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Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.
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Idebenone, an antioxidant used in treating oxidative damage-related diseases, has unclear neuroprotective mechanisms. Oxidative stress affects cell and mitochondrial membranes, altering Adp-ribosyl cyclase (CD38) and Silent message regulator 3 (SIRT3) protein expression and possibly impacting SIRT3's ability to deacetylate Tumor protein p53 (P53). This study explores the relationship between CD38, SIRT3, and P53 in H2O2-injured HT22 cells treated with Idebenone. Apoptosis was detected using flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after determining appropriate H2O2 and Idebenone concentrations.In this study, Idebenone was found to reduce apoptosis and decrease P53 and Caspase3 expression in H2O2-injured HT22 cells by detecting apoptosis-related protein expression. Through bioinformatics methods, CD38 was identified as the target of Idebenone, and it further demonstrated that Idebenone decreased the expression of CD38 and increased the level of SIRT3. An increased NAD+/NADH ratio was detected, suggesting Idebenone induces SIRT3 expression and protects HT22 cells by decreasing apoptosis-related proteins. Knocking down SIRT3 downregulated acetylated P53 (P53Ac), indicating SIRT3's importance in P53 deacetylation.These results supported that CD38 was used as a target of Idebenone to up-regulate SIRT3 to deacetylate activated P53, thereby protecting HT22 cells from oxidative stress injury. Thus, Idebenone is a drug that may show great potential in protecting against reactive oxygen species (ROS) induced diseases such as Parkinson's disease, and Alzheimer's disease. And it might be able to compensate for some of the defects associated with CD38-related diseases.
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ADP-Ribosil Ciclasa 1 , Apoptosis , Estrés Oxidativo , Sirtuina 3 , Proteína p53 Supresora de Tumor , Ubiquinona , Proteína p53 Supresora de Tumor/metabolismo , Estrés Oxidativo/efectos de los fármacos , ADP-Ribosil Ciclasa 1/metabolismo , Animales , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Ratones , Sirtuina 3/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Peróxido de Hidrógeno/toxicidad , Antioxidantes/farmacología , Glicoproteínas de Membrana/metabolismo , Fármacos Neuroprotectores/farmacologíaRESUMEN
Soil carbon loss is likely to increase due to climate warming, but microbiomes and microenvironments may dampen this effect. In a 30-year warming experiment, physical protection within soil aggregates affected the thermal responses of soil microbiomes and carbon dynamics. In this study, we combined metagenomic analysis with physical characterization of soil aggregates to explore mechanisms by which microbial communities respond to climate warming across different soil microenvironments. Long-term warming decreased the relative abundances of genes involved in degrading labile compounds (e.g. cellulose), but increased those genes involved in degrading recalcitrant compounds (e.g. lignin) across aggregate sizes. These changes were observed in most phyla of bacteria, especially for Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, and Planctomycetes. Microbial community composition was considerably altered by warming, leading to declined diversity for bacteria and fungi but not for archaea. Microbial functional genes, diversity, and community composition differed between macroaggregates and microaggregates, indicating the essential role of physical protection in controlling microbial community dynamics. Our findings suggest that microbes have the capacity to employ various strategies to acclimate or adapt to climate change (e.g. warming, heat stress) by shifting functional gene abundances and community structures in varying microenvironments, as regulated by soil physical protection.
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OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 107 CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- ß -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-ß-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS: CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
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Unravelling biosphere feedback mechanisms is crucial for predicting the impacts of global warming. Soil priming, an effect of fresh plant-derived carbon (C) on native soil organic carbon (SOC) decomposition, is a key feedback mechanism that could release large amounts of soil C into the atmosphere. However, the impacts of climate warming on soil priming remain elusive. Here, we show that experimental warming accelerates soil priming by 12.7% in a temperate grassland. Warming alters bacterial communities, with 38% of unique active phylotypes detected under warming. The functional genes essential for soil C decomposition are also stimulated, which could be linked to priming effects. We incorporate lab-derived information into an ecosystem model showing that model parameter uncertainty can be reduced by 32-37%. Model simulations from 2010 to 2016 indicate an increase in soil C decomposition under warming, with a 9.1% rise in priming-induced CO2 emissions. If our findings can be generalized to other ecosystems over an extended period of time, soil priming could play an important role in terrestrial C cycle feedbacks and climate change.
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Ecosistema , Pradera , Suelo , Carbono , Cambio ClimáticoRESUMEN
Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury (ALI), including acute respiratory distress syndrome (ARDS), in patients after cardiac surgery. We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles (eEVs) with components of coagulation and acute inflammatory responses. However, the mechanism underlying the onset of ALI owing to the release of eEVs after cardiopulmonary bypass, remains unclear. Plasma plasminogen-activated inhibitor-1 (PAI-1) and eEV levels were measured in patients with cardiopulmonary bypass. Endothelial cells and mice (C57BL/6, Toll-like receptor 4 knockout (TLR4-/-) and inducible nitric oxide synthase knockout (iNOS-/-)) were challenged with eEVs isolated from PAI-1-stimulated endothelial cells. Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass. Plasma PAI-1 elevation was positively correlated with the increase in eEVs. The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS. The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade identified as the Janus kinase 2/3 (JAK2/3)-signal transducer and activator of transcription 3 (STAT3)-interferon regulatory factor 1 (IRF-1) pathway, along with iNOS induction, and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice, ultimately contributing to ALI. ALI could be attenuated by JAK2/3 or STAT3 inhibitors (AG490 or S3I-201, respectively), and was relieved in TLR4-/- and iNOS-/- mice. eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1 (FSTL1), and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS. Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs, which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop, leading to ALI/ARDS after cardiac surgery. Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.
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Lesión Pulmonar Aguda , Vesículas Extracelulares , Proteínas Relacionadas con la Folistatina , Síndrome de Dificultad Respiratoria , Animales , Humanos , Ratones , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Células Endoteliales/metabolismo , Vesículas Extracelulares/metabolismo , Proteínas Relacionadas con la Folistatina/metabolismo , Proteínas Relacionadas con la Folistatina/uso terapéutico , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Pulmón/metabolismo , Ratones Endogámicos C57BL , Inhibidor 1 de Activador Plasminogénico/metabolismo , Inhibidor 1 de Activador Plasminogénico/uso terapéutico , Síndrome de Dificultad Respiratoria/etiología , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/uso terapéuticoRESUMEN
Purpose: The purpose of this study is to develop a freehand scan three-dimensional (3D) shear wave elasticity imaging (SWEI) method for characterizing the anisotropy of elastic properties in biological tissues. The motivation behind this work lies in addressing the limitations of traditional two-dimensional (2D) SWEI, which only measures shear wave speeds in a single direction, as well as fulfilling the clinical demand for improved medical imaging. Approach: Our imaging system utilizes a high-definition optical camera to continuously track the ultrasonic transducer, collecting spatial position-angle data of the transducer and corresponding two-dimensional SWEI data. By reconstructing three-dimensional SWEI images using these data, we achieved freehand SWEI. Results: We validated the accuracy of 2D SWEI on a standard elastic phantom, and then performed 3D SWEI on the pork tenderloin and the triceps brachii of two volunteers. We obtained shear wave speed of 1.82 to 3.12 m/s in the pork tenderloin, shear wave speed of 1.16 to 2.36 m/s in the triceps brachii of non-exercising volunteers, and shear wave speed of 0.55 to 1.63 m/s in the triceps brachii of exercising volunteers, and the maximum shear wave speed directions were generally aligned with the orientation of muscle fibers. Conclusions: We proposed a method that can overcome the limitations of 2D-SWEI regarding imaging angle while also extending the imaging angle of 3D-SWEI, which could have significant implications for improving the accuracy and safety of medical diagnoses.
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The influence of the P-M-P bite angle in diphosphine ligands on selectivity has been observed in various catalytic reactions. A better understanding of the ligand bite angle concept is important for the rational design of efficient catalytic systems. In the present work, the mechanism of cobalt-catalyzed C-H functionalization of aldehydes with enynes and how the diphosphine ligands alter regioselectivity were investigated by density functional theory (DFT) calculations. The catalytic cycle is initiated by the oxidative cyclization of enynes rather than the oxidative addition of aldehydes. Regioselectivity arises from competing σ-bond metathesis and migratory insertion steps, in which the steric effects of diphosphine ligands are the dominant factors influencing the activation barriers. The calculations indicate that σ-bond metathesis is more challenging and its feasibility is highly dependent on the ligand bite angle. The improved mechanistic understanding will enable further design of transition-metal-catalyzed selective cyclization reactions.
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OBJECTIVE: To investigate the effect of resveratrol (RSV) on the proliferation of multiple myeloma (MM) cells and its molecular mechanism. METHODS: MM cells (MM1.S, RPMI-8226 and U266) were treated with different concentrations of RSV for 24-72 h. The effect of RSV on the proliferation of MM cells was detected by CCK-8 (cell counting kit-8) assay. RPMI-8226 cells were divided into RSV, miR-21 mimic, RSV+miR-21 mimic, miR-21 inhibitor and RSV+miR-21 inhibitor groups, and transfected with corresponding plasmids. The cell cycle distribution of each group was detected by flow cytometry with propidium iodide (PI) single staining. The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining. The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR. The expression of KLF5 protein in each group was detected by Western blot. RESULTS: RSV inhibited the proliferation and induced apoptosis of MM cells in a time- and dose-dependent manner. After the MM cells were treated with RSV, the number of cells in sub-G1 phase was increased, and that in G2/M phase was decreased. Moreover, RSV significantly downregulated the expression of miR-21 in MM cells, and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV. CONCLUSION: RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.
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MicroARNs , Mieloma Múltiple , Humanos , Resveratrol/farmacología , Mieloma Múltiple/metabolismo , Proliferación Celular , Línea Celular Tumoral , Apoptosis , MicroARNs/genéticaRESUMEN
Sulfur mustard (SM) is an important chemical warfare agent (CWA) and has been used frequently in various conflicts. It is important to develop a facile, rapid, sensitive and selective detection method for SM. In this work, we constructed a novel fluorescent probe PCS capable of generating active sensing species for rapid and selective detection of SM and its simulant CEES (2-chloroethyl ethyl sulfide). PCS exhibits excellent chemical and photostability and can generate reactive species in situ for rapid (within 90 s, at 60 °C) and selective detection of SM and CEES in solution with high sensitivity (â¼nM level). Moreover, PCS could enable the detection of mustards in situ. A test strip with PCS and KOH was prepared and realized the sensitive and selective detection of CEES in the gas phase. In addition, the PCS probe can realize facile and rapid detection of CEES-contaminated surfaces by spraying its sensing system (ethanol solution containing PCS and KOH). The sensing mechanism was well demonstrated through the separation and characterization of the sensing product.
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Sustancias para la Guerra Química , Gas Mostaza , Gas Mostaza/análisis , Gas Mostaza/química , Colorantes Fluorescentes , Sustancias para la Guerra Química/análisisRESUMEN
Hemorrhagic fever with renal syndrome (HFRS), a natural epidemic disease caused by hantavirus (HV), is one of the viral diseases that pose a major threat to our health. Considering the increasing number of atypical-onset cases reported in some countries, it is important to be familiar with the symptoms of HFRS and the signs of HV infection. This report describes the case of a 55-year-old man with complaints of fever, vomiting, and diarrhea. His symptoms showed no significant improvement after routine anti-infective, antipyretic, and other symptomatic supportive treatments administered at a local clinic. During these treatments, the patient had progressive oliguria; after 3 days, he also developed multiple organ failures, such as the liver and kidney, and was examined for positive serum IgM antibodies to hemorrhagic fever during treatment at our hospital. The patient was finally diagnosed with HFRS followed by multiple organ failure. After antiviral therapy, including ribavirin, piperacillin, and tazobactam, continuous renal replacement therapy, fluid metabolism adjustment, and related supportive therapy were administered, which improved his liver and kidney function. He was discharged on the 25th day after hospitalization. It is difficult to manage patients who develop multiple organ failure after HFRS. Moreover, this condition is rare in clinical settings, with fever being the initial indication. For diseases with unknown origin such as refractory fever and diarrhea, it is crucial to differentiate them from common pathogenic infection and HV infections to provide timely treatment that improves the prognosis of patients.
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Fiebre Hemorrágica con Síndrome Renal , Orthohantavirus , Masculino , Humanos , Persona de Mediana Edad , Fiebre Hemorrágica con Síndrome Renal/complicaciones , Fiebre Hemorrágica con Síndrome Renal/diagnóstico , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Insuficiencia Multiorgánica/etiología , Riñón , Fiebre/complicaciones , Diarrea/complicacionesRESUMEN
Though common, the extraction of rectal foreign bodies is still a great challenge for surgeons. The foreign body's position can usually be verified by plain abdominal radiography. Given the potential of sexually transmitted disease, screening for HIV, hepatitis, and syphilis is warranted prior to intervention. The utilization and selection of surgical instruments need to be flexible, ingenious, and innovative.
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Cuerpos Extraños , Recto , Humanos , Recto/diagnóstico por imagen , Recto/cirugía , Zea mays , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugíaRESUMEN
Migratory insertions of alkenes into metal-carbon (M-C) bonds are elementary steps in diverse catalytic processes. In the present work, a radical-type migratory insertion that involves concerted but asynchronous M-C homolysis and radical attack was revealed by computations. Inspired by the radical nature of the proposed migratory insertion, a distinct cobalt-catalyzed radical-mediated carbon-carbon (C-C) cleavage mechanism was proposed for alkylidenecyclopropanes (ACPs). This unique C-C activation is key to rationalizing the experimentally observed selectivity for the coupling between benzamides and ACPs. Furthermore, the C(sp2)-H activation in the coupling reaction occurs via the proton-coupled electron transfer (PCET) mechanism rather than the originally proposed concerted metalation-deprotonation (CMD) pathway. The ring opening strategy may stimulate further development and discovery of novel radical transformations.
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Density dependence in an ecological community has been observed in many macro-organismal ecosystems and is hypothesized to maintain biodiversity but is poorly understood in microbial ecosystems. Here, we analyze data from an experiment using quantitative stable isotope probing (qSIP) to estimate per-capita growth and mortality rates of bacterial populations in soils from several ecosystems along an elevation gradient which were subject to nutrient addition of either carbon alone (glucose; C) or carbon with nitrogen (glucose + ammonium-sulfate; C + N). Across all ecosystems, we found that higher population densities, quantified by the abundance of genomes per gram of soil, had lower per-capita growth rates in C + N-amended soils. Similarly, bacterial mortality rates in C + N-amended soils increased at a significantly higher rate with increasing population size than mortality rates in control and C-amended soils. In contrast to the hypothesis that density dependence would promote or maintain diversity, we observed significantly lower bacterial diversity in soils with stronger negative density-dependent growth. Here, density dependence was significantly but weakly responsive to nutrients and was not associated with higher bacterial diversity.
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Ecosistema , Suelo , Microbiología del Suelo , Bacterias , CarbonoRESUMEN
Gd3+-doped quantum dots (QDs) have been widely used as small-sized bifunctional contrast agents for fluorescence/magnetic resonance (FL/MR) dual-modality imaging. However, Gd3+ doping will always compromise the FL of host QDs. Therefore, balancing the Gd3+ doping and the optical properties of QDs is crucial for constructing high-performance bifunctional nanoprobes. Additionally, most paramagnetic QDs are synthesized in the organic phase and need to be transferred to the aqueous phase for bioimaging. Herein, ingeniously designed shell-doped Cu-In-S/ZnS:Gd3+ QDs have been prepared in the aqueous phase. It has been demonstrated that isolating paramagnetic Gd3+ from fluorescent Cu-In-S core via doping Gd3+ into ZnS shell not only avoided the decrease of FL quantum yield (QY), but also ensured the water accessibility of paramagnetic Gd3+ ions, by which the FL QY and r1 relaxivity of Cu-In-S/ZnS:Gd3+ QDs achieved as much as 15.6% and 15.33 mM-1·s-1, respectively. These high-performance QDs with excellent stability, low biotoxicity, and good tumor permeability were successfully applied for in vivo tumor FL/MR dual-modality imaging, and have shown significant potential in the precision detection and diagnosis of diseases.
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Neoplasias , Puntos Cuánticos , Humanos , Sulfuros , Compuestos de Zinc , Neoplasias/patología , AguaRESUMEN
Study of life history strategies may help predict the performance of microorganisms in nature by organizing the complexity of microbial communities into groups of organisms with similar strategies. Here, we tested the extent that one common application of life history theory, the copiotroph-oligotroph framework, could predict the relative population growth rate of bacterial taxa in soils from four different ecosystems. We measured the change of in situ relative growth rate to added glucose and ammonium using both 18O-H2O and 13C quantitative stable isotope probing to test whether bacterial taxa sorted into copiotrophic and oligotrophic groups. We saw considerable overlap in nutrient responses across most bacteria regardless of phyla, with many taxa growing slowly and few taxa that grew quickly. To define plausible life history boundaries based on in situ relative growth rates, we applied Gaussian mixture models to organisms' joint 18O-13C signatures and found that across experimental replicates, few taxa could consistently be assigned as copiotrophs, despite their potential for fast growth. When life history classifications were assigned based on average relative growth rate at varying taxonomic levels, finer resolutions (e.g., genus level) were significantly more effective in capturing changes in nutrient response than broad taxonomic resolution (e.g., phylum level). Our results demonstrate the difficulty in generalizing bacterial life history strategies to broad lineages, and even to single organisms across a range of soils and experimental conditions. We conclude that there is a continued need for the direct measurement of microbial communities in soil to advance ecologically realistic frameworks.