ABSTRACT
Fruit softening, an irreversible process that occurs during fruit ripening, can lead to losses and waste during postharvest transportation and storage. Cell wall disassembly is the main factor leading to loss of fruit firmness, and several ripening-associated cell wall genes have been targeted for genetic modification, particularly pectin modifiers. However, individual knockdown of most cell wall-related genes has had minimal influence on cell wall integrity and fruit firmness, with the notable exception of pectate lyase. Compared to pectin disassembly, studies of the cell wall matrix, the xyloglucan-cellulose framework, and underlying mechanisms during fruit softening are limited. Here, a tomato (Solanum lycopersicum) fruit ripening-associated α-expansin (SlExpansin1/SlExp1) and an endoglucanase (SlCellulase2/SlCel2), which function in the cell wall matrix, were knocked out individually and together using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9-mediated genome editing. Simultaneous knockout of SlExp1 and SlCel2 enhanced fruit firmness, reduced depolymerization of homogalacturonan-type pectin and xyloglucan, and increased cell adhesion. In contrast, single knockouts of either SlExp1 or SlCel2 did not substantially change fruit firmness, while simultaneous overexpression of SlExp1 and SlCel2 promoted early fruit softening. Collectively, our results demonstrate that SlExp1 and SlCel2 synergistically regulate cell wall disassembly and fruit softening in tomato.
Subject(s)
Cellulase , Solanum lycopersicum , Fruit/metabolism , Solanum lycopersicum/genetics , Cellulase/genetics , Cellulase/metabolism , Plants, Genetically Modified/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Pectins/metabolism , Cell Wall/metabolismABSTRACT
Discovering effective anti-tumor drug combinations is crucial for advancing cancer therapy. Taking full account of intricate biological interactions is highly important in accurately predicting drug synergy. However, the extremely limited prior knowledge poses great challenges in developing current computational methods. To address this, we introduce SynergyX, a multi-modality mutual attention network to improve anti-tumor drug synergy prediction. It dynamically captures cross-modal interactions, allowing for the modeling of complex biological networks and drug interactions. A convolution-augmented attention structure is adopted to integrate multi-omic data in this framework effectively. Compared with other state-of-the-art models, SynergyX demonstrates superior predictive accuracy in both the General Test and Blind Test and cross-dataset validation. By exhaustively screening combinations of approved drugs, SynergyX reveals its ability to identify promising drug combination candidates for potential lung cancer treatment. Another notable advantage lies in its multidimensional interpretability. Taking Sorafenib and Vorinostat as an example, SynergyX serves as a powerful tool for uncovering drug-gene interactions and deciphering cell selectivity mechanisms. In summary, SynergyX provides an illuminating and interpretable framework, poised to catalyze the expedition of drug synergy discovery and deepen our comprehension of rational combination therapy.
Subject(s)
Drug Discovery , Lung Neoplasms , Humans , Catalysis , Combined Modality Therapy , Research DesignABSTRACT
Histone demethylase JMJD2D (also known as KDM4D) can specifically demethylate H3K9me2/3 to activate its target gene expression. Our previous study has demonstrated that JMJD2D can protect intestine from dextran sulfate sodium (DSS)-induced colitis by activating Hedgehog signaling; however, its involvement in host defense against enteric attaching and effacing bacterial infection remains unclear. The present study was aimed to investigate the role of JMJD2D in host defense against enteric bacteria and its underlying mechanisms. The enteric pathogen Citrobacter rodentium (C. rodentium) model was used to mimic clinical colonic infection. The responses of wild-type and JMJD2D-/- mice to oral infection of C. rodentium were investigated. Bone marrow chimeric mice were infected with C. rodentium. JMJD2D expression was knocked down in CMT93 cells by using small hairpin RNAs, and Western blot and real-time PCR assays were performed in these cells. The relationship between JMJD2D and STAT3 was studied by co-immunoprecipitation and chromatin immunoprecipitation. JMJD2D was significantly up-regulated in colonic epithelial cells of mice in response to Citrobacter rodentium infection. JMJD2D-/- mice displayed an impaired clearance of C. rodentium, more body weight loss, and more severe colonic tissue pathology compared with wild-type mice. JMJD2D-/- mice exhibited an impaired expression of IL-17F in the colonic epithelial cells, which restricts C. rodentium infection by inducing the expression of antimicrobial peptides. Accordingly, JMJD2D-/- mice showed a decreased expression of ß-defensin-1, ß-defensin-3, and ß-defensin-4 in the colonic epithelial cells. Mechanistically, JMJD2D activated STAT3 signaling by inducing STAT3 phosphorylation and cooperated with STAT3 to induce IL-17F expression by interacting with STAT3 and been recruited to the IL-17F promoter to demethylate H3K9me3. Our study demonstrates that JMJD2D contributes to host defense against enteric bacteria through up-regulating IL-17F to induce ß-defensin expression.
Subject(s)
Citrobacter rodentium , Colon , Enterobacteriaceae Infections , Interleukin-17 , Jumonji Domain-Containing Histone Demethylases , Mice, Knockout , Up-Regulation , beta-Defensins , Animals , Mice , beta-Defensins/metabolism , Enterobacteriaceae Infections/metabolism , Enterobacteriaceae Infections/immunology , Jumonji Domain-Containing Histone Demethylases/metabolism , Jumonji Domain-Containing Histone Demethylases/genetics , Interleukin-17/metabolism , Colon/metabolism , Colon/microbiology , Colon/pathology , Mice, Inbred C57BL , Colitis/metabolism , Colitis/microbiology , STAT3 Transcription Factor/metabolismABSTRACT
Epulopiscium spp. are the largest known heterotrophic bacteria; a large cigar-shaped individual is a million times the volume of Escherichia coli. To better understand the metabolic potential and relationship of Epulopiscium sp. type B with its host Naso tonganus, we generated a high-quality draft genome from a population of cells taken from a single fish. We propose the name Candidatus Epulopiscium viviparus to describe populations of this best-characterized Epulopiscium species. Metabolic reconstruction reveals more than 5% of the genome codes for carbohydrate active enzymes, which likely degrade recalcitrant host-diet algal polysaccharides into substrates that may be fermented to acetate, the most abundant short-chain fatty acid in the intestinal tract. Moreover, transcriptome analyses and the concentration of sodium ions in the host intestinal tract suggest that the use of a sodium motive force (SMF) to drive ATP synthesis and flagellar rotation is integral to symbiont metabolism and cellular biology. In natural populations, genes encoding both F-type and V-type ATPases and SMF generation via oxaloacetate decarboxylation are among the most highly expressed, suggesting that ATPases synthesize ATP and balance ion concentrations across the cell membrane. High expression of these and other integral membrane proteins may allow for the growth of its extensive intracellular membrane system. Further, complementary metabolism between microbe and host is implied with the potential provision of nitrogen and B vitamins to reinforce this nutritional symbiosis. The few features shared by all bacterial behemoths include extreme polyploidy, polyphosphate synthesis, and thus far, they have all resisted cultivation in the lab.
Subject(s)
Sodium , Vacuolar Proton-Translocating ATPases , Animals , Sodium/metabolism , Bacteria/metabolism , Clostridiales/metabolism , Vacuolar Proton-Translocating ATPases/metabolism , Adenosine Triphosphate/metabolismABSTRACT
Water responsive polymers represent a remarkable group of soft materials, acting as a laboratory for diverse water responsive physical phenomena and cutting-edge biology-electronics interfaces. We report on peculiarly distinctive viscoelastic behaviors of the biobased water responsive polymer cellulose 10-undecenoyl ester, while biobased regenerated cellulose displays stronger hydroplastic behaviors. We discovered a novel hydrous deformation mechanism involving the stretching of hydrogen bonds mediated by hydroxyl groups and water molecules, serving as a crucial factor in accommodating deformations. In parallel, the microstructure of cellulose 10-undecenoyl ester with unique coexisting nanoparticles and a continuous phase of entangled chains is mechanically resilient in the anhydrous state but enhances structural stiffness in the hydrous state. This variation arises from a different hydration level within the hydrous microstructure. Such a fundamental discovery offers valuable insights into the connection between the microscopic physical properties that can be influenced by water and the corresponding viscoelastic responses, extending its applicability to a wide range of hygroscopic materials.
ABSTRACT
Circular ribonucleic acids (RNAs) (circRNAs) are formed by covalently linking the downstream splice donor and the upstream splice acceptor. One of the most important functions of circRNAs is mainly exerted through binding RNA-binding proteins (RBPs). However, there is no efficient algorithm for identifying genome-wide circRNA-RBP interactions. Here, we developed a unique algorithm, circRIP, for identifying circRNA-RBP interactions from RNA immunoprecipitation sequencing (RIP-Seq) data. A simulation test demonstrated the sensitivity and specificity of circRIP. By applying circRIP, we identified 95 IGF2BP3-binding circRNAs based on the IGF2BP3 RIP-Seq dataset. We further identified 2823 and 1333 circRNAs binding to >100 RBPs in K562 and HepG2 cell lines, respectively, based on enhanced cross-linking immunoprecipitation (eCLIP) data, demonstrating the significance to survey the potential interactions between circRNAs and RBPs. In this study, we provide an accurate and sensitive tool, circRIP (https://github.com/bioinfolabwhu/circRIP), to systematically identify RBP and circRNA interactions from RIP-Seq and eCLIP data, which can significantly benefit the research community for the functional exploration of circRNAs.
Subject(s)
RNA, Circular , RNA , Genome , Immunoprecipitation , RNA/genetics , RNA/metabolism , Sequence Analysis, RNAABSTRACT
Changes in both lignin biosynthesis and DNA methylation have been reported to be associated with chilling stress in plants. When stored at low temperatures, red-fleshed loquat is prone to lignification, with increased lignin content and fruit firmness, which has deleterious effects on taste and eating quality. Here, we found that 5 °C storage mitigated the increasing firmness and lignin content of red-fleshed 'Dahongpao' ('DHP') loquat fruit that occurred during 0 °C storage. EjNAC5 was identified by integrating RNA sequencing with whole-genome bisulfite sequencing analysis of 'DHP' loquat fruit. The transcript levels of EjNAC5 were positively correlated with changes in firmness and negatively correlated with changes in DNA methylation level of a differentially methylated region in the EjNAC5 promoter. In white-fleshed 'Baisha' ('BS') loquat fruit, which do not undergo chilling-induced lignification at 0 °C, the transcripts of EjNAC5 remained low and the methylation level of the differentially methylated region in the EjNAC5 promoter was higher, compared with 'DHP' loquat fruit. Transient overexpression of EjNAC5 in loquat fruit and stable overexpression in Arabidopsis and liverwort led to an increase in lignin content. Furthermore, EjNAC5 interacts with EjERF39 and EjHB1 and activates the transcription of Ej4CL1 and EjPRX12 genes involved in lignin biosynthesis. This regulatory network involves different transcription factors from those involved in the lignification pathway. Our study indicates that EjNAC5 promoter methylation modulates EjNAC5 transcript levels and identifies novel EjNAC5-EjERF39-Ej4CL1 and EjNAC5-EjHB1-EjPRX12 regulatory modules involved in chilling induced-lignification.
Subject(s)
Cold Temperature , Eriobotrya , Fruit , Lignin , Plant Proteins , Transcription Factors , Eriobotrya/genetics , Eriobotrya/metabolism , Eriobotrya/physiology , Fruit/genetics , Fruit/metabolism , Lignin/metabolism , Lignin/biosynthesis , Transcription Factors/metabolism , Transcription Factors/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , DNA MethylationABSTRACT
OBJECTIVE: Our previous study found that overexpression of uncoupling protein-2 (UCP2) had a protective effect on lipopolysaccharide (LPS)-induced sepsis cardiomyocytes. The aim of this study was to explore the effect and mechanism of uncoupling protein-2 (UCP2) on myocardial ischemia-reperfusion injury. METHODS: In this study, we established hypoxia-reoxygenation (HR) injury model in rats and isolated cardiomyocytes of newborn rats. We also carried out following methods which include virus transfection technology, cell counting Kit-8 (CCK8), flow cytometry, enzyme linked immunosorbent assay (ELISA), Western blot (WB), quantitative reverse transcription PCR (RT qPCR), transmission electron microscopy, fluorescence colocalization and immunoprecipitation. MAIN RESULTS: The results of this study showed that hypoxia-reoxygenation treatment in cardiomyocytes increased UCP2, myocardial enzyme and myocardial apoptosis and weakened cardiomyocyte viability. We observed increased cardiomyocyte viability and mitochondrial membrane potential, decreased myocardial enzyme and myocardial apoptosis, Inhibition of oxidative stress when UCP2 was overexpressed in cardiomyocytes. It also can Increase ATP and stabilize mitochondrial dynamics. Further studies founded that Sirtuin-3(SIRT3) changed with the expression of UCP2, which was confirmed by fluorescence co-localization and immunoprecipitation. CONCLUSIONS: Our findings revealed that UCP2 and SIRT3 were important targets of anti-myocardial injury by inhibiting cellular oxidative stress and stabilizing mitochondrial dynamics.
Subject(s)
Sirtuin 3 , Animals , Rats , Hypoxia , Mitochondrial Dynamics , Oxidative Stress , Sirtuin 3/genetics , Sirtuin 3/metabolism , Uncoupling Protein 2/genetics , Uncoupling Protein 2/metabolismABSTRACT
Spermatogonial stem cells (SSCs) play a crucial role in mammalian spermatogenesis and maintain the stable inheritance of the germline in livestock. However, stress and bacterial or viral infections can disrupt immune homeostasis of the testes, thereby leading to spermatogenesis destruction and infertility, which severely affects the health and productivity of mammals. This study aimed to explore the effect of ubiquitin C-terminal hydrolase L1 (UCHL1) knockdown (KD) in goat SSCs and mouse testes and investigate the potential anti-inflammatory function of UCHL1 in a poly(I:C)-induced inflammation model to maintain microenvironmental homeostasis. In vitro, the downregulation of UCHL1 (UCHL1 KD) in goat SSCs increased the expression levels of apoptosis and inflammatory factors and inhibited the self-renewal and proliferation of SSCs. In vivo, the structure of seminiferous tubules and spermatogenic cells was disrupted after UCHL1 KD, and the expression levels of apoptosis- and inflammation-related proteins were significantly upregulated. Furthermore, UCHL1 inhibited the TLR3/TBK1/IRF3 pathway to resist poly(I:C)-induced inflammation in SSCs by antagonizing HSPA8 and thus maintaining SSC autoimmune homeostasis. Most importantly, the results of this study showed that UCHL1 maintained immune homeostasis of SSCs and spermatogenesis. UCHL1 KD not only inhibited the self-renewal and proliferation of goat SSCs and spermatogenesis but was also involved in the inflammatory response of goat SSCs. Additionally, UCHL1 has an antiviral function in SSCs by antagonizing HSPA8, which provides an important basis for exploring the specific mechanisms of UCHL1 in goat spermatogenesis.
Subject(s)
Goats , Spermatogonia , Animals , Male , Mice , Homeostasis , Inflammation/metabolism , Spermatogenesis/physiology , Spermatogonia/metabolism , Stem Cells , Testis/metabolismABSTRACT
An environmentally friendly electrochemical strategy for the synthesis of SCF3-containing oxindoles was developed. This electrochemical transformation was accomplished through a cascade trifluoromethylthiolation/cyclization of N-acrylamides with AgSCF3, obviating the requirement for external oxidants. A variety of functional groups were well tolerated in this transformation.
ABSTRACT
The significant function of circRNAs in cancer was recognized in recent work, so a well-organized resource is required for characterizing the interactions between circRNAs and other functional molecules (such as microRNA and RNA-binding protein) in cancer. We previously developed cancer-specific circRNA database (CSCD), a comprehensive database for cancer-specific circRNAs, which is widely used in circRNA research. Here, we updated CSCD to CSCD2 (http://geneyun.net/CSCD2 or http://gb.whu.edu.cn/CSCD2), which includes significantly more cancer-specific circRNAs identified from a large number of human cancer and normal tissues/cell lines. CSCD2 contains >1000 samples (825 tissues and 288 cell lines) and identifies a large number of circRNAs: 1 013 461 cancer-specific circRNAs, 1 533 704 circRNAs from only normal samples and 354 422 circRNAs from both cancer and normal samples. In addition, CSCD2 predicts potential miRNA-circRNA and RBP-circRNA interactions using binding motifs from >200 RBPs and 2000 microRNAs. Furthermore, the potential full-length and open reading frame sequence of these circRNAs were also predicted. Collectively, CSCD2 provides a significantly enhanced resource for exploring the function and regulation of circRNAs in cancer.
Subject(s)
Databases, Genetic , MicroRNAs/genetics , Neoplasms/genetics , RNA, Circular/genetics , Humans , Neoplasms/classification , RNA, Circular/classificationABSTRACT
BACKGROUND: In older stroke patients with frailty, nutritional deficiencies can amplify their susceptibility, delay recovery, and deteriorate prognosis. A precise predictive model is crucial to assess their nutritional risk, enabling targeted interventions for improved clinical outcomes. OBJECTIVE: To develop and externally validate a nutritional risk prediction model integrating general demographics, physical parameters, psychological indicators, and biochemical markers. The aim is to facilitate the early identification of older stroke patients requiring nutritional intervention. METHODS: This was a multicenter cross-sectional study. A total of 570 stroke patients were included, 434 as the modeling set and 136 as the external validation set. The least absolute shrinkage selection operator (LASSO) regression analysis was used to select the predictor variables. Internal validation was performed using Bootstrap resampling (1000 iterations). The nomogram was constructed based on the results of logistic regression. The performance assessment relied on the receiver operating characteristic curve (ROC), Hosmer--Lemeshow test, calibration curves, Brier score, and decision curve analysis (DCA). RESULTS: The predictive nomogram encompassed seven pivotal variables: Activities of Daily Living (ADL), NIHSS score, diabetes, Body Mass Index (BMI), grip strength, serum albumin levels, and depression. Together, these variables comprehensively evaluate the overall health and nutritional status of elderly stroke patients, facilitating accurate assessment of their nutritional risk. The model exhibited excellent accuracy in both the development and external validation sets, evidenced by AUC values of 0.934 and 0.887, respectively. Such performance highlights its efficacy in pinpointing elderly stroke patients who require nutritional intervention. Moreover, the model showed robust goodness of fit and practical applicability, providing essential clinical insights to improve recovery and prognosis for patients prone to malnutrition. CONCLUSIONS: Elderly individuals recovering from stroke often experience significant nutritional deficiencies. The nomogram we devised accurately assesses this risk by combining physiological, psychological, and biochemical metrics. It equips healthcare providers with the means to actively screen for and manage the nutritional care of these patients. This tool is instrumental in swiftly identifying those in urgent need of targeted nutritional support, which is essential for optimizing their recovery and managing their nutrition more effectively.
Subject(s)
Frailty , Nomograms , Nutritional Status , Stroke , Humans , Aged , Male , Female , Stroke/complications , Aged, 80 and over , Cross-Sectional Studies , Geriatric Assessment/methods , Activities of Daily Living , Nutrition Assessment , Risk Assessment/methods , Risk Factors , Frail Elderly , Malnutrition/diagnosisABSTRACT
INTRODUCTION: Quality evaluation of Huang-qin is significant to ensure its clinical efficacy. OBJECTIVE: This study aims to establish an accurate, rapid and comprehensive Huang-qin quality evaluation method to overcome the time-consuming and laborious shortcomings of traditional herbal medicine quality assessment methods. METHODS: The contents of baicalin, baicalein and scutellarin in Huang-qin from five different origins were analyzed by FT-IR and NIR spectra combined with multivariate data technology. The quality of Huang-qin from different origins was evaluated by TOPSIS and consistency analysis based on the content of three active ingredients. The correlation between ecological factors and the accumulation of active ingredients was explored. RESULTS: Satisfactory prediction results of PLS models were obtained. Relatively, the model based on FT-IR combined with the PLS regression method has higher R2 and smaller RMSE than the NIR combined with the PLS method. TOPSIS and consistency analysis results showed that the quality of Huang-qin from different geographical origins was significantly different. The results showed that the quality of Huang-qin produced in Shanxi Province was the best among the five origins studied. The results also found that the quality of Huang-qin in different growing areas of the same origin was not completely consistent. The correlation study showed that altitude, sunshine duration and rainfall were the main factors that caused the quality difference of medicinal materials in different geographical origins. CONCLUSION: This study provides a reference for the rapid quantitative analysis of the active components of herbal medicine and the quality evaluation of them.
Subject(s)
Drugs, Chinese Herbal , Spectroscopy, Near-Infrared , Spectroscopy, Near-Infrared/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Spectroscopy, Fourier Transform Infrared/methods , Flavonoids/analysis , Flavanones/analysis , Chemometrics/methods , Apigenin/analysis , Apigenin/chemistry , Quality Control , Glucuronates/analysis , Least-Squares Analysis , Scutellaria baicalensis/chemistryABSTRACT
Phytohormones, epigenetic regulation and environmental factors regulate fruit ripening but their interplay during strawberry fruit ripening remains to be determined. In this study, bagged strawberry fruit exhibited delayed ripening compared with fruit grown in normal light, correlating with reduced abscisic acid (ABA) accumulation. Transcription of the key ABA catabolism gene, ABA 8'-hydroxylase FaCYP707A4, was induced in bagged fruit. With light exclusion whole genome DNA methylation levels were up-regulated, corresponding to a delayed ripening process, while DNA methylation levels in the promoter of FaCYP707A4 were suppressed, correlating with increases in transcript and decreased ABA content. Experiments indicated FaCRY1, a blue light receptor repressed in bagged fruit and FaAGO4, a key protein involved in RNA-directed DNA methylation, could bind to the promoter of FaCYP707A4. The interaction between FaCRY1 and FaAGO4, and an increased enrichment of FaAGO4 directed to the FaCYP707A4 promoter in fruit grown under light suggests FaCRY1 may influence FaAGO4 to modulate the DNA methylation status of the FaCYP707A4 promoter. Furthermore, transient overexpression of FaCRY1, or an increase in FaCRY1 transcription by blue light treatment, increases the methylation level of the FaCYP707A4 promoter, while transient RNA interference of FaCRY1 displayed opposite phenotypes. These findings reveal a mechanism by which DNA methylation influences ABA catabolism, and participates in light-mediated strawberry ripening.
Subject(s)
Abscisic Acid , DNA Methylation , Fragaria , Fruit , Gene Expression Regulation, Plant , Light , Plant Proteins , Promoter Regions, Genetic , Abscisic Acid/metabolism , Fragaria/genetics , Fragaria/metabolism , Fragaria/growth & development , DNA Methylation/genetics , Fruit/genetics , Fruit/growth & development , Fruit/metabolism , Gene Expression Regulation, Plant/radiation effects , Plant Proteins/metabolism , Plant Proteins/genetics , Promoter Regions, Genetic/geneticsABSTRACT
Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. Combining high toughness and strong, persisting repeatable adhesion has always been a daunting challenge for adhesive gels. However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. The maximum adhesive strength and debonding work exceed 320 ± 0.50 KPa and 160.97 ± 0.20 J m-2 , respectively. After five cycles (re-lap after detaching), the adhesive strength still remains above 200 KPa. Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions.
ABSTRACT
RNA interference (RNAi)-based technologies are starting to be commercialized as a new approach for agricultural pest control. Horizontally transferred genes (HTGs), which have been transferred into insect genomes from viruses, bacteria, fungi or plants, are attractive targets for RNAi-mediated pest control. HTGs are often unique to a specific insect family or even genus, making it unlikely that RNAi constructs targeting such genes will have negative effects on ladybugs, lacewings and other beneficial predatory insect species. In this study, we sequenced the genome of a red, tobacco-adapted isolate of Myzus persicae (green peach aphid) and bioinformatically identified 30 HTGs. We then used plant-mediated virus-induced gene silencing (VIGS) to show that several HTGs of bacterial and plant origin are important for aphid growth and/or survival. Silencing the expression of fungal-origin HTGs did not affect aphid survivorship but decreased aphid reproduction. Importantly, although there was uptake of plant-expressed RNA by Coccinella septempunctata (seven-spotted ladybugs) via the aphids that they consumed, we did not observe negative effects on ladybugs from aphid-targeted VIGS constructs. To demonstrate that this approach is more broadly applicable, we also targeted five Bemisia tabaci (whitefly) HTGs using VIGS and demonstrated that knockdown of some of these genes affected whitefly survival. As functional HTGs have been identified in the genomes of numerous pest species, we propose that these HTGs should be explored further as efficient and safe targets for control of insect pests using plant-mediated RNA interference.
Subject(s)
Aphids , Animals , Aphids/genetics , RNA Interference , Plants, Genetically Modified/genetics , Base Sequence , Nicotiana/geneticsABSTRACT
Gene expression and immune status in human tissues are changed with aging. There is a need to develop a comprehensive platform to explore the dynamics of age-related gene expression and immune profiles across tissues in genome-wide studies. Here, we collected RNA-Seq datasets from GTEx project, containing 16 704 samples from 30 major tissues in six age groups ranging from 20 to 79 years old. Dynamic gene expression along with aging were depicted and gene set enrichment analysis was performed among those age groups. Genes from 34 known immune function categories and immune cell compositions were investigated and compared among different age groups. Finally, we integrated all the results and developed a platform named ADEIP (http://gb.whu.edu.cn/ADEIP or http://geneyun.net/ADEIP), integrating the age-dependent gene expression and immune profiles across tissues. To demonstrate the usage of ADEIP, we applied two datasets: severe acute respiratory syndrome coronavirus 2 and human mesenchymal stem cells-assoicated genes. We also included the expression and immune dynamics of these genes in the platform. Collectively, ADEIP is a powerful platform for studying age-related immune regulation in organogenesis and other infectious or genetic diseases.
Subject(s)
COVID-19/genetics , Organ Specificity/genetics , SARS-CoV-2/genetics , Adult , Aged , COVID-19/virology , Epithelial Cells/metabolism , Epithelial Cells/virology , Female , Gene Expression Regulation/genetics , Humans , Male , Middle Aged , RNA-Seq , Young AdultABSTRACT
MOTIVATION: Drug response prediction (DRP) plays an important role in precision medicine (e.g. for cancer analysis and treatment). Recent advances in deep learning algorithms make it possible to predict drug responses accurately based on genetic profiles. However, existing methods ignore the potential relationships among genes. In addition, similarity among cell lines/drugs was rarely considered explicitly. RESULTS: We propose a novel DRP framework, called TGSA, to make better use of prior domain knowledge. TGSA consists of Twin Graph neural networks for Drug Response Prediction (TGDRP) and a Similarity Augmentation (SA) module to fuse fine-grained and coarse-grained information. Specifically, TGDRP abstracts cell lines as graphs based on STRING protein-protein association networks and uses Graph Neural Networks (GNNs) for representation learning. SA views DRP as an edge regression problem on a heterogeneous graph and utilizes GNNs to smooth the representations of similar cell lines/drugs. Besides, we introduce an auxiliary pre-training strategy to remedy the identified limitations of scarce data and poor out-of-distribution generalization. Extensive experiments on the GDSC2 dataset demonstrate that our TGSA consistently outperforms all the state-of-the-art baselines under various experimental settings. We further evaluate the effectiveness and contributions of each component of TGSA via ablation experiments. The promising performance of TGSA shows enormous potential for clinical applications in precision medicine. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/violet-sto/TGSA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Neoplasms , Neural Networks, Computer , Humans , Algorithms , Software , Precision Medicine , ProteinsABSTRACT
Tactile sensing with stress and temperature sensing as core elements have shown promising prospects in intelligent robots and the human-machine interface. Mechanoluminescence (ML)-based stress sensing can realize the direct sensing of mechanical stimulation, whereas indirect temperature sensing based on luminescent sensing materials usually requires the stimulation of extra light or force. Herein, a trap-controlled material Sr2MgAl22O36:Mn2+ with bifunctional mechano/thermal sensing applications was developed and investigated in detail. Visualized bright green-emitting ML and thermally stimulated luminescence (TSL) directly and rapidly responded to mechano/thermal dual stimulation in the Sr2MgAl22O36:Mn2+/PDMS composite film. It is worth mentioning that this study proposed a new idea of direct temperature sensing by the initial intensity of TSL due to thermal-photo energy conversion, unlike previous temperature sensor technology. Based on this, we designed a flexible optical skin with a simple structure and verified its application prospect as a tactile sensing material with dual mechano/thermal response, establishing a unique imaging mode and providing a convenient, reliable, and sensitive way to remotely visualize the distribution of stress and temperature. This study paves a new way for the development of optical skins with simple structures and sensitive visibility in the application of intelligent robot tactile sensing.
ABSTRACT
An efficient electrochemical trifluoromethylation of coumarins using CF3SO2NHNHBoc as the source of the trifluoromethyl group was developed. Under catalyst-free and external oxidant-free electrolysis conditions, a range of 3-trifluoromethyl coumarins were obtained in moderate to good yields. The method could be easily scaled up with moderate efficiency.