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Many studies have confirmed that climate change leads to frequent urban flooding, which can lead to significant socioeconomic repercussions. However, most existing studies have not evaluated the impacts of climate change on urban flood from both event-scale and annual-scale dimensions. In addition, there are only few studies that simultaneously consider scenario and model uncertainties of climate change, and combine flood risk assessment and uncertainty analysis results to provide practical suggestions for urban drainage system management. This study uses the statistical downscaling method to calculate the design rainfall under ten rainfall return periods of four climate models and three climate change scenarios in 2040s, 2060s, and 2080s in various prefecture-level cities in China. The four climate models are HadGEM2- ES, MPI-ESM-MR, NorESM1-M and FGOALS-g2 models and the three climate change scenarios are constructed by different representative concentration pathways (RCP), namely RCP2.6, RCP4.5 and RCP8.5. On this basis, relying on the generated drainage systems using geographical information and other data, event-scale and annual-scale precipitation are combined to calculate the change ratio of annual flood volume expectation in prefecture-level cities in each future year compared with the current situation. Furthermore, the study evaluates scenario and model uncertainties of climate change, and then comprehensively integrates the flood risk and its uncertainties to provides suggestions for urban drainage system management.
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Ciudades , Cambio Climático , Inundaciones , Incertidumbre , China , Lluvia , Modelos Teóricos , Medición de RiesgoRESUMEN
Community coalescence related to bacterial mixing events regulates community characteristics and affects the health of estuary ecosystems. At present, bacterial coalescence and its driving factors are still unclear. The present study used a dataset from the Chesapeake Bay (2017) to address how bacterial community coalescence in response to variable hydrochemistry in estuarine ecosystems. We determined that variable hydrochemistry promoted the deterioration of water quality. Temperature, orthophosphate, dissolved oxygen, chlorophyll a, Secchi disk depth, and dissolved organic phosphorus were the key environmental factors driving community coalescence. Bacteria with high tolerance to environmental change were the primary taxa accumulated in community coalescence, and the significance of deterministic processes to communities was revealed. Community coalescence was significantly correlated with the pathways of metabolism and organismal systems, and promoted the co-occurrence of antibiotic resistance and virulence factor genes. Briefly, community coalescence under variable hydrochemical conditions shaped bacterial diversity and functional traits, to optimise strategies for energy acquisition and lay the foundation for alleviating environmental pressures. However, potential pathogenic bacteria in community coalescence may be harmful to human health and environmental safety. The present study provides a scientific reference for ecological management of estuaries.
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Bacterias , Bahías , Bahías/microbiología , Bacterias/genética , Microbiota/efectos de los fármacos , Biodiversidad , Calidad del Agua , EstuariosRESUMEN
Li-N2 batteries are a promising platform for electrochemical energy storage, but their performance is limited by the low activity of the cathode catalysts. In this work, density functional theory was used to study the catalytic activity of the pristine M2C and oxygen-functionalized M2CO2 MXenes (M = Sc, Ti, and V) as cathodes for Li-N2 batteries. The calculated results suggest that the pristine M2C MXenes (M = Sc, Ti, and V) show high electrical conductivity due to the Fermi level crossing the metal 3d states. The stable adsorption of N2 occurs on M2C MXenes via a side-on model and strengthens gradually with decreasing metal atomic number. Furthermore, the kinetics of N2 dissociation can be significantly accelerated by the coadsorption of Li on M2C MXenes. However, adsorption and dissociation of N2 on the M2CO2 surfaces are too difficult to occur due to strong electrostatic repulsion. The Li-mediated nitrogen reduction reaction during discharge proceeds favorably via (N + N)* â (LiN + N)* â (LiN + LiN)* â (Li2N + LiN)* â (Li2N + Li2N)* â (Li3N + Li2N)* â (Li3N + Li3N)* to form two isolated Li3N* on M2C MXenes. The calculated charge-discharge overpotentials decrease in the order of Sc2C < Ti2C < V2C. Notably, the Sc2C MXene has great potential as a cathode catalyst for Li-N2 batteries because of its high electrical conductivity, strong N2 adsorption, favorable Li-mediated N2 dissociation, and ultralow discharging, charging, and total overpotentials (0.07, 0.06, and 0.13 V). This study offers a theoretical foundation for future research on Li-N2 batteries.
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Modified Jiawei Juanbi decoction (MJD) is used for the treatment of early-stage knee osteoarthritis (KOA). Here, modified Jiawei Juanbi decoction (MJD) was employed for the treatment of early-stage knee osteoarthritis (KOA) and its mechanisms were assessed via metabonomics and network pharmacology. A total of 24 male Sprague-Dawley rats were randomly allocated into a normal control group, a model group, and an MJD group (n = 8 rats per group). Each rat group was further equally divided into two subgroups for investigation for either 14 or 28 days. A rat model of early-stage KOA was constructed and rats were treated with MJD. Effects were evaluated based on changes in knee circumference, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). We also analyzed histopathological changes in articular cartilage. High-resolution mass spectrometry was used to analyze the chemical profile of MJD, identifying 228 components. Using an LC-Q-TOF-MS metabonomics approach, 33 differential metabolites were identified. The relevant pathways significantly associated with MJD include arginine and proline metabolism, vitamin B6 metabolism, as well as the biosynthesis of phenylalanine, tyrosine and tryptophan. The system pharmacology paradigm revealed that MJD contains 1027 components and associates with 1637 genes, of which 862 disease genes are related to osteoarthritis. The construction of the MJD composition-target-KOA network revealed a total of 140 intersection genes. A total of 39 hub genes were identified via integration of betweenness centrality values greater than 100 using CytoHubba. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed several significantly affected signaling pathways including the HIF-1, AGE-RAGE (in diabetic complications), IL-17, rheumatoid arthritis and TNF pathways. Integrated-omics and network pharmacology approaches revealed a necessity for further detailed investigation focusing on two major targets, namely NOS2 and NOS3, along with their essential metabolite (arginine) and associated pathways (HIF-1 signaling and arginine and proline metabolism). Real-time PCR validated significantly greater downregulation of NOS2 and HIF-1É in the MJD as compared to the model group. Molecular docking analysis further confirmed the binding of active MJD with key active components. Our findings elucidate the impact of MJD on relevant pathophysiological and metabolic networks relevant to KOA and assess the drug efficacy of MJD and its underlying mechanisms of action.
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Our previous studies have demonstrated that Mito-Tempol (also known as 4-hydroxy-Tempo), a mitochondrial reactive oxygen species scavenger, alleviates oxidized low-density lipoprotein (ox-LDL)-triggered foam cell formation. Given the effect of oxidative stress on activating the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome, which promotes foam cell formation, we aimed to explore whether Mito-Tempo inhibits ox-LDL-triggered foam cell formation by regulating NLRP3 inflammasome. The results revealed that Mito-Tempo re-activated Nrf2 and alleviated macrophage foam cell formation induced by ox-LDL, whereas the effects were reversed by ML385 (a specific Nrf2 inhibitor). Mito-Tempo restored the expression and nuclear translocation of Nrf2 by decreasing ox-LDL-induced ubiquitination. Furthermore, Mito-Tempo suppressed ox-LDL-triggered NLRP3 inflammasome activation and subsequent pyroptosis, whereas the changes were blocked by ML385. Mito-Tempo decreased lipoprotein uptake by inhibiting CD36 expression and suppressed foam cell formation by regulating the NLRP3 inflammasome. Taken together, Mito-Tempo exhibits potent anti-atherosclerotic effects by regulating Nrf2/NLRP3 signaling.
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Células Espumosas , Lipoproteínas LDL , Factor 2 Relacionado con NF-E2 , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Lipoproteínas LDL/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Transducción de Señal/efectos de los fármacos , Ratones , Animales , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Piroptosis/efectos de los fármacos , Humanos , Células RAW 264.7 , Óxidos N-Cíclicos/farmacología , Antígenos CD36/metabolismo , Compuestos Organofosforados , PiperidinasRESUMEN
In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol's hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in pparγ and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Pparγ and Rxrα exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Pparγ and Rxrα protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture.
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Diabetes Mellitus Tipo 2 , Hiperlipidemias , Tocotrienoles , Humanos , Ratones , Ratas , Animales , Tocotrienoles/metabolismo , Pez Cebra/metabolismo , Dieta Alta en Grasa , Hiperlipidemias/metabolismo , Aceite de Salvado de Arroz , Diabetes Mellitus Tipo 2/metabolismo , PPAR gamma/metabolismo , ARN Mensajero/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismoRESUMEN
Flooding is an important process in natural fluvial floodplains. How the flood shapes aquatic community diversity in highland floodplains is still poorly understood. The aim of this study was to unravel the multi-faceted responses of benthic macroinvertebrate diversity to flooding and habitat environments in the Baihe River Basin from a taxonomic, phylogenetic, and functional perspective. We examined the alpha and beta diversity patterns of benthic macroinvertebrate communities in the mainstream, tributaries, and oxbow lakes during the normal water and flood periods. The results showed that the traditional alpha taxonomic diversity (TD) varied across habitats, despite minor changes after flood pulse. Alpha phylogenetic diversity (PD) decreased and alpha functional diversity (FD) markedly increased after flooding, with functional traits transiting toward risk avoidance. While all the three facets of beta diversity significantly responded to habitat differences, beta TD and PD shifted in response to flooding. Species turnover prominently increased in beta TD and PD after flood pulse, which contrasted with a weaker response of this process in FD. The explanatory power of significant environmental factors on both alpha and beta diversity was reduced by flooding. Compared with traditional TD, cooperating multi-faceted diversity could better depict the responses of benthic macroinvertebrate communities to flooding. The assessment and conservation of aquatic biodiversity in highland floodplains should take into account the three facets of alpha and beta diversity.
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Biodiversidad , Inundaciones , Invertebrados , Animales , Invertebrados/fisiología , China , Ríos , Filogenia , EcosistemaRESUMEN
We report on the detailed steps of a method to estimate the biomass of invasive plants based on UAV remote sensing and computer vision. To collect samples from the study area, we prepared a sample square assembly to randomize the sampling points. An unmanned aerial camera system was constructed using a drone and camera to acquire continuous RGB images of the study area through automated navigation. After completing the shooting, the aboveground biomass in the sample frame was collected, and all correspondences were labeled and packaged. The sample data was processed, and the aerial images were segmented into small images of 280 x 280 pixels to create an image dataset. A deep convolutional neural network was used to map the distribution of Mikania micrantha in the study area, and its vegetation index was obtained. The organisms collected were dried, and the dry weight was recorded as the ground truth biomass. The invasive plant biomass regression model was constructed using the K-nearest neighbor regression (KNNR) by extracting the vegetation index from the sample images as an independent variable and integrating it with the ground truth biomass as a dependent variable. The results showed that it was possible to predict the biomass of invasive plants accurately. An accurate spatial distribution map of invasive plant biomass was generated by image traversal, allowing precise identification of high-risk areas affected by invasive plants. In summary, this study demonstrates the potential of combining unmanned aerial vehicle remote sensing with machine learning techniques to estimate invasive plant biomass. It contributes significantly to the research of new technologies and methods for real-time monitoring of invasive plants and provides technical support for intelligent monitoring and hazard assessment at the regional scale.
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Computadores , Inteligencia , Biomasa , Análisis por Conglomerados , Aprendizaje AutomáticoRESUMEN
Drug repurposing is a strategy aiming at uncovering novel medical indications of approved drugs. This process of discovery can be effectively represented as a link prediction task within a medical knowledge graph by predicting the missing relation between the disease entity and the drug entity. Typically, the links to be predicted pertain to rare types, thereby necessitating the task of few-shot link prediction. However, the sparsity of neighborhood information and weak triplet interactions result in less effective representations, which brings great challenges to the few-shot link prediction. Therefore, in this paper, we proposed a meta-learning framework based on a multi-level attention network (MLAN) to capture valuable information in the few-shot scenario for drug repurposing. First, the proposed method utilized a gating mechanism and a graph attention network to effectively filter noise information and highlight the valuable neighborhood information, respectively. Second, the proposed commonality relation learner, employing a set transformer, effectively captured triplet-level interactions while remaining insensitive to the size of the support set. Finally, a model-agnostic meta-learning training strategy was employed to optimize the model quickly on each meta task. We conducted validation of the proposed method on two datasets specifically designed for few-shot link prediction in medical field: COVID19-One and BIOKG-One. Experimental results showed that the proposed model had significant advantages over state-of-the-art few-shot link prediction methods. Results also highlighted the valuable insights of the proposed method, which successfully integrated the components within a unified meta-learning framework for drug repurposing.
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COVID-19 , Reposicionamiento de Medicamentos , Humanos , AprendizajeRESUMEN
BACKGROUND: Apolipoprotein A1 (ApoA1) is a member of the apolipoprotein family with diverse functions. It is associated with the pathogenesis and prognosis of several types of tumors. However, the role of serum apolipoprotein A1 (ApoA1) in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to elucidate its influence on clinical outcomes in patients with DLBCL. METHODS: We retrospectively analyzed a cohort of 1583 consecutive DLBCL patients admitted to the Fujian Medical University Union Hospital between January 2011 and December 2021. 949 newly diagnosed DLBCL patients who met the inclusion criteria were enrolled for statistical analysis. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off value for serum ApoA1 levels for prognostic prediction among patients with DLBCL. The correlations between serum ApoA1 levels and clinical and laboratory parameters were analyzed. Prognostic significance was analyzed using univariate and multivariate Cox proportional hazards models. RESULTS: Newly diagnosed patients with DLBCL demonstrated low serum ApoA1 levels (< 0.925 g/L), had more B symptoms, higher levels of serum lactate dehydrogenase (LDH) (>upper limit of normal), poorer performance status (Eastern Cooperative Oncology Group score of 2-4), higher percentage of advanced stage and non-germinal center B-cell (non-GCB) subtype, more cases of > 1 extranodal site, higher International Prognostic Index (IPI) score (3-5), and higher incidence of relapse or refractory diseases compared with those with high serum ApoA1 levels (≥ 0.925 g/L). Low serum ApoA1 levels were an independent adverse prognostic factor for overall survival (OS) but not progression-free survival (PFS). CONCLUSIONS: Low serum ApoA1 levels were associated with poor treatment response and inferior survival in newly diagnosed patients with DLBCL.
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Apolipoproteína A-I , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/patología , Recurrencia Local de Neoplasia , Pronóstico , Estudios RetrospectivosRESUMEN
Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin-like modifier (SUMO)-mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO-specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA-binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co-activator yes-associated protein 1 in the Hippo pathway. Finally, adeno-associated virus serotype 9 is used to construct TEAD1 wild-type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy-related heart failure.
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Insuficiencia Cardíaca , Sumoilación , Humanos , Ratones , Animales , Cardiomegalia , Factores de Transcripción/metabolismo , Insuficiencia Cardíaca/metabolismo , Regulación de la Expresión Génica , Factores de Transcripción de Dominio TEARESUMEN
BACKGROUND: Various extracellular matrix (ECM) reshaping events are involved in inflammatory bowel disease (IBD). LAMB3 is a vital subunit of laminin-332, an important ECM component. Data on the biological function of LAMB3 in intestinal inflammation are lacking. Our aim is to discuss the effect of LAMB3 in IBD. METHODS: LAMB3 expression was assessed in cultured intestinal epithelial cells, inflamed mucosal tissues of patients and mouse colitis models. RNA sequencing, quantitative real-time polymerase chain reaction and Western blotting were used to detect the LAMB3 expression distribution and potential downstream target genes. Dual-luciferase assays and chromatin immunoprecipitation-quantitative polymerase chain reaction were used to determine whether P65 could transcriptionally activate LAMB3 under tumor necrosis factor α stimulation. RESULTS: LAMB3 expression was increased in inflammatory states in intestinal epithelial cells and colonoids and was associated with adverse clinical outcomes in Crohn's disease. Knockdown of LAMB3 inhibited the expression of proinflammatory cytokines. Mechanistically, LAMB3 expression was directly transcriptionally activated by P65 and was inhibited by nuclear factor kappa B inhibitors under tumor necrosis factor α stimulation. Furthermore, RNA sequencing and replenishment experiments revealed that LAMB3 upregulated SERPINA3 to promote intestinal inflammation via the integrin α3ß1/FAK pathway. CONCLUSION: We propose that LAMB3 could serve as a potential therapeutic target of IBD and a predictor of intestinal stenosis of Crohn's disease. Our findings demonstrate the important role of ECM in the progression of IBD and offer an experimental basis for the treatment and prognosis of IBD.
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Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Serpinas , Animales , Humanos , Ratones , Enfermedad de Crohn/patología , Inflamación/patología , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/patología , Serpinas/metabolismo , Serpinas/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To explore the expression of Exosome Component 4ï¼EXOSC4ï¼ in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance. METHODS: The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance. RESULTS: The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05). CONCLUSION: High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.
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Complejo Multienzimático de Ribonucleasas del Exosoma , Linfoma de Células B Grandes Difuso , Humanos , Relevancia Clínica , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Pronóstico , Estudios Retrospectivos , Complejo Multienzimático de Ribonucleasas del Exosoma/genéticaRESUMEN
Respiratory structures are crucial for vertebrate survival, as they serve not only to perform gas-exchange processes but also as entry points for opportunistic pathogens. Previous studies have demonstrated that fish contain gill mucosal-associated lymphoid tissue, and harbor a large number of commensal bacteria on their surface and contribute to maintaining fish health. However, by far, very limited information is known regarding the effects of viral infection on gill mucosal immunity and microbiota homeostasis. In this study, we conducted an infection model by bath with infectious hematopoietic necrosis virus (IHNV) and revealed a 27 % mortality rate among rainbow trout in the first two weeks after infection. Moreover, we found that diseased fish with the highest IHNV loads in gills exhibiting severe damage, as well as increased goblet cell counts in both primary lamellae (PL) and secondary lamellae (SL). Additionally, RT-qPCR and RNA-seq analyses revealed that IHNV infection induced a strong innate and adaptive antiviral immune responses. Interestingly, an antibacterial immune response was also observed, suggesting that a secondary bacterial infection occurred in trout gills after viral infection. Furthermore, 16S rRNA analysis of trout gills revealed a profound dysbiosis marked by a loss of beneficial taxa and expansion of pathobionts following IHNV infection. Overall, our finding demonstrates that IHNV infection induces significant changes of the microbial community in the fish respiratory surface, thus triggering local antiviral and bacterial mucosal immunity.
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Enfermedades de los Peces , Virus de la Necrosis Hematopoyética Infecciosa , Microbiota , Oncorhynchus mykiss , Infecciones por Rhabdoviridae , Animales , Virus de la Necrosis Hematopoyética Infecciosa/fisiología , Branquias , Inmunidad Mucosa , ARN Ribosómico 16SRESUMEN
Although the MAPK/MEK/ERK pathway is prevalently activated in colorectal cancer (CRC), MEK/ERK inhibitors show limited efficiency in clinic. As a downstream target of MAPK, ELK4 is thought to work primarily by forming a complex with SRF. Whether ELK4 can serve as a potential therapeutic target is unclear and the transcriptional regulatory mechanism has not been systemically analyzed. Here, it is shown that ELK4 promotes CRC tumorigenesis. Integrated genomics- and proteomics-based approaches identified SP1 and SP3, instead of SRF, as cooperative functional partners of ELK4 at genome-wide level in CRC. Serum-induced phosphorylation of ELK4 by MAPKs facilitated its interaction with SP1/SP3. The pathological neoangiogenic factor LRG1 is identified as a direct target of the ELK4-SP1/SP3 complex. Furthermore, targeting the ELK4-SP1/SP3 complex by combination treatment with MEK/ERK inhibitor and the relatively specific SP1 inhibitor mithramycin A (MMA) elicited a synergistic antitumor effect on CRC. Clinically, ELK4 is a marker of poor prognosis in CRC. A 9-gene prognostic model based on the ELK4-SP1/3 complex-regulated gene set showed robust prognostic accuracy. The results demonstrate that ELK4 cooperates with SP1 and SP3 to transcriptionally regulate LRG1 to promote CRC tumorigenesis in an SRF-independent manner, identifying the ELK4-SP1/SP3 complex as a potential target for rational combination therapy.
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Neoplasias Colorrectales , Regulación de la Expresión Génica , Humanos , Regiones Promotoras Genéticas , Neoplasias Colorrectales/genética , Carcinogénesis/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Proteína Elk-4 del Dominio ets/genética , GlicoproteínasRESUMEN
Importance: While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary. Objective: To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion. Design, Setting, and Participants: Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion. Exposure: Induced first-trimester abortion. Main Outcomes and Measures: The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion. Results: Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count. Conclusions and Relevance: Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.
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Aborto Inducido , Eritrocitos , Isoinmunización Rh , Adulto , Femenino , Humanos , Embarazo , Aborto Inducido/métodos , Inmunoglobulinas/sangre , Estudios Prospectivos , Isoinmunización Rh/diagnóstico , Isoinmunización Rh/inmunología , Isoinmunización Rh/terapia , Riesgo , Primer Trimestre del Embarazo/inmunología , Eritrocitos/inmunología , Adulto Joven , Negro o Afroamericano , BlancoRESUMEN
Exploring highly active oxygen reduction electrocatalysts with low precious metals content is imperative but remains a considerable challenge. Herein, a series of heterobimetallic multi-walled carbon nanotubes (MWCNTs) electrocatalysts based on metal complexes are presented. These electrocatalysts feature diverse transition metals (M=Mn, Fe, Co, Ni) 5,15-bromophenyl-10, 20-methoxyphenyl porphyrin (MBMP) and tetrakis(triphenylphosphine)palladium (0) (Pd[P(Ph3)4]) anchored non-covalently on its surface. The resulting NiBMP-based MWCNTs with Pd[P(Ph3)4] (PdNiN4/MWCNTs) display outstanding electrocatalytic oxygen reduction activity (onset potential, 0.941 V; half wave potential, 0.830 V) and robust long-term durability in alkaline electrolyte. While in neutral condition, the MnBMP-based MWCNTs with Pd[P(Ph3)4] (PdMnN4/MWCNTs) are the most active heterobimetallic ORR catalyst and produce ultra-low concentration hydrogen peroxide (H2O2yield, 1.2%-1.3%). Synergistically tuning the ORR electrocatalytic activity and electron transfer pathway is achieved by the formation of NiBMP/MnBMP-Pd[P(Ph3)4] active sites. This work indicates such metalloporphyrin-Pd[P(Ph3)4] active sites on MWCNTs have significantly positive influence on electrocatalytic ORR systems and provides facile and mild strategy for designing highly efficient ORR electrocatalysts with ultra-low loading precious metal.
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Floodplains are hotspots for biodiversity research and conservation worldwide. Hydrological disturbances can profoundly influence the ecological processes and functions of floodplain systems by altering key biological groups such as algae communities. However, the impacts of flood disturbance on the assembly processes and co-occurrence patterns of algae communities in floodplain ecosystems are still unclear. To ascertain the response patterns of algae communities to flood disturbance, we characterized planktonic and benthic algae communities in 144 water and sediment samples collected from the Tibetan floodplain during non-flood and flood periods based on 23S ribosomal RNA gene sequencing. Results showed that planktonic algae exhibited higher diversity and greater compositional variations compared with benthic communities after flood disturbance. Flooding promoted algae community homogenization at horizontal (rivers vs. oxbow lakes) and vertical levels (water vs. sediment). Stochastic processes governed the assembly of distinct algae communities, and their ecological impacts were enhanced in response to flooding. In the non-flood period, dispersal limitation (81.78 %) was the primary ecological process driving algae community assembly. In the flood period, the relative contribution of ecological drift (72.91 %) to algae community assembly markedly increased, with dispersal limitation (22.61 %) being less important. Flooding reduced the interactions among algae taxa, resulting in lower network complexity and stability. Compared with the planktonic algae subnetworks, the benthic subnetworks showed greater stability in the face of flooding. Findings of this study broaden our understanding of how algae communities respond to hydrological disturbances from an ecological perspective and could be useful for the management of highland floodplain ecosystems.
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With the rapid development of urbanization, the rate of abandonment of arable land in China's mountainous areas has accelerated. Solving the phenomenon of abandonment of arable land has become an important issue in managing the use of China's arable land, the key to which lies in the development of specialty agriculture using the unique natural environment of mountainous areas. This paper scrutinizes both the horizontal and vertical distribution of specialty agriculture in these areas, drawing upon the "One Village, One Product" dataset provided by the Chinese Ministry of Agriculture and Rural Development. The findings reveal that the horizontal distribution pattern of specialty agriculture exhibits the formation of eight primary clusters. It is intriguing to observe that a majority of these clusters are situated at the intersection of two or three provincial administrative units, with the largest cluster occurring at the border of Chengdu and Chongqing. In terms of the vertical distribution pattern, the specialty agriculture in China's mountainous areas are mainly distributed at low altitudes, i.e., below 500 m, and at gentle slopes of 4°-8°, and with increases in altitude or slope, the overall amount of specialty agriculture declines rapidly.
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Background: The previous researches show that infertile patients have a higher incidence of endometritis and endometrial polyps, and the occurrence of these two diseases is related to changes in the microbiota of the genital tract. We aim to determine the composition and changing characteristics of the microbiota in the genital tract (especially the endometrium) of infertile patients with chronic endometritis or endometrial polyps, and find the correlation between it and the occurrence of diseases. Methods: This is a prospective study. We collected genital tract biopsy samples from 134 asymptomatic infertile patients receiving assisted reproductive therapy before embryo transfer. Through pathological examination and 16S ribosomal RNA(16S rRNA) sequencing, we determined the distribution of chronic endometritis and endometrial polyps in these patients, as well as their distribution of reproductive tract microorganisms. Results: Compared with the normal control group, the microbial group of reproductive tract in patients with chronic endometritis and endometrial polyps is changed, and there are significant species differences and relative abundance differences in the vagina, cervix and uterine cavity. Lactobacillus, the dominant flora of female genital tract, showed a change in abundance in patients with endometrial diseases. Endometrial microbiota composed of Staphylococcus, Gardnerella, Atopobium, Streptococcus, Peptostreptococcus, Chlamydia, Fusobacterium, Acinetobacter, etc. are related to chronic endometritis and endometrial polyps. Conclusion: The results showed that, compared with the normal control group, the endometrial microbiota of infertile patients with chronic endometritis or endometrial polyps did have significant changes in the relative abundance distribution of species, suggesting that changes in local microecology may be an important factor in the occurrence of disease, or even adverse pregnancy outcomes. The further study of endometrial microecology may provide a new opportunity to further improve the diagnosis and treatment strategy of chronic endometritis.