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OBJECTIVE: The present study aimed to investigate the circadian rhythm and clinical characteristics of patients with acute myocardial infarction (AMI) combined with obstructive sleep apnea (OSA). METHODS: Patients with AMI combined with OSA were enrolled in the study, and those that met the inclusion criteria were divided into three time-period groups based on their sleep-wake rhythm (22:00-5:59, 6:00-13:59, and 14:00-21:59). The differences between the three groups of patients in sleep-monitoring data, blood routine, biochemical indicators, and coronary angiographic parameters were analyzed and compared. Count data were expressed as the number of cases, and the chi-square test was used for statistical analysis. Continuous data were expressed as mean ± standard deviation, and analysis of variance was used for the statistical analysis of these data. The characteristics of circadian rhythm and clinical features in patients with AMI combined with OSA were analyzed. RESULTS: Of the 148 patients, 90/148 (61%) had chest pain and 58/148 (39%) had non-chest pain symptoms. In the 22:00-05:59 group, there were 70/148 (47%) patients with AMI (of these, 46/70 [66%] had chest pain). In the 06:00-13:59 period group, there were 44/148 (30%) patients with AMI (of these, 26/44 [60%] had chest pain). In the 14:00-21:59 period group, there were 34/148 (23%) patients with AMI (of these, 17/34 [50%] had chest pain). There was no statistically significant difference in the apnea-hypopnea index (AHI) and SYNTAX score between patients in the 22:00-5:59 and 6:00-13:59 groups. However, the AHI and SYNTAX scores in the 22:00-5:59 and 6:00-13:59 groups were higher than those in the 14:00-21:59 group, and the differences were statistically significant. In patients in the 22:00-5:59 group, the levels of serum D-dimer (DD), hemoglobin (Hb), and oxygen desaturation index (ODI3) were higher, the sleep mean oxygen saturation (MeanSaO2 ) was lower and the percentage of nighttime spent with oxygen saturation of less than 90% (Tsat90 ) and less than 85% (Tsat85 ) was longer. CONCLUSION: The peak period for the onset of AMI in patients with OSA was 22:00-5:59, and the incidence of chest pain was high. During this period, patients had higher DD and Hb, higher ODI3, lower MeanSaO2 during sleep, and longer TSat90 and TSat85 . During the 22:00-5:59 and 6:00-13:59 periods, patients had higher AHI and a higher SYNTAX score.
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Infarto do Miocárdio , Apneia Obstrutiva do Sono , Ritmo Circadiano , Eletrocardiografia , Humanos , Infarto do Miocárdio/complicações , Oxigênio , Dor , Polissonografia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnósticoRESUMO
Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA, a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL phosphorylation in a positive feedback loop. Furthermore, deletion of PUMA partially rescues necroptosis-mediated developmental defects in FADD-deficient embryos. Collectively, our results reveal a signal amplification mechanism mediated by PUMA and cytosolic DNA sensors that is involved in TNF-driven necroptotic death in vitro and in vivo.
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Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Proteínas de Ligação a DNA/metabolismo , Glicoproteínas/metabolismo , Proteínas de Membrana/metabolismo , Necrose/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Citosol/metabolismo , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/genética , Glicoproteínas/genética , Humanos , Proteínas de Membrana/genética , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Necrose/genética , Necrose/fisiopatologia , Fosforilação , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas de Ligação a RNA , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Supressoras de Tumor/genéticaRESUMO
The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP. Expression of the individual gene, such as PGAP1, PIG-F, or PIG-C, into BxPC-3 cells does not result in phosphoinositide-specific phospholipase C sensitivity of PrP. However, when PIG-F but not PIG-P is expressed in PGAP1-expressing BxPC-3 cells, PrP on the surface of the cells becomes phosphoinositide-specific phospholipase C-sensitive. Thus, low expression of PIG-F and PGAP1 is the major factor contributing to the accumulation of pro-PrP. More importantly, BxPC-3 cells expressing GPI-anchored PrP migrate much slower than BxPC-3 cells bearing pro-PrP. In addition, GPI-anchored PrP-bearing AsPC-1 cells also migrate slower than pro-PrP bearing BxPC-3 cells, although both cells express filamin A. "Knocking out" PRNP in BxPC-3 cell drastically reduces its migration. Collectively, these results show that multiple gene irregularity in BxPC-3 cells is responsible for the formation of pro-PrP, and binding of pro-PrP to filamin A contributes to enhanced tumor cell motility.
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Movimento Celular , Glicosilfosfatidilinositóis/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Príons/metabolismo , Processamento de Proteína Pós-Traducional , Animais , Células CHO , Cricetinae , Cricetulus , Filaminas/genética , Filaminas/metabolismo , Glicosilfosfatidilinositóis/genética , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/patologia , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Príons/genéticaRESUMO
BACKGROUND: Axillary lymph nodes (ALN) are the most commonly involved site of disease in breast cancer that has spread outside the primary lesion. Although sentinel node biopsy is a reliable way to manage ALN, there are still no good methods of predicting ALN status before surgery. Since morbidity in breast cancer surgery is predominantly related to ALN dissection, predictive models for lymph node involvement may provide a way to alert the surgeon in subgroups of patients. MATERIAL AND METHODS: A total of 1325 invasive breast cancer patients were analyzed using tumor biological parameters that included age, tumor size, grade, estrogen receptor, progesterone receptor, lymphovascular invasion, and HER2, to test their ability to predict ALN involvement. A support vector machine (SVM) was used as a classification model. The SVM is a machine-learning system developed using statistical learning theories to classify data points into 2 classes. Notably, SVM models have been applied in bioinformatics. RESULTS: The SVM model correctly predicted ALN metastases in 74.7% of patients using tumor biological parameters. The predictive ability of luminal A, luminal B, triple negative, and HER2 subtypes using subgroup analysis showed no difference, and this predictive performance was inferior, with only 60% accuracy. CONCLUSIONS: With an SVM model based on clinical pathologic parameters obtained in the primary tumor, it is possible to predict ALN status in order to alert the surgeon about breast cancer counseling and in decision-making for ALN management.
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Axila/patologia , Neoplasias da Mama/patologia , Linfonodos/patologia , Metástase Linfática/diagnóstico , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Máquina de Vetores de SuporteRESUMO
The outer surface of chorionic villi in the human placenta consists of a single multinucleated cell called the syncytiotrophoblast (STB). The unique cellular ultrastructure of the STB presents challenges in deciphering its gene expression signature at the single-cell level, as the STB contains billions of nuclei in a single cell. There are many gaps in understanding the molecular mechanisms and developmental trajectories involved in STB formation and differentiation. To identify the underlying control of the STB, we performed comparative single nucleus (SN) and single cell (SC) RNA sequencing on placental tissue and tissue-derived trophoblast organoids (TOs). We found that SN was essential to capture the STB population from both tissue and TOs. Differential gene expression and pseudotime analysis of TO-derived STB identified three distinct nuclear subtypes reminiscent of those recently identified in vivo . These included a juvenile nuclear population that exhibited both CTB and STB marker expression, a population enriched in genes involved in oxygen sensing, and a fully differentiated subtype. Notably, suspension culture conditions of TOs that restore the native orientation of the STB (STB out ) showed elevated expression of canonical STB markers and pregnancy hormones, along with a greater proportion of the terminally differentiated mature STB subtype, compared to those cultivated with an inverted STB polarity (STB in ). Gene regulatory analysis identified novel markers of STB differentiation conserved in tissue and TOs, including the chromatin remodeler RYBP, that exhibited STB-specific RNA and protein expression. Finally, we compared STB gene expression signatures amongst first trimester tissue, full-term tissue, and TOs, identifying many commonalities but also notable variability across each sample type. This indicates that STB gene expression is responsive to its environmental context. Our findings emphasize the utility of TOs to accurately model STB differentiation and the distinct nuclear subtypes observed in vivo , offering a versatile platform for unraveling the molecular mechanisms governing STB functions in placental biology and disease.
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The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance of understanding these mechanisms and challenges in replicating trophoblast-pathogen interactions using in vitro models, we tested an existing stem-cell-derived model of trophoblast development for its relevance to infection with Toxoplasma gondii. We grew human trophoblast stem cells (TSCT) under conditions leading to either syncytiotrophoblast (TSSYN) or cytotrophoblast (TSCYT) and infected them with T. gondii. We evaluated T. gondii proliferation and invasion, cell ultrastructure, as well as for transcriptome changes after infection. TSSYNs cells showed similar ultrastructure compared to primary cells and villous explants when analyzed by transmission electron microscopy and scanning electron microscopy (SEM), a resistance to T. gondii adhesion could be visualized on the SEM level. Furthermore, TSSYNs were highly refractory to parasite adhesion and replication, while TSCYTs were not. RNA-seq data on mock-treated and infected cells identified differences between cell types as well as how they responded to T. gondii infection. We also evaluated if TSSC-derived SYNs and CYTs had distinct resistance profiles to another vertically transmitted facultative intracellular pathogen, Listeria monocytogenes. We demonstrate that TSSYNs are highly resistant to L. monocytogenes, while TSCYTs are not. Like T. gondii, TSSYN resistance to L. monocytogenes was at the level of bacterial adhesion. Altogether, our data indicate that stem-cell-derived trophoblasts recapitulate resistance profiles of primary cells to T. gondii and highlight the critical importance of the placental surface in cell-autonomous resistance to teratogens.IMPORTANCECongenital toxoplasmosis can cause a devastating consequence to the fetus. To reach the fetus's tissues, Toxoplasma gondii must cross the placenta barrier. However, how this parasite crosses the placenta and the precise molecular mechanisms of placental resistance to this parasite are still unknown. In this study, we aimed to characterize a new cellular model of human trophoblast stem cells to determine their resistance, susceptibility, and response to T. gondii. Syncytiotrophoblast derived from trophoblast stem cells recapitulate the resistance profile similarly to placenta cells. We also showed that these cells are highly resistant to Listeria monocytogenes, at the level of bacterial adhesion. Our results suggest that resisting pathogen adhesion/attachment may be a generalized mechanism of syncytiotrophoblast resistance, and trophoblast stem cells represent a promising model to investigate cell-intrinsic mechanisms of resistance to pathogen adhesion and replication.
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Listeria monocytogenes , Toxoplasma , Trofoblastos , Trofoblastos/microbiologia , Trofoblastos/parasitologia , Toxoplasma/genética , Toxoplasma/crescimento & desenvolvimento , Toxoplasma/fisiologia , Toxoplasma/ultraestrutura , Humanos , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/genética , Listeria monocytogenes/fisiologia , Feminino , Gravidez , Adesão Celular , Placenta/microbiologia , Placenta/parasitologia , Toxoplasmose/parasitologia , Células-TroncoRESUMO
Human trophoblast organoids (TOs) are a three-dimensional ex vivo culture model that can be used to study various aspects of placental development, physiology, and pathology. Previously, we showed that TOs derived from full-term human placental tissue could be used as models of trophoblast innate immune signaling and teratogenic virus infections. Here, we developed a method to culture TOs under conditions that recapitulate the cellular orientation of chorionic villi in vivo , with the multi-nucleated syncytiotrophoblast (STB) localized to the outer surface of organoids and the proliferative cytotrophoblasts (CTBs) located on the inner surface. We show that standard TOs containing the STB layer inside the organoid (STB in ) develop into organoids containing the STB on the outer surface (STB out ) when cultured in suspension with gentle agitation. STB out organoids secrete higher levels of select STB-associated hormones and cytokines, including human chorionic gonadotropin (hCG) and interferon (IFN)-λ2. Using membrane capacitance measurements, we also show that the outermost surface of STB out organoids contain large syncytia comprised of >50 nuclei compared to STB in organoids that contain small syncytia (<10 nuclei) and mononuclear cells. The growth of TOs under conditions that mimic the cellular orientation of chorionic villi in vivo thus allows for the study of a variety of aspects of placental biology under physiological conditions.
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Purpose: Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30-50%. Therefore, novel strategies to treat sepsis are urgently needed. Methods: Andrographolide (AD), the main active ingredient of Andrographis paniculata, reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Hence, this study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms. Results: Results showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity. Conclusion: These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis.
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3D genomics mainly focuses on the 3D position of single genes at the cell level, while spatial genomics focuses more on the tissue level. In this exciting new era of 3D/spatial genomics, half-century old FISH and its derivative methods, including Tn5-FISH, play important roles. In this review, we introduce the Tn5-FISH we developed recently, and present six different applications published by our collaborators and us, based on (Tn5-)FISH, which can be either general BAC clone-based FISH or Tn5-FISH. In these interesting cases, (Tn5-)FISH demonstrated its vigorous ability of targeting sub-chromosomal structures across different diseases and cell lines (leukemia, mESCs (mouse embryonic stem cells), and differentiation cell lines). Serving as an effective tool to image genomic structures at the kilobase level, Tn5-FISH holds great potential to detect chromosomal structures in a high-throughput manner, thus bringing the dawn for new discoveries in the great era of 3D/spatial genomics.
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The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance to understand these mechanisms and challenges in replicating trophoblast- pathogen interactions using in vitro models, we tested an existing stem-cell derived model of trophoblast development for its relevance to infection with Toxoplasma gondii . We grew human trophoblast stem cells (TS CT ) under conditions leading to either syncytiotrophoblast (TS SYN ) or cytotrophoblast (TS CYT ) and infected them with T. gondii . We evaluated T. gondii proliferation and invasion, cell ultrastructure, as well as for transcriptome changes after infection. TS SYNs cells showed similar ultrastructure compared to primary cells and villous explants when analyzed by TEM and SEM, a resistance to T. gondii adhesion could be visualized on the SEM level. Furthermore, TS SYNs were highly refractory to parasite adhesion and replication, while TS CYT were not. RNA-seq data on mock-treated and infected cells identified differences between cell types as well as how they responded to T. gondii infection. We also evaluated if TS SC -derived SYNs and CYTs had distinct resistance profiles to another vertically transmitted facultative intracellular pathogen, Listeria monocytogenes . We demonstrate that TS SYNs are highly resistant to L. monocytogenes , while TS CYTs are not. Like T. gondii , TS SYN resistance to L. monocytogenes was at the level of bacterial adhesion. Altogether, our data indicate that stem-cell derived trophoblasts recapitulate resistance profiles of primary cells to T. gondii and highlight the critical importance of the placental surface in cell-autonomous resistance to teratogens.
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Surfactant foam (SF) can be used to remediate petroleum-contaminated soil because of its easy transfer to inhomogeneous and low-permeability formations. Nanoparticles (NPs) not only stabilize SF under extreme conditions but also impart various functions, aiding the removal of petroleum contaminants. This review discusses the stabilization mechanisms of nanoparticle-stabilized SF (NP-SF) as well as the effects of NP size, chargeability, wettability, and NP-to-surfactant ratio on foam stability. SF stabilized by inert SiO2 NPs is most commonly used to remediate soil contaminated with crude oil and diesel. Low dose of SF stabilized by nano zero-valent iron is cost-effective for treating soil contaminated with chlorinated organics and heavy metal ions. The efficiency and recyclability of Al2O3/Fe3O4 NPs in the remediation of diesel and crude oil contamination could be enhanced by applying a magnetic field. This review provides a theoretical basis and practical guidelines for developing functional NP-SF to improve the remediation of petroleum-contaminated soils. Future research should focus on the structural design of photocatalytic NPs and the application of catalytic NP-SF in soil remediation.
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Nanopartículas , Petróleo , Surfactantes Pulmonares , Tensoativos , Dióxido de Silício , Aerossóis , SoloRESUMO
The facile and low-cost fabrication of fluorine-free superhydrophobic metal surfaces for anticorrosion remains a challenging issue. Here, we report a superhydrophobic coating based on polyacrylate/SiO2 nanoparticles/graphene oxide sheets through a simple yet environmentally friendly method. The as-prepared composite coating sprayed on metal surfaces exhibits excellent superhydrophobic and corrosion-resistant properties. Furthermore, the coating surface possesses good anti-wear performance and remains superhydrophobic after harsh abrasion tests. Prospectively, the developed non-fluorinated superhydrophobic coating opens up opportunities for the application in industrial anticorrosion field.
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Efficient and safe storage of hydrogen is an important link in the process of hydrogen energy utilization. Hydrogen storage with hydrogen storage materials as the medium has the characteristics of high volumetric hydrogen storage density and good safety. Among many hydrogen storage materials, only rare earth-based and titanium-based hydrogen storage alloys have been applied thus far. In this work, current state-of-the-art research and applications of Ti-Mn hydrogen storage alloys are reviewed. Firstly, the hydrogen storage properties and regulation methods of binary to multicomponent Ti-Mn alloys are introduced. Then, the applications of Ti-Mn alloys in hydrogen storage, hydrogen compression and catalysis are discussed. Finally, the future research and development of Ti-Mn hydrogen storage alloys is proposed.
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Agricultural biochar and arbuscular mycorrhizal fungi were used to promote the growth of Phragmites in the structural damaged and nutritional imbalanced littoral zone soils. Wheat straw biochar played a significant role in improving soil porosity and supplementing available phosphorus to 79.20 ± 3.20 mg/kg, compared with CK at 17.50 ± 0.88 mg/kg. The addition of Diversispora versiformis improved the plant net photosynthetic rate reaching up to 25.66 ± 0.65 µmol·m-2·s-1, which was 36.60 % higher than CK. The combination of biochar and fungi contributed to the whole plant dry weight biomass of 32.30 % and 234.00 % higher than the single biochar or AMF amendment groups, respectively. Meanwhile, the analysis of microbial co-occurrence networks showed the most relevant networks node species were mainly Talaromyces, Chaetomiacea and Gemmatimonadetes etc. Root lipid metabolite of Glycerophospholines further proved that phosphorus utilization was also enhanced endogenously in the rhizosphere soil. These results indicate that the combination of biochar and arbuscular mycorrhizal fungi play synergic role in enhancing phosphorus utilization endogenously and exogenously.
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Micorrizas , Rizosfera , Carvão Vegetal , Lipídeos , Micorrizas/metabolismo , Fósforo/metabolismo , Raízes de Plantas/metabolismo , Poaceae/metabolismo , Solo/química , Microbiologia do SoloRESUMO
Non-aqueous phase liquids (NAPLs) pose a serious risk to the soil-groundwater environment. Coupling surfactants with in situ chemical oxidation (ISCO) technology is a promising strategy, which is attributed to the enhanced desorption and solubilization efficiency of NAPL contaminants. However, the complex interactions among surfactants, oxidation systems, and NAPL contaminants have not been fully revealed. This review provides a comprehensive overview on the development of surfactant-coupled ISCO technology focusing on the effects of surfactants on oxidation systems and NAPLs degradation behavior. Specifically, we discussed the compatibility between surfactants and oxidation systems, including the non-productive consumption of oxidants by surfactants, the role of surfactants in catalytic oxidation systems, and the loss of surfactants solubilization capacity during oxidation process. The effect of surfactants on the degradation behavior of NAPL contaminants is then thoroughly summarized in terms of degradation kinetics, byproducts and degradation mechanisms. This review demonstrates that it is crucial to minimize the negative effects of surfactants on NAPL contaminants oxidation process by fully understanding the interaction between surfactants and oxidation systems, which would promote the successful implementation of surfactant-coupled ISCO technology in remediation of NAPLs-contaminated sites.
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Água Subterrânea , Surfactantes Pulmonares , Poluentes do Solo , Poluentes Químicos da Água , Oxidantes , Solo , Tensoativos , Poluentes Químicos da Água/análiseRESUMO
Infections at the maternal-fetal interface can directly harm the fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts and the maternal decidua must provide antimicrobial defenses at this critical interface without compromising its integrity. Here, we developed matched trophoblast (TO) and decidua organoids (DO) from human placentas to define the relative contributions of these cells to antiviral defenses at the maternal-fetal interface. We demonstrate that TO and DO basally secrete distinct immunomodulatory factors, including the constitutive release of the antiviral type III interferon IFN-λ2 from TOs, and differentially respond to viral infections through the induction of organoid-specific factors. Finally, we define the differential susceptibility and innate immune signaling of TO and DO to human cytomegalovirus (HCMV) and develop a co-culture model of TO and DO which showed that trophoblast-derived factors protect decidual cells from HCMV infection. Our findings establish matched TO and DO as ex vivo models to study vertically transmitted infections and highlight differences in innate immune signaling by fetal-derived trophoblasts and the maternal decidua.
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Decídua , Trofoblastos , Antivirais , Feminino , Humanos , Imunidade Inata , Organoides , Placenta , GravidezRESUMO
TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using trophoblasts as a model for cell fusion, we demonstrate that Ca2+ influx through the Ca2+ permeable transient receptor potential vanilloid channel TRPV4 is critical for TMEM16F activation and plays a role in subsequent human trophoblast fusion. GSK1016790A, a TRPV4 specific agonist, robustly activates TMEM16F in trophoblasts. We also show that TRPV4 and TMEM16F are functionally coupled within Ca2+ microdomains in a human trophoblast cell line using patch-clamp electrophysiology. Pharmacological inhibition or gene silencing of TRPV4 hinders TMEM16F activation and subsequent trophoblast syncytialization. Our study uncovers the functional expression of TRPV4 and one of the physiological activation mechanisms of TMEM16F in human trophoblasts, thus providing us with novel strategies to regulate CaPLSase activity as a critical checkpoint of physiologically and disease-relevant cell fusion events.
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Anoctaminas/metabolismo , COVID-19 , Infecções por HIV , Proteínas de Transferência de Fosfolipídeos/metabolismo , Cálcio/metabolismo , Feminino , Humanos , Placenta/metabolismo , Gravidez , RNA Viral , SARS-CoV-2 , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Trofoblastos/metabolismoRESUMO
Magnetic reconnection is a multi-faceted process of energy conversion in astrophysical, space and laboratory plasmas that operates at microscopic scales but has macroscopic drivers and consequences. Solar flares present a key laboratory for its study, leaving imprints of the microscopic physics in radiation spectra and allowing the macroscopic evolution to be imaged, yet a full observational characterization remains elusive. Here we combine high resolution imaging and spectral observations of a confined solar flare at multiple wavelengths with data-constrained magnetohydrodynamic modeling to study the dynamics of the flare plasma from the current sheet to the plasmoid scale. The analysis suggests that the flare resulted from the interaction of a twisted magnetic flux rope surrounding a filament with nearby magnetic loops whose feet are anchored in chromospheric fibrils. Bright cusp-shaped structures represent the region around a reconnecting separator or quasi-separator (hyperbolic flux tube). The fast reconnection, which is relevant for other astrophysical environments, revealed plasmoids in the current sheet and separatrices and associated unresolved turbulent motions.
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To promote the colonization of Phragmites in Cd polluted, nutrient deprived and structural damaged soil, the combined remediation using chemical and microbial modifiers were carried out in potting experiments. The co-application of Diversispora versiformis and sodium bentonite significantly improved the soil structure and phosphorus utilization of the plant, while decreasing the content of cadmium bound by diethylenetriaminepentaacetic acid by 77.72%. As a result, the Phragmites height, tillers, and photosynthetic capacity were increased by 71.60%, 38.37%, and 17.54%, respectively. Further analysis suggested the co-application increased the abundance of phosphorus-releasing microbial communities like Pseudomonassp. and Gemmatimonadetes. Results of rhizosphere metabolites also proved that the signal molecule of lysophosphatidylcholine regulated the phosphorus fixation and utilization by the plant. This work finds composite modifiers are effective in the colonization of Phragmites in Cd contaminated soil by decreasing the bioavailable Cd, increasing the abundance of functional microbial communities and regulating the phosphorus fixation.