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Fine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.
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Contaminantes Atmosféricos , Enfermedades Mitocondriales , Humanos , Contaminantes Atmosféricos/análisis , Fosforilcolina , Material Particulado/análisis , Pulmón , Carbono/análisis , Monitoreo del AmbienteRESUMEN
Upon infection with non-pathogenic microorganisms or treatment with natural or synthetic compounds, plants exhibit a more rapid and potent response to both biotic and abiotic stresses. However, the molecular mechanisms behind this phenomenon, known as defense priming, are poorly understood. ß-aminobutyric acid (BABA) is an endogenous stress metabolite that enhances plant tolerance to various abiotic stresses and primes plant defense responses, providing the ability to resist a variety of pathogens (broad-spectrum resistance). In this study, we identified an aspartyl-tRNA synthetase (AspRS), StIBI1 (named after Arabidopsis IMPAIRED IN BABA-INDUCED IMMUNITY 1; IBI1), as a BABA receptor in Solanum tuberosum. We elucidated the regulatory mechanisms by which StIBI1 interacts with two NAC (NAM, ATAF1, 2, and CUC2) transcription factors (TFs), StVOZ1 and StVOZ2 (VASCULAR PLANT ONE ZINC FINGER, VOZ), to activate BABA-induced resistance (BABA-IR). StVOZ1 represses, whereas StVOZ2 promotes, immunity to the late blight pathogen Phytophthora infestans. Interestingly, BABA and StIBI1 influence StVOZ1- and StVOZ2-mediated immunity. StIBI1 interacts with StVOZ1 and StVOZ2 in the cytoplasm, reducing the nuclear accumulation of StVOZ1 and promoting the nuclear accumulation of StVOZ2. Our findings indicate that StVOZ1 and StVOZ2 finely regulate potato resistance to late blight through distinct signaling pathways. In summary, our study provides insights into the interaction between the potato BABA receptor StIBI1 and the TFs StVOZ1 and StVOZ2, which affects StVOZ1 and StVOZ2stability and nuclear accumulation to regulate late blight resistance during BABA-IR. This research advances our understanding of the primary mechanisms of BABA-IR in potato and contributes to a theoretical basis for the prevention and control of potato late blight using BABA-IR.
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The deadly toxin α-amanitin is a bicyclic octapeptide biosynthesized on ribosomes. A phylogenetically disjunct group of mushrooms in Agaricales (Amanita, Lepiota, and Galerina) synthesizes α-amanitin. This distribution of the toxin biosynthetic pathway is possibly related to the horizontal transfer of metabolic gene clusters among taxonomically unrelated mushrooms with overlapping habitats. Here, our work confirms that two biosynthetic genes, P450-29 and FMO1, are oxygenases important for amanitin biosynthesis. Phylogenetic and genetic analyses of these genes strongly support their origin through horizontal transfer, as is the case for the previously characterized biosynthetic genes MSDIN and POPB. Our analysis of multiple genomes showed that the evolution of the α-amanitin biosynthetic pathways in the poisonous agarics in the Amanita, Lepiota, and Galerina clades entailed distinct evolutionary pathways including gene family expansion, biosynthetic genes, and genomic rearrangements. Unrelated poisonous fungi produce the same deadly amanitin toxins using variations of the same pathway. Furthermore, the evolution of the amanitin biosynthetic pathway(s) in Amanita species generates a much wider range of toxic cyclic peptides. The results reported here expand our understanding of the genetics, diversity, and evolution of the toxin biosynthetic pathway in fungi.
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Amanitinas , Toxinas Biológicas , Amanita/genética , Amanitinas/genética , Evolución Biológica , Vías Biosintéticas/genética , Transferencia de Gen HorizontalRESUMEN
The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Convalecencia , Citocinas , Dipéptidos , Inhibidores de la Dipeptidil-Peptidasa IV , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Formación de Anticuerpos , COVID-19/sangre , COVID-19/inmunología , Citocinas/sangre , Dipéptidos/sangre , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Aprendizaje Automático , Metaboloma , Ratones , SARS-CoV-2 , VacunaciónRESUMEN
BACKGROUND: Evolutionary radiation is widely recognized as a mode of species diversification, but the drivers of the rapid diversification of fungi remain largely unknown. Here, we used Amanitaceae, one of the most diverse families of macro-fungi, to investigate the mechanism underlying its diversification. RESULTS: The ancestral state of the nutritional modes was assessed based on phylogenies obtained from fragments of 36 single-copy genes and stable isotope analyses of carbon and nitrogen. Moreover, a number of time-, trait-, and paleotemperature-dependent models were employed to investigate if the acquisition of ectomycorrhizal (ECM) symbiosis and climate changes promoted the diversification of Amanitaceae. The results indicate that the evolution of ECM symbiosis has a single evolutionary origin in Amanitaceae. The earliest increase in diversification coincided with the acquisition of the ECM symbiosis with angiosperms in the middle Cretaceous. The recent explosive diversification was primarily triggered by the host-plant switches from angiosperms to the mixed forests dominated by Fagaceae, Salicaceae, and Pinaceae or to Pinaceae. CONCLUSIONS: Our study provides a good example of integrating phylogeny, nutritional mode evolution, and ecological analyses for deciphering the mechanisms underlying fungal evolutionary diversification. This study also provides new insights into how the transition to ECM symbiosis has driven the diversification of fungi.
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Evolución Biológica , Micorrizas , Filogenia , Simbiosis , Micorrizas/fisiología , Micorrizas/genética , Agaricales/genética , Agaricales/fisiología , BiodiversidadRESUMEN
Across ecology, and particularly within microbial ecology, there is limited understanding how the generation and maintenance of diversity. Although recent work has shown that both local assembly processes and species pools are important in structuring microbial communities, the relative contributions of these mechanisms remain an important question. Moreover, the roles of local assembly processes and species pools are drastically different when explicitly considering the potential for saturation or unsaturation, yet this issue is rarely addressed. Thus, we established a conceptual model that incorporated saturation theory into the microbiological domain to advance the understanding of mechanisms controlling soil bacterial diversity during forest secondary succession. Conceptual model hypotheses were tested by coupling soil bacterial diversity, local assembly processes and species pools using six different forest successional chronosequences distributed across multiple climate zones. Consistent with the unsaturated case proposed in our conceptual framework, we found that species pool consistently affected α-diversity, even while local assembly processes on local richness operate. In contrast, the effects of species pool on ß-diversity disappeared once local assembly processes were taken into account, and changes in environmental conditions during secondary succession led to shifts in ß-diversity through mediation of the strength of heterogeneous selection. Overall, this study represents one of the first to demonstrate that most local bacterial communities might be unsaturated, where the effect of species pool on α-diversity is robust to the consideration of multiple environmental influences, but ß-diversity is constrained by environmental selection.
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Biodiversidad , Microbiota , Bosques , Ecología , Bacterias/genética , Suelo , EcosistemaRESUMEN
During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62â% for internal transcribed spacer (ITS), 98.66-99.10â% for ribosomal small subunit (nrSSU), and 96.36-98.22â% for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.
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Ácidos Grasos , Mucorales , Animales , Filogenia , China , Análisis de Secuencia de ADN , Composición de Base , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Ácidos Grasos/química , InvertebradosRESUMEN
MicroRNAs (miRNAs) are small noncoding RNAs in eukaryotes. Plant endogenous miRNAs play pivotal roles in regulating plant development and defense responses. MicroRNA394 (miR394) has been reported to regulate plant development, abiotic stresses and defense responses. Previous reports showed that miR394 responded to P. infestans inoculation in potato, indicating that miR394 may be involved in defense responses. In this study, we further investigated its role in potato defense against P. infestans. Stable expression of miR394 in tobacco and potato enhances the susceptibility to P. infestans, which is accompanied with the reduced accumulation of ROS and down-regulation of the PTI (pattern-triggered immunity) marker genes. Besides well-known target StLCR, miR394 also targets StA/N-INVE, which encodes a chloroplast Alkaline/Neutral Invertases (A/N-INVE). Both StLCR and StA/N-INVE positively regulate late blight resistance, while miR394 degrades them. Interestingly, StA/N-INVE is located in the chloroplast, indicating that miR394 may manipulate chloroplast immunity. Degradation of StA/N-INVE may affect the chloroplast function and hence lead to the compromised ROS (reactive oxygen species) burst and reduced retrograde signaling from the chloroplast to the nucleus and cytoplasm. In summary, this study provides new information that miR394 targets and degrades StA/N-INVE and StLCR, which are positive regulators, to enhance potato susceptibility to P. infestans.
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MicroARNs , Phytophthora infestans , Solanum tuberosum , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Phytophthora infestans/genética , Phytophthora infestans/metabolismo , Plantas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
A method for generation of SVI sulfones from ß-sulfinyl esters (SIV) under transition-metal-free non-oxidative mild conditions is presented. Various sulfones have been achieved with moderate to excellent yields. The advantage of using ß-sulfinyl esters as masked aryl sulfinates has also been exemplified using brominated substrates. Oxygen isotope-labeling experiments indicated that the oxygen atoms incorporated into the sulfone product come from the sulfoxide of the ß-sulfinyl ester. Successive ß-elimination/O-addition/sulfinate esterification/ß-elimination processes are proposed for the mechanism of generating SVI from SIV.
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Driven by the global popularity of electric vehicles and the shortage of critical raw materials for batteries, the spent lithium-ion power battery (LIPB) recycling industry has exhibited explosive growth in both quantity and scale. However, relatively little information is known about the environmental risks posed by LIPB recycling, in particular with regards to perfluoroalkyl and polyfluoroalkyl substances (PFAS). In this work, suspect screening and nontarget analysis were carried out to characterize PFAS in soil, dust, water and sediment from a LIPB recycling area. Twenty-five PFAS from nine classes were identified at confidence level 3 or above, including 13 legacy and 12 emerging PFAS, as well as two ultrashort-chain PFAS. Based on the target analysis of 16 PFAS, at least nine were detected in each environmental sample, indicating their widespread presence in a LIPB recycling area. Perfluorodecanoic acid, perfluorooctanesulfonic acid and trifluoromethanesulfonamide showed significant differences in the four phenotypic parameters (growth, movement, survival and fecundity) of Caenorhabditis elegans and were the most toxic substances in all target PFAS at an exposure concentration of 200 µM. Our project provides first-hand information on the existence and environmental risk of PFAS, facilitating the formulation of regulations and green development of the LIPB recycling industry.
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Litio , Litio/toxicidad , Reciclaje , Fluorocarburos/toxicidad , Suministros de Energía Eléctrica , Monitoreo del Ambiente , AnimalesRESUMEN
Inhalation of fine particulate matter PM2.5-bound arsenic (PM2.5-As) may cause significant cardiovascular damage, due to its high concentration, long transmission range, and good absorption efficiency in organisms. However, both the contribution and the effect of the arsenic exposure pathway, with PM2.5 as the medium, on cardiovascular system damage in nonferrous smelting sites remain to be studied. In this work, a one-year site sample collection and analysis work showed that the annual concentration of PM2.5-As reached 0.74 µg/m3, which was 120 times the national standard. The predominant species in the PM2.5 samples were As (V) and As (III). A panel study among workers revealed that PM2.5-As exposure dominantly contributed to human absorption of As. After exposure of mice to PM2.5-As for 8 weeks, the accumulation of As in the high exposure group reached equilibrium, and its bioavailability was 24.5%. A series of animal experiments revealed that PM2.5-As exposure induced cardiac injury and dysfunction at the environmental relevant concentration and speciation. By integrating environmental and animal exposure assessments, more accurate health risk assessment models exposed to PM2.5-As were established for metal smelting areas. Therefore, our research provides an important scientific basis for relevant departments to formulate industry supervision, prevention and control policies.
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Arsénico , Material Particulado , Humanos , Ratones , Animales , Exposición Profesional , Enfermedades Cardiovasculares , Medición de Riesgo , Disponibilidad Biológica , Contaminantes Atmosféricos , MetalurgiaRESUMEN
Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovary morphology, affecting more and more women of reproductive age. Our study aimed to explore the molecular mechanism and effect of exosomal miR-4449 on granulosa cells (GCs). Two immortalized human ovarian granulosa cells (KGN and COV434 cells) were used for in vitro functional studies. Our study found that follicular fluid (FF) derived exosomal miR-4449 was significantly decreased in women with PCOS compared with the control patients. And exosomal miR-4449 could alleviate GCs oxidative stress (OS) and promote GCs proliferation, while the opposite trend was observed after inhibiting the expression of miR-4449. In addition, we demonstrated that Kelch-like ECH-associated protein 1(KEAP1) was a direct target of miR-4449 through dual-luciferase reporter assay, and the expression patterns of KEAP1 and miR-4449 in PCOS FF-derived exosomes were exactly opposite. In addition, KEAP1/NRF2 signaling pathway may play an important role in GCs proliferation and OS. Our results demonstrated that the decreased FF-derived exosomal miR-4449 expression in PCOS might aggravate the OS of GCs and inhibit GCs proliferation via KEAP1/NRF2 signaling pathway. Exosomal miR-4449 might be a potential biomarker for the diagnosis of PCOS. Our study contributes to a new understanding of the pathogenesis of PCOS.
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MicroARNs , Síndrome del Ovario Poliquístico , Humanos , Femenino , MicroARNs/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patología , Líquido Folicular/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Células de la Granulosa , Proliferación Celular/genética , ApoptosisRESUMEN
BACKGROUND: In the context of increasing exposure to silica nanoparticles (SiNPs) and ensuing respiratory health risks, emerging evidence has suggested that SiNPs can cause a series of pathological lung injuries, including fibrotic lesions. However, the underlying mediators in the lung fibrogenesis caused by SiNPs have not yet been elucidated. RESULTS: The in vivo investigation verified that long-term inhalation exposure to SiNPs induced fibroblast activation and collagen deposition in the rat lungs. In vitro, the uptake of exosomes derived from SiNPs-stimulated lung epithelial cells (BEAS-2B) by fibroblasts (MRC-5) enhanced its proliferation, adhesion, and activation. In particular, the mechanistic investigation revealed SiNPs stimulated an increase of epithelium-secreted exosomal miR-494-3p and thereby disrupted the TGF-ß/BMPR2/Smad pathway in fibroblasts via targeting bone morphogenetic protein receptor 2 (BMPR2), ultimately resulting in fibroblast activation and collagen deposition. Conversely, the inhibitor of exosomes, GW4869, can abolish the induction of upregulated miR-494-3p and fibroblast activation in MRC-5 cells by the SiNPs-treated supernatants of BEAS-2B. Besides, inhibiting miR-494-3p or overexpression of BMPR2 could ameliorate fibroblast activation by interfering with the TGF-ß/BMPR2/Smad pathway. CONCLUSIONS: Our data suggested pulmonary epithelium-derived exosomes serve an essential role in fibroblast activation and collagen deposition in the lungs upon SiNPs stimuli, in particular, attributing to exosomal miR-494-3p targeting BMPR2 to modulate TGF-ß/BMPR2/Smad pathway. Hence, strategies targeting exosomes could be a new avenue in developing therapeutics against lung injury elicited by SiNPs.
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Colágeno , Epigénesis Genética , Exosomas , Fibroblastos , Pulmón , MicroARNs , Nanopartículas , Transducción de Señal , Dióxido de Silicio , Factor de Crecimiento Transformador beta , Exosomas/metabolismo , Animales , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Dióxido de Silicio/química , Transducción de Señal/efectos de los fármacos , Ratas , Pulmón/metabolismo , Pulmón/patología , Colágeno/metabolismo , Humanos , Nanopartículas/química , MicroARNs/metabolismo , MicroARNs/genética , Línea Celular , Factor de Crecimiento Transformador beta/metabolismo , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/inducido químicamente , Masculino , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Ratas Sprague-Dawley , Epitelio/metabolismo , Epitelio/efectos de los fármacosRESUMEN
Lanmaoa asiatica G. Wu & Zhu L. Yang and L. macrocarpa N. K. Zeng, H. Chai & S. Jiang are two important gourmet bolete in China, and locally named "Jian Shou Qing" meaning their fruiting bodies turn blue after bruising. The genus represents a distinct lineage in Boletaceae. The pigment(s) associated with the discoloration in Lanmaoa has not been identified. The aim of this study was to determine the pigment(s) underpinning the bluing reaction of L. asiatica and L. macrocarpa when bruised. Potential compounds were isolated by HPLC and identified by LC-HRMS and NMR. In total five to six pigments of hydroxylated pulvinic acid derivatives were detected with similar distribution patterns in both L. asiatica and L. macrocarpa, which by abundance were variegatic acid, variegatorubin, xerocomic acid (and/or isoxerocomic acid), xerocomorubin, and atromentic acid. Variegatic acid, the most abundant pigment, was isolated by HPLC, and the structure was further characterized by NMR. The amount of variegatic acid increased after regular cooking, which may suggest its enhanced health benefit as human diet. The types of pigments that cause bluing reactions often differ among families of Boletales. Our results showed that the pigments in Lanmaoa belong to the category of hydroxylated pulvinic acid derivatives, the major bluing compounds in Boletaceae.
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Pigmentos Biológicos , Pigmentos Biológicos/química , Pigmentos Biológicos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Estructura Molecular , Agaricales/químicaRESUMEN
The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice. However, the detailed mechanisms remain elusive. CRC in situ nude mouse models were treated with CLG. Small animal magnetic resonance imaging (MRI) tracked tumor progression, and overall health metrics such as food and water intake, body weight, and survival were monitored. Posttreatment, tissues and blood were analyzed for indicators of tumor inhibition and systemic effects. Changes in vital organs were observed via stereoscope and hematoxylin-eosin staining. Immunohistochemistry quantified HIF-1α and P70S6K1 protein expression in xenografts. Double labeling was used to statistically analyze vascular endothelial growth factor (VEGF) and CD31 neovascularization. Enzyme-linked immunosorbent assay was used to determine the levels of VEGF, MMP-2, MMP-9, IL-6, and IL-10 in serum, tumors, and liver. Western blotting was used to assess the expression of the PI3K/Akt/mTOR signaling pathway-related factors TGF-ß1 and smad4 in liver tissues. CLG inhibited tumor growth, improved overall health metrics, and ameliorated abnormal blood cell counts in CRC nude mice. CLG significantly reduced tumor neovascularization and VEGF expression in tumors and blood. It also suppressed HIF-1α, EGFR, p-PI3K, Akt, p-Akt, and p-mTOR expression in tumors while enhancing PTEN oncogene expression. Systemic improvements were noted, with CLG limiting liver metastasis, reducing pro-inflammatory cytokines IL-6 and IL-10 in liver tissues, decreasing MMP-2 in blood and MMP-2 and MMP-9 in tumors, and inhibiting TGF-ß1 expression in liver tissues. CLG can enhance survival quality and inhibit tumor growth in CRC nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Ratones , Animales , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Crecimiento Transformador beta1 , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ratones Desnudos , Interleucina-10 , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Interleucina-6 , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Colorrectales/metabolismo , Línea Celular TumoralRESUMEN
Recent discoveries of noncanonical RNA caps, such as nicotinamide adenine dinucleotide (NAD+) and 3'-dephospho-coenzyme A (dpCoA), have expanded our knowledge of RNA caps. Although dpCoA has been known to cap RNAs in various species, the identities of its capped RNAs (dpCoA-RNAs) remained unknown. To fill this gap, we developed a method called dpCoA tagSeq, which utilized a thiol-reactive maleimide group to label dpCoA cap with a tag RNA serving as the 5' barcode. The barcoded RNAs were isolated using a complementary DNA strand of the tag RNA prior to direct sequencing by nanopore technology. Our validation experiments with model RNAs showed that dpCoA-RNA was efficiently tagged and captured using this protocol. To confirm that the tagged RNAs are capped by dpCoA and no other thiol-containing molecules, we used a pyrophosphatase NudC to degrade the dpCoA cap to adenosine monophosphate (AMP) moiety before performing the tagSeq protocol. We identified 44 genes that transcribe dpCoA-RNAs in mouse liver, demonstrating the method's effectiveness in identifying and characterizing the capped RNAs. This strategy provides a viable approach to identifying dpCoA-RNAs that allows for further functional investigations of the cap.
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Secuenciación de Nanoporos , Nanoporos , Animales , Ratones , Caperuzas de ARN/genética , Caperuzas de ARN/metabolismo , Coenzima A , MaleimidasRESUMEN
Ectomycorrhizal fungi (ECM) sustain nutrient recycling in most terrestrial ecosystems, yet we know little about what major biogeographical events gave rise to present-day diversity and distribution patterns. Given the strict relationship between some ECM lineages and their hosts, geographically well-sampled phylogenies are central to understanding major evolutionary processes of fungal biodiversity patterns. Here, we focus on Amanita sect. Vaginatae to address global diversity and distribution patterns. Ancestral-state-reconstruction based on a 4-gene timetree with over 200 species supports an African origin between the late Paleocene and the early Eocene (ca. 56 Ma). Major biogeographic "out-of-Africa" events include multiple dispersal events to Southeast Asia (ca. 45-21 Ma), Madagascar (ca. 18 Ma), and the current Amazonian basin (ca. 45-36 Ma), the last two likely trans-oceanic. Later events originating in Southeast Asia involve Nearctic dispersal to North America (ca. 20-5 Ma), Oceania (Australia and New Zealand; ca. 15 Ma), and Europe (ca. 10-5 Ma). Subsequent dispersals were also inferred from Southeast Asia to East Asia (ca. 4 Ma); from North America to East Asia (ca. 11-8 Ma), Southeast Asia (ca. 19-2 Ma), Northern Andes (ca. 15 Ma), and Europe (ca. 15-2 Ma), respectively; and from the Amazon to the Caribbean region (ca. 25-20 Ma). Finally, we detected a significant increase in the net diversification rates in the branch leading to most northern temperate species in addition to higher state-dependent diversification rates in temperate lineages, consistent with previous findings. These results suggest that species of sect. Vaginatae likely have higher dispersal ability and higher adaptability to new environments, in particular compared to those of its sister clade, sect. Caesareae. Overall, the much wider distribution of A. sect. Vaginatae, from pan-tropical to pan-arctic, provides a unique window to understanding niche conservatism across a species-rich clade of ECM fungi.
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Amanita , Ecosistema , Filogenia , Evolución Biológica , Américas , FilogeografíaRESUMEN
Hybrid organic-inorganic ferroelectrics (HOIFs) have a wide range of applications in the optoelectronic field in terms of rich optoelectronic properties. Particularly, lead-free HOIFs have attracted extensive attention due to their environmental friendliness, low heavy metal toxicity, and low synthesis cost. However, there are few reports about Zn-based HOIFs due to their uncontrollable ferroelectric synthesis and other reasons. Here, we designed and synthesized a zinc-based zero-dimensional (3,3-difluoropyrrolidine)2ZnCl4·H2O (DFZC) single crystal, which undergoes a phase transition from ferroelectric to paraelectric phase (space group from Pna21 to Pnma) at 295.5 K/288.9 K during the heating/cooling process. The systematic study shows that the ferroelectric phase transition is a displacive type. The ferroelectric hysteresis loop of DFZC was obtained by the double-wave method and the Sawyer-Tower method, which has a spontaneous polarization (Ps) of â¼0.4 µC/cm2. This work reveals the strategy to design new zinc-based lead-free HOIFs for potential applications in optoelectronic fields.
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para-Phenylenediamine quinones (PPD-Qs) are a newly discovered class of transformation products derived from para-phenylenediamine (PPD) antioxidants. These compounds are prevalent in runoff, roadside soil, and particulate matter. One compound among these, N-1,3-dimethylbutyl-n'-phenyl-p-phenylenediamine quinone (6PPD-Q), was found to induce acute mortality of coho salmon, rainbow trout, and brook trout, with the median lethal concentrations even lower than its appearance in the surface and receiving water system. However, there was limited knowledge about the occurrence and fate of these emerging environmental contaminants in wastewater treatment plants (WWTPs), which is crucial for effective pollutant removal via municipal wastewater networks. In the current study, we performed a comprehensive investigation of a suite of PPD-Qs along with their parent compounds across the influent, effluent, and biosolids during each processing unit in four typical WWTPs in Hong Kong. The total concentrations of PPDs and PPD-Qs in the influent were determined to be 2.7-90 and 14-830 ng/L. In the effluent, their concentrations decreased to 0.59-40 and 2.8-140 ng/L, respectively. The median removal efficiency for PPD-Qs varied between 53.0 and 91.0% across the WWTPs, indicating that a considerable proportion of these contaminants may not be fully eliminated through the current processing technology. Mass flow analyses revealed that relatively higher levels of PPD-Qs were retained in the sewage sludge (20.0%) rather than in the wastewater (16.9%). In comparison to PPDs, PPD-Qs with higher half-lives exhibited higher release levels via effluent wastewater, which raises particular concerns about their environmental consequences to aquatic ecosystems.
Asunto(s)
Benzoquinonas , Fenilendiaminas , Quinonas , Aguas Residuales , Contaminantes Químicos del Agua , Purificación del Agua , Agua , Ecosistema , Monitoreo del Ambiente , Hong Kong , Quinonas/análisis , Quinonas/toxicidad , Aguas del Alcantarillado/análisis , Eliminación de Residuos Líquidos , Aguas Residuales/análisis , Aguas Residuales/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Fenilendiaminas/análisis , Fenilendiaminas/toxicidad , Benzoquinonas/análisis , Benzoquinonas/toxicidad , Agua/análisis , Agua/químicaRESUMEN
Sonodynamic therapy (SDT) can noninvasively focus sound energy to deep tumor tissues and activate sonosensitizer (such as chlorin e6(Ce6)) to produce antitumor effects. However, due to the hypoxic microenvironment of the tumor, the effect of sonodynamic therapy is limited. In this work, we successfully synthesized Platinum-Boron-Phosphorus ternary nanoparticles (Pt-B-P NPs) for the first time to efficiently catalyze the decomposition of hydrogen peroxide (H2O2) in tumor tissues to produce sufficient oxygen (O2) and improve the effect of sonodynamic treatment of ovarian cancer. In vitro studies, we found that compared with Platinum nanoparticles (Pt NPs), Pt-B-P NPs have the significantly increased ability to catalyze the decomposition of H2O2 to produce oxygen and thus the hypoxic environment of tumor cells could be improved efficiently. Meanwhile, the bio-distribution, therapeutic effect and bio-safety of Pt-B-P NPs in vivo were evaluated using BALB/c-nu mouse model of ovarian cancer and the desired result had been achieved.