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The geometric structure, electronic properties, and optical characteristics of BAs/InS heterostructures are investigated in the present study through the first-principles calculations of Density Functional Theory (DFT). The analysis shows that H1-stacking BAs/InS heterostructures with an interlayer distance of 3.6 Å have excellent stability compared with monolayer materials. Furthermore, this heterostructure is classified as a Type-II heterostructure, which promotes the formation of photo-generated electron-hole pairs. The band alignment, direction and magnitude of electronic transfer in BAs/InS heterostructures can be fine-tuned by applying the external electric field and stress, which can also induce a transition from Type-II to Type-I behavior, the indirect bandgap to direct bandgap also occurs. Moreover, absorption coefficient of the heterostructure can also be moderately enhanced and adjusted by external electric fields and stress. These findings suggest that BAs/InS heterostructures have potential applications in photoelectric detectors and laser technology. .
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Oxidative stress (OS) is strongly implicated in the pathophysiology of major depressive disorder (MDD) but the molecular mechanisms remain largely unknown. The purpose of this study is to identify genes related to both OS and MDD, and further to evaluate the utility of these genes as diagnostic markers and potential treatment targets. We searched datasets related to MDD from the Gene Expression Omnibus (GEO) database for differentially expressed genes (DEGs) also related to OS according to GeneCards. Bioinformatics analyses and machine learning algorithms were used to identify hub genes mediating OS-MDD interactions. A summary data-based Mendelian randomization (SMR) approach was employed to identify possible causal genes for MDD from blood tissue eQLT data. These investigations identified 32 genes mediating OS-MDD interactions, while SMR analysis identified KCNE1 (OR = 1.057, 95%CI = 1.013-1.102, P value = 0.010), MAPK3 (OR = 1.023, 95%CI = 1.004-1.043, P value = 0.020), and STIP1 (OR = 0.792, 95%CI = 0.641-0.979, P value = 0.031) as OS-related causal genes for MDD. These genes may thus serve as useful diagnostic markers and potential therapeutic targets.
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Transtorno Depressivo Maior , Estresse Oxidativo , Humanos , Transtorno Depressivo Maior/genética , Estresse Oxidativo/genética , Análise da Randomização Mendeliana , Biologia Computacional , Aprendizado de Máquina , MultiômicaRESUMO
This paper provides a detailed description of the development and experimental results of the supercritical flow experiment payload carried on the TZ-6 cargo spacecraft, as well as a systematic verification of the out-of-cabin deployment experiment. The technical and engineering indicators of the payload deployment experiment are analyzed, and the functional modules of the payload are shown. The paper provides a detailed description of the design, installation location, size, weight, temperature, illumination, pressure, radiation, control, command reception, telemetry data, downlink data, and experimental procedures for the out-of-cabin payload in the extreme conditions of space. The paper presents the annular liquid surface state and temperature oscillation signals obtained from the space experiment and conducts ground matching experiments to verify the results, providing scientific references for the design and condition setting of space experiments and comparisons for the experimental results to obtain the flow field structure under supercritical conditions. The paper provides a specific summary and discussion of the space fluid science experiment project, providing useful references for future long-term in-orbit scientific research using cargo spacecraft.
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PURPOSE: We aim to determine the effectiveness of adding electroacupuncture to standard triple antiemetic therapy for treating chemotherapy-induced nausea and vomiting (CINV). METHODS: From March 2022 to December 2023, a randomized, blind, sham-controlled trial conducted across six Chinese hospitals investigated patients with breast cancer undergoing highly emetogenic chemotherapy (HEC). Patients were randomly assigned to either true electroacupuncture (n = 120) or sham electroacupuncture (n = 119) groups, with both groups receiving standard triple antiemetic therapy. The primary end point was the proportion of complete protection (no vomiting, no need for rescue treatment, and no significant nausea, as evaluated using the visual analog scale [VAS]) within 120 hours after receiving HEC. RESULTS: Among 239 randomly assigned patients, 235 (98.3%) completed the trial. In the full analysis set, compared with the sham electroacupuncture group, the true electroacupuncture group demonstrated a significant increase in the complete protection rate from 34.5% to 52.9% (P = .004). Additionally, true electroacupuncture also showed enhanced total control (4.3% v 13.4%; P = .014), no significant nausea (37.9% v 58.8%; P = .001), no nausea (4.3% v 13.4%; P = .014), and nausea VAS score = 0 mm (4.3% v 12.6%; P = .023). However, the occurrence of no vomiting in the overall stage was similar (76.7% v 73.9%; P = .622) in both groups. Post hoc exploratory analysis showed a significantly higher rate of complete protection during the delayed stage in the true electroacupuncture group compared with the sham electroacupuncture group, with no significant difference observed during the acute stage. CONCLUSION: Adding true electroacupuncture to standard triple antiemetic therapy significantly enhances the efficacy of CINV treatment in patients with breast cancer receiving HEC.
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Introduction: Aeromonas spp. are ubiquitous inhabitants of ecosystems, and many species are opportunistically pathogenic to humans and animals. Multidrug-resistant (MDR) Aeromonas species have been widely detected in hospitals, urban rivers, livestock, and aquatic animals. Results: In this study, we identified two Aeromonas isolates, namely Aeromonas veronii 0728Q8Av and Aeromonas caviae 1029Y16Ac, from coastal waters in Zhejiang, China. Both isolates exhibited typical biochemical characteristics and conferred MDR to 11 kinds of antibiotics, remaining susceptible to ceftazidime. Whole-genome sequencing revealed that both isolates harbored multiple antibiotic resistance genes (ARGs) and several mobile genetic elements (MGEs) on the chromosomes, each containing a resistance genomic island (GI), a typical class 1 integron, a transposon, and various insertion sequences (ISs). Most ARGs were situated within the multiple resistance GI, which contained a class 1 integron and a transposon in both Aeromonas isolates. Furthermore, a chromosomal mcr-3.16 gene was identified in A. veronii 0728Q8Av, while a chromosomal mcr-3.3 was found in A. caviae 1029Y16Ac. Both mcr-3 variants were not located within but were distanced from the multidrug resistance GI on the chromosome, flanking by multiple ISs. In addition, a mcr-3-like was found adjacent to mcr-3.16 to form a tandem mcr-3.16-mcr-3-like-dgkA structure; yet, Escherichia coli carrying the recombinants of mcr-3-like did not exhibit resistance to colistin. And an incomplete mcr-3-like was found adjacent to mcr-3.3 in A. caviae 1029Y16Ac, suggesting the possibility that mcr-3 variants originated from Aeromonas species. In vivo bacterial pathogenicity test indicated that A. veronii 0728Q8Av exhibited moderate pathogenicity towards infected ayu, while A. caviae 1029Y16Ac was non-virulent. Discussion: Thus, both Aeromonas species deserve further attention regarding their antimicrobial resistance and pathogenicity.
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OBJECTIVE: To investigate the effect of pre-treatment plasma Epstein-Barr virus (EBV) DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH). METHODS: The clinical characteristics, survival rate, and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study. Patients were divided into three groups, including the EBV DNA-negative group(<5.0×102 copies/ml), lower EBV-DNA loads group(5.0×102-8.51×104 copies/ml), and higher EBV-DNA loads group(ï¼8.51×104 copies/ml), according to pre-treatment plasma EBV-DNA copy number. Cox regression model was established for screening prognostic factors. Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index (C-index) and calibration curves were calculated to verify model predictive and discriminatory capacity. RESULTS: Among 171 adult sHLH patients, 84 patients were not infected with EBV (EBV DNA-negative group), and 87 with EBV (EBV DNA-positive group, 48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group). Consistent elevations in the levels of liver enzymes (ALT and AST), LDH, TG, ß 2-microglobulin and ferritin across the increasing of EBV-DNA load (all P <0.05), while the levels of fibrinogen decrease (P <0.001). The median follow-up time was 52 days (range 20-230 days), and 123 patients died. The overall survival (OS) rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group (median OS: 40 days vs 118 days, P <0.001). Higher EBV-DNA loads had worse OS (median OS: 24 days vs 45 days vs 118 days, P <0.0001 for trend) compared to lower EBV-DNA loads and EBV DNA-negative group. Multivariate Cox analysis revealed that higher EBV-DNA loads (P =0.005), fibrinogen≤1.5 g/L (P ï¼0.012), ferritin (P ï¼0.041), associated lymphoma (P ï¼0.002), and anti-tumor based strategy (P ï¼0.001) were independent prognostic factors for OS. The C-indexes of 30 day, 90 days, 365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability. Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women, ferritinï¼5 000 µg/L, ß2-microglobulinï¼7.4 mmol/L and regardless of age, etiologies, HScore points. CONCLUSION: The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH. The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.
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DNA Viral , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica , Carga Viral , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/virologia , Prognóstico , Estudos Retrospectivos , DNA Viral/sangue , Adulto , Infecções por Vírus Epstein-Barr/sangue , Taxa de Sobrevida , Feminino , MasculinoRESUMO
The concept of Yin-Yang, originating in ancient Chinese philosophy, symbolizes two opposing but complementary forces or principles found in all aspects of life. This concept can be quite fitting in the context of extracellular vehicles (EVs) and inflammatory diseases. Over the past decades, numerous studies have revealed that EVs can exhibit dual sides, acting as both pro- and anti-inflammatory agents, akin to the concept of Yin-Yang theory (i.e., two sides of a coin). This has enabled EVs to serve as potential indicators of pathogenesis or be manipulated for therapeutic purposes by influencing immune and inflammatory pathways. This review delves into the recent advances in understanding the Yin-Yang sides of EVs and their regulation in specific inflammatory diseases. We shed light on the current prospects of engineering EVs for treating inflammatory conditions. The Yin-Yang principle of EVs bestows upon them great potential as, therapeutic, and preventive agents for inflammatory diseases.
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Vesículas Extracelulares , Inflamação , Yin-Yang , Vesículas Extracelulares/metabolismo , Humanos , Inflamação/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications.
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Exossomos , RNA Mensageiro , SARS-CoV-2 , Exossomos/metabolismo , Exossomos/química , Humanos , RNA Mensageiro/genética , Animais , COVID-19/terapia , Técnicas de Transferência de Genes , Neoplasias/terapia , Sistemas de Liberação de Medicamentos/métodosRESUMO
Machine learning has been employed in recognizing protein localization at the subcellular level, which highly facilitates the protein function studies, especially for those multi-label proteins that localize in more than one organelle. However, existing works mostly study the qualitative classification of protein subcellular locations, ignoring fraction of one multi-label protein in different locations. Actually, about 50 % proteins are multi-label proteins, and the ignorance of quantitative information highly restricts the understanding of their spatial distribution and functional mechanism. One reason of the lack of quantitative study is the insufficiency of quantitative annotations. To address the data shortage problem, here we proposed a generative model, PLocGAN, which could generate cell images with conditional quantitative annotation of the fluorescence distribution. The model was a conditional generative adversarial network, in which the condition learning utilized partial label learning to overcome the lack of training labels and allowed training with only qualitative labels. Meanwhile, it used contrastive learning to enhance diversity of the generated images. We assessed the PLocGAN on four pixel-fused synthetic datasets and one real dataset, and demonstrated that the model could generate images with good fidelity and diversity, outperforming existing state-of-the-art generative methods. To verify the utility of PLocGAN in the quantitative prediction of protein subcellular locations, we replaced the training images with generated quantitative images and built prediction models, and found that they had a boosting effect on the quantitative estimation. This work demonstrates the effectiveness of deep generative models in bioimage analysis, and provides a new solution for quantitative subcellular proteomics.
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Aprendizado Profundo , Humanos , Proteínas/metabolismo , Proteínas/química , Proteínas/análise , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência/métodos , Aprendizado de MáquinaRESUMO
Proteorhodopsins have been suggested as an important strategy among phototrophs to capture solar energy in marine environments. The goals of this study was to investigate the diversity of proteorhodopsin genes and to explore their abundance, distribution, and expression in the coastal surface waters of the northern South China Sea, one of the largest marginal seas of the western North Pacific Ocean. Using 21 metagenomes, we recovered proteorhodopsin genes from a wide range of prokaryotic taxa, and chlorophyll a contributed significantly to the community composition of proteorhodopsin-containing microbes. Most proteorhodopsin sequences were predicted to encode green light-absorbing proton pumps and green light-absorbing proteorhodopsin genes were more abundant than blue-absorbing ones. The variations in the conserved residues involved in ion pumping and several uncharacterized proteorhodopsins were observed. The gene abundance pattern of proteorhodopsin types were significantly influenced by the levels of total organic carbon and soluble reactive phosphorus. Gene expression analysis confirmed the importance of proteorhodopsin-based phototrophy and revealed different expressional patterns among major phyla. In tandem, we screened 2295 metagenome-assembled genomes to describe the taxonomic distribution of proteorhodopsins. Bacteroidota are the key lineages encoding proteorhodopsins, but proteorhodopsins were predicated from members of Proteobacteria, Marinisomatota, Myxococcota, Verrucomicrobiota and Thermoplasmatota. Our study expanded the diversity of proteorhodopsins and improve our understanding on the significance of proteorhodopsin-mediated phototrophy in the marine ecosystem.
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Rodopsinas Microbianas , Rodopsinas Microbianas/genética , Rodopsinas Microbianas/metabolismo , China , Oceano Pacífico , Água do Mar/microbiologia , Água do Mar/química , Metagenoma , FilogeniaRESUMO
Human activities emitting carbon dioxide (CO2) have caused severe greenhouse effects and accelerated climate change, making carbon neutrality urgent. Seawater mineral carbonation technology offers a promising negative emission strategy. This work investigates current advancements in proposed seawater mineral carbonation technologies, including CO2 storage and ocean chemical carbon sequestration. CO2 storage technology relies on indirect mineral carbonation to fix CO2, involving CO2 dissolution, Ca/Mg extraction, and carbonate precipitation, optimized by adding alkaline substances or using electrochemical methods. Ocean chemical carbon sequestration uses natural seawater for direct mineral carbonation, enhanced by adding specific materials to promote carbonate precipitation and increase CO2 absorption, thus enhancing marine carbon sinks. This study evaluates these technologies' advantages and challenges, including reaction rates, costs, and ecological impacts, and analyzes representative materials' carbon fixation potential. Literature indicates that seawater mineral carbonation can play a significant role in CO2 storage and enhancing marine carbon sinks in the coming decades.
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Dióxido de Carbono , Sequestro de Carbono , Água do Mar , Água do Mar/química , Dióxido de Carbono/análise , Mudança Climática , Carbonatos/química , Minerais/químicaRESUMO
OBJECTIVES: Irritable bowel syndrome (IBS) is a common disorder in gut-brain interaction. Diet plays an important role in the pathophysiology of IBS. Therefore, we aimed to explore the potential causal effects of food-liking on IBS to provide better diet advice for patients. METHODS: Single-nucleotide polymorphisms associated with food-liking were selected as instrumental variables, which were obtained from the latest genome-wide association study (GWAS) conducted on 161 625 participants. The summary data of genetic associations with IBS were obtained from a recent GWAS with 433 201 European controls and 53 400 cases. We used inverse variance weighting as the main analysis. Sensitivity analyses were conducted to detect horizontal pleiotropy and heterogeneity. RESULTS: Significant evidence revealed the protective effects of a vegetarian diet-liking on IBS, including asparagus, avocadoes, globe artichoke, aubergine, and black olives, while onion-liking showed potential deleterious effects. For meat and fish, preference for sardines and fried fish was marginally associated with IBS risk, but salami and salmon were potential protective factors. In terms of desserts and dairy products, preferences for cake icing, ketchup, and cheesecake were suggestively associated with higher IBS risk, while goat cheese-liking was marginally correlated with lower IBS risk. Additionally and suggestively, significant causal effects of IBS on increased preferences for globe artichoke and salami were also found in a reverse Mendelian randomization (MR) study. CONCLUSION: Our study revealed potential causal associations between food preference and IBS from a genetic perspective, which provides a dietary reference for such patients.
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Preferências Alimentares , Estudo de Associação Genômica Ampla , Síndrome do Intestino Irritável , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/etiologia , Dieta Vegetariana , Dieta/efeitos adversos , Feminino , Fatores de RiscoRESUMO
Upland cotton accounts for a high percentage (95%) of the world's cotton production. Plant height (PH) and branch number (BN) are two important agronomic traits that have an impact on improving the level of cotton mechanical harvesting and cotton yield. In this research, a recombinant inbred line (RIL) population with 250 lines developed from the variety CCRI70 was used for constructing a high-density genetic map and identification of quantitative trait locus (QTL). The results showed that the map harbored 8298 single nucleotide polymorphism (SNP) markers, spanning a total distance of 4876.70 centimorgans (cMs). A total of 69 QTLs for PH (9 stable) and 63 for BN (11 stable) were identified and only one for PH was reported in previous studies. The QTLs for PH and BN harbored 495 and 446 genes, respectively. Combining the annotation information, expression patterns and previous studies of these genes, six genes could be considered as potential candidate genes for PH and BN. The results could be helpful for cotton researchers to better understand the genetic mechanism of PH and BN development, as well as provide valuable genetic resources for cotton breeders to manipulate cotton plant architecture to meet future demands.
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Exosomes are nanoscale membrane bound vesicles secreted by almost all types of cells. Their unique attributes, such as minimal immunogenicity and compatibility with biological systems, make them novel carriers for drug delivery. These native exosomes harbor proteins, nucleic acids, small molecule compounds, and fluorogenic agents. Moreover, through a combination of chemical and bioengineering methodologies, exosomes are tailored to transport precise therapeutic payloads to designated cells or tissues. In this review, we summarize the strategies for exosome modification and drug loading modalities in engineered exosomes. In addition, we provide an overview of the advances in the use of engineered exosomes for targeted drug delivery. Lastly, we discuss the merits and limitations of chemically engineered versus bioengineered exosome-mediated target therapies. These insights offer additional options for refining engineered exosomes in pharmaceutical development and hold promise for expediting the successful translation of engineered exosomes from the bench to the bedside.
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Sistemas de Liberação de Medicamentos , Exossomos , Exossomos/metabolismo , Humanos , Sistemas de Liberação de Medicamentos/métodos , Bioengenharia/métodos , Animais , Portadores de Fármacos/químicaRESUMO
BACKGROUND: Pharmacokinetic studies are pivotal in drug development, focusing on absorption, distribution, and excretion of active compounds. Effective sample preparation methods play a crucial role in these studies. Traditional techniques like protein precipitation and liquid-liquid extraction often involve toxic solvents and are time-consuming. Recently, deep eutectic solvent (DES) has emerged as an eco-friendly alternative due to its high efficiency, low cost, and low toxicity. This study introduces a novel sample pretreatment method using CO2-switchable DES in liquid-liquid microextraction (LLME) to enhance speed, accuracy, and sensitivity in complex biological samples analysis. RESULTS: A liquid-liquid microextraction sample pretreatment method based on switchable DES combined with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the analysis of urine and tissue samples. The method was optimized through systematic investigation of key parameters, including DES type, volume, molar ratio, pH, vortex time, gas purge time, and salt addition. The resulting procedure exhibited satisfying linearity (r2 ≥ 0.9958), good precision (RSD ≤6.01 %), desirable recovery (52.44%-98.12 %) and matrix effect (86.22%-119.30 %), and the accuracy and precision of stability were within the ±15 % limit. The proven methods were further applied to urinary excretion study and tissue distribution study of Nelumbinis plumula (NP) extract. The results indicated that the total cumulative excretion of liensinine, isoliensinine and neferine in urine within 240 h was 4.96 %, 0.66 % and 0.44 %, respectively. The tissue distribution study showed that alkaloids mainly distribute in liver, kidney, and spleen. SIGNIFICANCE: This research introduces a groundbreaking technique distinguished by its simplicity, speed, cost-effectiveness, and environmental friendliness. This approach, utilizing CO2-switchable DES as an extraction solvent for LLME, integrates deproteinization and removal of interfering molecules into a single step. This integration showcases its efficiency and convenience, demonstrating significant promise for various applications in the analysis of biological samples. Additionally, this study provides the first report on urinary excretion and tissue distribution of alkaloids from NP using a DES-LLME method. These findings offer valuable insights into the in vivo behavior of herbal medicine, enhancing understanding of pharmacological actions and facilitating clinical rational administration.
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Dióxido de Carbono , Solventes Eutéticos Profundos , Microextração em Fase Líquida , Espectrometria de Massas em Tandem , Microextração em Fase Líquida/métodos , Dióxido de Carbono/química , Solventes Eutéticos Profundos/química , Animais , Distribuição Tecidual , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Microplastics are accumulating rapidly in aquatic ecosystems, providing habitats for pathogens and vectors for antibiotic resistance genes (ARGs), potentially increasing pathogenic risks. However, few studies have considered microplastics as particulate organic matter (POM) to elucidate their pathogenic risks and underlying mechanisms. Here, we performed microcosm experiments with microplastics and natural POM (leaves, algae, soil), thoroughly investigating their distinct effects on the community compositions, functional profiles, opportunistic pathogens, and ARGs in Particle-Associated (PA) and Free-Living (FL) bacterial communities. We found that both microplastics and leaves have comparable impacts on microbial community structures and functions, enriching opportunistic pathogens and ARGs, which may pose potential environmental risks. These effects are likely driven by their influences on water properties, including dissolved organic carbon, nitrate, DO, and pH. However, microplastics uniquely promoted pathogens as keystone species and further amplified their capacity as hosts for ARGs, potentially posing a higher pathogenic risk than natural POM. Our research also emphasized the importance of considering both PA and FL bacteria when assessing microplastic impacts, as they exhibited different responses. Overall, our study elucidates the role and underlying mechanism of microplastics as an emerging POM in intensifying pathogenic risks of aquatic ecosystems in comparison with conventional natural POM.
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Bactérias , Ecossistema , Microplásticos , Material Particulado , Poluentes Químicos da Água , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Material Particulado/toxicidade , Bactérias/genética , Bactérias/efeitos dos fármacos , Folhas de Planta/microbiologia , Microbiota/efeitos dos fármacos , Microbiologia da ÁguaRESUMO
Prolyl hydroxylase domain (PHD) proteins are oxygen sensors that use intracellular oxygen as a substrate to hydroxylate hypoxia-inducible factor (HIF) α proteins, routing them for polyubiquitylation and proteasomal degradation. Typically, HIFα accumulation in hypoxic or PHD-deficient tissues leads to upregulated angiogenesis. Here, we report unexpected retinal phenotypes associated with endothelial cell (EC)-specific gene targeting of Phd2 (Egln1) and Hif2alpha (Epas1). EC-specific Phd2 disruption suppressed retinal angiogenesis, despite HIFα accumulation and VEGFA upregulation. Suppressed retinal angiogenesis was observed both in development and in the oxygen-induced retinopathy (OIR) model. On the other hand, EC-specific deletion of Hif1alpha (Hif1a), Hif2alpha, or both did not affect retinal vascular morphogenesis. Strikingly, retinal angiogenesis appeared normal in mice double-deficient for endothelial PHD2 and HIF2α. In PHD2-deficient retinal vasculature, delta-like 4 (DLL4, a NOTCH ligand) and HEY2 (a NOTCH target) were upregulated by HIF2α-dependent mechanisms. Inhibition of NOTCH signaling by a chemical inhibitor or DLL4 antibody partially rescued retinal angiogenesis. Taken together, our data demonstrate that HIF2α accumulation in retinal ECs inhibits rather than stimulates retinal angiogenesis, in part by upregulating DLL4 expression and NOTCH signaling.
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Animais Recém-Nascidos , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Células Endoteliais , Prolina Dioxigenases do Fator Induzível por Hipóxia , Receptores Notch , Neovascularização Retiniana , Transdução de Sinais , Regulação para Cima , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Camundongos , Receptores Notch/metabolismo , Receptores Notch/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Células Endoteliais/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Vasos Retinianos/metabolismo , AngiogêneseRESUMO
In this study, alumina ceramics with hierarchical pores were successfully fabricated using freeze casting. Experimental studies show that both the solid loading of the slurry and the thermal insulation layer at the interface of the slurry and cooling plate can influence the pore characteristics of cast samples. In order to examine the pore characteristics and evaluate the permeability of the freeze-cast samples fabricated under different conditions, a generative adversarial network (GAN) method was employed to reconstruct the three-dimensional (3D) microstructure from two-dimensional (2D) scanning electron microscopy (SEM) images of the samples. Furthermore, GAN 3D reconstruction was validated against X-ray tomography 3D reconstruction results. Based on the GAN reconstructed microstructures, the permeability and pore distribution of the various samples were analyzed. The sample cast with 35 wt.% solid loading shows an optimal permeability.
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The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 µm, 550 µm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 µm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.