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Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.
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Fator de Necrose Tumoral alfa , Receptor Nicotínico de Acetilcolina alfa7 , Humanos , Regulação para Cima , Lipopolissacarídeos/farmacologia , Neuroimunomodulação , Cumarínicos/farmacologia , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológicoRESUMO
In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) was used to analyze the plasma components of Danzhi Xiaoyao Formula after oral administration. Forty-nine plasma components were found in the serum of rats by comparing the compound extract, drug-containing serum, and blank serum. Components, such as 6-hydroxycoumarin, poricoic acid F, deoxoglabrolide, 30-norhederagenin, kanzonol R, 3',6'-di-O-galloylpaeoniflorin, 16α-hydroxytrametenolic acid, 16-deoxyporicoic acid B, 3-O-acetyl-16α-hydroxytrametenolic acid, and 16α,25-dihydroxydehydroeburiconic acid, were first found in rat serum. Behavioral tests, including the tail suspension test, novel object recognition test, and novelty-suppressed feeding test, were conducted for behavioral analysis. It was confirmed that this formula had therapeutic effects on perimenopausal depression. Furthermore, in combination with the network pharmacology method, 53 core targets including MAPK1, HRAS, AKT1, EGFR, and ESR1 were screened, and these targets participated in 165 signaling pathways, including PI3K-AKT, AMPK, VEGFA, MAPK, and HIF-1. In summary, the potential effects of Danzhi Xiaoyao Formula in treating perimenopausal depression are associated with mechanisms in accelerating inflammation repair, improving neuroplasticity, affecting neurotransmitters, regulating estrogen levels, and promoting new blood vessel formation.
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Depressão , Medicamentos de Ervas Chinesas , Animais , Ratos , Cromatografia Líquida de Alta Pressão , Depressão/tratamento farmacológico , Farmacologia em Rede , Perimenopausa , Fosfatidilinositol 3-Quinases , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento MolecularRESUMO
Lipophagy is a kind of selective autophagy, which can selectively identify and degrade lipid droplets and plays an important role in regulating cellular lipid metabolism and maintaining intracellular lipid homeostasis. Exercise can induce lipophagy and it is also an effective means of reducing body fat. In this review, we summarized the relationship between exercise and lipophagy in the liver, pancreas, adipose tissue, and the possible molecular mechanisms to provide a new clue for the prevention and treatment of fatty liver, obesity and other related metabolic diseases by exercise.
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Metabolismo dos Lipídeos , Doenças Metabólicas , Autofagia/fisiologia , Humanos , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/fisiologia , Fígado , Doenças Metabólicas/metabolismoRESUMO
OBJECTIVE: To translate and cross-culturally adapt the Malocclusion Impact Questionnaire (MIQ) into Chinese and to assess the psychometric properties of the Chinese version of the MIQ (MIQ/C) for use among adolescents with malocclusion in China. MATERIALS AND METHOD: First, the MIQ/C was developed according to international guidelines. Then, the MIQ/C was filled out by 536 adolescents between 10 and 16 years of age. This study used exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity, internal consistency, and test-retest reliability to evaluate the psychometric properties of the MIQ/C. RESULTS: Following EFA, three domains were extracted, accounting for 65.950% of the total variance. The CFA results showed that the fit indices of each factor in the three-factor model all reached the standard (chi-square/DF = 2.591, GFI = 0.919, TLI = 0.926, CFI = 0.928, RMSEA = 0.076). The scale evidenced a good relationship with the two global questions, indicating good convergent validity. The Cronbach alpha value and the intraclass correlation coefficients (ICC) value of the MIQ/C were 0.929 and 0.893, respectively. CONCLUSION: The MIQ/C demonstrated good reliability and validity and can be further studied and applied in Chinese adolescents with malocclusion. CLINICAL RELEVANCE: The MIQ/C can be applied to assess the psychosocial impact of malocclusion among Chinese adolescents.
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Má Oclusão , Adolescente , China , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
DNA hypomethylation plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Here we investigated whether 3-hydroxy butyrate dehydrogenase 2 (BDH2), a modulator of intracellular iron homeostasis, was involved in regulating DNA hypomethylation and hyper-hydroxymethylation in lupus CD4+ T cells. Our results showed that BDH2 expression was decreased, intracellular iron was increased, global DNA hydroxymethylation level was elevated, while methylation level was reduced in lupus CD4+ T cells compared with healthy controls. The decreased BDH2 contributed to DNA hyper-hydroxymethylation and hypomethylation via increasing intracellular iron in CD4+ T cells, which led to overexpression of immune related genes. Moreover, we showed that BDH2 was the target gene of miR-21. miR-21 promoted DNA demethylation in CD4+ T cells through inhibiting BDH2 expression. Our data demonstrated that the dysregulation of iron homeostasis in CD4+ T cells induced by BDH2 deficiency contributes to DNA demethylation and self-reactive T cells in SLE.
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Linfócitos T CD4-Positivos/metabolismo , Hidroxibutirato Desidrogenase/metabolismo , Ferro/metabolismo , Lúpus Eritematoso Sistêmico/genética , Adulto , Animais , Western Blotting , Estudos de Casos e Controles , Desmetilação do DNA , Metilação de DNA , Regulação para Baixo , Epigênese Genética , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Homeostase , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , MicroRNAs/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
OBJECTIVE: To investigate the value of the content of neutrophil elastase (NE) in the expressed prostatic secretion (EPS) and seminal plasma (SP) as a combined predictor in the diagnosis of type IIIA prostatitis with secondary infertility. METHODS: This study included 62 fathers (group A) and 67 infertile men (group B), all with type IIIA prostatitis, and another 57 controls with no genitourinary tract disease (group C). We measured the NE contents in the EPS and SP, obtained the results of routine semen and EPS examinations and Chronic Prostatitis Symptom Index (CPSI), and calculated the ratio of EPS NE/SP NE by binary logistic regression analysis. RESULTS: The combined predictor of type IIIA prostatitis with secondary infertility was SP NE-2 × EPS NE. Among the 129 patients with type IIIA prostatitis, the combined predictor was correlated strongly negatively with the WBC count in the EPS (r = ï¼0.914, P <0.01), negatively with CPSI, sperm concentration, sperm mobility and sperm viability (P <0.01), but not significantly with the WBC count or pH value in the SP (P >0.05). The mean values of the combined predictor in groups A, B, and C were ï¼2 238 (95% CI: ï¼2 595 to ï¼2 054), ï¼1 511 (95% CI: ï¼1 778 to ï¼1 307), and ï¼148 (95% CI: ï¼181 to ï¼118), respectively, with statistically significant differences between the cases and controls as well as between groups A and B (P <0.01). The area under the ROC curve of the combined predictor for the diagnosis of type IIIA prostatitis with secondary infertility was 0.71 (P <0.001). CONCLUSIONS: The content of neutrophil elastase in the EPS combined with that in the seminal plasma contributes to the diagnosis of type IIIA prostatitis with secondary infertility, which is superior to either the neutrophil elastase content in the EPS or that in the seminal plasma used alone.
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Ensaios Enzimáticos Clínicos/métodos , Elastase de Leucócito/análise , Prostatite/diagnóstico , Sêmen/enzimologia , Biomarcadores/análise , Doença Crônica , Pai , Humanos , Infertilidade/diagnóstico , Infertilidade/etiologia , Masculino , Prostatite/complicações , Análise do Sêmen , Motilidade dos EspermatozoidesRESUMO
OBJECTIVE: To construct eukaryotic expression plasmids of the Tac1 gene and explore the interaction between TAC1 and sperm-associated antigen 6 (SPAG6). METHODS: RNA was extracted from the heart, liver, spleen, lung, kidney, brain, muscle, and testis of 10 Kunming male mice and, after reverse transcription into cDNA, the expression of Tac1 in the above tissues was observed by RT-PCR. Tac1/pEGFP-N2 and Tac1/pGADT7 recombinant plasmids were constructed and Tac1/pEGFP-N2 was transfected into CHO and COS-1 cells, followed by localization and detection of the protein expression of TAC1 by immunofluorescence staining and Western blot. The interaction between TAC1 and SPAG6 was determined by yeast two-hybrid experiment and Western blot. RESULTS: Tac1 was expressed mainly in the testis, brain and heart. The results of restriction enzyme digestion and sequencing indicated successful construction of the recombinant plasmids, with the restriction fragment length of 390 bp. TAC1 was localized in the whole body of the CHO cells when transfected alone, but expressed in the microtubule of the cells when cotransfected with SPAG6, with the molecular weight of 40 000. Yeast two-hybrid experiment showed the colonies of TAC1 and SPAG6 on the culture plate without Leu, Trp and His, both contained in the yeast fusion protein. CONCLUSIONS: The Tac1 recombinant plasmid was constructed successfully and the interaction between TAC1 and SPAG6 was confirmed with the plasmid.
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Proteínas dos Microtúbulos/fisiologia , Taquicininas/fisiologia , Testículo/metabolismo , Animais , Western Blotting , Encéfalo/metabolismo , Células CHO , Cricetinae , Cricetulus , DNA Complementar , Masculino , Camundongos , Miocárdio/metabolismo , Plasmídeos , Proteínas Recombinantes/metabolismo , TransfecçãoRESUMO
Phytoplasmas have the smallest genome among bacteria and lack many essential genes required for biosynthetic and metabolic functions, making them unculturable, phloem-limited plant pathogens. In this study, we observed that transgenic Arabidopsis (Arabidopsis thaliana) expressing the secreted Aster Yellows phytoplasma strain Witches' Broom protein11 shows an altered root architecture, similarly to the disease symptoms of phytoplasma-infected plants, by forming hairy roots. This morphological change is paralleled by an accumulation of cellular phosphate (Pi) and an increase in the expression levels of Pi starvation-induced genes and microRNAs. In addition to the Pi starvation responses, we found that secreted Aster Yellows phytoplasma strain Witches' Broom protein11 suppresses salicylic acid-mediated defense responses and enhances the growth of a bacterial pathogen. These results contribute to an improved understanding of the role of phytoplasma effector SAP11 and provide new insights for understanding the molecular basis of plant-pathogen interactions.
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Arabidopsis/imunologia , Arabidopsis/microbiologia , Proteínas de Bactérias/metabolismo , Fosfatos/deficiência , Phytoplasma/metabolismo , Antocianinas/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Sequência de Bases , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genoma de Planta/genética , Homeostase/efeitos dos fármacos , Homeostase/genética , Ácidos Indolacéticos/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Dados de Sequência Molecular , Fenótipo , Phytoplasma/efeitos dos fármacos , Doenças das Plantas/microbiologia , Reguladores de Crescimento de Plantas/metabolismo , Imunidade Vegetal/efeitos dos fármacos , Imunidade Vegetal/genética , Folhas de Planta/anatomia & histologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Pseudomonas syringae/efeitos dos fármacos , Pseudomonas syringae/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
Olive fruit dreg (OFD), waste from olive softdrink processing, has caused disposal problems. Nevertheless, OFD is a good source of functional ingredients, such as phenolic compounds. This study investigated the extraction conditions of phenolic compounds from OFD by using subcritical water (SCW) extraction method, antioxidant activity of SCW extracts, and components of phenolic compounds by LC-MS. SCW extraction experiments were performed in a batch stainless steel reactor at temperatures ranging from 100 to 180 °C at residence time of 5 to 60 min, and at solid-to-liquid ratio of 1:20 to 1:60. Higher recoveries of phenolic compounds [37.52 ± 0.87 mg gallic acid equivalents (GAE)/g, dry weight (DW)] were obtained at 160 °C, solid-to-liquid ratio of 1:50, and extract time of 30 min than at 2 h extraction with methanol (1.21 ± 0.16 mg GAE/g DW), ethanol (0.24 ± 0.07 mg GAE/g DW), and acetone (0.34 ± 0.01 mg GAE/g DW). The antioxidant activities of the SCW extracts were significantly stronger than those in methanol extracts at the same concentration of total phenolic contents. LC-MS analysis results indicated that SCW extracts contained higher amounts of phenolic compounds, such as chlorogenic acid, homovanillic acid, gallic acid, hydroxytyrosol, quercetin, and syringic acid. SCW at 160 °C, 30 min, and solid-to-liquid ratio of 1:50 may be a good substitute of organic solvents, such as methanol, ethanol, and acetone to recover phenolic compounds from OFD.
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Ulcerative colitis (UC) is a common inflammatory bowel disease with a complex origin in clinical settings. It is frequently accompanied by negative emotional responses, including anxiety and depression. Enteric glial cells (EGCs) are important components of the gut-brain axis and are involved in the development of the enteric nervous system (ENS), intestinal neuroimmune, and regulation of intestinal motor functions. Since there is limited research encompassing the regulatory function of EGCs in anxiety- and depression-like behaviors induced by UC, this study aims to reveal their regulatory role in such behaviors and associated intestinal inflammation. This study applied morphological, molecular biological, and behavioral methods to observe the morphological and functional changes of EGCs in UC mice. The results indicated a significant activation of EGCs in the ENS of dextran sodium sulfate -induced UC mice. This activation was evidenced by morphological alterations, such as elongation or terminal swelling of processes. Besides EGCs activation, UC mice exhibited significantly elevated expression levels of pro-inflammatory cytokines in the peripheral blood, accompanied by anxiety- and depression-like behaviors. The inhibition of EGCs activity within the ENS can ameliorate the anxiety- and depression-like behaviors caused by UC. Our data suggest that UC and its resulting behaviors may be related to the activation of EGCs within the ENS. Moreover, the modulation of intestinal inflammation through inhibition of EGCs activation emerges as a promising clinical approach for alleviating UC-induced anxiety- and depression-like behaviors.
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Ansiedade , Colite Ulcerativa , Depressão , Neuroglia , Animais , Colite Ulcerativa/psicologia , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Ansiedade/psicologia , Ansiedade/metabolismo , Depressão/metabolismo , Depressão/psicologia , Neuroglia/metabolismo , Neuroglia/patologia , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Sulfato de Dextrana/toxicidade , Sistema Nervoso Entérico/metabolismo , Sistema Nervoso Entérico/patologia , Inflamação/metabolismo , Inflamação/patologia , Comportamento AnimalRESUMO
Arbuscular mycorrhizal fungi (AMF) establish symbiotic relationships with roots of most plants, contributing to plant water uptake and soil carbon (C) sequestration. However, the interactive contribution and of long-term field AMF inoculation and water conservation on maize yield and soil organic carbon (SOC) sequestration in drylands remain largely unknown. After 7-year long-term field inoculation with AMF Funneliformis mosseae, AMF suppression by fungicide benomyl, and no-AMF/no-benomyl control, and two water conservation practices of half-film and full-film mulching (â¼50 % and â¼100 crop planted area covered with plastic film), this study thus applied in situ 13CO2-C labeling and high-throughput sequencing to quantify newly photosynthetically assimilated C into different soil C pools including soil aggregates and respiration, and their effects on maize growth and productivity. Results showed that 7-year long-term AMF inoculation significantly increased the relative abundance of F. mosseae in rhizosphere soil and root AMF colonization, indicating that F. mosseae successfully dominated in AMF communities. Compared to no-AMF/no-benomyl control, AMF colonization significantly increased shoot biomass and maize yield by 17.9 % and 20.3 % while mitigated the less water conservation effects of half-film mulching on maize performance. The SOC content under field AMF inoculation SOC was increased from 7.9 to 8.4 g kg-1 and also the mean weight diameter of aggregates (1.21 to 1.35), e.g. aggregate stability. After 1 and/or 40 days 13C labeling, the enhanced 13C translocations into macro-aggregates with decreased 13C emissions from microbial decomposition under field AMF inoculation had contributed to SOC conservation in bulk soil. These results suggest that AMF inoculation in dryland crops is promising to increase crop yield while promoting more atmospheric CO2 fixation in soil aggregates. A long-term field AMF inoculation will enhance our understanding of applying beneficial mycorrhizal fungi to enhance soil C sequestration and also crop yield via plant-fixed atmospheric CO2 in semi-arid and arid farmlands.
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Carbono , Micorrizas , Solo , Zea mays , Zea mays/microbiologia , Micorrizas/fisiologia , Solo/química , Carbono/metabolismo , Microbiologia do Solo , Glomeromycota/fisiologia , Isótopos de Carbono , Sequestro de Carbono , Raízes de Plantas/microbiologiaRESUMO
Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.
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Aborto Espontâneo , Autofagia , Sirolimo , Serina-Treonina Quinases TOR , Humanos , Autofagia/efeitos dos fármacos , Feminino , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Gravidez , Animais , Transdução de Sinais/efeitos dos fármacos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Inibidores de MTOR/farmacologia , Inibidores de MTOR/uso terapêuticoRESUMO
PROBLEM: Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disorder, presents considerable therapeutic challenges due to its complex and elusive pathophysiology. METHOD OF STUDY: We employed three machine learning algorithms to identify potential biomarkers within a training dataset, comprising GSE138518, GSE155489, and GSE193123. The diagnostic accuracy of these biomarkers was rigorously evaluated using a validation dataset using area under the curve (AUC) metrics. Further validation in clinical samples was conducted using PCR and immunofluorescence techniques. Additionally, we investigate the complex interplay among immune cells in PCOS using CIBERSORT to uncover the relationships between the identified biomarkers and various immune cell types. RESULTS: Our analysis identified ACSS2, LPIN1, and NR4A1 as key mitochondria-related biomarkers associated with PCOS. A notable difference was observed in the immune microenvironment between PCOS patients and healthy controls. In particular, LPIN1 exhibited a positive correlation with resting mast cells, whereas NR4A1 demonstrated a negative correlation with monocytes in PCOS patients. CONCLUSION: ACSS2, LPIN1, and NR4A1 emerge as PCOS-related diagnostic biomarkers and potential intervention targets, opening new avenues for the diagnosis and management of PCOS.
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Biomarcadores , Mitocôndrias , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/imunologia , Síndrome do Ovário Policístico/metabolismo , Feminino , Biomarcadores/metabolismo , Mitocôndrias/metabolismo , Aprendizado de Máquina , Adulto , Mastócitos/imunologia , Mastócitos/metabolismoRESUMO
Plastic fragments are widely found in the soil profile of terrestrial ecosystems, forming plastic footprint and posing increasing threat to soil functionality and carbon (C) footprint. It is unclear how plastic footprint affects C cycling, and in particularly permanent C sequestration. Integrated field observations (including 13C labelling) were made using polyethylene and polylactic acid plastic fragments (low-, medium- and high-concentrations as intensifying footprint) landfilling in soil, to track C flow along soil-plant-atmosphere continuum (SPAC). The result indicated that increased plastic fragments substantially reduced photosynthetic C assimilation (p < 0.05), regardless of fragment degradability. Besides reducing C sink strength, relative intensity of C emission increased significantly, displaying elevated C source. Moreover, root C fixation declined significantly from 21.95 to 19.2 mg m-2, and simultaneously root length density, root weight density, specific root length and root diameter and surface area were clearly reduced. Similar trends were observed in the two types of plastic fragments (p > 0.05). Particularly, soil aggregate stability was significantly lowered as affected by plastic fragments, which accelerated the decomposition rate of newly sequestered C (p < 0.05). More importantly, net C rhizodeposition declined averagely from 39.77 to 29.41 mg m-2, which directly led to significant decline of permanent C sequestration in soil. Therefore, increasing plastic footprint considerably worsened C footprint regardless of polythene and biodegradable fragments. The findings unveiled the serious effects of plastic residues on permanent C sequestration across SPAC, implying that current C assessment methods clearly overlook plastic footprint and their global impact effects.
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Pegada de Carbono , Plásticos , Solo , Solo/química , Carbono/análise , Atmosfera/química , Ciclo do Carbono , Ecossistema , Plantas , Sequestro de Carbono , Monitoramento Ambiental/métodosRESUMO
Plant disease induced by Xanthomonas campestris pv. campestris depends on type III effectors but the molecular basis is poorly understood. Here, AvrXccC8004 was characterized, and it was found that the AvrB_AvrC domain was essential and sufficient to elicit defense responses in an Arabidopsis-resistant ecotype (Col-0). An upregulation of genes in responding to the AvrB_AvrC domain of AvrXccC8004 was shown in a profile of host gene expression. The molecular changes were correlated with morphological changes observed in phenotypic and ultrastructural characterizations. Interestingly, the abscisic acid (ABA)-signaling pathway was also a prominent target for the AvrB_AvrC domain of AvrXccC8004. The highly elicited NCED5, encoding a key enzyme of ABA biosynthesis, was increased in parallel with ABA levels in AvrXccC8004 transgenic plants. Consistently, the X. campestris pv. campestris 8004 ΔavrXccC mutant was severely impaired in the ability to manipulate the accumulation of ABA and induction of ABA-related genes in challenged leaves. Moreover, exogenous application of ABA also enhanced the susceptibility of Arabidopsis to the X. campestris pv. campestris strains. These results indicate that the AvrB_AvrC domain of AvrXccC8004 alone has the activity to manipulate ABA homeostasis, which plays an important role in regulating the interactions of X. campestris pv. campestris and Arabidopsis.
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Ácido Abscísico/metabolismo , Proteínas de Bactérias/metabolismo , Xanthomonas campestris/patogenicidade , Ácido Abscísico/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/microbiologia , Proteínas de Bactérias/genética , Interações Hospedeiro-Patógeno , Doenças das Plantas/microbiologia , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/microbiologia , Virulência/genética , Virulência/fisiologiaRESUMO
Inulin, a commonly used dietary fiber supplement, is capable of modulating the gut microbiome. Chronic inflammation resulting from metabolic abnormalities and gut flora dysfunction plays a significant role in the development of type 2 diabetes mellitus (T2DM). Our research has demonstrated that inulin administration effectively reduced colonic inflammation in T2DM mice by inducing changes in the gut microbiota and increasing the concentration of butyric acid, which in turn modulated the function of enteric glial cells (EGCs). Experiments conducted on T2DM mice revealed that inulin administration led to an increase in the Bacteroidetes/Firmicutes ratio and the concentration of butyric acid in the colon. The anti-inflammatory effects of altered gastrointestinal flora and its metabolites were further confirmed through fecal microbiota transplantation. Butyric acid was found to inhibit the activation of the κB inhibitor kinase ß/nuclear factor κB pathway, regulate the expression levels of interleukin-6 and tumor necrosis factor-α, suppress the abnormal activation of EGCs, and prevent the release of inflammatory factors by EGCs. Similar results were observed in vitro experiments with butyric acid. Our findings demonstrate that inulin, by influencing the intestinal flora, modifies the activity of EGCs to effectively reduce colonic inflammation in T2DM mice.
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The enteric nervous system (ENS) is one of the important systems that regulate gastrointestinal function. The ENS is made up of enteric glial cells (EGCs) and neurons. For a long time, it was believed that the function of EGCs was only to give structural support to neurons. However, recent evidence indicates EGCs are involved in most gut functions, including the development and plasticity of the ENS, epithelial barrier, and motility. However, it remains unclear whether EGCs have the potential to modify colonic motility following irritable bowel syndrome (IBS) with predominant diarrhea (IBS-D). This study aimed to investigate changes in EGCs during IBS-D and assessed the effects of manipulating EGCs. An IBS-D rat model was constructed using acetic acid and restraint stress, and DL-fluorocitric acid (FC), an inhibitor of EGCs, was administered. The changes in EGCs and colonic motility were studied by employing techniques comprising morphological, molecular biological and functional experiments. The results showed significant activation of EGCs in the myenteric plexus (MP) of the IBS-D-induced rat colon with accelerated colonic motility. FC significantly reduced the activation of EGCs and colonic motility caused by acetic acid and restraint stress. Hypercontraction of the colon caused by IBS-D may be associated with activation of EGCs in the MP of the colon and this was prevented by FC. Therefore, regulating colon hypercontraction through interference with the activation of EGCs has significant prospects for clinical application to alleviate diarrhea in patients with IBS-D.
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Síndrome do Intestino Irritável , Ratos , Animais , Ratos Sprague-Dawley , Motilidade Gastrointestinal/fisiologia , Colo , Diarreia , NeurogliaRESUMO
Unintentional ingestion of metal-contaminated soils may pose a great threat to human health. To accurately evaluate the health risks of heavy metal(loid)s in soils, their bioaccessibility has been widely determined by in vitro assays and increasingly employed to optimize the assessment parameters. Given that, using meta-analysis, we analyzed the literature on farmland heavy metal(loid)s (As, Cd, Cr, Cu, Hg, Pb, Ni, and Zn) in Chinese main grain production regions, and collected their total and bioaccessibility data to accurately assess their human health risks. Monte Carlo simulation was used to reduce the uncertainty in metal concentration, intake rate, toxicity coefficient, and body weight. We found that the mean concentration (0.47 mg/kg) and geological accumulation index (Igeo, 0-5.24) of Cd were the priority position of controlling metals. Moreover, children are more vulnerable to carcinogenic risks than adults. Soil mineralogy, physicochemical properties, Fe, and the types of in vitro assays are the influencing factors of bioaccessibility discrepancy. Furthermore, appropriate bioaccessibility determination methods can be adapted according to the differences in ecological receptors for the risk assessment, like developing a "personalized assessment" scheme for polluted farmland soil management. Collectively, bioaccessibility-based models may provide an accurate and effective approach to human health risk assessment.
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Metais Pesados , Poluentes do Solo , Criança , Adulto , Humanos , Solo/química , Poluentes do Solo/análise , Cádmio/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , China , Medição de Risco/métodos , Grão Comestível/químicaRESUMO
Introduction: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin-tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs. Methods: A monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae. Results: Of the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01). Discussion: In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.
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Infecções por Enterobacteriaceae , Pielonefrite , Infecções Urinárias , Adulto , Humanos , Meropeném/uso terapêutico , Piperacilina/efeitos adversos , Estudos Retrospectivos , Inibidores de beta-Lactamases/uso terapêutico , Ácido Penicilânico/efeitos adversos , Antibacterianos/efeitos adversos , Combinação Piperacilina e Tazobactam/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Pielonefrite/tratamento farmacológico , Enterobacteriaceae , Carbapenêmicos/uso terapêutico , beta-Lactamases/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológicoRESUMO
The rise of plasticulture as mulching material in farming systems has raised concerns about microplastics (MPs) in the agricultural landscape. MPs are emerging pollutants in croplands and water systems with significant ecological risks, particularly over the long term. In the soil systems, MPs polymer type, thinness, shape, and size induces numerous effects on soil aggregates, dissolved organic carbon (C), rapidly oxidized organic C, microbial biomass C, microbial biomass nitrogen (N), microbial immobilization, degradation of organic matter, N cycling, and production of greenhouse gas emissions (GHGs), thereby posing a significant risk of impairing soil physical and biochemical properties over time. Further, toxic chemicals released from polyethylene mulching (PMs) might indirectly harm plant growth by affecting soil wetting-drying cycles, releasing toxic substances that interact with soil matrix, and suppressing soil microbial activity. In the environment, accumulation of MPs poses a risk to human health by accelerating emissions of GHGs, e.g., methane and carbon dioxide, or directly releasing toxic substances such as phthalic acid esters (PAEs) into the soils. Also, larger sizes MPs can adhere to root surface and block stomata could significantly change the shape of root epidermal cells resulting in arrest plant growth and development by restricting water-nutrient uptake, and gene expression and altering the biodiversity of the soil pollutants. In this review, we systematically analyzed the potential risks of MPs to the soil-plant and human body, their occurrence, abundance, and migration in agroecosystems. Further, the impacts of MPs on soil microbial function, nutrient cycling, soil C, and GHGs are mechanistically reviewed, with emphasis on potential green solutions such as organic materials amendments along with future research directions for more eco-friendly and sustainable plastic management in agroecosystems.