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Conducting polymers (CPs) with high conductivity and solution processability have made great advances since the pioneering work on doped polyacetylene1-3, thus creating the new field of 'organic synthetic metals,4. Various high-performance CPs have been realized, which enable the applications of several organic electronic devices5,6. Nevertheless, most CPs exhibit hole-dominant (p-type) transport behaviour7,8, whereas the development of n-type analogues lags far behind and only a few exhibit metallic state, typically limited by low doping efficiency and ambient instability. Here we present a facilely synthesized highly conductive n-type polymer poly(benzodifurandione) (PBFDO). The reaction combines oxidative polymerization and in situ reductive n-doping, greatly increasing the doping efficiency, and a doping level of almost 0.9 charges per repeating unit can be achieved. The resultant polymer exhibits a breakthrough conductivity of more than 2,000 S cm-1 with excellent stability and an unexpected solution processability without extra side chains or surfactants. Furthermore, detailed investigations on PBFDO show coherent charge-transport properties and existence of metallic state. The benchmark performances in electrochemical transistors and thermoelectric generators are further demonstrated, thus paving the way for application of the n-type CPs in organic electronics.
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The simultaneous improvement of efficiency and stability of organic solar cells (OSCs) for commercialization remains a challenging task. Herein, we designed asymmetric acceptors DT-C8Cl and DT-C8BTz with functional haloalkyl chains, in which the halogen atoms could induce noncovalent interactions with heteroatoms like O, S, and Se, etc., thus leading to appropriately manipulated film morphology. Consequently, binary devices based on D18: DT-C8Cl achieved a champion power conversion efficiency (PCE) of 19.40 %. The higher PCE of D18: DT-C8Cl could be attributed to the enhanced π-π stacking, improved charge transport, and reduced recombination losses. In addition, the noncovalent interactions induced by haloalkyl chains could effectively suppress unfavorable morphology evolutions and thereby reduce trap density of states, leading to improved thermal and storage stability. Overall, our findings reveal that the rational design of asymmetric acceptors with functional haloalkyl chains is a novel and powerful strategy for simultaneously enhancing the efficiency and stability of OSCs.
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Open-shell conjugated polymers with a high intrinsic conductivity and high-spin ground state hold considerable promise for applications in organic electronics and spintronics. Herein, two novel acceptor-acceptor (A-A) conjugated polymers based on a highly electron-deficient quinoidal benzodifurandione unit have been developed, namely DPP-BFDO-Th and DPP-BFDO. The incorporation of the quinoidal moiety into the polymers backbones enables deeply aligned lower-lying lowest unoccupied molecular orbital (LUMO) levels of below -4.0â eV. Notably, DPP-BFDO exhibits an exceptionally low LUMO (-4.63â eV) and a high-spin ground state characterized by strong diradical characters. Moreover, a self-doping through intermolecular charge-transfer is observed for DPP-BFDO, as evidenced by X-ray photoelectron spectroscopy (XPS) studies. The high carrier concentration in combination with a planar and linear conjugated backbone yields a remarkable electrical conductivity (σ) of 1.04â S cm-1 in the "undoped" native form, ranking among the highest values reported for n-type radical-based conjugated polymers. When employed as an n-type thermoelectric material, DPP-BFDO achieves a power factor of 12.59â µW m-1 K-2. Furthermore, upon n-doping, the σ could be improved to 65.68â S cm-1. This study underscores the great potential of electron-deficient quinoidal units in constructing dopant-free n-type conductive polymers with a high-spin ground state and exceptional intrinsic conductivity.
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Intestinal stem cells (ISCs), which locate at the base of intestinal crypts, are key determinants of governing proliferation and differentiation of the intestinal epithelium. The surrounding cells of ISCs and their related growth factors form ISC niche, supporting ISC function and self-renewal. ISC has an underappreciated but emerging role as a sensor of dietary nutrients, which fate decisions is adjusted in response to nutritional states to regulate gut homeostasis. Here, we review endogenous and exogenous factors, such as caloric restriction, fasting, fat, glucose and trace element. They instruct ISCs via mTORC1, PPAR/CPT1α, PPARγ/ß-catenin, Wnt/GSK-3ß pathway, respectively, jointly affect intestinal homeostasis. These dietary responses regulate ISC regenerative capacity and may be a potential target for cancer prevention. However, without precise definitions of nutrition intervene, it will be difficult to generate sufficient data to extending our knowledge of the biological response of ISC on nutrients. More accurately modeling organoids or high-throughput automated organoid culture in microcavity arrays have provided unprecedented opportunities for modeling diet-host interactions. These major advances collectively provide new insights into nutritional regulation of ISC proliferation and differentiation and drive us ever closer to breakthroughs for regenerative medicine and disease treatment by nutrition intervention in the clinic.
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Mucosa Intestinal , Células-Tronco , Glicogênio Sintase Quinase 3 beta/metabolismo , Proliferação de Células , Mucosa Intestinal/metabolismo , Células-Tronco/metabolismo , Diferenciação Celular , Dieta , Homeostase , IntestinosRESUMO
The optoelectronic properties and photovoltaic performance of nonfullerene electron acceptors (NFEAs) in organic solar cells (OSCs) are greatly influenced by the rational structure regulation of the central core unit. This study introduces a novel type of six-membered fused electron-donating core containing BâN covalent bonds to construct acceptor-donor-acceptor (A-D-A)-type NFEAs. By modulating the branching alkyl chains on the nitrogen atom, two NFEAs, BN910 and BN1014, are synthesized and characterized. Both molecules exhibit strong near-infrared absorption, narrow bandgaps (≈1.45 eV), appropriate energy levels, and tunable molecular packing behaviors, positioning them as promising candidates for efficient NFEAs in OSCs. The investigation reveals that BN1014, with longer and C2-branched alkyl chains, demonstrates superior intermolecular packing and morphology within active layers, leading to enhanced exciton dissociation, improved charge transfer, and reduced charge recombination in OSCs. As a result, a power conversion efficiency (PCE) of 10.02% is achieved for D18:BN1014-based binary OSCs. Notably, BN1014 can be utilized as the third component in the D18:DT-Y6 binary system to fabricate the ternary OSCs, and a PCE of 17.65% is achieved, outperforming 17.05% of D18:DT-Y6-based binary OSCs. These findings highlight the potential of heteroarenes featuring BâN covalent bonds for constructing high-efficiency NFEAs in OSCs.
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Bandagens , Elétrons , Nitrogênio , OxidantesRESUMO
The elaborate control of the vertical phase distribution within an active layer is critical to ensuring the high performance of organic solar cells (OSCs), but is challenging. Herein, a self-stratification active layer is realised by adding a novel polyfluoroalkyl-containing non-fullerene small-molecule acceptor (NFSMA), EH-C8 F17 , as the guest into PM6:BTP-eC9 blend. A favourable vertical morphology was obtained with an upper acceptor-enriched thin layer and a lower undisturbed bulk heterojunction layer. Consequently, a power conversion efficiency of 18.03 % was achieved, higher than the efficiency of 17.40 % for the device without EH-C8 F17 . Additionally, benefiting from the improved charge transport and collection realised by this self-stratification strategy, the OSC with a thickness of 350â nm had an impressive PCE of 16.89 %. The results of the study indicate that polyfluoroalkyl-containing NFSMA-assisted self-stratification within the active layer is effective for realising an ideal morphology for high-performance OSCs.
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BACKGROUND: There is a big difference in the expression of miRNAs of plasma exosomes of patients with HBV infection. This study aims to analyze four molecular markers of peripheral blood plasma exosomes to evaluate their potential diagnostic values in HBV infection. METHODS: A total of 55 cases of patients with chronic hepatitis B were in Experimental Group 1; 49 cases of hepatitis B carriers were in Experimental Group 2, and 46 cases were in the healthy control group. The total RNA of the plasma exosome was used to analyze the specificity and sensitivity and draw ROC curves. RESULTS: There was a significant difference in the expression of miRNA-1246, miRNA-150-5p, miRNA-5787, and miRNA-8069 down-regulated by plasma exosomes in Experimental Group 1 and Group 2 and Control Group, with a p value of less than 0.05. CONCLUSIONS: The molecular markers down-regulated were miRNA-1246, miRNA-150-5p, miRNA-5787, and miRNA-8069. The four miRNAs were initially identified as new markers of miRNAs of peripheral blood plasma exosomes after HBV infection. It is better to use multiple markers for combined diagnosis.
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Exossomos , Hepatite B Crônica , MicroRNAs , Biomarcadores , Exossomos/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/genética , Humanos , MicroRNAs/genéticaRESUMO
Functional amino acids provide great potential for treating autophagy-related diseases by regulating autophagy. The purpose of the autophagy process is to remove unwanted cellular contents and to recycle nutrients, which is controlled by many factors. Disordered autophagy has been reported to be associated with various diseases, such as cancer, neurodegeneration, aging, and obesity. Autophagy cannot be directly controlled and dynamic amino acid levels are sufficient to regulate autophagy. To date, arginine, leucine, glutamine, and methionine are widely reported functional amino acids that regulate autophagy. As a signal relay station, mammalian target of rapamycin complex 1 (mTORC1) turns various amino acid signals into autophagy signaling pathways for functional amino acids. Deficiency or supplementation of functional amino acids can immediately regulate autophagy and is associated with autophagy-related disease. This review summarizes the mechanisms currently involved in autophagy and amino acid sensing, diverse signal transduction among functional amino acids and autophagy, and the therapeutic appeal of amino acids to autophagy-related diseases. We aim to provide a comprehensive overview of the mechanisms of amino acid regulation of autophagy and the role of functional amino acids in clinical autophagy-related diseases and to further convert these mechanisms into feasible therapeutic applications.
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Aminoácidos/metabolismo , Autofagia/fisiologia , Transdução de Sinais/fisiologia , Envelhecimento/fisiologia , Arginina/metabolismo , Glutamina/metabolismo , Humanos , Leucina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Metionina/metabolismo , Neoplasias/patologia , Doenças Neurodegenerativas/patologia , Obesidade/patologiaRESUMO
Aromaticity is one of the most important concepts in organic chemistry to understand the electronic properties of cyclic π-conjugated molecules. Over a century, different aromaticity rules have been developed and validated. For planar monocyclic conjugated polyenes (also known as [n]annulenes), they will be aromatic if they contain [4N + 2] π electrons according to Hückel's rule, or antiaromatic if they have [4N] π electrons. Topological change from a planar to a half-twisted Möbius strip will lead to [4N] ([4N + 2]) aromaticity (antiaromaticity), which is just inverse to Hückel's rule. When the molecules are excited into the first triplet excited state, the Hückel (anti)aromaticity observed in the ground state will become reversed according to Baird's rule. Strictly speaking, these basic rules are only applicable for monocyclic conjugated systems, but some polycyclic systems such as porphyrinoids may also follow these rules if there is a dominant [n]annulene-like conjugation pathway. On the other hand, all-benzenoid polycyclic aromatic hydrocarbons usually display local aromaticity with π electrons predominantly localized at certain benzene rings according to Clar's aromatic sextet rule. In recent years, some proaromatic and antiaromatic molecules with even number of paired electrons have been found to exhibit open-shell diradical character and unique optical, electronic, and magnetic activities. One of the major driving forces is their intrinsic tendency to become aromatic in the open-shell diradical/polyradical forms. A number of stable diradicaloids and linear polyradicaloids have been successfully synthesized by using thermodynamic and kinetic stabilizing strategies. Herein, our particular interest is a type of macrocyclic polyradicaloid in which multiple frontier π-electrons are antiferromagnetically coupled with each other in a cyclic mode. Formally, these free electrons may behave like normal π-electrons in the [n]annulenes, and thus, it raises questions about their possible global aromaticity and which rule they will follow. In the past 5 years, our group has synthesized a series of macrocyclic polyradicaloids and systematically investigated their global aromaticity and electronic properties. Some important findings include: (1) global (anti)aromaticity is generally observed, but there is a balance between local aromaticity and global aromaticity; (2) most of these molecules follow Hückel's rule in the singlet state and display respective (anti)aromatic characteristics; (3) in some special cases, both Hückel's rule and Baird's rule can be applicable, and a unique annulene-within-an-annulene super-ring structure was demonstrated for the first time; (4) global antiaromaticity in the transition state is also important and a slow valence tautomerization process was observed in a supercyclobutadiene tetraradicaloid. These studies demonstrate how these open-shell macrocyclic polyradicaloids adapt their geometry and spin state to reach the lowest-energy state (aromatic). In this Account, we will mainly discuss their synthesis, global aromaticity, and the fundamental structure-radical character-aromaticity-properties relationships. Various experimental methods (e.g., NMR, X-ray crystallographic analysis, and electronic absorption spectroscopy) and theoretical calculations (e.g., anisotropy of the induced current density, nucleus independent chemical shift, and isochemical shielding surface) have been used to elaborate their (anti)aromatic character. At the end, a perspective on the possible three-dimensional global aromaticity in fully conjugated cagelike diradicaloids or polyradicaloids will be also discussed.
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Exosomes shed by tumor cells have been recognized as promising biomarkers for cancer diagnostics due to their unique composition and functions. Quantification of low concentrations of specific exosomes present in very small volumes of clinical samples may be used for noninvasive cancer diagnosis and prognosis. We developed an immunosorbent assay for digital qualification of target exosomes using droplet microfluidics. The exosomes were immobilized on magnetic microbeads through sandwich ELISA complexes tagged with an enzymatic reporter that produces a fluorescent signal. The constructed beads were further isolated and encapsulated into a sufficient number of droplets to ensure only a single bead was encapsulated in a droplet. Our droplet-based single-exosome-counting enzyme-linked immunoassay (droplet digital ExoELISA) approach enables absolute counting of cancer-specific exosomes to achieve unprecedented accuracy. We were able to achieve a limit of detection (LOD) down to 10 enzyme-labeled exosome complexes per microliter (â¼10-17 M). We demonstrated the application of the droplet digital ExoELISA platform in quantitative detection of exosomes in plasma samples directly from breast cancer patients. We believe our approach may have the potential for early diagnosis of cancer and accelerate the discovery of cancer exosomal biomarkers for clinical diagnosis.
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Biomarcadores Tumorais/imunologia , Neoplasias da Mama/sangue , Ensaio de Imunoadsorção Enzimática , Exossomos/imunologia , Biomarcadores Tumorais/isolamento & purificação , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Contagem de Células , Exossomos/patologia , Feminino , Humanos , Limite de Detecção , Microfluídica/métodosRESUMO
BACKGROUND: Epithelial-mesenchymal transition (EMT) is regarded as a critical event during tumor metastasis. Recent studies have revealed changes and the contributions of proteins in/on exosomes during EMT. Besides proteins, microRNA (miRNA) is another important functional component of exosomes. We hypothesized that the miRNA profile of exosomes may change following EMT and these exosomal miRNAs may in return promote EMT, migration and invasion of cancer cells. RESULTS: The small RNA profile of exosomes was altered following EMT. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the specific miRNAs of M-exosomes have the potential to drive signal transduction networks in EMT and cancer progression. Co-culture experiments confirmed that M-exosomes can enter epithelial cells and promote migration, invasion and expression of mesenchymal markers in the recipient cells. CONCLUSION: Our results reveal changes in the function and miRNA profile of exosomes upon EMT. M-exosomes can promote transfer of the malignant (mesenchymal) phenotype to epithelial recipient cells. Further, the miRNAs specifically expressed in M-exosomes are associated with EMT and metastasis, and may serve as new biomarkers for EMT-like processes in lung cancer.
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Transição Epitelial-Mesenquimal , Exossomos/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Humanos , Transdução de Sinais , Células Tumorais CultivadasRESUMO
Antibiotic resistance associated with the mcr-1 gene of Gram-negative bacteria, which confers resistance to drugs of last resort and has the potential to spread via plasmids, is one of the most pressing issues facing global health today. Point-of-care testing for the mcr-1 gene is needed to aid in the identification of colistin resistance in the field and to control its horizontal transmission. Here, we report the successful development of an enzyme-free homogenous electrochemical strategy for sensitive detection of the antibiotic resistance gene mcr-1 using the hybridization chain reaction and mcr-1-specific toehold probe. The long double-stranded DNA polymer produced using this strategy could be detected by assessing the diffusion of methylene blue towards the surface of a screen-printed gold electrode. Under optimized conditions, a linear relationship was observed between the variation of peak current and the natural logarithm of the mcr-1 gene concentration in the range of 1 nM to 1 µM with a detection limit of 0.78 nM (S/N = 3). This enzyme-free, isothermal platform is a rapid, portable, disposable, and sensitive method for detection of plasmid-mediated colistin resistance.
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Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana , Técnicas Eletroquímicas/métodos , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Técnicas Biossensoriais/métodos , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Genes Bacterianos , Humanos , Plasmídeos/genéticaRESUMO
A stable cyclopenta-fused tetraphenanthrenylene macrocycle, CPTP-M, was synthesized, and the structure was confirmed by X-ray crystallographic analysis. It exhibits a large radical character (number of unpaired electron, NU =3.52) and a small singlet-triplet energy gap (ΔES-T =-2.8â kcal mol-1 by SQUID). Its backbone contains 60 ([4n]) conjugated πâ electrons and is globally antiaromatic. NMR measurements and theoretical calculations revealed that its dication/dianion is globally aromatic owing to the existence of [4n-2]/[4n+2] π-conjugated electrons. Remarkably, the ring-current map of the tetraanion shows a unique ring-in-ring structure, with a diamagnetic outer ring and a paramagnetic inner ring. Accordingly, both the inner-rim and outer-rim protons are deshielded in its 1 Hâ NMR spectrum. The tetraanion can be regarded as an isoelectronic structure of the known octulene, which shows similar electronic properties.
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Superbenzoquinone (SBQ) is a quinone derived from a classic polycyclic aromatic hydrocarbon (PAH), hexa-peri-hexabenzocoronene (so-called "superbenzene"), and is a challenging synthetic target. Herein we report the successful synthesis and characterization of its derivatives. We reveal that the high reactivity of SBQ is due to its intrinsic open-shell diradical character. Thus, two kinetically blocked SBQs, SBQ-Me and SBQ-Ph, were prepared by different synthetic strategies. 4-tert-Butylphenyl-substituted SBQ-Ph demonstrated good stability and could be isolated in crystalline form. Both compounds have an open-shell singlet ground state and show thermally populated paramagnetic activity. Our studies provide effective strategies toward stable quinone-based diradicaloids.
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Due to the upcoming data deluge of genome data, the need for storing and processing large-scale genome data, easy access to biomedical analyses tools, efficient data sharing and retrieval has presented significant challenges. The variability in data volume results in variable computing and storage requirements, therefore biomedical researchers are pursuing more reliable, dynamic and convenient methods for conducting sequencing analyses. This paper proposes a Cloud-based bioinformatics workflow platform for large-scale next-generation sequencing analyses, which enables reliable and highly scalable execution of sequencing analyses workflows in a fully automated manner. Our platform extends the existing Galaxy workflow system by adding data management capabilities for transferring large quantities of data efficiently and reliably (via Globus Transfer), domain-specific analyses tools preconfigured for immediate use by researchers (via user-specific tools integration), automatic deployment on Cloud for on-demand resource allocation and pay-as-you-go pricing (via Globus Provision), a Cloud provisioning tool for auto-scaling (via HTCondor scheduler), and the support for validating the correctness of workflows (via semantic verification tools). Two bioinformatics workflow use cases as well as performance evaluation are presented to validate the feasibility of the proposed approach.
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Biologia Computacional , Armazenamento e Recuperação da Informação , Análise de Sequência/instrumentaçãoRESUMO
The isolation and enrichment of specific extracellular vesicle (EV) subpopulations are essential in the context of precision medicine. However, the current methods predominantly rely on a single-positive marker and are susceptible to interference from soluble proteins or impurities. This limitation represents a significant obstacle to the widespread application of EVs in biological research. Herein, a novel approach that utilizes proximity ligation assay (PLA) and DNA-RNA hybridization are proposed to facilitate the binding of two proteins on the EV membrane in advance enabling the isolation and enrichment of intact EVs with double-positive membrane proteins followed by using functionalized magnetic beads for capture and enzymatic cleavage for isolated EVs release. The isolated subpopulations of EVs can be further utilized for cellular uptake studies, high-throughput small RNA sequencing, and breast cancer diagnosis. Hence, developing and implementing a specialized system for isolating and enriching a specific subpopulation of EVs can enhance basic and clinical research in this field.
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Neoplasias da Mama , Vesículas Extracelulares , Humanos , Feminino , Proteínas de Membrana/metabolismo , Neoplasias da Mama/metabolismo , Vesículas Extracelulares/metabolismo , RNA , Separação ImunomagnéticaRESUMO
Dioxins and the emerging dioxin-like compounds (DLCs) have recruited increasing concerns about their environmental contamination, toxicity, health impacts, and mechanisms. Based on the structural similarity of dioxins and many DLCs, their toxicity was predominantly mediated by the dioxin receptor (aryl hydrocarbon receptor, AHR) in animals (including human), which can be different in expression and function among species and then possibly produce the species-specific risk or toxicity. To date, characterizing the AHR of additional species other than human and rodents can increase the accuracy of toxicity/risk evaluation and increase knowledge about AHR biology. As a key model, the medaka AHR has not been clearly characterized. Through genome survey and phylogenetic analysis, we identified four AHRs (olaAHR1a, olaAHR1b, olaAHR2a, and olaAHR2b) and two ARNTs (olaARNT1 and olaARNT2). The medaka AHR pathway was conserved in expression in nine tested tissues, of which olaAHR2a represented the predominant subform with greater abundance. Medaka AHRs and ARNTs were functional and could be efficiently transactivated by the classical dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), although olaAHR1a did not seem to cooperate with olaARNT2. In terms of function/sensitivity, the EC50 values of medaka olaAHR1a (9.01 ± 1.43 nM), olaAHR1b (4.00 ± 1.10 nM), olaAHR2a (8.75 ± 3.34 nM), and olaAHR2b (3.06 ± 0.81 nM) showed slight differences; however, they were all at the nM level. The sensitivity of four medaka AHRs to TCDD was similar to that of zebrafish dreAHR2 (the dominant form, EC50 = 3.14 ± 4.19 nM), but these medaka AHRs were more sensitive than zebrafish dreAHR1b (EC50 = 27.05 ± 18.51 nM). The additional comparison also indicated that the EC50 values in various species were usually within the nM range, but AHRs of certain subforms/species can vary by one or two orders of magnitude. In summary, the present study will enhance the understanding of AHR and help improve research on the ecotoxicity of dioxins/DLCs.
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Dioxinas , Oryzias , Receptores de Hidrocarboneto Arílico , Poluentes Químicos da Água , Peixe-Zebra , Animais , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Dioxinas/toxicidade , Poluentes Químicos da Água/toxicidade , Filogenia , Especificidade da EspécieRESUMO
Ocean acidification (OA) driven by elevated carbon dioxide (CO2) levels is expected to disturb marine ecological processes, including the formation and control of harmful algal blooms (HABs). In this study, the effects of rising CO2 on the allelopathic effects of macroalgae Ulva pertusa to a toxic dinoflagellate Karenia mikimotoi were investigated. It was found that high level of CO2 (1000 ppmv) promoted the competitive growth of K. mikimotoi compared to the group of present ambient CO2 level (420ppmv), with the number of algal cell increased from 32.2 × 104 cells/mL to 36.75 × 104 cells/mL after 96 h mono-culture. Additionally, rising CO2 level weakened allelopathic effects of U. pertusa on K. mikimotoi, as demonstrated by the decreased inhibition rate (50.6 % under the original condition VS 34.3 % under the acidified condition after 96 h co-culture) and the decreased reactive oxygen species (ROS) level, malondialdehyde (MDA) content, antioxidant enzymes activity (superoxide dismutase (SOD), peroxidase (POD), glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT) and non-enzymatic antioxidants (glutathione (GSH) and ascorbic acid (ascorbate, vitamin C). Indicators for cell apoptosis of K. mikimotoi including decreased caspase-3 and -9 protease activity were observed when the co-cultured systems were under rising CO2 exposure. Furthermore, high CO2 level disturbed fatty acid synthesis in U. pertusa and significantly decreased the contents of fatty acids with allelopathy, resulting in the allelopathy weakening of U. pertusa. Collectively, rising CO2 level promoted the growth of K. mikimotoi and weakened allelopathic effects of U. pertusa on K. mikimotoi, indicating the increased difficulties in controlling K. mikimotoi using macroalgae in the future.
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Dinoflagellida , Alga Marinha , Dióxido de Carbono/toxicidade , Concentração de Íons de Hidrogênio , Água do Mar , Dinoflagellida/fisiologia , Proliferação Nociva de AlgasRESUMO
INTRODUCTION: Simultaneous detection of proteins and mRNA within a single extracellular vesicle (EV) enables comprehensive analysis of specific EVs subpopulations, significantly advancing cancer diagnostics. However, developing a sensitive and user-friendly approach for simultaneously detecting multidimensional biomarkers in single EV is still challenging. OBJECTIVES: To facilitate the analysis of multidimensional biomarkers in EVs and boost its clinical application, we present a versatile droplet digital system facilitating the concurrent detection of membrane proteins and mRNA at the single EV level with high sensitivity and specificity. METHODS: The antibody-DNA conjugates were firstly prepared for EVs protein biomarkers recognition and signal transformation. Coupling with the assembled triplex droplet digital PCR system, a versatile droplet digital analysis assay for simultaneous detection of membrane protein and mRNA at a single EV level was developed. RESULTS: Our new droplet digital system displayed high sensitivity and specificity. Additionally, its clinical application was validated in a breast cancer cohort. As expected, this assay has demonstrated superior performance in distinguishing breast cancer from healthy individuals and benign controls through combined detection of EVs protein and mRNA markers compared to any single kind marker detections, especially for patients with breast cancer at early stage (AUC=0.9229). CONCLUSION: Consequently, this study proposes a promising strategy for accurately identifying and analyzing specific EV subgroups through the co-detection of proteins and mRNA at the single EV level, holding significant potential for future clinical applications.