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Many of the biological functions performed by RNA are mediated by RNA-binding proteins (RBPs), and understanding the molecular basis of these interactions is fundamental to biology. Here, we present massively parallel RNA assay combined with immunoprecipitation (MPRNA-IP) for in vivo high-throughput dissection of RNA-protein interactions and describe statistical models for identifying RNA domains and parsing the structural contributions of RNA. By using custom pools of tens of thousands of RNA sequences containing systematically designed truncations and mutations, MPRNA-IP is able to identify RNA domains, sequences, and secondary structures necessary and sufficient for protein binding in a single experiment. We show that this approach is successful for multiple RNAs of interest, including the long noncoding RNA NORAD, bacteriophage MS2 RNA, and human telomerase RNA, and we use it to interrogate the hitherto unknown sequence or structural RNA-binding preferences of the DNA-looping factor CTCF. By integrating systematic mutation analysis with crosslinking immunoprecipitation, MPRNA-IP provides a novel high-throughput way to elucidate RNA-based mechanisms behind RNA-protein interactions in vivo.
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Proteínas de Unión al ARN , ARN , Humanos , Sitios de Unión , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Inmunoprecipitación , Levivirus/genética , Levivirus/metabolismo , Mutación , Conformación de Ácido Nucleico , Unión Proteica , ARN/metabolismo , ARN/química , ARN/genética , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/química , ARN Viral/metabolismo , ARN Viral/química , ARN Viral/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/química , Telomerasa/metabolismo , Telomerasa/genética , Modelos EstadísticosRESUMEN
Doping and alloying are fundamental strategies to improve the thermoelectric performance of bare materials. However, identifying outstanding elements and compositions for the development of high-performance thermoelectric materials is challenging. In this study, we present a data-driven approach to improve the thermoelectric performance of SnSe compounds with various doping. Based on the newly generated experimental and computational dataset, we built highly accurate predictive models of thermoelectric properties of doped SnSe compounds. A well-designed feature vector consisting of the chemical properties of a single atom and the electronic structures of a solid plays a key role in achieving accurate predictions for unknown doping elements. Using the machine learning predictive models and calculated map of the solubility limit for each dopant, we rapidly screened high-dimensional material spaces of doped SnSe and evaluated their thermoelectric properties. This data-driven search provided overall strategies to optimize and improve the thermoelectric properties of doped SnSe compounds. In particular, we identified five dopant candidate elements (Ge, Pb, Y, Cd, and As) that provided a high ZT exceeding 2.0 and proposed a design principle for improving the ZT by Sn vacancies depending on the doping elements. Based on the search, we proposed yttrium as a new high-ZT dopant for SnSe with experimental confirmations. Our research is expected to lead to novel high-ZT thermoelectric material candidates and provide cutting-edge research strategies for materials design and extraction of design principles through data-driven research.
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Thermoelectric materials generate electric energy from waste heat, with conversion efficiency governed by the dimensionless figure of merit, ZT. Single-crystal tin selenide (SnSe) was discovered to exhibit a high ZT of roughly 2.2-2.6 at 913 K, but more practical and deployable polycrystal versions of the same compound suffer from much poorer overall ZT, thereby thwarting prospects for cost-effective lead-free thermoelectrics. The poor polycrystal bulk performance is attributed to traces of tin oxides covering the surface of SnSe powders, which increases thermal conductivity, reduces electrical conductivity and thereby reduces ZT. Here, we report that hole-doped SnSe polycrystalline samples with reagents carefully purified and tin oxides removed exhibit an ZT of roughly 3.1 at 783 K. Its lattice thermal conductivity is ultralow at roughly 0.07 W m-1 K-1 at 783 K, lower than the single crystals. The path to ultrahigh thermoelectric performance in polycrystalline samples is the proper removal of the deleterious thermally conductive oxides from the surface of SnSe grains. These results could open an era of high-performance practical thermoelectrics from this high-performance material.
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Light-assisted hyperthermic therapy is a promising strategy to treat cancer. Graphene and their derivatives with unique physiochemical properties, intrinsic near infrared absorption, and ability to transduce the absorbed light energy into heat, have attracted researchers to use them for photothermal therapy (PTT). In addition, the presence of surface functional groups and large surface area that can facilitate interactions with hydrophobic molecules has favored the use of graphene allotropes for developing PTT-based combinatorial therapies. In this book chapter we have reviewed different graphene-based PTT-assisted photodynamic, gene, chemo, and immunotherapeutic strategies developed to improve the outcome of cancer treatment. We have also discussed how PTT from graphene derivatives can improve the therapeutic outcomes of gene, chemo, and immunotherapies. Finally, this book chapter provides promising insights to develop novel graphene-based multifunctional PTT-assisted combinatorial therapeutics with both imaging and therapeutic regimens to treat cancer.
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Grafito , Hipertermia Inducida , Neoplasias , Fotoquimioterapia , Grafito/química , Humanos , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , FototerapiaRESUMEN
Graphene has drawn tremendous interest in the field of nanoscience as a superior theranostic agent owing to its high photostability, aqueous solubility, and low toxicity. This monoatomic thick building block of a carbon allotrope exhibits zero to two-dimensional characteristics with a unique size range within the nanoscale. Their high biocompatibility, quantum yield, and photoluminescent properties make them more demandable in biomedical research. Its application in biomedical sciences has been limited due to its small-scale production. Large-scale production with an easy synthesis process is urgently required to overcome the problem associated with its translational application. Despite all possible drawbacks, the graphene-based drug/gene delivery system is gaining popularity day by day. To date, various studies suggested its application as a theranostic agent for target-specific delivery of chemotherapeutics or antibiotics against various diseases like cancer, Alzheimer's diseases, multidrug resistance diseases, and more. Also, studying the toxicological profile of graphene derivatives is very important before starting its practical use in clinical applications. This chapter has tried to abbreviate several methods and their possible incoming perspective as claimed by researchers for mass production and amplifying graphene-based treatment approaches.
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Grafito , Carbono , Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Medicina de PrecisiónRESUMEN
Herein, a bile acid-inspired triple padlock oral gene delivery platform is developed, facilitating the protection of the therapeutic gene from gastrointestinal degradation, selective intestinal accumulation through a bile acid-specific transporter, and transportation of pDNA NPs through the enterohepatic recycling system. This nonviral oral gene delivery nanoparticle exhibits excellent gene expression kinetics in in vitro, in vivo, and ex vivo studies. A single oral dose leads to maintaining normoglycemia for up to 7 days in three different diabetes mouse models and 14 days in diabetic monkeys. Also, the optimized dosage form can reduce nonfast blood glucose levels and hemoglobin A1C within a normal range from the last stage diabetes conditions with a reduction of weight gain from changes of food uptake behavior after treatment once weekly for 20 weeks. Taken together, the current findings could improve the current painful treatment experience of diabetics and thus improve their quality of life.
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Nanopartículas , Calidad de Vida , Animales , ADN/genética , Terapia Genética , Ratones , Plásmidos/genéticaRESUMEN
Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.
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Nanocompuestos , Fotoquimioterapia , Animales , Línea Celular Tumoral , Fotoquimioterapia/métodos , Nanocompuestos/uso terapéutico , Imagen por Resonancia Magnética , Óxidos de Nitrógeno , NitrógenoRESUMEN
Multi-functionalized carbon nanomaterials have attracted interest owing to their excellent synergic properties, such as plasmon resonance energy transfer and surface-enhanced Raman scattering. Particularly, nanoparticle (NP)-decorated graphene (GRP) has been applied in various fields. In this study, silver NP (AgNP)- and magnetic iron oxide NP (IONP)-decorated GRP were prepared and utilized as biosensing platforms. In this case, AgNPs and GRP exhibit plasmonic properties, whereas IONPs exhibit magnetic properties; therefore, this hybrid nanomaterial could function as a magnetoplasmonic substrate for the magnetofluoro-immunosensing (MFI) system. Conversely, exosomes were recently considered high-potential biomarkers for the diagnosis of diseases. However, exosome diagnostic use requires complex isolation and purification methods. Nevertheless, we successfully detected a prostate-cancer-cell-derived exosome (PC-exosome) from non-purified exosomes in a culture media sample using Ag/IO-GRP and dye-tetraspanin antibodies (Ab). First, the anti-prostate-specific antigen was immobilized on the Ag/IO-GRP and it could isolate the PC-exosome from the sample via an external magnetic force. Dye-tetraspanin Ab was added to the sample to induce the sandwich structure. Based on the number of exosomes, the fluorescence intensity from the dye varied and the system exhibited highly sensitive and selective performance. Consequently, these hybrid materials exhibited excellent potential for biosensing platforms.
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Técnicas Biosensibles , Exosomas , Grafito , Nanopartículas , Neoplasias , Técnicas Biosensibles/métodos , Oro/química , Grafito/química , Humanos , Masculino , Nanopartículas/químicaRESUMEN
This study aimed to investigate the effect of mixture of herbal extracts and supplementary formula (FNP-C) on hangovers and antioxidant enzymes in alcohol-induced liver damage in rats. HepG2 cells were used as the experimental cells and divided into five groups: non-treated control (normal), alcohol-induced control (control), mixture of herbal extracts (FNP-B), FNP-C, and a commercial treatment of liver diseases (Livers®); inhibition of detoxification and alcohol-induced damage was confirmed in vivo. Blood alcohol and acetaldehyde concentration after alcohol consumption were measured in a timely manner; alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), glutathione (GSH), glutathione transferase (GST), and lactate dehydrogenase (LDH) levels were measured in the liver. FNP-C exhibited the highest effect. When FNP-C was administered to alcohol-induced animals, blood alcohol and acetaldehyde concentration decreased compared to FNP-B and Livers®. FNP-C reduced ADH levels and improved LDH, GSH, GST, and SOD levels. The FNP-C group was effective in preventing alcohol-induced hangovers and liver damage. Thus, FNP-C improves hangovers and increases antioxidant activity in an alcohol-induced model. Adding amino acids and vitamins to natural ingredients can potentially enhance the effect of improving hangovers.
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RATIONALE & OBJECTIVE: Patients receiving twice-weekly or less-frequent hemodialysis (HD) may need to undergo higher ultrafiltration rates (UFRs) to maintain acceptable fluid balance. We hypothesized that higher UFRs are associated with faster decline in residual kidney function (RKF) and a higher rate of mortality. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 1,524 patients with kidney failure who initiated maintenance HD at a frequency of twice or less per week for at least 6 consecutive weeks at some time between 2007 and 2011 and for whom baseline data for UFR and renal urea clearance were available. PREDICTOR: Average UFR during the first patient-quarter during less-frequent HD (<6, 6-<10, 10-<13, and≥13mL/h/kg). OUTCOME: Time to all-cause and cardiovascular death, slope of decline in RKF during the first year after initiation of less-frequent HD (with slopes above the median categorized as rapid decline). ANALYTICAL APPROACH: Cox proportional hazards regression for time to death and logistic regression for the analysis of rapid decline in RKF. RESULTS: Among 1,524 patients, higher UFR was associated with higher all-cause mortality; HRs were 1.43 (95% CI, 1.09-1.88), 1.51 (95% CI, 1.08-2.10), and 1.76 (95% CI, 1.23-2.53) for UFR of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg). Higher UFR was also associated with higher cardiovascular mortality. Baseline RKF modified the association between UFR and mortality; the association was attenuated among patients with renal urea clearance≥5mL/min/1.73m2. Higher UFR had a graded association with rapid decline in RKF; ORs were 1.73 (95% CI, 1.18-2.55), 1.89 (95% CI, 1.12-3.17), and 2.75 (95% CI, 1.46-5.18) at UFRs of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg). LIMITATIONS: Residual confounding from unobserved differences across exposure categories. CONCLUSIONS: Higher UFR was associated with worse outcomes, including shorter survival and more rapid loss of RKF, among patients receiving regular HD treatments at a frequency of twice or less per week.
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Tasa de Filtración Glomerular/fisiología , Fallo Renal Crónico/terapia , Diálisis Renal/métodos , Ultrafiltración/estadística & datos numéricos , Anciano , Causas de Muerte/tendencias , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/fisiopatología , Masculino , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Eosinophils are traditionally known as moderators of allergic reactions; however, they have now emerged as one of the principal immune-regulating cells as well as predictors of vascular disease and mortality in the general population. Although eosinophilia has been demonstrated in hemodialysis (HD) patients, associations of eosinophil count (EOC) and its changes with mortality in HD patients are still unknown. METHODS: In 107 506 incident HD patients treated by a large dialysis organization during 2007-11, we examined the relationships of baseline and time-varying EOC and its changes (ΔEOC) over the first 3 months with all-cause mortality using Cox proportional hazards models with three levels of hierarchical adjustment. RESULTS: Baseline median EOC was 231 (interquartile range 155-339) cells/µL and eosinophilia (>350 cells/µL) was observed in 23.4% of patients. There was a gradual increase in EOC over time after HD initiation with a median ΔEOC of 5.1 (IQR -53-199) cells/µL, which did not parallel the changes in white blood cell count. In fully adjusted models, mortality risk was highest in subjects with lower baseline and time-varying EOC (<100 cells/µL) and was also slightly higher in patients with higher levels (≥550 cells/µL), resulting in a reverse J-shaped relationship. The relationship of ΔEOC with all-cause mortality risk was also a reverse J-shape where both an increase and decrease exhibited a higher mortality risk. CONCLUSIONS: Both lower and higher EOCs and changes in EOC over the first 3 months after HD initiation were associated with higher all-cause mortality in incident HD patients.
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Eosinofilia/mortalidad , Eosinófilos/patología , Fallo Renal Crónico/mortalidad , Diálisis Renal/mortalidad , Anciano , Eosinofilia/etiología , Femenino , Humanos , Incidencia , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pronóstico , Diálisis Renal/efectos adversos , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
Cancer therapeutics must be delivered to their targets for improving efficacy and reducing toxicity, though they encounter physiological barriers in the tumor microenvironment. They also face limitations associated with genetic instability and dynamic changes of surface proteins in cancer cells. Nanosized exosomes generated from the endosomal compartment, however, transfer their cargo to the recipient cells and mediate the intercellular communication, which affects malignancy progression, tumor immunity, and chemoresistance. In this review, we give an overview of exosomes' biological aspects and therapeutic potential as diagnostic biomarkers and drug delivery vehicles for oncotherapy. Furthermore, we discuss whether exosomes could contribute to personalized cancer immunotherapy drug design as efficient nanocommunicators.
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Sistemas de Liberación de Medicamentos , Exosomas/genética , Nanocompuestos/uso terapéutico , Neoplasias/genética , Comunicación Celular/genética , Exosomas/inmunología , Humanos , Inmunoterapia , Neoplasias/inmunología , Neoplasias/terapia , Microambiente Tumoral/inmunologíaRESUMEN
Transcription factors play a central role in pluripotency transcription circuitry for establishing pluripotent reprogramming. Master transcription factors Oct4, Nanog, and Sox2 are known to form the core of the pluripotency transcription network. Other transcription factors also play critical roles for further refining the core circuitry for pluripotency in induced pluripotent stem (iPS) cells. Here, we reported that Nac1 interacted with the master pluripotent factors Oct4 and Nanog co-occupies gene promoters bound by these transcriptional factors for establishing pluripotency. Moreover, this interaction coordinates gene expression with H3K4me3 in the somatic cell reprogramming. Knockdown of Nac1 suppressed somatic cell reprogramming, whereas overexpression of Nac1 resulted in enhanced efficiency of induced pluripotent cell generation. Altogether, these results reveal the genome wide role for Nac1 in the contribution to the pluripotency circuitry and the regulation of the establishing pluripotent state.
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Reprogramación Celular/genética , Proteínas del Tejido Nervioso/metabolismo , Células Madre Pluripotentes/metabolismo , Proteínas Represoras/metabolismo , Activación Transcripcional , Animales , Células Madre Pluripotentes Inducidas/metabolismo , Ratones , Células Madre Embrionarias de Ratones/metabolismo , Proteína Homeótica Nanog/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Regiones Promotoras Genéticas/genética , Unión ProteicaRESUMEN
Tailoring combinatorial therapies along with real-time monitoring strategies has been the major focus of overcoming multidrug resistance in cancer. However, attempting to develop a multifunctional nanoplatform in a single construct leads to compromising therapeutic outcomes. Herein, we developed a simple, theranostic nanoassembly containing a hyaluronic acid-stabilized redox-sensitive (HART) polyethylenimine polyplex composed of a doxorubicin (DOX) intercalated Bcl-2 shRNA encoded plasmid along with a green-synthesized hausmannite (Mn3O4) and hematite (Fe3O4) nanoparticle (GMF). The highly stable HART nanoassembly has enhanced CD44-mediated intracellular uptake along with hyaluronidase (hylase) and redox-responsive drug-gene release. With Bcl-2 gene silencing induced by the successful delivery of HART in multidrug-resistant MCF7 breast cancer cells, the synergistic cytotoxic effect of Bcl-2 silencing and DOX was achieved. In addition, the HART nanoassembly containing GMF exhibited excellent dual MRI contrast (T1/T2) by reducing artifact signals. Overall, the HART nanoassembly with its enhanced theranostic properties has the potential to improve the therapeutic efficacy in future preclinical and clinical trials.
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Neoplasias de la Mama/terapia , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Resistencia a Antineoplásicos/efectos de los fármacos , Terapia Genética/métodos , Ácido Hialurónico/química , Imagen por Resonancia Magnética/métodos , Nanopartículas del Metal/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Doxorrubicina/uso terapéutico , Composición de Medicamentos/métodos , Liberación de Fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Femenino , Compuestos Férricos/química , Silenciador del Gen , Humanos , Células MCF-7 , Compuestos de Manganeso/química , Proteínas Oncogénicas/genética , Oxidación-Reducción , Óxidos/química , Polietileneimina/química , Transfección , Proteínas Virales/genéticaRESUMEN
Underwater Sensor Networks (UWSN) have attracted huge attention due to their significance in oceanic observation and exploration. They offer a vast number of applications, many of which require routing the sensed data to a centralized location. This makes routing an important part of the design of such applications. In this paper, we present a comprehensive survey of recently proposed routing protocols for UWSNs. We evaluate the proposed schemes through an extensive set of parameters that define the core characteristics of a routing protocol. Moreover, we present a summary of the methods used by each scheme to familiarize readers with the basic operations of the schemes. We also present our view of the strengths and weakness of each scheme. For ease of description, the addressed routing protocols are divided into two categories: localization-based, and localization-free routing schemes. Each of the two categories is further divided into the protocols that consider node mobility, and those that do not. Lastly, we present our view on open research topics.
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Knowledge about the geographic coordinates of underwater sensor nodes is of primary importance for many applications and protocols of under water sensor networks (UWSNs) thus making localization of sensor nodes a crucial part of underwater network design. In case of mobile underwater sensor network, location estimation becomes challenging not only due to the need for periodic tracking of nodes, but also due to network partitioning caused by the pseudo-random mobility of nodes. Our proposed technique accomplishes the task of localization in two stages: (1) relative localization of sensor nodes with respect to a reference node at regular intervals during sensing operation. (2) Offline absolute localization of sensor nodes using absolute coordinates of the reference node and relative locations estimated during stage 1. As our protocol deals with mobile underwater sensor networks that may introduce network partitioning, we also propose a partition handling routine to deal with network partitions to achieve high localization coverage. The major design goal of our work is to maximize localization coverage while keeping communication overhead minimum, thus achieving better energy efficiency. Major contributions of this paper are: (1) Two energy efficient relative localization techniques, and (2) A partition handling strategy that ensures localization of partitioned nodes.
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Many applications of underwater sensor networks (UWSNs), such as target tracking, reconnaissance and surveillance, and marine life monitoring require information about the geographic locations of the sensed data. This makes the localization of sensor nodes a crucial part of such underwater sensing missions. In the case of mobile UWSNs, the problem becomes challenging, not only due to a need for the periodic tracking of nodes, but also due to network partitioning as a result of the pseudo-random mobility of nodes. In this work, we propose an energy efficient solution for localizing nodes in partitioned networks. Energy consumption is minimized by clustering unlocalized partitioned nodes and allowing only clusterheads to carry out a major part of the localization procedure on behalf of the whole cluster. Moreover, we introduce a retransmission control scheme that reduces energy consumption by controlling unnecessary transmission. The major design goal of our work is to maximize localization coverage while keeping communication overheads at a minimum, thus achieving better energy efficiency. The major contributions of this paper include a clustering technique for localizing partitioned nodes and a retransmission control strategy that reduces unnecessary transmissions.
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Oxidative stress during sepsis pathogenesis remains the most-important factor creating imbalance and dysregulation in immune-cell function, usually observed following initial infection. Hydrogen peroxide (H2O2), a potentially toxic reactive oxygen species (ROS), is excessively produced by pro-inflammatory immune cells during the initial phases of sepsis and plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation. In the present study, we constructed a peroxide scavenger mannosylated polymeric albumin manganese dioxide (mSPAM) nanoassembly to catalyze the decomposition of H2O2 responsible for the hyper-activation of pro-inflammatory immune cells. In a detailed manner, we investigated the role of mSPAM nanoassembly in modulating the expression and secretion of pro-inflammatory markers elevated in bacterial lipopolysaccharide (LPS)-mediated endotoxemia during sepsis. Through a facile one-step solution-phase approach, hydrophilic bovine serum albumin reduced manganese dioxide (BM) nanoparticles were synthesized and subsequently self-assembled with cationic mannosylated disulfide cross-linked polyethylenimine (mSP) to formulate mSPAM nanoassembly. In particular, we observed that the highly stable mSPAM nanoassembly suppressed HIF1α expression by scavenging H2O2 in LPS-induced macrophage cells. Initial investigation revealed that a significant reduction of free radicals by the treatment of mSPAM nanoassembly has reduced the infiltration of neutrophils and other leukocytes in a local endotoxemia animal model. Furthermore, therapeutic studies in a systemic endotoxemia model demonstrated that mSPAM treatment reduced TNF-α and IL-6 inflammatory cytokines in serum, in turn circumventing organ damage done by the inflammatory macrophages. Interestingly, we also observed that the reduction of these inflammatory cytokines by mSPAM nanoassembly further prevented IBA-1 immuno-positive microglial cell activation in the brain and consequently improved the cognitive function of the animals. Altogether, the administration of mSPAM nanoassembly scavenged H2O2 and suppressed HIF1α expression in LPS-stimulated macrophages and thereby inhibited the progression of local and systemic inflammation as well as neuroinflammation in an LPS-induced endotoxemia model. This mSPAM nanoassembly system could serve as a potent anti-inflammatory agent, and we further anticipate its successful application in treating various inflammation-related diseases.
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Disfunción Cognitiva/tratamiento farmacológico , Endotoxemia/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Nanocompuestos/administración & dosificación , Albúminas/química , Albúminas/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Endotoxemia/inducido químicamente , Endotoxemia/genética , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/toxicidad , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/patología , Lipopolisacáridos/toxicidad , Macrófagos/efectos de los fármacos , Macrófagos/patología , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Ratones , Nanocompuestos/química , Estrés Oxidativo/efectos de los fármacos , Óxidos/química , Óxidos/farmacología , Peroxidasa/química , Peroxidasa/genética , Peróxidos/química , Peróxidos/farmacología , Especies Reactivas de Oxígeno/toxicidad , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Introducing structural defects such as vacancies, nanoprecipitates, and dislocations is a proven means of reducing lattice thermal conductivity. However, these defects tend to be detrimental to carrier mobility. Consequently, the overall effects for enhancing ZT are often compromised. Indeed, developing strategies allowing for strong phonon scattering and high carrier mobility at the same time is a prime task in thermoelectrics. Here we present a high-performance thermoelectric system of Pb0.95(Sb0.033â¡0.017)Se1- yTe y (â¡ = vacancy; y = 0-0.4) embedded with unique defect architecture. Given the mean free paths of phonons and electrons, we rationally integrate multiple defects that involve point defects, vacancy-driven dense dislocations, and Te-induced nanoprecipitates with different sizes and mass fluctuations. They collectively scatter thermal phonons in a wide range of frequencies to give lattice thermal conductivity of â¼0.4 W m-1 K-1, which approaches to the amorphous limit. Remarkably, Te alloying increases a density of nanoprecipitates that affect mobility negligibly and impede phonons significantly, and it also decreases a density of dislocations that scatter both electrons and phonons heavily. As y is increased to 0.4, electron mobility is enhanced and lattice thermal conductivity is decreased simultaneously. As a result, Pb0.95(Sb0.033â¡0.017)Se0.6Te0.4 exhibits the highest ZT â¼ 1.5 at 823 K, which is attributed to the markedly enhanced power factor and reduced lattice thermal conductivity, in comparison with a ZT â¼ 0.9 for Pb0.95(Sb0.033â¡0.017)Se that contains heavy dislocations only. These results highlight the potential of defect engineering to modulate electrical and thermal transport properties independently. We also reveal the defect formation mechanisms for dislocations and nanoprecipitates embedded in Pb0.95(Sb0.033â¡0.017)Se0.6Te0.4 by atomic resolution spherical aberration-corrected scanning transmission electron microscopy.
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From a structural and economic perspective, tellurium-free PbSe can be an attractive alternative to its more expensive isostructural analogue of PbTe for intermediate temperature power generation. Here we report that PbSe0.998Br0.002-2%Cu2Se exhibits record high peak ZT 1.8 at 723 K and average ZT 1.1 between 300 and 823 K to date for all previously reported n- and p-type PbSe-based materials as well as tellurium-free n-type polycrystalline materials. These even rival the highest reported values for n-type PbTe-based materials. Cu2Se doping not only enhance charge transport properties but also depress thermal conductivity of n-type PbSe. It flattens the edge of the conduction band of PbSe, increases the effective mass of charge carriers, and enlarges the energy band gap, which collectively improve the Seebeck coefficient markedly. This is the first example of manipulating the electronic conduction band to enhance the thermoelectric properties of n-type PbSe. Concurrently, Cu2Se increases the carrier concentration with nearly no loss in carrier mobility, even increasing the electrical conductivity above â¼423 K. The resulting power factor is ultrahigh, reaching â¼21-26 µW cm-1 K-2 over a wide range of temperature from â¼423 to 723 K. Cu2Se doping substantially reduces the lattice thermal conductivity to â¼0.4 W m-1 K-1 at 773 K, approaching its theoretical amorphous limit. According to first-principles calculations, the achieved ultralow value can be attributed to remarkable acoustic phonon softening at the low-frequency region.