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N-glycosylation is a highly heterogeneous post-translational modification that modulates protein function. Defects in N-glycosylation are directly linked to various human diseases. Despite the importance of quantifying N-glycans with high precision, existing glycoinformatics tools are limited. Here, we developed nQuant, a glycoinformatics tool that enables label-free and isotopic labeling quantification of N-glycomics data obtained via LC-MS/MS, ensuring a low false quantitation rate. Using the label-free quantification module, we profiled the N-glycans released from purified glycoproteins and HEK293 cells as well as the dynamic changes of N-glycosylation during mouse corpus callosum development. Through the isotopic labeling quantification module, we revealed the dynamic changes of N-glycans in acute promyelocytic leukemia cells after all-trans retinoic acid treatment. Taken together, we demonstrate that nQuant enables fast and precise quantitative N-glycomics.
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Glicómica , Polisacáridos , Humanos , Glicómica/métodos , Animales , Células HEK293 , Polisacáridos/análisis , Polisacáridos/química , Polisacáridos/metabolismo , Ratones , Espectrometría de Masas en Tándem , Glicosilación , Glicoproteínas/análisis , Glicoproteínas/metabolismo , Glicoproteínas/química , Cromatografía Liquida , Tretinoina/metabolismo , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologíaRESUMEN
The heterogeneity of thrombi in terms of composition, structure, and blood rheology parameters presents a challenge for effective thrombus-targeting drug delivery. To address this, a self-adaptive nano-delivery system, termed D-PLT, is developed. It consists of platelet membrane-cloaked deformable mesoporous organic silicon dioxide nanocomposite, enabling it to respond to the challenge of the heterogeneity of thrombi in arteries and veins. The system exhibits progressive targeting, with the ability to target arterial and venous thrombosis and damaged blood vessels. D-PLT physically matches the pore structure of the thrombus by undergoing varied deformation, leading to advanced targeting and enrichment of arterial and venous thrombus. When co-loaded with the thrombolytic drug urokinase (UK) and the endothelium-protecting agent atorvastatin calcium (AT), the system improves rapid vascular opening of arterial and venous thrombosis in 90 min and provides up to 7 days of durable thrombolysis and recovery from endothelial dysfunction in vivo. This self-adaptive delivery system offers a promising strategy to overcome thrombus heterogeneity.
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Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.
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Alginatos , Microbioma Gastrointestinal , Oligosacáridos , Alginatos/metabolismo , Oligosacáridos/metabolismo , Ratones , Animales , Humanos , Colitis/microbiología , Colitis/inducido químicamente , Ratones Endogámicos C57BL , Ácidos Grasos Volátiles/metabolismo , Inflamación/metabolismo , Sulfato de Dextran , Fibras de la Dieta/metabolismoRESUMEN
Array configuration design is a critical issue for a high quality of the snapshot point spread function (PSF) and restored image in Michelson imaging interferometer. In classic design, the optimized configurations usually address the few specifications and single objective, which is unable to balance the requirements of both non-redundancy and sampling distribution. In this paper, we formalize mathematically the composite metric to trade-off the multiple demands of observation, and propose the hybrid-index-based array layout optimization strategy. The simulation results demonstrate that, in comparison with the typical distribution, the optimized array using the proposed optimization framework enables the acquisition of more comprehensive spectrum information while utilizing an equal number of apertures, providing superior imaging quality in different observation situations. Furthermore, the designed optimized array masks and the compared conventional array masks were fabricated and used for our experimental validation, further verifying the feasibility of this strategy. This array configuration optimization framework may not only find applications to Michelson interferometric imaging, but also provide a positive impact on all u-v sampling-based imaging modes, including radio interferometry, magnetic resonance imaging, and photonic integrated interferometric imaging.
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BACKGROUND: Malaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive. METHODS: We first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum. The potential antimalarial targets of Cel were then identified using a Cel activity probe based on the activity-based protein profiling (ABPP) technology. Subsequently, the antimalarial mechanism was analyzed by integrating with proteomics and transcriptomics. The binding of Cel to the identified key target proteins was verified by a series of biochemical experiments and functional assays. RESULTS: The results of the pharmacodynamic assay showed that Cel has favorable antimalarial activity both in vivo and in vitro. The ABPP-based target profiling showed that Cel can bind to a number of proteins in the parasite. Among the 31 identified potential target proteins of Cel, PfSpdsyn and PfEGF1-α were verified to be two critical target proteins, suggesting the role of Cel in interfering with the de novo synthesis of spermidine and proteins of the parasite, thus exerting its antimalarial effects. CONCLUSIONS: In conclusion, this study reports for the first time the potential antimalarial targets and mechanism of action of Cel using the ABPP strategy. Our work not only support the expansion of Cel as a potential antimalarial agent or adjuvant, but also establishes the necessary theoretical basis for the development of potential antimalarial drugs with pentacyclic triterpenoid structures, as represented by Cel. Video Abstract.
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Antimaláricos , Malaria , Animales , Ratones , Antimaláricos/farmacología , Antimaláricos/química , Antimaláricos/uso terapéutico , Espermidina/farmacología , Ratones Endogámicos C57BL , Malaria/tratamiento farmacológico , Malaria/parasitología , Triterpenos Pentacíclicos/uso terapéuticoRESUMEN
In view of the suitability assessment of forest land resources, a consistent fuzzy assessment method with heterogeneous information is proposed. Firstly, some formulas for transforming large-scale real data and interval data into fuzzy numbers are provided. To derive the unified representation of multi-granularity linguistic assessment information, a fuzzy quantitative transformation for multi-granularity uncertain linguistic information is proposed. The proofs of the desirable properties and some normalized formulas for the trapezoidal fuzzy numbers are presented simultaneously. Next, the objective weight of each assessment indicator is further determined by calculating the Jaccard-Cosine similarity between the trapezoidal fuzzy numbers. Moreover, the trapezoidal fuzzy numbers corresponding to the comprehensive assessment values of each alternative are obtained. The alternatives are effectively ranked according to the distance from the centroid of the trapezoidal fuzzy number to the origin. Finally, based on the proposed consistent fuzzy assessment method, the suitability assessment of forest land resources is achieved under a multi-source heterogeneous data setting.
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Conservación de los Recursos Naturales , Monitoreo del Ambiente , Bosques , Lógica Difusa , Monitoreo del Ambiente/métodos , Conservación de los Recursos Naturales/métodosRESUMEN
The development of nanotechnology has transformed many cutting-edge studies related to single-molecule analysis into nanoparticle (NP) detection with a single-NP sensitivity and ultrahigh resolution. While laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been successful in quantifying and tracking NPs, its quantitative calibration remains a major challenge due to the lack of suitable standards and the uncertain matrix effects. Herein, we frame a new approach to prepare quantitative standards via precise synthesis of NPs, nanoscale characterization, on-demand NP distribution, and deep learning-assisted NP counting. Gold NP standards were prepared to cover the mass range from sub-femtogram to picogram levels with sufficient accuracy and precision, thus establishing an unambiguous relationship between the sampled NP number in each ablation and the corresponding mass spectral signal. Our strategy facilitated for the first time the study of the factors affecting particulate sample capture and signal transductions in LA-ICP-MS analysis and culminated in the development of an LA-ICP-MS-based method for absolute NP quantification with single-NP sensitivity and single-cell quantification capability. The achievements would herald the emergence of new frontiers cut across a spectrum of toxicological and diagnostic issues related to NP quantification.
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Terapia por Láser , Nanopartículas , Espectrometría de Masas/métodos , Análisis Espectral , Rayos LáserRESUMEN
BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Humanos , Tumor de Klatskin/diagnóstico por imagen , Tumor de Klatskin/cirugía , Tumor de Klatskin/patología , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/cirugía , Colangiocarcinoma/patología , Imagenología Tridimensional , Estudios Retrospectivos , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/cirugía , Conductos Biliares Intrahepáticos/patologíaRESUMEN
Cyprinid herpesvirus 2 (CyHV-2), the etiological agent of herpesvirus haematopoietic necrosis (HVHN) in carp and goldfish, has caused significant economic losses in the aquaculture industry. During viral infection, the host initiates a series of active or passive defences to regulate the process of virus infection. Apoptosis is a key component of active cellular defence, and members of the Bcl-2 family have been shown to play a critical role in the apoptotic process. However, the mechanism of action of the Bcl-2 family in inducing apoptosis during CyHV-2 infection remains unclear. In this study, we revealed the molecular mechanism of miRNA-mediated silver crucian carp BAX (ccBax) in CyHV-2-induced apoptosis for the first time and demonstrated that the overexpression of miR-124 suppressed ccBax expression and significantly down-regulated apoptosis in caudal fin cells of Carassius auratus gibelio (GiCF), while miR-124 inhibitors were the opposite. These studies indicated that miR-124 inhibits CyHV-2-induced apoptosis by reducing the expression of ccBax. Furthermore, the fact that transfection of miR-124 mimics promoted CyHV-2 replication, whereas miR-124 inhibitors inhibited CyHV-2 replication, indicated that miR-124 inhibited CyHV-2-induced apoptosis and contributed to viral replication. All these results suggested that miR-124 suppresses virus-induced apoptosis and promotes viral replication by targeting and regulating ccBax expression.
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Carpas , Enfermedades de los Peces , Infecciones por Herpesviridae , Herpesviridae , Animales , Carpas/genética , Infecciones por Herpesviridae/veterinaria , Proteína X Asociada a bcl-2 , Herpesviridae/genética , Carpa Dorada/genética , Apoptosis , Replicación ViralRESUMEN
A formal [4 + 2] annulation of diamines and prop-2-ynyl sulfonium salts was developed. This strategy enables efficient access to tetrahydroquinoxalines in excellent yields.
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Diaminas , Sales (Química)RESUMEN
Breast cancer is the leading cause of cancer-related deaths in women and remains a formidable therapeutic challenge. Mitochondria participate in a myriad of essential cellular processes, such as metabolism, and are becoming an ideal target for cancer therapy. Artemisinin and its derivatives have demonstrated multiple activities in the context of various cancers. Mitochondrial autophagy(mitophagy) is one of the important anti-tumor mechanisms of artemisinin drugs. However, the lack of specific tumor targeting ability limits the anti-tumor efficacy of artemisinin drugs. In this study, a GSH-sensitive artesunate smart conjugate (TPP-SS-ATS) was synthesized and liposomes (TPP-SS-ATS-LS) that target tumor cells and mitochondria were further prepared. The advantages of TPP-SS-ATS-LS targeting to the breast tumor were verified by in vivo and in vitro evaluations. In our study, the cytotoxicity was obviously enhanced in vitro and tumor growth inhibition rate was increased from 37.7% to 56.4% at equivalent artesunate dosage in breast cancer orthotopic implanted mice. Meanwhile, mitochondrial dysfunction, suppression of ATP production and respiratory capacity were detected in breast cancer cells. We further discovered that TPP-SS-ATS-LS inhibited tumor cells proliferation through mitophagy by regulating PHB2 and PINK1 expression. These results provide new research strategies for the development of new artemisinin-based anti-tumor drugs.
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Artemisininas , Neoplasias , Profármacos , Animales , Artemisininas/metabolismo , Artemisininas/farmacología , Artesunato/metabolismo , Artesunato/farmacología , Femenino , Humanos , Liposomas/metabolismo , Ratones , Mitocondrias/metabolismo , Neoplasias/metabolismo , Profármacos/farmacologíaRESUMEN
BACKGROUND: Given the contrapositive link between the posterior tibial plateau and the femoral condyle and the similar injury cause, the fracture type should be the same as the well-known Hoffa fracture of the femoral condyle. This study aims to report a case series with Hoffa-like tibial plateau fractures to improve understanding. METHODS: We analysed six consecutive patients presented with Hoffa-like tibial plateau fractures in our hospital between October 2014 and December 2020, a period in which 1924 tibial plateau fractures were treated. Patients' data on demographics, radiographs, surgical therapy, and assessment at a 12-month follow-up were retrieved. RESULTS: The incidence of Hoffa-like tibial plateau fractures was 0.31% (6/1924). This study included three men and three women, with a mean age of 45.8 years. The injury mechanism was either a fall from a great height or a vehicle accident. On average, 7.5 days after the injury, patients were surgically treated with open reduction and internal fixation (ORIF) with place/screws via a lateral or posteromedial approach. At 10 to 15 weeks, all instances had osseous union on radiography. At 12-month follow-up, the HSS score of the operated knee ranged from 93 to 98 points (mean: 94.8), and Rasmussen radiograph score was from 15 to 18 (mean: 15.8). There were no intra-operative or post-operative problems. CONCLUSION: This Hoffa-like fracture of the tibial plateau is a rare condition; however, it can occur. Orthopaedic surgeons should pay attention to this neglected but actually familiar fracture type.
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Placas Óseas , Fracturas de la Tibia , Femenino , Fijación Interna de Fracturas , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tibia , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/epidemiología , Fracturas de la Tibia/cirugía , Resultado del TratamientoRESUMEN
OBJECT: The purpose of this study was to propose a new traction device, a multiplanar fracture reducer (MFR), for the treatment of tibial shaft fractures with intramedullary nails (IMN). The efficiencies of the multiplanar fracture reducer and manual traction (MT) in the treatment of tibial shaft fractures with IMN were compared. METHODS: From January 2019 to January 2020, a total of 79 patients were enrolled in this study, among whom 38 were treated with MFR while 41 were treated with MT. Their demographics and fracture characteristics, surgical data, and prognostic data between the two groups were compared. RESULTS: The mean number of intra-operative fluoroscopies in the MFR group was less than that in the MT group (19.4 vs 21.2, p < 0.001); surgical procedures involving open reduction were more in the MT group than in MFR group (0 vs 5, p = 0.026); there were less assistants in the MFR group than in the MT group (1 vs 1.9, p < 0.001), while the average Lysholm Knee Function Score and knee flexion were 92.7 ± 2.0 and 128.8 ± 1.4 in the MFR group, and 91.9 ± 2.1 and 127.5 ± 1.8 in the MT group, respectively. Both LKFS and knee flexion in the MFR group were significantly better than those in the MT group (p = 0.032 and p < 0.001). The remaining data between the two groups were comparable. CONCLUSION: MFR is a safe and effective device for the minimal invasive treatment of tibial shaft fractures fixed with IMN.
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Fijación Intramedular de Fracturas , Fracturas de la Tibia , Clavos Ortopédicos , Fijación Intramedular de Fracturas/métodos , Curación de Fractura , Humanos , Fracturas de la Tibia/cirugía , Tracción/métodos , Resultado del TratamientoRESUMEN
It is well established that the postoperative results were affected by the surgeon volume in a variety of elective and emergent orthopaedic surgeries; however, by far, no evidences have been available as for surgically treated displaced intra-articular calcaneal fractures (DIACFs). We aimed at investigating the relationship between surgeon volume and deep surgical site infection (DSSI) following open reduction and internal fixation (ORIF) of DIACFs. This was a further analysis of prospectively collected data from a validated database. Patients with DIACFs stabilised by ORIF between 2016 and 2019 were identified. Surgeon volume was defined as the number of surgically treated calcaneal fractures within one calendar year and was dichotomised based on the optimal cut-off value. The outcome measure was DSSI within 1 year postoperatively. Multivariate logistics regression analyses were performed to examine the relationship, adjusting for confounders. Among 883 patients, 19 (2.2%) were found to have a DSSI. The DSSI incidence was 6.5% in surgeons with a low volume (<6/year), 5.5 times as that in those with a high volume (≥6/year) (incidence rate, 1.2%; P < 0.001). The multivariate analyses showed a low volume <6/year was associated with a 5.8-fold increased risk of DSSI (95% confidence interval, 2.2-16.5, P < 0.001). This value slightly increased after multiple sensitivity analyses, with statistical significances still unchanged (OR range, 6.6-6.9; P ≤ 0.001). The inverse relationship indicates a need for at least six cases/year for a surgeon to substantially reduce the DSSIs following the ORIF of DIACFs.
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Traumatismos del Tobillo , Calcáneo , Traumatismos de los Pies , Fracturas Óseas , Traumatismos de la Rodilla , Cirujanos , Calcáneo/cirugía , Traumatismos de los Pies/cirugía , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Fracturas Óseas/complicaciones , Fracturas Óseas/cirugía , Humanos , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Celastrol (cel) was one of the earliest isolated and identified chemical constituents of Tripterygium wilfordii Hook. f. Based on a cel probe (cel-p) that maintained the bioactivity of the parent compound, the targets of cel in cerebral ischemia-reperfusion (I/R) injury were comprehensively analyzed by a quantitative chemical proteomics method. METHODS: We constructed an oxygen-glucose deprivation (OGD) model in primary rat cortical neurons and a middle cerebral artery occlusion (MCAO) model in adult rats to detect the direct binding targets of cel in cerebral I/R. By combining various experimental methods, including tandem mass tag (TMT) labeling, mass spectrometry, and cellular thermal shift assay (CETSA), we revealed the targets to which cel directly bound to exert neuroprotective effects. RESULTS: We found that cel inhibited the proinflammatory activity of high mobility group protein 1 (HMGB1) by directly binding to it and then blocking the binding of HMGB1 to its inflammatory receptors in the microenvironment of ischemia and hypoxia. In addition, cel rescued neurons from OGD injury in vitro and decreased cerebral infarction in vivo by targeting HSP70 and NF-κB p65. CONCLUSION: Cel exhibited neuroprotective and anti-inflammatory effects by targeting HSP70 and NF-κB p65 and directly binding to HMGB1 in cerebral I/R injury.
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Proteína HMGB1/metabolismo , Fármacos Neuroprotectores/farmacología , Triterpenos Pentacíclicos/farmacología , Daño por Reperfusión/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Masculino , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Proteoma/metabolismo , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Iron is essential for a broad range of biochemical processes in the brain, but the mechanisms of iron metabolism in the brain remain elusive. Here we show that iron functionally translocates among brain regions along specific axonal projections. We identified two pathways for iron transport in the brain: a pathway from ventral hippocampus (vHip) to medial prefrontal cortex (mPFC) to substantia nigra; and a pathway from thalamus (Tha) to amygdala (AMG) to mPFC. While vHip-mPFC transport modulates anxiety-related behaviors, impairment of Tha-AMG-mPFC transport did not. Moreover, vHip-mPFC iron transport is necessary for the behavioral effects of diazepam, a well-known anxiolytic drug. By contrast, genetic or pharmacological promotion of vHip-mPFC transport produced anxiolytic-like effects and restored anxiety-like behaviors induced by repeated restraint stress. Taken together, these findings provide key insights into iron metabolism in the brain and identify the mechanisms underlying iron transport in the brain as a potential target for development of novel anxiety treatments.
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Ansiedad/metabolismo , Axones/metabolismo , Encéfalo/metabolismo , Hierro/metabolismo , Animales , Transporte Biológico , Masculino , RatonesRESUMEN
Carbon one industry flux gas generated from fossil fuels, various industrial and domestic waste, as well as lignocellulosic biomass provides an innovative raw material to lead the sustainable development. Through the chemical and biological processing, the gas mixture composed of CO, CO2, and H2, also termed as syngas, is converted to biofuels and high-value chemicals. Here, the syngas fermentation process is elaborated to provide an overview. Sources of syngas are summarized and the influences of impurities on biological fermentation are exhibited. Acetogens and carboxydotrophs are the two main clusters of syngas utilizing microorganisms, their essential characters are presented, especially the energy metabolic scheme with CO, CO2, and H2. Synthetic biology techniques and microcompartment regulation are further discussed and proposed to create a high-efficiency cell factory. Moreover, the influencing factors in fermentation and products in carboxylic acids, alcohols, and others such like polyhydroxyalkanoate and poly-3-hydroxybutyrate are addressed. Biological fermentation from carbon one industry flux gas is a promising alternative, the latest scientific advances are expatiated hoping to inspire more creative transformation.
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Biocombustibles , Ciclo del Carbono , Bacterias/genética , Carbono , FermentaciónRESUMEN
The time-course association of soil physicochemical properties and fate of CeO2 nanoparticles (NPs) is not well understood. This study for the first time investigated the dissolution and retention of CeO2 NPs (<25 nm) during soil short-term (6 h) and long-term (30 d) aging processes with dynamic redox conditions. Under the additional reductant-induced initial reductive condition, theoretically, up to 220 of Ce(IV) was temporarily reductively dissolved within 10 min, accompanied by a slow retention process (180 min) of Ce species in soil solutions. Conversely, the dissolution and slow retention of Ce species were not significant in soil solutions without added reductant. X-ray absorption near edge spectroscopy (XANES) shows that most of Ce species were present as Ce(IV) (94.0%-97.8%) in all soils after a long-term aging process. These results indicate that the soil dynamic redox conditions induced by oxidant/reductant intrinsically determined the different time-course dissolution and retention of CeO2 NPs, highlighting the occasional reductive condition in soil solution that may contribute to the migration and diffusion of Ce species. The time-course study should be also adopted to develop a comprehensive understanding of the nano-soil interactions.
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Cerio , Nanopartículas del Metal , Nanopartículas , Oxidación-Reducción , Suelo , SolubilidadRESUMEN
BACKGROUND: Although lower temperature (< 45 °C) photothermal therapy (LPTT) have attracted enormous attention in cancer therapy, the therapeutic effect is still unsatisfying when applying LPTT alone. Therefore, combining with other therapies is urgently needed to improve the therapeutic effect of LPTT. Recently reported oxygen-irrelevant free radicals based thermodynamic therapy (TDT) exhibit promising potential for hypoxic tumor treatment. However, overexpression of glutathione (GSH) in cancer cells would potently scavenge the free radicals before their arrival to the specific site and dramatically diminish the therapeutic efficacy. METHODS AND RESULTS: In this work, a core-shell nanoplatform with an appropriate size composed of arginine-glycine-aspartate (RGD) functioned polydopamine (PDA) as a shell and a triphenylphosphonium (TPP) modified hollow mesoporous manganese dioxide (H-mMnO2) as a core was designed and fabricated for the first time. This nanostructure endows a size-controllable hollow cavity mMnO2 and thickness-tunable PDA layers, which effectively prevented the pre-matured release of encapsulated azo initiator 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI) and revealed pH/NIR dual-responsive release performance. With the mitochondria-targeting ability of TPP, the smart nanocomposites (AIBI@H-mMnO2-TPP@PDA-RGD, AHTPR) could efficiently induce mitochondrial associated apoptosis in cancer cells at relatively low temperatures (< 45 °C) via selectively releasing oxygen-irrelevant free radicals in mitochondria and facilitating the depletion of intracellular GSH, exhibiting the advantages of mitochondria-targeted LPTT/TDT. More importantly, remarkable inhibition of tumor growth was observed in a subcutaneous xenograft model of osteosarcoma (OS) with negligible side effects. CONCLUSIONS: The synergistic therapy efficacy was confirmed by effectively inducing cancer cell death in vitro and completely eradicating the tumors in vivo. Additionally, the excellent biosafety and biocompatibility of the nanoplatforms were confirmed both in vitro and in vivo. Taken together, the current study provides a novel paradigm toward oxygen-independent free-radical-based cancer therapy, especially for the treatment of hypoxic solid tumors.
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Radicales Libres , Nanopartículas del Metal/química , Mitocondrias , Sistema de Administración de Fármacos con Nanopartículas , Terapia Fototérmica , Animales , Compuestos Azo/química , Línea Celular Tumoral , Frío , Femenino , Radicales Libres/análisis , Radicales Libres/metabolismo , Humanos , Imidazoles/química , Compuestos de Manganeso/química , Ratones , Ratones Desnudos , Mitocondrias/química , Mitocondrias/metabolismo , Óxidos/químicaRESUMEN
Using black soldier fly (Hermetia illucens) larvae in treatment of livestock manure is a promising technology. In this study, high-throughput sequencing was used to analyze the microbial community in chicken manure before and after treatment with H. illucens larvae. In fresh chicken manure, the most abundant bacterial phylum was Firmicutes (55.58%) followed by Bacteroidetes (24.52%) and then Proteobacteria (12.29%). After treatment of the manure with H. illucens larvae for 15 days, the abundance of Firmicutes increased to 97.72% while that of Bacteroidetes and Proteobacteria decreased. Concomitantly, the most abundant genera of fungi in chicken manure changed from Kernia (46.19%) and Microascus (17.22%) to Penicillium (46.82%) and Aspergillus (45.22%). Correlation-network analysis showed the existence of strong and complex correlations between the dominant operational taxonomic units (OUT) of bacteria and fungi. While most of these correlations were positive, three specific genera, namely g_norank_f_Bacillaceae, Penicillium, and Aspergillus exhibited negative correlations with the remaining genera. These three genera were highly abundant in the intestines of H. illucens and in chicken manure treated with H. illucens larvae. Based on 16S rDNA microbiome-function predictions, the metabolic pathways associated with sugars, amino acids, and organic pollutants inside the intestinal tract of H. illucens were enriched versus those of the other three groups. In summary, the treatment of chicken manure with H. illucens larvae significantly reduced the microbial diversity, while strongly increasing organic metabolism in the intestinal bacteria. This technology shows the potential for applications in livestock manure treatment.