ABSTRACT
The disposable paper cups (DPCs) release millions of microplastics (MPs) when used for hot beverages. However, the tissue-specific deposition and toxic effects of MPs and associated toxins remain largely unexplored, especially at daily consumption levels. We administered MPs and associated toxins extracted from leading brand DPCs to pregnant mice, revealing dose-responsive harmful effects on fetal development and maternal physiology. MPs were detected in all 13 examined tissues, with preferred depositions in the fetus, placenta, kidney, spleen, lung, and heart, contributing to impaired phenotypes. Brain tissues had the smallest MPs (90.35 % < 10 µm). A dose-responsive shift in the cecal microbiome from Firmicutes to Bacteroidetes was observed, coupled with enhanced biosynthesis of microbial fatty acids. A moderate consumption of 3.3 cups daily was sufficient to alter the cecal microbiome, global metabolic functions, and immune health, as reflected by tissue-specific transcriptomic analyses in maternal blood, placenta, and mammary glands, leading to neurodegenerative and miscarriage risks. Gene-based benchmark dose framework analysis suggested a safe exposure limit of 2 to 4 cups/day in pregnant mice. Our results highlight tissue-specific accumulation and metabolic and reproductive toxicities in mice at DPC consumption levels presumed non-hazardous, with potential health implications for pregnant women and fetuses.
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Exercise has emerged as one of the important and effective non-drug therapies used for management of type 2 diabetes (T2D) in certain nations. The present report summarizes the latest findings from the research on the beneficial effect of exercise on T2D. The objectives were to provide references for the theoretical study and the clinical practice of exercise-based management of T2D, in addition to identify the limitations of the existing literature, thereby provide direction for future research in this field.
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Mesenteric and omental adipose tissue (MOAT) communicates directly with the heart through the secretion of bioactive molecules and indirectly through afferent signaling to the central nervous system. Myocardial infarction (MI) may induce pathological alterations in MOAT, which further affects cardiac function. Our study revealed that MI induced significant MOAT transcriptional changes in genes related with signal transduction, including adiponectin (APN), neuropeptide Y (NPY), and complement C3 (C3), potentially influencing afferent activity. We further found that MOAT sensory nerve denervation with capsaicin (CAP) prevented cardiac remodeling, improved cardiac function, and reversed cardiac sympathetic nerve hyperactivation in the MI group, accompanied by reduced serum norepinephrine. In addition, CAP reversed the elevated MOAT afferent input and brain-heart sympathetic outflow post-MI, increasing APN and NPY and decreasing C3 and serum proinflammatory factors. These results demonstrated that blockade of the MOAT afferent sensory nerve exerts a cardioprotective effect by inhibiting the brain-heart sympathetic axis.
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Although studies have revealed the significant impact of dietary fiber on growth performance and nutrient digestibility, the specific characteristics of the intestinal microbiota and gene regulation in pigs capable of digesting high-fiber diets remained unclear. To investigate the traits associated with roughage tolerance in the Chinese indigenous pig breed, we conducted comparative analysis of growth performance, apparent fiber digestibility, intestinal microbiota, SCFA concentrations and intestinal transcriptome in Tunchang pigs, feeding them diets with different wheat bran levels. The results indicated that the growth performance of Tunchang pigs was not significantly impacted, and the apparent total tract digestibility of crude fiber was significantly improved with increasing dietary fiber content. High-fiber diets altered the diversity of intestinal microbiota, and increased the relative abundance of Prevotella, CF231, as well as the concentrations of isobutyrate, valerate and isovalerate. The LDA analysis identified potential microbial biomarkers that could be associated with roughage tolerance, such as Prevotella stercorea, and Eubacterium biforme. In addition, appropriate high-fiber diets containing 4.34% crude fiber upregulated the mRNA expressions of PYY, AQP8, and SLC5A8, while downregulating the mRNA expressions of CKM and CNN1.This indicated that appropriate high-fiber diets may inhibit intestine motility and increase the absorption of water and SCFAs.
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Yield and its components are greatly affected by climate change. Adjusting the sowing date is an effective way to alleviate adverse effects and adapt to climate change. Aiming to determine the optimal sowing date of summer maize and clarify the contribution of climatic variables to grain yield and its components, a consecutive 4-year field experiment was conducted from 2016 to 2019 with four sowing dates at 10-day intervals from 5 June to 5 July. Analysis of historical meteorological data showed that more solar radiation (SR) was distributed from early June to mid-August, and the maximum temperature (Tmax) > 32°C appeared from early July to late August, which advanced and lasted longer in 1991-2020 relative to 1981-1990. Additionally, the precipitation was mainly distributed from early June to late July. The climate change in the growing season of summer maize resulted in optimal sowing dates ranging from 5 June to 15 June, with higher yields and yield stability, mainly because of the higher kernel number per ear and 1,000-grain weight. The average contribution of kernel number per ear to grain yield was 58.7%, higher than that of 1,000-grain weight (41.3%). Variance partitioning analysis showed that SR in 15 days pre-silking to 15 days post-silking (SS) and silking to harvest (SH) stages significantly contributed to grain yield by 63.1% and 86.4%. The extreme growing degree days (EDD) > 32°C, SR, precipitation, and diurnal temperature range (DTR) contributed 20.6%, 22.9%, 14.5%, and 42.0% to kernel number per ear in the SS stage, respectively. Therefore, we concluded that the early sowing dates could gain high yield and yield stability due to the higher SR in the growing season. Meanwhile, due to the decreasing trend in SR and increasing Tmax trend in this region, in the future, new maize varieties with high-temperature resistance, high light efficiency, shade tolerance, and medium-season traits need to be bred to adapt to climate change and increased grain yield.
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BACKGROUND: Recurrent spontaneous abortion (RSA) is a challenging condition that affects the health of women both physically and mentally, but its pathogenesis and treatment have yet to be studied in detail. In recent years, Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to be effective in treating various diseases. Current understanding of RSA treatment using WJ-MSCs is limited, and the exact mechanisms of WJ-MSCs action in RSA remains largely unclear. In this study, we explored the decidual deficiencies in RSA and the therapeutic potential of WJ-MSCs at single-cell resolution. METHODS: Three mouse models were established: a normal pregnancy group, an RSA group, and a WJ-MSC treatment group. Decidual tissue samples were collected for single-cell RNA sequencing (scRNA-seq) and functional verification, including single-cell resolution in situ hybridization on tissues (SCRINSHOT) and immunofluorescence. RESULTS: We generated a single-cell atlas of decidual tissues from normal pregnant, RSA, and WJ-MSC-treated mice and identified 14 cell clusters in the decidua on day 14. Among these cell populations, stromal cells were the most abundant cell clusters in the decidua, and we further identified three novel subclusters (Str_0, Str_1, and Str_2). We also demonstrated that the IL17 and TNF signaling pathways were enriched for upregulated DEGs of stromal cells in RSA mice. Intriguingly, cell-cell communication analysis revealed that Str_1 cell-related gene expression was greatly reduced in the RSA group and rescued in the WJ-MSC treatment group. Notably, the interaction between NK cells and other cells in the RSA group was attenuated, and the expression of Spp1 (identified as an endometrial toleration-related marker) was significantly reduced in the NK cells of the RSA group but could be restored by WJ-MSC treatment. CONCLUSION: Herein, we implemented scRNA-seq to systematically evaluate the cellular heterogeneity and transcriptional regulatory networks associated with RSA and its treatment with WJ-MSCs. These data revealed potential therapeutic targets of WJ-MSCs to remodel the decidual subpopulations in RSA and provided new insights into decidua-derived developmental defects at the maternal-foetal interface.
Subject(s)
Abortion, Habitual , Decidua , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Female , Animals , Mice , Decidua/cytology , Decidua/metabolism , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Pregnancy , Mesenchymal Stem Cell Transplantation/methods , Abortion, Habitual/therapy , Abortion, Habitual/metabolism , Abortion, Habitual/pathology , Single-Cell Analysis , Humans , Disease Models, Animal , Wharton Jelly/cytologyABSTRACT
Circadian rhythms are essential regulators of a multitude of physiological and behavioral processes, such as the metabolism and function of the liver. Circadian rhythms are crucial to liver homeostasis, as the liver is a key metabolic organ accountable for the systemic equilibrium of the body. Circadian rhythm disruption alone is sufficient to cause liver cancer through the maintenance of hepatic metabolic disorder. Although there is evidence linking CRD to hepatocarcinogenesis, the precise cellular and molecular mechanisms that underlie the circadian crosstalk that leads to hepatocellular carcinoma remain unknown. The expression of CRD-related genes in HCC was investigated in this study via bulk RNA transcriptomic analysis and single-cell sequencing. Dysregulated CRD-related genes are predominantly found in hepatocytes and fibroblasts, according to the findings. By using a combination of single-cell RNA sequencing and bulk RNA sequencing analyses, the dysregulated CRD-related genes ADAMTS13, BIRC5, IGFBP3, MARCO, MT2A, NNMT, and PGLYRP2 were identified. The survival analysis using the Kaplan-Meier method revealed a significant correlation between the expression levels of BIRC5 and IGFBP3 and the survival of patients diagnosed with HCC.
Subject(s)
Carcinoma, Hepatocellular , Circadian Rhythm , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Sequence Analysis, RNA , Single-Cell Analysis , Survivin , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Humans , Circadian Rhythm/genetics , Survivin/genetics , Survivin/metabolism , Gene Expression Profiling , Transcriptome , Insulin-Like Growth Factor Binding Protein 3ABSTRACT
Small extracellular vesicles (sEVs) have been shown to promote tumorigenesis, treatment resistance, and metastasis in multiple cancer types; however, sEVs in the aqueous humor (AH) of uveal melanoma (UM) patients have never previously been profiled. In this study, we used single particle analysis to characterize sEV subpopulations in the AH of UM patients by quantifying their size, concentration, and phenotypes based on cell surface markers, specifically the tetraspanin co-expression patterns of CD9, CD63, and CD81. sEVs were analyzed from paired pre- and post-treatment (brachytherapy, a form of radiation) AH samples collected from 19 UM patients. In post-brachytherapy samples, two subpopulations, CD63/81+ and CD9/63/81+ sEVs, were significantly increased. These trends existed even when stratified by tumor location and GEP class 1 and class 2 (albeit not significant for GEP class 2). In this initial report of single vesicle profiling of sEVs in the AH of UM patients, we demonstrated that sEVs can be detected in the AH. We further identified two subpopulations that were increased post-brachytherapy, which may suggest radiation-induced release of these particles, potentially from tumor cells. Further study of the cargo carried by these sEV subpopulations may uncover important biomarkers and insights into tumorigenesis for UM.
Subject(s)
Aqueous Humor , Brachytherapy , Extracellular Vesicles , Melanoma , Uveal Neoplasms , Humans , Uveal Neoplasms/radiotherapy , Uveal Neoplasms/metabolism , Uveal Neoplasms/pathology , Extracellular Vesicles/metabolism , Melanoma/radiotherapy , Melanoma/metabolism , Melanoma/pathology , Aqueous Humor/metabolism , Aqueous Humor/radiation effects , Female , Male , Middle Aged , Aged , Biomarkers, Tumor/metabolism , Adult , Aged, 80 and overABSTRACT
The reoccurrence of successive waves of SARS-CoV-2 variants suggests the exploration of more vaccine alternatives is imperative. Modified vaccinia virus Ankara (MVA) is a virus vector exhibiting excellent safety as well as efficacy for vaccine development. Here, a series of recombinant MVAs (rMVAs) expressing monomerized or trimerized S proteins from different SARS-CoV-2 variants are engineered. Trimerized S expressed from rMVAs is found predominantly as trimers on the surface of infected cells. Remarkably, immunization of mice with rMVAs demonstrates that S expressed in trimer elicits higher levels of binding IgG and IgA, as well as neutralizing antibodies for matched and mismatched S proteins than S in the monomer. In addition, trimerized S expressed by rMVA induces enhanced cytotoxic T-cell responses than S in the monomer. Importantly, the rMVA vaccines expressing trimerized S exhibit superior protection against a lethal SARS-CoV-2 challenge as the immunized animals all survive without displaying any pathological conditions. This study suggests that opting for trimerized S may represent a more effective approach and highlights that the MVA platform serves as an ideal foundation to continuously advance SARS-CoV-2 vaccine development. IMPORTANCE: MVA is a promising vaccine vector and has been approved as a vaccine for smallpox and mpox. Our analyses suggested that recombinant MVA expressing S in trimer (rMVA-ST) elicited robust cellular and humoral immunity and was more effective than MVA-S-monomer. Importantly, the rMVA-ST vaccine was able to stimulate decent cross-reactive neutralization against pseudoviruses packaged using S from different sublineages, including Wuhan, Delta, and Omicron. Remarkably, mice immunized with rMVA-ST were completely protected from a lethal challenge of SARS-CoV-2 without displaying any pathological conditions. Our results demonstrated that an MVA vectored vaccine expressing trimerized S is a promising vaccine candidate for SARS-CoV-2 and the strategy might be adapted for future vaccine development for coronaviruses.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccinia virus , Animals , Vaccinia virus/genetics , Vaccinia virus/immunology , Mice , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19/immunology , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Antibodies, Neutralizing/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Female , Humans , Mice, Inbred BALB C , Protein Multimerization , Immunoglobulin G/immunology , T-Lymphocytes, Cytotoxic/immunology , Immunoglobulin A/immunology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/genetics , Genetic VectorsABSTRACT
INTRODUCTION: Most COVID-19 survivors are troubled with chronic persistent symptoms, which have currently no definitive treatments. Bufei Huoxue (BFHX) capsule exerts clinical benefit, while the material basis and molecular mechanism remain unclear. AIM: The study aimed to elucidate the protective mechanisms of BFHX capsules against COVID-19 convalescence. UHPLC-HRMS and various databases were employed to explore potential compounds and targets. PPI, MCODE, transcription factor (TF), and miRNA analyses were conducted to receive hub targets and corresponding upstream regulators. METHOD: Molecular docking was applied to verify the binding activity of compound and target. Further, GO, KEGG, WIKI, and Reactome analyses were performed, and compound-targetsymptom and gene-disease networks were constructed. A total of 127 compounds and 313 targets were acquired. A sum of 10 hub targets were screened and showed good binding affinities with critical compounds. RESULT: MLLT1, CBFB, and EZH2 were identified as key TFs, and hsa-mir-146a-5p, hsa-mir- 26b-5p, and hsa-mir-24-3p were predicted to be important miRNAs. BFHX capsule may alleviate the symptoms by targeting TNF, IL-6, IFNG, and TGF-ß1. Besides, BFHX capsule may exert a therapeutic effect on respiratory disease (especially pulmonary fibrosis and lung infection) and multi-system damage during COVID-19 convalescence by regulating cytokine-cytokine receptor interaction, as well as TGF-ß, TNF, and Toll-like receptor signaling pathways. CONCLUSION: In summary, BFHX capsule may exert a therapeutic effect on multi-system damages during COVID-19 convalescence through multiple compounds (such as albiflorin, isopsoralen, and neobavaisoflavone), multiple targets (such as TNF, IL-6, and EGF) and multiple pathways (TGF-ß, TNF, and Toll-like receptor signaling pathways).
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The acidic CO2 reduction reaction (CO2RR) offers a promising approach to mitigate CO2 reactant loss and carbonate deposition, which are challenging issues in alkaline or neutral electrolytes. However, the hydrogen evolution reaction (HER) competes in the proton-rich environment near the catalyst surface as a side reaction, reducing the energy efficiency of generating multi-carbon (C2+) products. In this work, we proposed a palladium (Pd) doping strategy in a copper (Cu)-based catalyst to stabilize polarized Cu0-Cu+ sites, thus enhancing the CC coupling step during the CO2RR while suppressing HER. At an optimal doping ratio of 6%, the Pd dopants were well dispersed as single atoms without aggregation, allowing for the stabilization of subsurface oxygen (OSub), preserving the polarized Cu0-Cu+ active sites, and reducing the energy barrier of CC coupling. The Pd-doped Cu/Cu2O catalyst exhibited a peak Faradaic efficiency (FE) of 64.0% for C2+ products with a corresponding C2+ partial current density of 407.1 mAâcm-2 at -2.18 V versus a reversible hydrogen electrode, a high CO2 single-pass conversion efficiency (SPCE) of 73.2%, as well as a high electrochemical stability of â¼ 150 h at industrially relevant current densities, thus suggesting a potential approach for tuning the electrocatalytic CO2 performances in acidic environments with higher carbon conversion efficiencies.
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Introduction: The objective of this study was to report the clinicopathologic features of three cases of MYCN-amplified retinoblastoma identified genetically by aqueous humor sampling. Methods: Whole-genome sequencing was performed using isolated cell-free DNA (cfDNA) from aqueous humor of 3 retinoblastoma patients. We analyzed genomic copy number and mutational alterations, histologic and pathologic features, and clinical data. Results: The most common genetic alteration identified in these three retinoblastoma cases was a focal MYCN amplification on 2p. All tumors showed an early age of diagnosis with a median of 9 months. The tumor histopathologic features included neovascularization and subretinal seeding in case 1, diffuse nature with choroidal and prelaminar optic nerve invasion in case 2, and complete vitreous seeding in case 3. Case 1 expressed RB protein and had no RB1 mutation, case 2 did not express RB protein and had an RB1 mutation, and case 3 did not express RB protein and likely had an epigenetic effect on RB expression. Conclusions: Our report shows 3 cases of unilateral retinoblastomas diagnosed in patients ranging from 4 months to 18 months old. Genomic analysis from AH cfDNA revealed MYCN amplification with intact RB protein staining in case 1 and lack of RB staining in cases 2 and 3. RB1 mutational analysis in the AH confirmed a pathogenic variant in case 2. Clinical pathology showed features requiring aggressive treatment, specifically enucleation. Importance: MYCN-amplified retinoblastomas demonstrate unique pathogenesis and aggressive behavior, regardless if MYCN is a primary or secondary driver of disease. Genomic analysis from aqueous humor may be useful when deciding to enucleate as opposed to treating conservatively. Focal MYCN amplification on 2p might be relevant for tumor growth in this subset of the retinoblastoma population in terms of targeted therapeutics.
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Here we report a concise and divergent synthesis of scabrolide A and havellockate, representative members of polycyclic marine natural product furano(nor)cembranoids. The synthesis features a highly efficient exo-exo-endo radical cascade. Through the generation of two rings, three C-C bonds, and three contiguous stereocenters in one step, this remarkable transformation not only assembles the bowl-shaped, common 6-5-5 fused ring system from simple building blocks but also precisely installs the functionalities at desired positions and sets the stage for further divergent preparation of both target molecules. Further studies reveal that the robust and unusual 6-endo radical addition in the cascade is likely facilitated by the rigidity of the substrate.
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Accurate diagnosis and treatment assessment of liver fibrosis face significant challenges, including inherent limitations in current techniques like sampling errors and inter-observer variability. Addressing this, our study introduces a novel machine learning (ML) framework, which integrates light gradient boosting machine and multivariate imputation by chained equations to enhance liver status assessment using biomechanical markers. Building upon our previously established multiscale mechanical characteristics in fibrotic and treated livers, this framework employs Gaussian Bayesian optimization for post-imputation, significantly improving classification performance. Our findings indicate a marked increase in the precision of liver fibrosis diagnosis and provide a novel, quantitative approach for assessing fibrosis treatment. This innovative combination of multiscale biomechanical markers with advanced ML algorithms represents a transformative step in liver disease diagnostics and treatment evaluation, with potential implications for other areas in medical diagnostics.
Subject(s)
Liver Cirrhosis , Machine Learning , Biomechanical Phenomena , Humans , Mechanical Phenomena , Bayes Theorem , Animals , Biomarkers/metabolismABSTRACT
The efficient acetate conversion from CO electroreduction is challenging due to the poor selectivity at high reaction rate, which requires the competition with H2 and other C2+ (i. e., ethylene, ethanol, n-propanol) reduction products. Electrolyte engineering is one of the efficient strategies to regulate the reaction microenvironment. In this work, the adding of sulfite (SO3 2-) with high nucleophilicity in KOH electrolytes was demonstrated to enable improving the CO-to-acetate conversion via generating a S-O chemical bond between SO3 2- and oxygenated *C2 intermediates (i. e., *CO-CO, *CO-COH) compared with that in pure KOH system on both synthesized Cu(200)- and normal commercial Cu(111)-facets-exposed metallic Cu catalysts. As a result, the prepared Cu(200)-facets-exposed metallic Cu catalyst with surface ions modification showed an superior Faradaic efficiency of 63.6 % at -0.6â A â cm-2, and extraordinary absolute value of peak partial current density as high as 1.52â A â cm-2 with adding SO3 2- in KOH electrolytes, compared to the best reported values in both CO and CO2 electroreduction. Our work suggests an attractive strategy to introduce the oxyanion with high nucleophilicity in electrolytes to regulate the microenvironment for industrial-current-density electrosynthesis of acetate from CO electroreduction.
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The antiviral protein kinase R (PKR) is activated by viral double-stranded RNA and phosphorylates translation initiation factor eIF2α, thereby inhibiting translation and virus replication. Most poxviruses contain two PKR inhibitors, called E3 and K3 in vaccinia virus (VACV), which are determinants of viral host range. The prevailing model for E3 function is that it inhibits PKR through the non-specific sequestration of double-stranded (ds) RNA. Our data revealed that Syrian hamster PKR was resistant to E3, which is at odds with the sequestration model. However, Syrian hamster PKR was still sensitive to K3 inhibition. In contrast, Armenian hamster PKR showed opposite sensitivities, being sensitive to E3 and resistant to K3 inhibition. Mutational analyses of hamster PKRs showed that sensitivity to E3 inhibition was largely determined by the region linking the dsRNA-binding domains and the kinase domain of PKR, whereas two amino acid residues in the kinase domain (helix αG) determined sensitivity to K3. Expression of PKRs in congenic cells showed that Syrian hamster PKR containing the two Armenian hamster PKR residues in helix-αG was resistant to wild type VACV infection, and that cells expressing either hamster PKR recapitulated the phenotypes observed in species-derived cell lines. The observed resistance of Syrian hamster PKR to E3 explains its host range function and challenges the paradigm that dsRNA-binding PKR inhibitors mainly act by the sequestration of dsRNA. Significance: The molecular mechanisms that govern the host range of viruses are incompletely understood. A small number of poxvirus genes have been identified that influence the host range of poxviruses. We show that the host range functions of E3 and K3, two host range factors from vaccinia virus, are a result of species-specific interactions with the antiviral protein kinase R (PKR) and that PKR from closely related species displayed dramatic differences in their sensitivities to these viral inhibitors. While there is a substantial body of work demonstrating host-specific interactions with K3, the current model for E3-mediated PKR inhibition is that E3 non-specifically sequesters dsRNA to prevent PKR activation. This model does not predict species-specific sensitivity to E3; therefore, our data suggest that the current model is incomplete, and that dsRNA sequestration is not the primary mechanism for E3 activity.
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Color transfer aims to change the color information of the target image according to the reference one. Many studies propose color transfer methods by analysis of color distribution and semantic relevance, which do not take the perceptual characteristics for visual quality into consideration. In this study, we propose a novel color transfer method based on the saliency information with brightness optimization. First, a saliency detection module is designed to separate the foreground regions from the background regions for images. Then a dual-branch module is introduced to implement color transfer for images. Finally, a brightness optimization operation is designed during the fusion of foreground and background regions for color transfer. Experimental results show that the proposed method can implement the color transfer for images while keeping the color consistency well. Compared with other existing studies, the proposed method can obtain significant performance improvement. The source code and pre-trained models are available at https://github.com/PlanktonQAQ/SCTNet.
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Bound states in the continuum (BICs) allow to obtain an ultrahigh-quality-factor optical cavity. Nevertheless, BICs must be extended in one or more directions, substantially increasing the device footprint. Although super-cavity mode quasi-BICs supported by single nanopillars have been demonstrated recently, their low-quality factor and localized electromagnetic field inside the dielectric nanopillar are insufficient for high-sensitivity refractive index sensing applications. We propose a ring structure rotated by a dielectric sectorial nanostructure, which can achieve a high quality factor by breaking the rotational symmetry of the ring structure with a footprint as small as 3 µm2. As a straightforward application, we demonstrate high performance local refractive index and nanoscale film thickness sensing based on rotational symmetry breaking induced BICs. These BICs reach quality factor and sensitivity of one order of magnitude better than those of conventional super-cavity mode BICs. The proposed method provides insights into the design of compact high quality factor photonic devices, opening up new possibilities for applications in refractive index and nanoscale film thickness sensing.
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Enrichment analysis contextualizes biological features in pathways to facilitate a systematic understanding of high-dimensional data and is widely used in biomedical research. The emerging reporter score-based analysis (RSA) method shows more promising sensitivity, as it relies on P-values instead of raw values of features. However, RSA cannot be directly applied to multi-group and longitudinal experimental designs and is often misused due to the lack of a proper tool. Here, we propose the Generalized Reporter Score-based Analysis (GRSA) method for multi-group and longitudinal omics data. A comparison with other popular enrichment analysis methods demonstrated that GRSA had increased sensitivity across multiple benchmark datasets. We applied GRSA to microbiome, transcriptome and metabolome data and discovered new biological insights in omics studies. Finally, we demonstrated the application of GRSA beyond functional enrichment using a taxonomy database. We implemented GRSA in an R package, ReporterScore, integrating with a powerful visualization module and updatable pathway databases, which is available on the Comprehensive R Archive Network (https://cran.r-project.org/web/packages/ReporterScore). We believe that the ReporterScore package will be a valuable asset for broad biomedical research fields.