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Cartilage is severely limited in self-repair after damage, and tissue engineering scaffold transplantation is considered the most promising strategy for cartilage regeneration. However, scaffolds without cells and growth factors, which can effectively avoid long cell culture times, high risk of infection, and susceptibility to contamination, remain scarce. Hence, we developed a cell- and growth factor-dual free hierarchically structured nanofibrous sponge to mimic the extracellular matrix, in which the encapsulated core-shell nanofibers served both as mechanical supports and as long-lasting carriers for bioactive biomass molecules (glucosamine sulfate). Under the protection of the nanofibers in this designed sponge, glucosamine sulfate could be released continuously for at least 30 days, which significantly accelerated the repair of cartilage tissue in a rat cartilage defect model. Moreover, the nanofibrous sponge based on carboxymethyl chitosan as the framework could effectively fill irregular cartilage defects, adapt to the dynamic changes during cartilage movement, and maintain almost 100 % elasticity even after multiple compression cycles. This strategy, which combines fiber freeze-shaping technology with a controlled-release method for encapsulating bioactivity, allows for the assembly of porous bionic scaffolds with hierarchical nanofiber structure, providing a novel and safe approach to tissue repair.
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Cartilagem Articular , Quitosana , Glucosamina , Nanofibras , Alicerces Teciduais , Quitosana/química , Quitosana/análogos & derivados , Animais , Nanofibras/química , Cartilagem Articular/efeitos dos fármacos , Ratos , Glucosamina/química , Glucosamina/análogos & derivados , Alicerces Teciduais/química , Engenharia Tecidual , Ratos Sprague-Dawley , Tamanho da Partícula , Porosidade , Propriedades de SuperfícieRESUMO
Metal halides have drawn great interest as luminescent materials and scintillators due to their outstanding optical properties. Exploring new types of phosphors with easy production processes, excellent photophysical properties, high light yields, and environmentally friendly compositions is crucial and quite challenging. Herein, a novel Mn(II)-based metal halide (4-BTP)2MnBr4 was produced using a facile solvent evaporation method, which exhibited a strong green emission peaking at 524 nm from the d-d transition of tetrahedral-coordinated Mn2+ ion and a near-unity quantum yield. The prepared white light-emitting diode device has a wide color gamut of 100.7% NTSC with CIE chromaticity coordinates of (0.32, 0.32). In addition, (4-BTP)2MnBr4 demonstrates excellent characteristics in X-ray scintillation, including a high light yield of 98â¯000 photons/MeV, a sensitive detection limit of 37.4 nGy/s, excellent resistance to radiation damage, and successful demonstration of X-ray imaging with high resolution at 21.3 lp/mm, revealing the potential for application in diagnostic X-ray medical imaging and industry radiation detection.
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The long-term stability of perovskite solar cells (PSCs) is still challenging for commercialization and mainly linked to the life span of perovskite films. Herein, a spontaneous compositional-interfacial co-modification strategy is developed based on the ion exchange reaction by introducing ammonium hexafluorophosphate (NH4PF6) into antisolvent to form gradient structures through a simple one-step solvent engineering. With the assistance of the ion exchange reaction, NH4PF6 forms a multifunctional structure to protect perovskite films from both internal and external factors for the exceptionally long-term stability of photovoltaics. The reason for this is linked to the high hydrophobicity of NH4PF6 for preventing H2O invasion, suppressing ion migration by forming hydrogen bonding, and reducing perovskite defects. The resulting unencapsulated devices show exceptionally long-term stability under standardized the International Summit on Organic Photovoltaic Stability (ISOS) protocols, with over 94%, 81%, and 83% retained power conversion efficiencies after aging tests under N2 (ISOS-D-1I), ambient air (ISOS-D-1), and 85 °C (ISOS-D-2I) for 14016, 2500, and 1248 h, respectively. These performances compare well with the state-of-the-art stability of inverted PSCs. Further investigations are conducted to study the evolution of macroscopic morphology and microscopic crystal structure in aged perovskite films, aiming to provide evidence supporting the aforementioned improvements in stability.
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Perovskite solar cells (PSCs) have attracted significant attention due to their high efficiencies that are closely associated with the optimized interface of perovskite (PVK) films. However, during film deposition, tremendous interfacial defects are generated in PVK films, which suppress device performance. Herein, we employ an organic molten chloride salt of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) on the PVK surface to regulate the interface properties through surface reconstruction by heating to 110 °C, during which DMTMM undergoes an obvious phase transition from a solid to liquid molten salt. The mobile phase coordinates with unsaturated Pb2+ and halide vacancies to heal the structural defects. After the mixture cools to room temperature, a compact DMTMM interlayer is formed to protect PVKs from degradation in the air. Consequently, the DMTMM-treated MAPbI3-based PSCs yield a champion PCE approaching 20% with optimized stability. This molten-salt-assisted surface reconstruction strategy provides a new approach to establish highly stable hybrid perovskite films for high-performance PSCs.
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Incredible progress in photovoltaic devices based on hybrid perovskite materials has been made in the past few decades, and a record-certified power conversion efficiency (PCE) of over 26% has been achieved in single-junction perovskite solar cells (PSCs). In the fabrication of high-efficiency PSCs, the postprocessing procedures toward perovskites are essential for designing high-quality perovskite thin films; developing efficient and reliable post-treatment techniques is very important to promote the progress of PSCs. Here, recent post-treatment technological reforms toward perovskite thin films are summarized, and the principal functions of the post-treatment strategies on the design of high-quality perovskite films have been thoroughly analyzed by dividing into two categories in this review: thermal annealing (TA)-related technique and TA-free technique. The latest research progress of the above two types of post-treatment techniques is summarized and discussed, focusing on the optimization of postprocessing conditions, the regulation of perovskite qualities, and the enhancement of device performance. Finally, an outlook of the prospect trends and future challenges for the fabrication of the perovskite layer and the production of highly efficient PSCs is given.
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Organic-inorganic metal hybrid perovskites (OIHPs) have emerged as a promising class of materials for next-generation optoelectronic applications. However, the realization of red and near-infrared (NIR) room-temperature phosphorescence (RTP) in these materials remains limited. In this study, a very strong red RTP emission centered at 610 nm is achieved by doping Mn2+ ions into Cd-based 2D OIHPs. Notably, the optimized B-EACC:Mn2+ exhibited a high quantum yield of 44.11%, an ultralong lifetime of up to 378 ms, and excellent stability against high temperatures and various solvents, surpassing most reported counterparts of 2D OIHPs. Moreover, the B-EACC:Mn2+ can be used as a red emitter for coating an ultraviolet light-emitting diode chip, exhibiting an observable afterglow to the naked eye for approximately 4 s. In addition, the B-EACC:Mn2+ demonstrates interesting characteristics under X-ray excitation, exhibiting X-ray response at radiation doses in the range of 34.75-278 µGy s-1. This work suggests the infinite possibility of doping guest ions to realize red RTP in 2D OIHPs, promoting the development of long-persistent phosphorescent emitters for multifunctional light-emitting applications.
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Two-dimensional (2D) metal halide perovskites with highly efficient ultralong room-temperature phosphorescence (URTP) are rare due to their uncertain structures and complicated intermolecular interactions. Herein, by varying the alkyl length of organic units, we synthesized two single-component 2D metal hybrid perovskites, i.e., B-MACC and B-EACC, with obvious URTP emission. In particular, B-EACC exhibits a green-yellow URTP emission with an ultralong lifetime (579 ms) and a high efficiency (14.86%). It is found that the molecular packing of B-EA+ cations because of the presence one more carbon in the alkyl chain affords strong hydrogen bonding and π-π stacking interactions, which immobilizes and reduces the triplet exciton quenching. Moreover, B-MACC and B-EACC with space-time dual-resolved characteristics can be utilized for dynamic information encryption and optical logic gate applications. This study is the first to disclose the relation between the characteristics of molecular packing and the resultant URTP of 2D metal hybrid perovskites, significantly advancing the development of next-generation URTP materials for versatile applications.
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The growth of high-quality perovskite films is complicated by the fact of uncontrollable crystallization pathways from perovskite precursors. During solution processing, extensive undesired nonperovskite products including residual solvate intermediates are produced due to quick solvent evaporation, which will adversely affect the efficiency and stability of perovskite solar cells (PSCs). Herein, we developed a highly efficient phase-transition pathway using a polydimethylsiloxane (PDMS)-based facial mask (FM) incubation technique, which enables significant reduction of the perovskite crystallization rate and depression of perovskite aggregation behavior. A surprising finding reveals that this technique induces complete phase transition from solvate intermediates to the perovskite phase, thereby obtaining phase-pure perovskite film. Meanwhile, a high-quality perovskite film with a shiny smooth surface, decreased defect states, and alleviated lattice strain is achieved after utilizing the FM strategy. Consequently, the target-inverted PSCs deliver a respectable efficiency of â¼21% and superior stability in both shelf storage (over 3700 h with 90% of initial efficiency) and light soaking (over 1000 h with 80% of initial efficiency) conditions. Our work highlights the importance of eliminating residual solvate intermediates to construct high-quality perovskites with excellent phase purity for ongoing production of high-performance perovskite-based optoelectronic devices.
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Despite recent advances in single-molecule and structural analysis of condensin activity in vitro, mechanisms of functional condensin loading and loop extrusion that lead to specific chromosomal organization remain unclear. In Saccharomyces cerevisiae, the most prominent condensin loading site is the rDNA locus on chromosome XII, but its repetitiveness deters rigorous analysis of individual genes. An equally prominent non-rDNA condensin site is located on chromosome III (chrIII). It lies in the promoter of a putative non-coding RNA gene called RDT1, which is in a segment of the recombination enhancer (RE) that dictates MATa-specific chrIII organization. Here, we unexpectedly find that condensin is recruited to the RDT1 promoter in MATa cells through hierarchical interactions with Fob1, Tof2, and cohibin (Lrs4/Csm1), a set of nucleolar factors that also recruit condensin to the rDNA. Fob1 directly binds to this locus in vitro, while its binding in vivo depends on an adjacent Mcm1/α2 binding site that provides MATa cell specificity. We also uncover evidence for condensin-driven loop extrusion anchored by Fob1 and cohibin at RDT1 that unidirectionally extends toward MATa on the right arm of chrIII, supporting donor preference during mating-type switching. S. cerevisiae chrIII therefore provides a new platform for the study of programmed condensin-mediated chromosome conformation.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Ligação a DNA/metabolismo , Cromossomos/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , DNA Ribossômico/genética , DNA Ribossômico/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Nucleares/genéticaRESUMO
Acanthamoeba is an opportunistic protozoa, which exists widely in nature and is mainly distributed in soil and water. Acanthamoeba usually exists in two forms, trophozoites and cysts. The trophozoite stage is one of growth and reproduction while the cyst stage is characterized by cellular quiescence, commonly resulting in human infection, and the lack of effective monotherapy after initial infection leads to chronic disease. Acanthamoeba can infect several human body tissues such as the skin, cornea, conjunctiva, respiratory tract, and reproductive tract, especially when the tissue barriers are damaged. Furthermore, serious infections can cause Acanthamoeba keratitis, granulomatous amoebic encephalitis, skin, and lung infections. With an increasing number of Acanthamoeba infections in recent years, the pathogenicity of Acanthamoeba is becoming more relevant to mainstream clinical care. This review article will describe the etiological characteristics of Acanthamoeba infection in detail from the aspects of biological characteristic, classification, disease, and pathogenic mechanism in order to provide scientific basis for the diagnosis, treatment, and prevention of Acanthamoeba infection.
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Injectable hydrogels effectively remodel degenerative nucleus pulposus (NP) with a resemblance to the in vivo microenvironment. However, the pressure within the intervertebral disc requires load-bearing implants. The hydrogel must undergo a rapid phase transition upon injection to avoid leakage. In this study, an injectable sodium alginate hydrogel was reinforced with silk fibroin nanofibers with core-shell structures. The nanofiber-embedded hydrogel provided support to adjacent tissues and facilitated cell proliferation. Platelet-rich plasma (PRP) was incorporated into the core-shell nanofibers for sustained release and enhanced NP regeneration. The composite hydrogel exhibited excellent compressive strength and enabled leak-proof delivery of PRP. In rat intervertebral disc degeneration models, radiography and MRI signal intensities were significantly reduced after 8 weeks of injections with the nanofiber-reinforced hydrogel. The biomimetic fiber gel-like structure was constructed in situ, providing mechanical support for NP repair, promoting the reconstruction of the tissue microenvironment, and finally realizing the regeneration of NP.
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Nanofibras , Núcleo Pulposo , Animais , Ratos , Hidrogéis , Alginatos , BiomiméticaRESUMO
Structural defects in the bulk and on the surface of the perovskite layer serving as trap sites induce nonradiative recombination losses, limiting the performance improvement of perovskite solar cells (PSCs). Herein, we report a trometamol-induced dual passivation (TIDP) strategy to fix both bulk and surface defects of perovskites, where the trometamol molecule can simultaneously act as chemical additive and surface-modification agent. Studies show that trometamol as an additive can effectively reduce ionic defects and enhance the grain size of perovskites through Pb2+/-NH2 coordination bonds and I-/-OH hydrogen bonds. As a surface-modification agent, trometamol further passivates ionic defects at the upper surface of the perovskite layer. As a result of the TIDP approach, a remarkable efficiency augmentation from 17.25% to 19.17% and an optimized thermal stability under inert conditions have been realized. These results highlight the importance of the TIDP strategy in perovskite defect management for excellent photovoltaic properties, facilitating the fabrication of high-performance PSCs.
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Organic-inorganic metal halide perovskites are regarded as one of the most promising candidates in the photovoltaic field, but simultaneous realization of high efficiency and long-term stability is still challenging. Here, a one-step solution-processing strategy is demonstrated for preparing efficient and stable inverted methylammonium lead iodide (MAPbI3 ) perovskite solar cells (PSCs) by incorporating a series of organic molecule dopants of fluorophenylboronic acids (F-PBAs) into perovskite films. Studies have shown that the F-PBA dopant acts as a cross-linker between neighboring perovskite grains through hydrogen bonds and coordination bonds between F-PBA and perovskite structures, yielding high-quality perovskite crystalline films with both improved crystallinity and reduced defect densities. Benefiting from the repaired grain boundaries of MAPbI3 with the organic cross-linker, the inverted PSCs exhibit a remarkably enhanced performance from 16.4% to approximately 20%. Meanwhile, the F-PBA doped devices exhibit enhanced moisture/thermal/light stability, and specially retain 80% of their initial power conversion efficiencies after more than two weeks under AM 1.5G one-sun illumination. This work highlights the impressive advantages of the perovskite crystal cross-linking strategy using organic molecules with strong intermolecular interactions, providing an efficient route to prepare high-performance and stable planar PSCs.
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The aquaporins (AQPs) are a family of integral membrane proteins which play critical roles in controlling transcellular water movement in various tissues throughout the body. AQP1 helps mediate the cellular response to osmotic stress and tissue water permeability. However, the mechanism by which AQP1 mediates changes in cell volume is not completely clear. Here, we investigated how AQP1 responds to and controls cell volume upon osmotic stimuli during the early phase after the immediate response. Cells overexpressing AQP1 were exposed to hypotonic or hypertonic medium in the presence or absence of staurosporine or W-7 hydrochloride, and fluorescence imaging was performed at 0, 5, 10, and 15 min later. Osmotic stimuli induced redistribution of AQP1 into the cell membrane, hypotonic stimuli caused cell enlargement, and hypertonic stimuli induced a reduction in cell size, which was blocked by T157A/T239A mutations. Changes in cell size induced by osmotic stimuli were blocked by an antagonist of calmodulin kinase, W-7 hydrochloride, but not by the PKC inhibitor staurosporine. These results suggest that calmodulin kinase regulates AQP1 activity during the early response to osmotic stimuli.
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Aquaporina 1/metabolismo , Calmodulina/metabolismo , Aquaporina 1/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Calmodulina/antagonistas & inibidores , Membrana Celular/metabolismo , Tamanho Celular/efeitos dos fármacos , Meios de Cultura/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Mutação , Osmose/fisiologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Estaurosporina/farmacologia , Sulfonamidas/farmacologiaRESUMO
T2 toxin is a type A trichothecene mycotoxin. In order to reduce the side effects of T2 toxin and increase the tumor targeting ability, a pHsensitive liposome of T2 toxin (LPpHST2) was prepared and characterized in the present study. The cytotoxicity of LPpHST2 on A549, HepG2, MKN45, K562 and L929 cell lines was tested by 3(4,5dimethylthiazolyl2)2,5diphenyltetrazolium bromide assay, with T2 toxin as the control. The apoptotic and migratory effects of LPpHST2 on HepG2 cells were investigated. The preparation process of LPpHST2 involved the following parameters: Dipalmitoyl phosphatidylcholine: dioleoylphosphatidylethanolamine, 1:2; total phospholipid concentration, 20 mg/ml; phospholipid:cholesterol, 3:1; 4(2hydroxyethyl)1piperazineethanesulfonic acid buffer (pH 7.4), 10 ml; drug:lipid ratio, 2:1; followed by ultrasound for 10 min and extrusion. The encapsulation efficiency reached 95±2.43%. The average particle size of LPpHST2 after extrusion was 100 nm; transmission electron microscopy showed that the shape of LPpHST2 was round or oval and of uniform size. The release profile demonstrated a twophase downward trend, with fast leakage of T2 toxin in the first 6 h (~20% released), followed by sustained release up to 48 h (~46% released). From 4872 h, the leakage rate increased (~76% released), until reaching a minimum at 72 h. When LPpHST2 was immersed in 0.2 mol/l disodium phosphatesodium dihydrogen phosphate buffers (pH 6.5), the release speed was significantly increased and the release rate reached 91.2%, demonstrating strong pH sensitivity. Overall, antitumor tests showed that LPpHST2 could promote the apoptosis and inhibit the migration of HepG2 cells. The present study provided a new approach for the development of T2 toxinbased anticancer drugs.
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Antineoplásicos/farmacologia , Toxina T-2/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Células K562 , Lipossomos , Camundongos , Tamanho da Partícula , Toxina T-2/químicaRESUMO
Trap-assisted recombination loss in the cathode buffer layers (CBLs) is detrimental to the electron extraction process and severely restricts the power conversion efficiencies (PCEs) of organic solar cells (OSCs). Herein, a novel organic-inorganic hybrid film composed of zinc oxide (ZnO) and 2,3,5,6-tetrafluoro-7,7,8, 8-tetracyanoquinodimethane (F4TCNQ) is designed to fill the intrinsic charge traps of ZnO-based CBLs by doping F4TCNQ for high-performance inverted OSCs. Thus, constructed ZnO:F4TCNQ hybrid film exhibits enhanced surface hydrophobicity and adjustable energy levels, providing favorable interfacial condition for electron extraction process. Consequently, trap-assisted recombination loss in the CBLs was efficiently suppressed, leading to the significantly improved fill factor and PCEs of both fullerene- and non-fullerene-based OSCs using the ZnO:F4TCNQ hybrid CBLs. This work illustrates a convenient organic acceptor doping approach to suppress the internal charge traps of traditional inorganic CBLs, which will shed new light on the fabrication of high-performance CBLs with facile electron extraction processes in inverted OSC devices.
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The exploitation of thermally activated delayed fluorescence (TADF) emitters with aggregation-induced emission is highly prerequisite for the construction of highly efficient electroluminescent devices in materials science. Herein, two asymmetric TADF emitters of SFCOCz and SFCODPAC with charming aggregation-induced emission are expediently designed and prepared based on highly twisted strong electron-withdrawing acceptor (A) of sulfurafluorene (SF)-modified ketone (CO) and arylamine donor (D) in D1-A-D2 architecture by simple synthetic procedure in high yields. High photoluminescence quantum yields up to 73% and small singlet-triplet splitting of 0.03 eV; short exciton lifetimes are obtained in the resultant molecules. Strikingly, efficient non-doped and doped TADF organic light-emitting diodes (OLEDs) facilitated by these emitters show high luminance of 5,598 and 11,595 cd m-2, current efficiencies (CEs) of 16.8 and 35.6 cd/A, power efficiencies (PEs) of 9.1 and 29.8 lm/W, and external quantum efficiencies (EQEs) of 7.5 and 15.9%, respectively. This work furnishes a concrete instance in exploring efficient TADF emitter, which is highly conducive and encouraging in stimulating the development of TADF OLEDs with high brightness and excellent efficiencies simultaneously.
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The NAD+-dependent histone deacetylase Sir2 was originally identified in Saccharomyces cerevisiae as a silencing factor for HML and HMR, the heterochromatic cassettes utilized as donor templates during mating-type switching. MATa cells preferentially switch to MATα using HML as the donor, which is driven by an adjacent cis-acting element called the recombination enhancer (RE). In this study we demonstrate that Sir2 and the condensin complex are recruited to the RE exclusively in MATa cells, specifically to the promoter of a small gene within the right half of the RE known as RDT1. We also provide evidence that the RDT1 promoter functions as a locus control region (LCR) that regulates both transcription and long-range chromatin interactions. Sir2 represses RDT1 transcription until it is removed from the promoter in response to a dsDNA break at the MAT locus induced by HO endonuclease during mating-type switching. Condensin is also recruited to the RDT1 promoter and is displaced upon HO induction, but does not significantly repress RDT1 transcription. Instead condensin appears to promote mating-type donor preference by maintaining proper chromosome III architecture, which is defined by the interaction of HML with the right arm of chromosome III, including MATa and HMR. Remarkably, eliminating Sir2 and condensin recruitment to the RDT1 promoter disrupts this structure and reveals an aberrant interaction between MATa and HMR, consistent with the partially defective donor preference for this mutant. Global condensin subunit depletion also impairs mating-type switching efficiency and donor preference, suggesting that modulation of chromosome architecture plays a significant role in controlling mating-type switching, thus providing a novel model for dissecting condensin function in vivo.
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Cromossomos Fúngicos/genética , Genes Fúngicos Tipo Acasalamento/genética , Região de Controle de Locus Gênico/genética , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae/metabolismo , Sirtuína 2/metabolismo , Adenosina Trifosfatases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Loci Gênicos/genética , Complexos Multiproteicos/metabolismo , Regiões Promotoras Genéticas/genética , Recombinação Genética , Saccharomyces cerevisiae , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae/genética , Sirtuína 2/genéticaRESUMO
Orthodontic retainers are wearable customizable medical devices for dental protection or alignment. Here, clonidine hydrochloride (CH)-loaded wearable personalized 3D printed orthodontic retainers were studied for local sustained-release of drugs. CH powders were mixed with PEG 4000, Tween 80, poly(lactic acid), and polycaprolactone. The mixture was hot-melt extruded to form a filament that was 3D printed to a customizable original orthodontic retainer with the fused deposition modeling (FDM) method. The original retainer showed a burst release of CH in the early stage of the dissolution process though a sustained release appeared in the late stage. The in vivo burst release of CH would lead to unexpected side effect. The original retainer was modified by coating with hydrophilic polymers or washing with buffered solutions to obtain the coated or washed retainer. The coated retainer still showed a burst release while the washed retainer showed an optimal sustained release. Many CH microparticles existed on the surface of original retainers according to the scanning electron microscopic image so that the burst release was unavoidable. The hydrophilic polymer coating method did not change the release profile because the polymer was also rapidly dissolved. However, most of the surface CH can be eliminated by washing so that the burst release dissappeared in the washed retainer. Furthermore, the simulated CH concentration-time profiles in the circulation of humans of the washed retainer showed the stable and appropriate drug levels for more than 3 days. Wearable personalized 3D printed drug-loaded orthodontic retainers are a promising drug-device for sustained release of drugs.
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Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Clonidina/administração & dosagem , Preparações de Ação Retardada , Contenções Ortodônticas , Impressão Tridimensional , Dispositivos Eletrônicos Vestíveis , Adulto , Feminino , Humanos , PolímerosRESUMO
Sir2 is a highly conserved NAD+-dependent histone deacetylase that functions in heterochromatin formation and promotes replicative life span (RLS) in the budding yeast, Saccharomyces cerevisiae Within the yeast rDNA locus, Sir2 is required for efficient cohesin recruitment and maintaining the stability of the tandem array. In addition to the previously reported depletion of Sir2 in replicatively aged cells, we discovered that subunits of the Sir2-containing complexes silent information regulator (SIR) and regulator of nucleolar silencing and telophase (RENT) were depleted. Several other rDNA structural protein complexes also exhibited age-related depletion, most notably the cohesin complex. We hypothesized that mitotic chromosome instability (CIN) due to cohesin depletion could be a driver of replicative aging. Chromatin immunoprecipitation assays of the residual cohesin (Mcd1-Myc) in moderately aged cells showed strong depletion from the rDNA and initial redistribution to the point centromeres, which was then lost in older cells. Despite the shift in cohesin distribution, sister chromatid cohesion was partially attenuated in aged cells and the frequency of chromosome loss was increased. This age-induced CIN was exacerbated in strains lacking Sir2 and its paralog, Hst1, but suppressed in strains that stabilize the rDNA array due to deletion of FOB1 or through caloric restriction. Furthermore, ectopic expression of MCD1 from a doxycycline-inducible promoter was sufficient to suppress rDNA instability in aged cells and to extend RLS. Taken together, we conclude that age-induced depletion of cohesin and multiple other nucleolar chromatin factors destabilize the rDNA locus, which then results in general CIN and aneuploidy that shortens RLS.