RESUMO
INTRODUCTION: Pregnancy-associated gynecological cancer (PAGC) refers to cancers of the ovary, uterus, fallopian tube, cervix, vagina, and vulva diagnosed during pregnancy or within 12 months postpartum. We aimed to describe the incidence of, and perinatal outcomes associated with, invasive pregnancy-associated gynecological cancer. MATERIAL AND METHODS: We conducted a population-based historical cohort study using linked data from New South Wales, Australia. We included all women who gave birth between 1994 and 2013, with a follow-up period extending to September 30, 2018. Three groups were analyzed: a gestational PAGC group (women diagnosed during pregnancy), a postpartum PAGC group (women diagnosed within 1 year of giving birth), and a control group (women with control diagnosis during pregnancy or within 1 year of giving birth). We used generalized estimation equations to compare perinatal outcomes between study groups. RESULTS: There were 1 786 137 deliveries during the study period; 70 women were diagnosed with gestational PAGC and 191 with postpartum PAGC. The incidence of PAGC was 14.6/100 000 deliveries and did not change during the study period. Women with gestational PAGC (adjusted odds ratio [aAOR] 6.81, 95% confidence interval [CI] 2.97-15.62) and with postpartum PAGC (aOR 2.65, 95% CI 1.25-5.61) had significantly increased odds of a severe maternal morbidity outcome compared with the control group. Babies born to women with gestational PAGC were more likely to be born preterm (aOR 3.11, 95% CI 1.47-6.59) and were at increased odds of severe neonatal complications (aOR 3.47, 95% CI 1.45-8.31) compared with babies born to women without PAC. CONCLUSIONS: The incidence of PAGC has not increased over time perhaps reflecting, in part, the effectiveness of cervical screening and early impacts of human papillomavirus vaccination programs in Australia. The higher rate of preterm birth among the gestational PAGC group is associated with adverse outcomes in babies born to these women.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Nascimento Prematuro , Neoplasias do Colo do Útero , Gravidez , Recém-Nascido , Feminino , Humanos , New South Wales/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos de Coortes , Detecção Precoce de Câncer , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Austrália , Parto , Resultado da Gravidez/epidemiologiaRESUMO
The airway epithelium is a central modulator of innate and adaptive immunity in the lung. IL17A expression was found to be increased in the airway epithelium; however, the role of epithelium-derived IL17A in chronic obstructive pulmonary disease (COPD) remains unclear. In this study, we aimed to determine whether epithelium-derived IL17A regulates inflammation and mucus hyperproduction in COPD by using a cultured human bronchial epithelial (HBE) cell line in vitro and an airway epithelium IL17A-specific knockout mouse in vivo. Increased IL17A expression was observed in the mouse airway epithelium upon cigarette smoke (CS) exposure or in a mouse model of COPD that was induced by using CS and Eln (elastin). CS extract (CSE) also triggered IL17A expression in HBE cells. Blocking IL17A or IL17RA (IL17 receptor A) effectively attenuated CSE-induced MUC5AC and the inflammatory cytokines IL6, TNF-α, and IL1ß in HBE cells, suggesting that IL17A mediates CSE-induced inflammation and mucin production in an autocrine manner. CSE activated p-JUN (phospho-JUN) and p-JNK (phospho-c-Jun N-terminal kinase), which were also reduced by IL17RA siRNA, and JUN siRNA attenuated CSE-induced IL6 and MUC5AC. In vivo, selective knockout of IL17A in the airway epithelium markedly reduced the neutrophilic infiltration in BAL fluid, peribronchial inflammation, proinflammatory mediators (CXCL1 [CXC ligand 1] and CXCL2), and mucus production in a COPD mouse model. We showed a novel function of airway epithelium-derived IL17A, which can act locally in an autocrine manner to amplify inflammation and increase mucus production in COPD pathogenesis.
Assuntos
Fumar Cigarros/imunologia , Interleucina-17/imunologia , Muco/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Mucosa Respiratória/imunologia , Animais , Linhagem Celular , Fumar Cigarros/genética , Modelos Animais de Doenças , Humanos , Inflamação/genética , Inflamação/imunologia , Interleucina-17/genética , Camundongos , Camundongos Knockout , Infiltração de Neutrófilos/genética , Neutrófilos/imunologia , Doença Pulmonar Obstrutiva Crônica/genéticaRESUMO
INTRODUCTION: Eosinophils are critical in allergic disorders, and promoting eosinophil death effectively attenuates allergic airway inflammation. Ferroptosis is a recently described novel form of cell death; however, little is known about ferroptosis in eosinophils and related diseases. This study aimed to investigate the effects of ferroptosis-inducing agents (FINs) on eosinophil death and allergic airway inflammation, and to explore their potential synergistic effect with glucocorticoids (GCs). METHODS: Eosinophils isolated from the peripheral blood of humans or mice were incubated with FINs, and eosinophil ferroptosis was assessed. The in vivo effects of FINs alone or in combination with dexamethasone (DXMS) were examined in a mouse model of allergic airway inflammation. Bronchoalveolar lavage fluid and lung tissue were collected to examine airway inflammation. RESULTS: Treatment with FINs time and dose dependency induced cell death in human and mouse eosinophils. Interestingly, FINs induced non-canonical ferroptosis in eosinophils, which generated morphological characteristics unique to ferroptosis and was iron dependent but was independent of lipid peroxidation. The antioxidants glutathione and N-acetylcysteine significantly attenuated FIN-induced cell death. Treatment with FINs triggered eosinophil death in vivo and eventually relieved eosinophilic airway inflammation in mice. Furthermore, FINs exerted a synergistic effect with DXMS to induce eosinophil death in vitro and to alleviate allergic airway inflammation in vivo. CONCLUSIONS: FINs induced ferroptosis-like cell death of eosinophils, suggesting their use as a promising therapeutic strategy for eosinophilic airway inflammation, especially due to the advantage of their synergy with GCs in the treatment of allergic disorders.
Assuntos
Hiper-Reatividade Brônquica/tratamento farmacológico , Eosinófilos/citologia , Ferroptose , Animais , Artesunato/farmacologia , Benzilaminas/farmacologia , Hiper-Reatividade Brônquica/patologia , Líquido da Lavagem Broncoalveolar/citologia , Dexametasona/farmacologia , Sinergismo Farmacológico , Eosinófilos/patologia , Glucocorticoides/farmacologia , Humanos , Imidazóis/farmacologia , Indóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piperazinas/farmacologia , Quinazolinas/farmacologiaRESUMO
INTRODUCTION: Airway epithelial cells are recognised as an essential controller for the initiation and perpetuation of asthmatic inflammation, yet the detailed mechanisms remain largely unknown. This study aims to investigate the roles and mechanisms of the mechanistic target of rapamycin (MTOR)-autophagy axis in airway epithelial injury in asthma. METHODS: We examined the MTOR-autophagy signalling in airway epithelium from asthmatic patients or allergic mice induced by ovalbumin or house dust mites, or in human bronchial epithelial (HBE) cells. Furthermore, mice with specific MTOR knockdown in airway epithelium and autophagy-related lc3b-/- mice were used for allergic models. RESULTS: MTOR activity was decreased, while autophagy was elevated, in airway epithelium from asthmatic patients or allergic mice, or in HBE cells treated with IL33 or IL13. These changes were associated with upstream tuberous sclerosis protein 2 signalling. Specific MTOR knockdown in mouse bronchial epithelium augmented, while LC3B deletion diminished allergen-induced airway inflammation and mucus hyperproduction. The worsened inflammation caused by MTOR deficiency was also ameliorated in lc3b-/- mice. Mechanistically, autophagy was induced later than the emergence of allergen-initiated inflammation, particularly IL33 expression. MTOR deficiency increased, while knocking out of LC3B abolished the production of IL25 and the eventual airway inflammation on allergen challenge. Blocking IL25 markedly attenuated the exacerbated airway inflammation in MTOR-deficiency mice. CONCLUSION: Collectively, these results demonstrate that allergen-initiated inflammation suppresses MTOR and induces autophagy in airway epithelial cells, which results in the production of certain proallergic cytokines such as IL25, further promoting the type 2 response and eventually perpetuating airway inflammation in asthma.
Assuntos
Asma/metabolismo , Inflamação/metabolismo , Interleucina-17/biossíntese , Interleucinas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adulto , Idoso , Alérgenos , Animais , Asma/patologia , Asma/fisiopatologia , Autofagia/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Inflamação/patologia , Interleucina-13/metabolismo , Interleucina-13/farmacologia , Interleucina-33/metabolismo , Interleucina-33/farmacologia , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Mucosa Respiratória/fisiopatologia , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismoRESUMO
It is currently not understood whether cigarette smoke exposure facilitates sensitisation to self-antigens and whether ensuing auto-reactive T cells drive chronic obstructive pulmonary disease (COPD)-associated pathologies.To address this question, mice were exposed to cigarette smoke for 2â weeks. Following a 2-week period of rest, mice were challenged intratracheally with elastin for 3â days or 1â month. Rag1-/- , Mmp12-/- , and Il17a-/- mice and neutralising antibodies against active elastin fragments were used for mechanistic investigations. Human GVAPGVGVAPGV/HLA-A*02:01 tetramer was synthesised to assess the presence of elastin-specific T cells in patients with COPD.We observed that 2â weeks of cigarette smoke exposure induced an elastin-specific T cell response that led to neutrophilic airway inflammation and mucus hyperproduction following elastin recall challenge. Repeated elastin challenge for 1â month resulted in airway remodelling, lung function decline and airspace enlargement. Elastin-specific T cell recall responses were dose dependent and memory lasted for over 6â months. Adoptive T cell transfer and studies in T cells deficient Rag1-/- mice conclusively implicated T cells in these processes. Mechanistically, cigarette smoke exposure-induced elastin-specific T cell responses were matrix metalloproteinase (MMP)12-dependent, while the ensuing immune inflammatory processes were interleukin 17A-driven. Anti-elastin antibodies and T cells specific for elastin peptides were increased in patients with COPD.These data demonstrate that MMP12-generated elastin fragments serve as a self-antigen and drive the cigarette smoke-induced autoimmune processes in mice that result in a bronchitis-like phenotype and airspace enlargement. The study provides proof of concept of cigarette smoke-induced autoimmune processes and may serve as a novel mouse model of COPD.
Assuntos
Elastina , Doença Pulmonar Obstrutiva Crônica , Animais , Autoimunidade , Modelos Animais de Doenças , Humanos , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Fumaça/efeitos adversos , Fumar/efeitos adversosRESUMO
Increasing toxicological and epidemiological studies have demonstrated that ambient particulate matter (PM) could cause adverse health effects including inflammation in the lung. Alveolar macrophages represent a major type of innate immune responses to foreign substances. However, the detailed mechanisms of inflammatory responses induced by PM exposure in macrophages are still unclear. We observed that coarse PM treatment rapidly activated mechanistic target of rapamycin (MTOR) in mouse alveolar macrophages in vivo, and in cultured mouse bone marrow-derived macrophages, mouse peritoneal macrophages, and RAW264.7 cells. Pharmacological inhibition or genetic knockdown of MTOR in bone marrow-derived macrophages leads to an amplified cytokine production upon PM exposure, and mice with specific knockdown of MTOR or ras homolog enriched in brain in myeloid cells exhibit significantly aggregated airway inflammation. Mechanistically, PM activated MTOR through modulation of ERK, AKT serine/threonine kinase 1, and tuberous sclerosis complex signals, whereas MTOR deficiency further enhanced the PM-induced necroptosis and activation of subsequent NF κ light-chain-enhancer of activated B cells (NFKB) signaling. Inhibition of necroptosis or NFKB pathways significantly ameliorated PM-induced inflammatory response in MTOR-deficient macrophages. The present study thus demonstrates that MTOR serves as an early adaptive signal that suppresses the PM-induced necroptosis, NFKB activation, and inflammatory response in lung macrophages, and suggests that activation of MTOR or inhibition of necroptosis in macrophages may represent novel therapeutic strategies for PM-related airway disorders.
Assuntos
Macrófagos/imunologia , Material Particulado/toxicidade , Serina-Treonina Quinases TOR/imunologia , Animais , Morte Celular/fisiologia , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Serina-Treonina Quinases TOR/metabolismoRESUMO
Airway epithelial cell death and inflammation are pathological features of chronic obstructive pulmonary disease (COPD). Mechanistic target of rapamycin (MTOR) is involved in inflammation and multiple cellular processes, e.g., autophagy and apoptosis, but little is known about its function in COPD pathogenesis. In this article, we illustrate how MTOR regulates cigarette smoke (CS)-induced cell death, airway inflammation, and emphysema. Expression of MTOR was significantly decreased and its suppressive signaling protein, tuberous sclerosis 2 (TSC2), was increased in the airway epithelium of human COPD and in mouse lungs with chronic CS exposure. In human bronchial epithelial cells, CS extract (CSE) activated TSC2, inhibited MTOR, and induced autophagy. The TSC2-MTOR axis orchestrated CSE-induced autophagy, apoptosis, and necroptosis in human bronchial epithelial cells; all of which cooperatively regulated CSE-induced inflammatory cytokines IL-6 and IL-8 through the NF-κB pathway. Mice with a specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly augmented airway inflammation and airspace enlargement in response to CS exposure, accompanied with enhanced levels of autophagy, apoptosis, and necroptosis in the lungs. Taken together, these data demonstrate that MTOR suppresses CS-induced inflammation and emphysema-likely through modulation of autophagy, apoptosis, and necroptosis-and thus suggest that activation of MTOR may represent a novel therapeutic strategy for COPD.
Assuntos
Morte Celular/fisiologia , Células Epiteliais/metabolismo , Inflamação/metabolismo , Nicotiana/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fumaça/efeitos adversos , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Enfisema Pulmonar/metabolismo , Fumar/efeitos adversosRESUMO
Pulmonary epithelial cells form the first line of defense of human airways against foreign irritants and also represent as the primary injury target of these pathogenic assaults. Autophagy is a revolutionary conserved ubiquitous process by which cytoplasmic materials are delivered to lysosomes for degradation when facing environmental and/or developmental changes, and emerging evidence suggests that autophagy plays pivotal but controversial roles in pulmonary epithelial injury. Here we review recent studies focusing on the roles of autophagy in regulating airway epithelial injury induced by various stimuli. Articles eligible for this purpose are divided into two groups according to the eventual roles of autophagy, either protective or deleterious. From the evidence summarized in this review, we draw several conclusions as follows: 1) in all cases when autophagy is decreased from its basal level, autophagy is protective; 2) when autophagy is deleterious, it is generally upregulated by stimulation; and 3) a plausible conclusion is that the endosomal/exosomal pathways may be associated with the deleterious function of autophagy in airway epithelial injury, although this needs to be clarified in future investigations.
Assuntos
Autofagia/fisiologia , Células Epiteliais/patologia , Lesão Pulmonar/patologia , Animais , Células Epiteliais/metabolismo , Humanos , Lesão Pulmonar/metabolismo , Lisossomos/metabolismo , Lisossomos/patologia , Transdução de Sinais/fisiologiaRESUMO
Mucus hypersecretion is a common pathological feature of chronic airway inflammatory diseases including chronic obstructive pulmonary disease (COPD). However, the molecular basis for this condition remains incompletely understood. We have previously demonstrated a critical role of autophagy in COPD pathogenesis through mediating apoptosis of lung epithelial cells. In this study, we aimed to investigate the function of autophagy as well as its upstream and downstream signals in cigarette smoke-induced mucus production in human bronchial epithelial (HBE) cells and in mouse airways. Cigarette smoke extract (CSE), as well as the classical autophagy inducers starvation or Torin-1, significantly triggered MUC5AC expression, and inhibition of autophagy markedly attenuated CSE-induced mucus production. The CSE-induced autophagy was mediated by mitochondrial reactive oxygen species (mitoROS), which regulated mucin expression through the JNK and activator protein-1 pathway. Epidermal growth factor receptor (EGFR) was also required for CSE-induced MUC5AC in HBE cells, but it exerted inconsiderable effects on the autophagy-JNK signaling cascade. Airways of mice with dysfunctional autophagy-related genes displayed a markedly reduced number of goblet cells and attenuated levels of Muc5ac in response to cigarette smoke exposure. These results altogether suggest that mitoROS-dependent autophagy is essential for cigarette smoke-induced mucus hyperproduction in airway epithelial cells, and reemphasize autophagy inhibition as a novel therapeutic strategy for chronic airway diseases.
Assuntos
Autofagia/efeitos dos fármacos , Mucina-5AC/genética , Mucosa Respiratória/metabolismo , Fumar/metabolismo , Animais , Células Cultivadas , Receptores ErbB/metabolismo , Expressão Gênica , Células Caliciformes , Humanos , Pulmão/metabolismo , Pulmão/patologia , Camundongos Knockout , Mucina-5AC/metabolismo , Muco/metabolismo , Naftiridinas/farmacologia , Mucosa Respiratória/patologia , Transdução de Sinais , Nicotiana/química , Fator de Transcrição AP-1/metabolismoRESUMO
Petrochemical wastewater (PCWW) treatment poses challenges due to its unique and complex dissolved organic matter (DOM) composition, originating from various industrial processes. Despite the addition of advanced treatment units in PCWW treatment plants to meet discharge standards, the mechanisms of molecular-level sights into DOM reactivity of the upgraded full-scale processes including multiple biological treatments and advanced treatment remain unclear. Herein, we employ water quality indexes, spectra, molecular weight (MW) distribution, and Fourier transform ion cyclotron resonance mass spectrometry to systematically characterize DOM in a typical PCWW treatment plant including influent, micro-oxygen hydrolysis acidification (MOHA), anaerobic/oxic (AO), and micro-flocculation sand filtration-catalytic ozonation (MFSF-CO). Influent DOM is dominated by tryptophan-like and soluble microbial products with MW fractions ã 1 kDa and ã 100 kDa, and CHO with lignin and aliphatic/protein structures. MOHA effectively degrades macromolecular CHO (10.86 %) and CHON (5.24 %) compounds via deamination and nitrogen reduction, while AO removes CHOS compounds with MW < 10 kDa by desulfurization, revealing distinct DOM conversion mechanisms. MFSF-CO transforms unsaturated components to less aromatic and more saturated DOM through oxygen addition reactions and shows high CHOS and CHONS reactivity via desulfurization and deamination reactions, respectively. Moreover, the correlation among multiple parameters suggests UV254 combined with AImod as a simple monitoring indicator of DOM to access the chemical composition. The study provides molecular-level insights into DOM for the contribution to the improvement and optimization of the upgraded processes in PCWW.
Assuntos
Eliminação de Resíduos Líquidos , Águas Residuárias , Águas Residuárias/química , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Compostos Orgânicos/química , Poluentes Químicos da Água/química , Peso MolecularRESUMO
Background: Macrophage-derived matrix metalloproteinase 12 (MMP12) can cause destruction of lung tissue structure and plays a significant role in the development and progression of chronic obstructive pulmonary disease (COPD). MTOR is a serine/threonine kinase that plays a crucial role in cell growth and metabolism. The activity of MTOR in the lung tissues of COPD patients also shows significant changes. However, it is unclear whether MTOR can regulate the development and progression of COPD by controlling MMP12. This study primarily investigates whether MTOR in macrophages can affect the expression of MMP12 and participate in the progression of COPD. Methods: We tested the changes in MTOR activity in macrophages exposed to cigarette smoke (CS) both in vivo and in vitro. Additionally, we observed the effect of MTOR on the expression of MMP12 in macrophages and on lung tissue inflammation and structural damage in mice, both in vivo and in vitro, using MTOR inhibitors or gene knockout mice. Finally, we combined inhibitor treatment with gene knockout to demonstrate that MTOR primarily mediates the expression of MMP12 through the NF-κB signaling pathway. Results: Exposure to CS can enhance MTOR activity in mouse alveolar macrophages. Inhibiting the activity of MTOR or suppressing its expression leads to increased expression of MMP12. Myeloid-specific knockout of MTOR expression can promote the occurrence of CS-induced pulmonary inflammation and emphysema in mice. Inhibiting the activity of NF-κB can eliminate the effect of MTOR on MMP12. Conclusion: Macrophage MTOR can reduce the expression of MMP12 by inhibiting NF-κB, thereby inhibiting the occurrence of COPD inflammation and destruction of lung tissue structure. Activating the activity of macrophage MTOR may be beneficial for the treatment of COPD.
Assuntos
Fumar Cigarros , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Serina-Treonina Quinases TOR , Animais , Humanos , Camundongos , Fumar Cigarros/efeitos adversos , Inflamação/metabolismo , Pulmão , Macrófagos/metabolismo , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Pneumonia/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Enfisema Pulmonar/complicações , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Produtos do TabacoRESUMO
Monitoring endogenous glutathione (GSH) levels in living cells is essential for cancer diagnose and treatment. In this work, GSH responsive fluorescent nanoprobe with turn-on property was constructed using Zn-modified porphyrinic metal-organic frameworks (PCN-224-Zn). The introduced Zn2+ could quench the fluorescence of PCN-224 by the metallization of organic ligand (TCPP) and serves as sensing site for GSH. When exposed to GSH, the strong binding affinity of GSH generates the formation of Zn-GSH complex, eliminating the fluorescence quenching effect of Zn2+. Based on the constructed PCN-224-Zn nanoprobe, selective determination of GSH was achieved in the range of 0.01-6 µM with a detection limit of 1.5 nM. Furthermore, the constructed nanoprobe can realize the fluorescence imaging of endogenous GSH in MCF-7 and HeLa cells. Meanwhile, PCN-224-Zn could also monitor GSH in cell lysate with recovery rates from 93.8 % to 102.3 %. The performance of PCN-224-Zn demonstrates its capacities in the application of fluorescence sensing and bio-imaging fields.
Assuntos
Corantes , Pontos Quânticos , Humanos , Células HeLa , Glutationa/metabolismo , Pontos Quânticos/química , Zinco/química , Corantes Fluorescentes/toxicidade , Corantes Fluorescentes/químicaRESUMO
The WUSCHEL-related homeobox (WOX) gene family is vital for plant development and stress response. In this study, we conducted a comprehensive analysis of WOX genes in Cunninghamia lanceolata (C. lanceolata) and subsequently explored the potential roles of two ClWOX genes within the WUS clade. In total, six ClWOX genes were identified through a full-length transcriptome analysis. These genes, exhibiting conserved structural and functional motifs, were assigned to the ancient clade and Modern/WUS clade, respectively, through a phylogenetic analysis. Our expression analysis indicated that these ClWOX genes were highly expressed in the middle and late developmental stages of zygotic embryos in C. lanceolata. Moreover, only ClWOX5 and ClWOX6 within the Modern/WUS clade exhibited transcriptional activity, and their expressions were also induced in response to auxin and wounding. Overexpression of ClWOX5 and ClWOX6 in Arabidopsis caused a partially sterile phenotype, resulting in a very low seed setting rate. Transcriptomic analysis revealed that expressions of many embryo-defective (EMB) genes, phytohormone-related genes, and transcription factors (TFs) were dramatically altered in ClWOX5 and ClWOX6 transgenic plants, which suggested that ClWOX5 and ClWOX6 may play specific important roles in embryo development via complex gene networks. In addition, overexpression of ClWOX5 and ClWOX6 in leaf segments promoted shoot regeneration in tobacco, indicating that ClWOX5 and ClWOX6 can promote plant regeneration and could be used to improve genetic transformation. In conclusion, these results help to elucidate the function of the WOX gene and provide a valuable basis for future studies of the developmental regulation and applications of WOX genes in C. lanceolata.
Assuntos
Cunninghamia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cunninghamia/genética , Família Multigênica , Arabidopsis/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Filogenia , Plantas Geneticamente Modificadas/genética , Genes de PlantasRESUMO
COPD poses a significant global public health challenge, primarily characterised by irreversible airflow restriction and persistent respiratory symptoms. The hallmark pathology of COPD includes sustained airway inflammation and the eventual destruction of lung tissue structure. While multiple risk factors are implicated in the disease's progression, the underlying mechanisms remain largely elusive. The perpetuation of inflammation is pivotal to the advancement of COPD, emphasising the importance of investigating these self-sustaining mechanisms for a deeper understanding of the pathogenesis. Autoimmune responses constitute a critical mechanism in maintaining inflammation, with burgeoning evidence pointing to their central role in COPD progression; yet, the intricacies of these mechanisms remain inadequately defined. This review elaborates on the evidence supporting the presence of autoimmune processes in COPD and examines the potential mechanisms through which autoimmune responses may drive the chronic inflammation characteristic of the disease. Moreover, we attempt to interpret the clinical manifestations of COPD through autoimmunity.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Autoimunidade , Pulmão/patologia , Fatores de Risco , InflamaçãoRESUMO
Global aquaculture production is expected to rise to meet the growing demand for food worldwide, potentially leading to increased anthropogenic greenhouse gases (GHG) emissions. As the demand for fish protein increases, so will stocking density, feeding amounts, and nitrogen loading in aquaculture ponds. However, the impact of GHG emissions and the underlying microbial processes remain poorly understood. This study investigated the GHG emission characteristics, key microbial processes, and environmental drivers underlying GHG emissions in low and high nitrogen loading aquaculture ponds (LNP and HNP). The N2O flux in HNP (43.1 ± 11.3 µmol m-2 d-1) was significantly higher than in LNP (-11.3 ± 25.1 µmol m-2 d-1), while the dissolved N2O concentration in HNP (52.8 ± 7.1 nmol L-1) was 150 % higher than in LNP (p < 0.01). However, the methane (CH4) and carbon dioxide (CO2) fluxes and concentrations showed no significant differences (p > 0.05). N2O replaced CH4 as the main source of Global Warming Potential in HNP. Pond sediments acted as a sink for N2O but a source for CH4 and CO2. The â³N2O/(â³N2O + â³N2) in HNP (0.015 ± 0.007 %) was 7.7-fold higher than in LNP (0.002 ± 0.001 %) (p < 0.05). The chemical oxygen demand to NO2-N ratio was the most important environmental factor explaining the variability of N2O fluxes. Ammonia-oxidizing bacteria driven nitrification in water was the predominant N2O source, while comammox-driven nitrification and nosZII-driven N2O reduction in water were key processes for reducing N2O emission in LNP but decreased in HNP. The strong CH4 oxidization by Methylocystis and CO2 assimilation by algae resulted in low CH4 emissions and CO2 sink in the aquaculture pond. The Mantel test indicated that HNP increased N2O fluxes mainly through altering functional genes composition in water and sediment. Our findings suggest that there is a significant underestimation of N2O emissions without considering the significantly increased â³N2O/(â³N2O + â³N2) caused by increased nitrogen loading.
Assuntos
Gases de Efeito Estufa , Animais , Lagoas , Dióxido de Carbono/análise , Nitrogênio , Monitoramento Ambiental , Aquicultura/métodos , Água , Metano/análise , Óxido Nitroso/análise , SoloRESUMO
During the secondary thermoforming of carbon fiber-reinforced polyphenylene sulfide (CF/PPS) composites, a vital material for the aerospace field, varied thermal parameters profoundly influence the crystallization behavior of the PPS matrix. Notably, PPS exhibits a distinctive self-nucleation (SN) behavior during repeated thermal cycles. This behavior not only affects its crystallization but also impacts the processing and mechanical properties of PPS and CF/PPS composites. In this article, the effects of various parameters on the SN and non-isothermal crystallization behavior of PPS during two thermal cycles were systematically investigated by differential scanning calorimetry. It was found that the SN behavior was not affected by the cooling rate in the second thermal cycle. Furthermore, the lamellar annealing resulting from the heating process in both thermal cycles affected the temperature range for forming the special SN domain, because of the refined lamellar structure, and expelled various defects. Finally, this study indicated that to control the strong melt memory effect in the first thermal cycle, both the heating rate and processing melt temperature need to be controlled simultaneously. This work reveals that through collaborative control of these parameters, the crystalline morphology, crystallization temperature and crystallization rate in two thermal cycles are controlled. Furthermore, it presents a new perspective for controlling the crystallization behavior of the thermoplastic composite matrix during the secondary thermoforming process.
RESUMO
Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single-cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA-seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high-throughput and high-sensitivity method called snHH-seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full-length RNA-seq data is also established. snHH-seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan-cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full-length RNA at the single-nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.
Assuntos
Ecossistema , Neoplasias , Humanos , Análise de Sequência de RNA/métodos , RNA-Seq/métodos , Neoplasias/genética , RNA/genéticaRESUMO
With the widespread application of Ag+ in modern life and industry, the potential hazardous effects of Ag+ to environment and humans have attracted great concerns. Thus, effective and rapid strategies for Ag+ detection are highly desirable. In this paper, a novel ratiometric fluorescence sensor using CdSe quantum dots (QDs) has been constructed for sensitive and selective detection of Ag+, which is based on the formation of Ag2Se QDs. CdSe QDs were initially prepared and showed single wavelength emission at 510 nm. When Ag+ exists, a rising peak appeared at 650 nm and the emission at 510 nm declined, exhibiting distinct ratiometric fluorescence emission (I650/I510) characteristic with a linear response over the Ag+ concentration range of 0.01-4 µM. Significantly, the fluorescence changed from green to red. The detection limit of the constructed sensor is 1.4 nM. Furthermore, the sensing assay can be successfully applied to detect Ag+ in real water samples and living cells.
Assuntos
Compostos de Cádmio , Pontos Quânticos , Compostos de Selênio , Humanos , Corantes Fluorescentes , Espectrometria de Fluorescência , Limite de DetecçãoRESUMO
This study investigated the methane production potential of algal biomass by anerobic digestion with the addition of peroxymonosulfate (PMS), the removal of microcystin were analyzed and discussed. The microcystin concentration in the collected algal sludge was 1.20 µg/L in the liquid phase and 1393 µg/g in the algal sludge before anaerobic fermentation. The microcystin concentration decreased to 0.20-0.35 µg/L in the liquid phase and 4.16-11.51 µg/g in the sludge phase after 60 days of digestion. The initial PMS dose and residue microcystin concentration could be simulated with a logarithmic decay model (R2 > 0.87). Anaerobic digestion could recover energy from algal source in the form of methane gas, which was not affected in the presence of microcystin, and the microcystin removal rate was >99%. Digestion decreased the total contents of Cd and Zn in the liquid phase and increased the total contents of Cr and Pb in the liquid phase. The microbial community and function prediction results indicated that the PMS0.1 system had the highest methane production, which was attributed to the high abundance of Mechanosaeta (40.52%). This study provides insights into microbial mechanisms, microcystin detoxification and the heavy metal partitioning behavior of the algal biomass during methane production.
Assuntos
Metais Pesados , Esgotos , Anaerobiose , Biomassa , Reatores Biológicos , Metano , Microcistinas , Peróxidos , Esgotos/químicaRESUMO
Wearing face masks has become the new normal worldwide due to the global spread of the coronavirus disease 2019. The inhalation of microplastics due to the wearing of masks has rarely been reported. The present study used different types of commonly used masks to conduct breathing simulation experiments and investigate microplastic inhalation risk. Microplastic inhalation caused by reusing masks that underwent various treatment processes was also tested. Results implied that wearing masks considerably reduces the inhalation risk of particles (e.g., granular microplastics and unknown particles) even when they are worn continuously for 720 h. Surgical, cotton, fashion, and activated carbon masks wearing pose higher fiber-like microplastic inhalation risk, while all masks generally reduced exposure when used under their supposed time (<4 h). N95 poses less fiber-like microplastic inhalation risk. Reusing masks after they underwent different disinfection pretreatment processes can increase the risk of particle (e.g., granular microplastics) and fiber-like microplastic inhalation. Ultraviolet disinfection exerts a relatively weak effect on fiber-like microplastic inhalation, and thus, it can be recommended as a treatment process for reusing masks if proven effective from microbiological standpoint. Wearing an N95 mask reduces the inhalation risk of spherical-type microplastics by 25.5 times compared with not wearing a mask.