Trophic effects of jellyfish blooms on fish populations in ecosystems of the coastal waters of China.

Jellyfish play an important role in the material cycling and energy flow of food webs, and massive aggregations may have deleterious consequences for local fisheries; yet a theoretical framework of the trophic effects of jellyfish blooms on coastal fisheries is unclear. To address this knowledge gap, we assessed the trophic interactions between cooccurring bloom jellyfish and dominant fish groups (omnivorous fish and piscivorous fish) in the coastal waters of China (CWC) via stable isotope analysis; we subsequently discussed how jellyfish blooms may affect energy flow through coastal ecosystems. Our results indicate a considerable degree of trophic overlap (mean ratio > 65 %) between jellyfish and small omnivorous fish (< 10 cm), highlighting a similarity in feeding habits, while the overlap ratio decreased to <55 % of the large omnivorous fish group (> 10 cm). Relatively higher trophic levels and smaller overlaps of large omnivorous fish were found in the ecosystem with high jellyfish biomass, which suggested that they may reinforce the ontogenetic trophic shift pattern to alleviate the potential for resource competition with jellyfish under conditions of jellyfish explosion. The smallest trophic overlap (< 20 %) highlighted the strong trophic differentiation between jellyfish and piscivorous fish. Additionally, our study suggested that a massive aggregation of jellyfish can negatively influence zooplankton but may not transfer energy further up efficiently, implying a weak trophic coupling between jellyfish and upper-trophic levels in CWC ecosystems. Thus, we speculate that jellyfish play an important role in shaping pathways involved in the energy transfer of food webs and that large blooms may negatively affect fisheries through bottom-up control affecting prey availability. In general, these results hold strong potential to further improve the understanding of the trophic interactions between jellyfish and fish populations. Furthermore, this study provides valuable data for predicting the consequences of jellyfish blooms on ecosystems, and is crucial for ecosystem-based management of coastal fisheries.

Organophosphate esters (OPEs) pollution characteristics, bioaccumulation and human consumption implication in wild marine organisms from the Yellow River Estuary, China.

As the substitutes of polybrominated diphenyl ethers, organophosphate esters (OPEs) with high concentrations have accumulated in the estuaries, bays, and harbors. However, limited information is available about the OPEs in the estuary organism categories, especially under the multiple industrial pressure. This study investigated the occurrence, bioaccumulation and human consumption implication in wild marine organisms from the Yellow River Estuary, where located many petroleum and chemical manufacturing industries. This study found that concentrations of Σ13OPEs ranged from 547 ng/L to 1164 ng/L in seawater (median: 802 ng/L), from 384 to 1366 ng/g dw in the sediment (median: 601 ng/g dw), and from 419 to 959 ng/g dw (median: 560 ng/g dw) in the marine organisms. The congener compositions in the organisms were dominated by alkyl-OPEs (80.7 %), followed by halogenated-OPEs (18.8 %) and aryl-OPEs (0.5 %). Based on the principal component analysis, petrochemical pollution, and industrial wastewater discharge were distinguished as the main plausible sources of OPEs to the YRE ecosystem. Most OPEs had potential or strong bioaccumulation capacity on the organisms, with a positive correlation between log BAF (Bioaccumulation Factor) and log Kow of OPEs. The highest estimated daily intake value of OPEs was tri-n-propyl phosphate, exceeding 300 ng/kg·bw/day via consuming fish. The highest hazard quotients from OPEs ranged from 0.001 to 0.1, indicating a low risk to human health by consuming marine organisms in the YRE. As the consumption of OPEs increases year by year, the risks of OPEs still cannot be ignored.

Bio-inspired synthesis of N-doped TiO2/C nanocrystals using jellyfish mucus with high visible-light photocatalytic efficiency.

Non-metal doping of titanium dioxide (TiO2) has been widely investigated, because it can facilely improve the optical response of TiO2 under visible light excitation in environmental pollution treatments. In the ongoing efforts, however, little consideration has been given to the use of harmful marine organisms as dopants. Here, we employed the natural mucus proteins of the large harmful jellyfish Aurelia coerulea and Nemopilema nomurai, which have frequently bloomed in East Asian marginal seas in recent decades, to synthesize mesoporous nitrogen-doped TiO2 nanocrystals modified with carbon (N-TiO2/C) by a simple hydrothermal method. These nanocrystals were composed of predominantly anatase phase and a small amount of brookite phase TiO2. Their mesoporous structures changed with the variation of the volume ratio of jellyfish mucus added to tetrabutyl titanate (TBT). At the same ratio, larger surface area and pore volume but smaller pore size were observed in N-TiO2/C nanocrystals from N. nomurai rather than A. coerulea. Nitrogen was determinately doped into the lattice of the prepared nanocrystals and the carbon species were modified on their surfaces, which narrowed the band gap, facilitated the separation of photogenerated electron-hole pairs and favored the absorption of visible light, thus improving their visible light photocatalytic activity. The photocatalytic degradation efficiency of Rhodamine B (RhB) under visible light irradiation first increased and then decreased with the gradual increase of the volume ratio of jellyfish mucus proteins to TBT. The maximum reached 97.52% in 20 min from N-TiO2/C nanocrystals synthesized using N. nomurai mucus at the volume ratio of 4 : 1, which showed a remarkably strong visible light absorption, lower band gap energy and smaller electron transfer resistance. These N-TiO2/C nanocrystals also had a relatively stable crystal structure in multiple degradation reactions. The main active species including superoxide radicals (˙O2 -), photogenerated holes (h+) and hydroxyl radicals (˙OH) were found to play a major role in the degradation process of RhB. This study highlights the potential high-value reapplication of harmful jellyfish mucus as a natural organic matrix in fabricating advanced materials with optimized functional properties.

Exosomal MicroRNAs: Biomarkers of moyamoya disease and involvement in vascular cytoskeleton reconstruction.

Moyamoya disease currently lacks a suitable method for early clinical screening.This study aimed to identify a simple and feasible clinical screening index by investigating microRNAs carried by peripheral blood exosomes. Experimental subjects participated in venous blood collection, and exosomes were isolated using Exquick-related technology. Sequencing was performed on the extracted exosomal ribonucleic acids (RNAs) to identify differential microRNAs. Verification of the results involved selecting relevant samples from the genetic database. The study successfully pinpointed a potential marker for early screening, hsa-miR-328-3p + hsa-miR-200c-3p carried by peripheral blood exosomes. Enrichment analysis of target genes revealed associations with intercellular junctions, impaired cytoskeletal regulation, and increased fibroblast proliferation, leading to bilateral internal carotid artery neointimal expansion and progressive stenosis. These findings establish the diagnostic value of hsa-miR-328-3p+hsa-miR-200c-3p in screening moyamoya disease, while also contributing to a deeper understanding of its underlying pathophysiology. Significant differences in microRNA expressions derived from peripheral blood exosomes were observed between moyamoya disease patients and control subjects. Consequently, the utilization of peripheral blood exosomes, specifically hsa-miR-328-3p + hsa-miR-200c-3p, holds potential for diagnostic screening purposes.

Erratum: Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury: Erratum.

[This corrects the article DOI: 10.7150/thno.54550.].

Real-Time Detection of Unauthorized Unmanned Aerial Vehicles Using SEB-YOLOv8s.

Aiming at real-time detection of UAVs, small UAV targets are easily missed and difficult to detect in complex backgrounds. To maintain high detection performance while reducing memory and computational costs, this paper proposes the SEB-YOLOv8s detection method. Firstly, the YOLOv8 network structure is reconstructed using SPD-Conv to reduce the computational burden and accelerate the processing speed while retaining more shallow features of small targets. Secondly, we design the AttC2f module and replace the C2f module in the backbone of YOLOv8s with it, enhancing the model's ability to obtain accurate information and enriching the extracted relevant information. Finally, Bi-Level Routing Attention is introduced to optimize the Neck part of the network, reducing the model's attention to interfering information and filtering it out. The experimental results show that the mAP50 of the proposed method reaches 90.5% and the accuracy reaches 95.9%, which are improvements of 2.2% and 1.9%, respectively, compared with the original model. The mAP50-95 is improved by 2.7%, and the model's occupied memory size only increases by 2.5 MB, effectively achieving high-accuracy real-time detection with low memory consumption.

Identification of stable reference genes for relative quantification of long RNA expression in urinary extracellular vesicles.

Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV long RNAs are among the critical cargos capable of providing unique transcriptome information of the source cells. However, consensus regarding ideal reference genes for relative long RNAs quantification in uEVs is not available as of date. Here we explored stable reference genes through profiling the long RNA expression by RNA-seq following unsupervised analysis and validation studies. Candidate reference genes were identified using four algorithms: NormFinder, GeNorm, BestKeeper and the Delta Ct method, followed by validation. RNA profile showed uEVs contained abundant long RNAs information and the core transcriptome was related to cellular structures, especially ribosome which functions mainly as translation, protein and RNA binding molecules. Analysis of RNA-seq data identified RPL18A, RPL11, RPL27, RACK1, RPSA, RPL41, H1-2, RPL4, GAPDH, RPS27A as candidate reference genes. RT-qPCR validation revealed that RPL41, RPSA and RPL18A were reliable reference genes for long RNA quantification in uEVs from patients with diabetes mellitus (DM), diabetic nephropathy (DN), IgA nephropathy (IgAN) and prostate cancer (PCA). Interestingly, RPL41 also outperformed traditional reference genes in renal tissues of DN and IgAN, as well as in plasma EVs of several types of cancers. The stable reference genes identified in this study may facilitate development of uEVs as novel biomarkers and increase the accuracy and comparability of biomarker studies.

Signal integration and integral feedback control with biochemical reaction networks.

Biochemical reaction networks perform a variety of signal processing functions, one of which is computing the integrals of signal values. This is often used in integral feedback control, where it enables a system's output to respond to changing inputs, but to then return exactly back to some pre-determined setpoint value afterward. To gain a deeper understanding of how biochemical networks are able to both integrate signals and perform integral feedback control, we investigated these abilities for several simple reaction networks. We found imperfect overlap between these categories, with some networks able to perform both tasks, some able to perform integration but not integral feedback control, and some the other way around. Nevertheless, networks that could either integrate or perform integral feedback control shared key elements. In particular, they included a chemical species that was neutrally stable in the open loop system (no feedback), meaning that this species does not have a unique stable steady-state concentration. Neutral stability could arise from zeroth order decay reactions, binding to a partner that was produced at a constant rate (which occurs in antithetic control), or through a long chain of covalent cycles. Mathematically, it arose from rate equations for the reaction network that were underdetermined when evaluated at steady-state.

Neonicotinoid insecticides in well-developed agricultural cultivation areas: Seawater occurrence, spatial-seasonal variability and ecological risks.

Neonicotinoids (NEOs) are widely used insecticides and have been detected in aquatic environments globally. However, little is known about NEOs contamination in the coastal environments under the terrestrial pressure of multiple planting types simultaneously. This study investigated the occurrence, spatial-seasonal variability, and ecological risks of NEOs along the coast of the Shandong Peninsula during the dry and wet seasons, where located many largest fruit, vegetable, and grain production bases in China. The concentrations of ∑NEOs in seawater were higher in wet seasons (surface: 195.46 ng/L; bottom: 14.56 ng/L) than in dry seasons (surface: 10.07 ng/L; bottom: 8.45 ng/L). During the wet seasons, NEOs peaked in the northern and eastern areas of the Shandong Peninsula, where the inland fruit planting area is located. While dry seasons had higher concentrations in Laizhou Bay, influenced by rivers from vegetable-growing areas. Grain crops, fruit, and cotton planting were major NEOs sources during wet seasons, while wheat and vegetables dominated in dry seasons. Moderate or above ecological risks appeared at 53.8% of the monitoring sites. Generally, NEOs caused high risks in the wet seasons mainly caused by Imidacloprid, and medium risk in the dry seasons caused by Clothianidin, which should be prevented and controlled in advance.

Knockdown the moyamoya disease susceptibility gene, RNF213, upregulates the expression of basic fibroblast growth factor and matrix metalloproteinase-9 in bone marrow derived mesenchymal stem cells.

Moyamoya disease (MMD) is a chronic, progressive cerebrovascular occlusive disease. Ring finger protein 213 (RNF213) is a susceptibility gene of MMD. Previous studies have shown that the expression levels of angiogenic factors increase in MMD patients, but the relationship between the susceptibility gene RNF213 and these angiogenic mediators is still unclear. The aim of the present study was to investigate the pathogenesis of MMD by examining the effect of RNF213 gene knockdown on the expression of matrix metalloproteinase-9 (MMP-9) and basic fibroblast growth factor (bFGF) in rat bone marrow-derived mesenchymal stem cells (rBMSCs). Firstly, 40 patients with MMD and 40 age-matched normal individuals (as the control group) were enrolled in the present study to detect the levels of MMP-9 and bFGF in serum by ELISA. Secondly, Sprague-Dawley male rat BMSCs were isolated and cultured using the whole bone marrow adhesion method, and subsequent phenotypic analysis was performed by flow cytometry. Alizarin red and oil red O staining methods were used to identify osteogenic and adipogenic differentiation, respectively. Finally, third generation rBMSCs were transfected with lentivirus recombinant plasmid to knockout expression of the RNF213 gene. After successful transfection was confirmed by reverse transcription-quantitative PCR and fluorescence imaging, the expression levels of bFGF and MMP-9 mRNA in rBMSCs and the levels of bFGF and MMP-9 protein in the supernatant of the culture medium were detected on the 7th and 14th days after transfection. There was no significant difference in the relative expression level of bFGF among the three groups on the 7th day. For the relative expression level of MMP-9, there were significant differences on the 7th day and 14th day. In addition, there was no statistically significant difference in the expression of bFGF in the supernatant of the RNF213 shRNA group culture medium, while there was a significant difference in the expression level of MMP-9. The knockdown of the RNF213 gene affects the expression of bFGF and MMP-9. However, further studies are needed to determine how they participate in the pathogenesis of MMD. The findings of the present study provide a theoretical basis for clarifying the pathogenesis and clinical treatment of MMD.

Numerical investigation and optimal design of capillary barrier cover with passive gas collection pipes on the performance at limiting landfill gas emissions.

Relying solely on soil properties may not fully ensure the performance of capillary barrier covers at limiting landfill gas (LFG) emissions. This study proposed to install passive gas collection pipes in the coarse-grained soil layers of capillary barrier covers to enhance their performance at limiting LFG emissions. First, the LFG generation rate of municipal solid waste and its influencing factors were analyzed based on empirical formulas. This information provided necessary bottom boundary conditions for the analyses of LFG transport through capillary barrier covers with passive gas collection pipes (CBCPPs). Then, numerical simulations were conducted to investigate the LFG transport properties through CBCPPs and reveal relevant influencing factors. Finally, practical suggestions were proposed to optimize the design of CBCPPs. The results indicated that the maximum whole-site LFG generation rate occurred at the end of landfilling operation. The gas collection efficiency (E) of CBCPPs was mainly controlled by the ratio of the intrinsic permeability between the coarse- and fine-grained soil (K2/K1) and the laying spacing between gas collection pipes (D). E increased as K2/K1 increased but decreased as D increased. An empirical expression for estimating E based on K2/K1 and D was proposed. In practice, CBCPPs were supposed to be constructed once the landfilling operation finished. It is best to select the fine- and coarse-grained soils with K2/K1 exceeding 10,000 to construct CBCPPs.

Comprehensive single-cell analysis reveals heterogeneity of fibroblast subpopulations in ovarian cancer tissue microenvironment.

Background: Ovarian cancer, as a highly malignant tumor, features the critical involvement of tumor-associated fibroblasts in the ovarian cancer tissue microenvironment. However, due to the apparent heterogeneity within fibroblast subpopulations, the specific functions of these subpopulations in the ovarian cancer tissue microenvironment remain insufficiently elucidated. Methods: In this study, we integrated single-cell sequencing data from 32 ovarian cancer samples derived from four distinct cohorts and 3226 bulk RNA-seq data from GEO and TCGA-OV cohorts. Utilizing computational frameworks such as Seurat, Monocle 2, Cellchat, and others, we analyzed the characteristics of the ovarian cancer tissue microenvironment, focusing particularly on fibroblast subpopulations and their differentiation trajectories. Employing the CIBERSORTX computational framework, we assessed various cellular components within the ovarian cancer tissue microenvironment and evaluated their associations with ovarian cancer prognosis. Additionally, we conducted Mendelian randomization analysis based on cis-eQTL to investigate causal relationships between gene expression and ovarian cancer. Results: Through integrative analysis, we identified 13 major cell types present in ovarian cancer tissues, including CD8+ T cells, malignant cells, and fibroblasts. Analysis of the tumor microenvironment (TME) cell proportions revealed a significant increase in the proportion of CD8+ T cells and CD4+ T cells in tumor tissues compared to normal tissues, while fibroblasts predominated in normal tissues. Further subgroup analysis of fibroblasts identified seven subgroups, with the MMP11+Fib subgroup showing the highest activity in the TGFß signaling pathway. Single-cell analysis suggested that oxidative phosphorylation could be a key pathway driving fibroblast differentiation, and the ATRNL1+KCN + Fib subgroup exhibited chromosomal copy number variations. Prognostic analysis using a large sample size indicated that high infiltration of MMP11+ fibroblasts was associated with poor prognosis in ovarian cancer. SMR analysis identified 132 fibroblast differentiation-related genes, which were linked to pathways such as platinum drug resistance. Conclusions: In the context of ovarian cancer, fibroblasts expressing MMP11 emerge as the primary drivers of the TGF-beta signaling pathway. Their presence correlates with an increased risk of adverse ovarian prognoses. Additionally, the genetic regulation governing the differentiation of fibroblasts associated with ovarian cancer correlates with the emergence of drug resistance.

Decomprolute is a benchmarking platform designed for multiomics-based tumor deconvolution.

Tumor deconvolution enables the identification of diverse cell types that comprise solid tumors. To date, however, both the algorithms developed to deconvolve tumor samples, and the gold-standard datasets used to assess the algorithms are geared toward the analysis of gene expression (e.g., RNA sequencing) rather than protein levels. Despite the popularity of gene expression datasets, protein levels often provide a more accurate view of rare cell types. To facilitate the use, development, and reproducibility of multiomic deconvolution algorithms, we introduce Decomprolute, a Common Workflow Language framework that leverages containerization to compare tumor deconvolution algorithms across multiomic datasets. Decomprolute incorporates the large-scale multiomic datasets produced by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), which include matched mRNA expression and proteomic data from thousands of tumors across multiple cancer types to build a fully open-source, containerized proteogenomic tumor deconvolution benchmarking platform. http://pnnl-compbio.github.io/decomprolute.

Spatial and temporal variability and risk assessment of organophosphate esters in seawater and sediments of the Yangtze River estuary.

Organophosphate esters (OPEs) as substitutes for PBDEs have been widely detected in the marine environment, while little is known about the pollution characteristics and variation of OPEs in estuarine environments with complex hydrodynamic conditions and land-based input. Yangtze River Estuary (YRE) is a typical highly urbanized and industrialized estuary, with a complex hydrological environment and geochemical behavior. This study found that the concentrations of OPEs in both seawater and sediments in the YRE were higher in spring than in summer. Alkyl OPEs were the first contributor, with TnBP and TiBP as the main components, where the contribution of alkyl OPEs had exceeded 75 % in both seawater and sediments in spring, and 60 % in summer seawater, and even 80 % in sediments. In spring, OPEs peaked in the central to southern region near the YRE. In summer, OPEs were mainly concentrated in the southern branch waterway and southern nearshore area of the YRE and showed a decreasing trend to the northeast. The OPEs in the sediments were mainly concentrated in the Yangtze River Mud Area (YREMA) and the Zhe-Min Coastal Mud Area (ZMCMA). Based on the fugacity model and principal component analysis, sediments could be released into the aquatic environment as an endogenous source, and exogenous sources were mainly municipal and industrial sewage discharge sources, urban and marine traffic discharge sources, and atmospheric deposition sources. The ecological risk analysis showed that the Σ14OPEs had exhibited a low to moderate ecological risk in the southern branch waterway and the south-central region offshore.

Harnessing redox proteomics to study metabolic regulation and stress response in lignin-fed Rhodococci.

BACKGROUND: Rhodococci are studied for their bacterial ligninolytic capabilities and proclivity to accumulate lipids. Lignin utilization is a resource intensive process requiring a variety of redox active enzymes and cofactors for degradation as well as defense against the resulting toxic byproducts and oxidative conditions. Studying enzyme expression and regulation between carbon sources will help decode the metabolic rewiring that stymies lignin to lipid conversion in these bacteria. Herein, a redox proteomics approach was applied to investigate a fundamental driver of carbon catabolism and lipid anabolism: redox balance. RESULTS: A consortium of Rhodococcus strains was employed in this study given its higher capacity for lignin degradation compared to monocultures. This consortium was grown on glucose vs. lignin under nitrogen limitation to study the importance of redox balance as it relates to nutrient availability. A modified bottom-up proteomics workflow was harnessed to acquire a general relationship between protein abundance and protein redox states. Global proteomics results affirm differential expression of enzymes involved in sugar metabolism vs. those involved in lignin degradation and aromatics metabolism. As reported previously, several enzymes in the lipid biosynthetic pathways were downregulated, whereas many involved in ß-oxidation were upregulated. Interestingly, proteins involved in oxidative stress response were also upregulated perhaps in response to lignin degradation and aromatics catabolism, which require oxygen and reactive oxygen species and generate toxic byproducts. Enzymes displaying little-to-no change in abundance but differences in redox state were observed in various pathways for carbon utilization (e.g., ß­ketoadipate pathway), lipid metabolism, as well as nitrogen metabolism (e.g., purine scavenging/synthesis), suggesting potential mechanisms of redox-dependent regulation of metabolism. CONCLUSIONS: Efficient lipid production requires a steady carbon and energy flux while balancing fundamental requirements for enzyme production and cell maintenance. For lignin, we theorize that this balance is difficult to establish due to resource expenditure for enzyme production and stress response. This is supported by significant changes to protein abundances and protein cysteine oxidation in various metabolic pathways and redox processes.

Multi-omics data integration reveals the complexity and diversity of host factors associated with influenza virus infection.

Influenza viruses pose a significant and ongoing threat to human health. Many host factors have been identified to be associated with influenza virus infection. However, there is currently a lack of an integrated resource for these host factors. This study integrated human genes and proteins associated with influenza virus infections for 14 subtypes of influenza A viruses, as well as influenza B and C viruses, and built a database named H2Flu to store and organize these genes or proteins. The database includes 28,639 differentially expressed genes (DEGs), 1,850 differentially expressed proteins, and 442 proteins with differential posttranslational modifications after influenza virus infection, as well as 3,040 human proteins that interact with influenza virus proteins and 57 human susceptibility genes. Further analysis showed that the dynamic response of human cells to virus infection, cell type and strain specificity contribute significantly to the diversity of DEGs. Additionally, large heterogeneity was also observed in protein-protein interactions between humans and different types or subtypes of influenza viruses. Overall, the study deepens our understanding of the diversity and complexity of interactions between influenza viruses and humans, and provides a valuable resource for further studies on such interactions.

Exosomes derived from ovarian cancer cells regulate proliferation and migration of cancer-associated fibroblasts.

Cancer-associated fibroblast (CAF) is an essential risk factor for ovarian cancer. Exosomes can mediate cellular communication in the tumour microenvironment, but the interaction of tumour cell exosomes with CAF is less studied in Ovarian cancer. This study identified H19/miR-29c-3p/LOXL2-COL1A1 as a ceRNA regulatory network involved in regulating tumour matrix-associated signaling pathways associated with CAF. Cellular assays demonstrated that exosomes from ovarian cancer cell line SKOV3 significantly promoted the proliferation and migration of CAF. The results of mixed transplantation tumour experiments in nude mice showed that exosomes of SKOV3 significantly promoted tumour growth. Ovarian cancer tumour-derived exosomes can regulate CAF proliferation and migration through H19/miR-29c-3p/LOXL2-COL1A1. This study reveals the regulatory role of tumour exosomes on CAF, which may provide a theoretical basis for the development of therapeutic regimens targeting fibroblasts in ovarian cancer.

A Phosphoproteomics Data Resource for Systems-level Modeling of Kinase Signaling Networks.

Building mechanistic models of kinase-driven signaling pathways requires quantitative measurements of protein phosphorylation across physiologically relevant conditions, but this is rarely done because of the insensitivity of traditional technologies. By using a multiplexed deep phosphoproteome profiling workflow, we were able to generate a deep phosphoproteomics dataset of the EGFR-MAPK pathway in non-transformed MCF10A cells across physiological ligand concentrations with a time resolution of <12 min and in the presence and absence of multiple kinase inhibitors. An improved phosphosite mapping technique allowed us to reliably identify >46,000 phosphorylation sites on >6600 proteins, of which >4500 sites from 2110 proteins displayed a >2-fold increase in phosphorylation in response to EGF. This data was then placed into a cellular context by linking it to 15 previously published protein databases. We found that our results were consistent with much, but not all previously reported data regarding the activation and negative feedback phosphorylation of core EGFR-ERK pathway proteins. We also found that EGFR signaling is biphasic with substrates downstream of RAS/MAPK activation showing a maximum response at <3ng/ml EGF while direct substrates, such as HGS and STAT5B, showing no saturation. We found that RAS activation is mediated by at least 3 parallel pathways, two of which depend on PTPN11. There appears to be an approximately 4-minute delay in pathway activation at the step between RAS and RAF, but subsequent pathway phosphorylation was extremely rapid. Approximately 80 proteins showed a >2-fold increase in phosphorylation across all experiments and these proteins had a significantly higher median number of phosphorylation sites (~18) relative to total cellular phosphoproteins (~4). Over 60% of EGF-stimulated phosphoproteins were downstream of MAPK and included mediators of cellular processes such as gene transcription, transport, signal transduction and cytoskeletal arrangement. Their phosphorylation was either linear with respect to MAPK activation or biphasic, corresponding to the biphasic signaling seen at the level of the EGFR. This deep, integrated phosphoproteomics data resource should be useful in building mechanistic models of EGFR and MAPK signaling and for understanding how downstream responses are regulated.

Transverse oscillations and an energy source in a strongly magnetized sunspot.

The solar corona is two to three orders of magnitude hotter than the underlying photosphere, and the energy loss of coronal plasma is extremely strong, requiring a heating flux of over 1,000 W m-2 to maintain its high temperature. Using the 1.6 m Goode Solar Telescope, we report a detection of ubiquitous and persistent transverse waves in umbral fibrils in the chromosphere of a strongly magnetized sunspot. The energy flux carried by these waves was estimated to be 7.52 × 106 W m-2, three to four orders of magnitude stronger than the energy loss rate of plasma in active regions. Two-fluid magnetohydrodynamic simulations reproduced the high-resolution observations and showed that these waves dissipate significant energy, which is vital for coronal heating. Such transverse oscillations and the associated strong energy flux may exist in a variety of magnetized regions on the Sun, and could be the observational target of next-generation solar telescopes.

E2F family play important roles in tumorigenesis.

Tumors are serious threats to human health. The transcription factors are regarded as the potential targets for tumor treatment. As an important family of transcription factors, E2F family transcription factors (E2Fs) play vital roles in cell proliferation and regulation. However, the expression feature, gene functions, and molecular interactions of E2Fs in tumorigenesis are not clear. In this study, the transcriptome data, mutation data, and protein-protein interaction data of 10 high-incidence tumors in China from the TCGA database were integrated and analyzed to explore the expression, structure, function, mutation, and phylogenetic characteristics of E2Fs. The results showed that E2F1 and E2F7 were regularly upregulated in the tumor samples. Moreover, E2Fs participated in the regulation of the cell cycle, cell aging, and other signaling pathways. As an important regulator, E2F1 interacted with more proteins than other E2Fs. At the same time, the genetic mutation types of E2Fs varied in tumor type and patient sex, of which gene amplification accounts for the largest proportion. Phylogenetic analysis showed that E2Fs were conserved in 41 species, including fruit flies, nematodes, and humans. Meanwhile, E2Fs had a tendency for gene expansion during evolution. In conclusion, this study clarified the expression pattern, mutation characteristics, and evolutionary trend of E2Fs in high-incidence tumors in China, and suggested that E2F family transcription factors could be novel diagnostic markers for tumor diseases. Furthermore, this work can provide a theoretical basis for the development of anti-tumor-targeted drugs.