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The escalating demand for portable near-infrared (NIR) light sources has posed a formidable challenge to the development of NIR phosphors characterized by high efficiency and exceptional thermal stability. Taking inspiration from the chemical unit co-substitution strategy, high-performance tunable (Lu3- xCax)(Ga5- xGex)O12:6%Cr3+ (x = 0-3) phosphors are designed with an emission center from 704 to 780 nm and a broadest full width at half maximum (FWHM) of up to 172 nm by introducing Ca2+ and Ge4+ ions into the garnet structure. In particular, Lu3Ga5O12:6%Cr3+ demonstrates an anti-thermal quenching phenomenon (I423K = 113.1%). Compared to Lu3Ga5O12:6%Cr3+, Lu2CaGa4GeO12:6%Cr3+ exhibits significantly improved FWHM and IQE by 108 nm and 25.5%, respectively, while maintaining good thermal stability (I423K = 80.4%). Finally, Lu2CaGa4GeO12:6%Cr3+ phosphor is combined with a 465 nm blue LED chip to fabricate NIR LED devices, exhibiting a NIR electroluminescence efficiency of 13.31%@100 mA and demonstrating successful applications in nocturnal illumination and biomedical imaging technology. This work offers a fresh perspective on the design of highly efficient NIR garnet phosphors.
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Mechanoluminescence (ML) materials are featured with the characteristic of "force to light" in response to external stimuli, which have made great progress in artificial intelligence and optical sensing. However, how to effectively enable ML in the material is a daunting challenge. Here, a Lu3Al2Ga3O12:Cr3+ (LAGO: Cr3+) near infrared (NIR) ML material peaked at 706 nm is reported, which successfully realizes the key to unlock ML by the lattice-engineering strategy Ga3+ substitution for Al3+ to "grow" oxygen vacancy (Ov) defects. Combined with thermoluminescence measurements, the observed ML is due to the formation of defect levels and the ML intensity is proportional to it. It is confirmed by X-ray photoelectron spectroscopy and electron paramagnetic resonance that such a process is dominated by Ov, which plays a crucial role in turning on ML in this compound. In addition, potential ML emissions from 4T2 and 2E level transitions are discussed from both experimental and theoretical aspects. This study reveals the mechanism of the change in ML behavior after cation substitution, and it may have important implications for the practical application of Ov defect-regulated turn-on of ML.
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Mechanoluminescence (ML) phosphors have found various promising utilizations such as in non-destructive stress sensing, anti-counterfeiting, and bio stress imaging. However, the reported NIR MLs have predominantly been limited to bulky particle size and weak ML intensity, hindering the further practical applications. For this regard, a nano-sized ZnGa2O4: Cr3+ NIR ML phosphor is synthesized by hydrothermal method. By improving the synthesis method and regulating the chemical composition, the NIR ML (600-1000 nm) intensity of such nano-materials has been further enhanced about four times. The reasons for the ML performance difference between micro-/nano- sized phosphors also have been preliminarily analyzed. Additionally, this work probes into the ML mechanism deeply in traps' aspect from band structure and defect formation energy, which can supply significant references for a new approach to develop efficient NIR ML nanoparticles. Finally, due to excellent tissue penetration capability, nano-sized ZnGa2O4:Cr3+ NIR ML phosphor shows great potential applications in biomedical fields such as for the detection of clinical oral diseases.
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BACKGROUND: Both functional brain imaging studies and autopsy reports have indicated the presence of synaptic loss in the brains of depressed patients. The activated microglia may dysfunctionally engulf neuronal synapses, leading to synaptic loss and behavioral impairments in depression. However, the mechanisms of microglial-synaptic interaction under depressive conditions remain unclear. METHODS: We utilized lipopolysaccharide (LPS) to induce a mouse model of depression, examining the effects of LPS on behaviors, synapses, microglia, microglial phagocytosis of synapses, and the C1q/C3-CR3 complement signaling pathway. Additionally, a C1q neutralizing antibody was employed to inhibit the C1q/C3-CR3 signaling pathway and assess its impact on microglial phagocytosis of synapses and behaviors in the mice. RESULTS: LPS administration resulted in depressive and anxiety-like behaviors, synaptic loss, and abnormal microglial phagocytosis of synapses in the hippocampal dentate gyrus (DG) of mice. We found that the C1q/C3-CR3 signaling pathway plays a crucial role in this abnormal microglial activity. Treatment with the C1q neutralizing antibody moderated the C1q/C3-CR3 pathway, leading to a decrease in abnormal microglial phagocytosis, reduced synaptic loss, and improved behavioral impairments in the mice. CONCLUSIONS: The study suggests that the C1q/C3-CR3 complement signaling pathway, which mediates abnormal microglial phagocytosis of synapses, presents a novel potential therapeutic target for depression treatment.
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Complemento C1q , Complemento C3 , Depressão , Modelos Animais de Doenças , Microglia , Fagocitose , Transdução de Sinais , Sinapses , Animais , Complemento C1q/metabolismo , Microglia/metabolismo , Sinapses/metabolismo , Camundongos , Transdução de Sinais/fisiologia , Depressão/metabolismo , Fagocitose/fisiologia , Complemento C3/metabolismo , Masculino , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BLRESUMO
X-ray crystallography has for most of the last century been the standard technique to determine the high-resolution structure of biological macromolecules, including multi-subunit protein-protein and protein-nucleic acids as large as the ribosome and viruses. As such, the successful application of X-ray crystallography to many biological problems revolutionized biology and biomedicine by solving the structures of small molecules and vitamins, peptides and proteins, DNA and RNA molecules, and many complexes-affording a detailed knowledge of the structures that clarified biological and chemical mechanisms, conformational changes, interactions, catalysis and the biological processes underlying DNA replication, translation, and protein synthesis. Now reaching well into the first quarter of the twenty-first century, X-ray crystallography shares the structural biology stage with cryo-electron microscopy and other innovative structure determination methods, as relevant and central to our understanding of biological function and structure as ever. In this chapter, we provide an overview of modern X-ray crystallography and how it interfaces with other mainstream structural biology techniques, with an emphasis on macromolecular complexes.
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Biologia Molecular , Proteínas , Cristalografia por Raios X , Microscopia Crioeletrônica/métodos , Proteínas/química , Substâncias Macromoleculares/químicaRESUMO
Near-infrared light sources have potential applications in many fields. Cr3+ is a good luminescence centre to prepare near-infrared phosphors. Improving the performance of existing near-infrared luminescent materials has indeed attracted great interest from researchers. The luminescence properties of Zn2TiO4:Cr3+ were improved by crystal field engineering strategies. Zn2+-Ti4+ was partially replaced using a Li+-Nb5+ ion pair based on the Zn2TiO4:Cr3+ phosphors. Luminescence Cr3+-activated luminescent materials are sensitive to changes in the local crystal structure and crystal field environment. Doping of Li+-Nb5+ increased the luminescence intensity up to 2.7 times that of the undoped sample. Also, the thermal stability of the phosphor was greatly increased by the replacement of Li+-Nb5+.
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Raios Infravermelhos , Luminescência , Íons , Lítio , ZincoRESUMO
Persistent luminescent nanomaterials (PLNPs) Zn0.8Ga2O4: Cr3+, Zr3+ with high brightness and good dispersion were prepared by hydrothermal method. The PLNPs were used as luminescent units, and CoOOH nanosheets were used as quenching agents. Based on the fluorescence internal filtering effect, the luminescence of PLNPs were effectively quenched by CoOOH modification on the surface of PLNPs. However, the introduction of ascorbic acid (AA) restored the luminescence of PLNPs and successfully achieved highly sensitive and selective detection of AA. This was due to a selective redox reaction between CoOOH and AA, in which CoOOH was reduced to Co2+. The degree of luminescence recovery of PLNPs showed a good linear relationship with AA concentration in the range 5-250 µM, with a detection limit of 0.72 µM. The recovery of actual spiked samples were 97.9-102.2%. This method is expected to provide reference for the study of other redox substances in biological systems.
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The pollution of heavy metals in soil to the environment is becoming more and more serious, resulting in the reduction of crop production and the occurrence of medical accidents. In order to remove heavy metal ions from soil and reduce the harm of heavy metals to the environment, modified peanut shell was used to adsorb Cr3+ in this article. The effects of different adsorption conditions on the adsorption rate and adsorption capacity of Cr3+ on ZnCl2 modified peanut shell were studied, the best adsorption conditions were explored, and the relationship of kinetics, thermodynamics and adsorption isotherm properties of adsorption process were explored. The results showed that the optimum adsorption pH value, dosage, initial concentration, adsorption temperature and contact time of ZnCl2 modified peanut shell were 2.5, 2.5â g/L, 75â µg/mL, 25 °C and 40â min, respectively. The prepared materials were characterized and analyzed by scanning electron microscope (SEM) and X-ray diffraction (XRD) analyzer. It was concluded that the modified peanut shell had a good adsorption capacity to Cr3+ . The kinetic study showed that the adsorption process of Cr3+ on peanut shell modified by zinc chloride was in accordance with the quasi-second-order kinetic model. The adsorption process belonged to exothermic reaction and belonged to spontaneous reaction process. In summary, it is proved that zinc chloride modified peanut shell can efficiently adsorb Cr3+ , which can be used for the treatment of heavy metal wastes in industry, which is beneficial to environmental protection and avoid heavy metal pollution.
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Metais Pesados , Poluentes Químicos da Água , Cromo/análise , Cromo/química , Arachis , Adsorção , Cinética , Termodinâmica , Solo , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Cr3+-doped Sr3Ga2Ge4O14:0.03Cr3+ (SGGO:0.03Cr3+) phosphor was synthesized via a high-temperature solid-phase method. Considering the tunable structure of SGGO, Ga3+ ions in the matrix were substituted with In3+ ions at a certain concentration. The tuned phosphor produced a red-shifted emission spectrum, with its luminescence intensity at 423 K maintained at 63% of that at room temperature; moreover, the internal quantum efficiency increased to 65.60%, and the external quantum efficiency correspondingly increased to 21.94%. On this basis, SGIGO:0.03Cr3+ was encapsulated into a pc-LED, which was applied in non-destructive testing (NDT) experiments, successfully realizing the recognition of water and anhydrous ethanol, proving its potential application in the field of NDT.
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Cr(VI) is a hazardous environmental pollutant that poses significant risks to ecosystems and human health. We successfully isolated a novel strain of Bacillus mobilis, strain CR3, from Cr(VI)-contaminated soil. Strain CR3 showed 86.70% removal capacity at 200 mg/L Cr(VI), and a good Cr(VI) removal capacity at different pH, temperature, coexisting ions, and electron donor conditions. Different concentrations of Cr(VI) affected the activity of CR3 cells and the removal rate of Cr(VI), and approximately 3.46% of total Cr was immobilized at the end of the reaction. The combination of SEM-EDS and TEM-EDS analysis showed that Cr accumulated both on the cell surface and inside the cells after treatment with Cr(VI). XPS analysis showed that both Cr(III) and Cr(VI) were present on the cell surface, and FTIR results indicated that the presence of Cr on the cell surface was mainly related to functional groups, such as O-H, phosphate, and -COOH. The removal of Cr(VI) was mainly achieved through bioreduction, which primarily occurred outside the cell. Metabolomics analysis revealed the upregulation of five metabolites, including phenol and L-carnosine, was closely associated with Cr(VI) reduction, heavy metal chelation, and detoxification mechanisms. In addition, numerous metabolites were linked to cellular homeostasis exhibited differential expression. Cr(VI) exerted inhibitory effects on the division rate and influenced critical pathways, including energy metabolism, nucleotide metabolism, and amino acid synthesis and catabolism. These findings reveal the molecular mechanism of Cr(VI) removal by strain CR3 and provide valuable insights to guide the remediation of Cr(VI)-contaminated sites.
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Bacillus , Ecossistema , Humanos , Bacillus/genética , Bacillus/metabolismo , Cromo/toxicidade , Cromo/metabolismo , Biodegradação AmbientalRESUMO
Axon regenerative failure in the mature CNS contributes to functional deficits following many traumatic injuries, ischemic injuries, and neurodegenerative diseases. The complement cascade of the innate immune system responds to pathogen threat through inflammatory cell activation, pathogen opsonization, and pathogen lysis, and complement is also involved in CNS development, neuroplasticity, injury, and disease. Here, we investigated the involvement of the classical complement cascade and microglia/monocytes in CNS repair using the mouse optic nerve injury (ONI) model, in which axons arising from retinal ganglion cells (RGCs) are disrupted. We report that central complement C3 protein and mRNA, classical complement C1q protein and mRNA, and microglia/monocyte phagocytic complement receptor CR3 all increase in response to ONI, especially within the optic nerve itself. Importantly, genetic deletion of C1q, C3, or CR3 attenuates RGC axon regeneration induced by several distinct methods, with minimal effects on RGC survival. Local injections of C1q function-blocking antibody revealed that complement acts primarily within the optic nerve, not retina, to support regeneration. Moreover, C1q opsonizes and CR3+ microglia/monocytes phagocytose growth-inhibitory myelin debris after ONI, a likely mechanism through which complement and myeloid cells support axon regeneration. Collectively, these results indicate that local optic nerve complement-myeloid phagocytic signaling is required for CNS axon regrowth, emphasizing the axonal compartment and highlighting a beneficial neuroimmune role for complement and microglia/monocytes in CNS repair.SIGNIFICANCE STATEMENT Despite the importance of achieving axon regeneration after CNS injury and the inevitability of inflammation after such injury, the contributions of complement and microglia to CNS axon regeneration are largely unknown. Whereas inflammation is commonly thought to exacerbate the effects of CNS injury, we find that complement proteins C1q and C3 and microglia/monocyte phagocytic complement receptor CR3 are each required for retinal ganglion cell axon regeneration through the injured mouse optic nerve. Also, whereas studies of optic nerve regeneration generally focus on the retina, we show that the regeneration-relevant role of complement and microglia/monocytes likely involves myelin phagocytosis within the optic nerve. Thus, our results point to the importance of the innate immune response for CNS repair.
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Axônios/metabolismo , Complemento C1q/metabolismo , Complemento C3/metabolismo , Células Mieloides/metabolismo , Traumatismos do Nervo Óptico/metabolismo , Células Ganglionares da Retina/metabolismo , Animais , Axônios/imunologia , Complemento C1q/imunologia , Complemento C3/imunologia , Feminino , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides/imunologia , Regeneração Nervosa/fisiologia , Traumatismos do Nervo Óptico/imunologia , Traumatismos do Nervo Óptico/patologia , Células Ganglionares da Retina/imunologiaRESUMO
ß-glucans are a diverse group of polysaccharides composed of ß-1,3 or ß-(1,3-1,4) linked glucose monomers. They are mainly synthesized by fungi, plants, seaweed and bacteria, where they carry out structural, protective and energy storage roles. Because of their unique physicochemical properties, they have important applications in several industrial, biomedical and biotechnological processes. ß-glucans are also major bioactive molecules with marked immunomodulatory and metabolic properties. As such, they have been the focus of many studies attesting to their ability to, among other roles, fight cancer, reduce the risk of cardiovascular diseases and control diabetes. The physicochemical and functional profiles of ß-glucans are deeply influenced by their molecular structure. This structure governs ß-glucan interaction with multiple ß-glucan binding proteins, triggering myriad biological responses. It is then imperative to understand the structural properties of ß-glucans to fully reveal their biological roles and potential applications. The deconstruction of ß-glucans is a result of ß-glucanase activity. In addition to being invaluable tools for the study of ß-glucans, these enzymes have applications in numerous biotechnological and industrial processes, both alone and in conjunction with their natural substrates. Here, we review potential applications for ß-glucans and ß-glucanases, and explore how their functionalities are dictated by their structure.
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Neoplasias , beta-Glucanas , Fungos/metabolismo , Estrutura Molecular , Neoplasias/tratamento farmacológico , Plantas/metabolismo , Polissacarídeos/química , beta-Glucanas/químicaRESUMO
A typical structure of thermal spray coatings consisted of molten particles, semi-molten particles, oxides, pores, and cracks. These factors caused the porosity of sprayed coatings, leading to a significant influence on the coating properties, especially their wear-corrosion resistance. In this study, a post-spray sealing treatment of Cr3C2-NiCr/Al2O3-TiO2 plasma-sprayed coatings was carried out, and then, their corrosion properties were evaluated, before and after the treatment. For the sealing process, aluminum phosphate (APP) containing Al2O3 nanoparticles (~10 nm) was used. The permeability of APP into the sprayed coating was analyzed by SEM-EDS. The treatment efficiency for porosity and corrosion resistance of sprayed coatings was evaluated by electrochemical measurements, such as the potentiodynamic polarization and electrochemical impedance spectroscopy. The wear-corrosion resistance of the coating was examined in 3.5 wt.% NaCl circulation solution containing 0.25% SiO2 particles. The sealing efficiency was evaluated by the percentage of the treated open pores in the coating. The obtained results showed that APP penetrated deeply through the coating and the incorporation of Al2O3 nanoparticles into APP sealant improved the sealing efficiency by 20% of open pores in comparison with the sealant without nano-Al2O3. The effect of the post-treatment on corrosion protection of the sprayed coating has been discussed.
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The minimization of thermal quenching, which leads to luminescence loss at high temperatures, is one of the most important issues for near-infrared phosphors. In the present work, we investigated the properties of near-infrared Ca(Sc,Mg)(Al, Si)O6 : Cr3+ phosphors with a pyroxene-type structure under blue light excitation. The CaScAlSiO6 : Cr3+ end member of Ca(Sc,Mg)(Al,Si)O6 : Cr3+ phosphor led to broadband emission at a full-width half maximum of 215â nm, whereas the CaMgSi2 O6 : Cr3+ end member exhibited high thermal stability at 150 °C, with an intensity of 88.4 % of that at room temperature. The structural analysis and density functional theory calculations revealed the absence of soft conformations and local space confinement contributed to the high structural rigidity and weakened the thermal quenching effect.
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Integrins are cell membrane receptors that are involved in essential physiological and serious pathological processes. Their main role is to ensure a closely regulated link between the extracellular matrix and the intracellular cytoskeletal network enabling cells to react to environmental stimuli. Complement receptor type 3 (CR3, αMß2, CD11b/CD18) and type 4 (CR4, αXß2, CD11c/CD18) are members of the ß2-integrin family expressed on most white blood cells. Both receptors bind multiple ligands like iC3b, ICAM, fibrinogen or LPS. ß2-integrins are accepted to play important roles in cellular adhesion, migration, phagocytosis, ECM rearrangement and inflammation. Several pathological conditions are linked to the impaired functions of these receptors. CR3 and CR4 are generally thought to mediate overlapping functions in monocytes, macrophages and dendritic cells, therefore the potential distinctive role of these receptors has not been investigated so far in satisfactory details. Lately it has become clear that a functional segregation has evolved between the two receptors regarding phagocytosis, cellular adhesion and podosome formation. In addition to their tasks on myeloid cells, the expression and function of CR3 and CR4 on lymphocytes have also gained interest recently. The picture is further complicated by the fact that while these ß2-integrins are expressed by immune cells both in mice and humans, there are significant differences in their expression level, functions and the pathological consequences of genetic defects. Here we aim to summarize our current knowledge on CR3 and CR4 and highlight the functional differences between these receptors, involving their expression in myeloid and lymphoid cells of both men and mice.
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Complemento C3/metabolismo , Complemento C4/metabolismo , Linfócitos/metabolismo , Células Mieloides/metabolismo , Animais , Complemento C3/imunologia , Complemento C4/imunologia , Humanos , Linfócitos/imunologia , Masculino , CamundongosRESUMO
The Bordetella adenylate cyclase toxin-hemolysin (CyaA) and the α-hemolysin (HlyA) of Escherichia coli belong to the family of cytolytic pore-forming Repeats in ToXin (RTX) cytotoxins. HlyA preferentially binds the αLß2 integrin LFA-1 (CD11a/CD18) of leukocytes and can promiscuously bind and also permeabilize many other cells. CyaA bears an N-terminal adenylyl cyclase (AC) domain linked to a pore-forming RTX cytolysin (Hly) moiety, binds the complement receptor 3 (CR3, αMß2, CD11b/CD18, or Mac-1) of myeloid phagocytes, penetrates their plasma membrane, and delivers the AC enzyme into the cytosol. We constructed a set of CyaA/HlyA chimeras and show that the CyaC-acylated segment and the CR3-binding RTX domain of CyaA can be functionally replaced by the HlyC-acylated segment and the much shorter RTX domain of HlyA. Instead of binding CR3, a CyaA1-710/HlyA411-1024 chimera bound the LFA-1 receptor and effectively delivered AC into Jurkat T cells. At high chimera concentrations (25 nm), the interaction with LFA-1 was not required for CyaA1-710/HlyA411-1024 binding to CHO cells. However, interaction with the LFA-1 receptor strongly enhanced the specific capacity of the bound CyaA1-710/HlyA411-1024 chimera to penetrate cells and deliver the AC enzyme into their cytosol. Hence, interaction of the acylated segment and/or the RTX domain of HlyA with LFA-1 promoted a productive membrane interaction of the chimera. These results help delimit residues 400-710 of CyaA as an "AC translocon" sufficient for translocation of the AC polypeptide across the plasma membrane of target cells.
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Toxina Adenilato Ciclase/metabolismo , Bordetella , Citosol/metabolismo , Antígeno-1 Associado à Função Linfocitária/metabolismo , Antígeno de Macrófago 1/metabolismo , Animais , Células CHO , Cricetulus , Feminino , Humanos , Células Jurkat , Camundongos , Camundongos Endogâmicos BALB C , Transporte Proteico , Células THP-1RESUMO
Persistent luminescent nanocrystals (PLNCs) in the sub-10â nm domain are considered to be the most fascinating inventions in lighting technology owing to their excellent performance in anti-counterfeiting, luminous paints, bioimaging, security applications, etc. Further improvement of persistent luminescence (PersL) intensity and lifetime is needed to achieve the desired success of PLNCs while keeping the uniform sub-10â nm size. In this work, the concept of molten salt confinement to thermally anneal as-synthesized ZnGa2 O4 :Cr3+ (ZGOC) colloidal NCs (CNCs) in a molten salt medium at 650 °C is introduced. This method led to significantly monodispersed and few agglomerated NCs with a much improved photoluminescence (PL) and PersL intensity without much growth in the size of the pristine CNCs. Other strategies such as i) thermal annealing, ii) overcoating, and iii) the core-shell strategy have also been tried to improve PL and PersL but did not improve them simultaneously. Moreover, directly annealing the CNCs in air without the assistance of molten salt could significantly improve both PL and PersL but led to particle heterogeneity and aggregation, which are highly unsuitable for inâ vivo imaging. We believe this work provides a novel strategy to design PLNCs with high PL intensity and long PersL duration without losing their nanostructural characteristics, water dispersibility and biocompatibility.
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Nanopartículas , Nanoestruturas , Luminescência , ÁguaRESUMO
Quantitative characterization of Cr3+, an important element revealing human metabolism and biological environmental variation, is still difficult to achieve by conventional biochemical methods due to the lack of high-sensitivity, real-time techniques with rapid response detection. Using surface-enhanced Raman scattering (SERS), we construct an Au/Ag composite-based SERS nanoprobe for the quantitative characterization of Cr3+ content in solution, in which DL-mercaptosuccinic acid (DL-MSA) is employed for Raman signal enhancement, and 4-mercaptobenzoic acid (4-MBA) is chosen as the Raman reporter. The achieved result demonstrates obvious advantages of the synthesized Au/Ag composite-based SERS nanoprobe in sensitivity and response speed. Importantly, this Au/Ag composite-based SERS nanoprobe might provide a new strategy for dynamic monitoring of Cr3+ content in human metabolism.
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Cromo/análise , Ouro/química , Nanopartículas Metálicas/química , Sondas Moleculares/química , Prata/química , Análise Espectral Raman/métodos , Células HEK293 , Humanos , Microscopia Eletrônica de Transmissão , Soluções , Espectrofotometria UltravioletaRESUMO
The parasitic protozoan Leishmania infantum resides primarily in macrophages throughout mammalian infection. Infection is initiated by deposition of the metacyclic promastigote into the dermis of a mammalian host by the sand fly vector. Promastigotes enter macrophages by ligating surface receptors such as complement receptor 3 (CR3), inducing phagocytosis of the parasite. At the binding site of metacyclic promastigotes, we observed large asymmetrical aggregates of macrophage membrane with underlying actin, resembling membrane ruffles. Actin accumulation was observed at the point of initial contact, before phagosome formation and accumulation of peri-phagosomal actin. Ruffle-like structures did not form during phagocytosis of attenuated promastigotes or during phagocytosis of the intracellular amastigote form of L. infantum. Entry of promastigotes through massive actin accumulation was associated with a subsequent delay in fusion of the parasitophorous vacuole (PV) with the lysosomal markers LAMP-1 and Cathepsin D. Actin accumulation was also associated with entry through CR3, since macrophages from CD11b knockout (KO) mice did not form massive aggregates of actin during phagocytosis of metacyclic promastigotes. Furthermore, intracellular survival of L. infantum was significantly decreased in CD11b KO compared to wild type macrophages, although entry rates were similar. We conclude that both promastigote virulence and host cell CR3 are needed for the formation of ruffle-like membrane structures at the site of metacyclic promastigote phagocytosis, and that formation of actin-rich aggregates during entry correlates with the intracellular survival of virulent promastigotes.
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Actinas/metabolismo , Leishmania infantum/fisiologia , Leishmaniose Visceral/parasitologia , Antígeno de Macrófago 1/fisiologia , Fagocitose/fisiologia , Animais , Catepsina D/metabolismo , Membrana Celular/ultraestrutura , Cricetinae , Humanos , Leishmania infantum/patogenicidade , Leishmania infantum/ultraestrutura , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Macrófagos/parasitologia , Masculino , Mesocricetus , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microscopia Confocal , Vacúolos/parasitologia , VirulênciaRESUMO
Understanding the host anti-fungal immunity induced by beta-glucan has been one of the most challenging conundrums in the field of biomedical research. During the last couple of decades, insights on the role of beta-glucan in fungal disease progression, susceptibility, and resistance have been greatly augmented through the utility of various beta-glucan cognate receptor-deficient mouse models. Analysis of dectin-1 knockout mice has clarified the downstream signaling pathways and adaptive effector responses triggered by beta-glucan in anti-fungal immunity. On the other hand, assessment of CR3-deficient mice has elucidated the compelling action of beta-glucans in neutrophil-mediated fungal clearance, and the investigation of EphA2-deficient mice has highlighted its novel involvement in host sensing and defense to oral mucosal fungal infection. Based on these accounts, this review focuses on the recent discoveries made by these gene-targeted mice in beta-glucan research with particular emphasis on the multifaceted aspects of fungal immunity.