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Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Microesferas , Terapia Fototérmica , Pneumonia Estafilocócica/terapia , Terapia por Fagos/métodos , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Verde de Indocianina/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Administração por Inalação , Humanos , Bacteriófagos/químicaRESUMO
The inherently huge volume expansion during Li uptake has hindered the use of Si-based anodes in high-energy lithium-ion batteries. While some pore-forming and nano-architecting strategies show promises to effectively buffer the volume change, other parameters essential for practical electrode fabrication, such as compaction density, are often compromised. Here we propose a new in situ Mg doping strategy to form closed-nanopore structure into a micron-sized SiOx particle at a high bulk density. The doped Mg atoms promote the segregation of O, so that high-density magnesium silicates form to generate closed nanopores. By altering the mass content of Mg dopant, the average radii (ranged from 5.4 to 9.7â nm) and porosities (ranged from 1.4 % to 15.9 %) of the closed pores are precisely adjustable, which accounts for volume expansion of SiOx from 77.8 % to 22.2 % at the minimum. Benefited from the small volume variation, the Mg-doped micron-SiOx anode demonstrates improved Li storage performance towards realization of a 700-(dis)charge-cycle, 11-Ah-pouch-type cell at a capacity retention of >80 %. This work offers insights into reasonable design of the internal structure of micron-sized SiOx and other materials that undergo conversion or alloying reactions with drastic volume change, to enable high-energy batteries with stable electrochemistry.
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Translation is one of the many critical cellular activities regulated by viruses following host-cell invasion, and studies of viral mRNA translation kinetics and subcellular localization require techniques for the dynamic, real-time visualization of translation. However, conventional tools for imaging mRNA translation often require coding region modifications that may affect native translation. Here, we achieve dynamic imaging of translation with a tool that labels target mRNAs with unmodified coding regions using a CRISPR/dCas13 system with specific complementary paired guide RNAs. This system enables a real-time dynamic visualization of the translation process and is a promising tool for further investigations of the mechanisms of translation.
Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Vírus , RNA Mensageiro/genética , Vírus/genética , Diagnóstico por Imagem , Biossíntese de ProteínasRESUMO
BACKGROUND: Soybeans and defatted soybeans, commonly used as protein ingredients, have different flavors of their fermented soy sauce. Clarifying the differences between the two soy sauces, as well as the formation mechanism, is an important prerequisite for improving the flavor of defatted soybean soy sauce. To this goal, the aroma characteristics of two soy sauces and their volatile profiles were compared by sensory evaluation and gas chromatography-mass spectrometry, and eight enzyme activities and volatile profiles of matured koji were determined. RESULTS: Sensory results showed that the acids, fruity and cooked potato-like attributes were higher in whole soybean fermented soy sauce, whereas defatted soybean soy sauce exhibited higher smoky and malty attributes, closely related to the contents of aroma-active compounds in soy sauce, such as isobutyl acetate, 2/3-methylbutanal, acetic acid and 2/3-methylbutanoic acid. The content of most volatiles in the matured kojis showed a consistent trend with that of soy sauce: alcohols, acids, furan(one)s and ketones. Interestingly, acid protease and cellulase activities were 3.3 and 1.6 times higher in the whole soybean koji than in defatted soybean koji, respectively, whereas neutral protease, aminopeptidase, glucoamylase and ß-glucosidase were approximately 2.0 times higher in defatted soybean koji. CONCLUSION: In summary, the flavor differences between soybean and defatted soybean fermented soy sauce were not only caused by the differences in the content of flavor precursors in the materials, but also closely related to the differences in the enzymatic profiles accumulated during the koji-making process. © 2022 Society of Chemical Industry.
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Alimentos de Soja , Alimentos de Soja/análise , Glycine max/metabolismo , Fermentação , Odorantes/análise , Peptídeo Hidrolases/metabolismoRESUMO
Real-time visualization of individual viral mRNA translation activities in live cells is essential to obtain critical details of viral mRNA dynamics and to detect its transient responses to environmental stress. Fluorogenic RNA aptamers are powerful tools for real-time imaging of mRNA in live cells, but monitoring the translation activity of individual mRNAs remains a challenge due to their intrinsic photophysical properties. Here, we develop a genetically encoded turn-on 3,5-difluoro-4-hydroxybenzylidene imidazolinone (DFHBI)-binding RNA nanozipper with superior brightness and high photostability by in situ self-assembly of multiple nanozippers along single mRNAs. The nanozipper enables real-time imaging of the mobility and dynamic translation of individual viral mRNAs in live cells, providing information on the spatial dynamics and translational elongation rate of viral mRNAs.
Assuntos
Biossíntese de Proteínas , RNA , RNA/química , RNA Mensageiro/metabolismo , Diagnóstico por Imagem , RNA Viral/genéticaRESUMO
Ether solvents with superior reductive stability promise excellent interphasial stability with high-capacity anodes while the limited oxidative resistance hinders their high-voltage operation. Extending the intrinsic electrochemical stability of ether-based electrolytes to construct stable-cycling high-energy-density lithium-ion batteries is challenging but rewarding. Herein, the anion-solvent interactions were concerned as the key point to optimize the anodic stability of the ether-based electrolytes and an optimized interphase was realized on both pure-SiOx anodes and LiNi0.8 Mn0.1 Co0.1 O2 cathodes. Specifically, the small-anion-size LiNO3 and tetrahydrofuran with high dipole moment to dielectric constant ratio realized strengthened anion-solvent interactions, which enhance the oxidative stability of the electrolyte. The designed ether-based electrolyte enabled a stable cycling performance over 500â cycles in pure-SiOx ||LiNi0.8 Mn0.1 Co0.1 O2 full cell, demonstrating its superior practical prospects. This work provides new insight into the design of new electrolytes for emerging high-energy density lithium-ion batteries through the regulation of interactions between species in electrolytes.
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In Li-ion batteries, functional cosolvents could significantly improve the specific performance of the electrolyte, for example, the flame retardancy. In case the cosolvent shows strong Li+-coordinating ability, it could adversely influence the electrochemical Li+-intercalation reaction of the electrode. In this work, a noncoordinating functional cosolvent was proposed to enrich the functionality of the electrolyte while avoiding interference with the Li storage process. Hexafluorocyclotriphosphazene, an efficient flame-retardant agent with proper physicochemical properties, was chosen as a cosolvent for preparing functional electrolytes. The nonpolar phosphazene molecules with low electron-donating ability do not coordinate with Li+ and thus are excluded from the primary solvation sheath. In graphite-anode-based Li-ion batteries, the phosphazene molecules do not cointercalate with Li+ into the graphite lattice during the charging process, which helps to maintain integral anode structure and interface and contributes to stable cycling. The noncoordinating cosolvent was also applied to other types of electrode materials and batteries, paving a new way for high-performance electrochemical energy storage systems with customizable functions.
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Rechargeable lithium-metal batteries with a cell-level specific energy of >400â Wh kg-1 are highly desired for next-generation storage applications, yet the research has been retarded by poor electrolyte-electrode compatibility and rigorous safety concerns. We demonstrate that by simply formulating the composition of conventional electrolytes, a hybrid electrolyte was constructed to ensure high (electro)chemical and thermal stability with both the Li-metal anode and the nickel-rich layered oxide cathodes. By employing the new electrolyte, Liâ¥LiNi0.6 Co0.2 Mn0.2 O2 cells show favorable cycling and rate performance, and a 10â Ah Liâ¥LiNi0.8 Co0.1 Mn0.1 O2 pouch cell demonstrates a practical specific energy of >450â Wh kg-1 . Our findings shed light on reasonable design principles for electrolyte and electrode/electrolyte interfaces toward practical realization of high-energy rechargeable batteries.
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The plasma membranes (PM) of mammalian cells contain diverse lipids, proteins, and carbohydrates that are important for systemic recognition and communication in health and disease. Cell membrane coating technology that imparts unique properties of natural plasma membranes to the surface of encapsulated nanoparticles is thus becoming a powerful platform for drug delivery, immunomodulation, and vaccination. However, current coating methods fail to take full advantage of the natural systems because they disrupt the complex and functionally essential features of PMs, most notably the chemical diversity and compositional differences of lipids in two leaflets of the PM. Herein, a new lipid coating approach is reported in which the lipid composition is optimized through a combination of biomimetic and systematic variation approaches for the custom design of nanocarrier systems for precision drug delivery. Nanocarriers coated with the optimized lipids offer unique advantages in terms of bioavailability and efficiency in tumor targeting, tumor penetration, cellular uptake, and drug release. This pilot study provides new insight into the rational design and optimization of nanocarriers for cancer chemotherapeutic drugs and lays the foundation for further customization of cell membrane-mimicking nanocarriers through systematic incorporation of other components.
Assuntos
Nanopartículas , Neoplasias , Animais , Membrana Celular/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Mamíferos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Projetos Piloto , HumanosRESUMO
The high-capacity advantage of lithium metal anode was compromised by common use of copper as the collector. Furthermore, lithium pulverization associated with "dead" Li accumulation and electrode cracking deteriorates the long-term cyclability of lithium metal batteries, especially under realistic test conditions. Here, we report an ultralight, integrated anode of polyimide-Ag/Li with dual anti-pulverization functionality. The silver layer was initially chemically bonded to the polyimide surface and then spontaneously diffused in Li solid solution and self-evolved into a fully lithiophilic Li-Ag phase, mitigating dendrites growth or dead Li. Further, the strong van der Waals interaction between the bottommost Li-Ag and polyimide affords electrode structural integrity and electrical continuity, thus circumventing electrode pulverization. Compared to the cutting-edge anode-free cells, the batteries pairing LiNi0.8Mn0.1Co0.1O2 with polyimide-Ag/Li afford a nearly 10% increase in specific energy, with safer characteristics and better cycling stability under realistic conditions of 1× excess Li and high areal-loading cathode (4 milliampere hour per square centimeter).
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Micron-sized Si anode promises a much higher theoretical capacity than the traditional graphite anode and more attractive application prospect compared to its nanoscale counterpart. However, its severe volume expansion during lithiation requires solid electrolyte interphase (SEI) with reinforced mechanical stability. Here, we propose a solvent-induced selective dissolution strategy to in situ regulate the mechanical properties of SEI. By introducing a high-donor-number solvent, gamma-butyrolactone, into conventional electrolytes, low-modulus components of the SEI, such as Li alkyl carbonates, can be selectively dissolved upon cycling, leaving a robust SEI mainly consisting of lithium fluoride and polycarbonates. With this strategy, raw micron-sized Si anode retains 87.5% capacity after 100 cycles at 0.5 C (1500 mA g-1, 25°C), which can be improved to >300 cycles with carbon-coated micron-sized Si anode. Furthermore, the Si||LiNi0.8Co0.1Mn0.1O2 battery using the raw micron-sized Si anode with the selectively dissolved SEI retains 83.7% capacity after 150 cycles at 0.5 C (90 mA g-1). The selective dissolution effect for tailoring the SEI, as well as the corresponding cycling life of the Si anodes, is positively related to the donor number of the solvents, which highlights designing high-donor-number electrolytes as a guideline to tailor the SEI for stabilizing volume-changing alloying-type anodes in high-energy rechargeable batteries.
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The carbon-coated silicon monoxide (SiOx@C) has been considered as one of the most promising high-capacity anodes for the next-generation high-energy-density lithium-ion batteries (LIBs). However, the relatively low initial Coulombic efficiency (ICE) and the still existing huge volume expansion during repeated lithiation/delithiation cycling remain the greatest challenges to its practical application. Here, we developed a lithium and boron (Li/B) co-doping strategy to efficiently enhance the ICE and alleviate the volume expansion or pulverization of SiOx@C anodes. The in situ generated Li silicates (LixSiOy) by Li doping will reduce the active Li loss during the initial cycling and enhance the ICE of SiOx@C anodes. Meanwhile, B doping works to promote the Li+ diffusion and strengthen the internal bonding networks within SiOx@C, enhancing its resistance to cracking and pulverization during cycling. As a result, the enhanced ICE (83.28%), suppressed volume expansion, and greatly improved cycling (85.4% capacity retention after 200 cycles) and rate performance could be achieved for the Li/B co-doped SiOx@C (Li/B-SiOx@C) anodes. Especially, the Li/B-SiOx@C and graphite composite anodes with a capacity of 531.5 mA h g-1 were demonstrated to show an ICE of 90.1% and superior cycling stability (90.1% capacity retention after 250 cycles), which is significant for the practical application of high-energy-density LIBs.
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An artificial "salt-in-polymer" SEI, composed of poly-(1,3-dioxolane) and high-modulus fluorinated products generated from the in situ decomposition of Li salts, was constructed on the surface of Li-MSiOx particles. This LiF-rich SEI helps to maintain the structural integrity of Li-MSiOx particles and improves the Li storage reversibility of the Li-MSiOx anode.
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In recent years, micrometer-sized Si-based anode materials have attracted intensive attention in the pursuit of energy-storage systems with high energy and low cost. However, the significant volume variation during repeated electrochemical (de)alloying processes will seriously damage the bulk structure of SiOx microparticles, resulting in rapid performance fade. This work proposes to address the challenge by preparing in situ magnesium-doped SiOx (SiMgy Ox ) microparticles with stable structural evolution against Li uptake/release. The homogeneous distribution of magnesium silicate in SiMgy Ox contributes to building a bonding network inside the particle so that it raises the modulus of lithiated state and restrains the internal cracks due to electrochemical agglomeration of nano-Si. The prepared micrometer-sized SiMgy Ox anode shows high reversible capacities, stable cycling performance, and low electrode expansion at high areal mass loading. A 21700 cylindrical-type cell based on the SiMgy Ox -graphite anode and LiNi0.8 Co0.15 Al0.05 O2 cathode demonstrates a 1000-cycle operation life using industry-recognized electrochemical test procedures, which meets the practical storage requirements for consumer electronics and electric vehicles. This work provides insights on the reasonable structural design of micrometer-sized alloying anode materials toward realization of high-performance Li-ion batteries.
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Carbon-coated SiOx microparticles (SiOx/C) demonstrate attractive potential for anode use in high-energy-density lithium-ion batteries due to high capacity and proper cycling stability. However, the excessive irreversible consumption of Li ions during the initial cycling remains a serious challenge arising from the limited lithium in full cells. Here, we endow SiOx/C anode with high initial Coulombic efficiency using the chemical pre-lithiation strategy. The lithium silicate is uniformly pregenerated in SiOx/C microparticles, which could effectively counteract the irreversible consumption of Li ions and avoid the complicated pre-lithiation process. Moreover, this strategy guarantees the structural integrity and processability of anode materials because of the homogeneous Li-organic complex solution pre-lithiation and high-temperature calcination process. The obtained SiOx/C microparticles can be applied as anode materials by directly mixing with commercial graphite, which demonstrates proper specific capacity, high initial Coulombic efficiency, and excellent cycling performance. Furthermore, the pouch cells using LiNi0.8Co0.1Mn0.1O2 cathodes and the as-prepared anodes exhibit high energy density (301 Wh kg-1) and satisfactory cycling stability (93.3% capacity retention after 100 cycles).