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The cyclization of 3-hydroxy alkynes and the carboxylation of terminal alkynes both with CO2 are two attractive strategies to simultaneously reduce CO2 emission and produce value-added chemicals. Herein, the differential activation of alkynes over atomically precise Ag nanoclusters (NCs) supported on Metal-organic framework-derived highly-open mesoporous CeO2 (HM-CeO2) by reserving or removing their surface captopril ligands is reported. The ligand-capped Ag NCs possess electron-rich Ag atoms as efficient π-activation catalytic sites in cyclization reactions, while the naked Ag NCs possess partial positive-charged Ag atoms as perfect σ-activation catalytic sites in carboxylation reactions. Impressively, via coupling with HM-CeO2 featuring abundant basic sites and quick mass transfer, the ligand-capped Ag NCs afford 97.9% yield of 4,4-dimethyl-5-methylidene-1,3-dioxolan-2-one for the cyclization of 2-methyl-3-butyn-2-ol with CO2, which is 4.5 times that of the naked Ag NCs (21.7%), while the naked Ag NCs achieve 98.5% yield of n-butyl 2-alkynoate for the carboxylation of phenylacetylene with CO2, which is 15.6 times that of ligand-capped Ag NCs (6.3%). Density functional theory calculations reveal the ligand-capped Ag NCs can effectively activate alkynyl carbonate ions for the intramolecular ring closing in cyclization reaction, while the naked Ag NCs are highly affiliative in stabilizing terminal alkynyl anions for the insertion of CO2 in carboxylation reaction.
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Water splitting technology can convert renewable energies such as solar and wind into hydrogen energy, which is key to achieving a low-carbon hydrogen economy cycle. However, Pt-based catalysts for hydrogen evolution reaction (HER) are too expensive, thus it needs to develop efficient non-noble metal catalysts as alternatives. Herein, Ni-BDC-loaded carbon cloth (CC) is co-pyrolyzed with urea to obtain a composite structure of carbon nanotubes (CNT) and porous carbon (PC) embedded with W-doped Ni nanoparticles on CC, resulting in NiW-CNT/PC/CC. Benefiting from the synergistic effect between Ni and W, the high conductivity of CNT, and the high mass transfer rate of PC, NiW-CNT/PC/CC exhibits excellent HER activity in KOH, which only requires a low overpotential of 45 mV to drive a current density of 10 mA cm-2 with stability exceeding 40 h. Simulation calculations confirm that the W doping in metal Ni can optimize its electronic structure by lowering the d-band center and weakening hydrogen adsorption, thus reducing its HER barrier.
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Metal-organic frameworks (MOFs) are proved to be good precursors to derive various nanomaterials with desirable functions, but so far the controllable synthesis of ordered mesoporous derivatives from MOFs has not been achieved. Herein, this work reports, for the first time, the construction of MOF-derived ordered mesoporous (OM) derivatives by developing a facile mesopore-inherited pyrolysis-oxidation strategy. This work demonstrates a particularly elegant example of this strategy, which involves the mesopore-inherited pyrolysis of OM-CeMOF into a OM-CeO2 @C composite, followed by the oxidation removal of its residual carbon, affording the corresponding OM-CeO2 . Furthermore, the good tunability of MOFs helps to allodially introduce zirconium into OM-CeO2 to regulate its acid-base property, thus boosting its catalytic activity for CO2 fixation. Impressively, the optimized Zr-doped OM-CeO2 can achieve above 16 times higher catalytic activity than its solid CeO2 counterpart, representing the first metal oxide-based catalyst to realize the complete cycloaddition of epichlorohydrin with CO2 under ambient temperature and pressure. This study not only develops a new MOF-based platform for enriching the family of ordered mesoporous nanomaterials, but also demonstrates an ambient catalytic system for CO2 fixation.
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Seawater electrolysis is a promising method to produce H2 without relying on scarce freshwater resource, but its high energy consumption and inevitable accompany of competitive chlorine oxidation reaction (ClOR) are still great technological challenges. Herein, a metal-organic framework (MOF)-templated pyrolysis strategy to prepare uniform cobalt/nitrogen-codoped carbon nanosheet arrays on carbon cloth (CC@CoNC) as highly-efficient but low-cost bifunctional electrocatalysts for hydrazine-assisted seawater electrolysis is explored. The optimized CoNC nanosheet arrays can be used as an efficient bifunctional electrocatalyst to catalyze hydrazine oxidation reaction and hydrogen evolution reaction, remarkably reducing the energy consumption and nicely overcome the undesired anodic corrosion problems caused by ClOR. Impressively, a hydrazine-assisted water electrolysis system is successfully assembled by using the optimized CC@CoNC as both cathode and anode, which only needs an ultra-low cell voltage of 0.557 V and an electricity consumption of 1.22 kW h per cubic meter of H2 to achieve 200 mA cm-2 . Furthermore, the optimized CC@CoNC can also show greatly improved stability in the hydrazine-assisted seawater electrolysis system for H2 production, which can work steadily for above 40 h at ≈10 mA cm-2 . This study may offer great opportunities for obtaining hydrogen energy from infinite ocean resource by an eco-friendly method.
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The controlled pyrolysis of metal/carbon-containing precursors is commonly used for fabricating multifunctional metal/carbon-based catalysts, nevertheless, the inevitable agglomeration of these precursors in pyrolysis is extremely negative for efficient catalysis. This study reports the first example of suppressing the interfacial fusion and agglomeration of metal/carbon-based catalyst in its pyrolysis-involved fabrication process by developing a facile morphology-engineering strategy. Metal-organic framework precursors are chosen as a proof of concept and five Co/N-doped hollow carbons with different morphologies (rhombic dodecahedron, cube, plate, interpenetration twin, and rod) are synthesized via the pyrolysis of their corresponding core-shell ZIF-8@ZIF-67 precursors. It is demonstrated that the interpenetration twin precursor shows the minimum interfacial contact of interparticles due to its partly-concave morphology with abundant facets, which endows it with the best resistibility from interfacial fusion and thus aggregation of interparticles during pyrolysis. Benefiting from its unique anti-aggregated structure with high specific surface area, abundant fully-exposed active sites, and good dispersibility, the resultant 36-facet Co/N-doped hollow carbon exhibit remarkably improved catalytic property for biomass upgrading as compared with its aggregated counterparts. This study highlights the crucial role of engineering morphology to prevent metal/carbon-containing precursors from detrimental agglomeration during pyrolysis, demonstrating a new approach to constructing anti-aggregated metal/carbon-based catalysts.
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COVID-19 struck the world suddenly and unexpectedly. Since traditional education requires face-to-face communication, to avoid further spreading of the virus a majority part of that education has moved online. Our study attempts to compare the differences between online medical education with a unique course design and traditional face-to-face education. We conducted a retrospective analysis of a total of 4,098 medical students between 2019 and 2020, including two groups of students who received online education and classroom education for the same subjects, respectively. Freshmen enrolled in September 2018 received traditional classroom physiology and pharmacology education in the spring semester of 2019. Because of the impact of the COVID-19 pandemic, freshmen who were enrolled in September 2019 received online physiology and pharmacology education in the spring semester of 2020. The final marks of the two groups of students were recorded and compared. Data on students participating in online discussions, learning, homework, and watching instructional videos were also recorded. There was no significant difference in the final academic performance between the two groups [average mark: 55.93 (online education) vs. 56.27 (classroom education), P = 0.488]. Further analysis showed that student participation rates in online discussions, online learning, and online viewing of instructional videos were closely correlated with final grades in online courses (P < 0.01). In conclusion, our results suggest that the pedagogical effects of online education during COVID-19 were promising, and we provide a well-designed medical online course to inspire further improvements in online education.NEW & NOTEWORTHY The COVID-19 pandemic has led to a massive temporary conversion of offline education to online education worldwide. Previous studies have noted that more students believed they had better learning experience in face-to-face learning. However, with our method of online teaching, we still showed a relatively similar performance result compared with offline education.
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COVID-19 , Educação a Distância , Educação Médica , Estudantes de Medicina , Humanos , Estudos Retrospectivos , PandemiasRESUMO
Metal-organic frameworks (MOFs) have been increasingly applied in oxygen evolution reaction (OER), and the surface of MOFs usually undergoes structural transformation to form metal oxyhydroxides to serve as catalytically active sites. However, the controllable regulation of the reconstruction process of MOFs remains as a great challenge. Here we report a defect engineering strategy to facilitate the structural transformation of MOFs to metal oxyhydroxides during OER with enhanced activity. Defective MOFs (denoted as NiFc'x Fc1-x ) with abundant unsaturated metal sites are constructed by mixing ligands of 1,1'-ferrocene dicarboxylic acid (Fc') and defective ferrocene carboxylic acid (Fc). NiFc'x Fc1-x series are more prone to be transformed to metal oxyhydroxides compared with the non-defective MOFs (NiFc'). Moreover, the as-formed metal oxyhydroxides derived from defective MOFs contain more oxygen vacancies. NiFc'Fc grown on nickel foam exhibits excellent OER catalytic activity with an overpotential of 213â mV at the current density of 100â mA cm-2 , superior to that of undefective NiFc'. Experimental results and theoretical calculations suggest that the abundant oxygen vacancies in the derived metal oxyhydroxides facilitate the adsorption of oxygen-containing intermediates on active centers, thus significantly improving the OER activity.
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Water electrolysis has attracted immense research interest, nevertheless the lack of low-cost but efficient bifunctional electrocatalysts for both hydrogen and oxygen evolution reactions greatly hinders its commercial applications. Herein, the controllable synthesis of ultrathin defect-rich layered double hydroxide (LDH) nanoarrays assembled on metal-organic framework (MOF)-derived Co-NC microarrays for boosting overall water splitting is reported. The Co-NC microarrays can not only provide abundant nucleation sites to produce a large number of LDH nuclei for favoring the growth of ultrathin LDHs, but also help to inhibit their tendency to aggregate. Impressively, five types of ultrathin bimetallic LDH nanoarrays can be electrodeposited on the Co-NC microarrays, forming desirable nanoarray-on-macroarray architectures, which show high uniformity with thicknesses from 1.5 to 1.9 nm. As expected, the electrocatalytic performance is significantly enhanced by exploiting the respective advantages of Co-NC microarrays and ultrathin LDH nanoarrays as well as the potential synergies between them. Especially, the optimal Co-NC@Ni2 Fe-LDH as both cathode and anode can afford the lowest cell voltage of 1.55 V at 10 mA cm-2 , making it one of the best earth-abundant bifunctional electrocatalysts for water electrolysis. This study provides new insights into the rational design of highly-active and low-cost electrocatalysts and facilitates their promising applications in the fields of energy storage and conversion.
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Estruturas Metalorgânicas , Água , Hidrogênio , HidróxidosRESUMO
Single-atom sites can not only act as active centers, but also serve as promising catalyst regulators and/or promoters. However, in many complex reaction systems such as electrochemical CO2 reduction reaction (CO2 RR), the introduction of single-atom regulators may inevitably induce the competitive hydrogen evolution reaction (HER) and thus reduce the selectivity. Here, the authors demonstrate that introducing HER-inert main-group metal single atoms adjacent to transition-metal single atoms can modify their electronic structure to enhance the CO2 RR to CO without inducing the HER side reaction. Dual-metal Cu and In single-site atoms anchored on mesoporous nitrogen-doped carbon (denoted as Cu-In-NC) are prepared by the pyrolysis of a multimetallic metal-organic framework. Cu-In-NC shows a high faradic efficiency of 96% toward CO formation at -0.7 V versus reversible hydrogen electrode, superior to that of its monometallic single-atom counterparts. Density functional theory studies reveal that the HER-inert In sites can activate the adjacent Cu sites through electronic modifications, strengthening the binding of *COOH intermediate and thus boosting the electrochemical reduction of CO2 to CO.
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Dióxido de Carbono , Elementos de Transição , Dióxido de Carbono/química , Catálise , Hidrogênio , Metais/químicaRESUMO
Neospora caninum, a cyst-forming apicomplexan parasite, is a leading cause of neuromuscular diseases in dogs as well as fetal abortion in cattle worldwide. The importance of the domestic and sylvatic life cycles of Neospora, and the role of vertical transmission in the expansion and transmission of infection in cattle, is not sufficiently understood. To elucidate the population genomics of Neospora, we genotyped 50 isolates collected worldwide from a wide range of hosts using 19 linked and unlinked genetic markers. Phylogenetic analysis and genetic distance indices resolved a single genotype of N. caninum Whole-genome sequencing of 7 isolates from 2 different continents identified high linkage disequilibrium, significant structural variation, but only limited polymorphism genome-wide, with only 5,766 biallelic single nucleotide polymorphisms (SNPs) total. Greater than half of these SNPs (â¼3,000) clustered into 6 distinct haploblocks and each block possessed limited allelic diversity (with only 4 to 6 haplotypes resolved at each cluster). Importantly, the alleles at each haploblock had independently segregated across the strains sequenced, supporting a unisexual expansion model that is mosaic at 6 genomic blocks. Integrating seroprevalence data from African cattle, our data support a global selective sweep of a highly inbred livestock pathogen that originated within European dairy stock and expanded transcontinentally via unisexual mating and vertical transmission very recently, likely the result of human activities, including recurrent migration, domestication, and breed development of bovid and canid hosts within similar proximities.
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Genoma , Interações Hospedeiro-Parasita , Neospora/genética , Animais , Bovinos , Genótipo , Recombinação GenéticaRESUMO
Nanozyme-based chemodynamic therapy (CDT) has emerged as an effective cancer treatment because of its low side effects and without the requirement of exogenous energy. The therapeutic effect of CDT highlights the pivotal importance of active sites, H2 O2 supplement and the glutathione (GSH) depletion of a nanozyme. The construction of a single kind of catalyst with multiple functions for the enhanced CDT is still a big challenge. In this work, seven types of bimetallic nanoparticles are synthesized using a metal-organic framework (MOF) as a stable host instead of a Fenton or Fenton-like ions supplier. Among them, Cu-Pd@MIL-101 with an alloy loading of 9.5 wt% modified by PEG (9.5% CPMP) is found to exhibit the highest peroxidase (POD) like activity combined with a superoxide dismutase (SOD) mimic activity and the function of GSH depletion. The in vivo results suggest that the stable and ultrafine nanoparticles possess favorable CDT effect for tumor and good biosafety as well as biocompatibility. This work has provided a credible strategy to construct nanozymes with an excellent activity and may pave a new way for the design of enhanced tumor CDT treatment.
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Estruturas Metalorgânicas , Nanopartículas , Ligas , Linhagem Celular Tumoral , Peróxido de HidrogênioRESUMO
Neuroinflammation is critically involved in the repair of spinal cord injury (SCI), and macrophages associated with inflammation propel the degeneration or recovery in the pathological process. Currently, efforts have been focused on obtaining efficient therapeutic anti-inflammatory drugs to treat SCI. However, these drugs are still unable to penetrate the blood spinal cord barrier and lack the ability to target lesion areas, resulting in unsatisfactory clinical efficacy. Herein, a polymer-based nanodrug delivery system is constructed to enhance the targeting ability. Because of increased expression of matrix metalloproteinases (MMPs) in injured site after SCI, MMP-responsive molecule, activated cell-penetrating peptides (ACPP), is introduced into the biocompatible polymer PLGA-PEI-mPEG (PPP) to endow the nanoparticles with the ability for diseased tissue-targeting. Meanwhile, etanercept (ET), a clinical anti-inflammation treatment medicine, is loaded on the polymer to regulate the polarization of macrophages, and promote locomotor recovery. The results show that PPP-ACPP nanoparticles possess satisfactory lesion targeting effects. Through inhibited consequential production of proinflammation cytokines and promoted anti-inflammation cytokines, ET@PPP-ACPP could decrease the percentage of M1 macrophages and increase M2 macrophages. As expected, ET@PPP-ACPP accumulates in lesion area and achieves effective treatment of SCI; this confirmed the potential of nano-drug loading systems in SCI immunotherapy.
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Traumatismos da Medula Espinal , Anti-Inflamatórios/uso terapêutico , Humanos , Imunoterapia , Macrófagos , Metaloproteinases da Matriz/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológicoRESUMO
Neonicotinoid insecticides (NEOs) are widely used for pest control worldwide. The profile of NEOs in paired urine and indoor dust has not yet been reported in China. In this study, 40 paired samples (i.e., 160 urine and 40 indoor dust) were collected from university students and dormitories from Guangzhou City of China to measure the concentrations of six NEOs and their three metabolites. Target analytes were frequently detected in paired urine (81%-98%) and indoor dust (75%-95%) samples, with median concentrations ranging from 0.02 [specific gravity (SG) adjusted: 0.02] to 2.08 (SG-adjusted: 2.38) ng/mL in urine and from 0.05 to 2.74 ng/g in indoor dust. 5-Hydroxy-imidacloprid was predominant in urine, while N-desmethyl acetamiprid was predominant in indoor dust samples, accounting for 56% and 37%, respectively. 1-Methyl-3-(tetrahydro-3-furylmethyl) urea, a dinotefuran degradate, was measured for the first time in indoor dust, with the median level of 1.02 ng/g. Significant gender-related differences (p < 0.05) in the urinary concentrations of most NEOs were found. We calculated the estimated daily intake (EDI) of target compounds from urine and indoor measurements. The EDIs of target analytes varied among all urine and indoor dust samples, with median values ranging from 0.51 (SG-adjusted: 0.56) to 51.6 (SG-adjusted: 52.8) ng/kg bw/day and from 0.04 to 2.10 pg/kg bw/day, respectively. Moreover, the median EDIsurine of most target analytes in females were significantly higher than (p < 0.05) those in males. The median EDIsdust of target compounds in dust from female dormitories were slightly higher than that in dust from male dormitories. These findings indicated that females were more exposed to NEO than males. Thus, the potential health risks of exposure to NEOs and their metabolites in female adults should be addressed in future studies. To our knowledge, this study is the first to report the profiles of NEOs and their metabolites in paired urine and indoor dust samples from young adults in China.
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Poluição do Ar em Ambientes Fechados , Inseticidas , China , Poeira/análise , Feminino , Habitação , Humanos , Inseticidas/análise , Masculino , Neonicotinoides/análise , Adulto JovemRESUMO
Perforin plays an important role in autoimmune and infectious diseases, but its function in immune inflammatory responses after spinal cord injury (SCI) has received insufficient attention. The goal of this study is to determine the influence of perforin after spinal cord injury (SCI) on secondary inflammation. Compared recovery from SCI in perforin knockout (Prf1-/-) and wild-type(WT)mice, WT mice had significantly lower the Basso mouse score (BMS), CatWalk XT, and motor-evoked potentials (MEPs) than Prf1-/- mice. Spinal cord lesions were also more obvious through glial fibrillary acidic protein (GFAP), Nissl, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. Furthermore, the blood-spinal cord barrier (BSCB) disruption was more severe and inflammatory cytokine levels were higher. Flow cytometry indicated that perforin mainly originated from CD8 T cells. With flow cytometry and enzyme-linked immunosorbent assay (ELISA), human cerebrospinal fluid (CSF) yielded similar results. Together, this study firstly demonstrated that CD8 T cell-derived perforin is detrimental to SCI recovery in the mouse model. Mechanistically, this effect occurs because perforin increases BSCB permeability, causing inflammatory cells and related cytokines to infiltrate and disrupt the nervous system.
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Linfócitos T CD8-Positivos/imunologia , Perforina/imunologia , Traumatismos da Medula Espinal/imunologia , Animais , Apoptose , Barreira Hematoneural/imunologia , Barreira Hematoneural/lesões , Barreira Hematoneural/fisiopatologia , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Perforina/líquido cefalorraquidiano , Perforina/deficiência , Perforina/genética , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Insertion of microRNA target sequences into the flavivirus genome results in selective tissue-specific attenuation and host-range restriction of live attenuated vaccine viruses. However, previous strategies for miRNA-targeting did not incorporate a mechanism to prevent target elimination under miRNA-mediated selective pressure, restricting their use in vaccine development. To overcome this limitation, we developed a new approach for miRNA-targeting of tick-borne flavivirus (Langat virus, LGTV) in the duplicated capsid gene region (DCGR). Genetic stability of viruses with DCGR was ensured by the presence of multiple cis-acting elements within the N-terminal capsid coding region, including the stem-loop structure (5'SL6) at the 3' end of the promoter. We found that the 5'SL6 functions as a structural scaffold for the conserved hexanucleotide motif at its tip and engages in a complementary interaction with the region present in the 3' NCR to enhance viral RNA replication. The resulting kissing-loop interaction, common in tick-borne flaviviruses, supports a single pair of cyclization elements (CYC) and functions as a homolog of the second pair of CYC that is present in the majority of mosquito-borne flaviviruses. Placing miRNA targets into the DCGR results in superior attenuation of LGTV in the CNS and does not interfere with development of protective immunity in immunized mice.
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Proteínas do Capsídeo/genética , Vírus da Encefalite Transmitidos por Carrapatos/genética , Genoma Viral , MicroRNAs/genética , RNA Viral/química , Animais , Encéfalo/virologia , Chlorocebus aethiops , Vírus da Encefalite Transmitidos por Carrapatos/crescimento & desenvolvimento , Vírus da Encefalite Transmitidos por Carrapatos/fisiologia , Encefalite Transmitida por Carrapatos/imunologia , Encefalite Transmitida por Carrapatos/virologia , Genes Duplicados , Camundongos , Mutação , Nucleotídeos/química , Fases de Leitura Aberta , Especificidade de Órgãos , Regiões Promotoras Genéticas , Sequências Reguladoras de Ácido Ribonucleico , Vacinas Atenuadas , Células Vero , Vacinas Virais , Replicação ViralRESUMO
Strongyloides stercoralis is a soil-transmitted helminth organism that infects ~50 to 100 million people worldwide. Despite its widespread prevalence, very little is known about the immune response that characterizes human S. stercoralis infection. To study the systemic cytokine profile characteristic of Strongyloides infection, we measured the circulating levels of a large panel of pro- and anti-inflammatory cytokines in asymptomatic, infected individuals (n = 32) and compared them to those in uninfected, controls (n = 24). Infected individuals exhibited significantly lower circulating levels of proinflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-1ß [IL-1ß]) and significantly higher levels of anti-inflammatory cytokines (IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-37, and transforming growth factor ß [TGF-ß]). Moreover, treatment of Strongyloides infection resulted in a significant reversal of the cytokine profile, with increased levels of proinflammatory (IFN-γ, TNF-α, IL-2, IL-17A, IL-17F, IL-22, IL-23, and IL-1ß) and decreased levels of anti-inflammatory (IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-37, and TGF-ß) cytokines following treatment. Thus, S. stercoralis infection is characterized by alterations in the levels of systemic cytokines, reflecting major alterations in the underlying immune response to this chronic helminth infection.
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Antinematódeos/uso terapêutico , Citocinas/sangue , Strongyloides stercoralis/imunologia , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/imunologia , Adolescente , Adulto , Animais , Doenças Assintomáticas , Feminino , Humanos , Interferon gama/sangue , Interleucina-5/sangue , Masculino , Pessoa de Meia-Idade , Estrongiloidíase/diagnóstico , Estrongiloidíase/parasitologia , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
It has long been recognized that oncogenic viruses often integrate close to common fragile sites. The papillomavirus E2 protein, in complex with BRD4, tethers the viral genome to host chromatin to ensure persistent replication. Here, we map these targets to a number of large regions of the human genome and name them Persistent E2 and BRD4-Broad Localized Enrichments of Chromatin or PEB-BLOCs. PEB-BLOCs frequently contain deletions, have increased rates of asynchronous DNA replication, and are associated with many known common fragile sites. Cell specific fragile sites were mapped in human C-33 cervical cells by FANCD2 ChIP-chip, confirming the association with PEB-BLOCs. HPV-infected cells amplify viral DNA in nuclear replication foci and we show that these form adjacent to PEB-BLOCs. We propose that HPV replication, which hijacks host DNA damage responses, occurs adjacent to highly susceptible fragile sites, greatly increasing the chances of integration here, as is found in HPV-associated cancers.
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Sítios Frágeis do Cromossomo , Proteínas de Ligação a DNA/metabolismo , Genoma Humano , Genoma Viral , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/genética , Fatores de Transcrição/metabolismo , Replicação Viral , Proteínas de Ciclo Celular , Células Cultivadas , Reparo do DNA/genética , Feminino , Genoma Humano/genética , Interações Hospedeiro-Patógeno , Humanos , Ligação Proteica , Integração Viral/genética , Replicação Viral/genéticaRESUMO
IL-4 plays an important role in the pathogenesis of atopic dermatitis (AD), a common chronic inflammatory skin disease. We have generated IL-4 transgenic (Tg) mice by over-expressing IL-4 in the epidermis. These mice spontaneously develop chronic pruritic inflammatory skin lesions, which meet the clinical and histological diagnostic criteria for human AD. Systemic survey of immune-related genes in this mouse model, however, has not been performed. In this study, we utilize PCR array technique to examine hundreds of inflammation-related genes in the IL-4 Tg mice before and after the onset of skin lesions as well as in their wild type (WT) littermates. Only those genes with at least 2-fold up-regulation or down-regulation and with a P-value of less than 0.05 in comparison to WT controls were identified and analyzed. In the skin lesions, many chemokines, pro-inflammatory cytokines, and other AD-related factors are dysregulated compared to the wild type mice. Particularly, CXCL5, IL-1ß, IL-24, IL-6, oncostatin M, PTGS2, FPR1 and REG3γ are up-regulated several hundred-fold. In the pre-lesional group that shows no obvious skin abnormality on clinical observation, 30 dysregulated genes are nevertheless identified though the fold changes are much less than that of the lesional group, including CCL6, CCL8, CCL11, CCL17, CXCL13, CXCL14, CXCR3 and IL-12Rß2. Finally using ELISA, we demonstrate that 4 most dramatically up-regulated factors in the skin are also elevated in the peripheral blood of the IL-4 Tg mice. Taken together, our data have identified hundreds of dysregulated factors in the IL-4 Tg mice before and after the onset of skin lesions. Future detailed examination of these factors will shed light on our understanding of the development and progression of AD and help to discover important biomarkers for clinical AD diagnosis and treatment.
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Dermatite Atópica/genética , Perfilação da Expressão Gênica/métodos , Inflamação/genética , Interleucina-4/genética , Pele/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Humanos , Inflamação/sangue , Inflamação/metabolismo , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Camundongos Transgênicos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Pele/patologia , Regulação para CimaRESUMO
BACKGROUND: Genome sequencing of Anopheles gambiae was completed more than ten years ago and has accelerated research on malaria transmission. However, annotation needs to be refined and verified experimentally, as most predicted transcripts have been identified by comparative analysis with genomes from other species. The mosquito midgut-the first organ to interact with Plasmodium parasites-mounts effective antiplasmodial responses that limit parasite survival and disease transmission. High-throughput Illumina sequencing of the midgut transcriptome was used to identify new genes and transcripts, contributing to the refinement of An. gambiae genome annotation. RESULTS: We sequenced ~223 million reads from An. gambiae midgut cDNA libraries generated from susceptible (G3) and refractory (L35) mosquito strains. Mosquitoes were infected with either Plasmodium berghei or Plasmodium falciparum, and midguts were collected after the first or second Plasmodium infection. In total, 22,889 unique midgut transcript models were generated from both An. gambiae strain sequences combined, and 76% are potentially novel. Of these novel transcripts, 49.5% aligned with annotated genes and appear to be isoforms or pre-mRNAs of reference transcripts, while 50.5% mapped to regions between annotated genes and represent novel intergenic transcripts (NITs). Predicted models were validated for midgut expression using qRT-PCR and microarray analysis, and novel isoforms were confirmed by sequencing predicted intron-exon boundaries. Coding potential analysis revealed that 43% of total midgut transcripts appear to be long non-coding RNA (lncRNA), and functional annotation of NITs showed that 68% had no homology to current databases from other species. Reads were also analyzed using de novo assembly and predicted transcripts compared with genome mapping-based models. Finally, variant analysis of G3 and L35 midgut transcripts detected 160,742 variants with respect to the An. gambiae PEST genome, and 74% were new variants. Intergenic transcripts had a higher frequency of variation compared with non-intergenic transcripts. CONCLUSION: This in-depth Illumina sequencing and assembly of the An. gambiae midgut transcriptome doubled the number of known transcripts and tripled the number of variants known in this mosquito species. It also revealed existence of a large number of lncRNA and opens new possibilities for investigating the biological function of many newly discovered transcripts.
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Anopheles/genética , Mucosa Intestinal/metabolismo , Anotação de Sequência Molecular/métodos , Transcriptoma , Animais , Anopheles/embriologia , Anopheles/parasitologia , Variação Genética , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Plasmodium berghei/fisiologia , Plasmodium falciparum/fisiologia , RNA Mensageiro/genética , Análise de Sequência de RNARESUMO
Tuning the coordination structures of metal sites is intensively studied to improve the performances of single-atom site catalysts (SASC). However, the pore structure of SASC, which is highly related to the accessibility of active sites, has received little attention. In this work, single-atom ZnN4 sites embedded in P-functionalized carbon with hollow-wall and 3D ordered macroporous structure (denoted as H-3DOM-ZnN4 /P-C) are constructed. The creation of hollow walls in ordered macroporous structures can largely increase the external surface area to expose more active sites. The introduction of adjacent P atoms can optimize the electronic structure of ZnN4 sites through long-rang regulation to enhance the intrinsic activity and selectivity. In the electrochemical CO2 reduction reaction, H-3DOM-ZnN4 /P-C exhibits high CO Faradaic efficiency over 90% in a wide potential window (500 mV) and a large turnover frequency up to 7.8 × 104 h-1 at -1.0 V versus reversible hydrogen electrode, much higher than its counterparts without the hierarchically ordered structure or P-functionalization.