnaire (MCMQ) were used to assess stress level, family function, and coping mode, respectively.The PSS score was 28 (interquartile range: 20-43). The total FAD score was 128.1±27.1. The subscale scores were problem-solving, affective responsiveness, communication, roles, behavior control, affective involvement, and general function, in order of decreasing score. Significant correlations were noted between PSS score and total FAD score, affective responsiveness, problem-solving, communication, roles, affective involvement, and behavior control (all P0.05). PSS score was significantly correlated with "Escape" (P=0.016) and "Yield" (P0.001) in the MCMQ. Single-factor analysis showed that education level, average household income, and FAD total score were significantly different in those with a low or high PSS score. Logistic regression indicated the FAD total score as an independent factor for the PSS score.Women with pregnancy-induced hypertension syndrome with a high PSS score tended to adopt the "Escape" and "Yield" coping modes. Family function integrity is essential for reducing PSS scores.

Kenaf is one of the most important natural fiber crops. The lack of molecular markers has resulted in a large gap in the improvement of kenaf. Previously, de novo 90,175 unigenes in kenaf were assembled. In this study, 7453 small InDels were called from these uingenes. The indel size 10 bp have frequencies of 71.50%, 23.05%, and 5.45%. 337 InDels locating in genes encoding transcription factors were used to survey polymorphisms with 24 kenaf accessions. Of 337 InDels, 305 (90.5%) successfully amplified at least one fragment and detected polymorphism among the 24 diverse genotypes. Furthermore, one InDel marker, HcID266, was co-segregated with leaf shape, which was inherited as a single Mendelian locus, in the F2 population with 390 individuals. To our knowledge, this is the first large-scale InDels development for kenaf. These InDel markers will be helpful for genetic researches in kenaf.

When searching for which products to buy, consumers are typically bombarded with options. Some suppliers try and simplify the issue of decision-making for their potential buyers in some way. One typical procedure used to ease the decision-making process for potential customers is to present the products in sequential pages and request shoppers to select an item from each page, entering them into a wish list from which the final choice will be made. This study experimentally investigates how the final decision is affected by the number of items on each page and, hence, by the number of items in a wish list. The parameters of a stochastic model are estimated to ‘explain’ the data, in particular, examining the noisiness of the choices at each stage. The results show that procedure matters and that the trade-off between an increased number of options per page and an increased number of pages is indeed influential.

Antigen (Ag)-mediated mast cell activation plays a critical role in the immunopathology of IgE-dependent allergic diseases. Restraining the signaling cascade that regulates the release of mast cell-derived inflammatory mediators is an attractive therapeutic strategy to treat allergic diseases. Orosomucoid-like-3 (ORMDL3) regulates the endoplasmic reticulum stress (ERS)-induced unfolded protein response (UPR) and autophagy. Although ERS/UPR/autophagy pathway is crucial in Ag-induced mast cell activation, it is unknown whether ORMDL3 regulates the ERS/UPR/autophagy pathway during mast cell activation. In this study, we found that ORMDL3 expression was downregulated in Ag-activated MC/9 cells. Overexpression of ORMDL3 significantly inhibited degranulation, and cytokine/chemokine production, while the opposite effect was observed with ORMDL3 knockdown in MC/9 cells. Importantly, ORMDL3 overexpression upregulated mediators of ERS-UPR (SERCA2b, ATF6) and autophagy (Beclin 1 and LC3BII). Knockdown of ATF6 and/or inhibition of autophagy reversed the decreased degranulation and cytokine/chemokine expression caused by ORMDL3 overexpression. Moreover, in vivo knockdown of ORMDL3 and/or ATF6 enhanced passive cutaneous anaphylaxis (PCA) reactions in mouse ears. These data indicate that ORMDL3 suppresses Ag-mediated mast cell activation via an ATF6 UPR-autophagy dependent pathway and thus, attenuates anaphylactic reaction. This highlights a potential mechanism to intervene in mast cell mediated diseases.

A practical automatic textual math word problems (MWPs) solver should be able to solve various textual MWPs while most existing works only focused on one-unknown linear MWPs. Herein, we propose a simple but efficient method called Universal Expression Tree (UET) to make the first attempt to represent the equations of various MWPs uniformly. Then a semantically-aligned universal tree-structured solver (SAU-Solver) based on an encoder-decoder framework is proposed to resolve multiple types of MWPs in a unified model, benefiting from our UET representation. Our SAU-Solver generates a universal expression tree explicitly by deciding which symbol to generate according to the generated symbols' semantic meanings like human solving MWPs. Besides, our SAU-Solver also includes a novel subtree-level semanticallyaligned regularization to further enforce the semantic constraints and rationality of the generated expression tree by aligning with the contextual information. Finally, to validate the universality of our solver and extend the research boundary of MWPs, we introduce a new challenging Hybrid Math Word Problems dataset (HMWP), consisting of three types of MWPs. Experimental results on several MWPs datasets show that our model can solve universal types of MWPs and outperforms several state-of-the-art models., EMNLP2020

Extracting the topical information from documents is important for public opinion analysis, text classification, and information retrieval tasks. Compared with identifying a wide variety of topics from long documents, it is challenging to generate a concentrated topic distribution for each short message. Although this problem can be tackled by adjusting the hyper-parameters in traditional topic models such as Latent Dirichlet Allocation, it remains an open problem in neural topic modelling. In this paper, we focus on adapting the popular Auto-Encoding Variational Bayes based neural topic models to short texts, by exploring the Archimedean copulas to guide the estimated topic distributions derived from linear projected samples of re-parameterized posterior distributions. Experimental results show the superiority of our method when compared with existing neural topic models in terms of perplexity, topic coherence, and classification accuracy.

The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion, sputum, and peripheral blood biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion. The mechanistic investigation identified a group of CD14+ monocytes and macrophages highly expressing CD163 and MRC1 in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated IL10, CCL18, APOE, CSF1 (M-CSF), and CCL2 signaling pathways. Further, SARS-CoV-2-specific T cells were observed in pleural effusion earlier than in peripheral blood. Together, our results suggest that severe SARS-CoV-2 infection causes immune dysregulation by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.

Gamification has been widely employed in online learning systems to enhance users’ gratification and to retain them from dropping out. Compared with core learning modules, gamification modules provide more hedonic value, which increases user engagement in the short term but these modules may also cause distraction and impede learning performance. Thus, time management and self-control are crucial for users of online learning systems. Our study proposes that users tend to treat on-the-hour time points (i.e., the strike of the traditional clock) as temporal cues, which substantially influence their interactions with the core learning versus gamification modules, as well as both the instrumental and experiential outcomes of these interactions. Through a set of three multi-method studies that focus on the sharp clock-striking time points, we find that i) users are more (versus less) likely to begin using core learning modules (versus gamification modules) after clock-striking time points; ii) beginning the use of core learning modules at clock-striking time points has a positive relationship with learning persistence and learning performance; iii) beginning the use of gamification modules at clock-striking time points results in a lower level of perceived enjoyment than beginning at random time points. Further, the results of studies 2 and 3 indicate that clock-striking time points can activate users’ implemental mindset, which supports them in building a longer learning persistence and achieving better learning performance. Our findings add to the design of online learning systems by understanding the mindset effects of temporal cues in user-system interactions of gamified learning systems, based on which notification and reminder systems can be implemented to further facilitate the effectiveness of online learning.

Mast cells (MCs) are known to participate in a variety of patho-physiological processes depending largely on the intragranular mediators and the production of cytokines and chemokines during degranulation. Recently, extracellular vesicles (EVs) have been implicated important functions for MCs, but the components of MC-derived EVs have not yet been well-characterized. In this study, we aimed to identify signatures of proteins, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) in EVs derived from resting (Rest-EV) and degranulated (Sti-EV) MCs by differential ultracentrifugation. Using tandem mass tag (TMT)-based quantitative proteomics technology and RNA sequencing, we identified a total of 1988 proteins, 397 lncRNAs, and 272 miRNAs in Rest-EV and Sti-EV. The proteins include common EVs markers (cytoskeletal proteins), MCs markers (FcεRI and tryptase), and some preformed MCs mediators (lysosomal enzymes) as well. The global expression profiles of lncRNAs and miRNAs identified, for the first time, from Rest-EV and Sti-EV, strongly suggest a potential regulatory function of MC-derived EVs. We have also performed Western blotting and qRT-PCR analysis to further verify some of the proteins, lncRNAs, and miRNAs identified from Rest-EV and Sti-EV. Our findings will help to elucidate the functions of MC-derived EVs, and provide a reference dataset for future translational studies involving MC-derived EVs.

Summary Polycomb repressive complex 1 (PRC1) plays essential roles in cell-fate determination. Recent studies have found that the composition of mammalian PRC1 is particularly varied and complex; however, little is known about the functional consequences of these variant PRC1 complexes on cell-fate determination. Here, we show that Kdm2b promotes Oct4-induced somatic reprogramming through recruitment of a variant PRC1 complex (PRC1.1) to CpG islands (CGIs). Furthermore, we find that bone morphogenetic protein (BMP) represses Oct4/Kdm2b-induced somatic reprogramming selectively. Mechanistically, BMP-SMAD pathway attenuates PRC1.1 occupation and H2AK119 ubiquitination at genes linked to development, resulting in the expression of mesendodermal factors such as Sox17 and a consequent suppression of somatic reprogramming. These observations reveal that PRC1.1 participates in the establishment of pluripotency and identify BMP4 signaling as a modulator of PRC1.1 function.

Online health communities (OHCs) often struggle to retain active users because they endow users with both a positive and a stigmatized social identity that respectively encourages and discourages their engagement. We integrate social identity theory with the concepts of social stigma, psychological capital, and digital divide to investigate this phenomenon. We collected survey data from 221 users from one large online lymphoma community in November 2017. We find that users' positive social identity had a positive influence on how they perceived the effectiveness of OHCs and this influence was stronger for the high socio-economic status (SES) group; at the same time, a stigmatized social identity had a negative influence on perceived effectiveness of OHCs and this influence was stronger for the low SES group. Moreover, users’ perceived effectiveness of OHCs had positive influences on their participation and recommendation intentions, and the influences on participation and recommendation intentions were stronger for the high and the low SES group, respectively. Our study highlights the dual influences of valenced social identities on user engagement with OHCs through their effectiveness perceptions and interprets these influences through the lens of digital divide. The findings also offer practical insights for the effective management of OHCs.

Reactions between arynes and alkyl sulfides have been extensively studied over the past few decades. These reactions commonly end with a dealkylation process and thus deliver thioethers as final products. In contrast, the transformation described furnishes valuable triarylsulfonium salts, in lieu of thioethers, from arynes and diarylsulfides. The reaction features mild conditions and a broad substrate scope. A suite of functional groups such as ketones, esters, nitriles, aryl ethers and aryl halides is tolerated, which can be issues faced by traditional synthetic methods. The practicality of the reaction and its extension to the synthesis of triphenyl selenonium salt are also exhibited herein.

Allergies affect a significant proportion of the world's population, and existing vaccination strategies to restrict their adverse pathologies often render side-effects. The aim of this study was to design a new vaccine for allergen-specific immunotherapy (SIT), and to investigate its preventive effects during allergic inflammation. We constructed ovalbumin (OVA)-conjugated celastrol-loaded nanomicelles (OVA-NMs-celastrol), wherein celastrol (a bioactive anti-inflammatory compound) was loaded into carboxyl-functioned polymeric nanomicelles using a thin-film hydration method. OVA was used as a model allergen and conjugated on nanomicelles. The OVA-NMs-celastrol obtained were characterized based on particle size, morphology, drug encapsulation efficiency, and drug loading percentage. Further, the preventive effect of OVA-NMs-celastrol was evaluated in a mouse model of allergic asthma. Our results showed that OVA-NMs-celastrol possessed valuable characteristics such as small particle size (50.72 ± 0.98 nm) and spherical-like shape, with celastrol encapsulation efficiency of 99.89 ± 0.85% and a drug loading percentage of 4.76 ± 0.03%. Further, in vivo results showed that treatment with OVA-NMs-celastrol could decrease OVA specific IgE and histamine levels, Th2 cytokine (IL-4, IL-5) levels, and inflammatory cell infiltration in the lung tissues. Moreover, it could enhance the OVA specific IgG1 and IgG2a levels and decrease the IgE / IgG2a ratio. These results demonstrate the successful construction of OVA-NMs-celastrol as a potential vaccine candidate for use in SIT for allergic inflammation.

Previous studies with biological and genetic evidence indicate that the myo‐inositol monophosphatase 2 (IMPA2) gene may influence schizophrenia. We performed a genetic association study in Han Chinese cohorts. Five single nucleotide polymorphisms within IMPA2 promoter region (rs971363, rs971362, rs2075824, rs111410794 and rs111610121), as well as one (rs45442994, in intron 1) that was positively associated in another study, were selected for genotyping in 1397 patients with schizophrenia and 1285 mentally healthy controls. Genotype and allele frequencies were assessed by gender stratification. Interestingly, rs2075824 showed a strong association with schizophrenia (P = 4.1 × 10−4), and the T allele was more frequent in cases than controls [P = 5.6 × 10−5, OR (95% CI) = 1.26 (1.13–1.41)]. In vitro promoter assay showed that the transcription activity of the T allele promoter was higher than that of the C allele promoter and the T allele of rs2075824 contributed to risk for schizophrenia. By stratifying males and females, we found a gender‐specific association for IMPA2 and schizophrenia: the T allele of rs2075824 was more frequent in male cases compared with male controls [P = 1.4 × 10−4, OR (95% CI) = 1.33 (1.15–1.55)]. Our data suggest that a promoter polymorphism of IMPA2 possibly contributed to risk for schizophrenia by elevating transcription activity in Han Chinese individuals.

Crowdsourcing platforms specialize in hosting open contests and usually charge a percentage of the prizes as service fees. While prior research has studied the design of contests and the behavior of contestants, the strategy of a crowdsourcing platform has remained largely unexplored. We develop a game-theoretic model of crowdsourcing services and find the optimal fee structure of a platform. We prove for the case of a single contest that the service fees should be an increasing concave function of task prizes and show that this also holds true for the case of multiple contests. We further find that for a platform with many users and tasks, there is an optimal ratio of the number of contestants and contests. Our research is one of the first to focus on the strategies of crowdsourcing platforms and our results have interesting managerial implications. We show that the linear fee schedule widely used in practice is not optimal and that a platform is better off lowering the fee rate for contests with high prizes. It is also in the best interests of a platform to develop both sides of the crowdsourcing market proportionally and keep the ratio of contestants and contests at the optimal level. [web URL: http://onlinelibrary.wiley.com/doi/10.1111/deci.12201/full]

Mast cells and basophils are effector cells in the pathophysiology of allergic diseases. Targeted elimination of these cells may be a promising strategy for the treatment of allergic disorders. Our present study aims at targeted delivery of anti-FceRIα Fab-conjugated celastrol-loaded micelles toward FceRIα receptors expressed on mast cells and basophils to have enhanced anti-allergic effect. To achieve this aim, we prepared celastrol-loaded (PEO-block-PPO-block-PEO, Pluronic) polymeric nanomicelles using thin-film hydration method. The anti-FceRIα Fab Fragment was then conjugated to carboxyl groups on drug-loaded micelles via EDC amidation reaction. The anti-FceRIα Fab-conjugated celastrol-loaded micelles revealed uniform particle size (93.43 ± 12.93 nm) with high loading percentage (21.2 ± 1.5% w/w). The image of micelles showed oval and rod like. The anti-FceRIα Fab-conjugated micelles demonstrated enhanced cellular uptake and cytotoxity toward target KU812 cells than non-conjugated micelles in vitro. Furthermore, diffusion of the drug into the cells allowed an efficient induction of cell apoptosis. In mouse model of allergic asthma, treatment with anti-FceRIα Fab-conjugated micelles increased lung accumulation of micelles, and significantly reduced OVA-sIgE, histamine and Th2 cytokines (IL-4, IL-5, TNF-α) levels, eosinophils infiltration and mucus production. In addition, in mouse model of passive cutaneous anaphylaxis, anti-FceRIα Fab-conjugated celastrol-loaded micelles treatment significantly decreased extravasated evan's in the ear. These results indicate that anti-FceRIα Fab-conjugated celastrol-loaded micelles can target and selectively kill mast cells and basophils which express FceRIα, and may be efficient reagents for the treatment of allergic disorders and mast cell related diseases.

Mast cells (MCs) degranulation is a key process during the allergic inflammatory response. MCs release their preformed and new synthesized granules after activation. We found that granules were released partially and selectively after the activation of bone marrow-derived mouse mast cells (BMMCs). Next, we investigated the response of degranulated MCs to a new challenge. BMMCs were activated by antibody/antigen (IgE/Ag) or compound 48/80 (C48/80). The degranulated BMMCs were then reactivated by either IgE/Ag or C48/80 without time intervals. Flow cytometry was used to detect the expression of CD117, FcεRI, and intracellular granules of BMMCs, and BMMCs degranulation was detected using the β-hexosaminidase release assay. The morphology of BMMCs was observed by staining with toluidine blue. Degranulated BMMCs activated by IgE/Ag failed to respond to the same IgE/Ag challenge and released β-hexosaminidase independent of unoccupied FcεRI, but responded to C48/80. Degranulated BMMCs activated by C48/80 responded to either IgE/Ag or C48/80. These results indicated that degranulated BMMCs could be reactivated and released granule mediators again, this revealed the unique mediator releasing mechanism of degranulated MCs and their potential function in maintaining inflammation or causing hypersensitivity.

Hierarchical Dirichlet Process (HDP) has attracted much attention in the research community of natural language processing. Given a corpus, HDP is able to determine the number of topics automatically, possessing an important feature dubbed nonparametric that overcomes the challenging issue of manually specifying a suitable topic number in parametric topic models, such as Latent Dirichlet Allocation (LDA). Nevertheless, HDP requires a much higher computational cost than LDA for parameter estimation. By taking the advantage of multi-threading, a parallel Gibbs sampling algorithm is proposed to estimate parameters for HDP based on the equivalence between HDP and Gamma-Gamma Poisson Process (G2PP) in terms of the generative process. Unfortunately, the above parallel Gibbs sampling algorithm requires to apply the finite approximation on the number of topics manually (i.e., predefine the topic number), thus can not retain the nonparametric feature of HDP. Another drawback of the above models is the lack of capturing the semantic dependencies between words, because the topic assignment of words is independent with each other. Although some works have been done in phrase-based topic modelling, these existing methods are still limited by either enforcing the entire phrase to share a common topic or requiring much complex and time-consuming phrase mining methods. In this paper, we aim to develop a copula guided parallel Gibbs sampling algorithm for HDP which can adjust the number of topics dynamically and capture the latent semantic dependencies between words that compose a coherent segment. Extensive experiments on real-world datasets indicate that our method achieves low perplexities and high topic coherence scores with a small time cost. In addition, we validate the effectiveness of our method on the modelling of word semantic dependencies by comparing the extracted topical phrases with those learned by state-of-the-art phrase-based baselines.

The World Cancer Research Fund International has released 32 anticancer effects (ACEs) that targeted every stage of cancer processes. Thus, we designed two formulas of natural food combination Diet I and Diet II, mainly produced by elite crop varieties rich in ACEs with different mixture ratios, and evaluated their cancer preventive effects on N‐nitrosodiethylamine (NDEA)‐induced hepatocarcinogenesis. After 20 weeks of dietary intervention, Diet I and Diet II reduced incidence, size, and number of hepatic nodules (p

Cell makes fate decision with intrinsic and extrinsic cues. It has been difficult to define the precise decision process due to cellular heterogeneity. Here we map the cell fate continuum generated during somatic reprogramming by Oct4, Sox2 and Klf4 at single cell resolution. We show that the reprogramming cells initially march through mesenchyme-epithelial transition, then bifurcate into non-reprogramming (NR) and reprogramming (R) fates. The R cells continue to acquire Oct4 activation and then bifurcate again into Dppa5a chimera competent and Dppa5a- chimera incompetent cells. Mechanistically, we show that the NR/R bifurcation is controlled by Klf4 and Sox2 and the final Dppa5a rate-limiting step in part by IFN-γ, a cytokine activated during reprogramming. Our study identifies two previously unknown cell fate checkpoints along the reprogramming pathway, highlighting single-cell analysis as a tool to understand cell fate decisions.

Graphene plasmons, owing to their diverse applications including electro-optical modulation, optical sensing, spectral photometry and tunable lighting at the nanoscale, have recently attracted much attention. One key challenge in advancing this field is to precisely control the propagation of graphene plasmons. Here, we propose an on-chip integrated platform to engineer the wave front of the graphene plasmons through a metasurface with a refractive index of zero. We demonstrate that a well-designed graphene/photonic-crystal metasurface can possess conical plasmonic dispersion at the Brillouin zone center with a triply degenerate state at the Dirac frequency, giving rise to the zero-effective-index of graphene plasmons. Plane-wave-emission and focusing effects of the graphene plasmons are achieved by tailoring such a zero-index metasurface. In addition to the tunable Dirac point frequency enabled by the electrical tuning of the graphene Fermi level, our highly integrated system also provides stable performance even when defects exist. This actively controllable on-chip platform can potentially be useful for integrated photonic circuits and devices.

Genetic diversity analysis and DNA finger printing are very useful in breeding programs, seed conservation and management. Jute (Corchorus spp.) is the second most important natural fiber crop after cotton. DNA fingerprinting studies in jute using SSR markers are limited. In this study, 58 jute accessions, including two control varieties (Huangma 179 and Kuanyechangguo) from the official variety registry in China were evaluated with 28 pairs of SSR primers. A total of 184 polymorphic loci were identified. Each primer detected 3 to 15 polymorphic loci, with an average of 6.6. The 58 jute accessions were DNA-fingerprinted with 67 SSR markers from the 28 primer pairs. These markers differentiated the 58 jute accessions from one another, with CoSSR305-120 and CoSSR174-195 differentiating Huangma 179 and Kuanyechangguo, respectively. NTSYS-pc2.10 software was used to analyze the genetic diversity in the 58 jute accessions. Their genetic similarity coefficients ranged from 0.520 to 0.910 with an average of 0.749, indicating relatively great genetic diversity among them. The 58 jute accessions were divided into four groups with the coefficient 0.710 used as a value for classification, consistent with their species and pedigrees. All these results may be useful both for protection of intellectual property rights of jute accessions and for jute improvement.

The purpose of this study was to use cotyledonary nodes as explants to establish an efficient regeneration protocol for jute (Corchorus capsularis L.) on Murashige and Skoog (MS) basal medium. Research into the different growth regulators using the orthogonal design L16 (45) revealed that the best shoot induction medium is MS medium containing 8% (w/v) agar and 3% (w/v) sucrose supplemented with 1.0 mg/L 6BA and 0.25 mg/L NAA. The average number of shoots per explant and the explant induction rate were 9.8 and 100%. After 3 weeks, 2–3 cm shoots were rooting on 1/2 MS medium containing 8% (w/v) agar and 3% (w/v) sucrose supplemented with 1.0 mg/L 6-BA + 0.2 mg/L NAA. Moreover, we optimized Agrobacterium-mediated transformation using the GUS gene transient expression system. The best condition for obtaining higher transformation rate consisted of the use of fresh explants to which 100 μM acetosyringone was added for a co-culture time of 10 min, the OD value of Agrobacterium liquid is 0.5 at 600 nm. These da...

White jute ( Corchorus capsularis L.) is recognized as an important industrial raw material fibre crop owing to its elite characters. However, little information is known about its molecular basis and genomics. In this study, a complementary DNA library of white jute was constructed and expressed sequence tags (ESTs) were characterized. The titers of original and amplified libraries were 2.32 × 10 7 and 1.07 × 10 9 pfu/mL, respectively. The recombinant frequency was 98.3% in the library. Most of the sequences ranged from 500 to 1500 bp with an average length of 750 bp. Results show 203 (73%) ESTs exhibited significant similarity with known or putative functional nucleotide sequences in the GenBank databases. Cluster analysis allowed the identification of 61 unique sequences. These genes were classified into six types by Gene Ontology (GO) annotation. The results also indicated that unigenes of C. capsularis have higher homology to Populus trichocarpa , Ricinus communis and Corchorus olitorius . This report will provide a valuable resource for the further investigations in the gene cloning, transcription or expression for white jute. Key words: White jute, Corchorus capsularis, cDNA library, construction, ESTs, analysis.

The Yamanaka factors convert mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) through a highly heterogeneous process. Here we profile single cells undergoing an optimized 7-day reprogramming process and show that cells start reprogramming relatively in sync, but diverge into two branches around day 2. The first branch of cells expressing Cd34/Fxyd5/Psca become nonpluripotent. The second one contains cells that are first Oct4+, then Dppa5a+ and pluripotent. We show that IFN-γ blocks this late transition. Our results reveal the heterogeneous nature of somatic cell reprogramming, identify Dppa5a as a marker for pluripotent and innate immunity as a potential barrier for reprogramming.One Sentence SummarySingle cell RNA sequencing reveals a continuum of cell fates from somatic to pluripotent and Dppa5a as a marker for chimera-competent iPSCs.

Background Genetic mapping and quantitative trait locus (QTL) detection are powerful methodologies in plant improvement and breeding. White jute (Corchorus capsularis L.) is an important industrial raw material fiber crop because of its elite characteristics. However, construction of a high-density genetic map and identification of QTLs has been limited in white jute due to a lack of sufficient molecular markers. The specific locus amplified fragment sequencing (SLAF-seq) strategy combines locus-specific amplification and high-throughput sequencing to carry out de novo single nuclear polymorphism (SNP) discovery and large-scale genotyping. In this study, SLAF-seq was employed to obtain sufficient markers to construct a high-density genetic map for white jute. Moreover, with the development of abundant markers, genetic dissection of fiber yield traits such as plant height was also possible. Here, we present QTLs associated with plant height that were identified using our newly constructed genetic linkage groups. Results An F8 population consisting of 100 lines was developed. In total, 69,446 high-quality SLAFs were detected of which 5,074 SLAFs were polymorphic; 913 polymorphic markers were used for the construction of a genetic map. The average coverage for each SLAF marker was 43-fold in the parents, and 9.8-fold in each F8 individual. A linkage map was constructed that contained 913 SLAFs on 11 linkage groups (LGs) covering 1621.4 cM with an average density of 1.61 cM per locus. Among the 11 LGs, LG1 was the largest with 210 markers, a length of 406.34 cM, and an average distance of 1.93 cM between adjacent markers. LG11 was the smallest with only 25 markers, a length of 29.66 cM, and an average distance of 1.19 cM between adjacent markers. ‘SNP_only’ markers accounted for 85.54% and were the predominant markers on the map. QTL mapping based on the F8 phenotypes detected 11 plant height QTLs including one major effect QTL across two cultivation locations, with each QTL accounting for 4.14–15.63% of the phenotypic variance. Conclusions To our knowledge, the linkage map constructed here is the densest one available to date for white jute. This analysis also identified the first QTL in white jute. The results will provide an important platform for gene/QTL mapping, sequence assembly, genome comparisons, and marker-assisted selection breeding for white jute.

White jute (Corchorus capsularis) and dark jute (Corchorus olitorius) are two important cultivated crops that are used for natural fibre production. Some genetic maps have been developed for dark jute, but the genetic map information for white jute (C. capsularis) is limited. In this study, a linkage map comprising 44 sequence-related amplified polymorphisms (SRAPs), 57 intersimple sequence repeats (ISSRs) and 18 randomly amplified polymorphic DNA (RAPD) covering 2185.7 cM with a mean density of 18.7 cM per locus was constructed in an F2 population consisting of 185 individuals derived from a cross between two diverse genotypes of ‘Xinxuan No. 1’ and ‘Qiongyueqing’ in white jute. These markers were evenly distributed in the linkage groups without any clustering. This genetic linkage map construction will facilitate the mapping of agronomic traits and marker-assisted selection breeding in white jute.

To elucidate the hemicelluloses degradation and dissolution during hydrothermal pretreatment, hemicelluloses separated from both hydrolysate and pretreated substrate were investigated. Along with the pretreatment proceeding, some hemicelluloses fractions dissolved and diffused into the bulk liquor; MW (molecular weight) of these hemicelluloses fractions increased first and then decreased as well as amount of the fractions. Based on the definition of MW of the soluble hemicellulose, it has been concluded that some insoluble hemicellulose fractions appeared in the hydrolysate. In contrast, the hemicellulose degradation occurred continually and had been observed by the gradual decrease of MW of the hemicellulose isolated from pretreated substrate. Lingering dissolution at the later stage might attribute to the facts that some soluble fractions were still entrapped in the substrate. 5–15% hemicellulose fractions remained in the pretreated substrate at the later stage were composed of soluble species.