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Idiopathic pulmonary fibrosis (IPF) is a fibrotic age-related chronic lung disease characterized by the accumulation of senescent cells. Whether impaired immune response is responsible for the accumulation of senescent cells in the IPF lung remains unknown. In this study, we characterized the NK phenotype in IPF lungs via flow cytometry using 5-dodecanoylaminofluorescein di-ß-d-galactopyranoside, markers of tissue residence, and chemokine receptors. The effect of the lung microenvironment was evaluated using lung fibroblast (LF) conditioned media (CM), and the bleomycin-induced pulmonary fibrosis mouse model was used to assess the in vivo relationship between NK cells and the accumulation of senescent cells. We found that NK cells from the lower lobe of IPF patients exhibited immune-senescent and impaired CD57-NKG2A+ phenotype. We also observed that culture of NK cells from healthy donors in CM from IPF lower lobe lung fibroblasts induced a senescent-like phenotype and impaired cytotoxic capacity. There is an impaired NK recruitment by LF, and NKs presented decreased migration toward their CM. In addition, NK cell-depleted mice treated with bleomycin showed increased collagen deposition and accumulation of different populations of senescent cells compared with controls. The IPF lung microenvironment induces a dysfunctional NK phenotype limiting the clearance of lung senescent cells and the resolution of lung fibrosis. We propose that impaired NK activity could be one of the mechanisms responsible for perpetuating the accumulation of senescent cells in IPF lungs.
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Antineoplásicos , Fibrosis Pulmonar Idiopática , Ratones , Animales , Pulmón/patología , Fibrosis Pulmonar Idiopática/inducido químicamente , Bleomicina/efectos adversos , Fibrosis , Antineoplásicos/farmacología , FibroblastosRESUMEN
BACKGROUND: Leaves are important sites for photosynthesis and can convert inorganic substances into organic matter. Photosynthetic performance is an important factor affecting crop yield. Leaf colour is closely related to photosynthesis, and leaf colour mutants are considered an ideal material for studying photosynthesis. RESULTS: We obtained a yellow-green leaf mutant jym165, using ethyl methane sulfonate (EMS) mutagenesis. Physiological and biochemical analyses indicated that the contents of chlorophyll a, chlorophyll b, carotenoids, and total chlorophyll in the jym165 mutant decreased significantly compared with those in Jiyu47 (JY47). The abnormal chloroplast development of jym165 led to a decrease in net photosynthetic rate and starch content compared with that of JY47. However, quality traits analysis showed that the sum of oil and protein contents in jym165 was higher than that in JY47. In addition, the regional yield (seed spacing: 5 cm) of jym165 increased by 2.42% compared with that of JY47 under high planting density. Comparative transcriptome analysis showed that the yellow-green leaf phenotype was closely related to photosynthesis and starch and sugar metabolism pathways. Genetic analysis suggests that the yellow-green leaf phenotype is controlled by a single recessive nuclear gene. Using Mutmap sequencing, the candidate regions related of leaf colour was narrowed to 3.44 Mb on Chr 10. CONCLUSIONS: Abnormal chloroplast development in yellow-green mutants leads to a decrease in the photosynthetic pigment content and net photosynthetic rate, which affects the soybean photosynthesis pathway and starch and sugar metabolism pathways. Moreover, it has the potentiality to increase soybean yield under dense planting conditions. This study provides a useful reference for studying the molecular mechanisms underlying photosynthesis in soybean.
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Mapeo Cromosómico , Glycine max , Mutación , Fotosíntesis , Hojas de la Planta , Fotosíntesis/genética , Glycine max/genética , Glycine max/crecimiento & desarrollo , Glycine max/fisiología , Glycine max/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Hojas de la Planta/fisiología , Clorofila/metabolismo , Fenotipo , Almidón/metabolismo , Cloroplastos/metabolismoRESUMEN
In brief: The metabolic processes of the gestation period in pandas remain poorly understood. Our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas. Abstract: There has been remarkable progress in the conservation and reproduction of giant pandas. However, the physiology of the gestation period in pandas remains poorly understood. The metabolic processes from estrus to pregnancy are dynamic and precisely regulated, playing a crucial role in pregnancy and related dysfunctions. In this study, we conducted a metabolomic analysis of 37 blood samples collected from pandas in estrus, acyclic, and potential pregnant states, employing rigorous screening to minimize the influence of diet. Our findings suggest that a reduced appetite can serve as an indicator for evaluating implantation time, representing a characteristic response to pregnancy and aiding in the prediction of delivery time in pregnant pandas. Metabolomic results indicate great metabolism variation from estrus to pregnancy, highlighting the association between amino acid metabolism and pregnancy outcomes. Compared to other pandas, individuals who successfully bred exhibit significantly elevated levels of arginine and histidine, even 2 months before experiencing a reduced appetite. Furthermore, the lipid profile undergoes distinct dynamic changes only in estrus samples. In summary, our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.
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Aminoácidos , Biomarcadores , Metabolómica , Resultado del Embarazo , Ursidae , Femenino , Embarazo , Animales , Ursidae/sangre , Ursidae/fisiología , Aminoácidos/sangre , Aminoácidos/metabolismo , Biomarcadores/sangre , Preñez/sangre , Preñez/metabolismo , Arginina/sangre , Arginina/metabolismo , Metaboloma , Histidina/sangre , Histidina/metabolismoRESUMEN
Developing a bifunctional oxygen electrocatalyst is crucial to improve the reversibility and cycle life of a rechargeable zinc-air battery (RZAB). Here, transition metal phosphides (TMPs) with a leaf-like hierarchical structure and multiphase composition can be synthesized by the "alloying-dealloying-phosphating" strategy. The as-prepared P-NiCo(1:1) electrode takes advantage of its internal dense nanoholes and synergistic effects induced by NiCoP-containing polyphase to reveal multifunctional catalysis, such as OER and ORR. In combination of these advantages, P-NiCo(1:1) exhibits an extremely low OER overpotential of 220 mV at 10 mA cm-2, a higher half-wave potential of 0.79 V for ORR, and a smaller potential difference (ΔE) of 0.66 V. The liquid RZAB with P-NiCo(1:1) as a cathodic bifunctional catalyst delivers a higher open-circuit voltage (OCV), a larger power density of 175 mW cm-2, and longer cycling life for more than 180 h. Even when applied in solid-state flexible RZABs, the lightweight module could start high-power devices. With theoretical confirmation, the major phase NiCoP of P-NiCo(1:1) is helpful to increase the density of states, regulate the d-band center, and decrease the energy barrier to 2.13 eV, which are significantly superior to those of Co2P and Ni2P. It is believable that the synthetic strategy and activity-promoting mechanism acquired from this research can offer a guide to designing a promising rechargeable zinc-air battery system.
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BACKGROUND: Exercise is crucial for pulmonary rehabilitation and improving the prognosis of lung transplantation (LTx) patients. However, many LTx patients in China have low exercise tolerance and compliance, and the reasons behind these challenges have not been fully elucidated. Therefore, this qualitative research aims to identify the barriers to and facilitators of exercise rehabilitation in LTx patients. METHODS: From January to July 2023, 15 stable LTx patients were recruited and participated in in-depth, semi-structured, face-to-face interviews at Henan Provincial People's Hospital. The interview transcripts were analyzed using the COM-B model and the Theoretical Domains Framework (TDF). RESULTS: Six general themes including 19 barriers and 14 facilitators for the exercise rehabilitation of LTx patients were identified based on the COM-B model and TDF. The barriers to exercise included physical limitations, insufficient exercise endurance, lack of knowledge, and lack of motivation. The facilitators of exercise included motivation, self-efficacy, perceived significance of exercise rehabilitation, and social support. CONCLUSION: The study offers detailed insight into the development and implementation of exercise rehabilitation intervention strategies for LTx patients. By combining COM-B model and TDF, the study provides strong evidence that active behavior change strategies are required for LTx patients to promote their participation in exercise rehabilitation. Professional support, pulmonary rehabilitation training, behavior change technology, and digital health tools are essential for strengthening the evidence system for reporting exercise efficacy and effectiveness.
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Ejercicio Físico , Trasplante de Pulmón , Adulto , Humanos , Investigación Cualitativa , Terapia por Ejercicio , Apoyo Social , MotivaciónRESUMEN
Andrographolide (Andro), a labdane diterpene, possesses anti-inflammatory properties and has been used to treat numerous inflammatory diseases. Novel findings revealed that Andro might be vital in regulating pain. However, the contribution of Andro to chronic inflammatory pain has yet to be determined, and its underlying mechanism of action remains unknown. In this study, we observed that Andro attenuated mechanical allodynia in inflammatory pain mice induced by injecting complete Freund's adjuvant (CFA) into the right hind paws. This analgesic effect of Andro is mainly dependent on its inhibition of microglial overactivation and the release of proinflammatory cytokines (TNF and IL-1ß) in lumbar spinal cords of inflammatory pain model mice. More importantly, our data in vivo and in vitro revealed a negative role for Andro in regulating the TLR4/NF-κB signaling pathway, which might contribute to the inhibition of spinal microglial activation and proinflammatory cytokines production, and the improvement of paw withdrawal thresholds in a mouse model of chronic inflammatory pain evoked by CFA. We further found the potential interaction of Andro with TLR4/myeloid differentiation factor 2 heterodimer using molecular modeling, implying that TLR4 might be a potential target for Andro to exert an analgesic effect. Taken together, our findings demonstrated that the modulation of spinal microglial activation by Andro might be substantially conducive to managing chronic pain triggered by neuroinflammation.
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Diterpenos , Hiperalgesia , Ratones , Animales , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Microglía/metabolismo , Inflamación/metabolismo , Receptor Toll-Like 4/metabolismo , Dolor/tratamiento farmacológico , Dolor/metabolismo , Diterpenos/farmacología , Diterpenos/uso terapéutico , Diterpenos/metabolismo , Citocinas/metabolismo , Médula Espinal , Analgésicos/farmacología , Analgésicos/uso terapéuticoRESUMEN
Epidemiological evidence on the health effects of pesticide exposure among greenhouse workers is limited, and the mechanisms are lacking. Building upon our team's previous population study, we selected two pesticides, CPF and EB, with high detection rates, based on the theoretical foundation that the liver serves as a detoxifying organ, we constructed a toxicity model using HepG2 cells to investigate the impact of individual or combined pesticide exposure on the hepatic metabolism profile, attempting to identify targeted biomarkers. Our results showed that CPF and EB could significantly affect the survival rate of HepG2 cells and disrupt their metabolic profile. There were 117 metabolites interfered by CPF exposure, which mainly affected ABC transporter, biosynthesis of amino acids, center carbon metabolism in cancer, fatty acid biosynthesis and other pathways, 95 metabolites interfered by EB exposure, which mainly affected center carbon metabolism in cancer, HIF-1 signaling pathway, valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis and other pathways. The cross analysis and further biological experiments confirmed that CPF and EB pesticide exposure may affect the HIF-1 signaling pathway and valine, leucine and isoleucine biosynthesis in HepG2 cells, providing reliable experimental evidence for the prevention and treatment of liver damage in greenhouse workers.
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Cloropirifos , Insecticidas , Ivermectina/análogos & derivados , Plaguicidas , Humanos , Cloropirifos/toxicidad , Cloropirifos/metabolismo , Plaguicidas/toxicidad , Células Hep G2 , Leucina , Isoleucina , Carbono , Valina , Ácidos Grasos , Insecticidas/toxicidad , Insecticidas/metabolismoRESUMEN
Soil salinization is a widespread hindrance that endangers agricultural production and ecological security. High salt concentrations in saline soils are primarily caused by osmotic stress, ionic toxicity and oxidative stress, which have a negative impact on plant growth and development. In order to withstand salt stress, plants have developed a series of complicated physiological and molecular mechanisms, encompassing adaptive changes in the structure and function of various plant organs, as well as the intricate signal transduction networks enabling plants to survive in high-salinity environments. This review summarizes the recent advances in salt perception under different tissues, physiological responses and signaling regulations of plant tolerance to salt stress. We also examine the current knowledge of strategies for breeding salt-tolerant plants, including the applications of omics technologies and transgenic approaches, aiming to provide the basis for the cultivation of salt-tolerant crops through molecular breeding. Finally, future research on the application of wild germplasm resources and muti-omics technologies to discover new tolerant genes as well as investigation of crosstalk among plant hormone signaling pathways to uncover plant salt tolerance mechanisms are also discussed in this review.
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Fitomejoramiento , Tolerancia a la Sal , Tolerancia a la Sal/genética , Fitomejoramiento/métodos , Plantas Tolerantes a la Sal/genética , Regulación de la Expresión Génica de las Plantas , Productos Agrícolas/genética , Productos Agrícolas/crecimiento & desarrollo , Transducción de Señal , Salinidad , Plantas Modificadas Genéticamente/genéticaRESUMEN
Spinach (Spinacia oleracea L.) is a dioecious, diploid, wind-pollinated crop cultivated worldwide. Sex determination plays an important role in spinach breeding. Hence, this study aimed to understand the differences in sexual differentiation and floral organ development of dioecious flowers, as well as the differences in the regulatory mechanisms of floral organ development of dioecious and monoecious flowers. We compared transcriptional-level differences between different genders and identified differentially expressed genes (DEGs) related to spinach floral development, as well as sex-biased genes to investigate the flower development mechanisms in spinach. In this study, 9189 DEGs were identified among the different genders. DEG analysis showed the participation of four main transcription factor families, MIKC_MADS, MYB, NAC, and bHLH, in spinach flower development. In our key findings, abscisic acid (ABA) and gibberellic acid (GA) signal transduction pathways play major roles in male flower development, while auxin regulates both male and female flower development. By constructing a gene regulatory network (GRN) for floral organ development, core transcription factors (TFs) controlling organ initiation and growth were discovered. This analysis of the development of female, male, and monoecious flowers in spinach provides new insights into the molecular mechanisms of floral organ development and sexual differentiation in dioecious and monoecious plants in spinach.
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Flores , Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , Spinacia oleracea , Factores de Transcripción , Spinacia oleracea/genética , Spinacia oleracea/crecimiento & desarrollo , Flores/genética , Flores/crecimiento & desarrollo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica , Ácido Abscísico/metabolismo , Giberelinas/metabolismoRESUMEN
Rubisco small subunit (RbcS), a core component with crucial effects on the structure and kinetic properties of the Rubisco enzyme, plays an important role in response to plant growth, development, and various stresses. Although Rbcs genes have been characterized in many plants, their muti-functions in soybeans remain elusive. In this study, a total of 11 GmRbcS genes were identified and subsequently divided into three subgroups based on a phylogenetic relationship. The evolutionary analysis revealed that whole-genome duplication has a profound effect on GmRbcSs. The cis-acting elements responsive to plant hormones, development, and stress-related were widely found in the promoter region. Expression patterns based on the RT-qPCR assay exhibited that GmRbcS genes are expressed in multiple tissues, and notably Glyma.19G046600 (GmRbcS8) exhibited the highest expression level compared to other members, especially in leaves. Moreover, differential expressions of GmRbcS genes were found to be significantly regulated by exogenous plant hormones, demonstrating their potential functions in diverse biology processes. Finally, the function of GmRbcS8 in enhancing soybean resistance to soybean mosaic virus (SMV) was further determined through the virus-induced gene silencing (VIGS) assay. All these findings establish a strong basis for further elucidating the biological functions of RbcS genes in soybeans.
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Regulación de la Expresión Génica de las Plantas , Glycine max , Filogenia , Reguladores del Crecimiento de las Plantas , Potyvirus , Glycine max/genética , Glycine max/virología , Glycine max/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo , Potyvirus/patogenicidad , Ribulosa-Bifosfato Carboxilasa/genética , Ribulosa-Bifosfato Carboxilasa/metabolismo , Perfilación de la Expresión Génica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/genética , Genoma de Planta , Estudio de Asociación del Genoma Completo , Resistencia a la Enfermedad/genética , Familia de MultigenesRESUMEN
Given environmental persistence, potential for bioaccumulation, and toxicity of Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the scientific community has increasingly focused on researching their toxicology and degradation methods. This paper presents a survey of recent research advances in the toxicological effects and degradation methods of PFOA and PFOS. Their adverse effects on the liver, nervous system, male reproductive system, genetics, and development are detailed. Additionally, the degradation techniques of PFOA and PFOS, including photochemical, photocatalytic, and electrochemical methods, are analyzed and compared, highlighted the potential of these technologies for environmental remediation. The biotransformation pathways and mechanisms of PFOA and PFOS involving microorganisms, plants, and enzymes are also presented. As the primary green degradation pathway for PFOA and PFOS, Biodegradation uses specific microorganisms, plants or enzymes to remove PFOA and PFOS from the environment through redox reactions, enzyme catalysis and other pathways. Currently, there has been a paucity of research conducted on the biodegradation of PFOA and PFOS. However, this degradation technology is promising owing to its specificity, cost-effectiveness, and ease of implementation. Furthermore, novel materials/methods for PFOA and PFOS degradation are presented in this paper. These novel materials/methods effectively improve the degradation efficiency of PFOA and PFOS and provide new ideas and tools for the degradation of PFOA and PFOS. This information can assist researchers in identifying flaws and gaps in the field, which can facilitate the formulation of innovative research ideas.
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Ácidos Alcanesulfónicos , Biodegradación Ambiental , Caprilatos , Fluorocarburos , Fluorocarburos/metabolismo , Caprilatos/metabolismo , Ácidos Alcanesulfónicos/metabolismo , Ácidos Alcanesulfónicos/toxicidad , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/toxicidad , Animales , Tecnología Química Verde/métodosRESUMEN
Mining activities have resulted in a substantial accumulation of cadmium (Cd) in agricultural soils, particularly in southern China. Long-term Cd exposure can cause plant growth inhibition and various diseases. Rapid identification of the extent of soil Cd pollution and its driving factors are essential for soil management and risk assessment. However, traditional geostatistical methods are difficult to simulate the complex nonlinear relationships between soil Cd and potential features. In this study, sequential extraction and hotspot analyses indicated that Cd accumulation increased significantly near mining sites and exhibited high mobility. The concentration of Cd was estimated using three machine learning models based on 3169 topsoil samples, seven quantitative variables (soil pH, Fe, Ca, Mn, TOC, Al/Si and ba value) and three quantitative variables (soil parent rock, terrain and soil type). The random forest model achieved marginally better performance than the other models, with an R2 of 0.78. Importance analysis revealed that soil pH and Ca and Mn contents were the most significant factors affecting Cd accumulation and migration. Conversely, due to the essence of controlling Cd migration being soil property, soil type, terrain, and soil parent materials had little impact on the spatial distribution of soil Cd under the influence of mining activities. Our results provide a better understanding of the geochemical behavior of soil Cd in mining areas, which could be helpful for environmental management departments in controlling the diffusion of Cd pollution and capturing key targets for soil remediation.
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Cadmio , Aprendizaje Automático , Minería , Contaminantes del Suelo , Suelo , Cadmio/análisis , Contaminantes del Suelo/análisis , China , Suelo/química , Monitoreo del Ambiente/métodos , Concentración de Iones de HidrógenoRESUMEN
Atmospheric particulate matter (PM) exacerbates the risk factor for Alzheimer's and Parkinson's diseases (PD) by promoting the alpha-synuclein (α-syn) pathology in the brain. However, the molecular mechanisms of astrocytes involvement in α-syn pathology underlying the process remain unclear. This study investigated PM with particle size <200 nm (PM0.2) exposure-induced α-syn pathology in ICR mice and primary astrocytes, then assessed the effects of mammalian target of rapamycin inhibitor (PP242) in vitro studies. We observed the α-syn pathology in the brains of exposed mice. Meanwhile, PM0.2-exposed mice also exhibited the activation of glial cell and the inhibition of autophagy. In vitro study, PM0.2 (3, 10 and 30 µg/mL) induced inflammatory response and the disorders of α-syn degradation in primary astrocytes, and lysosomal-associated membrane protein 2 (LAMP2)-mediated autophagy underlies α-syn pathology. The abnormal function of autophagy-lysosome was specifically manifested as the expression of microtubule-associated protein light chain 3 (LC3II), cathepsin B (CTSB) and lysosomal abundance increased first and then decreased, which might both be a compensatory mechanism to toxic α-syn accumulation induced by PM0.2. Moreover, with the transcription factor EB (TFEB) subcellular localization and the increase in LC3II, LAMP2, CTSB, and cathepsin D proteins were identified, leading to the restoration of the degradation of α-syn after the intervention of PP242. Our results identified that PM0.2 exposure could promote the α-syn pathological dysregulation in astrocytes, providing mechanistic insights into how PM0.2 increases the risk of developing PD and highlighting TFEB/LAMP2 as a promising therapeutic target for antagonizing PM0.2 toxicity.
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Astrocitos , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Proteína 2 de la Membrana Asociada a los Lisosomas , Lisosomas , Ratones Endogámicos ICR , Material Particulado , alfa-Sinucleína , Animales , Astrocitos/efectos de los fármacos , alfa-Sinucleína/metabolismo , Autofagia/efectos de los fármacos , Ratones , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Material Particulado/toxicidad , Contaminantes Atmosféricos/toxicidadRESUMEN
Nelumbo lutea (American lotus), which differs from Nelumbo nucifera (Asian lotus) morphologically, is one of the two remaining species in the basal eudicot family Nelumbonaceae. Here, we assembled the 843-Mb genome of American lotus into eight pseudochromosomes containing 31 382 protein-coding genes. Comparative analyses revealed conserved synteny without large chromosomal rearrangements between the genomes of American and Asian lotus and identified 29 533 structural variants (SVs). Carotenoid and anthocyanin pigments determine the yellow and red petal colors of American and Asian lotus, respectively. The structural genes encoding enzymes of the carotenoid and anthocyanin biosynthesis pathways were conserved between two species but differed in expression. We detected SVs caused by repetitive sequence expansion or contraction among the anthocyanin biosynthesis regulatory MYB genes. Further transient overexpression of candidate NnMYB5 induced anthocyanin accumulation in lotus petals. Alternative oxidase (AOX), uncoupling proteins (UCPs), and sugar metabolism and transportation contributed to carpel thermogenesis. Carpels produce heat with sugars transported from leaves as the main substrates, because there was weak tonoplast sugar transporter (TST) activity, and with SWEETs were highly expressed during thermogenesis. Cell proliferation-related activities were particularly enhanced in the warmer carpels compared with stamens during the cold night before blooming, which suggested that thermogenesis plays an important role in flower protogyny. Population genomic analyses revealed deep divergence between American and Asian lotus, and independent domestication affecting seed, rhizome, and flower traits. Our findings provide a high-quality reference genome of American lotus for exploring the genetic divergence and variation between two species and revealed possible genomic bases for petal color, carpel thermogenesis and domestication in lotus.
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Genoma de Planta , Nelumbo , Antocianinas/análisis , Carotenoides/análisis , Domesticación , Flores/química , Flores/genética , Nelumbo/genética , Nelumbo/metabolismo , Azúcares/metabolismo , TermogénesisRESUMEN
HIV-related neuropathic pain (HRNP) is a neurodegeneration that gradually develops during the long-term course of acquired immune deficiency syndrome (AIDS) and manifests as abnormal sock/sleeve-like symmetrical pain and nociceptive hyperalgesia in the extremities, which seriously reduces patient quality of life. To date, the pathogenesis of HRNP is not completely clear. There is a lack of effective clinical treatment for HRNP and it is becoming a challenge and hot spot for medical research. In this study, we conducted a systematic review of the progress of HRNP research in recent years including (1) the etiology, classification and clinical symptoms of HRNP, (2) the establishment of HRNP pathological models, (3) the pathological mechanisms underlying HRNP from three aspects: molecules, signaling pathways and cells, (4) the therapeutic strategies for HRNP, and (5) the limitations of recent HRNP research and the future research directions and prospects of HRNP. This detailed review provides new and systematic insight into the pathological mechanism of HRNP, which establishes a theoretical basis for the future exploitation of novel target drugs. HIV infection, antiretroviral therapy and opioid abuse contribute to the etiology of HRNP with symmetrical pain in both hands and feet, allodynia and hyperalgesia. The pathogenesis involves changes in cytokine expression, activation of signaling pathways and neuronal cell states. The therapy for HRNP should be patient-centered, integrating pharmacologic and nonpharmacologic treatments into multimodal intervention.
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Infecciones por VIH , Neuralgia , Humanos , Animales , Hiperalgesia/metabolismo , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , VIH , Experimentación Humana Terapéutica , Calidad de Vida , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Modelos Animales de EnfermedadRESUMEN
A new method to access flavones in a convergent fashion has been developed, based on the Stork-Danheiser reaction. By this method, 4-methoxy coumarins are allowed to react with organolithium at low temperatures (-78 °C to -40 °C) and then acidic workup gives the desired flavones in 18-86% yields. This method features transition metal-free conditions, readily available starting materials, and simple operation. It is particularly efficient when rapid generation of B ring flavone derivatives is desired.
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Neonicotinoids (NEOs) are fourth generation pesticides, which emerged after organophosphates, pyrethroids, and carbamates and they are widely used in vegetables, fruits, cotton, rice, and other industrial crops to control insect pests. NEOs are considered ideal substitutes for highly toxic pesticides. Multiple studies have reported NEOs have harmful impacts on non-target biological targets, such as bees, aquatic animals, birds, and mammals. Thus, the remediation of neonicotinoid-sullied environments has gradually become a concern. Microbial degradation is a key natural method for eliminating neonicotinoid insecticides, as biodegradation is an effective, practical, and environmentally friendly strategy for the removal of pesticide residues. To date, several neonicotinoid-degrading strains have been isolated from the environment, including Stenotrophomonas maltophilia, Bacillus thuringiensis, Ensifer meliloti, Pseudomonas stutzeri, Variovorax boronicumulans, and Fusarium sp., and their degradation properties have been investigated. Furthermore, the metabolism and degradation pathways of neonicotinoids have been broadly detailed. Imidacloprid can form 6-chloronicotinic acid via the oxidative cleavage of guanidine residues, and it is then finally converted to non-toxic carbon dioxide. Acetamiprid can also be demethylated to remove cyanoimine (=N-CN) to form a less toxic intermediate metabolite. A few studies have discussed the neonicotinoid toxicity and microbial degradation in contaminated environments. This review is focused on providing an in-depth understanding of neonicotinoid toxicity, microbial degradation, catabolic pathways, and information related to the remediation process of NEOs. Future research directions are also proposed to provide a scientific basis for the risk assessment and removal of these pesticides.
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Insecticidas , Plaguicidas , Abejas , Animales , Insecticidas/toxicidad , Insecticidas/análisis , Neonicotinoides/toxicidad , Neonicotinoides/análisis , Insectos/metabolismo , Nitrocompuestos/toxicidad , Nitrocompuestos/metabolismo , Productos Agrícolas/metabolismo , Biodegradación Ambiental , Mamíferos/metabolismoRESUMEN
Beta-cypermethrin is one of the widely used pyrethroid insecticides, and problems associated with the accumulation of its residues have aroused public attention. Thus, there is an urgent need to effectively remove the beta-cypermethrin that is present in the environment. Biodegradation is considered a cost-effective and environmentally friendly method for removing pesticide residues. However, the beta-cypermethrin-degrading microbes that are currently available are not optimal. In this study, Pseudomonas aeruginosa PAO1 was capable of efficiently degrading beta-cypermethrin and its major metabolite 3-phenoxybenzaldehyde in water/soil environments. Strain PAO1 could remove 91.4% of beta-cypermethrin (50 mg/L) in mineral salt medium within 120 h. At the same time, it also possesses a significant ability to metabolize 3-phenoxybenzaldehyde-a toxic intermediate of beta-cypermethrin. The Andrews equation showed that the maximum substrate utilization concentrations of beta-cypermethrin and 3-phenoxybenzaldehyde by PAO1 were 65.3558 and 49.6808 mg/L, respectively. Box-Behnken design-based response surface methodology revealed optimum conditions for the PAO1 strain-based degradation of beta-cypermethrin as temperature 30.6 °C, pH 7.7, and 0.2 g/L inoculum size. The results of soil remediation experiments showed that indigenous micro-organisms helped to promote the biodegradation of beta-cypermethrin in soil, and beta-cypermethrin half-life in non-sterilized soil was 6.84 days. The bacterium transformed beta-cypermethrin to produce five possible metabolites, including 3-phenoxybenzyl alcohol, methyl 2-(4-hydroxyphenoxy)benzoate, diisobutyl phthalate, 3,5-dimethoxyphenol, and 2,2-dimethyl-1-(4-phenoxyphenyl)propanone. Among them, methyl 2-(4-hydroxyphenoxy)benzoate and 3,5-dimethoxyphenol were first identified as the intermediate products during the beta-cypermethrin degradation. In addition, we propose a degradation pathway for beta-cypermethrin that is metabolized by strain PAO1. Beta-cypermethrin could be biotransformed firstly by hydrolysis of its carboxylester linkage, followed by cleavage of the diaryl bond and subsequent metabolism. Based on the above results, P. aeruginosa PAO1 could be a potent candidate for the beta-cypermethrin-contaminated environmental bioremediation.
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Piretrinas , Contaminantes del Suelo , Pseudomonas aeruginosa , Biodegradación Ambiental , Piretrinas/metabolismo , Benzoatos , Suelo , Contaminantes del Suelo/metabolismoRESUMEN
Chlorpyrifos (CPF) is associated with depression, cognitive dysfunction, and other neurological disorders. Increasing evidence has suggested that the gut microbiota plays a vital role in regulating the development of depression. However, it is unknown whether gut microbiota is associated with CPF-related depression. This study aimed to explore the effect of CPF on depressive-like behavior in mice and investigated the role of gut microbiota in this behavior. In our study, we selected fifty male C57BL/6 J mice for the model and subjected them to CPF poisoning by gavage for 14 days. The depressive-like behaviors of mice were assessed by the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Furthermore, we selected the high-dose group (CPF10) with obvious changes in depressive-like behaviors for the hippocampus and colon histopathological analysis, examined the changes in the gut microbiota by 16 S rRNA sequencing, screened the different microbiota among groups by linear discriminant analysis effect size (LEfSe), analyzed the correlation between intestinal bacteria and depression-like behavior indicators by Spearman analysis, and evaluated the predictive ability of different bacteria to CPF-induced depressive-like behavior using the receiver operator characteristic (ROC) curve. The results showed that CPF caused depressive-like behaviors with pathological changes in the hippocampus and colon. CPF induced changes in gut microbiota, including 49 differential bacteria. Among the top 10 abundant bacteria, Actinobacteria and Deferribacteres were increased, and Cyanobacteria, Patescibacteria and Verrucomicrobia were decreased at the phylum level. Muribaculum, Ruminococcaceae.UCG.014 and uncultured Bacteroides bacterium were decreased at the genus level. Correlation analysis demonstrated that 18 differentially abundant bacteria were correlated with CPF-induced depression. ROC curves revealed that Deferribacteres, Mucispirillum, Rikenella and GCA900066575 are potential biomarkers for depression caused by CPF. These findings will provide an experimental basis for the neurological health of the pesticide-exposed population.
Asunto(s)
Cloropirifos , Microbioma Gastrointestinal , Plaguicidas , Ratones , Masculino , Animales , Cloropirifos/toxicidad , Ratones Endogámicos C57BL , Depresión/inducido químicamente , Plaguicidas/farmacología , Conducta AnimalRESUMEN
Co-contamination of arsenic and fluoride is widely distributed in groundwater. However, little is known about the interactively influence of arsenic and fluoride, especially the combined mechanism in cardiotoxicity. Cellular and animal models exposure to arsenic and fluoride were established to assess the oxidative stress and autophagy mechanism of cardiotoxic damage using the factorial design, a widely used statistical method for assessing two factor interventions. In vivo, combined exposure to high arsenic (50 mg/L) and high fluoride (100 mg/L) induced myocardial injury. The damage is accompanied by accumulation of myocardial enzyme, mitochondrial disorder, and excessive oxidative stress. Further experiment identified that arsenic and fluoride induced the accumulation of autophagosome and increased expression level of autophagy related genes during the cardiotoxicity process. These findings were further demonstrated through the in vitro model of arsenic and fluoride-treated the H9c2 cells. Additionally, combined of arsenic-fluoride exposure possesses the interactively influence on oxidative stress and autophagy, contributing to the myocardial cell toxicity. In conclusion, our data suggest that oxidative stress and autophagy are involved in the process of cardiotoxic injury, and that these indicators showed interaction effect in response to the combined exposure of arsenic and fluoride.