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Layered sodium-ion oxides hold considerable promise in achieving high-performance sodium-ion batteries. However, the notorious phase transformation during charging, attributed to increased O2-âO2- repulsion, results in substantial performance decay. Here, a hierarchical layer modification strategy is proposed to stabilize interlayer repulsion. During desodiation, migrated Li+ from the transition metal layer and anchored Ca2+ in sodium sites maintain the cationic content within the sodium layer. Meanwhile, partial oxygen substitution by fluorine and the involvement of oxygen in redox reactions increase the average valence of the oxygen layer. This sustained cation presence and elevated anion valence collectively mitigate increasing O2-âO2- repulsion during sodium extraction, enabling the Na0.61Ca0.05[Li0.1Ni0.23Mn0.67]O1.95F0.05 (NCLNMOF) cathode to retain a pure P2-type structure across a wide voltage range. Unexpected insights reveal the interplay between different doping elements: the robust LiâF bonds and Ca2+ steric effects suppressing Li+ loss. The NCLNMOF electrode exhibits 82.5% capacity retention after 1000 cycles and a high-rate capability of 94 mAh g-1 at 1600 mA g-1, demonstrating the efficacy of hierarchical layer modification for high-performance layered oxide cathodes.
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All-solid-state batteries (ASSBs) have garnered considerable attention as promising candidates for next-generation energy storage systems due to their potentially simultaneously enhanced safety capacities and improved energy densities. However, the solid future still calls for materials with high ionic conductivity, electrochemical stability, and favorable interfacial compatibility. In this study, we present a series of halide solid-state electrolytes (SSEs) utilizing a doping strategy with highly valent elements, demonstrating an outstanding combination of enhanced ionic conductivity and oxidation stability. Among these, Li2.6In0.8Ta0.2Cl6 emerges as the standout performer, displaying a superionic conductivity of up to 4.47 mS cm-1 at 30 °C, along with a low activation energy barrier of 0.321 eV for Li+ migration. Additionally, it showcases an extensive oxidation onset of up to 5.13 V (vs Li+/Li), enabling high-voltage ASSBs with promising cycling performance. Particularly noteworthy are the ASSBs employing LiCoO2 cathode materials, which exhibit an extended cyclability of over 1400 cycles, with 70% capacity retention under 4.6 V (vs Li+/Li), and a capacity of up to 135 mA h g-1 at a 4 C rate, with the loading of active materials at 7.52 mg cm-2. This study demonstrates a feasible approach to designing desirable SSEs for energy-dense, highly stable ASSBs.
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The resolution limit of chromatin conformation capture methodologies (3Cs) has restrained their application in detection of fine-level chromatin structure mediated by cis-regulatory elements (CREs). Here, we report two 3C-derived methods, Tri-4C and Tri-HiC, which utilize multirestriction enzyme digestions for ultrafine mapping of targeted and genome-wide chromatin interaction, respectively, at up to one hundred basepair resolution. Tri-4C identified CRE loop interaction networks and quantitatively revealed their alterations underlying dynamic gene control. Tri-HiC uncovered global fine-gauge regulatory interaction networks, identifying >20-fold more enhancer:promoter (E:P) loops than in situ Hi-C. In addition to vastly improved identification of subkilobase-sized E:P loops, Tri-HiC also uncovered interaction stripes and contact domain insulation from promoters and enhancers, revealing their loop extrusion behaviors resembling the topologically associating domain boundaries. Tri-4C and Tri-HiC provide robust approaches to achieve the high-resolution interactome maps required for characterizing fine-gauge regulatory chromatin interactions in analysis of development, homeostasis, and disease.
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Cromosomas , Genoma , Mapeo Cromosómico/métodos , Genoma/genética , Cromatina/genética , Secuencias Reguladoras de Ácidos Nucleicos/genéticaRESUMEN
Pyriproxyfen is a juvenile hormone analogue. The physiological effects of its low-concentration drift during the process of controlling agricultural and forestry pests on non-target organisms in the ecological environment are unpredictable, especially the effects on organs that play a key role in biological function are worthy of attention. The silk gland is an important organ for silk-secreting insects. Herein, we studied the effects of trace pyriproxyfen on autophagy and apoptosis of the silk gland in the lepidopteran model insect, Bombyx mori (silkworm). After treating fifth instar silkworm larvae with pyriproxyfen for 24 h, we found significant shrinkage, vacuolization, and fragmentation in the posterior silk gland (PSG). In addition, the results of autophagy-related genes of ATG8 and TUNEL assay also demonstrated that autophagy and apoptosis in the PSG of the silkworm was induced by pyriproxyfen. RNA-Seq results showed that pyriproxyfen treatment resulted in the activation of juvenile hormone signaling pathway genes and inhibition of 20-hydroxyecdysone (20E) signaling pathway genes. Among the 1808 significantly differentially expressed genes, 796 were upregulated and 1012 were downregulated. Among them, 30 genes were identified for autophagy-related signaling pathways, such as NOD-like receptor signaling pathway and mTOR signaling pathway, and 30 genes were identified for apoptosis-related signaling pathways, such as P53 signaling pathway and TNF signaling pathway. Further qRT-PCR and in vitro gland culture studies showed that the autophagy-related genes Atg5, Atg6, Atg12, Atg16 and the apoptosis-related genes Aif, Dronc, Dredd, and Caspase1 were responsive to the treatment of pyriproxyfen, with transcription levels up-regulated from 24 to 72 h. In addition, ATG5, ATG6, and Dronc genes had a more direct response to pyriproxyfen treatment. These results suggested that pyriproxyfen treatment could disrupt the hormone regulation in silkworms, promoting autophagy and apoptosis in the PSG. This study provides more evidence for the research on the damage of juvenile hormone analogues to non-target organisms or organs in the environment, and provides reference information for the scientific and rational use of juvenile hormone pesticides.
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Bombyx , Animales , Bombyx/fisiología , Seda/genética , Seda/metabolismo , Seda/farmacología , Apoptosis , Larva/metabolismo , Autofagia , Hormonas Juveniles/farmacología , Hormonas Juveniles/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismoRESUMEN
Genome-wide association studies (GWAS) have pinpointed the chromosomal locus 9p21.3 as a genetic hotspot for various age-related disorders. Common genetic variants in this locus are linked to multiple traits, including coronary artery diseases, cancers, and diabetes. Centenarians are known for their reduced risk and delayed onset of these conditions. To investigate whether this evasion of disease risks involves diminished genetic risks in the 9p21.3 locus, we sequenced this region in an Ashkenazi Jewish centenarian cohort (centenarians: n = 450, healthy controls: n = 500). Risk alleles associated with cancers, glaucoma, CAD, and T2D showed a significant depletion in centenarians. Furthermore, the risk and non-risk genotypes are linked to two distinct low-frequency variant profiles, enriched in controls and centenarians, respectively. Our findings provide evidence that the extreme longevity cohort is associated with collectively lower risks of multiple age-related diseases in the 9p21.3 locus.
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Enfermedad de la Arteria Coronaria , Neoplasias , Anciano de 80 o más Años , Humanos , Centenarios , Judíos/genética , Estudio de Asociación del Genoma Completo , Longevidad/genética , Enfermedad de la Arteria Coronaria/genética , Polimorfismo de Nucleótido Simple , Predisposición Genética a la EnfermedadRESUMEN
Glaucoma is a leading cause of irreversible blindness, with advanced age being the single most significant risk factor. However, the mechanisms underlying the relationship between aging and glaucoma remain unclear. Genome-wide association studies (GWAS) have successfully identified genetic variants strongly associated with increased glaucoma risk. Understanding how these variants function in pathogenesis is crucial for translating genetic associations into molecular mechanisms and, ultimately, clinical applications. The chromosome 9p21.3 locus is among the most replicated glaucoma risk loci discovered by GWAS. Nonetheless, the absence of protein-coding genes in the locus makes interpreting the disease association challenging, leaving the causal variant and molecular mechanism elusive. In this study, we report the identification of a functional glaucoma risk variant, rs6475604. By employing computational and experimental methods, we demonstrated that rs6475604 resides in a repressive regulatory element. Risk allele of rs6475604 disrupts the binding of YY1, a transcription factor known to repress the expression of a neighboring gene in 9p21.3, p16INK4A, which plays a crucial role in cellular senescence and aging. These findings suggest that the glaucoma disease variant contributes to accelerated senescence, providing a molecular link between glaucoma risk and an essential cellular mechanism for human aging.
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Inhibidor p16 de la Quinasa Dependiente de Ciclina , Glaucoma , Humanos , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Glaucoma/genética , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Factores de Transcripción/genéticaRESUMEN
Glaucoma is a leading cause of irreversible blindness, with advanced age being the single most significant risk factor. However, the mechanisms underlying the relationship between aging and glaucoma remain unclear. Genome-wide association studies (GWAS) have successfully identified genetic variants strongly associated with increased glaucoma risk. Understanding how these variants function in pathogenesis is crucial for translating genetic associations into molecular mechanisms and, ultimately, clinical applications. The chromosome 9p21.3 locus is among the most replicated glaucoma risk loci discovered by GWAS. Nonetheless, the absence of protein-coding genes in the locus makes interpreting the disease association challenging, leaving the causal variant and molecular mechanism elusive. In this study, we report the identification of a functional glaucoma risk variant, rs6475604. By employing computational and experimental methods, we demonstrated that rs6475604 resides in a repressive regulatory element. Risk allele of rs6475604 disrupts the binding of YY1, a transcription factor known to repress the expression of a neighboring gene in 9p21.3, p16INK4A, which plays a crucial role in cellular senescence and aging. These findings suggest that the glaucoma disease variant contributes to accelerated senescence, providing a molecular link between glaucoma risk and an essential cellular mechanism for human aging.
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Though ecofriendly, pure Al2O3 has never been used for activation of peroxodisulfate (PDS) to degrade pollutants. We report the fabrication of Al2O3 nanotubes by ureasolysis method for efficient activating PDS degradation of antibiotics. The fast ureasolysis in aqueous AlCl3 solution produces NH4Al(OH)2CO3 nanotubes, which are calcined to porous Al2O3 nanotubes, and the release of ammonia and carbon dioxide engineers the surface features of large surface area, numerous acidic-basic sites and suitable Zeta potentials. The synergy of these features facilitates the adsorption of the typical antibiotics ciprofloxacin and PDS activation, which is proved by experiment results and density functional theory simulation. The proposed Al2O3 nanotubes can catalyze 92-96% degradation of 10 ppm ciprofloxacin within 40 min, with chemical oxygen demand removal of 65-66% in aqueous, and 40-47% in whole including aqueous and catalysts. Ciprofloxacin at high concentration, other fluoroquinolones and tetracycline can also be effectively degraded. These data demonstrate the Al2O3 nanotubes prepared by the nature-inspired ureasolysis method has unique features and great potentials for antibiotics degradation.
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Nanotubos , Contaminantes Químicos del Agua , Antibacterianos , Ciprofloxacina , FluoroquinolonasRESUMEN
Acne is an inflammatory skin disease mainly caused by Propionibacterium acnes, which can cause local inflammatory reactions and develop into chronic inflammatory diseases in severe cases. To avoid the use of antibiotics and to effectively treat the site of acne, we report a sodium hyaluronate microneedle patch that mediates the transdermal delivery of ultrasound-responsive nanoparticles for the effective treatment of acne. The patch contains nanoparticles formed by zinc porphyrin-based metal-organic framework and zinc oxide (ZnTCPP@ZnO). We demonstrated activated oxygen-mediated killing of P. acnes with an antibacterial efficiency of 99.73% under 15 min of ultrasound irradiation, resulting in a decrease in levels of acne-related factors, including tumor necrosis factor-α, interleukins, and matrix metalloproteinases. The zinc ions up-regulated DNA replication-related genes, promoting the proliferation of fibroblasts and, consequently, skin repair. This research leads to a highly effective strategy for acne treatment through the interface engineering of ultrasound response.
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Acné Vulgar , Infecciones Bacterianas , Humanos , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/microbiología , Propionibacterium acnes , Interleucinas , Antibacterianos/farmacologíaRESUMEN
Photocatalysts for regeneration of reduced nicotinamide adenine dinucleotide (NADH) usually work with continuous lighting and electron mediators, which causes impracticability under dark conditions, risk of NADH reoxidation, and complex separation. To solve these problems, we present a new catalyst of tiny Pt nanoparticles photodeposited on chromium-doped zinc gallate (CZGO@Pt). Upon being light-triggered, the photogenerated electrons are stored in the traps of CZGO and then gradually released and transferred by Pt to directly reduce NAD+ after stoppage of illumination. Three lighting modes are compared to demonstrate the feasibility and advantage of this light-triggered dark catalysis. Within 4 h of reaction, the in-the-dark NADH yield reaches 75.0% under prelighting CZGO@5%Pt and it reaches 80.0% under prelighting CZGO@5%Pt and triethanolamine (TEOA). However, the NADH yield is only 53.5% under continuous lighting of CZGO@5%Pt, TEOA, and NAD+. Consequently, the light-triggered dark catalytic regeneration of NADH not only saves energy and operates easily but also significantly elevates the NADH yield. It thus would secure wide interests and applications in places where no light or only intermittent light is available.
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Light-induced phase segregation in mixed halide perovskites is a major roadblock for commercialization of optoelectronics utilizing these materials. We investigate the phenomenon in a model material system consisting of only surfaces and the bulk of a single-crystalline-like microplate. We utilize environmental in-situ time-dependent photoluminescence spectroscopy to observe the bandgap evolution of phase segregation under illumination. This enables analysis of the evolution of the iodide-rich phase composition as a function of the environment (i.e., surface defects) and carrier concentration. Our study provides microscopic insights into the relationship among photocarrier generations, surface structural defects, and subsequently iodide ion migrations that result in the complex evolution of phase segregation. We elucidate the significance of surface defects with respect to the evolution of phase segregation, which may provide new perspectives for modulating ion migration by engineering of defects and carrier concentrations.
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Conferring catalytic defects in sonosensitizers is of paramount importance in reinforcing sonodynamic therapy. However, the formation of such 0D defects is governed by the Schottky defect principle. Herein, 2D catalytic planar defects are designed within Ti3 C2 sheets to address this challenge. These specific planar slip dislocations with abundant Ti3+ species (Ti3 C2 -SD(Ti3+ )) can yield surface-bound O due to the effective activation of O2 , thus resulting in a substantial amount of 1 O2 generation and the 99.72% ± 0.03% bactericidal capability subject to ultrasound (US) stimulation. It is discovered that the 2D catalytic planar defects can intervene in electron transfer through the phonon drag effect-a coupling effect between surface electrons and US-triggered phonons-that simultaneously contributes to a dramatic decrease in O2 activation energy from 1.65 to 0.06 eV. This design has achieved a qualitative leap in which the US catalytic site has transformed from 0D to 2D. Moreover, it is revealed that the electron origin, electron transfer, and visible O2 activation pathway triggered by US can be attributed to the phonon-electron coupling effect. After coating with neutrophil membrane (NM) proteins, the NM-Ti3 C2 -SD(Ti3+ ) sheets further demonstrate a 6-log10 reduction in methicillin-resistant Staphylococcus aureus burden in the infected bony tissue.
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Staphylococcus aureus Resistente a Meticilina , Fonones , Antibacterianos , Huesos , Catálisis , Proteínas de la MembranaRESUMEN
Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in aging and metabolism regulation. Targeted sequencing of SIRT6 locus in a population of 450 Ashkenazi Jewish (AJ) centenarians and 550 AJ individuals without a family history of exceptional longevity identified enrichment of a SIRT6 allele containing two linked substitutions (N308K/A313S) in centenarians compared with AJ control individuals. Characterization of this SIRT6 allele (centSIRT6) demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double-strand break repair, and more robustly kill cancer cells compared with wild-type SIRT6. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+ concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which was correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA.
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Lamina Tipo A , Sirtuinas , Anciano de 80 o más Años , Humanos , Centenarios , Alelos , Inestabilidad GenómicaRESUMEN
LiNiO2 (LNO) is a promising cathode material for next-generation Li-ion batteries due to its exceptionally high capacity and cobalt-free composition that enables more sustainable and ethical large-scale manufacturing. However, its poor cycle life at high operating voltages over 4.1 V impedes its practical use, thus motivating efforts to elucidate and mitigate LiNiO2 degradation mechanisms at high states of charge. Here, a multiscale exploration of high-voltage degradation cascades associated with oxygen stacking chemistry in cobalt-free LiNiO2 , is presented. Lattice oxygen loss is found to play a critical role in the local O3-O1 stacking transition at high states of charge, which subsequently leads to Ni-ion migration and irreversible stacking faults during cycling. This undesirable atomic-scale structural evolution accelerates microscale electrochemical creep, cracking, and even bending of layers, ultimately resulting in macroscopic mechanical degradation of LNO particles. By employing a graphene-based hermetic surface coating, oxygen loss is attenuated in LNO at high states of charge, which suppresses the initiation of the degradation cascade and thus substantially improves the high-voltage capacity retention of LNO. Overall, this study provides mechanistic insight into the high-voltage degradation of LNO, which will inform ongoing efforts to employ cobalt-free cathodes in Li-ion battery technology.
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The authors proposed a novel template-free strategy, urease-mediated interfacial growth of NH4 Ga(OH)2 CO3 nanotubes at 20-50 °C, to fabricate the porous Ga2 O3 nanotubes. The subtlety of the proposed strategy is all the products from urea enzymolysis are utilized in formation of NH4 Ga(OH)2 CO3 precipitates, and the key for interfacial growth of NH4 Ga(OH)2 CO3 nanotubes is the dynamic match between the rate of CO2 bubble fusion and NH4 Ga(OH)2 CO3 precipitation. The proposed strategy works well for the doped porous Ga2 O3 nanotubes. As a proof-of-concept, the porous ß-Ga2 O3 and ß-Ga2 O3 :Cr0.001 nanotubes are used as photocatalysts or co-catalysts with Pt, for H2 evolution from water splitting. The H2 evolution rate of porous ß-Ga2 O3 nanotubes reach 39.3 mmol g-1 h-1 with solar-to-hydrogen (STH) conversion efficiency of 2.11% (Hg lamp) or 498 µmol g-1 h-1 with STH of 0.03% (Xe lamp) respectively, both about 3 times of ß-Ga2 O3 nanoparticles synthesized at pH 9.0 without urease. The Cr-doping enhances the in-the-dark H2 evolution rate pre-lighted by Hg lamp, and Pt co-catalysis further elevates the H2 evolution rate, for instance, the H2 evolution rate of Pt-loaded ß-Ga2 O3 :Cr0.001 nanotubes reaches 54.7 mmol g-1 h-1 with STH of 2.94% under continuous lighting of Hg lamp and 1062 µmol g-1 h-1 in-the-dark.
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Carbonatos , Galio , Hidrógeno , Nanotubos , Ureasa , Catálisis , PorosidadRESUMEN
Type 1 diabetes (T1D) is an organ-specific autoimmune disease, whereby immune cell-mediated killing leads to loss of the insulin-producing ß cells in the pancreas. Genome-wide association studies (GWAS) have identified over 200 genetic variants associated with risk for T1D. The majority of the GWAS risk variants reside in the non-coding regions of the genome, suggesting that gene regulatory changes substantially contribute to T1D. However, identification of causal regulatory variants associated with T1D risk and their affected genes is challenging due to incomplete knowledge of non-coding regulatory elements and the cellular states and processes in which they function. Here, we performed a comprehensive integrated post-GWAS analysis of T1D to identify functional regulatory variants in enhancers and their cognate target genes. Starting with 1,817 candidate T1D SNPs defined from the GWAS catalog and LDlink databases, we conducted functional annotation analysis using genomic data from various public databases. These include 1) Roadmap Epigenomics, ENCODE, and RegulomeDB for epigenome data; 2) GTEx for tissue-specific gene expression and expression quantitative trait loci data; and 3) lncRNASNP2 for long non-coding RNA data. Our results indicated a prevalent enhancer-based immune dysregulation in T1D pathogenesis. We identified 26 high-probability causal enhancer SNPs associated with T1D, and 64 predicted target genes. The majority of the target genes play major roles in antigen presentation and immune response and are regulated through complex transcriptional regulatory circuits, including those in HLA (6p21) and non-HLA (16p11.2) loci. These candidate causal enhancer SNPs are supported by strong evidence and warrant functional follow-up studies.
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Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Presentación de Antígeno , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Análisis por Conglomerados , Elementos de Facilitación Genéticos , Epigenoma , Epigenómica , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Variación Genética , Genoma , Estudio de Asociación del Genoma Completo , Genómica , Humanos , Sistema Inmunológico , Polimorfismo de Nucleótido Simple , Probabilidad , Sitios de Carácter Cuantitativo , ARN Largo no Codificante , RiesgoRESUMEN
Although efforts have been devoted to develop new antibacterial agents and techniques, the challenge of bacterial infection remains unresolved and is even increasing. Sonodynamic therapy (SDT) driven by ultrasound (US) has demonstrated effectiveness in terms of penetration and it can help to clinically address the problem of deep tissue bacterial infection. In recent years, a variety of sonosensitizers, which were originally designed for photodynamic therapy, have been adopted for SDT. Yet, their unstable chemical stability and ineffective electron-hole separation are not favorable for clinical applications. Hence, we designed a new type of antibacterial sonosensitizer-namely, Au@Cu2O hybrid nanocubes-in which an interfacial Schottky junction was built between a p-type semiconductor Cu2O and a noble metal Au. When US stimulation was applied, the electrons from Cu2O could be excited at the junction and transferred to Au. Since the formed Schottky barrier could block the backflow of US-excited electrons, a prolonged electron-hole separation can be successfully established. Additionally, because of the boosted sonocatalytic activity, the Au@Cu2O hybrid nanocubes could produce a large amount of reactive oxygen species (ROS), which are subject to US stimulation. Furthermore, we found that the sonocatalytic activity of the Au@Cu2O hybrid nanocubes could be reinforced by increasing the amount of Au, enabling 99.67% of Staphylococcus aureus (S. aureus) to be killed by US stimulation for 15 minutes. The cytocompatibility of Au@Cu2O hybrid nanocubes was improved by a red blood cell membrane (RBC) coating over the surface, and the membrane did not sacrifice its superior antibacterial properties.
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Infecciones Estafilocócicas , Staphylococcus aureus , Antibacterianos/farmacología , Humanos , Especies Reactivas de OxígenoRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections after orthopedic implant increase the risk of failure and potentially cause amputation of limbs or life-threatening sepsis in severe cases. Additionally, satisfactory bone-implant integration is another important indicator of an ideal implant. Here, an antibiotic-free antibacterial nanofilm based on oxide perovskite-type calcium titanate (CTO)/fibrous red phosphorus (RP) on titanium implant surface (Ti-CTO/RP) in which the P-N heterojunction and internal electric field are established at the heterointerface, is designed. Near-infrared light-excited electron-hole pairs are effectively separated and transferred through the synergism of the internal electric field and band offset, which strongly boosts the photocatalytic eradication of MRSA biofilms by reactive oxygen species with an efficacy of 99.42% ± 0.22% in vivo. Additionally, the charge transfer endows the heterostructure with hyperthermia to assist biofilm eradication. Furthermore, CTO/RP nanofilm provides a superior biocompatible and osteoconductive platform that enables the proliferation and osteogenic differentiation of mesenchymal stem cells, thus contributing to the subsequent implant-to-bone osseointegration after eradicating MRSA biofilms.
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Biopelículas , Compuestos de Calcio/farmacología , Calcio/farmacología , Staphylococcus aureus Resistente a Meticilina , Oseointegración/fisiología , Óxidos/farmacología , Fósforo/farmacología , Fototerapia/métodos , Titanio/farmacología , Animales , Técnicas In Vitro , Rayos Infrarrojos , Modelos Animales , Prótesis e Implantes , RatasRESUMEN
Proper immune responses are critical for successful biomaterial implantation. Here, four scales of honeycomb-like TiO2 structures were custom made on titanium (Ti) substrates to investigate cellular behaviors of RAW 264.7 macrophages and their immunomodulation on osteogenesis. We found that the reduced scale of honeycomb-like TiO2 structures could significantly activate the anti-inflammatory macrophage phenotype (M2), in which the 90-nanometer sample induced the highest expression level of CD206, interleukin-4, and interleukin-10 and released the highest amount of bone morphogenetic protein-2 among other scales. Afterward, the resulting immune microenvironment favorably triggered osteogenic differentiation of murine mesenchymal stem cells in vitro and subsequent implant-to-bone osteointegration in vivo. Furthermore, transcriptomic analysis revealed that the minimal scale of TiO2 honeycomb-like structure (90 nanometers) facilitated macrophage filopodia formation and up-regulated the Rho family of guanosine triphosphatases (RhoA, Rac1, and CDC42), which reinforced the polarization of macrophages through the activation of the RhoA/Rho-associated protein kinase signaling pathway.